1

Philippine National Formulary

8th Edition

Published by

Department of Health
Manila, Philippines

2019
 DISCLAIMER
The list of medicines and the prescribing information contained in this edition of
the Formulary were collated as meticulously as possible through the collaborative efforts of
the Formulary Executive Council (FEC), pharmacists, medical specialists, and specialty
societies applying the standard clinical practice current at the time of the undertaking. Thus,
the medicines and the accompanying prescribing information in this edition are the most
recent only insofar as the dates of the actual collaboration are concerned. There is no
guarantee, therefore, that after the final drafting for this edition, the new medicines or new
information that may subsequently become available will be included.

While diligent effort has been made to ensure the accuracy of each entry, it is
essential to bear in mind that the information presented here is a synopsis of key points in
the official product labeling, and that the complete labeling contains additional precautionary
information that may be of significance in specific cases. Thus, the editors do not warrant
that the information contained herein is in every aspect accurate.

Since a manual of this volume cannot be as exhaustive, the editors have included
only the information which they consider to be essential, and the most relevant and useful
for rapid reference by the physicians. It is the hope of the editors that this Formulary is
perceived as a readily accessible, easily understandable, up-to-date source of independent
medicine information. Nevertheless, this Formulary should be supplemented, where
necessary, by more recent and comprehensive materials and publications.

Moreover, the recommendations incorporated into this Formulary are intended to

serve only as guides that will supplement and not replace the best clinical judgment of the
prescribing clinicians. Readers are enjoined to confirm the information contained herein with
other sources, particularly with regard to new or the latest updates.

ISBN 978-621-95540-3-9

All rights reserved 2019

The Formulary Executive Council

Pharmaceutical Division, Health Regulation Team

Published by:
Department of Health
San Lazaro Compound, Rizal Ave., Sta. Cruz, Manila, Philippines, 1003

Any part or the whole book may be reproduced or transmitted without any alteration, in any form
or by any means, with permission from DOH provided it is not sold commercially.
THE PHILIPPINE NATIONAL FORMULARY
8th Edition
2019

DEPARTMENT OF HEALTH

FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health

ROLANDO ENRIQUE D. DOMINGO, MD, DPBO

Undersecretary of Health
Health Regulation Team

ANNA MELISSA S. GUERRERO, MD, MPH (HTA)

Chief
Pharmaceutical Division

FORMULARY EXECUTIVE COUNCIL

Froilan A. Bagabaldo, RPh, Ll.B.
Cleotilde H. How, MD, FPSECP, FPPS
Cecilia A. Jimeno, MD, FPCP, FPSEDM
Cecilia C. Maramba-Lazarte, MD, MScID, MScCT, FPPS, FPIDSP,
FPSECP
Paul Matthew Pasco, MD, FPNA
Imelda G. Peña, RPh, MS, DrPH
John Q. Wong, MD, MSc
THE PHILIPPINE NATIONAL FORMULARY
8th Edition
2019

EDITORIAL TEAM
Yolanda R. Robles, RPh, MPharm, PhD
Shiela Mae J. Nacabu-an, RPh, MHPEd
Christine Aileen C. Benosa, RPh, MPH
Ian Theodore G. Cabaluna, RPh, MD GDip (Epi)
Editors

Jeanne Genevive A. Pillejera, RPh

Associate Editor

Joshua Elijah M. Chavez, RPh

Ena Elizabeth L. Naoe, RPh
Kristel Keith N. Nieva, RPh
Frances Lois U. Ngo
Jarvin Enosh T. Tan, RPh
Rose Charisse L. Traballo, RPh
Ryan Joseph C. Tuzon
Mikaella B. Santos
Martha O. de la Paz
Arizaldo E. Castro, MSc
Leo Miguel S. Vergeire
Technical Writers

Irene V. Florentino-Fariñas, RPh, MD, MNSA

Joyce Anne D. Ceria-Pereña, RPh, MPM
Johanna B. Mallari, RPh
Kate D. Dunlao, RPh
April Rose B. Macandog, RPh
Members of the Editorial Team

John Michael L. Roque

Technical Assistant
 CONTRIBUTORS

DOH Disease Prevention and Control Bureau

DOH Family Health Office

National Antiobiotic Guidelines Committee

National Center for Mental Health

Rodney Ribleza Boncajes, MD

National Kidney and Transplant Institute

Jean Anne B. Toral, MD, MSc
Lynn B. Bonifacio, MD
Chrystal Catli Burog, MD
Teresita Dumagay, MD
Roxan Perez, MD

National Poison Management and Control Center

Pediatric Infectious Disease Society of the Philippines

Philippine Academy of Ophthalmology

Philippine Academy of Pediatric Pulmonologists

Philippine Children’s Medical Center

Marilou A. Abrera, MD
Cecilia Cruz, MD

Philippine College of Chest Physicians

Philippine College of Geriatric Medicine

Philippine College of Radiology

Philippine Dermatological Society

Philippine Heart Association

Philippine Heart Center

Maria Teresa B. Abola, MD
Eden A. Gabriel, MD
 Philippine Neurological Association

Philippine Obstetrical and Gynecological Society

Philippine Orthopaedic Association

Philippine Psychiatric Association

Philippine Rheumatology Association

Philippine Society of Allergy, Asthma and Immunology, Inc.

Philippine Society of Anesthesiologists, Inc.

Angel M. Gomez, MD

Philippine Society of Endocrinology, Diabetes and Metabolism

Philippine Society of Gastroenterology

Philippine Society of Hematology and Blood Transfusion

Philippine Society of Medical Oncology

Mary Claire V. Soliman, MD, FPCP, FPSMO
Marcelo Severino B. Imasa, MD, FPCP

Philippine Society for Microbiology and Infectious Diseases

Philippine Society of Nephrology

Philippine Society of Newborn Medicine

Philippine Society of Otolaryngology, Head and Neck Surgery

Philippine Society of Parenteral and Enteral Nutrition

Philippine Society of Pediatric Metabolism and Endocrinology

Philippine Society of Pediatric Oncology

Philippine Urological Association

Stroke Society of the Philippines

 Department of Health - Office of the Secretary

Message

The revitalization of the Fourmula One Plus for Health as the framework of the
healthcare reform agenda of the national government is anchored on the values of
equitable and inclusive health system, transparent and accountable provision of
quality health services, and efficient use of resources.

The 8th edition of the Philippine National Formulary (PNF) is a tool to exercise
these values while contributing to the achievement of the objectives of financial
protection and better health outcomes.

Its previous editions have been the basis of tailored procurement of medicines in
public health facilities while providing efficient use of limited resources. It is also the
basis of the Philippine Health Insurance Corporation (PhilHealth) in reimbursing
claims to end-users for medicines use.

With its new format and content, the PNF 8th edition can now maximize the PNF’s
contribution to the rational use of medicines. Its abridged content is intended to
provide concise evidence-based drug information which is vital in medical practice.

The latest PNF is a useful tool to ensure rational prescribing, dispensing, and
administration of medicines. I would like to encourage our health professionals to fully
utilize it in their medicines procurement as well as in their day-to-day clinical decision-
making.

Let us continue to work for our shared vision of all for health towards health for all!

Mabuhay!

FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health
 Department of Health – Health Regulation Team

Message

Greetings!

The Philippine National Formulary (PNF) plays a vital role in promoting the rational
use of medicines in the country. As mandated by Republic Act 9502, otherwise known
as the “Universally Accessible Cheaper and Quality Medicines Act of 2008,” and in
accordance with Republic Act 9184, also known as “Government Procurement
Reform Act,” the PNF serves as the basis of procurement of medicines in all
government agencies, including government units.

PNF requires continuous revisions and updating to ensure its relevance. It is part
of the important role of the Department of Health (DOH) in regulating health products
and services and providing technical assistance to health providers and stakeholders.
While the FDA ensures that only quality medicines are available in the market, the
PNF helps assure that only safe, effective, and affordable medicines are procured by
public health facilities.

The 8th edition of the PNF includes critical revisions that would facilitate the work
of physicians, nurses, pharmacists, and other healthcare professionals. Thus, in
behalf of the DOH, particularly the Health Regulation Team, I would like to commend
the movers behind the PNF in promoting rational prescribing, dispensing, and use of
medicines. Their valuable efforts in revising the National Formulary enable the country
to ACHIEVE better health outcomes.

Congratulations!

ROLANDO ENRIQUE D. DOMINGO, MD, DPBO

Undersecretary of Health
Health Regulation Team
 ACKNOWLEDGMENTS

This Formulary is adapted from the World Health Organization (WHO) Model
Formulary (2008) with the publisher’s permission. We acknowledge, with sincere
thanks, the work of the WHO in producing the Model Formulary so that countries and
organizations can compile and produce their own national formularies.

For their invaluable contribution to the current edition of the Philippine National
Formulary (PNF), sincere gratitude is also due to the following:

Members of the Formulary Executive Council (FEC) who thoroughly reviewed the
list of essential medicines and the Formulary monographs: Atty. Froilan Bagabaldo,
Dr. Cleotilde H. How, Dr. Cecilia A. Jimeno, Dr. Hilton Y. Lam, Dr, Cecilia C. Maramba-
Lazarte, Dr, Paul Matthew Pasco, Dr. Imelda G. Peña, and Dr. John Q. Wong;

Hospitals who participated in the pilot run of the formulary: Philippine Children’s
Medical Center, Philippine Heart Center, Lung Center of the Philippines, National
Kidney and Transplant Institute, Luis Hora Memorial Regional Hospital, Bicol Medical
Center, and San Lazaro Hospital; and

All the experts from the national health programs (NHA), specialty hospitals, and
professional medical societies who participated in the review of the content of the
Formulary and provided valuable and indispensable comments and corrections.
 TABLE OF CONTENTS
GENERAL GUIDE ON THE USE OF THIS FORMULARY ......................................................................................... i
MEDICINE MONOGRAPH KEY ............................................................................................................................ ii
FDA PREGNANCY RISK CATEGORIES .................................................................................................................. iii
SYMBOLS AND ABBREVIATIONS ........................................................................................................................ iv
GENERAL GUIDE TO PRESCRIBING
A. RATIONAL APPROACH TO THERAPEUTICS ............................................................................................. v
B. VARIATION IN DOSE RESPONSE
1. PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES ................................................................. vii
2. MEDICINE DISTRIBUTION ................................................................................................................ ix
3. MEDICINE METABOLISM AND EXCRETION ................................................................................... ix
4. PHARMACODYNAMIC VARIABLES ................................................................................................... ix
5. DISEASE VARIABLES ........................................................................................................................ ix
6. ENVIRONMENTAL VARIABLES ......................................................................................................... x
C. ADHERENCE TO (COMPLIANCE WITH) MEDICINE TREATMENT .............................................................. x
1. PATIENT-RELATED REASONS .......................................................................................................... x
2. DISEASE-RELATED REASONS ......................................................................................................... xi
3. DOCTOR-RELATED REASONS .......................................................................................................... xi
4. THE DOCTOR-PATIENT INTERACTION ............................................................................................. xi
5. PRESCRIPTION-RELATED REASONS .............................................................................................. xi
6. PHARMACIST-RELATED REASONS ................................................................................................. xi
7. RECOMMENDATIONS TO THE PRESCRIBERS ............................................................................... xi
D. ADVERSE EFFECTS
1. ADVERSE DRUG REACTIONS (ADR) ................................................................................................ xii
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS ............................................................ xii
E. PRESCRIPTION WRITING
1. PRESCRIPTION FORM ....................................................................................................................... xiii
2. INCORRECT PRESCRIPTIONS .......................................................................................................... xiv
3. NARCOTICS AND CONTROLLED SUBSTANCES .............................................................................. xiv
F. PATIENT COUNSELING ............................................................................................................................... xv
1. WHAT TO COUNSEL ......................................................................................................................... xv
2. WHO AND WHEN TO COUNSEL ....................................................................................................... xv
3. COUNSELING: PROCESS STEPS ..................................................................................................... xvi
ANTIMICROBIAL RESISTANCE ............................................................................................................................. xvii

MEDICINE AND THERAPEUTIC INFORMATION

A – ALIMENTARY TRACT AND METABOLISM 1
DRUGS FOR ACID RELATED DISORDERS ................................................................................................... 1
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS .................................................................. 8
ANTIEMETICS AND ANTINAUSEANTS ......................................................................................................... 11
BILE AND LIVER THERAPY .......................................................................................................................... 13
DRUGS FOR CONSTIPATION ....................................................................................................................... 14
ANTIDIARRHEALS, INTESTINAL ANTIINFLAMMATORY/ANTIINFECTIVE AGENTS .................................... 17
DRUGS USED IN DIABETES ........................................................................................................................ 22
VITAMINS ..................................................................................................................................................... 26
MINERAL SUPPLEMENTS ........................................................................................................................... 33
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS ................................................................... 41
B – BLOOD AND BLOOD FORMING ORGANS 43
ANTITHROMBOTIC AGENTS ........................................................................................................................ 43
ANTIHEMORRHAGICS ................................................................................................................................. 57
ANTIANEMIC PREPARATIONS ..................................................................................................................... 61
BLOOD SUBSTITUTES AND PERFUSION SOLUTIONS ............................................................................... 66
C – CARDIOVASCULAR SYSTEM 94
CARDIAC THERAPY ...................................................................................................................................... 94
AGENTS ACTING ON ARTERIOLAR SMOOTH MUSCLE............................................................................... 112
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM......................................................................... 115
BETA-BLOCKING AGENTS............................................................................................................................ 124
CALCIUM CHANNEL BLOCKERS ................................................................................................................. 129
CENTRALLY ACTING ANTIADRENERGIC AGENTS....................................................................................... 139
DIURETICS.................................................................................................................................................... 140
 LIPID MODIFYING AGENTS ......................................................................................................................... 148
D – DERMATOLOGICALS 152
ANTIFUNGALS FOR DERMATOLOGICAL USE ............................................................................................. 152
EMOLLIENTS AND PROTECTIVES ............................................................................................................... 156
ANTIPRURITICS, INCLUDING ANTIHISTAMINES, ANESTHETICS, ETC. ...................................................... 156
ANTIPSORIATICS ......................................................................................................................................... 156
ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE ............................................... 158
CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS ........................................................................ 160
ANTISEPTICS AND DISINFECTANTS ........................................................................................................... 162
ANTI-ACNE PREPARATIONS ........................................................................................................................ 165
G – GENITO URINARY SYSTEM AND SEX HORMONES 167
ANTIINFECTIVES AND ANTISEPTICS, EXCLUDING COMBINATIONS WITH CORTICOSTEROIDS ...... ……. 167
OTHER GYNECOLOGICALS ........................................................................................................................ 167
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM ............................................................. 170
UROLOGICALS ............................................................................................................................................. 184
H – SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS 187
PITUTARY AND HYPOTHALAMIC HORMONES AND ANALOGUES .............................................................. 187
CORTICOSTEROIDS FOR SYSTEMIC USE ................................................................................................... 189
THYROID THERAPY ...................................................................................................................................... 197
J – ANTIINFECTIVES FOR SYSTEMIC USE 202
ANTIBACTERIALS FOR SYSTEMIC USE ....................................................................................................... 202
ANTIFUNGALS FOR SYSTEMIC USE ............................................................................................................ 250
ANTIMYCOBACTERIALS .............................................................................................................................. 255
ANTIVIRALS FOR SYSTEMIC USE ................................................................................................................ 266
IMMUNE SERA AND IMMUNOGLOBULINS ............................................................................................... 280
VACCINES .................................................................................................................................................... 287
L – ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 312
ANTINEOPLASTIC AGENTS ........................................................................................................................ 312
ENDOCRINE THERAPY ................................................................................................................................ 366
IMMUNOSTIMULANTS ................................................................................................................................ 374
IMMUNOSUPPRESSANTS ........................................................................................................................... 381
M – MUSCULO-SKELETAL SYSTEM 397
ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS ......................................................................... 397
MUSCLE RELAXANTS .................................................................................................................................. 406
ANTIGOUT PREPARATIONS ......................................................................................................................... 415
DRUGS FOR TREATMENT OF BONE DISEASE ............................................................................................ 417
OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM............................................... 420
N – NERVOUS SYSTEM 424
ANESTHETICS .............................................................................................................................................. 424
ANALGESICS ................................................................................................................................................ 438
ANTIEPILEPTICS .......................................................................................................................................... 465
ANTI-PARKINSON DRUGS ........................................................................................................................... 481
PSYCHOLEPTICS ......................................................................................................................................... 487
PSYCHOANALEPTICS .................................................................................................................................. 519
OTHER NERVOUS SYSTEM DRUGS ............................................................................................................ 529
P – ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS 540
ANTIPROTOZOALS ....................................................................................................................................... 540
ANTHELMINTICS ......................................................................................................................................... 548
ECTOPARASITICIDES, INCLUDING SCABICIDES, INSECTICIDES, AND REPELLENTS .............................. 551
R – RESPIRATORY SYSTEM 553
NASAL PREPARATIONS ............................................................................................................................... 553
THROAT PREPARATIONS ............................................................................................................................ 554
DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES ......................................................................................... 555
COUGH AND COLD PREPARATIONS ........................................................................................................... 571
ANTIHISTAMINES FOR SYSTEMIC USE ...................................................................................................... 572
OTHER RESPIRATORY SYSTEM PRODUCTS ............................................................................................. 575
S – SENSORY ORGANS 579
OPHTHALMOLOGICALS .............................................................................................................................. 579
OTOLOGICALS ............................................................................................................................................. 601
EAR, NOSE, AND THROAT PREPARATIONS ................................................................................................ 603
V – VARIOUS 605
ALL OTHER THERAPEUTIC PRODUCTS ...................................................................................................... 605
DIAGNOSTIC AGENTS ................................................................................................................................ 631
 GENERAL NUTRIENTS ................................................................................................................................. 633
CONTRAST MEDIA ....................................................................................................................................... 640
DIAGNOSTIC RADIOPHARMACEUTICALS ................................................................................................... 650
THERAPEUTIC RADIOPHARMACEUTICALS ................................................................................................. 651
X – HERBAL PREPARATIONS 653

APPENDICES
SUMMARY STATISTICS .............................................................................................................................. A1
LIST OF DRUG MOLECULES ADDED TO THE PNF 8TH EDITION................................................................ A2
LIST OF DRUG MOLECULES DELETED FROM THE PNF 7th EDITION....................................................... A4
LIST OF ESSENTIAL MEDICINES INCLUDED IN THE PNF BUT NOT REGISTERED WITH THE FDA .......... A6
LIST OF DANGEROUS DRUG PREPARATIONS INCLUDED IN THE PNF.................................................... A9
LIST OF CONTROLLED CHEMICALS INCLUDED IN THE PNF.................................................................... A10
LIST OF ESSENTIAL MEDICINES WITH NARROW THERAPEUTIC RANGE................................................. A11
LIST OF RESTRICTED ANTIMICROBIALS ................................................................................................... A12
LIST OF MEDICINAL PLANT PRODUCTS REGISTERED WITH THE FDA AND INCLUDED IN THE PNF A13
DEFINITION OF DOSAGE FORMS .............................................................................................................. A14
FDA ADVERSE DRUG REACTION (ADR) REPORTING FORM ...................................................................... A17

DIRECTORY ........................................................................................................................................................... A20

REFERENCES ........................................................................................................................................................ A22
ISSUANCES ........................................................................................................................................................... A26
INDEX .................................................................................................................................................................... A93
GENERAL
GUIDANCE
 GENERAL GUIDANCE
ON THE USE OF THIS FORMULARY

The Philippine National Formulary 8th Edition allows healthcare practitioners – physicians,
dentists, pharmacists, nurses, and other allied healthcare professionals – to find important
medicine information to guide them in the rational use of medicines.

In this new edition of the PNF, the essential medicines list and monographs have been
integrated into a single manual. The medicines are arranged using the Anatomical Therapeutic
Chemical (ATC) Classification System. Medicines with more than one therapeutic indication
appear in more than one category. Each monograph consists of:

• Generic Name
• Dosage Form/Strength
• Indications
• Contraindications
• Dosage (weight and/or age-specific dosage recommendations)
• Dose Adjustments (for patients with renal or hepatic disease; or the elderly patients)
• Precautions/Warnings
• Adverse Drug Reactions
• Drug Interactions
• Administration Guide
• Pregnancy Category
• ATC Code

The therapeutic information in this Formulary have been adapted from various current and
comprehensive references (refer to Appendix M. This edition also followed and adapted previously
approved format and contents of the Philippine National Formulary Manual for Primary Healthcare.

i
 MEDICINE MONOGRAPH KEY
The medicine monograph key summarizes and describes the types of information contained
in this edition that the physicians and dentists can utilize in prescribing medicines for their
patients. This key also shows the format of how the prescribing information is arranged.

GENERIC NAME

DOSAGE FORM/STRENGTH

INDICATION/S: This section only includes Philippine FDA-approved indications. In addition, the
indications listed for the Anti-Infective Agents are restricted to those included in the most current
local clinical practice guidelines that were made available to the editors and/or the latest
published recommendations of the Philippine Antimicrobial Resistance Surveillance Program
(ARSP).

CONTRAINDICATION/S: This section details disease states where and patient populations for
whom the medicine should not be used.

DOSE: This section lists dosages of the medicines for adult, child and elderly patients, if
specified, as indicated in the official FDA-approved labeling and/or other main references.

DOSE ADJUSTMENT/S: This section gives dosage adjustment recommendations for the elderly,
or for patients with renal or hepatic impairment.

PRECAUTIONS: This section details (1) harmful conditions related to the use of the medicine
(e.g., exacerbations, increased risk of adverse effects), and (2) disease states or patient
populations where caution is advised. This may also include precautions for breastfeeding
mothers and nursing infants. Black Box Warnings are included.

ADVERSE DRUG REACTIONS: This section denotes side effects and adverse drug reactions
(ADRs) listed in the official FDA-approved labeling. Only Common ADRs are listed in this
Formulary. A complete listing of ADRs can be viewed on the online copy of the formulary.

DRUG INTERACTION/S: This section includes the effects and implications of the concomitant
administration of different medicines, or their use together with food.

ADMINISTRATION: This section lists recommendations on the proper intake or administration of

the medicines.

PREGNANCY CATEGORY: This section is based on the US FDA Pregnancy Risk Categories.

ATC CODE: This section is based on the WHO ATC/DDD Index 2016. (WHO Collaborating Centre
for Drug Statistics Methodology).

ii
 US FDA PREGNANCY RISK CATEGORIES
The FDA-assigned pregnancy categories as used in the Drug Formulary are as follows:

Category Interpretation

A CONTROLLED STUDIES SHOW NO RISK.

Adequate and well-controlled studies in pregnant women have failed to

demonstrate a risk to the fetus in the first trimester of pregnancy (and there
is no evidence of risk in later trimesters).

B NO EVIDENCE OF RISK IN HUMANS.

Animal reproduction studies have failed to demonstrate a risk to the fetus and
there are no adequate and well-controlled studies in pregnant women.

C RISK CANNOT BE RULED OUT.

Animal reproduction studies have shown an adverse effect on the fetus and
there are no adequate and well-controlled studies in humans, but potential
benefits may warrant use of the drug in pregnant women despite potential
risks.

D POTENTIAL EVIDENCE OF RISK.

There is positive evidence of human fetal risk based on adverse reaction

data from investigational or marketing experience or studies in humans, but
potential benefits may warrant use of the drug in pregnant women despite
potential risks.

X CONTRAINDICATED IN PREGNANCY.

Studies in animals or humans have demonstrated fetal abnormalities

and/or there is positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience, and the risks
involved in the use of the drug in pregnant women clearly outweigh potential
benefits.

iii
 SYMBOLS AND ABBREVIATIONS
ACE - Angiotensin-converting (IM) - Intramuscular
enzyme Inj. - Injection
ADR - Adverse drug reaction INR - International Normalized
AIDS - Acquired Ratio
Immunodeficiency IU - International Unit(s)
Syndrome (IV) - Intravenous
a.m. - Morning; before noon L - Liter
Amp - Ampule LA - Long-Acting
AV - Atrioventricular lin. - Liniment
BCG - Bacille Calmette-Guérin lot. - Lotion
BP - Blood pressure MAOI - Monoamine Oxidase
BSA - Body surface area Inhibitor
cap., caps - Capsule(s) MDI - Metered Dose Inhaler
CNS - Central Nervous System MDR-TB - Multidrug-resistant
comp. - Compound tuberculosis
cr., crm. - Cream mEq - Milliequivalent
CR - Controlled-release Mg - Milligram
CSF - Cerebrospinal fluid mL - Milliliter
D5NS - Glucose (dextrose) 5% in Mmol - Millimole
normal saline (0.9%) MR - Modified release
D5W - Glucose (dextrose) 5% [includes CR, ER, SR, LA]
solution nebul. - Spray
DOTS - Directly observed NSAID - Non-steroidal Anti-
treatment, short-course Inflammatory Drugs
DMARD - Disease modifying agents p.m. - Afternoon / Evening
in rheumatoid disorders RE - Retinol Equivalent
DPI - Dry powder inhaler Resp. Soln. - Respiratory Solution
EC - Enteric-coated Rx - Prescription
ECG - Electrocardiogram (SC) - Subcutaneous
emuls. - Emulsion (SL) - Sublingual; under the
EPS - Extrapyramidal syndrome tongue
ER - Extended Release sig. - Signa / write on label
FC - Film-coated Soln. - Solution
G - Gram spp. - Species
GFR - Glomerular Filtration Rate SR - Sustained Release
GI - Gastrointestinal SSRI - Selective Serotonin
gtt(s) - Drop(s) Reuptake Inhibitor
h, hr. - Hour supp. - Suppository
HAI - Hospital-Acquired susp. - Suspension
Infections syr. - Syrup
HIV - Human tab., tabs. - Tablet(s)
Immunodeficiency Virus TB - Tuberculosis
HRT - Hormone Replacement top. - Topical
Therapy XDR-TB - Extensively Drug-resistant
(ID) - Intradermal Tuberculosis

iv
 GENERAL GUIDE TO PRESCRIBING

A RATIONAL APPROACH TO THERAPEUTICS

Rational use of medicines (RUM) is the fundamental concept where patients receive
medicines, when these are needed, that are appropriate for the clinical needs, in doses
that meet the individual requirements, for an adequate period of time, at the lowest
possible cost, and administered correctly by the right person.

The problem of irrational use of medicines concerns the following:

a. This is one of the most critical causes of unsuccessful treatment outcomes, health
hazards that include antimicrobial resistance (AMR), wastage of resources, and
increased health costs.
b. Worldwide, 50% of medicines are prescribed, dispensed or sold inappropriately;
moreover, half of the patient population fails to take them correctly.
c. In the Philippines, many irrational practices are prevalent such as rationing (often
termed as “diby-diby”), prescribing of inappropriate alternative medicines, “shotgun”
therapy, misuse and overuse of antibiotics, dispensing of antibiotics without a
prescription, self-medication, buying medicines piecemeal (“tingi”), and failure to
complete treatment.
d. The problems that underlie the irrational practices are far-reaching and include
inadequate supplies of medicines that are in turn due to the sheer number of patients
coming for consultation, the lack of funds or poor support from the government
officials, poverty, inherent limitations of the National Formulary, anomalous
transactions, geographical isolation and poor health literacy of patients and even
some health care providers.

The solutions for many of the causes of irrational practices are often beyond the
control of the physicians. However, the physicians, as stewards of the people’s health,
must lead by example the efforts to adhere faithfully to the principles of RUM. The
basic tenets of RUM include:
a. Prescribing medicines only when these are necessary;
b. Prescribing appropriately; and,
c. Considering the benefits of administering medicines in relation to the risks
involved.

The key points of the systematic processes that will assist in determining the proper
treatment are:
a. Defining the patient’s problem;
b. Specifying the therapeutic objective; and,
c. Selecting the therapeutic strategy.

The selected strategy for achieving a health outcome should be agreed upon
with the patient. The total costs for all therapeutic options should be considered.
Strategies can either be non-pharmacologic and/or pharmacologic.
1) Non-pharmacologic Treatment
This implies that patients do not always need medicine for the treatment
of their conditions. This includes changes in lifestyle or diet, use of
physiotherapy or exercise, provision of adequate psychological support,
and other non-pharmacologic treatments. This is of equal importance as
prescription medicines; instructions for such treatments must be written,
explained, and monitored in the same way.

v
 2) Pharmacologic Treatment
a) Selecting the correct group of medicines:
There are two fundamental principles for rational therapeutics:
i. Knowledge about the pathophysiology involved in the clinical
situation of each patient
ii. Pharmacodynamics of the chosen group of medicines

b) Verifying the suitability of the chosen pharmaceutical treatment:

i. Is the active substance chosen suitable for the patient?
ii. Is the dosage form suitable for the patient?
iii. Is the standard dosage schedule suitable for the patient?
iv. Is the standard duration of treatment suitable for the patient?

c) Prescription Writing:
i. This serves as the link between the prescriber, the pharmacist (or
dispenser), and the patient.
ii. This is vital to the successful management of presenting
medical conditions (see detailed Prescription Writing below).
iii. In the Philippines, only validly registered medical doctors and
dentists (as well as veterinarians) are allowed to prescribe.

d) Giving information, instructions, and warnings:

This is essential in ensuring patient adherence.

e) Monitoring treatment:
i. The evaluation of the follow-up and the outcome of treatment
allows for possible termination of treatment (if the patient’s
problem is solved), or its reformulation when necessary.
ii. This step gives rise to important information about the effects
of medicines, contributing to the pool of knowledge on
pharmacovigilance; that in turn is needed to promote the
rational use of medicines.

B VARIATION IN DOSE-RESPONSE
Correct dose regimen is necessary for the success in medicine treatment. The use of
standard doses in the marketing literature suggests that standard responses are the rule,
but in reality there is considerable variation in medicine response. The reasons for the
variation include: adherence (see Adherence with Medicine Treatment), medicine
formulation, body weight and age, composition, variation in medicine absorption,
distribution, metabolism, and excretion, variation in pharmacodynamics, disease variables,
and genetic and environmental variables.

MEDICINE FORMULATION
a. Poorly formulated medicines may fail to disintegrate or to dissolve.
b. Enteric-coated medicines may pass through the GI tract intact. Changes in
absorption can produce sudden changes in medicine concentrations of
medicines with a narrow therapeutic-to-toxic ratio.
For such medicines, quality control surveillance should be carried out.

BODY WEIGHT AND AGE

Although the concept of varying the dose with the body weight or age of children
has long been a tradition, adult doses have been assumed to be the same irrespective
of size or shape. However, adult weights vary 2- to 3-folds. Furthermore, a patient with
vi
 a large fat mass can store large excesses of highly lipid-soluble medicines compared
with a lean patient of the same weight.

Age can also be important. Adolescents may metabolize some medicines relatively
more rapidly than adults, while the elderly may have reduced renal function and
eliminate some medicines more slowly.

DOSE CALCULATION IN CHILDREN

Many children’s doses are standardized by weight (and therefore require multiplying
by the body-weight in kilograms to determine the child’s dose). Occasionally, the
doses have been standardized by body surface area (BSA) in m2.

To calculate a child’s medication based on BSA, use the formula:

child′ s BSA
× adult dose = child′ s dose
1.73
with the BSA computed as follows:
W × H
A = �
3600
where:
A – patient’s BSA (m2)
W – patient’s weight in kg
H – patient’s height in cm
3600 – conversion / correction factor (kg/m2)

If the weight is expressed in pounds (lbs) and the height in inches (in):

W × H
A = �
3131

o Young children may require a higher dose for each kilogram than adults because
of their faster metabolic rates.
o Calculation by body weight in an overweight child may result in higher than
necessary doses being administered. In such cases, doses should be calculated
using an ideal weight, related to height and age.
o Nomograms can also be used to calculate body surface values based on a
child’s height and weight.
o Where the dose for children is not readily available, prescribers should seek
specialist advice before prescribing for a child.

PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES

a. Pharmacokinetics
This area of study deals with changes of concentration in the drug product, or in a drug
and its metabolites, in the body, after it has been administered. This includes the time
course of drug absorption, distribution, metabolism, and elimination.
A basic understanding of the factors which control drug concentration at the site of
action (e.g., bioavailability, area under the curve, and half-life) is important for the
optimal use of drugs.
1) Bioavailability
This refers to the amount of medicine from an administered dosage form which
enters the systemic circulation, and the rate at which it appears in the bloodstream.
Changes in a drug’s bioavailability may be thought of in terms of changes in

vii
 exposure to the drug which, if substantial, can relate to safety and efficacy
concerns.

2) Bioequivalence
This indicates that a drug in two or more similar dosage forms reaches the
general circulation at the same relative rate and the same relative extent (i.e.,
that the plasma level profiles of the drug obtained using the two dosage forms
are the same).
This is an important consideration in several key situations involving lot-to-lot
consistency, innovator to generic product therapeutic equivalence, and
situations where a marketed product undergoes changes in certain aspects
(formulation, manufacturing process, and dosage strength).

3) Half-life
This indicates the time required to reduce the amount of medicine in the body
or the plasma concentration by 50%.
This is a clinically useful pharmacokinetic parameter because this indicates
when the next dose of a medicine needs to be administered, and thus helpful
in determining an optimal dosing regimen.

b. Medicine absorption rates may vary widely among individuals and in the same individual
at different times and in different physiological states.
Medicines taken after a meal are delivered to the small intestine more slowly than in
the fasting state, leading to much lower medicine concentrations. In pregnancy, gastric
emptying is also delayed, while some medicines may increase or decrease gastric
emptying, and affect absorption of other medicines.

MEDICINE DISTRIBUTION
a. Fat-soluble medicines (vitamins A, D, E, and K) are stored in adipose tissues.
b. Water-soluble medicines are distributed chiefly in the extracellular space.
c. Acidic medicines bind strongly to plasma albumin.
d. Basic medicines go to muscle cells.
e. Hence, variations in plasma albumin concentration, fat content, or muscle mass may
all contribute to dose variation.

MEDICINE METABOLISM AND EXCRETION

a. Medicine metabolism is affected by genetic, environmental, and disease-state
factors.
b. Medicine acetylation shows genetic polymorphism, where individuals fall clearly into either
fast or slow acetylator types. This means that some patients can metabolize medicines
more rapidly (fast acetylators) than the others (slow acetylators).
c. Medicine oxidation, however, is polygenic.
Although a small proportion of the population can be classified as very slow
oxidizers of some medicines, there is a normal distribution of medicine-
metabolizing capacity for most medicines and most subjects.
d. Many medicines are eliminated by the kidneys without being metabolized.
e. Renal disease or toxicity of some medicines on the kidney can slow excretion of some
medicines.
f. Hepatic disease or toxicity of some medicines on the liver can slow excretion of some
medicines.

viii
PHARMACODYNAMIC VARIABLES
Significant variations in receptor response to some medicines (especially CNS
responses, such as pain and sedation) are attributed to genetic factors, tolerance,
medicine interactions, and medicine dependence.

DISEASE VARIABLES
a. Both liver and kidney diseases can have major effects on metabolism and elimination,
respectively (resulting in increasing toxicity), but also through effects on plasma
albumin (resulting in increasing free medicine and thus toxicity).
b. Heart failure can also affect metabolism of medicines with rapid hepatic clearance
(e.g., lidocaine).
c. Respiratory disease and hypothyroidism can impair oxidation of drugs.

ENVIRONMENTAL VARIABLES
a. Many medicines and environmental toxins can induce the hepatic microsomal
enzyme oxidizing system or cytochrome P450 oxygenases, leading to more rapid
metabolism and elimination, and thus less effective treatment.
b. Environmental pollutants, anesthetic medicines, and other compounds, such as
pesticides, can also induce metabolism.
c. Diet and nutritional status also affect pharmacokinetics:
1) In malnourished infantile and elderly populations, medicine oxidation rates are
decreased.
2) High protein diets, charcoal-cooked foods, and certain other foods act as
metabolizing enzyme inducers.
3) Chronic alcohol use induces oxidation of some medicines; but in the presence
of high circulating alcohol concentrations, medicine metabolism may be
inhibited.

C ADHERENCE TO (COMPLIANCE WITH) MEDICINE TREATMENT

One of the most important reasons for treatment failure is poor adherence to
(compliance with) the treatment plan.

Reasons for non-compliance may be related to: (1) the patient, (2) the disease, (3) the
doctor, (4) the prescription, (5) the pharmacist, or (6) the health system.
o For instance, patients' perceptions of the risk and severity of adverse drug
reactions may differ from those of the healthcare provider and may affect
adherence.
o Poor prescribing or a dispensing error may also create a problem, which patients
may have neither the insight nor the courage to question. Even with good
prescribing though, failure to adhere to treatment is common.

Valid reasons for poor adherence include the ff.: the medicine may be poorly tolerated,
may cause obvious adverse effects, or may be prescribed in a toxic dose. Failure to adhere
with such a prescription has been described as “intelligent non-compliance”.

Low-cost strategies for improving adherence increase effectiveness of health

interventions and reduce costs. Such strategies must be tailored to the individual patient.
Healthcare providers should be familiar with techniques for improving adherence and they
should employ systems to assess adherence and to determine what influences it.

ix
 1. PATIENT-RELATED REASONS
a. Women tend to be more adherent than men.
b. Younger patients and the very elderly tend to be less adherent.
c. People living alone are less adherent than those living with partners or spouses.
d. Specific education interventions have been reported and shown to improve
adherence and compliance.
e. Some patient disadvantages include illiteracy, poor eyesight, or cultural
attitudes, which includes preference for traditional or alternative medicines, and
distrust of modern medicines.
f. Economic factors affect patient adherence, compliance and maintenance.

2. DISEASE-RELATED REASONS
Conditions with a known worse prognosis (e.g., cancer) or painful conditions (e.g.,
rheumatoid arthritis) elicit better adherence than asymptomatic “perceived as
benign” conditions such as hypertension.

3. DOCTOR-RELATED REASONS
a. Failure to inspire confidence in the treatment offered
b. Little or no explanation provided
c. Too many medicines prescribed
d. Errors in prescribing
e. Overall attitude to the patient

4. THE DOCTOR-PATIENT INTERACTION

a. Quality of the doctor–patient interaction is crucial to adherence and compliance.
b. “Satisfaction with the interview” is one of the best predictors of good adherence.
c. If they are in doubt or dissatisfied, they may turn to alternative options, including
complementary medicine.

5. PRESCRIPTION-RELATED REASONS
a. Illegible or inaccurate prescriptions may discourage patients to adhere to
medications.
b. Lost prescriptions may delay patients to start or continue medications.
c. Prescriptions not refilled as intended or instructed for a chronic disease may
reduce maintenance.
d. Too complex prescriptions (greater number of different medicines, poorer
adherence).
e. Multiple doses decrease adherence and compliance especially if more than two
doses per day are given.
f. Adverse effects, like drowsiness, impotence, or nausea, reduce adherence.

6. PHARMACIST-RELATED REASONS
a. Manner and professionalism
b. Pharmacist information and counseling can serve as a valuable reinforcement,
as long as they agree with the physician’s advice.

7. RECOMMENDATIONS TO THE PRESCRIBERS

a. Review the prescription to make sure it is correct.
b. Spend time explaining the health problem and the reason for the medicine.
c. Establish good rapport with the patient.
d. Explore problems, such as difficulty with reading the label or getting the
prescription filled.
x
 e. Encourage patients to bring their medication to the clinic so that tablet counts
can be done to monitor compliance.
f. Encourage patients to learn the names of their medicines, and review their
regimen with them. Write notes for them.
g. Keep treatment regimens simple.
h. Communicate with other healthcare professionals to develop a team approach
and to collaborate on helping and advising the patient.
i. Involve the partner or another family member.
j. Listen to the patient.

D ADVERSE EFFECTS AND INTERACTIONS

1. ADVERSE DRUG REACTIONS (ADR)
Any response to a medicine which is noxious, unintended and occurs at doses
normally used for prophylaxis, diagnosis, or therapy. These reactions are different
from accidental OR deliberate excessive dosage or medicine maladministration.

2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS

a. EXTREMES OF AGE
1) The very old and the very young populations are more susceptible to ADRs.
Examples of which are: hypnotics, antihypertensives, Non-Steroidal Anti-
inflammatory Drugs (NSAIDs), psychotropics, diuretics, and digoxin.
2) All children, particularly neonates, differ from adults in their response to
medicines.
Some medicines are likely to cause problems in
o Neonates, but are generally tolerated in children
o Children of all ages, who are at increased risk of ADRs for
other medicines

b. INTERCURRENT ILLNESSES/COMORBIDITIES
This occurs when a patient suffers from another disease aside from the
current condition being treated (kidney, liver or heart disease). The genetic
make-up of the individual patient plays a role.

c. MEDICINE INTERACTIONS
These may occur among medicines which compete for the same receptor, or
which act on the same physiological system.
1) These may occur indirectly when a medicine-induced disease, or a change
in fluid/electrolyte balance, alters the response to another medicine.
2) These may occur when one medicine alters the absorption, distribution, or
elimination of another medicine, such that the amount which reaches the
site of action is either increased or decreased.

Drug–drug interactions are some of the most common causes of adverse effects. When
two medicines are administered to a patient, they may either act independently of each
other, or interact with each other. Interaction may increase or decrease the effects of the
medicines concerned and may cause unexpected toxicity. As newer and more potent
medicines become available, the frequency of serious drug interactions is likely to increase.

NOTE: Interactions which modify the effects of a medicine may involve non-prescription
medicines, non-medicinal chemical agents, and social drugs such as alcohol,
marijuana and tobacco, and traditional remedies, as well as certain types of food.
The physiological changes in individual patients, caused by such factors as age and
sex, also influence the predisposition to ADRs resulting from drug interactions.

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 d. INCOMPATIBILITIES BETWEEN MEDICINES AND IV FLUIDS
Medicines should not be added to blood, amino acid solutions, or fat emulsions.
o Certain medicines, when combined with intravenous fluids, may be
inactivated by pH changes, precipitation, or chemical reaction.

e. ADVERSE EFFECTS CAUSED BY TRADITIONAL MEDICINES

Patients who have been, or are taking, traditional herbal remedies may
develop ADRs. In these types of preparation, it is not always easy to identify the
responsible constituents. Refer to the medicine and toxicology information
service if available or to suitable literature.

f. EFFECT OF FOOD ON MEDICINE ABSORPTION

Food delays gastric emptying and reduces the rate of absorption of many
medicines; however, the total amount of medicine absorbed may or may not be
reduced. On the other hand, some medicines are taken with food, either to
increase absorption or to decrease the irritant effect on the stomach.

E PRESCRIPTION WRITING
1. PRESCRIPTION FORM
Administrative Order No. 62 (series of 1989) on the rules and regulations to
implement prescribing requirements under the Generics Act defines a prescription as
a written order and instruction of a validly-registered physician, dentist or veterinarian
for the use of a specific medicine (or medical device) for a specific patient.

The most important requirement for a prescription is that it should be clear. It

should be legible and indicate precisely what should be given. The language used may
be in English, Filipino, or the local dialect.

In accordance with R.A. 5921, or the Pharmacy Act as amended, all prescriptions
should contain the following information:
o The patient’s name, age and sex;
o The prescriber’s name, office address, professional registration number, and
professional tax receipt number; and,
o Date of the prescription

In addition, Section 3 of the Generics Act lists the following specific guidelines to
prescribing:
o Generic names shall be used in all prescriptions. For drugs with a single active
ingredient, the generic name of that active ingredient shall be used in
prescribing. For drugs with two or more active ingredients, the generic name as
determined by the Philippine FDA shall be used.
o The generic name must be written in full, but the salt or chemical form may be
abbreviated. The symbol Rx means prescription which originated in medieval
manuscripts as an abbreviation of the Latin verb recipe. The imperative form is
recipere which means “to take” or “take thus.”)
o The generic name must be clearly written immediately after the Rx symbol or on
the order chart.
o The pharmaceutical form (e.g., “tablet”, “oral solution”, “eye ointment”) should
also be stated.
o The strength of the medicine should be stated in standard units using
abbreviations which are consistent with the Système International (SI) [Refer to
Appendices for abbreviations and symbols].

xii
 o Avoid decimals whenever possible. If this is unavoidable, a zero should be
written before the decimal point.

2. INCORRECT PRESCRIPTIONS
Three types of incorrect prescriptions may be identified:
a. Erroneous prescription:
o Where the brand name precedes the generic name
o Where the generic name is the one in parenthesis
o Where the brand name is not in parenthesis

b. Violative prescription:
o Where the generic name is not written
o Where the generic name is not legible, and a brand name which is
legible is written
o Where the brand name is indicated and instructions added (such as
the phrase “no substitution”) which tend to obstruct, hinder or
prevent proper dispensing

c. Impossible prescription:
o When only the generic name is written, but it is not legible
o When the generic name does not correspond to the brand name
o When both the generic and brand names are not legible
o When the drug product prescribed is not registered with the
Philippine Food and Drug Administration

If an erroneous prescription is received, the prescription may be filled but it should

be kept and reported to the nearest Department of Health (DOH) office for appropriate
action. In contrary, violative and impossible prescriptions are not to be filled and
should also be kept and reported to the nearest DOH office.

3. NARCOTICS AND CONTROLLED SUBSTANCES

The prescribing of a medicinal product which is liable to abuse requires special
attention and may be subjected to specific statutory requirements. Practitioners may
need to be authorized to prescribe controlled substances. In such cases, it might be
necessary to indicate details of the authority on the prescription.

In particular, the strength, directions, and the quantity of the controlled substance
to be dispensed should be stated clearly, with all quantities written in words, as well
as in figures to prevent alteration. Other details, such as patient particulars and date,
should also be filled in carefully to avoid alteration.

F PATIENT COUNSELING
One-to-one, dynamic interaction between a health care practitioner and a patient and/or
caregiver, which should include an assessment if the information was received as
intended, and that the patient understands how to use the information to improve the
probability of positive therapeutic outcomes.

1. WHAT TO COUNSEL
Routinely, effectively and appropriately educate patients on the following: (1) when
dispensing prescription and non-prescription drugs, (2) when counseling on discharge
medications, and (3) when providing recommendations about management of
specific drug-related problems:
a. The medication’s name (generic), indication and when appropriate to use;

xiii
 b. The medication’s expected onset of action and what to do if the action
does not occur;
c. The medication’s route, dosage form, dosage and administration schedule
(including duration of therapy);
d. Directions for use including education about drug devices;
e. Proper storage requirements;
f. Common or important drug-drug or drug-food interactions;
g. Potential common and severe adverse effects, and actions to prevent or
minimize their occurrence;
h. What the patient should do to monitor his/her therapeutic response or
when side effects develop;
i. What actions the patient should take if the intended therapeutic response
is not obtained or if side effects develop; and,
j. Proper disposal of contaminated, discontinued or unused medications.

2. WHO AND WHEN TO COUNSEL

a. Patients who should always be counseled together with their families and
caregivers:
o Confused patients;
o Patients who are sight- or hearing-impaired;
o Patients with poor literacy;
o Patients whose profiles show change in medications or
dosing;
o New patients, or those receiving a medication for the first time; and,
o Patients who have medications with significant side effects, specific
storage requirements, and complicated directions.
b. Patients who should be counseled at certain intervals:
o Asthmatic patients;
o Diabetic patients;
o Patients taking four (4) or more prescribed medications;
o Patients who are mentally ill;
o Epileptic patients; and,
o Patients with skin complaints.

3. COUNSELING: PROCESS STEPS

Steps in patient education and counseling process will vary according to the health
system’s policies and procedures, environment, and practice setting. Generally, the
following steps are appropriate for patients receiving new medications or returning
for refills:

a. Establish caring relationship with the patient as appropriate to the practice

setting, and stage in the patient’s health care management. Show interest
in the patient verbally and non-verbally
o Explain the purpose and expected length of sessions.
o Obtain the patient’s agreement to participate.
b. Assess the patient’s knowledge about his or her health problems,
medications, physical and mental capability to use the medications
appropriately, and attitude towards the health problems and medications.
o Ask why the patient is being prescribed with the medication
(if known), or the medication’s use, expected benefits and
action.
o Provide information orally, and use demonstrations or visual
aids to fill the patient’s gaps in knowledge and
understanding.

xiv
 o Open the medication containers and show patient what the
medication looks like, or demonstrate use. Explain how to
take the medication.
o Discuss when to take and how long to take the medication.
o Plan what to do if a dose is missed.
o Determine any special precautions to heed and follow.
Explain how to store the medication.
o Demonstrate if the prescription can be refilled, and if so,
determine when it is done.
o Give specific details on how the patient will know if the
medication is working.
c. Verify patient’s knowledge and understanding of medication use.
o Ask the patient to describe (or show) how the medication
should be used, and its effects.
o Ask the patient if they have any questions.

xv
 ANTIMICROBIAL RESISTANCE
A. DEFINITION OF ANTIMICROBIAL RESISTANCE
1. Antimicrobial Resistance (AMR) refers to the resistance of a micro-organism
(including bacteria, viruses and some parasites) to an antimicrobial agent to which it
was previously sensitive. Resistant organisms withstand attack by antibacterials,
antivirals, or antimalarials. Thus, standard treatments become ineffective, allowing
infections to persist and spread.
2. AMR which is a consequence of the use or misuse of antimicrobials develops when
the organism mutates or acquires a resistance gene.

B. CAUSES OF ANTIMICROBIAL RESISTANCE

1. Although the ultimate causes of AMR are microbial, clinical, and programmatic in
nature, it is essentially a man-made occurrence.
2. The proliferation of drug-resistant strains is associated with various management,
healthcare provider, and patient-related issues. Table 1 enumerates several of the
causes leading to drug resistance.
3. The general categories of the causes, i.e., therapeutic protocols, drug characteristics,
and drug selling and purchasing practices, provide opportunities where potential
strategies to combat AMR arise.

Table 1. Causes of inadequate treatment which may contribute to emergence of drug

resistance
Drugs:
Healthcare providers: Patients:
Inadequate
Inadequate regimens Inadequate drug intake
supply/quantity
- Inappropriate guidelines - Poor quality - Poor adherence (or poor
- Noncompliance with - Unavailability of certain directly observed
guidelines drugs (stock-outs or therapy)
- Absence of guidelines delivery disruptions) - Lack of information
- Poor training - Poor storage conditions - Lack of money (no
- No treatment monitoring - Wrong dose or treatment available free
- Poorly organized or combinations of charge
funded control - Lack of transportation
programs - Adverse effects
- Social barriers
- Malabsorption
- Substance dependency
disorders
Source: Final Report, Country Situation Analysis on Antimicrobial Resistance, Philippines,
2012.

C. ANTIMICROBIAL RESISTANCE: A GROWING GLOBAL CONCERN

1. The WHO cites the following alarming reasons: AMR is already a global concern, AMR kills,
AMR challenges control of infectious disease, AMR threatens a return to the pre-antibiotic
era, AMR increases the costs of health care, AMR jeopardizes healthcare gains to society,
and AMR compromises health security, and damages trade and economy.

2. Furthermore, the following facts collated by WHO1 indisputably demonstrate the

potential and real dangers that AMR causes and has caused:
a. About 440,000 new cases of multi-drug resistant TB (MDR-TB which is defined
as resistance to Rifampicin and Isoniazid) emerge annually, causing at least

xvi
 150,000 deaths. Therapy of MDR-TB requires 18-24 months of treatment with
expensive second-line drugs, like capreomycin and kanamycin.
b. Extensively drug-resistant TB (XDR-TB defined as MDR plus resistance to any
member of the quinolone family and at least to any second-line anti-TB
injectable, such as kanamycin, capreomycin or amikacin) is a global threat with
a case-fatality rate of 50%. XDR-TB is a big problem because there are very few
options for treatment, which probably accounts for the high mortality rate among
them.
c. Resistance to earlier generation antimalarial medicines such as chloroquine
and sulfadoxine-pyrimethamine is widespread in most malaria-endemic
countries. Falciparum malaria parasites resistant to artemisinins are emerging
in Southeast Asia; infection showed delayed clearance after the start of
treatment (indicating resistance).
d. Ciprofloxacin is the only antibiotic currently recommended by WHO for the
management of bloody diarrhea due to Shigella, now that wide-spread
resistance has developed to any previously effective antibiotics. But rapidly
increasing prevalence of resistance to Ciprofloxacin in Shigellosis is reducing
the options for safe and efficacious treatment especially for children. New
antibiotics suitable for oral use are badly needed.
e. AMR has become a serious problem for treatment of gonorrhea (caused by
Neisseria gonorrhoea), involving even “last-line” oral cephalosporins, and this is
increasing in prevalence worldwide. In multidrug-resistant N. gonorrhoea,
resistance is found against tetracyclines, macrolides (including azithromycin),
sulfonamide and trimethoprim combinations and more recently, to quinolones.
Untreatable gonococcal infections will result in higher rates of illness and death
thus reversing the gains made in the control of the sexually transmitted
infections.
f. ESBLs (extended-spectrum beta-lactamases) are resistant to third-generation
cephalosporins (ceftazidime, cefotaxime and cefpodoxime) as well as
monobactams (aztreonam); common in the Enterobacteriaceae, particularly
E.coli and K. pneumoniae.
g. New resistance mechanisms, such as the beta-lactamase NDM-1 (New Delhi metalo-
beta-lactamase 1), have emerged among several gram-negative bacilli. This is
considered as a new superbug that has resistance to broad spectrum antibiotics that
are often the last defense against multi-resistant bacterial strains.
h. A high percentage of hospital acquired infections is caused by highly resistant
bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and
vancomycin resistant enterococci.
i. Resistance is an emerging concern for treatment of HIV infection, following the
rapid expansion in access to anti-retroviral medicines in recent years.

D. STATUS OF ANTIMICROBIAL RESISTANCE IN THE PHILIPPINES

1. The need to approach the problem of AMR in the Philippines with a sense of urgency
is clearly elucidated by several evidence of the dangers it poses.
a. The most dreaded recognized AMR gene, the NDM-1, was identified in the
Escherichia coli isolated from the urine of a 33 year old female in 2011. The
gene can render even the most powerful antibiotics ineffective.
b. Many of the causative bacterial pathogens that cause infections included in the Top
Ten causes of morbidity in the Philippines have already become resistant to multiple
antibiotics. At the forefront is TB, with MDR-TB and even XDR-TB already present in
the Philippines which ranked 6th among 27 identified countries with MDR-TB. In 2006,
the occurrence of MDR-TB was 4% among new cases and a high 27% among
previously treated patients.

xvii
 2. The DOH established in 1988 the Antimicrobial Resistance Surveillance Program (ARSP) to
determine the current status and developing trends of antimicrobial resistance of selected
bacteria to specific antimicrobials. The ARSP, which now has 24 sentinel sites hospital
bacteriology laboratories in 16 regions of the Philippines and 2 gonococcal surveillance
sites, submits and publishes annual summary reports focusing on aerobic bacterial
pathogens of public health importance causing common infectious diseases.

All readers are enjoined to refer to the yearly published ARSP surveillance data
provided by RITM for updated information and proper guidance.

3. The ARSP found alarming rates of resistance among various bacterial pathogens. 1,2
a. The ESBL enzyme, which can render pathogens resistant to many antibiotics,
has been identified in Escherichia coli and Klebsiella spp.
b. Multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. which
account for 43% of all hospital-acquired pneumonia have been identified.
c. The percent resistance, in all ARSP sites from January-December of 2013 of
Streptococcus pneumonia (which causes acute respiratory tract infections) to
penicillin was 5% compared to 0 in 2010. Resistance to cotrimoxazole was 20%
in 2013.²
d. The percent resistance of non-typhoidal Salmonella from January-December,
2013, to ampicillin and cotrimoxazole were 56% and 34%, respectively. ²
e. There is a steady increase in the resistance rates of Staphylococcus aureus and
consequently higher prevalence of MRSA which is also an important cause of hospital
acquired infections.
f. In the period 2012-2013, there were very high resistance rates of Neisseria
gonorrhoea to ciprofloxacin (74%), penicillin (80%), and tetracycline (55%). ²

4. These alarming increasing trends of AMR in the country are clearly demonstrated in
Table 2 which summarized the results of a comparison of the antimicrobial resistance
of selected organisms in 1993 and 2011.

Please refer to the Antimicrobial Resistance Surveillance Program (ARSP) Summary Report
for antimicrobial resistance patterns of specific organisms.

E. RECOMMENDATIONS OF THE PHILIPPINE ANTIMICROBIAL RESISTANCE

SURVEILLANCE PROGRAM
Below are the recommendations of the ARSP regarding antibiotic treatment for aerobic
bacterial pathogens of public health importance based on the reported antimicrobial
resistance surveillance data for 2013 (Carlos, C, 2013):

1. Respiratory Bacterial Pathogens:

a. Infections secondary to Streptococcus pneumoniae can still be covered with
penicillin or one of the anti-pneumococcal macrolides, although there is a need
to closely monitor the changing trends of resistance among pneumococci.
Improved local data on serotype distribution will allow for better surveillance
information especially needed for vaccination recommendations.
b. Due to high resistance rate of Haemophilus influenzae to ampicillin, this
antibiotic is no longer recommended for empiric therapy for infections
secondary to the pathogen.
c. Recommended empiric treatment for suspected H. influenzae infections may
consist of beta-lactam-beta-lactamase inhibitor combinations, extended
spectrum oral cephalosporins and the newer macrolides.
xviii
 2. Bacterial Enteric Pathogens:
a. For suspected uncomplicated enteric fever, empiric treatment can still consist
of either chloramphenicol or cotrimoxazole or amoxicillin/ampicillin. There are
increasing reports of nalidixic acid resistance and ciprofloxacin non-
susceptibility which may result to clinical treatment failures when treating
enteric fever using fluoroquinolones. Microbiological data is recommended for
pathogen directed therapy.
b. In Salmonella gastroenteritis, increasing rates of ciprofloxacin resistance should
remind clinicians to use antibiotics judiciously as this is usually a self-limiting
disease.
c. Due to the emerging resistance of Shigellae to the quinolones and limited data
available, more vigilant surveillance of the resistance pattern of this organism
should be pursued by encouraging clinicians to send specimens for culture.
d. For cholera, tetracycline, chloramphenicol and cotrimoxazole remain to be good
treatment options.

3. Sexually-Transmitted Bacterial Pathogens:

a. Limited data is available on N. gonorrhoeae in recent years, but based on
reported isolates, ceftriaxone remains as empiric antibiotic of choice for
gonococcal infections. More vigilant surveillance of the resistance patterns of
this organism must be pursued by encouraging clinicians to send specimens for
culture.

4. Gram-positive Cocci:
a. In view of the continuous high rates of methicillin/oxacillin resistance among
staphylococci, there may be an indication to shift empiric treatment of
suspected staphylococcal infections from oxacillin to alternative agents such as
cotrimoxazole, doxycycline, clindamycin, linezolid or vancomycin.

5. Gram-negative Bacilli:
a. Hospitals should base their treatment recommendations for the Enterobacteriaceae
on their institution’s prevailing resistance patterns as these have been found to be
variable from hospital to hospital. The high percentage of possible ESBL-producing
isolates complicates treatment of serious infections caused by these organisms and
may lead to the increased use of carbapenems that may favor the spread of the
carbapenem-resistant Enterobacteriaceae.
b. Increasing resistance among the bacterial organisms Pseudomonas aeruginosa
and Acinetobacter baumannii continue to be a concern as both carry intrinsic
resistance to a number of antimicrobial classes and acquisition of additional
resistance severely limits the available treatment options.
c. Prudent antimicrobial use, monitoring of resistance patterns and antimicrobial
use, and improved standards of infection control are essential in addressing the
clinical and public health concerns.

All readers are enjoined to refer to the yearly published ARSP surveillance data
provided by RITM for updated information and proper guidance.

F. DRIVING FORCES BEHIND ANTIMICROBIAL RESISTANCE

1. The inappropriate and irrational use of medicines provides favorable
conditions for resistant microorganisms to emerge and spread. WHO enumerates the
following as the underlying factors that drive AMR:
a. Inadequate national commitment to a comprehensive, coordinated response,
ill-defined accountability, and insufficient engagement of communities;
xix
 b. Weak or absent surveillance and monitoring systems;
c. Inadequate systems to ensure quality and uninterrupted supply of medicines;
d. Inappropriate and irrational use of medicines, in both clinical practice and
animal husbandry, and aquaculture;
e. Poor infection prevention and control practices; and,
f. Depleted arsenals of diagnostics, medicines, and vaccines as well as
insufficient research and development of new products.

G. THE RESPONSE OF THE NATIONAL GOVERNMENT TO THE RISING

ANTIMICROBIAL RESISTANCE
1. Creating an Inter-Agency Committee on AMR (ICAMR).
2. Developing a National Plan that will include, but not limited to, the following
strategies:
a. Establishing short and long term programs to address the different aspects of
response to AMR;
b. Strengthening the surveillance system and laboratory detection capacity of AMR
in both humans and animals;
c. Ensuring accessibility, affordability, availability and quality of antimicrobial drugs
for humans and its appropriate use in food producing animals including banning
the use of antibiotics as growth promoters;
d. Developing relevant and utilizable essential medicines list for human and
veterinary use;
e. Monitoring the rational use of antimicrobials in humans, animal husbandry and
aquaculture;
f. Advocating the rational use of antimicrobials to consumers and community
through media and the academe;
g. Training and educating on, and promotion of infection prevention and control
measures in health care facilities and the community;
h. Conducting researches to develop new antimicrobials and innovative technology
to improve diagnosis and treatment;
i. Monitoring and evaluating compliance with existing policies and on the proper
execution of the AMR control plan;
j. Engaging all relevant stakeholders such as government agencies, healthcare
providers, non-government institutions, professional organizations, drug
industry, veterinary and aquaculture groups, consumer groups, researchers and
civil societies; and,
k. Ensuring that activities are well financed for sustainability.

H. ACTION PLANS, WHICH THE PRIMARY PHYSICIANS AND DENTISTS CAN

ADOPT TO HELP COMBAT ANTIMICROBIAL RESISTANCE
1. Assuring the judicious use of antimicrobial agents through faithful adherence to the
principles of rational use of medicines and utilizing antimicrobial agents only for the
appropriate indications as recommended by the Antimicrobial Resistance
Surveillance Program (ARSP) or the task force for Clinical Practice Guidelines and
included in the Philippine National Formulary. The choice of antibiotics must strictly
conform to the best standard treatment guidelines or clinical practice guidelines (e.g.,
National Antibiotic Guidelines), and guided by the latest findings and
recommendations of the ARSP;
2. Keeping abreast of the latest information on AMR through reviews of the latest
antibiotic susceptibility data published by the ARSP, literature search, attendance in
seminars, and participation in continuing medical education programs;
3. Devoting sufficient time to educate the patients and their families and caregivers about the
appropriate use of antibiotics and the reasons behind the need for strict adherence to the

xx
 prescribed dosage schedule and completion of full course of treatment as well as to
educate them on the prevention of AMR;
4. Careful monitoring of the patients’ compliance and their response to the antimicrobial
agents;
5. Submitting specimen for culture when indicated (e.g., for suspected gonococcal
infections);
6. Complying with the rules on prescribing, and other regulations in the Pharmacy Law;
7. Developing better communication with pharmacists and other dispensers;
8. Educating other healthcare providers (nurses, midwives, barangay health workers)
about the RUM and prevention of AMR; and,
9. Educating the community continually on the need for and proper ways of maintaining
good personal hygiene and sanitation, avoidance of vices or unhealthy habits,
sanitation, and prevention of infections, including maintaining cleanliness of their
surroundings.

xxi
MEDICINE AND
THERAPEUTIC
INFORMATION
ALIMENTARY TRACT AND METABOLISM
ALIMENTARY TRACT AND METABOLISM
DRUGS FOR ACID-RELATED
DISORDERS
ANTACIDS
ALUMINUM HYDROXIDE +
OTC
MAGNESIUM HYDROXIDE
Oral: 200 mg aluminum hydroxide + 100 mg magnesium
hydroxide tablet
225 mg aluminum hydroxide + 200 mg magnesium
hydroxide per 5 mL suspension, 60 mL and 120 mL
An antacid that combines aluminum hydroxide and
magnesium hydroxide to reduce effect on bowel
movement and to relieve epigastric pain from peptic
ulcer through acid neutralization.
Indication: Symptomatic relief of symptoms related to
hyperacidity from heartburn, hiatal hernia, upset
stomach, peptic ulcer, peptic esophagitis, or gastritis.
Contraindications: Severe renal impairment;
hypophosphatemia; undiagnosed GI and rectal bleeding;
porphyria; appendicitis.
Dose:
Hyperacidity, by mouth, ADULT, 10-20 mL 4 times daily
(maximum 80 mL daily).
Dose Adjustment:
Renal Impairment:
Use with caution due to risk of accumulation and toxicity.
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, avoid use and refer patient to a
specialist.
Precautions:
WARNING: Aluminum and magnesium salts may be
hazardous in patients with renal insufficiency. If
intensive antacid therapy is to be used, only non-
systemic (non-absorbable) antacids should be
considered because of the potential danger of
alkalosis with systemic therapy.
Acute porphyria; prolonged antacid therapy may result in
hypophosphatemia (i.e., decreased phosphate
absorption in the GI tract); dehydration; fluid restriction;
constipation; diarrhea; hepatic impairment; renal
impairment; GI disorders associated with decreased
bowel motility or obstruction; some products may contain
phenylalanine.
Elderly (may be predisposed to diarrhea or constipation);
children.
Adverse Drug Reactions:
Common: Constipation, diarrhea, GI irritation.
Less Common: Chalky taste, fecal discoloration,
hypophosphatemia, nausea, vomiting.
Rare: Anemia, encephalopathy, fecal impaction,
A
hypermagnesemia, hypophosphatemia, intestinal
obstruction, osteomalacia, proximal myopathy.
Drug Interactions:
Monitor closely with:
Increases excretion due to urine alkalinization:
Acetylsalicylic Acid
Reduces absorption of the following drugs:
Azithromycin, Chloroquine, Digoxin, Enalapril, Isoniazid,
Rifampicin
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs
Bisphosphonates e.g., Alendronate, Iron, Ketoconazole,
Quinolones e.g., Nalidixic acid, Rosuvastatin,
Tetracyclines, e.g., Doxycycline. [Separate dosing by at
least 2 hours before, or 4–6 hours after the antacid]:
Administration: Shake well before use.
Best given 1–3 hours after the last meal to neutralize and
buffer the acid produced.
NOTE: Antacids should preferably not be taken at the same
time as other oral drugs since they may impair
absorption (interactions may be avoided by having an
interval of at least 2 hours between taking an antacid
and the other drug).
Pregnancy Category: B
ATC Code: A02AD01
OTC SODIUM BICARBONATE
Oral: 325 mg and 650 mg tablet
A short-acting, potent systemic antacid that rapidly
neutralizes gastric acid to form sodium chloride, carbon
dioxide, and water. After absorption of sodium
bicarbonate, plasma alkali reserve is increased, and
excess sodium and bicarbonate ions are excreted in
urine, rendering urine less acid.
Indications: Symptomatic relief of hyperacidity (belching,
heartburn, indigestion, gas pains), gastritis, and peptic
ulcer; urine alkalinizer.
Contraindications: Diuretics known to produce
hypochloremic alkalosis; edema; hypertension;
hypocalcemia; hypochloremia; hypernatremia; impaired
renal function; metabolic alkalosis; respiratory alkalosis
or acidosis; any situation where administration of sodium
could be clinically detrimental.
Dose:
Antacid, by mouth, ADULT, 2–8 tablets every 4 hours
(maximum, 48 tablets in 24 hours); ADULT ≥60 years, 2–
4 tablets every 4 hours (maximum, 24 tablets in 24
hours.
1
 ALIMENTARY TRACT AND METABOLISM

Urine alkalinizer, by mouth, ADULT, initially 3.94 g, then FOR PEPTIC ULCER AND GASTRO-ESOPHAGEAL
0.97–1.95 g every 4 hours; CHILD, 84–840 mg/kg daily, REFLUX DISEASE (GERD)
in divided doses.
A

H2-RECEPTOR ANTAGONISTS
Dose Adjustment:
Geriatric, Renal and Hepatic Impairment:
Dose adjustment may be required. Rx (Inj.)
OTC (Oral)
FAMOTIDINE
Precautions:
Oral: 20 mg tablet
WARNING: Ask attending physician before use if on a Inj.: 10 mg/mL, 2 mL ampule / vial (IM, IV)
sodium restricted diet.
A competitive inhibitor of histamine H2­receptor, inhibiting
Do not use maximum dose for more than 2 weeks. both daytime and nocturnal basal gastric acid secretion,
as well as food-stimulated and pentagastrin-stimulated
gastric acid secretion.
Cardiac, liver, or renal disease;
Fluid or solute overload;
Indications: Relief and prevention of heartburn; treatment
Postoperative patients with cardiovascular or renal
and maintenance of active duodenal ulcers, pathological
insufficiency (e.g., sodium or water retention and edema
hypersecretory conditions (e.g., Zollinger-Ellison
which may result in serious pulmonary edema);
Syndrome or multiple endocrine adenomas),
Arrested patients with preexisting metabolic acidosis,
Gastroesophageal Reflux Disease (GERD) and active
hyperkalemia, or tricyclic or barbiturate overdose;
benign gastric ulcer.
Elderly;
Pregnancy (restrict intake in hypertension and toxemia).
Contraindications: Cirrhosis of the liver; impaired renal or
hepatic function; lactation; other H2 antagonists.
Adverse Drug Reactions:
Common: Belching, gastric distention, flatulence, metabolic
Dose:
alkalosis, electrolyte imbalance, (sodium overload,
Duodenal ulcer, acute therapy, by mouth, ADULT, 40 mg
hypocalcemia, hypokalemia, milk-alkali syndrome,
daily at bedtime (or 20 mg twice daily) for 4-8 weeks.
dehydration), reduction in CSF pressure, intracranial
Duodenal ulcer, maintenance therapy, by mouth, ADULT, 20
hemorrhage, severe tissue damage following
mg daily at bedtime.
extravasation of IV solution, renal calculi or crystals,
Gastric ulcer, acute therapy, by mouth, ADULT, 40 mg daily
impaired kidney function
at bedtime.
Peptic ulcer, by mouth, CHILD 1-16 years, 0.5 mg/kg daily
Drug Interactions:
at bedtime or divided twice daily (maximum dose, 40 mg
Monitor closely with:
daily) (doses of up to 1 mg/kg daily have been used in
Decreases the absorption of Ketoconazole
clinical studies); by IV injection, CHILD 1-16 years, 0.25
mg/kg every 12 hours (maximum dose, 40 mg daily)
Decreases therapeutic effect of the following drugs:
(doses of up to 0.5 mg/kg have been used in clinical
Chlorpropamide, Lithium Carbonate, Salicylates,
studies).
Tetracyclines
GERD, by mouth, ADULT, 20 mg twice daily for 6 weeks;
CHILD 1-16 years, 1 mg/kg daily divided twice daily
Increases therapeutic effect of the following drugs:
(maximum dose, 40 mg twice daily) (doses of up to 2
Appetite Suppressants (e.g., Amphetamines), Flecainide,
mg/kg/day have been used in clinical studies); CHILD 3-
Mecamylamine, Quinidine, Sympathomimetics (e.g.,
12 months, 0.5 mg/kg twice daily; CHILD <3 months, 0.5
Ephedrine, Dopamine)
mg/kg once daily.
Esophagitis and accompanying symptoms due to GERD, by
NOTE: Sodium bicarbonate raises intra-gastric pH, which
mouth, ADULT, 20 mg or 40 mg twice daily for up to 12
may affect the absorption of certain drugs.
weeks.
Hypersecretory conditions, by mouth, ADULT, initially, 20 mg
Administration: Should be taken on an empty stomach.
every 6 hours, may increase in increments up to 160 mg
Tablets may be swallowed whole or dissolved in water
every 6 hours.
prior to use.
Patients unable to take oral medication, by IV injection,
ADULT, 20 mg every 12 hours.
Do NOT add oral preparation to calcium-containing
solutions.
Dose Adjustment:
Renal Impairment:
Pregnancy Category: C
For creatinine clearance <50, reduce dose by half or
increase dosing interval to 36–48 hours.
ATC Code: A02AH
Precautions:
Increases risk of community-acquired pneumonia with
prolonged use; prolonged treatment (≥2 years) may lead
to vitamin B12 malabsorption and subsequent vitamin
B12 deficiency; gastric malignancy.

2
ALIMENTARY TRACT AND METABOLISM
Elderly >50 years.
Lactation (excreted into breast milk).
Adverse Drug Reactions:
Common: Headache, dizziness, constipation, diarrhea,
nausea and vomiting, anxiety, confusion.
Less Common: Acne, pruritus, urticaria, dry skin, fever,
hypertension, flushing, musculoskeletal pain, arthralgia,
tinnitus
Drug Interactions:
Monitor closely with:
Decreases absorption of the following drugs:
Cefpodoxime, Cefuroxime, Iron salts
Decreases serum concentration of the following drugs:
Indinavir, Multivitamins / Minerals with ADEK,
Folate, Iron
Increases the absorption of: Methylphenidate
Increases serum concentration of Famotidine:
Bupropion
Avoid concomitant use with:
Decreases absorption of Famotidine:
Antacid
Decreases absorption of Diazepam
Decreases serum concentration of the following drugs:
Atazanavir, Cefditoren, Itraconazole
Ketoconazole (systemic)
Increases serum concentration of Risedronate
Administration:
For oral administration, may be taken with or without
food
For IV injection or IV push, inject over at least 2 minutes.
If administered by IV infusion, administer over 15–30
minutes.
Pregnancy Category: B
ATC Code: A02BA03
Rx RANITIDINE
Oral: 150 mg and 300 mg tablet (as hydrochloride)
75 mg/5 mL syrup (as hydrochloride), 60 mL and 150
mL
Inj.: 25 mg/mL, 2 mL ampule / vial (IM, IV, IV infusion) (as
hydrochloride)
A competitive inhibitor of histamine H2­receptor, inhibiting
both daytime and nocturnal basal gastric acid secretion,
as well as food- and pentagastrin-stimulated gastric acid
secretion. Ranitidine is also a weak cytochrome P-450
enzyme inhibitor.
Indications: Relief and prevention of heartburn.
Management of duodenal ulcer, erosive esophagitis,
gastric ulcer, GERD, pathological hypersecretory
conditions (e.g., Zollinger-Ellison syndrome, systemic
mastocytosis)
A
Contraindications: Cirrhosis of the liver; impaired renal or
hepatic function; acute porphyria
Dose:
Duodenal ulcer, acute therapy, by mouth, ADULT, 150 mg
twice daily, or 300 mg once daily after the evening meal
or at bedtime; INFANT, CHILD, and ADOLESCENT ≤16
years, 4-8 mg/kg daily divided twice daily (maximum,
300 mg daily).
Duodenal ulcers, maintenance therapy, by mouth, ADULT,
150 mg once daily at bedtime; INFANT, CHILD, and
ADOLESCENT ≤16 years, 4–8 mg/kg daily divided twice
daily; 2–4 mg/kg once daily (maximum, 150 mg daily);
by IM injection, ADULT, 50 mg every 6–8 hours;
by IV intermittent bolus or IV infusion, ADULT, 50 mg
every 6–8 hours (if increased doses are necessary utilize
more frequent administration up to a maximum of 400
mg daily);
by IV injection, INFANT, CHILD, and ADOLESCENT ≤16
years, 2–4 mg/kg daily divided every 6–8 hours
(maximum dose, 50 mg/dose);
by continuous IV infusion, ADULT, 6.25 mg/hour.
Benign gastric ulcer, acute therapy, by mouth, ADULT, 150
mg twice daily; INFANT, CHILD, and ADOLESCENT ≤16
years, 4-8 mg/kg daily divided twice daily (maximum,
300 mg daily).
Benign gastric ulcer, maintenance therapy, by mouth,
ADULT, 150 mg once daily at bedtime; INFANT, CHILD,
and ADOLESCENT ≤16 years, 2-4 mg/kg once daily
(maximum, 150 mg daily).
Erosive esophagitis, acute therapy, by mouth, ADULT, 150
mg 4 times daily, INFANT, CHILD, and ADOLESCENT ≤16
years, 5-10 mg/kg daily divided twice daily (maximum,
300 mg daily).
Erosive esophagitis, maintenance therapy, by mouth,
ADULT, 150 mg twice daily.
Gastroesophageal reflux disease (GERD), by mouth, ADULT,
150 mg twice daily; INFANT, CHILD, and ADOLESCENT
≤16 years, 5-10 mg/kg daily divided twice daily
(maximum, 300 mg daily).
Heartburn, prevention, by mouth, CHILD ≥12 years, 75-150
mg 30-60 minutes before eating food or drinking
beverages that cause heartburn (maximum, 2 doses
daily), not to be used for more than 14 days.
Pathological hypersecretory conditions (e.g. Zollinger Ellison
Syndrome), by mouth, ADULT, 150 mg twice daily, adjust
dose or frequency as clinically indicated (doses of up to
6 g daily have been used in patients with severe
disease);
by IM injection, ADULT, 50 mg every 6–8 hours;
by continuous IV infusion, ADULT, 6.25 mg/hour, initially,
1 mg/kg per hour (measure gastric acid output at 4
hours, if >10 mEq or if patient is symptomatic, increase
dose in increments of 0.5 mg/kg per hour) (doses of up
to 2.5 mg/kg per hour (220 mg/hour) have been used
by IV intermittent bolus or infusion); 50 mg every 6–8
hours (if increased doses are necessary utilize more
frequent administration up to a maximum of 400 mg
daily).
Patients not able to take oral medication, by IM injection,
ADULT, 50 mg every 6–8 hours;
3

by IV intermittent bolus or infusion, ADULT, 50 mg every
6–8 hours; 50 mg every 6–8 hours (if increased doses
are necessary utilize more frequent administration up to
A
a maximum of 400 mg daily);
by continuous IV infusion, ADULT, 6.25 mg/hour; by IV
injection, INFANT, CHILD, and ADOLESCENT <16 years,
2–4 mg/kg daily divided every 6–8 hours (maximum
dose, 50 mg/dose).
Dose Adjustment:
Renal Impairment:
For patients with creatinine clearance <50 mL/minute,
adjust dose cautiously. Adjust dosing schedule to not
coincide with the end of hemodialysis.
Precautions:
WARNING: NOT to be used if there is trouble or pain
when swallowing food, vomiting with blood, or bloody
or black stools.
NOT to be used in combination with other acid
reducers. Avoid the use of 150 mg tablet for patients
with kidney disease.
Relief of symptoms does not preclude the presence
of a gastric malignancy.
Rare cases of reversible confusion have been associated
with use, usually among elderly or severely ill patients, or
in patients with renal or hepatic impairment.
Prolonged treatment (≥2 years) may lead to vitamin B12
malabsorption and subsequent vitamin B12 deficiency.
Decreased renal or hepatic function (use with caution).
Elderly (use with caution)
Pregnancy; lactation (excreted into breast milk; use with
caution).
Adverse Drug Reactions:
Common: Headache, abdominal pain, constipation,
diarrhea, nausea, and vomiting.
Less Common: Asystole, atrioventricular block, bradycardia
(with rapid IV administration), premature ventricular
beats, tachycardia, vasculitis.
Drug Interactions:
Monitor closely with:
Decreases absorption of the following drugs:
Cephalosporins, Iron salts [except ferric carboxymaltose,
ferric citrate, ferric gluconate, ferric pyrophosphate
citrate, iron dextran complex, iron sucrose]
Enhances therapeutic effect of: Procainamide
Reduces therapeutic effect of:
Warfarin (decreased prothrombin time)
Avoid concomitant use with:
Decreases absorption of the following drugs:
Cyanocobalamin / Vitamin B12
Decreases serum concentration of Azoles, e.g.,
Ketoconazole
Decreases therapeutic effect of Ranitidine:
Cigarette smoking
4
ALIMENTARY TRACT AND METABOLISM
Decreases therapeutic effect of Diazepam
Administration:
For IM administration, no dilution is required.
For IV administration, solution must be diluted. May be
administered by intermittent bolus, intermittent IV
infusion, or continuous IV infusion.
Pregnancy Category: B
ATC Code: A02BA02
PROTON PUMP INHIBITORS
Rx LANSOPRAZOLE
Oral: 15 mg and 30 mg capsule
15 mg and 30 mg MR tablet
A substituted benzimidazole, which acts as a proton pump
inhibitor (PPI), by blocking the final step of acid
production. It acts by inhibiting the H+/K+–ATPase
system at the parietal cells of the stomach, suppressing
both basal and stimulated gastric acid secretion.
Indications: Management of acid-related dyspepsia, erosive
esophagitis, Gastroesophageal Reflux Disease (GERD),
peptic ulcer, Helicobacter pylori infection, NSAID-
associated ulcer, Zollinger-Ellison syndrome.
Contraindication: Known severe hypersensitivity to
lansoprazole or any ingredient in the formulation
Dose:
Acid-related dyspepsia, by mouth, ADULT, 15–30 mg once
daily in the morning for 2–4 weeks.
GERD, acute therapy, by mouth, ADULT, 15–30 mg once
daily in the morning for 4–8 weeks.
GERD, maintenance therapy, by mouth, ADULT,
maintenance therapy, 15–30 mg once daily (adjust
dosing according to response); CHILD 12–17 years, 15
mg once daily for up to 8 weeks; CHILD 1–11 years (≤30
kg), 15 mg once daily in the morning for up to 12 weeks;
CHILD >30 kg, 30 mg once daily in the morning for up to
12 weeks (may increase doses up to 30 mg twice daily if
patient is still symptomatic after 2 or more weeks of
treatment).
Erosive esophagitis, acute therapy, by mouth, ADULT, 30 mg
once in the morning for up to 8 weeks; by IV injection,
ADULT, 30 mg over 30 minutes for up to 7 days; CHILD
12–17 years, 30 mg once daily for up to 8 weeks; CHILD
1–11 years (≤30 kg), 15 mg once daily in the morning for
up to 12 weeks; CHILD >30 kg, 30 mg once daily in the
morning for up to 12 weeks (may increase doses up to
30 mg twice daily if patient is still symptomatic after 2 or
more weeks of treatment).
Erosive esophagitis, maintenance therapy, by mouth,
ADULT, 15 mg once daily.
Peptic ulcer, acute therapy, by mouth, ADULT, 15 mg once
daily.
Peptic ulcer, maintenance therapy, by mouth, ADULT, 30 mg
once daily in the morning for up to 4 weeks (for duodenal
ulcer) or up to 8 weeks (for gastric ulcer).
ALIMENTARY TRACT AND METABOLISM
Helicobacter pylori infection, by mouth, ADULT, 1-week
triple therapy, 30 mg twice daily (administered with
clarithromycin and amoxicillin or metronidazole; see
under Chapter 1: Alimentary Tract and Metabolism –
Drugs for eradication of H. pylori).
NSAID-associated ulceration, treatment, by mouth, ADULT,
30 mg once daily in the morning for 4 to 8 weeks.
NSAID-associated ulceration, prophylaxis, by mouth, ADULT,
15–30 mg once daily in the morning.
Zollinger-Ellison syndrome, by mouth, ADULT, initially 60 mg
once daily in the morning to be adjusted as required
(daily doses >120 mg should be given in 2 divided
doses).
Dose Adjustment:
Hepatic Impairment:
Adjust the dose in patients with severe hepatic impairment
(maximum dose, 30 mg daily).
Precautions:
Gastric malignancy should be ruled out;
Hepatic impairment;
Lactation (not known if excreted in breastmilk; potential for
serious adverse reactions in the nursing infant).
Adverse Drug Reactions:
Common: Abdominal pain, constipation, diarrhea,
flatulence, headache, nausea, vomiting.
Less Common: Decreased absorption of vitamin B12,
dizziness, drowsiness, dry mouth, fatigue, insomnia,
malaise, paresthesia, pruritus, rash, somnolence,
urticarial, vertigo, atopic gastritis, Clostridium difficile-
associated diarrhea (CDAD), anaphylaxis (potentially
fatal), Stevens-Johnson syndrome (potentially fatal),
toxic epidermal necrolysis (potentially fatal).
Rare: Alopecia, arthralgia, blurred vision, confusion,
dermatitis, gynecomastia, hemolytic anemia,
hypersensitivity reactions, hypomagnesemia, hepatitis,
interstitial nephritis, jaundice, leukopenia, microscopic
colitis, myalgia, myopathy pancreatitis, peripheral
edema, raised liver enzymes, skin reactions, taste
disturbance, thrombocytopenia.
Drug Interactions:
Monitor closely with:
Decreases bioavailability of Azoles, e.g., Itraconazole,
Ketoconazole
Increases risk of adverse or toxic effects of the following
drugs:
Digoxin (hypomagnesemia), Diuretics
(hypomagnesemia)
Reduces bioavailability of Lansoprazole
Antacids, Sucralfate
Avoid concomitant use with:
Decreases serum concentration and therapeutic effects of
the following drugs (possibly fatal):
Atazanavir, Ripivirine
Administration: To be taken on an empty stomach,
preferably before meals. Swallow whole. Do NOT crush or
chew.
For patients with swallowing difficulties, the contents of
the capsules (enteric-coated granules) can be sprinkled
on a small amount of soft food (such as yogurt or apple
A
sauce) or mixed with a little fruit juice and swallowed.
For dosage by nasogastric tube, the contents of a
capsule may be mixed with 40 mL of apple juice and
flushed with additional apple juice.
Pregnancy Category: B
ATC Code: A02BC03
Rx OMEPRAZOLE
Oral: 20 mg and 40 mg capsule
Inj.: 40 mg powder, vial + 10 mL solvent, ampule/vial (IV)
A benzimidazole, which acts as a proton pump inhibitor
(PPI), by blocking the final step of acid production. It acts
by inhibiting the H+/K+–ATPase system at the parietal
cells of the stomach, suppressing both basal, and
stimulated gastric acid secretion.
Indications: Management of duodenal ulcer, gastric ulcer,
and NSAID-associated gastric and duodenal ulcers and
erosions, symptomatic GERD, reflux esophagitis, acid-
related dyspepsia; H. pylori eradication in peptic ulcer
disease prophylaxis of acid aspiration before surgery, or
aspiration of gastric contents during general anesthesia.
Dose:
Duodenal ulcer, by mouth, ADULT, 20–40 mg daily for at
least 4 weeks; CHILD >20 kg, 20 mg daily; CHILD 10–20
kg, 10 mg daily; CHILD 5–10 kg, 5 mg daily.
Gastric ulcer, by mouth, ADULT, 20–40 mg daily for 4–8
weeks; CHILD >20 kg, 20 mg daily; CHILD 10–20 kg, 10
mg daily; CHILD 5–10 kg, 5 mg daily.
Erosive esophagitis, by mouth, ADULT, 20–40 mg for at
least 4 weeks; maintenance, 20 mg daily for up to one
year; CHILD >20 kg, 20 mg daily; CHILD 10–20 kg, 10
mg daily; CHILD 5–10 kg, 5 mg daily.
Helicobacter pylori infection, by mouth, ADULT, 40 mg every
12 hours for 10 days, WITH amoxicillin at 1 g every 12
hours, AND clarithromycin at 500 mg every 12 hours for
10–14 days; CHILD >20 kg, 20 mg daily; CHILD 10–20
kg, 10 mg daily; CHILD 5–10 kg, 5 mg daily.
Hypersecretory conditions (e.g., Zollinger-Ellison Syndrome),
by mouth, ADULT, 60 mg daily (initial) up to 360 mg daily
divided every 8 hours; if dose >80 mg, divide it;
by IV injection, ADULT, initially 60 mg once daily, higher
doses may be required; administer doses >60 mg in 2
divided doses.
Alternative to oral therapy, by IV injection, ADULT, 40 mg
once daily at a rate no greater than 4 mL/minute; shift to
oral omeprazole as soon as feasible.
Dose Adjustment:
Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
5

Precautions:
GI infection; Gastric malignancy; Fractures;
Hypomagnesemia; Hepatic impairment; Surgery;
A
Lactation.
Adverse Drug Reactions:
Common: Abdominal pain, constipation, diarrhea,
flatulence, headache, nausea, vomiting.
Less Common: Decreased absorption of vitamin B12,
dizziness, drowsiness, dry mouth, fatigue, insomnia,
malaise, paresthesia, pruritus, rash, somnolence,
urticarial, vertigo.
Rare: Alopecia, arthralgia, blurred vision, confusion,
dermatitis, gynecomastia, hemolytic anemia, hepatitis,
hypersensitivity reactions, hypomagnesemia, interstitial
nephritis, jaundice, leukopenia, microscopic colitis,
myalgia, myopathy pancreatitis, peripheral edema,
raised liver enzymes, skin reactions, taste disturbance,
thrombocytopenia.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Anticoagulants, e.g., Warfarin, Anti-epileptic agents e.g.
Phenytoin, Digoxin
Reduces therapeutic effect of the following drugs:
Azoles, e.g., Ketoconazole, Clopidogrel (antiplatelet
activity), Iron salts, Mycophenolate
Administration:
For IV administration, administer by slow IV injection (not
less than 2.5 minutes) at a rate of no greater than 4
mL/minute. Do NOT administer as an IV infusion.
For oral administration, take 30 minutes before meals,
preferably at breakfast if to be taken once a day.
For patients with swallowing difficulties, capsules can be
opened, and the contents swallowed or suspended in a
slightly acidic fluid, e.g., fruit juice or in non-carbonated
water. Drink the suspension within 30 minutes.
Alternatively, the contents of the capsule can be sucked
and swallowed. Do NOT chew or crush the contents of
the capsule.
Pregnancy Category: C
ATC Code: A02BC01
Rx RABEPRAZOLE
Oral: 10 mg and 20 mg tablet
A substituted benzimidazole, gastric proton-pump inhibitor
that suppresses gastric secretion by inhibiting gastric
H+/K+ ATPase at the parietal cells.
Indications: Management of active duodenal ulcer, active
benign gastric ulcer, anastomotic ulcer, symptomatic
erosive or Gastroesophageal Reflux Disease (GERD);
pathological hypersecretory conditions (e.g. Zollinger
Ellison Syndrome; eradication of Helicobacter pylori
peptic ulcer disease.
6
ALIMENTARY TRACT AND METABOLISM
Contraindication: Lactation
Dose:
GERD, acute therapy, by mouth, ADULT, 20 mg daily for 4–
8 weeks; CHILD ≥12 years, 20 mg once daily in the
morning for up to 8 weeks.
GERD, maintenance therapy, by mouth, ADULT, 10 or 20 mg
once daily in the morning.
Helicobacter pylori eradication, by mouth, ADULT, 1–week
triple therapy, 20 mg twice daily (combined with
clarithromycin 500 mg twice daily and amoxicillin 1 g
twice daily or combined with clarithromycin 250 mg
twice daily and metronidazole 400 mg twice daily).
Zollinger-Ellison Syndrome, by mouth, ADULT, initially, 60
mg once daily in the morning, adjusted to maximum dose
of 120 mg daily, if needed; daily doses >100 mg should
be given in 2 divided doses.
Peptic ulcer, by mouth, ADULT, initially, 20 mg once daily in
the morning for 4–8 weeks (duodenal ulcer) or for 6–12
weeks (gastric ulcer).
Erosive esophagitis, acute therapy, by mouth, ADULT,
initially, 20 mg daily for 4–8 weeks; may continue for
another 8 weeks if healing is incomplete.
Erosive esophagitis, maintenance therapy, by mouth,
ADULT, initially, 10 or 20 mg daily once in the morning.
Dose Adjustment:
Geriatric:
Consider dose adjustment.
Precautions:
Symptomatic response to therapy does not preclude the
presence of gastric malignancy.
Elderly (greater sensitivity is possible).
Lactation (not known if excreted in breast milk; potential for
serious adverse reactions in the nursing infant).
Adverse Drug Reactions:
Common: Headache, GI upset, diarrhea, insomnia,
nervousness, rash, itching, dry mouth, dizziness,
peripheral edema, hepatic enzyme increase, hepatitis,
hepatic encephalopathy, myalgia, arthralgia.
Less Common: Rectal hemorrhage, melena, anorexia,
cholelithiasis, mouth ulceration, convulsions, myocardial
infarction.
Rare: agranulocytosis, hemolytic anemia, leukopenia,
pancytopenia, thrombocytopenia, sudden death, coma,
jaundice, rhabdomyolysis, disorientation, delirium,
anaphylaxis (potentially fatal), angioedema, bullous,
severe dermatologic reactions (e.g., toxic epidermal
necrolysis, potentially fatal), Stevens-Johnson syndrome
(potentially fatal), erythema multiforme, interstitial
pneumonia, interstitial nephritis.
Drug Interactions:
Monitor closely with:
Decreases bioavailability of Rabeprazole:
Sucralfate
Decreases bioavailability of the following drugs:
Azoles, e.g., Itraconazole, Ketoconazole, Clopidogrel
Enhances therapeutic effect of Warfarin (prothrombin time
and INR)
ALIMENTARY TRACT AND METABOLISM

Increases risk of adverse or toxic effects of the following Cimetidine, Digoxin, Ketoconazole, Phenytoin
drugs: Ranitidine, Tetracyclines, Theophylline
Digoxin (hypomagnesemia), Diuretics

A
(hypomagnesemia) Increases risk of adverse and toxic effects of Citrate-
containing preparations
Avoid concomitant use with:
Decreases serum concentration and therapeutic effects of Avoid concomitant use with:
the following drugs (possibly fatal): Reduces therapeutic effect of Sucralfate:
Atazanavir, Ripivirine Antacids (take at least 30 minutes apart)

Administration: May be taken with or without food. Administration: To be taken 1 hour before meals or 2 hours
after meals
Pregnancy Category: C
NOTE: Dosing Intervals. Ensure a dosing interval of at least
ATC Code: A02BC04 2 hours between sucralfate and other non-antacid
medications, an interval of at least 30 minutes between
sucralfate and antacids, and an interval of at least 1 hour
DRUGS FOR THE MANAGEMENT OF ACID PEPTIC between sucralfate and enteral feeding.
DISEASE
Pregnancy Category: B

Rx SUCRALFATE ATC Code: A02BX02

Oral: 1 g tablet
An anionic sulfated disaccharide, that acts as an inhibitor of
pepsin. It also acts as an antiulcer agent by binding to
the surface of ulcers, forming a protective barrier.
Indications: Management of duodenal ulcer, gastric ulcer
and chronic gastritis.
Contraindication: Patients undergoing dialysis
DRUGS FOR ERADICATION OF Helicobacter pylori
Helicobacter pylori treatment should be preceded by H.
pylori diagnostic testing. Eradication treatment includes
the standard triple regimen reflected on Table A.
Antibiotics should NOT be used singly (i.e., should use 2-
3 antibiotic combination) because of risk of emergence
of drug resistance.

Dose: Table A. Standard triple H. pylori eradication regimen

Chronic gastritis, acute therapy, by mouth, ADULT, 1 g 4 Regimen Dosage Duration
times daily for 4–8 weeks for up to 12 weeks, if needed. If not allergic to Penicillin
Chronic gastritis, maintenance therapy, by mouth, ADULT, 1
g twice daily to prevent the recurrence of duodenal ulcers Omeprazole Standard dose
10–14
(maximum, 8 g daily); CHILD 12–18 years, 1 g 4–6 times Clarithromycin 500 mg twice a day
days
daily; CHILD 2–12 years, 500 mg 4–6 times daily; CHILD Amoxicillin 1 g twice a day
1 month to 2 years, 250 mg 4–6 times daily. If Allergic to Penicillin
GI hemorrhage from stress ulceration, prophylaxis, by
mouth, ADULT, 1 g 6 times daily (maximum, 8 g daily); Omeprazole Standard dose
10–14
CHILD 12–18 years, 1 g 4–6 times daily; CHILD 2–12 Metronidazole 500 mg thrice a day
days
years, 500 mg 4–6 times daily; CHILD 1 month to 2 Clarithromycin 500 mg twice a day
years, 250 mg 4–6 times daily.

Precautions:
Chronic renal failure (e.g., systemic aluminum toxicity). AMOXICILLIN
Children; neonates.
Lactation (not known if excreted in breastmilk).
See Amoxicillin under Chapter 7 Antiinfectives under Beta-
Lactam Antibacterials, Penicillins
Adverse Drug Reactions:
Common: Constipation, diarrhea, nausea, vomiting,
dizziness, dry mouth, flatulence, GI disturbances, rash,
pruritus, headache, vertigo, back pain, drowsiness. CLARITHROMYCIN
Less Common: Insomnia, hypersensitivity reactions (e.g.,
pruritus, edema, urticaria, respiratory difficulty, rhinitis,
laryngospasm, facial swelling). See Clarithromycin under Chapter 7 Antiinfectives under
Rare: Urticaria (hives), angioedema, respiratory difficulty, Macrolides, Lincosamides and Streptogramins
rhinitis, bezoars.
METRONIDAZOLE
Drug Interactions:
Monitor closely with:
Decreases absorption of the following drugs:

7
 ALIMENTARY TRACT AND METABOLISM

See Metronidazole under Chapter 7 Anti-infectives under Precautions:

Other Antibacterials GI disorders; pyrexia and in warm environments; Down
syndrome; prostatic enlargement; cardiac disorders;
A

hypoxia; constipation; delirium; tachycardia; or fever

from any cause.
DRUGS FOR FUNCTIONAL Elderly; children.
GASTROINTESTINAL DISORDERS Lactation (may cause anti-muscarinic effects in infants).

ANTICHOLINERGICS NOTE: Since atropine has a short duration, late unopposed

bradycardia may result. Close monitoring is necessary.

Rx ATROPINE Adverse Drug Reactions:

Common: Blurred vision, constipation, cycloplegia, delirium,
dryness of mouth, nose and skin, difficulty in micturition
Oral: 600 micrograms (as sulfate) (equivalent to 500
and swallowing, fever, flushing, mydriasis, palpitations,
micrograms atropine) tablet
photophobia, thirst, transient bradycardia followed by
Inj.: 500 micrograms/mL, 600 micrograms/mL, and 1
tachycardia, urinary retention.
mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
Less Common: Agitation, arrhythmias, ataxia, confusion (in
elderly), disorientation, excitement, headache, heat
A naturally occurring tertiary amine anti-muscarinic alkaloid
prostration, hyperpyrexia, hypertension, paralytic ileus,
from Atropa belladonna that competitively blocks
psychosis, rapid respiration, rash, restlessness,
acetylcholine action in central and peripheral muscarinic
vomiting.
autonomic receptors.
Drug Interactions:
Indications: Pre-operative medication to reduce salivary,
Monitor closely with:
bronchial, and nasal secretions; treatment of functional
Decreases oral absorption of Atropine:
disturbances of GI motility such as irritable bowel
Antacids
syndrome.
Increases risk of adverse or toxic effects of the following
NOTE: Has limited efficacy as an anti-muscarinic and should
drugs:
be used only if other measures (e.g., diet, sedation,
Alcohol (CNS depression), Chlorpromazine (anti-
counseling, amelioration of environmental factors) have
muscarinic)
been of little or no benefit.
Increases bioavailability of Beta Blockers, e.g., Metoprolol
Contraindications: Angle-closure glaucoma; severe
inflammatory GI disease or GI obstruction; prostatic
Avoid concomitant use with:
hypertrophy; prostatism and urinary obstruction;
Decreases serum concentration of the following drugs,
myasthenia gravis; thyrotoxicosis; organochlorine
decreasing their therapeutic effects:
poisoning; pyloric stenosis; poisoning caused by CNS
Haloperidol (schizophrenic symptoms may worsen)
adrenergic stimulants, phenothiazines, tricyclic
antidepressants; and, other anticholinergics.
Enhances therapeutic effect of Atropine:
Drugs with anticholinergic effects, e.g., Amantadine,
Dose:
Belladonna Alkaloids, Ipratropium
Diverticular disease, irritable bowel syndrome, non-ulcer
dyspepsia, by mouth, ADULT, 0.6–1.2 mg as a single
Enhances therapeutic effect of the following drugs:
dose at bedtime.
Digoxin, Norepinephrine (pressor effect; blocks its reflex
Premedication in balanced anesthesia, by IM or SC
bradycardia)
injection, ADULT, 300–600 micrograms 30–60 minutes
before anesthesia; CHILD >20 kg, 300 to 600
Increases risk of adverse or toxic effects of Atropine:
micrograms 30–60 minutes before anesthesia; CHILD
Drugs with anticholinergic effects, e.g., Amantadine,
12–16 kg, 300 micrograms 30–60 minutes before
Belladonna Alkaloids, Ipratropium (central
anesthesia; CHILD 7–9 kg, 200 micrograms 30–60
anticholinergic delirium)
minutes before anesthesia; CHILD 3 kg, 100 micrograms
30 to 60 minutes before anesthesia;
Increases risk of adverse or toxic effect of the following
by IV injection, ADULT, 300–600 micrograms
drugs:
immediately before induction of anesthesia.
Digoxin, Phenylephrine eye drops (severe
hypertension)
Dose Adjustment:
Renal Impairment:
Increases serum concentration of Digoxin
For mild-to-moderate renal impairment, dose reduction, or
less frequent doses, after initial atropinization is
Reduces therapeutic effect of Atropine:
warranted (since atropine may be eliminated more
Anticholinesterases, e.g., Neostigmine, Pyridostigmine
slowly).
(antagonizes anticholinergic effect of Atropine)
For severe impairment, the patient should be referred to a
specialist.
Reduces therapeutic effect of Metoclopramide
(antagonism)

8
ALIMENTARY TRACT AND METABOLISM
Administration:
For oral administration, may be taken with or without
food.
For IV administration, administer undiluted by rapid IV
injection.
Pregnancy Category: C
ATC Code: A03BA01
Rx DICYCLOVERINE (DICYCLOMINE)
Oral: 10 mg tablet (as hydrochloride)
10 mg/5 mL syrup (as hydrochloride), 60 mL
An anti-muscarinic agent used primarily as anti-spasmodic.
It has a much less marked anti-muscarinic action than
atropine and may also have some direct action on
smooth muscle.
Indications: Treatment of patients with functional bowel or
irritable bowel syndrome; adjunct in GI disorders
characterized as functional disturbances of
gastrointestinal motility.
Contraindications: Obstructive diseases of the GI tract;
severe ulcerative colitis; reflux esophagitis; unstable
cardiovascular status in acute hemorrhage; obstructive
uropathy; glaucoma; myasthenia gravis; breastfeeding;
infants <6 months of age; hypersensitivity to
dicycloverine or any component of the formulation.
Dose:
Gastrointestinal motility disorders or irritable bowel, by
mouth, ADULT, 20 mg 4 times daily for 7 days; after 1
week, may increase to 40 mg 4 times daily; CHILD 2–12
years, 10 mg per dose 3–4 times daily; INFANT 6–24
months, 5 mg per dose 3–4 times daily.
NOTE: In adults, if doses <80 mg daily does not achieve
desired results or if adverse effects occur, discontinue
therapy. Safety data are not available for doses >80 mg
daily for duration >2 weeks.
Dose Adjustment:
Geriatric:
Use with caution. Lower doses may be warranted.
Renal and Hepatic Impairment:
Dose adjustment in this population has not been studied.
Use with caution.
Precautions:
WARNING: Do NOT administer to children <6 months.
Diarrhea;
Hot weather and/or exercise (heat exhaustion may occur);
Psychosis and delirium;
Elderly (avoid long-term use);
Infants (serious respiratory reactions, central nervous
system symptoms, and deaths have been reported).
SKILLED TASKS. May cause drowsiness or blurred vision. Avoid
performing tasks, which require mental alertness, e.g., operating
machinery or driving.
A
Adverse Drug Reactions:
Common: Dizziness, xerostomia, nausea, blurred vision,
somnolence, nervousness, weakness.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Dicycloverine:
Anticholinergic Agents e.g., Atropine
Increases risk of adverse or toxic effects of Opioid
Analgesics (constipation; urinary retention)
Avoid concomitant use with:
Enhances therapeutic effect of Dicycloverine:
Ipratropium, Oral Inhalation (anticholinergic effect)
Administration: May be taken before or after meals
Pregnancy Category: B
ATC Code: A03AA07
Rx HYOSCINE (HYOSCYAMINE)
Oral: 10 mg tablet (as N-butyl bromide)
5 mg/5 mL syrup (as N-butyl bromide), 60 mL
Inj.: 20 mg/mL (as N-butyl bromide), 1 mL ampule (IM, IV,
SC)
A poorly-absorbed, quaternary amine, anticholinergic agent
that is used to relax smooth muscles, and reduce GI
motility and spasm.
Indication: Smooth muscle spasm of the genito-urinary or GI
tract (e.g., renal and biliary spasm).
Contraindications: Glaucoma; megacolon; myasthenia
gravis; stenotic lesions of the GI tract; paralytic ileus;
acute hemorrhage; tachycardia; angina or heart failure;
obstructive prostatic hypertrophy; IM administration in
patients with anticoagulant therapy; hypersensitivity to
hyoscine or any component of the formulation.
Dose:
Acute therapy of smooth muscle spasm, by mouth, ADULT,
10–20 mg daily; prolonged therapy, by mouth, ADULT,
10 mg 3–5 times daily (maximum, 60 mg daily);
by IM, IV, or SC injection, 10–20 mg (maximum, 100 mg
daily); CHILD >6 years, 10 mg 3 times daily.
NOTE: Doses can be repeated after 30 minutes if needed
(may need to be repeated more frequently in endoscopy).
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
For patients with renal failure, use of this drug is not
recommended.
9
 ALIMENTARY TRACT AND METABOLISM

Precautions: Indications: Symptomatic relief of abdominal pain and

CNS effects; Idiosyncratic reactions (e.g., acute toxic cramps, bowel disturbances and intestinal discomfort
psychosis, agitation, confusion, delusions, associated with irritable bowel syndrome; GI spasm
A

hallucinations, paranoid behavior, and rambling secondary to organic diseases.

speech);
Visual disturbances; Contraindication: Paralytic ileus
Withdrawal (e.g., dizziness, headache, nausea, and
vomiting, following abrupt discontinuation); Dose:
Dementia; Irritable bowel syndrome, by mouth, ADULT, 135 mg 3 times
Fever, high ambient temperature; daily before meals (or 100 mg 4 times daily), may
Cardiovascular disease; GI obstruction or atony; gradually reduce after several weeks of symptomatic
Genitourinary disease and obstruction; relief.
Glaucoma; Gastrointestinal smooth muscle spasm, symptomatic relief,
Hiatal hernia; by mouth, ADULT and CHILD >10 years, 135 mg 3 times
Hyperthyroidism; daily (or 100 mg 4 times daily), may gradually reduce
Psychosis; after several weeks when desired effect has been
Seizure disorders; obtained; CHILD 8-10 years, 100 mg 3 times daily; CHILD
Ulcerative colitis; 4–8 years, 50 mg 3 times daily; CHILD 3–4 years, 25 mg
Renal and hepatic impairment; 3 times daily.
Anaphylaxis;
Elderly (avoid use); Precautions:
Children (increased risk of adverse effects). Cardiac disorders, e.g., heart block; renal and hepatic
impairment.
SKILLED TASKS. May cause drowsiness or blurred vision. Avoid Lactation (no data available, use with caution).
performing tasks, which require mental alertness, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Adverse Drug Reactions: Common: Urticaria, angioedema, face edema, exanthema,
Less Common: Diarrhea, dry mouth, nose, throat, or skin, anaphylactic reactions.
dyshidrosis, headache, increased eye pressure, itching, Less Common: Gastrointestinal disturbances, dizziness,
mydriasis, nausea, skin reactions (e.g., urticaria, headache, insomnia, anorexia, decreased heart rate.
pruritus, erythema, rash), tachycardia, vomiting.
Drug Interactions: No information found
Drug Interactions:
Monitor closely with: Administration: To be taken 20 minutes before meals.
Enhances therapeutic effect of Alcohol (CNS depressant) Swallow whole with at least 100 mL of water. Do NOT
chew or crush.
Increases risk of adverse or toxic effects of the following
drugs: Pregnancy Category: Not available
Topiramate (hyperthermia; decreased sweating),
Zonisamide (hyperthermia; decreased sweating) ATC Code: A03AA04

Avoid concomitant use with:

Enhances therapeutic and toxic effects of Anticholinergic PROPULSIVES
Drugs, e.g., Atropine

Reduces therapeutic of Anticholinesterases, e.g.,

Rx DOMPERIDONE
Neostigmine
Oral: 10 mg tablet
Administration: Swallow tablets whole with full glass of 1 mg/mL suspension, 60 mL
water.
A peripheral dopamine-receptor blocker that facilitates
Pregnancy Category: C gastric emptying by increasing esophageal peristalsis,
enhancing gastroduodenal coordination and lower
ATC Code: A03BA03 esophageal sphincter pressure, as well as gastric motility
and peristalsis.

Indication: Gastrointestinal motility disorders e.g., diabetic

Rx MEBEVERINE gastroparesis and gastritis.

Oral: 100 mg tablet (as hydrochloride) Contraindications: Prolactin-releasing pituitary tumor

An antispasmodic with direct effects on smooth muscles of
the gastrointestinal (GI) tract without altering normal gut
motility.
(prolactinoma); known existing prolongation of cardiac
conduction intervals, particularly QT; significant
electrolyte disturbances; underlying cardiac disease
(e.g., heart failure); moderate or severe hepatic
impairment; patients with GI hemorrhage, mechanical
obstruction, or perforation; concomitant use with potent

10
ALIMENTARY TRACT AND METABOLISM
CYP3A4 inhibitors, macrolides (e.g., erythromycin),
protease inhibitors, or nefazodone; concomitant use with
QT-prolonging drugs.
Dose:
Gastrointestinal motility disorders, by mouth, ADULT, 10 mg
3 times daily (maximum, 30 mg daily), (use the lowest
effective dose for the shortest duration necessary);
ADOLESCENT <35 kg, CHILD <12 years, and INFANT,
0.25 mg/kg up to 3 times daily (maximum, 0.75 mg/kg
daily or 30 mg daily).
Gastroparesis, by mouth, ADULT, initially 10 mg 3 times
daily.
Dose Adjustment:
Geriatric:
In patients >60 years, there is an increased risk of serious
ventricular arrhythmia or sudden cardiac death. Use with
caution
Renal Impairment:
In severe renal impairment, reduce dose or dosing
frequency with prolonged treatment.
Hepatic Impairment:
In mild hepatic impairment, use with caution (undergoes
hepatic metabolism).
In moderate to severe hepatic impairment, use is
contraindicated.
Precautions:
WARNING: Prolongs QT interval and poses a risk of
torsades de pointes. Consult with physician prior to
concomitant use of a vasoconstrictor. Use
epinephrine, mepivacaine, and levonordefrin with
caution.
Cardiac conduction disorders or cardiac disease; Moderate
or severe hepatic impairment;
Prolactinoma;
In patients >60 years, there is an increased risk of serious
ventricular arrhythmia or sudden cardiac death.
Adverse Drug Reactions:
Common: Headache, migraine, xerostomia
Less Common: Abdominal cramps, appetite changes,
conjunctivitis, constipation, diarrhea, dizziness, drug
intolerance, dysuria, edema, extrapyramidal symptoms
(EPS).
Rare: Galactorrhea, gynecomastia, heartburn, hot flashes,
insomnia, irritability, lethargy, leg cramps, mastalgia,
menstrual irregularities, nausea, nervousness,
palpitation, increased prolactin, pruritus, rash,
regurgitation, stomatitis, sudden death, thirst, torsade
de pointes, urinary frequency, urticaria, weakness.
Drug Interactions:
Monitor closely with:
Decreases therapeutic effects of both Domperidone and
MAO Inhibitors e.g., Selegeline
Increases risk of adverse or toxic effects of Domperidone:
MAO Inhibitors e.g., Selegeline
Avoid concomitant use with:
Enhances QTc-prolonging effect of the following drugs:
Ivabradine, Mifepristone, QTc-prolonging Agents
Increase serum concentration Domperidone:
A
Conivaptan, CYP3A4 Inhibitors, Fusidic Acid
Administration: To be taken 15–30 minutes before meals.
It should be taken on an empty stomach.
Pregnancy Category: C
ATC Code: A03FA03
ANTIEMETICS AND ANTINAUSEANTS
SEROTONIN (5HT3) ANTAGONISTS
Rx ONDANSETRON
Oral: 8 mg tablet (as hydrochloride dihydrate)
Inj.: 2 mg/mL (as hydrochloride), 2 mL and 4 mL ampule
(IM, IV)
A selective type 3 serotonin (5-HT3) receptor inhibitor that
acts as an antiemetic by blocking the effect of serotonin
on the vagal afferent nerves.
Indications: Treatment of nausea and vomiting induced by
cytotoxic chemotherapy and radiotherapy; prevention
and treatment of postoperative nausea and vomiting.
Contraindication: Concomitant use of apomorphine;
Dose:
Prevention of nausea and vomiting associated with
chemotherapy, by mouth, ADULT, 8 mg twice daily; by IV
injection, ADULT, 0.15 mg/kg per dose (maximum, 16
mg/dose) administered over 15 minutes for 3 doses,
beginning 30 minutes prior to chemotherapy, followed by
subsequent doses 4–8 hours after the first dose;
ADOLESCENT, CHILD, and INFANT ≥6 months, 0.15
mg/kg per dose (maximum, 16 mg/dose) over 15
minutes for 3 doses, beginning 30 minutes prior to
chemotherapy, followed by subsequent doses
administered 4–8 hours after the first dose.
Prevention of nausea and vomiting associated with highly
emetogenic chemotherapy, by mouth, ADULT, 24 mg 30
minutes prior to the start of single-day chemotherapy.
Prevention of nausea and vomiting associated with
moderately emetogenic chemotherapy, by mouth,
ADULT, 8 mg 30 minutes prior to the beginning of
chemotherapy, repeat dose 8 hours after initial dose,
then 8 mg every 12 hours for 1 to 2 days after completion
of chemotherapy; CHILD 4–11 years, 4 mg 30 minutes
prior to chemotherapy, repeat 4 and 8 hours after the
first dose, then 4 mg every 8 hours for 1–2 days after
completion of chemotherapy.
Prevention of radiation therapy-induced nausea and
vomiting, total body irradiation, by mouth, ADULT, 8 mg
1–2 hours before each fraction of radiotherapy.
Prevention of radiation therapy-induced nausea and
vomiting, single high-dose fraction radiotherapy to
abdomen, by mouth, ADULT, 8 mg 1–2 hours before
11

irradiation, then 8 m every 8 hours after first dose for 1–
2 days after completion of radiotherapy.
Prevention of radiation therapy-induced nausea and
A
vomiting, daily fractionated radiotherapy to abdomen, by
mouth, ADULT, 8 mg 1–2 hours before irradiation, then
8 mg every 8 hours after first dose for each day of
radiotherapy.
Prevention of postoperative nausea and vomiting, by IM or
IV injection, ADULT, 4 mg as a single dose (over 2–5
minutes if by IV), administered approximately 30 minutes
before the end of anesthesia or as treatment if vomiting
occurs after surgery, repeat doses are generally
ineffective;
by IV injection, CHILD >40 kg, 4 mg as a single dose over
2–5 minutes; CHILD ≤40 kg, 0.1 mg/kg as a single dose
over 2–5 minutes.
NOTE: Single IV doses >16 mg is not recommended due to
the potential for QT prolongation.
Dose Adjustment:
Hepatic Impairment:
For severe hepatic impairment, maximum daily dose for oral
and parenteral administration is 8 mg.
Precautions:
QT prolongation (e.g., torsade de pointes); ileus or gastric
distention.
Adverse Drug Reactions:
Common: Headache, fatigue, malaise, constipation,
drowsiness, sedation, dizziness, agitation, anxiety,
paresthesia, sensation of cold, pruritus, skin rash,
diarrhea, urinary retention, elevated ALT and AST,
injection site reaction, hypoxia, fever.
Less Common: Abdominal pain, accommodation
disturbance, anaphylaxis, angina pectoris, angioedema,
atrial fibrillation, anaphylactoid reaction, bradycardia,
bronchospasm, cardiac arrhythmia, cardiorespiratory
arrest, bullous skin disease, chest pain, chills,
depression of ST segment on ECG, dyspnea, dystonic
reaction, ECG changes, extrapyramidal reaction,
hypersensitivity reaction, hypokalemia, hepatic failure,
hypotension, ischemic heart disease, laryngeal edema,
laryngospasm, mucosal tissue reaction, myocardial
infarction, neuroleptic malignant syndrome, oculogyric
crisis, palpitations, positive lymphocyte transformation
test, prolonged Q­T interval on ECG, second-degree
atrioventricular block, serotonin syndrome, shock,
Stevens-Johnson syndrome, stridor, supraventricular
tachycardia, syncope, tachycardia, tonic-clonic seizures,
torsade de pointes, toxic epidermal necrolysis, transient
blindness (≤48 hours), transient blurred vision (following
infusion), urticaria, vascular occlusive events, ventricular
premature contractions, ventricular tachycardia,
weakness, xerostomia.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
QTc-prolonging agents, Serotonin Modulators
(serotonergic effect)
Increases risk of adverse or toxic effects of Serotonin
Modulators
12
ALIMENTARY TRACT AND METABOLISM
Reduces therapeutic effect of the following drugs:
Tapentadol (analgesic effect), Tramadol (analgesic
effect)
Avoid concomitant use with:
Decreases serum concentration of Ondansetron:
CYP3A4 Inducers, Dabrafenib, Mitotane
Increases risk of adverse or toxic effects of the following
drugs:
Apomorphine (hypotensive effect), Ivabradine,
Mifepristone, QTc-prolonging agents (QTc-prolonging
effect)
Increases serum concentration of the following drugs:
Tizanidine [if concomitant use cannot be avoided, initiate
tizanidine at 2 mg and increase in 2–4 mg increments
based on patient response]
Administration:
For oral administration, administer 30 minutes prior to
chemotherapy, 1–2 hours before radiotherapy, or 1 hour
prior to induction of anesthesia.
For IM injection, administer undiluted.
For IVPB, infuse diluted solution over 15–30 minutes.
For IV push, single doses may be administered by IV
injection as undiluted solution over 2–5 minutes.
For IV infusion, dilute in 50 mL D5W or NS.
Pregnancy Category: B
ATC Code: A04AA01
Rx METOCLOPRAMIDE
Oral: 10 mg tablet (as hydrochloride)
5 mg/5 mL syrup (as base and as hydrochloride), 60
mL
Inj.: 5 mg/mL (as base and as hydrochloride), 2 mL
ampule (IM, IV)
A dopamine (D2) antagonist that blocks receptors in the
chemoreceptor trigger zone of the medulla, resulting in
potent anti-nausea and antiemetic action; also blocks
receptors in the GI tract, stimulating gastric emptying
and small intestinal transit.
Indications: Management of nausea and vomiting in GI
disorders, in migraine, and in chemotherapy and
radiotherapy; disorders of decreased gastrointestinal
motility such as gastroparesis or ileus; Gastroesophageal
Reflux Disease (GERD).
NOTE: In children and adolescents <20 years, use is
restricted to treatment of severe intractable vomiting of
known etiology, as an aid to GI intubation, management
of radiotherapy and chemotherapy-induced nausea and
vomiting, and as premedication.
ALIMENTARY TRACT AND METABOLISM
Contraindications: Pheochromocytoma; GI obstruction; 3 to
4 days after GI surgery; perforation or hemorrhage;
convulsive disorders.
Dose:
Nausea and vomiting, GERD, gastroparesis, by mouth, IM
injection, or slow IV injection (over 1–2 minutes), ADULT,
10 mg 3 times daily; YOUNG ADULT 15–19 years (under
60 kg), 5 mg 3 times daily; CHILD 9–14 years (30 kg and
over), 5 mg 3 times daily; CHILD 5–9 years (20 to 29 kg),
2.5 mg 3 times daily; CHILD 3–5 years (15–19 kg), 2 mg
2–3 times daily; CHILD 1–3 years (10–14 kg), 1 mg 2–3
times daily; INFANT <1 year (or up to 10 kg), 1 mg twice
daily; (usual maximum 500 micrograms/kg daily,
particularly for children and young adults).
NOTE: High-dose use in cytotoxic chemotherapy is reserved for
patients at a high risk of emesis or when other therapies are
ineffective.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Precautions:
WARNING: Can cause tardive dyskinesia (TD). Avoid
treatment >12 weeks unless therapeutic benefit is
thought to outweigh the risk of developing TD.
May mask underlying disorders, such as cerebral irritation;
Avoid for 3–4 days after GI surgery.
for short-term use only, i.e., <12 weeks (increased risk of
tardive dyskinesia with cumulative dose and length of
treatment).
Edematous conditions; Parkinson’s disease; Depression;
epilepsy; hypertension; porphyria; severe renal
impairment.
Elderly (more sensitive to adverse effects); young adults and
children (increased risk of EPS).
Breastfeeding (present in milk; adverse effects may develop
in infants).
SKILLED TASKS. May cause drowsiness or blurred vision. Avoid
performing tasks, which require mental alertness, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Common: Akathisia, dizziness, drowsiness, fatigue,
headache, somnolence.
Less Common: Bronchospasm, constipation, depression,
diarrhea, edema, EPS, hyperprolactinemia leading to
galactorrhea, hypertension, hypotension, pruritus, rash,
restlessness, urticaria.
Drug Interactions:
Monitor closely with:
Decreases absorption of Digoxin
Enhances therapeutic effect of the following drugs:
Alcohol (CNS depressant effects)
Analgesics, e.g., aspirin, paracetamol (analgesic
effect)
Increases absorption of Alcohol (accelerated gastric
emptying)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
A
Extrapyramidal reactions-causing drugs, e.g.,
Chlorpromazine, Fluphenazine, Haloperidol
Reduces therapeutic effect of Metoclopramide
Opioid-containing Medications
Administration: Administer by IV injection over 1–2 minutes
to lessen transient agitation and restlessness.
Pregnancy Category: B
ATC Code: A03FA01
BILE AND LIVER THERAPY
BILE ACID PREPARATIONS
URSODEOXYCHOLIC ACID
Rx
(URSODIOL)
Oral: 250 mg capsule/tablet
500 mg tablet
A naturally occurring bile acid that decreases the cholesterol
content of bile and bile stones by reducing the secretion
of cholesterol from the liver and the fractional
reabsorption of cholesterol by the intestines. It is used as
a gallstone dissolution agent for its cholelitholytic or
anticholestatic action.
Indications: Management of Primary biliary cirrhosis;
prevention and dissolution of gallstones.
Contraindications: Calcified cholesterol stones, radiopaque
stones, or radiolucent bile pigment stones; unremitting
acute cholecystitis, cholangitis, biliary obstruction,
gallstone pancreatitis, or biliary-gastrointestinal fistula;
allergy to bile acids; hypersensitivity to ursodeoxycholic
acid or any component of the formulation.
Dose:
Primary biliary cirrhosis, by mouth, ADULT, 13–15 mg/kg
daily in 2–4 divided doses.
Gallstone dissolution, by mouth, ADULT, 8–10 mg/kg daily
in 2–3 divided doses for 6–12 months.
Gallstone prevention, by mouth, ADULT, 300 mg twice daily.
Precautions:
Biliary obstruction; non-visualizing gallbladder.
Adverse Drug Reactions:
Common: Headache, dizziness, diarrhea, constipation,
dyspepsia nausea, back pain, upper respiratory tract
infection, alopecia, skin rash, hyperglycemia, vomiting,
peptic ulcer, urinary tract infection, leukopenia,
thrombocytopenia, cholecystitis, hypersensitivity
reaction, viral infection, arthritis, musculoskeletal pain,
pharyngitis, bronchitis, cough, flu-like symptoms.
Less Common: biliary colic, esophagitis, facial edema, fever,
hepatobiliary disease, jaundice, laryngeal edema,
13

malaise, metallic taste, myalgia, peripheral edema,
pruritus, urticaria, weakness.
A
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Ursodeoxycholic Acid:
Estrogen Derivatives e.g. estriol, Fibric Acid Derivatives
e.g. clofibrate
Avoid concomitant use with:
Decreases absorption of Nitrendipine
Decreases serum concentration of Ursodeoxycholic Acid:
Aluminum Hydroxide [administer Ursodeoxycholic Acid 2
hours before or 6 hours after Aluminum-containing
Antacid products], Bile Acid Sequestrants [administer
Ursodeoxycholic Acid at least 5 hours after Bile Acid
Sequestrants]
Administration: To be taken with food.
Pregnancy Category: B
ATC Code: A05AA02
DRUGS FOR CONSTIPATION
LAXATIVES
OTC BISACODYL
Oral: 5 mg tablet
5 mg MR tablet
Rectal: 5 mg suppository (for children)
10 mg suppository (for adults)
A diphenylmethane stimulant laxative that acts by
stimulating peristalsis by directly irritating the smooth
muscle of the large intestine. It also alters water and
electrolyte secretion, producing net interstitial fluid
accumulation and laxation.
Indications: Bowel evacuation before investigational
procedures or surgery; management of constipation.
Contraindications: Acute abdominal conditions (e.g.
appendicitis, intestinal inflammatory bowel disease);
intestinal obstruction; ileus; severe dehydration; severe
abdominal pain associated w/ nausea and vomiting;
anal fissures or ulcerative colitis w/ mucosal damage
(rectal).
Dose:
Bowel evacuation, by mouth, ADULT, initially 10–20 mg the
night before the procedure followed by 10 mg rectal
suppository the next morning (or 10 mg on each of the 2
nights before the procedure); CHILD 4–10 years, 5 mg
the night before the procedure and 5 mg rectal
suppository the following morning.
Constipation, by mouth, ADULT, 5–10 mg at night, up to 20
mg may be given as necessary; CHILD 4 to 10 years, 5
mg at night;
14
ALIMENTARY TRACT AND METABOLISM
by rectum, ADULT, 10 mg in the morning; CHILD ≤10
years, 5 mg in the morning.
Precautions:
Intestinal obstruction or acute abdominal conditions such
as appendicitis; inflammatory bowel disease; severe
dehydration; anal fissures, proctitis, ulcerated
hemorrhoids (avoid use of suppositories).
Adverse Drug Reactions:
Common: Abdominal discomfort, diarrhea, electrolyte
disturbance, nausea, vertigo, vomiting, hematochezia.
Less Common: Irritation, proctitis (rectal)
Rare: Hypersensitivity reactions
Drug Interactions: No information found
Administration: To be taken on an empty stomach.
For tablets, administer the evening before if a morning
bowel movement is desired. MR tablets must be
swallowed whole and not crushed or chewed. Do NOT
take within 1 hour of antacids or milk.
For suppositories, administer at the time a bowel
movement is desired.
Pregnancy Category: C
ATC Code: A06AB02
OTC CASTOR OIL
Oral: USP grade
A fixed oil obtained from the seeds of Ricinus communis
that is used as a stimulant laxative. It is hydrolyzed to
ricinoleic acid in the small intestine, which reduces net
absorption of fluid and electrolytes and stimulates
peristalsis.
Indication: Temporary relief of occasional constipation;
bowel evacuation.
Contraindications: Abdominal pain, nausea, vomiting
Dose:
Bowel evacuation / constipation, by mouth, ADULT, 15 to 60
mL as a single dose; CHILD 2–11 years, 5 to 15 mL as a
single dose.
Precautions:
WARNING: Do NOT use for >1 week or when
abdominal pain, nausea, vomiting, or rectal
bleeding are present unless directed by health care
provider.
Elderly (e.g., severe fluid and electrolyte loss, which may
affect mental function);
Pregnancy (associated with induction of labor).
ALIMENTARY TRACT AND METABOLISM
Adverse Drug Reactions:
Dizziness, electrolyte disturbance, abdominal cramps,
diarrhea, nausea, pelvic congestion
Drug Interactions: No known significant interactions
Administration: Should be administered on an empty
stomach, with juice or carbonated beverages.
Do NOT administer at bedtime because of rapid onset of
action.
Shake emulsions well before use. May be mixed with
120–240 mL of water, milk, fruit juice, or soft drink
before administration.
Pregnancy Category: Not available
ATC Code: A06AB05
OTC GLYCEROL (GLYCERIN)
Oral: USP grade (liquid)
Rectal: 2 g suppository
An osmotic dehydrating agent that possesses hygroscopic
and lubricating properties. It increases osmotic pressure,
drawing water into the colon and stimulating evacuation.
Indication: Management of constipation
Contraindications: No information found
Dose:
Constipation, by rectum, ADULT, 2.250 g suppository, as
needed; CHILD, 1.375 g suppository, as needed.
Precautions:
May cause rectal discomfort or a burning sensation;
Hypovolemia, cardiac failure, or renal disease (e.g.,
circulatory overload, pulmonary edema, and heart
failure)
Dehydration;
Diabetes mellitus.
Adverse Drug Reactions: Local irritation (e.g., rectal
discomfort, burning sensation), cramping pain,
tenesmus.
Drug Interactions: No information found
Administration: Insert suppository high in the rectum and
retain for approximately 15 minutes. Suppository does
not need to melt to produce response.
Pregnancy Category: Not available
ATC Code: A06AX01
Rx LACTULOSE
A
Oral: 3.3 g/5 mL (3.35 g/5 mL) syrup, 120 mL
A synthetic lactose derivative that can act as an ammonia
(NH3) detoxicant. It is degraded by bacteria in the gut
resulting in an acidic pH, which inhibits NH3 diffusion into
the blood, while enhancing the diffusion of NH3 from the
blood into the gut. It also produces an osmotic effect in
the colon with resultant distention, promoting peristalsis
and reducing blood ammonia concentration to reduce
the degree of portal systemic encephalopathy.
Indications: Prevention and treatment of hepatic
encephalopathy, management of constipation
Contraindication: Patients requiring low galactose diet
Dose:
Constipation, by mouth, ADULT, 10–20 g (15–30 mL) daily,
may be increased to 40 g (60 mL) daily if necessary.
Portal Systemic Encephalopathy (PSE), prevention, by
mouth, ADULT, 20–30 g (30–45 mL) 3–4 times daily
(adjust dose every 1–2 days to produce 2 to 3 soft stools
daily); CHILD, 26.7–60 g daily (40–90 mL daily) in
divided doses (adjust dosage to produce 2–3 stools
daily); INFANT, 1.7–6.7 g daily (2.5–10 mL daily) in
divided doses (adjust dosage to produce 2–3 stools
daily).
Acute PSE, treatment, by mouth, ADULT, 20–30 g (30–45
mL) every 1 hour to induce rapid laxation, reduce to 20–
30 g (30–45 mL) 3–4 times daily after laxation is
achieved (titrate to produce 2–3 soft stools/day).
Overt Hepatic Encephalopathy (OHE), treatment, by mouth,
ADULT, 20–30 g 16.7 g (25 mL) every 1 to 2 hours until
at least 2 soft or loose bowel movements are produced
daily (titrate to maintain 2–3 bowel movements daily).
Precautions:
Electrolyte imbalance (monitor periodically for electrolyte
imbalance when used >6 months or in patients
predisposed to electrolyte abnormalities);
Hepatic disease.
Diabetes (contains galactose and lactose; use with caution).
Elderly (may predispose electrolyte imbalance; more likely
to show CNS signs of dehydration and electrolyte loss;
sorbitol is equally effective as a laxative and less
expensive, however, sorbitol cannot be substituted in the
treatment of hepatic encephalopathy); infants; may
develop hyponatremia and dehydration).
Adverse Drug Reactions:
Common and Less Common: Dehydration, hypernatremia,
hypokalemia, abdominal discomfort, abdominal
distention, belching, cramping, diarrhea, flatulence,
nausea, vomiting.
Rare: Lactic acidosis
Drug Interactions:
Monitor closely with:
Reduces the therapeutic effect of Lactulose:
Glutamine (ammonia-lowering effects)
Administration: May mix with fruit juice, water, or milk. When
administered via a gastric tube, dilute to prevent
15
 ALIMENTARY TRACT AND METABOLISM

induction of vomiting and the possibility of aspiration

pneumonia. Drug Interactions:
Monitor closely with:
A

Pregnancy Category: B Increases risk of adverse or toxic effects of the following

drugs:
ATC Code: A06AD11 Calcium-containing Antacids (ectopic calcification),
Calcium Supplements (ectopic calcification)

MONOBASIC / DIBASIC Avoid concomitant use with:

OTC
SODIUM PHOSPHATE
Oral: 48 g/18 g per 100 mL solution, 45 mL bottle
A saline laxative that promotes bowel movements by
increasing water retention in the intestines.
Indication: Management of constipation
NOTE: NOT for bowel cleansing.
Contraindications: Previous kidney problem, congestive
heart failure, impaired renal functions, decreased
intervascular volume, dehydration, uncorrected
electrolyte abnormalities, children under 5 years.
Dose:
Constipation, by mouth, ADULT, 15 mL (1 tablespoon)
(maximum dose, 30–45 mL or 2–3 tablespoons); CHILD
10–11 years, 15 mL (1 tablespoon) (maximum dose, 15
mL or 1 tablespoon); CHILD 5–9 years, 7.5 mL (½
tablespoon) (maximum dose, 7.5 mL or ½ tablespoon).
NOTE: Not to be administered in children under 5 years.
1 tablespoon = 3 teaspoons
Dose Adjustment:
Renal Impairment:
Do not administer in severe renal impairment.
Precautions:
WARNING: Taking more than the recommended dose
in 24 hours can be harmful.
Increases absorption of Phosphates:
Vitamin D (decreases laxative effect)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics, Drugs that affect serum electrolytes
(hyperphosphatemia, hypocalcemia, hypernatremia),
(Vitamin D (hyperphosphatemia)
Reduced therapeutic effects of Phosphates:
Aluminum Salts, Calcium Salts, Magnesium Salts
Administration: Recommended doses are to be diluted in 1
full glass (8 fl. oz.) of cool water, followed with at least 1
additional full glass (8 fl. oz.) of cool water.
NOTE: Drink plenty of water after use to prevent dehydration
associated with significant loss of liquid when using this
product.
Pregnancy Category: Not available
ATC Code: A06AD17
(CALCIUM SENNOSIDES) STANDARD
OTC SENNA
CONCENTRATE
Oral: 187 mg and 374 mg tablet
8.77 mg and 17.54 mg (calculated as sennoside B)
tablet (as Calcium sennosides, equivalent to
Standardized Senna Concentrate)

An anthraquinone glycoside preparation consisting of the

Low serum calcium concentrations; dried leaflet of Cassia acutifolia or Cassia angustifolia,
Infected phosphate renal calculi; with sennosides A and B as active cathartic principles.
Hyperkalemia;
Congestive heart failure; Indications: Short-term treatment of constipation;
Hypertension; evacuation of colon for bowel or rectal examinations.
Edema;
GI obstruction; Contraindications: Intestinal obstruction, acute intestinal
Inflammatory bowel disease; inflammation (e.g., Crohn Disease), colitis ulcerosa,
Conditions where there is likely to be increased colonic appendicitis, abdominal pain of unknown origin.
absorption;
Debilitated patients; Dose:
Patients with pre­existing electrolyte disturbances. Bowel evacuation, by mouth, ADULT, 130 mg between 2–4
Elderly. in the afternoon of the day prior to the procedure.
Adverse Drug Reactions: Constipation, by mouth, ADULT, 15 mg once daily
Common and Less Common: Nausea, vomiting, diarrhea, (maximum, 70–100 mg daily taken in 2 divided doses);
abdominal pain hyperkalemia, hypernatremia, CHILD 6–12 years, initially 7.5–8.6 mg once daily
dehydration, hypokalemia, hyperphosphatemia and (maximum, 50 mg daily taken in 2 divided doses); CHILD
hypocalcemia (resulting in tetany and death), 2–6 years, initially 3.75 mg once daily (maximum, 15 mg
generalized tonic-clonic seizures and/or loss of daily taken in 2 divided doses).
consciousness.
Rare: Acute renal failure, nephrocalcinosis.

16
ALIMENTARY TRACT AND METABOLISM

Precautions:
WARNING: Taking more than the recommended dose
WARNING: NOT recommended for use in patients in 24 hours can be harmful.
experiencing stomach pain, nausea, vomiting, or

A
sudden change in bowel movements which lasts >2 Adverse Drug Reactions: Local irritation, hyperkalemia,
weeks. hypernatremia, dehydration, hypokalemia,
hyperphosphatemia and hypocalcemia (resulting in
NOT recommended for use in children <2 years. tetany and death), rectal gangrene (elderly).

Administration: Administer additional liquid during therapy

Prolonged use (has been associated with finger clubbing,
to ensure adequate hydration.
hypokalemia, tetany, hypertrophic osteoarthropathy,
See under Alimentary Tract and Metabolism – Drugs for
hypogammaglobulinemia, intermittent urinary excretion
Constipation, Laxatives for more information.
of aspartyl glucosamine, reversible cachexia, hepatitis,
or hepatic failure);
Pregnancy Category: Not available
Nausea or vomiting;
Undiagnosed abdominal pain;
ATC Code: A06AG01
Intestinal obstruction;
Inflammatory bowel disease;
Elderly (increased risk for dehydration due to predisposition
to constipation and decreased thirst reflex). ANTIDIARRHEALS,
INTESTINAL ANTIINFLAMMATORY/
Adverse Drug Reactions: ANTIINFECTIVE AGENTS
Common: Abdominal discomfort (e.g., colic, cramps),
diarrhea with excessive loss of water and electrolytes,
yellowish-brown discoloration of the urine at acid pH and INTESTINAL ANTIINFECTIVES
red at alkaline pH
Less Common: Reversible melanosis coli ANTIBIOTICS
Rare: Atonic non-functioning colon

Drug Interactions: No known significant interactions Rx RIFAXIMIN

Administration: Once daily doses should be taken at
Oral: 200 mg tablet
bedtime.
Rifaximin inhibits bacterial RNA synthesis by binding to
Pregnancy Category: Not available bacterial DNA-dependent RNA polymerase. It lowers
incidence of hepatic encephalopathy due to its broad-
ATC Code: A06AB06 spectrum activity against ammonia-producing enteric
bacteria.

ENEMAS Indication: Prevention and treatment of hepatic

encephalopathy.
MONOBASIC / DIBASIC
OTC Contraindications: Hypersensitivity to rifaximin, other
SODIUM PHOSPHATE rifamycin antibiotics, or any component of the
formulation.
Rectal: 19 g/7 g solution per 66 mL and 133 mL bottle
Dose:
A saline laxative that promotes bowel movements by Hepatic encephalopathy, by mouth, ADULT, 400 mg every 8
increasing water retention in the intestines. hours for 5-10 days.
Indications: Management of constipation Dose Adjustment:
Renal and Hepatic impairment:
NOTE: Not for bowel cleansing.
No dosage adjustment necessary; use with caution.
Contraindications: Previous kidney problem, congestive
Precautions:
heart failure, impaired renal functions, decreased
Hypersensitivity (e.g., exfoliative dermatitis, rash, urticarial,
intervascular volume, dehydration, uncorrected
flushing, angioneurotic edema, pruritus, and
electrolyte abnormalities, children under 2 years.
anaphylaxis);
Superinfection (Prolonged use may result in fungal or
Dose:
bacterial superinfection, i.e. C. difficile-associated
Constipation, by rectum, CHILD 5–11 years, one 66 mL
diarrhea (CDAD) and pseudomembranous colitis, CDAD
bottle; CHILD 2–5 years, one–half 66 mL bottle.
has been observed >2 months post-antibiotic
treatment);
NOTE: Not to be administered in children under 2 years.
Hepatic impairment (Monitor patients with severe hepatic
impairment for increased systemic exposure).

17
 ALIMENTARY TRACT AND METABOLISM

Dose Adjustment:
Adverse Drug Reactions: Renal Impairment:
Common: Peripheral edema, dizziness, fatigue, ascites, and Select doses with care.
A

nausea.
Less Common: Headache, depression, pruritus, skin rash,
abdominal pain, pseudomembranous colitis, anemia,
muscle spasm, arthralgia, nasopharyngitis, dyspnea,
epistaxis, and fever.
Rare: Anaphylaxis, angioedema, Clostridium difficile-
associated diarrhea, exfoliative dermatitis, flushing,
hypersensitivity reaction, and urticarial.
Drug Interactions:
Avoid concomitant use with:
BCG, intravesical (live), Cholera vaccine (Do not administer
cholera vaccine to patients who have received oral or
parenteral antibiotics within 14 days prior to
vaccination.)
Precautions:
Renal impairment; severe dehydration should be treated
with IV electrolyte solutions.
Adverse Drug Reactions:
Rare: Hypernatremia, vomiting
Drug Interactions: No information found
Administration: May be taken with or without food.
Reconstitute with clean potable water. Discard unused
reconstituted solution after 24 hours.
Pregnancy Category: C

Administration: May be taken with or without food. ATC Code: A07CA

Pregnancy Category: C
ANTIPROPULSIVES
ATC Code: A07AA11

OTC LOPERAMIDE
ORAL REHYDRATION SALT FORMULATIONS
Oral: 2 mg capsule (as hydrochloride)
ORAL REHYDRATION SALTS
OTC A synthetic pethidine derivative that inhibits gut motility and
(ORS 75-REPLACEMENT)
may also reduce gastrointestinal secretions. It acts
Oral: Composition: (Reduced osmolarity ORS per liter of directly on circular and longitudinal muscles through the
water, as recommended by WHO) opioid receptor to inhibit peristalsis and prolong transit
time.
Composition g/L mmol/L
Indications: Inhibition of gut motility for the reduction of
Sodium 2.6 75
gastrointestinal secretion; symptomatic control of acute
Chloride
and chronic non-specific diarrhea; adjunct to fluid
Trisodium 2.9 10 electrolytes replacement in the management of acute
citrate dihydrate and chronic non-specific diarrhea; management of
Potassium 1.5 20 colostomies or ileostomies.
chloride
Glucose, 13.5 75 Contraindications: Hypersensitivity to loperamide or any
anydrous component of the formulation; abdominal pain without
Total weight 20.5 diarrhea; children <2 years.

Dose:
An oral rehydration salt formulation containing reduced
Acute diarrhea, by mouth, ADULT, initially 4 mg, followed by
osmolar concentration of sodium and glucose that is
2 mg after each loose stool (maximum, 16 mg daily,
widely used in treating children with acute non-cholera
usual dose is 6-8 mg); CHILD 8–12 years (>30 kg), 2 mg
diarrhea, and in adults and children with cholera.
3 times daily; CHILD 6–8 years (20–30 kg), 2 mg twice
daily; CHILD 2–5 years (13–20 kg), 1 mg 3 times daily.
Indications: Replacement of fluid and electrolyte losses in
Chronic diarrhea, by mouth, ADULT, initially 4 mg, followed
mild to moderate dehydration due to acute diarrhea or
by 2 mg after each loose stool (maximum, 16 mg daily),
vomiting; replacement of continuing loss from vomiting
maintenance dose must be slowly titrated downward to
or diarrhea.
minimum required to control symptoms (typically 4–8 mg
daily, in divided doses), if no improvement is seen after
Contraindications: Severe dehydration; severe and
treatment with 16 mg for at least 10 days, further use is
sustained vomiting; diarrhea; glucose malabsorption; to
unlikely to be of benefit.
patients with difficulty in drinking.
Traveler’s diarrhea, by mouth, ADULT, initially 4 mg after
first loose stool, followed by 2 mg after each subsequent
Dose:
stool (maximum, 8 mg daily); CHILD 9–11 years, 2 mg
Fluid and electrolyte loss in acute diarrhea, by mouth,
after first loose stool, followed by 1 mg after each
ADULT, 200–400 mL solution after every loose motion;
subsequent stool (maximum dose, 6 mg daily); CHILD 6–
INFANT and CHILD, refer to WHO IMCI.
8 years, 2 mg after first loose stool, followed by 1 mg
after each subsequent stool (maximum dose, 4 mg daily)

18
ALIMENTARY TRACT AND METABOLISM

Ulcerative colitis, acute treatment, by mouth, ADULT,

NOTE: NOT recommended for infants and children <2 years. Asacol 400 mg
Initially 2.4 g daily in divided
tablet
Precautions: doses

A
Ipocol tablet
WARNING: If diarrhea lasts longer than 2 days, Mezavant Initially 2.4–4.8 g once daily
symptoms worsen, or abdominal swelling or Initially up to 4 g daily in 2–3
bulging develops, discontinue use and consult Pentasa tablet
divided doses
healthcare provider.
Initially up to 4 g daily in 2–4
Pentasa granules
Ileus and constipation; abdominal distension; divided doses
Acute inflammatory bowel disease; Initially 1.5–3 g daily in 3
Antibiotic-associated colitis; Salofalk tablet
divided doses
Dysentery;
Hepatic impairment;
Ulcerative colitis, maintenance, by mouth, ADULT,
Children;
Asacol 400 mg
Pregnancy. 1.2–2.4 g once daily or in
tablet
divided doses
Ipocol tablet
Adverse Drug Reactions:
Common: Dizziness, constipation, abdominal cramping, Asacol 800 mg Up to 2.4 g daily in divided
nausea. tablet doses
Less Common: Abdominal distention, abdominal pain, Mezavant 2.4 g once daily
allergic reactions, anaphylactic shock, anaphylactoid
reactions, angioedema, drowsiness, dyspepsia, fatigue, Initially 2 g once daily, then
Pentasa tablet
flatulence, hypersensitivity, paralytic ileus, megacolon, adjusted individually
pruritus rash, toxic megacolon, urinary retention, Pentasa granule 2 g once daily
urticarial, vomiting, xerostomia.
Rare: Bullous eruption, erythema multiforme, Stevens- Salofalk granules 1.5 g daily in 3 divided doses
Johnson Syndrome, toxic epidermal necrolysis.
Ulcerative colitis, acute exacerbations, by mouth, ADULT,
Drug Interactions:
Monitor closely with: MILD: 2.4 g daily in divided doses
Asacol 800
Enhances therapeutic effects Loperamide: mg tablet
Ramosetron (constipation effects) MODERATE: 4.8 g daily in divided
doses
Administration: May be taken with or without food.
Ulcerative colitis, by mouth, CHILD ≥6 years, <40 kg,
Pregnancy Category: C ACUTE MAINTENANCE
ATTACK OF REMISSION
ATC Code: A07DA03
Initially 30–
INTESTINAL ANTI-INFLAMMATORY AGENTS 50 mg/kg
Ipocol tablet daily in Initially 15–30
Salofalk divided mg/kg daily in
OTC MESALAZINE tablet doses, then divided doses,
Salofalk adjusted then adjusted
granules individually individually
Oral: 500 mg enteric coated tablet (maximum,
500 mg enteric MR tablet 75 mg/kg)
Rectal: 250 mg suppository

A 5-aminosalicylic acid derivative that modulates local Ulcerative proctitis, by rectum, ADULT,
chemical mediators of the inflammatory response, ACUTE MAINTENANCE
especially leukotrienes. ATTACK OF REMISSION
Initially 15–30
Indications: Ulcerative colitis, ulcerative proctitis 0.75–1.5 g mg/kg daily in
Asacol supp. daily in divided doses,
Contraindications: GFR < 20ml/min; hypersensitivity to divided doses then adjusted
mesalazine, aminosalicylates, salicylates, or any individually
component of the formulation (including suppository
Pentasa 1 g daily for –-
vehicle of vegetable fatty acid esters). 1 g daily
supp. 4 weeks
Dose: Salofalk 0.5–1 g 2–3
NOTE: Dose is dependent on product used. supp. times daily

19

Dose Adjustment:
Renal Impairment:
Dose adjustment may be necessary because mesalazine is
A
renally eliminated. Use with caution.
If GFR <20 mL/min, use is contraindicated.
Hepatic Impairment:
Use with caution.
Precautions:
Elderly (may have difficulty administering and retaining
rectal suppositories).
Adverse Drug Reactions:
Common: Headache, abdominal pain, eructation, nausea,
exacerbation of ulcerative colitis, nasopharyngitis,
pharyngitis, chest pain, peripheral edema, vasodilation,
hypertension, dizziness, chills, fatigue, vertigo, anxiety,
migraine, nervousness, paresthesia, insomnia, malaise,
skin rash, diaphoresis, pruritus, alopecia, acne vulgaris,
weight loss, diarrhea, dyspepsia, flatulence,
constipation, vomiting, intolerance syndrome, abnormal
stools, gastroenteritis, gastrointestinal hemorrhage,
rectal hemorrhage, tenesmus, bloody diarrhea,
pancreatitis, rectal pain, sclerosing cholangitis,
abdominal distention, anorectal pain (on insertion of
enema tip), hemorrhoids, polyuria, decreased hematocrit
and hemoglobin, abnormal hepatic function tests,
infection, back pain, hypertonia, arthralgia, myalgia,
weakness, arthritis, musculoskeletal pain, visual
disturbance, conjunctivitis, tinnitus, otalgia, hematuria,
decreased creatinine clearance, sinusitis, rhinitis, cough,
flu-like symptoms, dyspnea, bronchitis.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Thiopurine Analogues e.g.,
azathioprine
Decreases serum concentration of Cardiac Glycosides e.g.,
Digoxin
Increases risk of adverse or toxic effects of Mesalazine:
NSAIDs (nephrotoxic effect)
Increases risk of adverse or toxic effects of Heparin (risk for
bleeding / bruising)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Varicella virus-
containing Vaccines (potential development of Reye’s
Syndrome)
Reduces therapeutic effect of Mesalazine
Antacids (separate administration and/or lower antacid
doses to prevent interaction)
H2-Antagonists, Proton Pump Inhibitors
Administration:
For tablets, swallow whole. Do NOT break, chew, or
crush. Do NOT administer with antacids.
For suppositories, remove foil wrapper prior to
administration. Avoid excessive handling. Retain for at
least 1–3 hours to achieve maximum benefit.
20
ALIMENTARY TRACT AND METABOLISM
Pregnancy Category: B / C (product specific)
ATC Code: A07EC02
HORMONAL DRUGS USED FOR ESOPHAGEAL
VARICES
HYPOTHALAMIC HORMONES
Rx OCTREOTIDE
Inj.: 100 micrograms/mL and 500 micrograms/mL (as
acetate), 1 mL ampule (IV infusion) wort
Octreotide is a synthetic polypeptide related to
somatostatin, a. growth hormone inhibiting factor.
Indication: For hemostasis for esophageal varices
Dose:
For esophageal varices bleeding, by IV injection, ADULT, IV
bolus of 25–100 micrograms (usual bolus dose, 50
micrograms) followed by continuous IV infusion of 25–
50 micrograms per hour for 2–5 days; may repeat bolus
in first hour if hemorrhage is not controlled. [NOTE:
Withdraw yearly for a 4-week interval (8 for depot
injection) in patients who have received irradiation.
Resume if levels increase and signs or symptoms recur].
For vasoactive intestinal peptide tumors (VIPomas), by IV
injection, ADULT, 200–300 micrograms daily in 2–4
divided doses for the first 2 weeks; titrate dose based on
response or tolerance (range, 150–750 micrograms
daily; doses >450 micrograms daily are rarely required).
Dose Adjustment:
Geriatric:
Dose adjustment may be required. Begin dosing at the lower
end of dosing range. Elimination half-life is increased by
46% and clearance is decreased by 26%.
Renal Impairment:
If dialysis-dependent, no specific dose adjustments
indicated. However, dose adjustment may be needed
since clearance is reduced by ~50%.
Precautions:
Cholelithiasis; Glucose regulation; Hypothyroidism;
Pancreatitis; Cardiovascular disease; Excessive fluid
loss.
Prophylactic cholecystectomy is recommended in patients
with gastrointestinal or pancreatic neuroendocrine
tumors undergoing abdominal surgery if octreotide
treatment is planned
Patients on TPN (periodically monitor for elevations in zinc
levels).
TEST INTERACTION. Chronic treatment has been associated
with abnormal Schillings test.
Adverse Drug Reactions:
Common: Sinus bradycardia, fatigue, headache, malaise,
dizziness, pruritus, hyperglycemia, fever, abdominal
pain, loose stools, nausea, diarrhea, flatulence,
ALIMENTARY TRACT AND METABOLISM
cholelithiasis, biliary sludge, constipation, vomiting,
biliary duct dilatation, injection site pain, back pain,
arthropathy, myalgia, upper respiratory tract infection,
dyspnea, antibodies to octreotide, flu symptoms
Less Common: Hypertension, conduction abnormalities,
arrhythmia, palpitation, peripheral edema, pain, anxiety,
confusion, hypoesthesia, insomnia, rash, alopecia,
dyspepsia, steatorrhea, tenesmus, anorexia, cramping,
arthralgia, myalgia, paresthesia, anemia, weakness,
earache, renal calculus, cough, pharyngitis, rhinitis,
sinusitis, allergy, diaphoresis, angina, cardiac failure,
edema, flushing, hematoma, phlebitis, abnormal gait,
amnesia, depression, dysphonia, hallucinations,
nervousness, neuralgia, somnolence, vertigo, acne,
rigors, bruising, cellulitis, hypoglycaemia, hypokalemia,
gout, cachexia, breast pain, impotence, colitis,
diverticulitis, dysphagia, gastritis, gastroenteritis,
gingivitis, glossitis, melena, stomatitis, taste perversion,
xerostomia, incontinence, urinary tract infection,
injection site hematoma, fat malabsorption,
hyperkinesia, hypertonia, joint pain, neuropathy, tremor,
blurred vision, visual disturbance, tinnitus, renal
abscess, bronchitis, epistaxis, bacterial infection,
moniliasis
Rare: Amenorrhea, anaphylactic shock, anaphylactoid
reactions, aneurysm, aphasia, appendicitis, arthritis,
ascending cholangitis, ascites, atrial fibrillation, basal
cell carcinoma, Bell's palsy, biliary obstruction, breast
carcinoma, cardiac arrest, cerebral vascular disorder,
CHF, cholecystitis, cholestatic hepatitis, CK increased,
creatinine increased, deafness, diabetes insipidus,
diabetes mellitus, facial edema, fatty liver, galactorrhea,
GI bleeding, GI hemorrhage, GI ulcer, glaucoma,
gynecomastia, gallbladder polyp, hematuria,
hemiparesis, hemorrhoids, hearing impairment,
hepatitis, hyperesthesia, hypertensive reaction,
hypoadrenalism, hypoxia (children), intestinal
obstruction, intracranial hemorrhage, intraocular
pressure increased, iron deficiency, ischemia, jaundice,
joint effusion, increased LFTs, decreased libido,
malignant hyperpyrexia, MI, necrotizing enterocolitis
(neonates), migraine, nephrolithiasis, neuritis,
oligomenorrhea, pancreatitis, orthostatic hypotension,
pancytopenia, paranoia, paresis, petechiae, pituitary
apoplexy, pleural effusion, pneumonia, pneumothorax,
polymenorrhea, pulmonary embolism, pulmonary
hypertension, pulmonary nodule, QT prolongation,
Raynaud’s syndrome, rectal bleeding, renal failure, renal
insufficiency, retinal vein thrombosis, scotoma, seizures,
status asthmaticus, suicide attempt, syncope,
tachycardia, thrombocytopenia, thrombophlebitis,
thrombosis, urticaria, vaginitis, visual field defect,
vitamin B12 deficiency, weight loss, wheal or erythema
Drug Interactions:
Monitor closely with:
Decreases metabolism of Codeine [impairs formation of two
major metabolites, morphine and norcodeine]
Enhances therapeutic effect of the following drugs:
Antidiabetic Agents, Bradycardia-causing Agents,
Ivabradine (bradycardic effect)
Increases risk of adverse or toxic effects of Octreotide:
Androgens [except Danazol] (hypoglycemic effect),
Bretylium (bradycardic effect; AV blockade), Herbs with
Hypoglycemic Properties (hypoglycemic effect), MAO
Inhibitors (hypoglycemic effect), Other Hypoglycemia-
associated Agents (hypoglycemic effect), Pegvisomant
A
(hypoglycemic effect), Quinolone Antibiotics
(hypoglycemic effect), Ruxolitinib (bradycardic effect),
Salicylates (hypoglycemic effect), Selective Serotonin
Reuptake Inhibitors e.g. fluoxetine (hypoglycemic effect),
Tofacitinib (bradycardic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Lacosamide (AV-blocking effect), Moderate Risk QTc-
Prolonging Agents (QTc-prolonging effect), Pegvisomant
(significant elevations of liver enzymes)
Reduces therapeutic effect of Octreotide:
Quinolone Antibiotics e.g. Levofloxacin
Reduces therapeutic effect of Antidiabetic Agents
Avoid concomitant use with:
Decreases serum concentration of Cyclosporine (Systemic)
Increases risk of adverse or toxic effects of the following
drugs:
Ceritinib (bradycardic effect), Highest-Risk QTc-
Prolonging Agent (QTc-prolonging effect), Mifepristone
(QTc-prolonging effect)
Administration: Administer IV injections between meals to
decrease GI effects. May alter absorption of dietary fats.
Pregnancy Category: B
ATC Code: H01CB02
Rx SOMATOSTATIN
Inj.: 250 micrograms and 3 mg ampule / vial (IV, IV
infusion)
A cyclic tetradecapeptide that inhibits the release of human
growth hormone
Indication: Hemostatic medicines for esophageal varices
Contraindications: Pregnancy or breastfeeding (consult
specific product labeling)
Dose:
For esophageal varices bleeding, by IV bolus, ADULT, initially
250 micrograms over at least 1 minute, followed by
maintenance dose as continuous IV infusion at 250
micrograms/hour for 2–5 days, may repeat initial bolus
in first hour if hemorrhage is not controlled.
Dose Adjustment:
Renal Impairment:
For CrCl ≤30 mL/minute, administer 50% of the usual dose.
Precautions:
Glucose regulation; Insulin-dependent diabetes; Oliguria;
Cardiovascular disease (monitor vital functions closely,
especially following initial bolus injection).
21

Adverse Drug Reactions: AV block, bradycardia,
hypertension, hypotension, hyperglycemia,
hypoglycemia, vertigo, flushing (rapid administration),
A
abdominal discomfort, diarrhea, nausea, vomiting
(infusion greater than 50 micrograms/minute),
bronchospasm, allergic reaction, severe water retention,
hyponatremia
Drug Interactions:
Monitor closely with:
Decreases metabolism of the following drugs:
Codeine [impairs formation of 2 major codeine
metabolites, morphine and norcodeine]
Increases risk of adverse or toxic effects of Somatostatin,
specifically, those associated with its hypoglycemic
effect:
Androgens [except Danazol], Antidiabetic Agents, Herbs
with Hypoglycemic Properties, MAO Inhibitors, Other
Hypoglycemia-associated Agents, Pegvisomant,
Quinolone Antibiotics Levofloxacin, Salicylates, Selective
Serotonin Reuptake Inhibitors
Increases serum concentration of the following drugs:
Bromocriptine (delays Bromocriptine absorption and
time to maximum plasma concentrations)
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Pegvisomant (significant elevations
of liver enzymes)
Avoid concomitant use with:
Decreases metabolism of Cyclosporine (Systemic)
Increases risk of adverse or toxic effects of Barbiturates e.g.
Phenobarbital (sedative effects)
Administration: Administer IV bolus slowly over at least 1
minute, followed immediately by continuous infusion. If
infusion is interrupted for more than 3–5 minutes, re-
administer initial bolus dose to maintain continuous
treatment.
NOTE: Avoid abrupt discontinuation of therapy; decrease
infusion gradually for 24 hours before discontinuing.
Pregnancy Category: B
ATC Code: H01CB01
22
ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
INSULIN
GENERAL INFORMATION
Insulin is a polypeptide hormone of complex structure
produced by the pancreas that plays a key role in the
metabolism of carbohydrate, fat, and protein. All insulins
are developed by recombinant DNA technology but the
amino acid sequence of human and analogue insulins
differ. These explain the differences in pharmacokinetics
between human and analogue insulins.
Mode of Action: Increase or restore ability to metabolize
glucose by enhancing cellular glucose uptake; inhibit
endogenous glucose output and lipolysis.
Types of Insulin: The various formulations of insulin are
classified according to their duration of action after
subcutaneous injection, as: short-acting and rapid-acting
insulins, intermediate-acting insulins, and long-acting
insulins and ultra- long acting insulins. The intermediate-
acting and long-acting insulins are given for the basal
requirements, while the short-acting and rapid-actin
insulins are given before meals to control post-prandial
hyperglycemia.
Indications:
Management of type 1 diabetes mellitus; type 2 diabetes
mellitus inadequately controlled with diet, exercise, and
oral antidiabetic medications, and where oral therapy
cannot be used (e.g., during surgery, or in pregnant
women with Type 2 DM when diet alone fails to control
the diabetes), children with diabetes; diabetic
emergencies (e.g. diabetic ketoacidosis and
hyperosmolar hyperglycemic states).
Contraindications: Hypoglycemia
Dose:
Dose of insulin and regimen depend on the individual
treatment endpoints and are adjusted according to
(capillary) blood glucose monitoring.
Dose of human insulin is always expressed in units. Do NOT
abbreviate the word “unit.” One unit of human insulin,
which is contained in 0.03846 mg of the first
International Standard (1986) is equivalent to the
amount of insulin required to reduce the concentration
of blood glucose to 45 mg/dL in a fasting rabbit.
NOTE: Diabetes self-management education (DSME) is
essential to maximize the effectiveness of therapy.
Dose Adjustment:
Renal Impairment:
In mild-to-moderate impairment, reduce dose.
In severe impairment, refer to a specialist.
CrCl 10–50 Administer at 75% of normal dose
mL/minute and monitor glucose closely
CrCl <10 Administer at 25% to 50% of normal
mL/minute dose and monitor glucose closely
ALIMENTARY TRACT AND METABOLISM
Hepatic Impairment:
Insulin requirements may be decreased in patients with
hepatic impairment.
Precautions:
Acute illness or conditions, e.g., trauma,
Myocardial Infarction;
Infections;
Stroke;
Coma;
Infections;
Diabetic ketoacidosis
Surgery;
Renal impairment;
Exercise;
Pregnancy
SKILLED TASKS. Driving may be hazardous when
hypoglycemic since awareness is impaired. Check blood
glucose concentration before driving, and at intervals of
approximately 2 hours when on long journeys.
MONITORING: The facility should have monitoring at the
point of care. Blood glucose concentration varies
throughout the day. Diabetes patients should aim to
maintain their blood glucose concentration between 4–
9 mmol/L for most of the time [ideally, 80-130 mg/dL
(4–7 mmol/L before meals and <180 mg/dL (<9
mmol/L) after meals]. Prevent blood glucose
concentration from falling below 72mg/dL (4 mmol/L)
because of the risk of hypoglycemia. Glycated
hemoglobin concentration (HbA1c) should be <7% (53
mmol/L).
STABILITY and STORAGE: Insulin preparations should be
stored in a refrigerator at 2–8oC, protected from light and
not allowed to freeze. Patients should be advised not to
expose their vials or cartridges to excessive heat or
sunlight.
Adverse Drug Reactions:
Common: Hypoglycemia
Less Common: Edema, lipodystrophy (either as lipoatrophy
or lipohypertrophy) at the site of injection, weight gain.
Rare: Localized reactions (e.g., redness, swelling, itching),
generalized hypersensitivity reactions (including rash
over the whole body, shortness of breath, wheezing,
hypotension, tachycardia, sweating, or very rarely,
anaphylactic reactions).
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Insulin:
ACE Inhibitors, e.g., Enalapril, Beta Blockers, e.g.,
Atenolol, Propranolol (hypoglycemic effect), Alcohol
(inhibits hepatic glucose output; decreases blood
glucose concentratin)
Increases risk of adverse effects of Insulin:
Alcohol (hypoglycemia; masks warning symptoms), Beta
Blockers, e.g., Atenolol, Propranolol (masks warning
signs of hypoglycemia), Drugs increasing blood glucose
concentration, e.g., Glucocorticoids, Antipsychotics,
Calcineurin Inhibitors, High-dose Thiazide Diuretics
(alters diabetes control of insulin)
Nifedipine (impairs glucose tolerance),
Thiazolidinediones (increases risk of edema and heart
failure)
A
Reduces therapeutic effect of Insulin:
Drugs increasing blood glucose concentration, e.g.,
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
High-dose Thiazide Diuretics
Avoid concomitant use with:
Reduces therapeutic effect of Insulin:
Contraceptives, Oral, e.g., Levonorgestrel,
Medroxyprogesterone (Corticosteroids, e.g.,
Dexamethasone, Hydrocortisone, Prednisolone;
Diuretics, e.g., Furosemide, Hydrochlorothiazide)
Administration: Administered via injection because it is
easily inactivated by the body enzymes.
The SC route is ideal in most situations, usually injected
in the upper arms, thighs, buttocks, or abdomen. The
rate of absorption from different sites may vary
depending on local blood flow (absorption in the arm is
faster than in the buttock or thigh).
Do NOT administer mixtures of insulin formulations
intravenously.
REGULAR INSULIN
Rx
(RECOMBINANT DNA, HUMAN)
Inj.: 100 IU/mL, 3 mL pre-filled syringe (SC, IV/IM)
100 IU/mL, 5 mL and 10 mL vial (SC, IV/IM)
A short-acting, regular crystalline zinc insulin, which is
prepared as a sterile, clear aqueous solution. It contains
a polypeptide hormone structurally identical to the
human insulin synthesized through rDNA technology for
treatment of diabetes.
Regular or soluble insulin is the most appropriate form of
insulin for use in diabetic emergencies and during
surgery, and in these cases, are typically given in an
intravenous infusion (insulin drip). When injected IV, it
has a very short half-life of only about 5 minutes and its
effect disappears within 30 minutes.
Indications: Management of diabetes mellitus; diabetic
ketoacidosis.
Dose:
Diabetes mellitus, by SC, IM, IV injection or IV infusion (IV
route is reserved for urgent treatment, e.g., DKA and for
fine control in serious illness and peri-operatively),
according to requirements. [see under Insulin and
Analogues].
Administration: Shake the suspension gently before
withdrawing a dose. Do NOT use if solution is viscous or
cloudy. Use only if clear and colorless. Follow
manufacturer’s instructions.
See General Information on Insulin and Analogues listed
above for further information.
Pregnancy Category: B
23

ATC Code: A10AB01
A
ISOPHANE HUMAN INSULIN /
Rx NPH HUMAN INSULIN
(RECOMBINANT DNA)
Inj.: 100 IU/mL, 3 mL pre-filled syringe (SC)
100 IU/mL, 5 mL and 10 mL vial (SC)
Neutral Protamine Hagedorn (NPH Insulin) or isophane
insulin is a crystalline suspension of human insulin with
protamine and zinc providing an intermediate-acting
insulin with a slower onset of action (within about 2
hours), with peak activity at about 10-12 hours and a
longer duration of activity (up to about 24 hours) than
that of regular insulin. It is of particular value for the
initiation of twice-daily insulin regimens. NPH insulin is
often combined with regular insulin to achieve a more
rapid onset of action compared to NPH insulin alone.
Indication: Management of diabetes mellitus
Administration: For SC injection only. Shake the suspension
gently before withdrawing a dose. Follow manufacturer’s
instructions.
WARNING: NEVER administer intravenously.
NOT suitable for the emergency treatment of diabetic
ketoacidosis.
See General Information on Insulin and Analogues listed
above for further information.
Pregnancy Category: B
ATC Code: A10AC01
BIPHASIC ISOPHANE HUMAN
Rx INSULIN 70/30
(RECOMBINANT DNA)
Inj.: 70% isophane suspension + 30% soluble insulin in:
100 IU/mL, 5 mL and 10 mL vial (SC)
100 IU/mL, 3 mL disposable syringe (SC)
100 IU/mL, 3 mL glass cartridge (SC)
A fixed ratio premix recombinant human insulin formulation
containing a short-acting insulin and an intermediate-
acting insulin (70% isophane insulin and 30% soluble
insulin). Human insulin is produced by recombinant DNA
technology utilizing a non-pathogenic laboratory strain of
Escherichia coli. It is a suspension of crystals produced
from combining human insulin and protamine sulfate
under appropriate conditions for crystal formation and
mixing with human insulin injection.
Indication: Management of diabetes mellitus
WARNING: NEVER administer intramuscularly or
intravenously.
24
ALIMENTARY TRACT AND METABOLISM
NOT suitable for the emergency treatment of
diabetic ketoacidosis.
Administration: For SC injection only. Administer 30–45
minutes before meals. Shake the suspension gently
before withdrawing a dose. Follow manufacturer’s
instructions.
Inspect visually prior to use. It should not contain
particulate matter and should appear uniformly cloudy
after mixing. Do NOT use if particulate matter is seen. Do
NOT mix with other insulins or diluents.
See General Information on Insulin and Analogues listed
above for further information.
Pregnancy Category: B
ATC Code: A10AB30; A10AC30
BLOOD GLUCOSE LOWERING DRUGS, EXCLUDING
INSULINS
BIGUANIDES
Rx METFORMIN
Oral: 500 mg tablet / film-coated tablet (as hydrochloride)
850 mg tablet (as hydrochloride)
A biguanide that exerts its effects by inhibiting hepatic
gluconeogenesis and increasing peripheral glucose
utilization and is useful in overweight and obese patients
since it does not increase weight or provoke
hypoglycemia when used.
Indication: Management of type 2 diabetes mellitus
Contraindications: Ketoacidosis; severe infection or trauma;
dehydration; alcohol misuse; moderate to severe heart
failure; risk of tissue hypoxia caused by sepsis,
respiratory failure, recent MI, or hepatic impairment.
Dose:
Diabetes mellitus, by mouth, ADULT and CHILD >10 years,
initially 500 mg with breakfast for at least 1 week, then
500 mg with breakfast and evening meal for at least 1
week, then 500 mg with breakfast, lunch, and evening
meal, or 850 mg every 12 hours with or after food (usual
maximum, 2.5 g daily in divided doses).
Dose Adjustment:
Geriatric:
Use with caution. Reduce dose or discontinue, if necessary.
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
ALIMENTARY TRACT AND METABOLISM
Precautions:
WARNING: May cause lactic acidosis rarely but with
potentially severe consequences.
Use of iodine-containing X-ray contrast media (do not restart
metformin until renal function returns to normal);
Use of general anesthesia (suspend metformin on the
morning of surgery and restart when renal function
returns to normal);
Monitor renal function before treatment and once or twice
annually;
Substitute insulin during severe infection, trauma, or
surgery;
Severe renal and hepatic impairment;
Moderate-to-severe heart failure;
Surgery (stop metformin before surgery; monitor plasma
glucose concentration; restart when patient is no longer
fasting and renal function has recovered);
Pregnancy (avoid use during all trimesters; may be given for
pregnant women previously diagnosed with PCOS as
prescribed by the physician);
Lactation (monitor infant).
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, asthenia, diarrhea,
disturbance in taste, dyspepsia, headache, indigestion,
flatulence, metallic taste, nausea, upper respiratory tract
infection, vitamin B12 malabsorption, vomiting
Less Common: Erythema, pruritus, rash, urticaria
Rare: Acute hepatitis, lactic acidosis
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Metformin:
Alcohol (decreases blood glucose concentration);
Enalapril (hypoglycemic effect)
Increases risk of adverse or toxic effects of Metformin:
Alcohol (hypoglycemia; masks warning symptoms); Beta
Blockers e.g. Propranolol (masks warning signs of
hypoglycemia; increases risk of lactic acidosis), Drugs
increasing blood glucose concentration, e.g.,
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
High-dose Thiazide Diuretics (alters diabetes control of
insulin)
Nifedipine (impairs glucose tolerance);
Thiazolidinediones (increases risk of edema and heart
failure)
Reduces therapeutic effect of Metformin:
Drugs increasing blood glucose concentration, e.g.,
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
High-dose Thiazide Diuretics
Avoid concomitant use with:
Reduces therapeutic effect of Metformin:
Contraceptives (Oral); Furosemide Hydrocortisone
Administration: Take with meals to reduce stomach upset.
Pregnancy Category: B
ATC Code: A10BA02
SULFONYLUREAS
Rx GLICLAZIDE
A
Oral: 80 mg tablet (immediate-release)
30 mg and 60 mg MR tablet
A second-generation sulfonylurea, which acts by increasing
the pancreatic insulin secretion. Elevated insulin levels
are only seen with acute exposure to the drug.
Indication: Management of type 2 diabetes mellitus
Contraindications: Type 1 diabetes mellitus (insulin-
dependent, IDDM); diabetic ketoacidosis; diabetic
precoma and coma; severe renal or hepatic impairment;
stress conditions (e.g., serious infection, trauma,
surgery); porphyria; pregnancy; breastfeeding;
sulfonamide “sulfa” allergy (risk of cross-reaction);
Dose:
NOTE: There is no fixed-dosage regimen for the
management of diabetes mellitus with gliclazide.
Individualize doses based on frequent blood glucose
monitoring during dose titration and throughout
maintenance.
Type 2 diabetes, by mouth, ADULT,
as modified-release tablet, initially 30 mg once daily,
titrate in 30 mg increments every 2 weeks based on
blood glucose levels (maximum, 120 mg once daily);
as immediate-release tablet, initially 80 mg twice daily,
titrate based on blood glucose levels, usual dosage
range, 80-320 mg daily (maximum, 320 mg daily);
dosage of ≥160 mg should be divided into 2 equal parts
for twice-daily administration.
Dose Adjustment:
Renal Impairment:
In severe renal impairment, avoid use.
Precautions:
Acute illness, including MI, coma, trauma, or infection;
Hypoglycemia;
G6PD deficiency;
Renal impairment;
Severe hepatic disease;
Stress-related states e.g. surgery.
Elderly;
Pregnancy;
Lactation (monitor infants).
Adverse Drug Reactions:
Common: Dizziness, hypoglycemia, weight gain
Less Common: Abdominal pain, angina pectoris, arthralgia,
arthrosis, back pain, bronchitis, constipation, cough,
diarrhea, dyspepsia, headache, hypertension, metallic
taste, nausea, rash, rhinitis, upper respiratory infection,
urinary tract infection, viral infection, vomiting
Rare: Allergic reactions, blood disorders, erythema
multiforme, exfoliative dermatitis, fever, hepatic failure,
hepatitis, jaundice, malaise, photosensitivity, Stevens-
Johnson syndrome
25
 ALIMENTARY TRACT AND METABOLISM

Drug Interactions:
Monitor closely with:
Enhances adverse effect of the following drugs: VITAMINS
A

Alcohol (flushing reaction; decreases blood glucose

concentration), Beta Blockers [except Levobunolol,
MULTIVITAMINS, PLAIN
Metipranolol] (may mask symptoms of hypoglycemia),
Carbocisteine (may enhance adverse effects of alcohol
present in liquid formulations), Porfimer, Verteporfin OTC MULTIVITAMINS
(photosensitizing effect)

Enhances hypoglycemic effect of Gliclazide: Oral:

Alcohol (masks warning symptoms, Alpha-Lipoic Acid; For infants, drops, per 1 mL contains:
Androgens [except Danazol]; Antidiabetic Agents; Beta Vitamin A 325–380 micrograms RE
Blockers [except Levobunolol, Metipranolol]; Cyclic Vitamin B1 0.2–0.4 mg
Antidepressants; Fibric Acid Derivatives Vitamin B2 0.3–0.4 mg
Hypoglycemia-associated Agents; MAO Inhibitors; Vitamin B6 0.3–0.6 mg
Miconazole; Pegvisomant Vitamin B12 0.3–0.4 micrograms
Quinolone Antibiotics; Salicylates; SSRIs; Sulfonamide Vitamin C 30 mg
Derivatives; Vitamin K Antagonists, e.g., Warfarin Vitamin D 200 – 400 IU (5 - 10 micrograms)
Enhances therapeutic effect Vitamin K Antagonists, e.g., Vitamin E 3–4 mg
Warfarin (anticoagulant effect) Folic Acid 20–65 micrograms
Niacin 1–5 mg
Increases risk of adverse or toxic effects of Gliclazide:
Dexketoprofen For children, syrup, per 5 mL contains:
Reduces therapeutic effect of Gliclazide: Vitamin A 350–400 micrograms RE
Corticosteroids, systemic, Hyperglycemia-associated Vitamin B1 0.5–1.0 mg
Agents, Loop Diuretics (hypoglycemic effect), Quinolone Vitamin B2 0.7–0.9 mg
Antibiotics (loss of blood sugar control may occur), Vitamin B6 0.9–1.6 mg
Thiazide Diuretics Vitamin B12 0.9–3.0 micrograms
Vitamin C 35–55 mg
Avoid concomitant use with: Vitamin D 200 – 400 IU (5 - 10 micrograms)
Decreases serum concentration of Gliclazide: Vitamin E 5–7 mg
CYP2C9 Inducers, Dabrafenib, Rifampin Folic Acid 40–300 micrograms
Niacin 5–18 mg
Enhances hypoglycemic effect of Gliclazide:
DPP-IV Inhibitors, Glucagon-like Peptide-1 Agonists / For adults, tablet or capsule, each tablet / capsule contains:
GLP­1 Agonists, Sodium Glucose Cotransporter Inhibitors Vitamin A 600–700 micrograms RE
/ SGLT2 Inhibitors (consider dose reduction of (2000 – 2500 IU)
gliclazide), Thiazolidinedione Vitamin B1 1.3–1.7 mg
Vitamin B2 0.7–1.3 mg
Increases risk of adverse or toxic effects of Gliclazide: Vitamin B6 1.6–2 mg
CYP2C9 Inhibitors, Fluconazole, (hypoglycemia) Vitamin B12 2–6 micrograms
Vitamin C 60–80 mg
Increases risk of adverse or toxic effects of Mecamylamine Vitamin D 400 IU (10 micrograms)
Vitamin E 6–10 mg (15 – 30 IU)
Increases serum concentration of Gliclazide: Folic Acid 400 micrograms
CYP2C9 Inhibitors, Fluconazole, Mifepristone (monitor Niacin 13–23 mg
closely for adverse effects, during and in the 2 weeks
following mifepristone treatment) A dietary supplement containing essential multivitamins
and minerals that are needed for good health, growth,
Reduces therapeutic effect of Gliclazide: and development.
Dabrafenib, Rifampin
Indications: Dietary supplementation, management of
Administration: vitamin deficiencies
Take immediate-release tablets before meals.
Contraindications: Known hypersensitivity to any
Take MR tablets with food to minimize the risk of component of the preparations
hypoglycemia.
Dose:
Pregnancy Category: C Prevention or treatment of vitamin deficiencies, by mouth,
ADULT, 1 tablet or capsule daily.
ATC Code: A10BB09
Precautions:
Avoid taking similar vitamin products.

26
ALIMENTARY TRACT AND METABOLISM

NOTE: Not all products can be used in children of all age manifesting as hypocalcemia, by mouth, ADULT,
groups. Consult specific product labeling prior to use. Do ADOLESCENT, and CHILD ≥6 years, initially 0.25
NOT exceed recommended doses. micrograms once daily in the morning; may be increased

Drug Interactions:
Decreases serum concentration of certain components of
Multivitamins:
Food, e.g., eggs, milk (inhibits absorption of iron)
Administration: May be taken with or without food.
May be taken with meals for better absorption or if GI
discomfort occurs.
Pregnancy Category: Not available
A
at 2– to 4–week intervals; maintenance, 0.5-2
micrograms once daily; CHILD 1-5 years, 0.25-0.75
micrograms daily; NEONATE and INFANT, 0.25
micrograms daily.
Vitamin D-dependent rickets, by mouth, ADULT,
ADOLESCENT, and CHILD, 1 microgram once daily.
Postmenopausal osteoporosis, by mouth,
POSTMENOPAUSAL FEMALES, 0.25 micrograms twice
daily; modify dose according to serum calcium
concentration.
Osteoporosis, by mouth, CHILD, 1-2 micrograms/kg daily
given in 4-6 divided doses.

ATC Code: A11BA Precautions:

WARNING: Administration of more than the daily
requirement can cause hypercalcemia,
VITAMIN A AND D hypercalciuria, and hyperphosphatemia.

Rx CALCITRIOL Renal impairment;

Oral: 0.25 micrograms capsule
Also known as 1,25­dihydroxy-cholecalciferol, it is the active
form of vitamin D3 (cholecalciferol). Calcitriol is
structurally similar to calcifediol and plays an important
role in maintaining calcium balance and in the regulation
of parathyroid hormone (PTH). It is the preferred form for
the management of hypocalcemia in dialysis-dependent
renal failure patients.
Indications: Management of Hypocalcemia due to
secondary hyperparathyroidism, and resultant metabolic
bone disease; hypocalcemia associated with vitamin D
deficiency; postsurgical hypoparathyroidism; vitamin D-
dependent rickets; postmenopausal osteoporosis and
osteoporosis
Contraindications: Accidental exposure; arteriosclerosis;
breastfeeding; cardiac disease; dehydration; geriatric;
hypercalcemia; hyperphosphatemia; hypervitaminosis D;
occlusive dressing; ocular exposure; pregnancy; renal
failure; sarcoidosis; sunlight (UV) exposure
Dose:
NOTE: Serum calcium, phosphorus, alkaline phosphatase,
and creatinine concentrations should be determined
initially, monthly for 6 months, then periodically. Serum
PTH should be monitored initially and every 3–4 months.
Hypocalcemia, secondary hyperparathyroidism, and
resultant metabolic bone disease (renal osteodystrophy)
in patients with chronic kidney disease, by mouth,
ADULT, initially 0.25 micrograms daily; may increase
dose to 0.5 micrograms daily if necessary; titrate doses
as necessary to obtain target range; ADOLESCENT and
CHILD 1-2 years, initially 0.25 micrograms daily.
Management of hypocalcemia associated with vitamin D
deficiency, by mouth, ADOLESCENT, CHILD, and INFANT,
0.05 micrograms/kg daily (maximum, 0.5 micrograms
daily) until calcium levels normalize.
Postsurgical hypoparathyroidism, idiopathic
hypoparathyroidism, and pseudohypoparathyroidism
Hepatic and biliary disease;
Excessive doses;
Immobilized patients.
Adverse Drug Reactions:
Common: Hypervitaminosis D, hypercalcemia, fatigue,
weakness, headache, nausea, vomiting, abdominal pain,
constipation, diarrhea, vertigo, tinnitus, ataxia, myalgia,
arthralgia, irritability, hypercalciuria,
hyperphosphatemia, metallic taste.
Drug Interactions:
Monitor closely with:
Decreases intestinal absorption of Calcitriol:
Cholestyramine, Colestipol, Mineral Oil, Orlistat
Increases risk of adverse or toxic effects of the following
drugs:
Calcium-containing Antacids (hypercalcemia); Cardiac
Glycosides, e.g., Digoxin (hypercalcemia; cardiac
arrhythmias)
Reduces therapeutic effect of Calcitriol:
Anticonvulsants, e.g., Phenobarbital, Primidone,
Phenytoin, Fosphenytoin
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Calcitriol:
Phosphorus Salts
Increases risk of adverse or toxic effects of the following
drugs:
Aluminum-containing Antacids (aluminum retention and
toxicity); Vitamin D Analogues (additive effects and
toxicity)
Administration: May be administered without regard to
meals. Protect from light.
NOTE: Patients must receive an adequate amount of
calcium while taking Calcitriol. Advise patients to have a
dietary intake of calcium of at least 600 mg daily.

27

Calcitriol is readily absorbed from the intestine.
Absorption can be delayed in patients with hepatic,
biliary, or GI disease.
A
Pregnancy Category: C
ATC Code: A11CC04
Rx RETINOL (VITAMIN A)
Oral: 10,000 IU, 25,000 IU, and 50,000 IU soft gel capsule
(as palmitate)
100,000 IU and 200,000 IU soft gel capsule with
nipple (as palmitate) [only for DOH program]
A fat-soluble vitamin and dietary supplement that is
required by the eyes for the transduction of light into
neural signs necessary for vision.
Indications: For the prevention and treatment of vitamin A
deficiency states (e.g., xerophthalmia and night
blindness); prevention of complications of measles.
Contraindications: Hypervitaminosis A; known
hypersensitivity to vitamin A, or any component of the
formulation; dosages exceeding the Recommended
Energy and Nutrient Intake (RENI); women who are, or
may become, pregnant.
Dose:
Prevention of vitamin A deficiency (universal or targeted
distribution programs), by mouth, ADULT, 200,000 IU
every 6 months; ADULT (pregnant woman), maximum of
10,000 IU daily or maximum 25,000 IU weekly; ADULT
(woman of childbearing age), 200,000 IU at delivery or
within 8 weeks of delivery; CHILD >1 year (preschool),
200,000 IU every 4–6 months; INFANT 6–12 months,
100,000 IU every 4–6 months, preferably at measles
vaccination; INFANT <6 months, 50,000 IU. [NOTE:
Administer an additional dose the next day in
hospitalized children with measles infection.]
Treatment of xerophthalmia, by mouth, ADULT (except
woman of childbearing age) and CHILD >1 year, 200,000
IU on diagnosis, repeated the next day and again after 2
weeks; ADULT (woman of childbearing age with severe
signs of xerophthalmia), as for other adults; ADULT
(woman of childbearing age with less severe symptoms,
e.g., night blindness), either 5,000 to 10,000 IU daily for
at least 4 weeks or up to 25,000 IU weekly; INFANT 6–
12 months, 100,000 IU immediately on diagnosis,
repeated the next day and again after 2 weeks; INFANT
under 6 months, 50,000 IU on dis, repeat the next day
and again after 2 weeks. [NOTE: Oral vitamin A
preparations are preferred for the prevention and
treatment of vitamin A deficiency.]
Dose Adjustment:
Pregnant women susceptible to vitamin A deficiency during
the third trimester:
Should be given low dose vitamin A supplements on a daily
or weekly basis.
28
ALIMENTARY TRACT AND METABOLISM
Precautions:
WARNING: Severe congenital malformations may occur
in infants of mothers consuming large amounts of
oral retinoids for acne treatment.
Patients on prolonged daily administration over 25,000 IU
should be under close supervision;
Chronic intake of vitamin A at levels 10–20 times the RDA
can lead to hypervitaminosis A;
Pregnancy (excessive doses during the first trimester may
be teratogenic);
Breastfeeding (there is theoretical risk of toxicity in infants
of mothers taking large doses).
NOTE: Dietary reference intakes (DRIs): Tolerable upper
intake level (UL) for adults is 3,000 micrograms daily of
preformed vitamin A, based on teratogenicity as the
critical adverse effect for women of childbearing age and
liver pathology for all other adults.
Adverse Drug Reactions:
Less Common: Diplopia, headache, nausea, symmetric
papilledema, vomiting
Rare: Birth defects (e.g., tense and bulging fontanelle in
infants), dry hair, enlarged liver, increased intracranial
pressure
Drug Interactions:
Monitor closely with:
Increases therapeutic effect of Warfarin (anticoagulant
effect)
Avoid concomitant use with:
Decreases absorption of Retinol:
Bile Acid–binding Resins, e.g., Cholestyramine,
Colestipol
Increases risk of adverse or toxic effects of the following
drugs:
Retinoid Drugs, e.g., Acitretin, All-trans-retinoic Acid,
Isotretinoin (hypervitaminosis A); Tetracyclines (benign
intracranial hypertension)
Administration: This vitamin is absorbed along with fat in the
diet. Take it with food.
Pregnancy Category: A; X if dose is greater than RENI
ATC Code: A11CA01
ALIMENTARY TRACT AND METABOLISM
VITAMIN B1, PLAIN AND IN COMBINATION WITH
VITAMIN B6 AND B12
(Oral) OTC
(Inj.) Rx
THIAMINE (VITAMIN B1)
Oral: 100 mg and 300 mg tablet (as hydrochloride)
Inj.: 100 mg/mL, 1 mL ampule / vial (IV)
100 mg/mL, 10 mL vial (as hydrochloride) (IM, IV)
A water-soluble vitamin found in yeast, cereal grains,
legumes, peas, nuts, pork, and beef. It is used to prevent
peripheral neuritis associated with pellagra (Vitamin B3
deficiency) and pregnancy. It combines with adenosine
triphosphate (ATP) to form thiamine pyrophosphate, an
essential coenzyme in carbohydrate metabolism.
Indications: Management of beriberi (Vitamin B1 deficiency,
maple syrup urine disease (MSUD) and Wernicke /
Korsakoff syndrome; nutritional supplementation.
Contraindications: Breast-feeding; encephalopathy;
pregnancy
Dose:
Nutritional supplementation, by mouth, ADULT and
ADOLESCENT (pregnant or lactating female), 1.4 mg
daily; ADULT and ADOLESCENT (male), 1.2 mg daily;
ADULT (female), 1.1 mg daily; ADOLESCENT (females), 1
mg daily; CHILD 9–13 years, 0.9 mg daily; CHILD 4-8
years, 0.6 mg daily; CHILD 1–3 years, 0.5 mg daily;
INFANT 7–12 months, 0.3 mg daily; INFANT 0–6 months,
0.2 mg daily.
Prevention of thiamine deficiency in patients receiving total
parenteral nutrition (TPN), by IV injection, ADULT, 3 mg
daily admixed with TPN.
Beriberi, by mouth, ADULT, 5–30 mg once daily or in 3
divided doses for 1 month; CHILD and INFANT, 10–50
mg once daily for 2 weeks, then 5-10 mg once daily for 1
month;
by IV or IM injection, ADULT, initially 5–30 mg once daily
or in 3 divided doses, then convert to oral route once
patient is taking PO (total treatment duration, 1 month);
CHILD and INFANT, 10–25 mg daily for 2 weeks, then 5–
10 mg once daily for 1 month. [NOTE: If beriberi occurs
in a breast-fed infant, both lactating mother and infant
should receive treatment.]
Wernicke/Korsakoff Syndrome, by IV or IM injection, ADULT,
initially 100 mg, followed by 50–100 mg daily until
normal dietary intake is established (clinical practice
guidelines recommend 200–500 mg 3 times daily for 5–
7 days or until there is no further improvement in
symptoms).
Metabolic disorders including necrotizing
encephalomyelopathy, maple syrup urine disease
(MSUD), and lactic acidosis associated with pyruvate
carboxylase deficiency, by mouth, ADULT, 10–20 mg
daily as a single dose, up to 4 g daily in divided doses.
Precautions:
WARNING: Serious hypersensitivity or anaphylactic
reactions can occur, especially after repeated
administration.
Hepatic impairment; Lactation (not known if excreted in
breastmilk).
A
Adverse Drug Reactions:
Common: Sneezing, pruritus (generalized), warmth,
urticaria, weakness, diaphoresis, nausea, restlessness,
tightness of throat, angioedema, cyanosis, pulmonary
edema, GI bleeding, injection site reaction
Rare: Hypersensitivity reactions
Drug Interactions:
Avoid concomitant use with:
Decreases serum concentration of Thiamine:
Ethyl Alcohol, Chronic Consumption (results in deficiency
of several nutrients)
Administration:
For oral administration, may be taken without regards to
meals.
Parenteral administration is reserved for patients for
which oral thiamine is not feasible.
Inspect visually for particulate matter and discoloration
prior to administration.
For slow IV push, no dilution is necessary.
For continuous IV infusion, dilute thiamine in a
compatible infusion solution. Administer at a rate
prescribed by the physician.
Pregnancy Category: A
ATC Code: A11DA01
(Oral) OTC
(Inj.) Rx
VITAMIN B1 B6 B12
Oral: 100 mg B1 + 5 mg B6 + 50 micrograms B12 per tablet
/ capsule
10 mg B1 + 5 mg B6 + 5 micrograms B12 per 0.6 mL
drops, 15 mL
Inj.: 100 mg B1 + 100 mg B6 + 1 mg B12 per 3 mL, ampule
(IV)
100 mg B1 + 100 mg B6 + 1 mg B12 per mL, 10 mL
vial (IV)
A dietary supplement, which contains vitamins B1, B6, and
B12 for nerve cell metabolism, and for vitamin B-complex
deficiencies.
Indications: Prevention and treatment of vitamin B complex
deficiencies; adjunct in the management of
neuromuscular pain responsive to vitamin B1, B6, and
B12, including neuralgia, neuritis and neuropathies.
Contraindications: Leber’s disease or tobacco amblyopia;
known hypersensitivity to any component of the
formulation.
Dose:
Prevention and treatment of vitamin B complex deficiency,
by mouth, ADULT, 1–2 tablets or capsules daily; by slow
IV injection, ADULT, 0.25–2 mL.
29
 ALIMENTARY TRACT AND METABOLISM

Precautions: once daily; CHILD 1–3 years, 15 mg once daily; INFANT,

Vitamin B12 >10 micrograms daily may produce 40–50 mg once daily.
hematological response in folic acid deficiency. Scurvy, by mouth, ADULT, 100–250 mg 1–2 times daily;
A

Neurotoxicity (long-term administration of large doses >2 g CHILD, 100–300 mg daily in divided doses; INFANT, 50–
daily) 100 mg daily in divided doses.
Malabsorption; Anemia; Neuropathy; Undiagnosed vitamin Adjunct to deferoxamine therapy in the treatment of chronic,
B12 deficiency. iron toxicity, by mouth, ADULT, 100–200 mg once daily
initiated 1–2 hours after deferoxamine infusion is
Adverse Drug Reactions: started.
Less Common: Headache, peripheral neuropathy (high Chronic recurrent furunculosis in patients with neutrophil
doses) dysfunction, by mouth, ADULT, 1,000 mg daily for 4–6
Rare: Hypersensitivity reactions weeks [NOTE: Studies show that ascorbic acid does not
alter the course of furunculosis in patients without
Drug Interactions: neutrophil dysfunction].
Avoid concomitant use with:
Decreases therapeutic effect of Levodopa Dose Adjustment:
Renal Impairment:
Administration: Removed by hemodialysis. Adjust dosing accordingly.
For oral administration, may be taken with or without For patients receiving intermittent hemodialysis, doses
food. May be taken with meals to reduce GI discomfort. greater than 200 mg daily are not recommended.

High concentration IV solutions may be diluted using Precautions:

parenteral infusion solutions Heart failure (do not administer concurrently with
deferoxamine without approval of their health care
Pregnancy Category: A; C (doses greater than RENI) professional);
Hyperoxaluria;
ATC Code: A11DB Renal impairment;
Lactation

ASCORBIC ACID (VITAMIN C) Adverse Drug Reactions:

Common: Renal tubular obstruction (oxalate, urate, or
cystine renal stones), lower back pain (costovertebral),
OTC ASCORBIC ACID (VITAMIN C) hyperoxaluria, flushing, headache, nausea, vomiting,
abdominal cramps, diarrhea, flatulence, heartburn,
dental caries (chewable tablets), fatigue, insomnia,
Oral: 100 mg and 500 mg tablet
sleepiness
100 mg/mL drops, 15 mL and 30 mL
Less Common: Hemolytic anemia
100 mg/5 mL syrup, 60 mL and 120 mL
Rare: Sickle-cell crisis
Inj.: 250 mg/mL, 2 mL ampul (IV)
Drug Interactions:
A water-soluble vitamin that acts as a free radical, an
NOTE: Decreases urine pH, which may cause an increase in
antioxidant scavenger, and plays a major role in
the excretion of alkaline drugs and an increase in renal
oxidation-reduction reactions. Ascorbic acid is a cofactor
tubular reabsorption of acidic compounds.
for enzymes involved in the biosynthesis of collagen,
carnitine, and neurotransmitters.
Monitor closely with:
Decreases therapeutic effect of the following drugs:
Indications: Nutritional supplementation; management of
Mexiletine;
iron toxicity, scurvy and furunculosis
Propranolol [take ascorbic acid at least 1 hour prior to
propranolol] (bradycardic effect)
Contraindications: Anemia, breastfeeding, diabetes
mellitus, G6PD deficiency, hemochromatosis,
Increase absorption of the following drugs:
nephrolithiasis, pregnancy, sideroblastic anemia,
Iron Salts, Polysaccharide-Iron Complex
sodium restriction, sulfite hypersensitivity, tartrazine dye
hypersensitivity, thalassemia
Avoid concomitant use with:
Decreases therapeutic effect of the following drugs:
Dose:
Disulfiram; Warfarin (anticoagulation effects)
Nutritional supplementation, by mouth, ADULT (male), 90
mg once daily, or 100 mg once or twice daily; ADULT
Increases risk of adverse or toxic effects of the following
(female), 75 mg once daily, or 100 mg once or twice
drugs:
daily; ADULT and ADOLESCENT (pregnant female), 80-85
Deferoxamine (e.g., impairment of cardiac function,
mg once daily; ADULT and ADOLESCENT (lactating
causing cardiac decompensation)
female), 115–120 mg once daily; ADULT (male
smokers), 125 mg once daily; ADULT (female smokers),
Administration: May be taken without regard to meals.
110 mg once daily; ADOLESCENT (male), 75 mg once
Administer with a full glass of water.
daily; ADOLESCENT (female), 65 mg once daily; CHILD 9–
13 years, 45 mg once daily; CHILD 4–8 years, 25 mg
Pregnancy Category: C

30
ALIMENTARY TRACT AND METABOLISM

ATC Code: A11GA01 Adverse Drug Reactions: Flushing, malaise, erythema,

pruritus, rash, bronchospasm, allergic reaction

A
OTHER PLAIN VITAMIN PREPARATIONS Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Raltitrexed
Rx FOLIC ACID
Administration: May be administered by deep IM injection.
Oral: 400 micrograms, 800 micrograms, 1 mg and For IV injection or infusion, administer ≤5 mg dose
5 mg tablet / capsule undiluted over ≥1 minute or dilute ≤5 mg in 50 mL of NS
2.5 mg/mL pediatric drops or D5W and infuse over 30 minutes. May be added to IV
5 mg/5 mL syrup maintenance solutions and given as an infusion.
Also known as Vitamin B9, it is reduced in the body to Pregnancy Category: A
tetrahydrofolate, which is a coenzyme for various
metabolic processes, including the synthesis of purine ATC Code: Not available
and pyrimidine nucleotides, and hence in the synthesis
of DNA. It is also involved in some amino acid
conversions, and in the formation and utilization of
formate. Folic acid is also used in women of child­bearing Rx MECOBALAMIN
potential and pregnant women to protect against neural
tube defects in their offspring.
Oral: 500 micrograms tablet
Indications: Treatment of megaloblastic and macrocytic Inj.: 500 micrograms/mL, 1 mL ampule (IM, IV)
anemias due to folate deficiency; used for diarrhea in
pediatric patients Vitamin B12, a water-soluble vitamin, occurs in the body
mainly as methylcobalamin (mecobalamin), and as
adenosylcobalamin (cobamamide) and
Contraindication: Hypersensitivity to folic acid or any
hydroxocobalamin. Mecobalamin and cobamamide act
component of the formulation
as coenzymes in nucleic acid synthesis. Mecobalamin is
Dose: also closely involved with folic acid in several important
Anemia, by mouth, IV, IM, or SC injection, ADULT, 0.4 mg metabolic pathways.
daily; PREGNANT AND LACTATING WOMEN, 0.8 mg daily;
CHILD <4 years, up to 0.3 mg daily; INFANT, 0.1 mg daily. Indications: Symptomatic treatment of peripheral
Adequate intake (expressed as folate equivalents), by neuropathy associated with vitamin B12 deficiency (e.g.,
mouth, INFANT 7–12 months, 80 micrograms daily; numbness, pain, paralysis), including diabetic
INFANT 1–6 months, 65 micrograms daily. neuropathy and polyneuropathy and megaloblastic
Recommended daily allowance, RDA (expressed as dietary anemia associated with vitamin B12 deficiency.
folate equivalents), by mouth, ADULT, 400 micrograms
daily; PREGNANT WOMEN, 600 micrograms daily; Dose:
LACTATING WOMEN, 500 micrograms daily; CHILD 9–13 Peripheral neuropathy, by mouth, ADULT, 500 micrograms
years, 300 micrograms daily; CHILD 4–8 years, 200 3 times daily;
micrograms daily; CHILD 1–3 years, 150 micrograms by IV or IM injection, ADULT, 500 micrograms 3 times
weekly.
daily.
Megaloblastic anemia, by IV or IM injection, ADULT, initially
Dose Adjustment: 500 micrograms 3 times weekly; (maintenance dose
Geriatric: given after approximately 2 months of treatment, 500
Vitamin B12 deficiency must be ruled out before initiating micrograms every 1–3 months).
folate therapy due to frequency of combined nutritional
deficiencies. RDA requirements, 400 micrograms daily Precautions:
(minimum, 0.4 mg). Anaphylactoid reactions;
CNS effects;
Precautions: Hypokalemia;
Anemia (not appropriate for monotherapy with pernicious, Thrombocytosis;
aplastic, or normocytic anemias when anemia is present Pregnancy and lactation (vitamin B12 requirements may be
with vitamin B12 deficiency); pernicious anemia (doses increased).
>0.1 mg daily may obscure pernicious anemia with
continuing irreversible nerve damage progression); Adverse Drug Reactions:
Depressed hematopoiesis, alcoholism, and deficiencies of Common: Decreased blood pressure, diaphoresis,
other vitamins. induration at injection site, pain at injection site,
Elderly; dyspnea.
Neonates;
Lactation (excreted in breastmilk; increased folate Drug Interactions:
requirement).
Monitor closely with:
Decreases therapeutic effect of Mecobalamin:
Chloramphenicol

31

Administration: Administer immediately after removing from
package to limit direct exposure to light.
For IM administration, avoid multiple injections at the
A
same site. Do NOT inject near highly innervated regions.
NOTE: Do NOT use for more than 1 month without clear
signs of clinical improvement. Avoid long term use in
patients regularly exposed to mercury or mercury
compounds.
Pregnancy Category: C
ATC Code: Not available
PHYTOMENADIONE
Rx
(PHYTONADIONE, VITAMIN K1)
Oral: 2 mg/0.2 mL pediatric ampule (as mixed micelle)
Inj.: 2 mg/0.2 mL pediatric ampule (as mixed micelle) (IM,
IV)
10 mg/mL, 1 mL ampule (as mixed micelle) (IM, IV,
SC)
10 mg/mL, 1 mL ampule (as aqueous colloidal
solution with benzyl alcohol) (IM, IV, SC)
A fat-soluble vitamin that is an essential cofactor in the
synthesis of blood coagulation factors: prothrombin (II),
proconvertin (VII), plasma thromboplastin component
(IX), Stuart factor (X), and proteins C and S.
Indications: Management of anticoagulant-induced
prothrombin deficiency caused by indanedione or
coumarin derivatives such as warfarin; treatment and
prophylaxis against hemorrhagic disease of the newborn.
Contraindications: Known hypersensitivity to
phytomenadione or any component of the formulation;
avoid IM if bleeding; pregnancy (3rd trimester); it is not
effective in hereditary hypoprothrombinemia caused by
liver disease.
Dose:
Prophylaxis of hemorrhagic disease of the newborn, by IM
injection, NEONATE, 0.5-1 mg as single dose;
by mouth, NEONATE, 2 mg followed by a second dose
after 4-7 days and for breastfed babies a third dose after
1 month.
Treatment of hemorrhagic disease of the newborn, by slow
IV or IM injection, NEONATE, 1 mg (with further doses if
necessary, at 8-hour intervals).
Dose Adjustment:
Geriatric:
Dose should be at the lower end of the recommended
range.
Hepatic Impairment:
For mild-to-moderate impairment, use with caution.
For severe impairment, refer patient to a specialist.
Precautions:
Hepatic impairment; Elderly.
NOTE: Fat-soluble Vitamin. Patients with fat malabsorption,
especially in biliary obstruction or hepatic disease may
become Vitamin K deficient.
32
ALIMENTARY TRACT AND METABOLISM
Adverse Drug Reactions:
Common: Erythema, flushing, nausea, pain, tenderness,
tiredness, vomiting, warmth sensation
Less Common: Allergic reactions (including anaphylaxis),
bradycardia, bronchospasm, dizziness, dyspnea,
hypotension, rebound bleeding
Rare: Anaphylactoid reactions, hemolytic anemia,
hyperbilirubinemia, kernicterus
Drug Interactions:
Monitor closely with:
Decreases therapeutic effect of Phytomenadione:
Anticonvulsants, e.g., Phenobarbital, Phenytoin, Anti-
tuberculosis Drugs, e.g., Isoniazid, Rifampicin (may
cause vitamin K deficiency bleeding on the first day of
life in newborns)
Avoid concomitant use with:
Decreases therapeutic effect of the following drugs:
Anticoagulants, e.g., Warfarin (increases synthesis of
blood clotting factors)
Administration: IV administration should be slow, over 30
seconds. Rapid infusion can cause dyspnea, chest pain,
and back pain.
Pregnancy Category: C; X in 3rd trimester or near term
ATC Code: Not available
OTC PYRIDOXINE (VITAMIN B6)
Oral: 100 mg tablet (as hydrochloride)
A naturally occurring, water-soluble vitamin. It is converted
in erythrocytes to its active moiety, pyridoxal phosphate,
which acts as coenzymes in metabolic processes,
including metabolism of fat, protein, and carbohydrate.
Indications: Nutritional supplementation; Management of
cystathionuria, management of homocystinuria,
hyperoxaluria, neuritis, pregnancy-inducednausea and
vomiting, premenstrual syndrome (PMS), pyridoxine-
dependent seizures, sideroblastic anemia, vitamin B6
deficiency and xanthurenic aciduria.
Contraindications: Breastfeeding, pregnancy, premature
neonates, renal impairment.
Dose:
Nutritional supplementation, by mouth, ADULT and
ADOLESCENT (pregnant female), 1.9 mg daily; ADULT
and ADOLESCENT (lactating female), 2 mg daily; ADULT
(male ≥51 years), 1.5 mg daily; ADULT (female ≥51
years), 1.7 mg once daily; ADULT, 1.3 mg daily;
ADOLESCENT (male), 1.3 mg daily (RDA); ADOLESCENT
(female), 1.2 mg daily (RDA); CHILD 9-13 years, 1 mg
daily (RDA); CHILD 4-8 years, 0.6 mg daily (RDA); CHILD
1-3 years, 0.5 mg daily (RDA); INFANT >6 months, 0.3 mg
daily (weight-based dosing is approximately 0.033
mg/kg daily); INFANT ≤6 months and NEONATE, 0.1 mg
daily (weight-based dosing is approximately 0.014
mg/kg daily); PREMATURE NEONATE, 150 TO 210
micrograms/kg daily.
ALIMENTARY TRACT AND METABOLISM

Vitamin B6 deficiency including neuritis (not drug-induced),

by mouth, ADULT (without neuritis), 2.5-10 mg daily; may MINERAL SUPPLEMENTS
be adjusted to 2-5 mg daily once deficiency has been

A
corrected; ADULT (with neuritis), 100-200 mg daily for 3
CALCIUM
weeks, then 25-100 mg daily thereafter; CHILD (without
neuritis), 5-25 mg daily for 3 weeks, then 1.5-2.5 mg
daily (may be supplemented in a multivitamin product); GENERAL INFORMATION
CHILD (with neuritis), 10-50 mg daily for 3 weeks, then
1-2 mg daily (may be supplemented in a multivitamin An essential cation for the maintenance of the nervous,
product. muscular, and skeletal systems, as well as for cell
Sideroblastic anemia, by mouth, ADULT, 200-600 mg daily; membrane and capillary permeability. It is the primary
following an adequate response, 30-50 g daily may be component of skeletal tissue, providing structural
used. integrity and support for individual growth.
Selected metabolic disorders, including primary
cystathioniuria, primary homocystinuria, or xanthurenic Indications: Cardiac arrest; cardiopulmonary resuscitation;
aciduria, by mouth, ADULT, 100 to 500 mg daily or more, exchange transfusion-induced hypocalcemia
adjusted to clinical response; CHILD, 200-1000 mg daily, prophylaxis; hyperkalemia; hypermagnesemia;
adjusted to clinical response. hyperphosphatemia; hypocalcemia; nutritional
Primary hyperoxaluria, in combination with oral supplementation; osteoporosis prophylaxis.
orthophosphate therapy, by mouth, ADULT and CHILD,
initially 1.8-7 mg/kg daily with a final dose of 1-7 mg/kg Contraindications: Breastfeeding; cardiac arrhythmias;
daily. dehydration; digitalis toxicity; extravasation;
Premenstrual syndrome (PMS), by mouth, ADULT, 80-500 hypercalcemia; hypercalciuria; necrotizing enterocolitis;
mg daily. hyperphosphatemia; hypoparathyroidism; pregnancy;
Pregnancy-induced nausea / vomiting, by mouth, ADULT, sarcoidosis; ventricular fibrillation; diarrhea; vitamin D
10-25 mg 3 times daily; ADOLESCENT, 25-100 mg daily; toxicity.
CHILD, 1-2 mg daily.
Pyridoxine-dependent seizures, maintenance, by mouth, Dose Adjustment:
CHILD, INFANT, and NEONATE, initially 5 mg/kg once or Renal Impairment:
divided twice daily; titrate as needed to suppress In end-stage renal disease, administer with meals (e.g., 10–
seizures. 15 minutes before or during).

Precautions: Adverse Drug Reactions:

Seizures (associated with high-dose administration).
Adverse Drug Reactions:
Common: Nausea, vomiting, headache, paresthesia,
hyperesthesia, somnolence, low serum folic acid levels,
peripheral neuropathy.
Less Common: Neuronopathy syndrome, unstable gait,
perioral numbness, “stocking-globe” sensory loss,
seizures, metabolic acidosis.
Drug Interactions:
Monitor closely with:
Decreases therapeutic effect of Pyridoxine:
Cycloserine (secondary niacin deficiency)
Decreases therapeutic effect of Levodopa
Common: Mild to severe local irritation, chalky taste,
flushing, tingling sensation, hypotension (dizziness,
syncope), sinus bradycardia, cardiac arrhythmias,
cardiac arrest, diarrhea, gastric irritation.
Less Common: Milk-alkali syndrome, muscle cramps
Drug Interactions:
Monitor closely with:
Decreases absorption of Calcium:
Corticosteroids
Decreases absorption of the following drugs:
Dibasic Sodium Phosphate, Anhydrous, Monobasic
Sodium Phosphate, Monohydrate, Phenytoin (forms non-
absorbable complexes), Phosphorus Salts, Strontium-89
Chloride

Avoid concomitant use with: Decreases therapeutic effect of Magnesium Salts

Not to be administered concomitantly without consent of (neutralized by Calcium)
healthcare provider:
Altretamine, Cisplatin Increases risk of adverse or toxic effects of the following
drugs:
Administration: Administer whole. Do not crush, break, or Calcitriol (hypercalcemia), Vitamin D Analogs (Vitamin D-
chew. induced hypercalcemia)

Pregnancy Category: A Avoid concomitant use with:

Decreases absorption of Bisphosphonates e.g. Alendronate
ATC Code: A11HA02 (administer at least 2 hours apart)

Decreases bioavailability of the following drugs:

Fluoroquinolones e.g., Levofloxacin, Quinolones
[administer at least 2 hours before or 6 hours after
Calcium Salts], Tetracyclines [administer at least 1 hour

33

before Calcium Salts], Thyroid Hormones [administer at
least 4 hours before or after Calcium Salts] (forms non-
absorbable complexes)
A
Decreases therapeutic effect of Calcium:
Vitamin A
Decreases therapeutic effect of the following drugs:
Calcitonin, Nondepolarizing Neuromuscular Blockers,
Sucralfate [stagger doses], Thyroid Hormones
(hypothyroidism)
Increases risk of adverse effects of Calcium:
Vitamin A (bone loss)
Increases risk of adverse effects of the following drugs:
Cardiac Glycosides e.g., digoxin (arrhythmias),
Ceftriaxone (fatal reactions involving ceftriaxone-
calcium precipitates in the lungs and kidneys), Sodium
Bicarbonate, Thiazide Diuretics (milk-alkali syndrome),
Pregnancy Category: C
OTC CALCIUM CARBONATE
Oral: tablet or chewable tablet (equivalent to 500 mg and
600 mg elemental calcium)
An inorganic Calcium salt useful in the treatment of
hyperphosphatemia secondary to chronic renal failure.
Indications: Management of hyperphosphatemia,
hypocalcemia, and premenstrual syndrome (PMS);
nutritional supplementation; prevention of osteoporosis.
Contraindications: Breastfeeding; constipation;
dehydration; GI bleeding; GI obstruction; hypercalcemia;
hyperparathyroidism; ileus; hypercalciuria; necrotizing
enterocolitis; neoplastic disease; nephrolithiasis; peptic
ulcer disease; pregnancy; renal disease; sarcoidosis.
Dose:
Oral hypocalcemia, by mouth, ADULT, 5–10 g daily
(equivalent to 2–4 g elemental calcium), given in 3–4
divided doses; CHILD, 112.5–162.5 mg/kg daily
(equivalent to 45–65 mg/kg), given in 4 divided doses;
NEONATE, 125–375 mg/kg daily (equivalent to 50–150
mg/kg), given in 4–6 divided doses (maximum dose, 1 g
daily).
Nutritional supplementation and prevention of
osteoporosis, by mouth, ADULT ≥51 years, 2,500–3,750
mg daily (equivalent to 1,000 to 1,500 mg elemental
calcium); ADULT 19–50 years, 2,500 mg daily
(equivalent to 1,000 mg elemental calcium);
ADOLESCENT and CHILD 9–18 years, 3,250 mg daily
(equivalent to 1,300 mg elemental calcium); CHILD 4–8
years, 2,000 mg daily (equivalent to 800 mg elemental
calcium); CHILD 1–3 years, 1,250 mg daily (equivalent
to 500 mg elemental calcium); INFANT 6–12 months,
equivalent to 270 mg elemental calcium, based on total
intake; INFANT <6 months and NEONATE, equivalent to
210 mg elemental calcium, based on total intake.
34
ALIMENTARY TRACT AND METABOLISM
Dose Adjustment:
Renal Impairment:
In CrCl <30 mL/min, use with caution.
Precautions:
Renal impairment;
Hypoparathyroid disease;
Hypercalcemia-associated diseases;
Achlorhydria;
History of kidney stones.
Adverse Drug Reactions:
Common: Gastric hypersecretion, acid rebound, flatulence,
gastric distention, constipation, eructation
Less Common: Hypercalcemia, nephrolithiasis, milk-alkali
syndrome, renal failure
Rare: Hypophosphatemia
Drug Interactions:
Monitor closely with:
Decreases absorption of Calcium:
Corticosteroids, systemic
Increases risk of adverse effects of the following drugs:
Calcipotriene, Calcitriol (hypercalcemia), Mefloquine,
Thiazide Diuretics (hypercalcemia), Vitamin D Analogues
(Vitamin D-induced hypercalcemia)
Avoid concomitant use with:
Decreases absorption of the following drugs:
Bisacodyl [administer at least 1 hour apart]
Bisphosphonates e.g., Alendronate [administer at least 2
hours apart]
Decreases absorption of the following drugs:
Cefuroxime, oral [administer at least 1 hour before or 2
hours after Calcium Carbonate]
Delavirdine [administer at least 1 hour apart]
Ethotoin [administer Calcium Carbonate at least 1 hour
before or 6 hours after Ethotoin]
Itraconazole [administer at least 2 hours after
Itraconazole]
Ketoconazole, Oral [administer at least 2 hours after
Ketoconazole]
Phenytoin, oral [administer Calcium Carbonate at least 1
hour before or 6 hours after Phenytoin]
Rifampin [administer at least 1 hour apart]
Decreases bioavailability of the following drugs:
Fluoroquinolones e.g., Levofloxacin [administer at least
2 hours before or 6 hours after Calcium Salts],
Quinolones [administer at least 2 hours before or 6 hours
after Calcium Salts], Tetracyclines [administer at least 1
hour before Calcium Salts], Thyroid Hormones
[administer at least 4 hours before or after Calcium
Salts] (forms non-absorbable complexes)
Decreases serum concentration of the following drugs:
Ezetimibe and Rosuvastatin [administer at least 1 hour
before or 2 hours after Calcium Carbonate]
Gefitinib [administer at least 6 hours apart]
Decreases therapeutic effect of Calcium:
Vitamin A
ALIMENTARY TRACT AND METABOLISM
Decreases therapeutic effect of the following drugs:
Calcitonin, Cefuroxime (decrease antibiotic efficacy),
Methenamine, Sucralfate [stagger doses], Thyroid
Hormones (leads to hypothyroidism)
Decreases urinary excretion of Quinidine
Increases risk of adverse effects of Calcium:
Vitamin A (bone loss)
Increases risk of adverse effects of the following drugs:
Cysteamine [administer at least 1 hour apart] (increased
WBC cystine concentration)
Sodium Bicarbonate (milk-alkali syndrome)
Not to be use concomitantly with Calcium Carbonate:
Ammonium Chloride
Administration: Administer with meals to improve
absorption. Follow each dose with appropriate fluid
intake.
Separate administration with other medicines to prevent
interactions.
Pregnancy Category: C
ATC Code: A12AA04
Rx CALCIUM GLUCONATE (IV)
Inj.: 10% solution, 10 mL ampule (IV)
10% solution, 20 mL and 25 mL bottle (IV)
An organic Calcium salt used to prevent or treat negative
calcium balance. It also helps facilitate nerve and muscle
performance as well as normal cardiac function.
Indications: Hypocalcemia; hyperkalemia;
hypermagnesemia; nutritional supplementation.
Dose:
Hypocalcemia, by IV infusion, ADULT, 2-3 g slowly at a rate
not exceeding 5 mL/minute, repeat every 6 hours, as
needed (maximum dose, 15 g daily); alternatively, 15
mg/kg elemental calcium over 4–6 hours if symptoms
recur after initial IV calcium replacement; CHILD and
INFANT, 200 to 500 mg/kg daily as continuous IV
infusion or in 4 divided doses at a rate not exceeding 5
mL/minute; may be repeated after 6 hours or followed
by 500 mg/kg daily as continuous IV infusion or in 3–4
divided doses; NEONATE, 200–800 mg/kg daily as
continuous IV infusion or in 3–4 divided doses, followed
by 500 mg/kg daily as continuous IV infusion or in 3–4
divided doses.
Hyperkalemia, hypermagnesemia, and ionized
hypocalcemia, including life-threatening cardiac
arrhythmias, or during cardiopulmonary resuscitation
(CPR) associated with suspected or documented
hypermagnesemia, hyperkalemia, or ionized
hypocalcemia, by IV injection, ADULT, 500–800 mg of
10% solution (maximum dose, 3 g); CHILD and INFANT,
60–100 mg/kg (maximum dose, 3 g).
CNS depression due to hypermagnesemia, by slow IV
infusion, ADULT, 500–2,000 mg at a rate not exceeding
200 mg/minute (2 mL/minute of a 10% solution).
A
Nutritional supplementation to prevent hypocalcemia in
patients receiving total parenteral nutrition (TPN), by IV
injection, ADULT, 10–15 mEq daily admixed with TPN.
Exchange transfusion-induced hypocalcemia, prophylaxis,
by IV injection, NEONATE, 97 mg after each 100 mL of
citrated blood exchanged.
Precautions:
Impaired renal function; cardiac disease; hypercalcemia-
associated diseases, e.g., sarcoidosis.
Lactation (excreted in breastmilk; use with caution).
Administration: Administer by slow IV injection as a 10%
solution slowly through a small needle into a large vein
to avoid too rapid increase in serum calcium and
extravasation of calcium solution into the surrounding
tissue that may lead to tissue necrosis. Following IV
injection, the patient should remain recumbent for a
short time.
Visually inspect parenteral products for particulate
matter and discoloration prior to administration.
Close monitoring of serum calcium concentrations is
essential during IV administration of calcium.
Oral administration of calcium supplements or calcium-
rich foods should replace IV calcium therapy as soon as
possible.
NOTE: Do NOT administer by IM or SC route.
Closely monitor serum calcium concentrations during IV
administration of calcium.
Oral administration of calcium supplements or calcium-
rich foods should replace IV calcium therapy as soon as
possible.
See General Information on Calcium listed above for other
information.
ATC Code: A12AA03
OTC CALCIUM LACTATE
Oral: tablet (equivalent to 500 mg elemental calcium)
An organic Calcium salt used to prevent or treat negative
calcium balance. It also helps to prevent or reduce the
rate of bone loss, moderate nerve and muscle
performance and allow normal cardiac function.
Indications: Management of hypocalcemia; nutritional
supplementation
Dose:
Hypocalcemia, by mouth, ADULT, 15.4–30 g daily divided
every 8 hours; CHILD, 345–500 mg/kg daily in divided
doses every 6–8 hours (maximum dose, 9 g daily);
35

INFANT, 400–500 mg/kg daily in divided doses every 4–
6 hours.
Nutritional supplementation, by mouth, ADULT, 1000 mg
A
daily; ADOLESCENT and CHILD ≥9 years, 1300 mg daily;
CHILD 4–8 years, 800 mg daily; CHILD 1–3 years, 500
mg daily; INFANT 6–12 months, 270 mg daily; INFANT <6
months and NEONATE, 210 mg daily.
Precautions:
WARNING: Avoid IV administration of calcium in
patients on cardiac glycosides e.g. Digoxin,
digitoxin
Renal impairment;
Sarcoidosis;
History of nephrolithiasis
Hypoparathyroidism;
History of kidney stones (use with caution).
Administration: Administer 1–1.5 hours after meals or with
a demulcent (e.g., milk). Follow each dose with
appropriate fluid intake. Separate administration with
other medicines to prevent interactions.
See General Information on Calcium listed above for other
information.
ATC Code: A12AA05
CALCIUM CARBONATE +
OTC CHOLECALCIFEROL
(VITAMIN D3)
Oral: equivalent to 500 mg elemental calcium + 400 IU
vitamin D3
equivalent to 600 mg elemental calcium + 400 IU
vitamin D3
A two-component dietary supplement of calcium and fat-
soluble vitamin D, which serves to increase the calcium
pool available for GI absorption and assimilation into
bones.
Indications: Adjunct inosteoporosis; therapeutic
supplementation (e.g., lactose intolerance or with milk
allergy; established vitamin D dependent osteomalacia;
post-menopausal women; chronic kidney disease with or
without renal replacement therapy);
hyperphosphatemia.
Contraindications: hypercalcemia; hyperparathyroidism;
renal calculi; hypophosphatemia; vitamin D toxicity;
abnormal sensitivity to the effects of vitamin D;
malabsorption syndrome; renal failure or severe renal
impairment; known hypersensitivity to the preparation or
any of the excipients (e.g. soya oil).
Dose:
Calcium deficiency, by mouth, ADULT, supplementary intake
to achieve a total elemental calcium dosage of 1 g in 2
divided doses for male and premenopausal female
patients; 1.2–1.5 g in 3 divided doses for post-
menopausal women; not recommended for children <12
years.
36
ALIMENTARY TRACT AND METABOLISM
Dose Adjustment:
NOTE: Check Recommended Energy and Nutrient Intakes (RENI) per
day for Calcium and Vitamin D for dose of different population
groups.
Precautions:
Should not be used in osteoporosis due to prolonged
immobilization, renal stones, or severe hypercalciuria;
Mild to moderate renal failure or mild hypercalciuria
(supervise carefully, including periodic checks of plasma
calcium levels and urinary calcium excretion);
History of renal stones;
Patients receiving treatment for cardiovascular diseases;
Rare hereditary problems of glucose-galactose
malabsorption or fructose intolerance;
Achlorhydria;
Hypercalcemia and hypercalciuria.
NOTE: Allowances should be made for calcium and vitamin
D supplements from other sources.
Adverse Drug Reactions:
Less Common: Hypercalcemia, hypercalciuria
Rare: Abdominal pain, acid rebound, anorexia, arrhythmia,
bone or muscle pain, constipation or diarrhea,
headache, hypophosphatemia, flatulence, loss of
appetite, metallic taste, milk-alkali syndrome, nausea,
pruritus, rash, urticaria, vomiting, xerostomia
Drug Interactions:
Monitor closely with:
Decreases absorption of Calcium:
Corticosteroids
Decreases absorption of Quinolone Antibiotics, e.g.,
Ciprofloxacin
Increases risk of adverse effects of the following drugs:
Digoxin (hypercalcemia), Thiazide Diuretics
(hypercalcemia; milk-alkali syndrome with high doses)
Avoid concomitant use with:
Decreases absorption of the following drugs:
Iron Salts, Levothyroxine, Tetracyclines, Zinc Salts
Decreases serum concentration of Bisphosphonate e.g.,
Alendronate
Decreases therapeutic effect of Calcium Channel Blockers
e.g., Amlodipine
FOOD INTERACTION. Foods that are rich in oxalic acid (e.g.,
spinach) and phytic acid (e.g., whole cereals) may reduce
calcium absorption due to formation of insoluble calcium
salts. Do NOT take calcium products within 2 hours of
eating such foods.
Administration: Administer, preferably with food, 2 hours
before or after other medications.
Maintain adequate fluid intake. Administration is
followed by increased serum gastric acid secretion,
within 2 hours.
Pregnancy Category: C
ALIMENTARY TRACT AND METABOLISM

ATC Code: A12AX

Rx POTASSIUM CITRATE

A
POTASSIUM Oral: 10 mEq tablet

A major cation of the intracellular fluid that plays an active

Rx POTASSIUM CHLORIDE
Oral: 600 mg tablet
750 mg durules (equivalent to approximately 10 mEq
potassium)
1 mmol/mL syrup, 30 mL and 60 mL
Inj.: 2 mEq/mL, 2 mL and 5 mL ampul (IV infusion)
2 mEq/mL, 10 mL and 20 mL vial (IV infusion)
A major cation of the intracellular fluid that plays an active
role in the conduction of nerve impulses in the heart,
brain, and skeletal muscle.
Indication: Treatment and prevention of hypokalemia
role in the conduction of nerve impulses in the heart,
brain, and skeletal muscle.
Indications: Management of renal lithiasis, hypocitraturia,
chronic formers of calcium oxalate, phosphate calculi,
uric acid lithiasis and renal tubular acidosis with calcium
nephrolithiasis.
Contraindications: Renal insufficiency; persistent alkaline
urinary infections; urinary tract obstruction;
hyperpotassemia; adrenal insufficiency; respiratory or
metabolic alkalosis; active peptic ulcer; intestinal
obstruction; patients on anticholinergic therapy; slow
gastric emptying.

Contraindications: Hyperchloremia; severe renal or adrenal Dose:

insufficiency Severe hypocitraturia, by mouth, ADULT, initially 60 mEq
daily in 3 divided doses.
Dose: Mild hypocitraturia, by mouth, ADULT, initially 30 mEq daily
Hypokalemia, prophylaxis, by mouth, ADULT, 20 mEq daily. in 3 divided doses.
Hypokalemia, treatment, by mouth, ADULT, 40-100 mEq
daily; give in divided doses if >20 mEq daily. Precautions:
Altered potassium excretion mechanism; Renal
Precautions: insufficiency.
WARNING: Monitor urine output, plasma potassium, Adverse Drug Reaction:
and other electrolyte concentrations. Discontinue if Common: Slight GI disturbances
severe nausea, vomiting, or abdominal distress
develops. Drug Interactions:
Avoid concomitant use with:
Renal impairment (e.g., accumulation of potassium); Increases risk of adverse or toxic effects of the following
adrenocortical insufficiency; cardiac disease; acute drugs:
dehydration; extensive tissue destruction. Potassium-sparing Diuretics e.g., Spironolactone
(hyperkalemia)
Adverse Drug Reactions: GI ulceration, hyperkalemia,
nausea, vomiting, diarrhea, abdominal cramps Administration: To be taken 30 minutes after meals. Do NOT
chew, crush, or dilute tablets.
Drug Interactions:
Monitor closely with: Determine urinary citrate and pH approximately 24 hours
Increases risk of adverse or toxic effects of Antimuscarinics after the first dose and adjust dose accordingly. Do NOT
(GI adverse effects) exceed 100 mEq daily.

Avoid concomitant use with: Pregnancy Category: A

Increases risk of adverse or toxic effects of the following
drugs: ATC Code: A12BA02
ACE Inhibitors, Potassium-containing Drugs, Potassium-
sparing Diuretics e.g. Spironolactone (hyperkalemia),

Administration: Should be taken with food.

Pregnancy Category: C

ATC Code: A12BA01

37
 ALIMENTARY TRACT AND METABOLISM

ZINC (elemental zinc) daily for 10-14 days; INFANT <6 months,
10 mg (elemental zinc) daily for 10-14 days.
GENERAL INFORMATION
A

See General Information on Zinc listed above for other

An essential, mineral supplement in the diet, which is used information.
as an adjunct to oral rehydration in the treatment of
acute and persistent diarrhea. Pregnancy Category: C

Indication: Adjunct to oral rehydration therapy in acute and ATC Code: A12CB02
persistent diarrhea

Contraindication: Severe renal impairment OTC ZINC SULFATE

Precaution:
Acute renal failure (may accumulate).
Adverse Drug Reactions:
Common: Diarrhea, dry mouth, dyspepsia, GI upset, mouth
irritation, nausea, regurgitation and vomiting (in
children), unpleasant taste
Less Common: Gastritis, headache, irritability, lethargy,
copper deficiency (with prolonged use)
Drug Interactions:
Avoid concomitant use with:
Decreases absorption of Zinc:
Calcium Salts [separate doses by 2–3 hours],
Ethambutol, Ferrous Salts, Food, e.g., milk, phytates
present in cereals, rice, corn, or legumes
Decreases absorption of the following drugs:
Bisphosphonates e.g., Alendronate; Ferrous Salts e.g.,
Ferrous sulfate; Quinolones, e.g., Ofloxacin, Ciprofloxacin
[separate doses by at least 2 hours]; Tetracyclines
[separate administration by at least 2 hours]
Oral: 88 mg dispersible tablet (equivalent to 20 mg zinc)
solution (equivalent to 10 mg elemental zinc/mL)
drops (as monohydrate), 15 mL
solution (equivalent to 20 mg elemental zinc/5 mL)
syrup (as monohydrate), 60 mL
Zinc sulfate is widely distributed in the body but is
concentrated in the muscle, bone, skin, and prostatic
fluids.
Indication: Adjunct to oral rehydration therapy in acute and
persistent diarrhea
Dose:
Oral rehydration therapy in acute and persistent diarrhea
(adjunct), by mouth, CHILD 6 months to 5 years, 20 mg
(elemental zinc) daily for 10-14 days; INFANT <6 months,
10 mg (elemental zinc) daily for 10-14 days.
See General Information on Zinc listed above for other
information.

Decreases therapeutic effect of the following drugs: Pregnancy Category: C

Tetracyclines (anti-infective activity)
ATC Code: A12CB01
Administration: Tablets may be dispersed in breastmilk, oral
rehydration solution, or water on a small spoon. Older
children may chew the tablets or swallow them with OTHER MINERAL PRODUCTS
water.

Pregnancy Category: C OTC FERROUS SALT

Oral: tablet (equivalent to 60 mg elemental iron)

OTC ZINC GLUCONATE solution (equivalent to 15 mg elemental iron/0.6 mL)
drops, 15 mL and 30 mL
solution (equivalent to 30 mg elemental iron/5 mL)
Oral: tablet (equivalent to 30 mg elemental zinc) (as syrup, 60 mL
trihydrate)
chewable tablet (equivalent to 10 mg elemental zinc) NOTE: The elemental iron content of a ferrous salt depends on
70 mg/5 mL syrup (equivalent to 10 mg elemental the type of preparation as follows:
zinc), 60 mL and 120 mL Ferrous fumarate 33%
Ferrous gluconate 12%
Zinc gluconate is commonly used to treat and to prevent Ferrous lactate 19%
zinc deficiency, as well as for other purposes. Ferrous sulfate, hydrated 20%
Ferrous sulfate, desiccated 32%
Indication: Adjunct to oral rehydration therapy in acute and
persistent diarrhea An essential trace element required for the formation of
hemoglobin and for the efficient oxygen transport in the
Dose: blood.
Oral rehydration therapy in acute and persistent diarrhea
(adjunct), by mouth, CHILD 6 months to 5 years, 20 mg

38
ALIMENTARY TRACT AND METABOLISM
Indications: Treatment of iron-deficiency anemia and
supplement and prophylaxis in people on hemodialysis
receiving erythropoietin.
Contraindications: Anemia not due to iron deficiency;
parenteral iron therapy; in patients receiving repeated
blood transfusions; hemochromatosis; hemosiderosis
Dose:
Iron-deficiency anemia, by mouth, ADULT, elemental iron,
100–200 mg daily in divided doses.
Prevention of iron-deficiency anemia (in those at risk), by
mouth, ADULT (woman), elemental iron 60 mg daily;
CHILD >5 years, elemental iron 30 mg daily; CHILD <5
years, elemental iron 2 mg/kg daily (maximum, 30 mg).
NOTE: For women and children >5 years, folic acid may also
be given.
Precautions:
WARNING: May exacerbate GI bleeding. Use with
caution in patients with GI disorders.
Not to be administered for longer than 6 months (monitor
closely for potential complications);
Transfusion-dependent anemia;
Peptic ulcer;
Regional enteritis;
Ulcerative colitis;
Intestinal strictures;
Diverticula;
Pregnancy (avoid use in the first trimester; administer only
in women with low-normal hemoglobin).
NOTE: In cases of overdose, initiate therapy with
deferoxamine. Before administration of deferoxamine,
the stomach should be emptied by gastric lavage (with a
wide-bore tube), preferable within one hour of ingesting
a significant quantity of iron or if radiography reveals
tablets in the stomach.
Adverse Drug Reactions:
Common: Abdominal pain, black discoloration of feces,
constipation, diarrhea, nausea, vomiting
Less Common: Black discoloration of teeth
Rare: Anaphylaxis, GI erosion and perforation,
hemosiderosis
Drug Interactions:
Monitor closely with:
Decreases bioavailability of Methyldopa (interferes with
blood pressure control)
Avoid concomitant use with:
Decreases absorption of Iron:
Antacids, e.g., Aluminum or Magnesium Hydroxide,
Calcium, Doxycycline, Food, e.g., eggs, milk,
Tetracyclines, Zinc Salts
Decreases absorption of the following drugs:
Bisphosphonates e.g., Alendronate, Doxycycline,
Levothyroxine [administer at least 2 hours apart],
Quinolones, e.g., Ciprofloxacin, Tetracyclines, Zinc Salts
Decreases therapeutic effect of the following drugs:
Bisphosphonates e.g., Alendronate, Quinolones, e.g.,
Ciprofloxacin, Tetracyclines (anti-infective activity)
A
Administration: Best absorbed on an empty stomach but
may be taken after food to reduce GI adverse effects.
Dilute with water liquid preparations containing iron
salts, and if possible swallow through a drinking straw to
prevent teeth discoloration.
Pregnancy Category: C
ATC Code: Not available
Rx FERROUS SALT + FOLIC ACID
Oral: 60 mg elemental iron + 400 micrograms folic acid per
tablet / capsule / film-coated tablet
A two-component, nutritional supplement of iron and folic
acid given during pregnancy.
Indications: Prevention of iron and folic acid deficiencies,
especially in pregnancy; nutritional supplement during
pregnancy.
NOTE: Low doses of folic acid in combination preparations
are inadequate for the treatment of megaloblastic
anemia, overdose, and therapy with deferoxamine.
Contraindications: Hemolytic anemia; hemochromatosis;
hemosiderosis; repeated blood transfusions of
parenteral iron therapy; pernicious anemia
Dose:
Prevention of iron and folate deficiencies in pregnancy, by
mouth, ADULT, elemental iron, 100 mg + folic acid, 350–
400 micrograms daily throughout pregnancy.
Severe anemia, by mouth, ADULT, elemental iron, 120 mg
+ folic acid 400 micrograms daily for 3 months; CHILD
2–12 years, elemental iron 60 mg + folic acid, 400
micrograms daily for 3 months; CHILD <2 years,
elemental iron, 25 mg + folic acid 100–400 micrograms
daily for 3 months.
Dose Adjustment:
Renal Impairment:
Give iron supplementation when the patient is anemic, and
iron saturation is <20%.
Precautions:
WARNING: Iron salts can exacerbate GI bleeding; thus,
it should be used with caution in patients with GI
disorders.
Transfusion-dependent anemia;
Peptic ulcer, regional enteritis, ulcerative colitis, intestinal
strictures, diverticula;
Pernicious anemia;
Elderly and children;
Pregnancy (avoid use in the first trimester; administer only
in women with low-normal hemoglobin).
39
 ALIMENTARY TRACT AND METABOLISM

Adverse Drug Reactions:

Common: Abdominal pain, black discoloration of feces, OTC MICRONUTRIENT POWDER
constipation, diarrhea, nausea, vomiting
Less Common: Black discoloration of teeth
A

Oral: per 1-gram sachet contains:

Rare: Anaphylaxis, bronchospasm, fever, GI erosion and
perforation, hemosiderosis, irritability, rash, sleep Vitamin A 400 micrograms RE
disturbance Vitamin C 30 mg
Vitamin D 5 micrograms
Drug Interactions: Vitamin E 5 mg a-TE
Monitor closely with: Vitamin B1 0.5 mg
Decreases bioavailability of Methyldopa (interferes with Vitamin B2 0.5 mg
blood pressure control) Vitamin B6 0.5 mg
Vitamin B12 0.9 micrograms
Avoid concomitant use with: Folic acid 150 micrograms
Decreases absorption of Iron: Niacin 6 mg
Antacids, e.g., Aluminum or Magnesium Hydroxide Iron 10 mg
(separate administration times as long as possible), Zinc 4.1 mg
Calcium, Doxycycline, Food, e.g., eggs, milk, Copper 0.56 mg
Tetracyclines e.g., Doxycyline, Zinc Salts Iodine 90 micrograms
Selenium 17 micrograms
Decreases absorption of the following drugs:
Bisphosphonates e.g., Alendronate, Doxycycline, Single-dose packets vitamins and minerals, in powder form,
Levothyroxine [administer at least 2 hours apart], which can be sprinkled onto any ready-to-eat semisolid
Quinolones, e.g., Ciprofloxacin, Levofloxacin, food.
Tetracyclines, Zinc Salts
Indications: Prevent vitamin and mineral deficiencies;
Decreases serum concentration of Folic Acid: improve iron status and reduce anemia among infants
Folic Acid Antagonists, e.g., Methotrexate, and children 6-23 months of age.
Pyrimethamine, Triamterene, Sulfonamides,
Trimethoprim Contraindications: Children with specific conditions, such as
HIV infection or TB (effects and safety of the intervention
Decreases therapeutic effect of the following drugs: have not been evaluated).
Bisphosphonates e.g., Alendronate, Quinolones, e.g.,
Ciprofloxacin, Levofloxacin, Tetracyclines e.g., Dose:
Doxycycline (anti-infective activity) Prevention of vitamin and mineral deficiencies, improving
iron status, and reducing anemia, by mouth, CHILD and
Administration: To be taken on an empty stomach, at least INFANT 6-23 months, 1 sachet daily, add a mixture of
1 hour before or 2 hours after meals. micronutrients in powder form to any semisolid food.

Avoid taking antacids or antibiotics within 2 hours before Precautions:

or after administration. Programs involving the use of multiple micronutrient
powders for fortification at home of foods should be
Pregnancy Category: A preceded by an evaluation of the nutritional status
among children <5 years of age, and existing measures
ATC Code: Not available to control anemia and vitamin A deficiency (e.g.,
hookworm control programs, provision of supplements,
and use of other products for home fortification of foods
and fortified complementary foods), to ensure that daily
micronutrient needs are met and not exceeded.

Adverse Drug Reactions:

Common: Diarrhea
Less Common to Rare: Darkening of the stools, staining of
child’s teeth

Drug Interactions: No information found.

Administration: At minimum, for a period of 2 months,

followed by a period of 3–4 months off supplementation
(so that use of the micronutrient powders is started every
6 months.

Pregnancy Category: Not available

ATC Code: Not available

40
ALIMENTARY TRACT AND METABOLISM
OTHER ALIMENTARY TRACT AND
METABOLISM PRODUCTS
ENZYMES
Rx IMIGLUCERASE
Inj.: 400 U powder, 20 mL vial (IV infusion)
NOTE: Special Category: Drug for Compassionate Use
An analogue of the enzyme β-glucocerebrosidase (β-D-
glucosyl-N-acylsphingosine glucohydrolase), produced by
recombinant DNA technology. It is a lysosomal
glycoprotein enzyme, which catalyzes the hydrolysis of
the glycolipid glucocerebroside to glucose and ceramide.
Indication: Long-term enzyme replacement therapy in type
1 Gaucher disease that results in anemia,
thrombocytopenia, bone disease, or hepatomegaly /
splenomegaly.
Contraindications: No known contraindications
NOTE: Carefully re-evaluate treatment if there is
significant clinical evidence of hypersensitivity to the
product.
Dose:
NOTE: Individualize dose to each patient based on disease
severity and therapeutic goals.
Enzyme replacement therapy, by IV infusion, ADULT, initially
2.5 U/kg 3 times weekly to 60 U/kg once every 2 weeks.
Dose Adjustment: No information available
Precautions:
WARNING: Hypersensitivity reactions have occurred in
patients who developed IgG antibody to
imiglucerase.
Pulmonary hypertension and pneumonia (known
complications of Gaucher);
Previous treatment with alglucerase;
Carcinogenesis;
Mutagenesis;
Fertility (effect on reproductive capacity not known);
Children (use with caution).
STORAGE. Store products at 2–8oC (36–46oF).
Adverse Drug Reactions:
Common: Hypersensitivity reactions (pruritus, flushing,
urticaria, angioedema, chest discomfort, dyspnea,
coughing, cyanosis, hypotension), anaphylactoid
reaction, nausea, abdominal pain, vomiting, diarrhea,
rash, fatigue, headache, fever, dizziness, chills,
backache, tachycardia.
Drug Interactions: No information available
Administration: Administer via IV infusion over 1–2 hours.
Reconstitute as per manufacturer’s instruction. After
reconstitution, visually inspect prior to administration.
Slight flocculation (thin translucent fibers) may
A
occasionally occur after dilution. Do NOT use if there are
opaque particles or discoloration.
Pregnancy Category: C
ATC Code: A16AB02
ANTI-HYPOGLYCEMICS
Rx GLUCOSE (DEXTROSE)
Inj.: 50%, 10 mL and 20 mL ampule (IV)
50%, 50 mL vial (IV)
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV)
A sterile, hypertonic solution of glucose, which provides a
source of calories in a minimal volume of water and is
used in restoring blood glucose concentrations in the
treatment of hypoglycemia.
Indications: Fluid replacement without significant
electrolyte deficit; management of severe hypoglycemia
in an adult who is unable to take oral food or fluids.
Contraindications: Hyperglycemia; use of hyperosmotic
solutions in patients with anuria; diabetic coma; glucose-
galactose malabsorption syndrome; dehydrated patients
with delirium; intracranial or intraspinal hemorrhage;
should not be used after ischemic attacks.
Dose:
Fluid replacement, by IV infusion, ADULT and CHILD,
determined based on clinical data and, whenever
possible, electrolyte monitoring.
Treatment of hypoglycemia, by IV infusion (50% glucose
solution into a large vein), ADULT, 25-50 mL.
Dose Adjustment:
Renal Impairment:
Select doses with care.
Precautions:
May result in hypophosphatemia, hypokalemia and
hypomagnesemia;
Observe for signs of mental confusion and loss of
consciousness;
Prolonged use (may affect insulin production);
Diabetes mellitus.
Adverse Drug Reactions:
NOTE: Administration of glucose without adequate thiamine
levels may precipitate overt deficiency states e.g.,
Wernicke's encephalopathy.
Less Common: Pain at the injection site, phlebitis, tissue
necrosis, venous irritation, venous thrombosis.
Rare: Dehydration, edema or water intoxication, fluid and
electrolyte imbalance, glycosuria, hyperglycemia,
hypokalemia, hypomagnesemia, hypophosphatemia.
Drug Interactions:
41
 ALIMENTARY TRACT AND METABOLISM

Monitor closely with: Drug Interactions:

Associated with lower fasting glucose and insulin: Avoid concomitant use with:
Magnesium salts Enhances therapeutic effect of Anticoagulants, e.g.,
A

Warfarin (anticoagulant effect)

Administration: Should be administered by IV infusion via a
large central vein (e.g., into a secure IV cannula in an
antecubital vein) to minimize damage at the site of
injection (e.g., thrombophlebitis). Do not administer
glucose solutions through the same infusion equipment
as whole blood since hemolysis and clumping may occur.
Administration: Administer parenterally because glucagon is
destroyed in the GI tract.
Reconstitute as per manufacturer’s instructions. Use
reconstituted glucagon immediately. Discard any unused
portion.

Visually inspect parenteral products for particulate Do NOT use at concentrations greater than 1 mg/mL (1
matter and discoloration prior to administration. unit/mL).

NOTE: Rapid administration of hypertonic glucose solutions NOTE: Patients with Type 1 diabetes may have less of an
may produce substantial hyperglycemia and increase in blood glucose levels compared with a stable
hyperosmolar syndrome. Type 2 patient. Administer supplementary carbohydrate
as soon as possible, especially to pediatric patients.
Pregnancy Category: C
Pregnancy Category: B
ATC Code: Not available
ATC Code: Not available

Rx GLUCAGON

Inj.: 1 mg lyophilized powder (as hydrochloride) + solvent

(IM, IV, SC)

A polypeptide that is produced by α cells of islets of

Langerhans in the pancreas. It stimulates adenylate
cyclase to produce cAMP, promoting hepatic
glycogenolysis and gluconeogenesis, which causes an
increase in blood glucose levels. Glucagon is synthesized
using genetically altered Escherichia coli bacteria.

Indication: For life-threatening hypoglycemia

Contraindications: Pheochromocytoma; known

hypersensitivity to glucagon or any of its components

Dose:
Severe hypoglycemia, by IV, IM, or SC injection, ADULT ≥25
kg, initially 1 mg; if not responsive within 10 minutes,
administer IV glucose; repeat glucagon dose if
necessary; ADULT <25 kg, initially 0.5 mg; if not
responsive within 10 minutes, administer IV glucose;
repeat glucagon dose if necessary.

Precautions:

WARNING: Effective in treating hypoglycemia only if

sufficient liver glycogen is present.

Insulinoma;
Glucagonoma;
Pheochromocytoma;
Renal impairment;
Hepatic impairment;
Lactation (not known if excreted in breastmilk).

Adverse Drug Reactions:

Common: Nausea, vomiting, diarrhea, hypokalemia,
hypoglycemia
Less Common: Generalized allergic reactions

42
BLOOD AND BLOOD FORMING ORGANS
BLOOD AND BLOOD FORMING ORGANS
ANTITHROMBOTIC AGENTS
VITAMIN K ANTAGONISTS
Rx WARFARIN
Oral: 1 mg, 2.5 mg, and 5 mg tablet (as sodium salt)
A coumarin derivative anticoagulant that exerts its effect by
interfering with the hepatic synthesis of vitamin K-
dependent coagulation factors II (prothrombin), VII, IX,
and X, as well as the anticoagulant proteins C and S.
Indications: Prophylaxis and treatment of thromboembolic
disorders (e.g., venous, pulmonary) and embolic
complications arising from atrial fibrillation or cardiac
valve replacement; adjunct to reduce risk of systemic
embolism (e.g., recurrent MI, stroke) after myocardial
infarction; acute coronary syndrome.
Contraindications: Hemorrhagic tendencies (e.g., cerebral
aneurysm, cerebrovascular hemorrhage, dissecting
aortic aneurysm, spinal puncture, other diagnostic or
therapeutic procedures with potential for significant
bleeding, history of bleeding disorders); recent or
potential surgery of the eye or CNS; major regional or
lumbar block anesthesia or traumatic surgery resulting
in large, open surfaces; blood dyscrasias; severe
uncontrolled or malignant hypertension; pericarditis or
pericardial effusion; bacterial endocarditis;
unsupervised patients with conditions associated with a
high potential for nonadherence; eclampsia or
pre­eclampsia; threatened abortion; pregnancy (except
in women with mechanical heart valves at high risk for
thromboembolism).
Dose:
NOTE: Carefully individualize dose based on clinical and
laboratory findings (i.e., INR, hepatic function, cardiac
function, age, nutritional status, concurrent therapy, risk
of bleeding, prior dose response, clinical situation).
Consider other patient related factors when determining
initial dose (e.g., age, body weight, concomitant
medications, comorbidities). Determine optimum dose
and duration of therapy by the condition being treated.
Adjust dosage in small increments and carefully monitor
patient response.
Thrombosis or embolism, prevention and/or treatment, by
mouth, ADULT, start with 2–5 mg once daily for 2 days or
for healthy individuals, 10 mg once daily for 2 days; lower
doses (e.g., 5 mg once daily) are recommended for
patients with confirmed heparin induced
thrombocytopenia (HIT) once platelet recovery has
occurred; in patients with acute venous
thromboembolism, initiation may begin on the first or
second day of low molecular weight heparin or
unfractionated heparin therapy; adjust dose according to
INR results; maintenance dose, 2–10 mg daily; CHILD, if
baseline INR is 1–1.3, initiate at 0.2 mg/kg (maximum
10 mg/dose); adjust dose based on INR to maintain INR
of 2–3; administer 0.09–0.33 mg/kg daily; INFANT <12
months, may require an average dose of 0.33 mg/kg
daily to maintain an INR of 2–3.
B
NOTE: Consistent anticoagulation may be difficult to
maintain in children <5 years.
Overlapping parenteral anticoagulant and warfarin by at
least 5 days is necessary in the treatment of DVT/PE
even if the INR is therapeutic earlier than 5 days.
Dose Adjustment:
Geriatric:
Initiate at ≤5 mg. Usual maintenance dose is 2–5 mg daily.
May require lower doses to produce a therapeutic level
of anticoagulation.
Precautions:
WARNING: Administration of large loading doses (i.e.,
>10 mg) is NOT recommended due to possible
increased risk of hemorrhage or necrosis.
Can cause major or fatal bleeding. Perform regular
monitoring of international normalized ratio (INR) on
all treated patients. Drugs, dietary changes, and
other factors affect INR levels achieved with warfarin
therapy. Instruct patients about prevention
measures to minimize the risk of bleeding and to
report immediately to their healthcare provider signs
and symptoms of bleeding.
Risk factors for bleeding include high intensity
anticoagulation (INR >4), age (≥65 years), variable INRs,
history of GI bleeding, hypertension, cerebrovascular
disease, serious heart disease, anemia, severe diabetes,
malignancy, trauma, renal insufficiency, polycythemia
vera, vasculitis, open wound, history of PUD, indwelling
catheters, menstruating and postpartum women, drug-
drug interactions, long duration of therapy, or known
genetic deficiency in CYP2C9 activity.
Anaphylaxis or hypersensitivity; skin necrosis or gangrene.
Artheroemboli or cholesterol microemboli;
Infection (use with caution in acute infection or active TB, or
any disruption of normal GI flora).
Dietary insufficiency (e.g. vitamin K deficiency);
Heparin-induced thrombocytopenia and DVT (limb
ischemia, necrosis, and gangrene have occurred).
Hepatic impairment; renal impairment; thyroid disease.
Surgery (discontinue for approximately 5 days before
surgery; may reinstitute warfarin therapy ~12–24 hours
after surgery).
Patients with genomic variants in CYP2C9 and/or VKORC1.
Elderly (may be more sensitive to anticoagulant therapy;
risk of bleeding complications has been associated with
increased age).
Lactation (carefully monitor breastfeeding women to avoid
excessive anticoagulation; monitor nursing infants for
bruising or bleeding).
Adverse Drug Reactions: Vasculitis, signs or symptoms of
bleeding (e.g., dizziness, fatigue, fever, headache,
lethargy, malaise, pain), alopecia, bullous eruptions,
dermatitis, rash, pruritus, urticaria, abdominal pain,
43

diarrhea, flatulence, gastrointestinal bleeding, nausea,
taste disturbance, vomiting, hematuria, anemia,
retroperitoneal hematoma, unrecognized bleeding sites
(e.g., colon cancer), hepatitis (including cholestatic
hepatitis), osteoporosis (potential association with long-
term use), paralysis, paresthesia, weakness, respiratory
B
tract bleeding, tracheobronchial calcification,
anaphylactic reaction, hypersensitivity / allergic
reactions, skin necrosis, gangrene, “purple toe”
syndrome.
Drug Interactions:
Monitor closely with:
Decreases absorption of Warfarin:
Bile Acid Sequestrants, Lixisenatide
Enhances anticoagulant effect of Warfarin:
Paracetamol, Agents with Antiplatelet Properties, e.g.,
P2Y12 Inhibitors, Amikacin, Amoxicillin, Bupropion.
Cephalosporins e.g., Cefuroxime, Chloramphenicol,
Chondroitin Sulfate, Cloxacillin, Systemic
Corticosteroids, COX-2 Inhibitors e.g., Celecoxib,
Cyclophosphamide, Etoposide, Exenatide, Fibrates e.g.,
Fenofibrate, Gefitinib, Gemcitabine, Glucagon,
Glucosamine, HMG-CoA Reductase Inhibitors [except
Atorvastatin], Ifosfamide, systemic Ivermectin,
Leflunomide, Levocarnitine, Mirtazapine, Multivitamins
with Fluoride with ADE
Enhances anticoagulant effect of Warfarin:
Multivitamins and Minerals with AE, no Iron, Neomycin,
Nonsteroidal Anti-Inflammatory Agents, Omega-3 Fatty
Acids, Orlistat, Other Anticoagulants, Penicillins [except
Dicloxacillin, Nafcillin, Pentoxifylline, Proguanil,
Propacetamol, Quinidine, Quinine, Quinolone Antibiotics
e.g. Levofloxacin, Salicylates, Selective Serotonin
Reuptake Inhibitors e.g. Sertraline, Sugammadex,
Sulfonylureas e.g., Gliclazide, Tetracycline Derivatives
e.g. Clarithromycin, Thrombolytic Agents e.g. Alteplase,
Thyroid Products, Tibolone, Tramadol, Tricyclic
Antidepressants e.g., Amitriptyline, Vitamin E
Enhances therapeutic effect of Sulfonylureas e.g., Gliclazide
(hypoglycemic effect)
Increases metabolism of Warfarin:
Anticholinergic/Sedative combination, Bosentan,
Rifamycin Derivatives
Increases risk of adverse or toxic effects of Warfarin (may
increase INR/ risk of bleeding):
Ampicillin, Clindamycin, Desvenlafaxine, Prostacyclin
Analogues e.g., Quinidine, Venlafaxine, Vitamin E
Increases risk of adverse or toxic effects (bleeding effect) of
the following drugs:
Deferasirox, Deoxycholic Acid, Nintedanib,
Obinutuzumab, Regorafenib, Iodine I131
Reduces anticoagulant effect of Warfarin:
Azathioprine, Cloxacillin, Coenzyme Q-10, Dicloxacillin,
Flucloxacillin, Floxacillin, Mercaptopurine, Multivitamins
and Minerals with ADEK, Folate, Iron
44
BLOOD AND BLOOD FORMING ORGANS
Avoid concomitant use with:
Counteracts anticoagulant effect of Warfarin:
Estrogen Derivatives or Progestins (potential
prothrombotic effects)
Decreases absorption of Warfarin:
Sucralfate [administer Warfarin at least 2 hours before
or 6 hours after Sucralfate]
Decreases metabolism of Warfarin and increases PT/ INR:
Acute alcoholism, strong CYP2C9 Inhibitors, Imatinib,
Sulfinpyrazone
Decreases protein binding of Warfarin:
Sulfinpyrazone
Decreases serum concentration of Warfarin:
Carbamazepine, Dabrafenib, Enzalutamide, Sucralfate
Enhances anticoagulant effect of Warfarin:
Allopurinol, Amiodarone, Androgens, Apixaban,
Cimetidine, Clopidogrel, Dabigatran Etexilate, Fibric Acid
Derivatives, Fosphenytoin, Imatinib, NSAID, Phenytoin,
Salicylates [except Salsalate], Sorafenib, Streptokinase,
Sulfonamide Derivatives
Enhances therapeutic effect of Rivaroxaban (anticoagulant
effect)
Increases metabolism of Warfarin and decreases PT / INR:
Chronic alcoholism, Barbiturates e.g., Phenobarbital,
strong CYP2C9 Inducers
Increases serum concentration of Warfarin:
Amiodarone [reduce Warfarin dose by 30 to 50%],
Capecitabine, Ceritinib, Fluconazole, systemic and
topical Fluorouracil, Fosphenytoin, systemic Fusidic Acid,
systemic Metronidazole, topical Miconazole, Phenytoin,
Sorafenib, Tamoxifen
Reduces anticoagulant effect of Warfarin:
Antithyroid Agents e.g., PTU, Contraceptives, e.g.,
Estrogens, Progestins, Phytonadione, Sucralfate
FOOD/SUPPLEMENT INTERACTIONS.
Cranberry juice, Ginkgo biloba, herbs with anticoagulant or
antiplatelet properties, e.g., alfalfa, anise, bilberry
(bleeding) may increase warfarin effect.
Vitamin K-rich foods, including green tea (Camellia
sinensis), chewing tobacco, a variety of oils (canola, corn,
olive, peanut, safflower, sesame seed, soybean, or
sunflower, may decrease anticoagulant effects of
Warfarin.
Administration: May be taken with or without food. Take at
the same time each day. Maintain a consistent diet.
Avoid drastic changes in diet which decrease efficacy of
warfarin. Consult prescriber before making changes in
diet.
NOTE: Instruct patients to report bleeding, accidents, or falls
as well as any new or discontinued medications, herbal
or alternative products used, or significant changes in
smoking or dietary habits. Unrecognized bleeding sites
BLOOD AND BLOOD FORMING ORGANS
(e.g., colon cancer) may be uncovered by
anticoagulation.
Pregnancy Category: D (women with mechanical heart
valves); X (other indications)
ATC Code: B01AA03
HEPARIN GROUP
GENERAL INFORMATION
Heparin is a heterogenous mixture of sulfated
mucopolysaccharides.
High-molecular-weight (HMW) heparin, also known as
unfractionated heparin (UFH), are fractions of heparin
with high affinity for antithrombin. UFH has a molecular
weight range of 5,000–30,000.
In contrast, the shorter chain low-molecular-weight (LMW)
fractions of heparin inhibit activated factor X but have
less effect on thrombin than the HMW species. LMW
heparins, in comparison with UFH, may have equal
efficacy, increased bioavailability from the subcutaneous
site of injection, and less frequent dosing requirements.
Mode of Action: Heparin acts as an anticoagulant by
enhancing the inhibition rate of clotting proteases such
as antithrombin III, whose action inhibits the activity of
clotting factors IXa, Xa, and thrombin (factor IIa).
Indications: Management of acute coronary syndrome,
peripheral artery occlusive disease and thrombosis or
thromboembolism.
Precautions:
WARNING: Bleeding is the major adverse effect of
anticoagulants. Hemorrhage may occur at virtually
any site. At recommended doses, single injections
do NOT significantly influence platelet aggregation
or affect global clotting time.
May contain benzyl alcohol as a preservative. Use
in neonates, infants, and pregnant or nursing
mothers has been associated with the
development of gasping syndrome in newborns.
May contain sodium metabisulfite, which may
cause allergic-type reactions, including
anaphylactic symptoms and life-threatening
asthmatic episodes.
Bleeding (discontinue if bleeding occurs; protamine may be
considered as a partial reversal agent in overdose
situations); Thrombocytopenia; Hyperkalemia; GI
ulceration; Renal impairment; Hepatic impairment;
Prosthetic heart valves; Low weight patients (risk of
bleeding may be increased in women <45 kg and in men
<57 kg); Obesity (consult with a specialist regarding
dosing in bariatric surgery patients and other obese
patients who may require higher LMWH doses); Surgical
patients (discontinue use 12–24 hours prior to CABG
and dose with unfractionated heparin as per institutional
practice); Extreme body weights (use with caution in
patients <45 kg or >120 kg); Elderly; Pregnancy;
Lactation.
NOTE: Some products are derived from porcine intestinal
mucosa.
B
Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Heparins:
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, SSRIs e.g., Fluoxetine
Antithrombin III, Aspirin, NSAIDS, Omega-3 Fatty Acids,
Other Anticoagulants, Pentoxifylline, Salicylates e.g.
Aspirin, Sugammadex, Thrombolytic Agents e.g.,
Streptokinase, Tibolone, Vitamin E
Increases risk of adverse or toxic effects (bleeding or
antiplatelet effects) of Heparins:
5­ASA Derivatives, Dextran, Dipyridamole,
Hydroxychloroquine, Prostacyclin Analogues
Increases risk of adverse or toxic effects of the following
drugs:
Hyperkalemic effect: ACE Inhibitors e.g., Enalapril,
Aliskiren, Angiotensin II Receptor Blockers e.g., Losartan,
Canagliflozin, Potassium salts (hyperkalemic effect),
Potassium-sparing Diuretics e.g., Spironolactone
Bleeding complications: Antithrombin III,
injection site bruising and/or bleeding: Deoxycholic acid,
Nintedanib, Obinutuzumab, Iodine I131
GI ulceration or irritation and/or bleeding: Deferasirox
Reduces anticoagulant effect of Heparins:
Antihistamines e.g., diphenhydramine, Digitalis,
Nicotine, Nitroglycerine, Tetracyclines
Avoid concomitant use with:
Enhances anticoagulant effect of Heparins:
Apixaban, Dabigatran Etexilate, Streptokinase
Enhances therapeutic effects of Rivaroxaban
(anticoagulant effect)
Increases risk of adverse or toxic effects (bleeding) of
Heparins:
Herbs with anticoagulant or antiplatelet properties, e.g.,
Alfalfa, Anise, Bilberry, Vorapaxar
Reduces anticoagulant effect of Heparins:
Estrogen Derivatives, Progestins,
Rx ENOXAPARIN
Inj.: 100 mg/mL, 0.2 mL, 0.4 mL, and 0.6 mL pre-filled
syringe (SC) (as sodium salt)
A low molecular weight heparin (LMWH). LMWHs strongly
inhibit factor Xa but have a small effect on the activated
partial thromboplastin time. Enoxaparin has an
approximate anti-factor Xa activity of 100 units/mg.
Indications: Management of acute coronary syndrome (e.g.,
unstable angina, non-ST-elevation myocardial infarction
(NSTEMI), ST-elevation myocardial infarction (STEMI)),
45

peripheral artery occlusive disease and thrombosis /
thromboembolism (e.g., deep vein thrombosis (DVT)).
Contraindications: Thrombocytopenia associated with a
positive in vitro test for antiplatelet antibodies in the
presence of enoxaparin; active major bleeding; In
B
neonates, infants, and pregnant or nursing mothers.
Dose:
NOTE: 1 mg enoxaparin = 100 units anti-Xa activity
Weight-based doses (e.g., 1 mg/kg) are commonly
rounded to the nearest 10 mg.
Deep Vein Thrombosis (DVT) prophylaxis in abdominal
surgery, by SC injection, ADULT, 40 mg once daily, with
initial dose given 2 hours prior to surgery; continue until
risk of DVT has diminished, usually 7–10 days.
DVT prophylaxis in hip replacement surgery, by SC injection,
ADULT, 30 mg twice daily (every 12 hours), with initial
dose within 12–24 hours after surgery, and every 12
hours for at least 10 days or until risk of DVT has
diminished or the patient is adequately anticoagulated
on warfarin; or
40 mg once daily, with initial dose within 9–15 hours
before surgery, and daily for at least 10 days (or up to 35
days postoperatively) or until risk of DVT has diminished
or the patient is adequately anticoagulated on warfarin.
DVT prophylaxis in knee replacement surgery, by SC
injection, ADULT, 30 mg every 12 hours, with initial dose
within 12–24 hours after surgery, and every 12 hours for
at least 10 days or until risk of DVT has diminished or the
patient is adequately anticoagulated on warfarin.
DVT prophylaxis in medical patients with severely restricted
mobility during acute illness, by SC injection, ADULT, 40
mg once daily; continue until risk of DVT has diminished,
usually 6–11 days [NOTE: Start warfarin on the first or
second treatment day and continue enoxaparin until INR
is ≥2 for at least 24 hours (usually 5–7 days)].
DVT, acute treatment in inpatients with or without
pulmonary embolism, by SC injection, ADULT, 1 mg/kg
per dose every 12 hours or 1.5 mg/kg every 24 hours.
DVT, acute treatment in outpatients without pulmonary
embolism, by SC injection, ADULT, 1 mg/kg per dose
every 12 hours.
STEMI, by SC injection, ADULT ≥75 years, initially 0.75
mg/kg every 12 hours, do NOT administer by IV bolus
(maximum dose, 75 mg for first 2 doses), for
maintenance, after the first 2 doses, 0.75 mg/kg every
12 hours;
by IV bolus, ADULT <75 years, initially 30 mg once by IV
bolus plus 1 mg/kg once by SC injection, followed by 1
mg/kg by SC injection, every 12 hours (maximum, 100
mg for the first 2 doses).
STEMI, maintenance, by SC injection,
1 mg/kg every 12 hours (administer the first
maintenance dose 12 hours after the second SC dose)
[NOTE: Therapy may be continued for up to 8 days or until
revascularization. Unless contraindicated, all patients
should receive aspirin (indefinitely) and clopidogrel. In
patients with STEMI receiving thrombolytics, initiate
enoxaparin dosing between 15 minutes before and 30
minutes after fibrinolytic therapy.].
Unstable angina or NSTEMI, by SC injection, ADULT, 1
mg/kg every 12 hours in conjunction with oral aspirin
therapy; continue for the duration of hospitalization, at
least 2 days for up to 8 days.
46
BLOOD AND BLOOD FORMING ORGANS
Dose Adjustment:
Geriatric:
Dose adjustment may be required if renal impairment is
present.
In patients ≥75 years being treated for STEMI, administer a
lower dose of 0.75 mg/kg every 12 hours and omit IV
bolus dose.
Renal Impairment:
Primarily eliminated via the renal route. Reduce doses and
frequently monitor anti-Xa levels as accumulation may
occur with repeated doses.
For patients with CrCl <30 mL/minute, if used for DVT
prophylaxis in abdominal surgery, hip replacement, knee
replacement, or in medical patients during acute illness,
by SC injection, 30 mg once daily.
For patients with CrCl <30 mL/minute, if used for DVT
treatment, for both inpatient or outpatient treatment in
conjunction with warfarin, by SC injection, 1 mg/kg once
daily.
For patients with CrCl <30 mL/minute, if used for STEMI, by
SC injection, ADULT ≥75 years, maintenance, 1 mg/kg
once daily;
by IV bolus, ADULT <75 years, initially 30 mg with the first
dose of the SC maintenance regimen (maintenance, by
SC injection, 1 mg/kg once daily.
For patients with CrCl <30 mL/minute, if used for unstable
angina or NSTEMI, by SC injection, ADULT 1 mg/kg once
daily.
Obesity:
Use actual body weight to calculate dose. Dose capping is
not recommended. Twice daily dosing preferred.
CONVERSION:
Conversion from IV unfractionated heparin (UFH)
infusion to SC enoxaparin: Calculate specific dose for
enoxaparin based on indication. Discontinue UFH and
begin enoxaparin within 1 hour.
Conversion from SC enoxaparin to IV UFH infusion:
Discontinue enoxaparin, calculate specific dose for IV
UFH infusion based on indication. Omit heparin bolus or
loading dose.
Converting from SC enoxaparin dosed every 12 hours:
Start IV UFH infusion 10–11 hours after last enoxaparin
dose.
Converting from SC enoxaparin dosed every 24 hours:
Start IV UFH infusion 22–23 hours after last enoxaparin
dose.
Precautions:
WARNING: NOT to be used interchangeably (unit for
unit) with heparin or any other LMWH.
NOT recommended for use in patients with current
heparin-induced thrombocytopenia (HIT) or HIT with
thrombosis due to high cross-reactivity to heparin-
platelet factor-4 antibody.
BLOOD AND BLOOD FORMING ORGANS
Epidural or spinal hematomas may occur in patients
who are anticoagulated with LMWHs or heparinoids
and are receiving neuraxial anesthesia or
undergoing spinal puncture. May result in long-term
or permanent paralysis.
Renal impairment; Hepatic impairment; Elderly (increased
injection-associated bleeding and serious adverse
reactions; increased incidence of bleeding with doses of
1.5 mg/kg daily or 1 mg/kg every 12 hours).
Adverse Drug Reactions:
Common: Confusion, pain, nausea, diarrhea, major
hemorrhage (intracranial, retroperitoneal, or
intraocular), moderate thrombocytopenia, anemia,
bruise, hematuria, fever, and hematoma, irritation,
bruising, erythema, or pain at injection site,
Less Common: Alopecia, anaphylaxis, anaphylactoid
reaction, eczematous rash (plaques), eosinophilia,
epidural hematoma after spinal puncture, headache,
hepatic injury (hepatocellular and cholestatic),
hyperkalemia, hypersensitivity angiitis, hypersensitivity
reaction, osteoporosis (long-term use), pruritic
erythematous rash (patches), pruritus, purpura,
retroperitoneal hemorrhage, severe anemia
(hemorrhagic), skin necrosis, thrombocythemia,
thrombocytopenia, thrombosis (prosthetic valve;
enoxaparin-induced thrombocytopenia), shock, urticaria,
vesiculobullous rash
Rare: Intracranial hemorrhage
Administration: Administer by deep SC injection alternating
between the left or right anterolateral and left or right
posterolateral abdominal wall.
Do NOT administer intramuscularly.
Do NOT rub injection site to minimize bruising.
Do NOT expel the air bubble from the syringe prior to
injection to avoid loss of drug from the 30 mg and 40 mg
prefilled syringes.
Do NOT mix with other infusions or injections.
See General Information on Heparin Group under
Antithrombotic Agents for further information.
Pregnancy Category: B
ATC Code: B01AB05
HEPARIN SODIUM
Rx (UNFRACTIONATED,
BOVINE ORIGIN)
Inj.: 1,000 IU/mL and 5,000 IU/mL, 5 mL and 30 mL vial
(IV infusion, SC)
It is a sulfated mucopolysaccharide prepared from the lungs
of oxen or the intestinal mucosa of oxen, pigs, or sheep.
Heparin inhibits clotting of blood by enhancing the action
of antithrombin III, which inhibits the activity of activated
clotting factors including thrombin (factor IIa) and
activated factor X (factor Xa).
Indications: Prophylaxis and treatment of thromboembolic
disorders (e.g, venous thromboembolism, acute arterial
thrombosis); acute coronary syndrome (e.g., unstable
angina, non-ST-elevation myocardial infarction (NSTEMI),
ST-elevation myocardial infarction (STEMI));
anticoagulant for extracorporeal and dialysis
B
procedures.
Contraindications: Severe thrombocytopenia; uncontrolled
active bleeding except when due to disseminated
intravascular coagulation (DIC); not for use when
appropriate blood coagulation tests cannot be obtained
at appropriate intervals; neonates; infants; pregnant or
nursing mothers
Dose:
STEMI, as adjunct to fibrinolysis with full-dose alteplase,
reteplase, or tenecteplase, by IV infusion, ADULT, initially
60 units/kg (maximum, 4000 units), then 12 units/kg
every hour (maximum, 1000 units/hour) as continuous
IV infusion, check aPTT every 4–6 hours; adjust to target
of 1.5–2 times the upper limit of control (50–70
seconds); continue for a minimum of 48 hours,
preferably for the duration of hospitalization (up to 8
days) or until revascularization.
Unstable angina or NSTEMI, by IV bolus, ADULT, initially 60
units/kg (maximum, 4000 units) followed by an initial IV
infusion of 12 units/kg every hour (maximum, 1000
units/hour); check aPTT every 4–6 hours; adjust to target
of 1.5–2 times the upper limit of control (50–70
seconds); recommended duration is 48 hours or until
percutaneous coronary intervention is performed
Anticoagulation, intermittent administration, by IV infusion,
ADULT, initially 10,000 units, then 50 to 70 units/kg
(5,000–10,000 units) every 4–6 hours.
Maintenance of line patency or line flushing, by IV infusion,
ADULT and CHILD, 100 units/mL; INFANT, 10 units/mL
[NOTE: Capped PVC catheters and peripheral heparin
locks require flushing more frequently (e.g., every 6–8
hours). The volume of heparin flush is similar or slightly
greater than the volume of catheter. Additional flushes
should be given when stagnant blood is observed in
catheter, after catheter is used for drug or blood
administration, and after blood withdrawal from
catheter.].
Thromboprophylaxis for venous thromboembolism
prevention, by SC injection, ADULT, 5,000 units every 8–
12 hours; in acutely ill hospitalized medical patients at
increased risk of thrombosis and selected surgical
patients; and for a minimum of 10–14 days is
recommended for patients undergoing total hip
arthroplasty, total knee arthroplasty, or hip fracture
surgery.
Treatment in venous thromboembolism (VTE), by IV or SC
injection, ADULT, For patients starting intravenous
unfractionated heparin (UFH), the initial bolus and initial
rate of the continuous infusion should be weight-
adjusted (bolus 80 units/kg, immediately followed by 18
units/kg/hour for venous thromboembolism (VTE); bolus
70 units/kg immediately followed by 15 units/kg/hour
for cardiac or stroke patients). Subsequent dose
adjustment should be guided by monitoring with
activated partial thromboplastin time (aPTT) testing 6
hours after UFH bolus/infusion is started with
therapeutic aPTT range of 1.5 – 2.5 times control. For
outpatients with VTE treated with subcutaneous UFH,
47
 BLOOD AND BLOOD FORMING ORGANS

use weight-adjusted dosing (first dose 333 units/kg,
then 250 units/kg after 12 hours and every 12 hours
thereafter with no need for monitoring. Unless there are
contraindications or further plans for surgery, start
warfarin on the first or second treatment day and
continue heparin until INR is ≥2 for at least 24 hours
B
conjunctivitis (allergic reaction), lacrimation, hematuria,
asthma, hemoptysis, pulmonary hemorrhage, rhinitis,
allergic reactions, anaphylactoid reactions, heparin
resistance, hypersensitivity (including chills, fever, and
urticaria)
Less Common: Erythematous plaques, bronchospasm

(usually 5–7 days).

Prophylaxis for cardiac catheterization, arterial approach, by
IV bolus, CHILD, 100 units/kg.
Systemic heparinization, by IV infusion, CHILD, initially 75
units/kg given over 10 minutes; adjust dose to maintain
aPTT of 60–85 seconds (assuming this reflects an anti-
factor Xa level of 0.35–0.7 units/mL);
For maintenance, CHILD >1 year, 20 units/kg per hour;
CHILD <1 year, 28 units/kg per hour.
Pediatric Protocol for Systemic Heparin Adjustment:
Obtain blood for aPTT 4 hours after heparin loading dose
and 4 hours after every infusion rate change.
Obtain daily CBC and aPTT after aPTT is therapeutic.
TEST INTERACTIONS. Increased thyroxine level (competitive
protein binding), increased PT
Precautions:
Thrombocytopenia; Elderly (has higher serum levels and
clinical response, e.g., longer aPTTs).
NOTE: NOT interchangeable with Heparin lock flush
solution.
Administration:
For IV administration by continuous IV infusion, infuse
via infusion pump. If preparing solution, mix thoroughly
prior to administration.

aPTT Time to For IV administration via heparin lock, inject via injection
Dose Adjustment cap using positive pressure flushing technique.
(seconds) repeat aPTT
50 units/kg bolus
4 h after rate For IV administration by central venous catheters, flush
<50 and increase rate by
change with heparin solution when newly inserted, daily at the
10%.
time of tubing change, after blood withdrawal or
Increase infusion 4 h after rate transfusion, and after an intermittent infusion through
50-59
rate by 10%. change an injectable cap. At least 10 mL of blood should be
60-85 Keep rate the same. Next day removed and discarded from a heparinized line before
blood samples are sent for coagulation testing.
Decrease infusion 4 h after rate
86-95
rate by 10%. change For SC administration, injection sites should be rotated,
Hold infusion for 30 usually left and right portions of the abdomen, above iliac
minutes and 4 h after rate crest.
96-120
decrease infusion change
rate by 10%. Do NOT administer by IM due to pain, irritation, and
Hold infusion for 60 hematoma formation.
minutes and 4 h after rate
>120
decrease infusion change NOTE:
rate by 15%. Do NOT use 100 unit/mL concentration to flush heparin
locks, IV lines, or intra­arterial lines in neonates or infants
Dose Adjustment: <10 kg as systemic anticoagulation may occur.
Geriatric:
Lower doses may be required. The 10 unit/mL flush concentration may inadvertently
cause systemic anticoagulation in infants <1 kg who
Renal and Hepatic Impairment: receive frequent flushes.
No dose adjustment required. Adjust therapeutic heparin
according to aPTT or anti-Xa activity. See General Information on Heparin Group under
Antithrombotic Agents for further information.
Adverse Drug Reactions:
Common: Allergic vasospastic reaction, chest pain, Pregnancy Category: C
hemorrhagic shock, shock, thrombosis, chills, fever,
headache, alopecia, unexplained bruising, cutaneous ATC Code: B01AB01
necrosis, dysesthesia pedis, eczema, urticaria, purpura,
adrenal hemorrhage, hyperkalemia, ovarian
hemorrhage, rebound hyperlipidemia on
discontinuation, constipation, hematemesis, nausea, Rx TINZAPARIN
tarry stools, vomiting, frequent or persistent erection,
bleeding from gums, epistaxis, hemorrhage, ovarian Inj.: 10,000 anti-Xa IU/mL, 0.35 mL and 0.45 mL pre-filled
hemorrhage, retroperitoneal hemorrhage, syringe (SC) (as sodium)
thrombocytopenia, liver enzymes increased, irritation, 10,000 anti-Xa IU/mL, 2 mL vial (SC) (as sodium)
erythema, pain, hematoma, and ulceration have been
rarely reported with deep SC injections, peripheral A low molecular weight heparin with anticoagulant
neuropathy, osteoporosis (chronic therapy), properties used in the prevention and treatment of

48
BLOOD AND BLOOD FORMING ORGANS
venous thromboembolism and to prevent clotting during
extracorporeal circulation.
Indications: Treatment of deep vein thrombosis (DVT)
and/or pulmonary embolism (PE) (except in patients with
severe hemodynamic instability) ; prevention of venous
thromboembolism (VTE) following orthopedic surgery or
following general surgery in patients at high risk of VTE;
prevention of clotting in indwelling intravenous lines and
extracorporeal circuit during hemodialysis (in patients
without high bleeding risk).
Contraindications: Active bleeding; history of confirmed or
suspected immunologically mediated heparin-induced
thrombocytopenia (HIT) or positive in vitro platelet
aggregation test in the presence of tinzaparin; acute or
subacute endocarditis; generalized hemorrhage
tendency and other conditions involving increased risks
of hemorrhage (e.g., severe hepatic insufficiency,
imminent abortion); hemophilia or major blood clotting
disorders; acute cerebral insult or hemorrhagic
cerebrovascular accidents without systemic emboli;
uncontrolled severe hypertension; diabetic or
hemorrhagic retinopathy; injury or surgery involving the
brain, spinal cord, eyes or ears; spinal / epidural
anesthesia in patients requiring treatment dosages of
tinzaparin; use of multi-dose vials containing benzyl
alcohol in children <2 years of age, premature infants,
and neonates; pregnant or nursing mothers
Dose:
NOTE: 1 mg of tinzaparin equals 70­120 units of anti-Xa
activity.
DVT and/or PE, treatment, by SC injection, ADULT, 175 anti-
Xa units/kg once daily (maximum, 18,000 anti-Xa
units/day), start warfarin on the first or second treatment
day and continue tinzaparin until INR is ≥2 for at least 24
hours, usually 5–7 days [NOTE: May use body weight dosing
using prefilled syringes].
DVT, prophylaxis in hip replacement surgery, by SC injection,
ADULT, preoperative regimen, 50 anti-Xa units/kg given
2 hours preoperatively followed by 50 anti-Xa units/kg
once daily for 7–10 days;
postoperative regimen, 75 anti-Xa units/kg once daily,
with initial dose given postoperatively and continued for
7–10 days [NOTE: Initiate of LMWH ≥12 hours preoperatively or
≥12 hours postoperatively, may extend duration up to 35 days].
DVT, prophylaxis in knee replacement surgery, by SC
injection, ADULT, 75 anti-Xa units/kg once daily, with
initial dose given postoperatively and continued for 7–10
days [NOTE: Initiate of LMWH ≥12 hours preoperatively or ≥12
hours postoperatively, may extend duration up to 35 days; may
use body weight dosing using prefilled syringes].
DVT, prophylaxis in general surgery, by SC injection, ADULT,
3,500 anti-Xa units once daily, with initial dose given 2
hours prior to surgery and then continued
postoperatively for 7–10 days.
Anticoagulant in extracorporeal circuit during hemodialysis,
for stable patients with chronic renal failure, by IV bolus,
ADULT, for dialysis session ≤4 hours and no hemorrhage
risk, initially 4,500 anti-Xa units at beginning of dialysis,
typically achieves plasma concentrations of 0.5–1 anti-
Xa units/mL, may give larger bolus for dialysis sessions
>4 hours; [NOTE: For subsequent dialysis sessions, may adjust
dose as necessary in increments of 500 anti-Xa units based on
previous outcome];
For dialysis sessions ≤4 hours with hemorrhage risk,
initially 2,250 anti-Xa units at beginning of dialysis [NOTE:
Do NOT add to dialysis circuit. For subsequent dialysis sessions,
adjust dose as necessary to achieve plasma concentrations of
0.2­0.4 anti-Xa units/mL].
B
Dose Adjustment:
Geriatric:
Use is not recommended in patients >70 years of age with
renal impairment.
Renal Impairment:
For patients with CrCl ≥30 mL/minute, no dose adjustment
needed provided it primarily undergoes renal
elimination.
For patients with CrCl <30 mL/minute, consider dose
reduction.
Hepatic Impairment:
No dosage adjustment needed provided it does not undergo
hepatic metabolism.
Precautions:
WARNING: Contraindicated in patients with HIT or HIT with
thrombosis due to high cross-reactivity to heparin-platelet
factor­4 antibody.
Hepatic impairment (use with caution); Renal impairment
(use with caution); Elderly (increased sensitivity may be
possible due to a decline in renal function).
Adverse Drug Reactions:
Common: chest pain, angina pectoris, arrhythmia, coronary
thrombosis or MI, dependent edema, thromboembolism,
fever, headache, pain, bullous eruption, erythematous
rash, maculopapular rash, skin necrosis, nausea,
abdominal pain, constipation, diarrhea, vomiting, urinary
tract infection, bleeding events, granulocytopenia,
thrombocytopenia, injection site hematoma or cellulitis,
back pain, epistaxis, dyspnea, allergic reaction,
neoplasm.
Less Common: Agranulocytosis, angioedema,
anaphylactoid reaction, hemoptysis, hypoaldosteronism,
hyperkalemia, metabolic acidosis, ocular hemorrhage,
osteopenia, osteoporosis, priapism, pruritus, rash, spinal
epidural hematoma, Stevens-Johnson syndrome,
thrombocytosis, toxic epidermal necrolysis, urticaria.
Administration: For SC use only.
Administer by deep SC injection into the lower abdomen,
outer thigh, lower back, or upper arm. Patient should be
lying down or sitting. Vary injection site daily.
Do NOT rub the injection site to minimize bruising.
May be administered by IV injection in hemodialysis
patients.
Do NOT administer by IM route and avoid IM
administration of other medications due to the risk of
hematoma formation.
49

See General Information on Heparin Group under
Antithrombotic Agents for further information.
Pregnancy Category: B
ATC Code: B01AB10
B
PLATELET AGGREGATION INHIBITORS, EXCLUDING
HEPARIN
Rx ASPIRIN
Oral: 80 mg, 100 mg, 300 mg, and 325 mg tablet
An irreversible, cyclo-oxygenase (COX) inhibitor, which
inhibits platelet aggregation. It is useful in the long-term
management and prevention of MI and stroke,
Indications: Primary prevention of acute MI and stroke in
patients with risk factors; secondary prevention of
thrombotic cardiovascular or cerebrovascular disease,
and following bypass surgery; management of acute MI
and acute ischemic stroke.
Contraindications: Children and adolescents <16 years (risk
of Reye’s syndrome); active peptic ulceration or bleeding
GI ulcers; hemophilia and other bleeding disorders;
aspirin-sensitive asthma; thrombocytopenia; ulcerative
colitis; lactating mothers; acute hemorrhagic stroke or
intracerebral bleeding.
Dose:
Acute ischemic infarction, by mouth, ADULT, 80–100 mg
once daily.
Transient ischemic attack (early specific treatment), by
mouth, ADULT, 50–325 mg once daily.
Prophylaxis of myocardial infarction or cerebrovascular
disease, by mouth, ADULT, 80–100 mg once daily.
Treatment of acute MI, by mouth, ADULT, 160–300 mg
once daily.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate impairment (CrCl >10 mL/min), dose
adjustments are not necessary.
For severe impairment, use is not recommended.
Hepatic Impairment:
Avoid use in severe liver disease.
Precautions:
Gastritis and GI bleeding; Asthma; Urticaria; Allergic
disease; Uncontrolled hypertension; Dehydration; Gout;
Renal impairment (avoid use); hepatic impairment;
G6PD-deficiency; Elderly; Pregnancy (use in third
trimester may lead to impaired platelet function and risk
of hemorrhage, delayed onset and increased duration of
labor with increased blood loss; avoid analgesic doses in
the last few weeks; with high doses, closure of fetal
ductus arteriosus in utero and possibly persistent
pulmonary hypertension in the newborn; risk of
kernicterus in jaundiced neonates; risk of Reye’s
syndrome).
50
BLOOD AND BLOOD FORMING ORGANS
Adverse Drug Reactions:
Common: Abdominal pain, asymptomatic blood loss, back
pain, increased bleeding time, diarrhea, dyspepsia,
dyspnea, epistaxis, fatigue, GI irritation, headache,
malaise, melena, nausea, vomiting.
Less Common: Anorexia, asthenia, confusion, dizziness,
fever, flushing, gastritis, hemorrhage rectum,
hemorrhoids, hyperglycemia, hypoglycemia (children),
hypotension, myalgia, palpitations, syncope,
tachycardia, thirst, tinnitus, vertigo.
Rare: Arrhythmia, convulsions, deafness, edema, GI ulcer
and perforation, intracranial hemorrhage,
hypersensitivity reactions (including Stevens-Johnson
syndrome); interstitial nephritis, iron-deficiency anemia,
myocarditis, paresthesia, renal insufficiency, seizures,
thrombocytopenia, toxic epidermal necrolysis.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effects of the following drugs:
Oral Hypoglycemics (hypoglycemic effect), Phenytoin,
Valproic Acid
Increases risk of adverse or toxic effects of the following
drugs:
Anticoagulant Therapy, e.g., Heparin, Warfarin
(bleeding), Corticosteroids (GI bleeding and ulceration),
Valproic Acid (increases effects on blood coagulation
and platelet function)
Avoid concomitant use with:
Increases excretion of Aspirin by alkaline urine:
Antacids, e.g., Aluminum and Magnesium Hydroxide
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors, e.g., Enalapril (renal impairment with
Aspirin doses of >300 mg daily), NSAIDs, e.g., Ibuprofen,
Naproxen (gastric ulceration)
Reduces therapeutic effect of the Aspirin:
NSAIDs, e.g., Ibuprofen, Naproxen (anti-platelet activity
of low-dose aspirin)
Reduces therapeutic effect of the following drugs:
ACE Inhibitors, e.g., Enalapril (hyponatremic and
hypotensive effect), Diuretics, e.g., Spironolactone
(inhibition of renal prostaglandins), NSAIDs, e.g.,
Ibuprofen, Naproxen (cardioprotective effect)
Administration: Take tablets from packaging just before use.
Should be taken with food or immediately after meals.
Pregnancy Category: C; D in 3rd trimester
ATC Code: B01AC06
BLOOD AND BLOOD FORMING ORGANS
Rx CILOSTAZOL
Oral: 50 mg and 100 mg tablet
50 mg (20% w/w) powder, 0.25 g sachet
100 mg (20% w/w) powder, 0.5 g sachet
A quinolinone derivative selective phosphodiesterase (PDE)
type III inhibitor with antiplatelet and vasodilating
activity. It prevents the degradation of cyclic adenosine-
3′,5′-monophosphate (cAMP) in platelets and blood
vessels resulting in arterial vasodilation and inhibition of
platelet aggregation.
Indication: Reduction of symptoms of intermittent
claudication.
Contraindications: Heart failure; hemostatic disorders or
active pathologic bleeding, such as bleeding peptic ulcer
or intracranial bleeding.
Dose:
Intermittent claudication, by mouth, ADULT, 100 mg twice
daily in combination with Aspirin or Clopidogrel.
NOTE: Discontinue treatment if symptoms are not improved
after 3 months of therapy.
Dose Adjustment:
Renal Impairment:
In patients with CrCl <25 mL/minute, use is
contraindicated. Severe.
In patients with end-stage renal disease (ESRD) and on
dialysis, dose adjustment has not been studied,
however, high protein binding makes removal by dialysis
unlikely.
Hepatic Impairment:
Use with caution in patients with moderate to severe
impairment. Dose adjustment has not been studied.
Concomitant Medications:
CYP2C19 Inhibitors, e.g., Fluconazole, Omeprazole and
Strong or Moderate CYP3A4 Inhibitors, e.g., Diltiazem,
Erythromycin, Itraconazole, Ketoconazole, ADULT, 50 mg
Cilostazol twice daily.
Precautions:
Cardiovascular effects; Cardiovascular disease; Hemostatic
disorders (avoid use); Hematologic effects; Hepatic
impairment; Renal impairment; Elderly (must be
evaluated for cardiac status; CHF is common among
elderly); Lactation
Adverse Drug Reactions:
Common: Headache, abnormal stools, diarrhea, increased
susceptibility to infection, rhinitis, peripheral edema,
palpitations, tachycardia, dizziness, vertigo, dyspepsia,
nausea, abdominal pain, flatulence, back pain, myalgia,
pharyngitis, cough.
Less Common: Albuminuria, amblyopia, anemia, anorexia,
anxiety, arthralgia, asthma, atrial fibrillation, atrial flutter,
blindness, bursitis, cardiac arrest, cardiac failure,
cerebral infarction, chills, cholelithiasis, colitis,
conjunctivitis, cystitis, diabetes mellitus, diplopia,
duodenal ulcer, duodenitis, ecchymoses, edema,
epistaxis, esophageal hemorrhage, esophagitis, facial
edema, fever, furunculosis, gastric ulcer, gastritis,
gastroenteritis, gingival hemorrhage, gout,
hematemesis, hemorrhage, hemorrhage (eye),
hemoptysis, hyperuricemia, hypotension, insomnia, iron
deficiency anemia, malaise, melena, myocardial
B
infarction, neck stiffness, neuralgia, nodal arrhythmia,
orthostatic hypotension, ostealgia, otalgia, pelvic pain,
peptic ulcer, periodontal abscess, pneumonia,
polycythemia, purpura, rectal hemorrhage, retinal
hemorrhage, retroperitoneal hemorrhage, sinusitis, skin
hypertrophy, supraventricular tachycardia, syncope,
tinnitus, tongue edema, urinary frequency, urticaria,
vaginal hemorrhage, vaginitis, varicose veins,
vasodilation, ventricular premature contractions,
ventricular tachycardia, xeroderma.
Rare: Abnormal hepatic function tests, agranulocytosis,
aplastic anemia, cerebrovascular accident, chest pain,
coronary thrombosis (stent), fixed drug eruption,
gastrointestinal hemorrhage, granulocytopenia,
hematoma (extradural), hemorrhagic diathesis, hepatic
insufficiency, hot flash, hyperglycemia, increased blood
pressure, interstitial pneumonitis, intracranial
hemorrhage, jaundice, leukopenia, pain, pulmonary
hemorrhage, pruritus, prolonged Q­T interval on ECG,
Stevens-Johnson syndrome, subdural hematoma,
thrombocytopenia, thrombosis, torsade de pointes.
Drug Interactions:
NOTE: Cilostazol is a weak inhibitor of CYP3A4.
Monitor closely with:
Enhances therapeutic effect of Cilostazol:
antiplatelet effect: Agents with Antiplatelet Properties,
e.g., P2Y12 Inhibitors, NSAIDs, SSRIs; Glucosamine;
Multivitamins / Fluoride with Vitamins ADE;
Multivitamins / Minerals with Vitamins ADEK, Folate,
Iron; Multivitamins / Minerals with Vitamins AE, no Iron;
Omega­3 Fatty Acids; Vitamin E; Pentoxifylline,
Prostacyclin Analogues
anticoagulant effect: Other Anticoagulants, Thrombolytic
Agents
Increases risk of adverse or toxic effects of Cilostazol:
Anagrelide, Ibrutinib
Increases risk of adverse or toxic effects of the following
drugs:
Bleeding: Deoxycholic Acid, Obinutuzumab, Salicylates
(bleeding), Iodine I131
Avoid concomitant use with:
Decreases serum concentration of Cilostazol:
Dabrafenib
Enhances anticoagulant effect of Cilostazol:
Dabigatran Etexilate
Enhances therapeutic effect of Rivaroxaban (Anticoagulant
effect)
Increases risk of adverse or toxic effects of Cilostazol:
Herbs with anticoagulant or antiplatelet properties, e.g.,
Alfalfa, Anise, Bilberry (bleeding); Grapefruit Juice;
Stiripentol
51

Increases risk of adverse or toxic effects of Apixaban
(bleeding)
Increases serum concentration of Cilostazol:
Fusidic Acid (systemic), Grapefruit Juice
B
Increases serum concentration of Dabigatran Etexilate
FOOD INTERACTION. A high-fat meal may increase peak concentration
by 90% and increase AUC by 25%
Administration: Administer 30 minutes before or 2 hours
after meals (breakfast and dinner).
Pregnancy Category: C
ATC Code: B01AC23
Rx CLOPIDOGREL
Oral: 75 mg tablet
A thienopyridine-derived, platelet aggregation inhibitor that
has no effect on prostaglandin metabolism unlike
aspirin. It is used as an alternative for patients who are
unable to take aspirin in the treatment of thrombosis.
Indications: Prevention of atherothrombotic events in:
peripheral arterial disease, or within 35 days of MI, or
within 6 months of ischemic stroke; in acute coronary
syndrome without ST-segment elevation (unstable
angina or non-Q wave MI), including patients undergoing
stent placement following percutaneous coronary
intervention (in combination with aspirin); in acute MI
with ST-segment elevation, and in combination with ASA
in medically-treated patients eligible for thrombolytic
therapy; in patients with atrial fibrillation where oral
anticoagulation is unsuitable; neurologic indications;
transient ischemic attack and acute ischemic cerebral
infarction (for early specific treatment or secondary
prevention of ischemic stroke).
Contraindications: Severe liver impairment; intracranial
hemorrhage, peptic ulcer or other pathological bleeding;
breastfeeding.
Dose:
Acute coronary syndrome, unstable angina or NSTEMI, by
mouth, ADULT, 300 mg loading dose, then 75 mg daily
in combination with aspirin 75–100 mg daily.
Acute coronary syndrome, STEMI, by mouth, ADULT, 75 mg
daily (in combination with aspirin 162–325 mg daily,
then 81–162 mg daily).
Acute ischemic infarction and secondary prevention of
acute ischemic stroke, by mouth, ADULT, 75 mg once
daily.
Coronary artery disease, by mouth, ADULT, 75 mg once
daily.
Recent MI, stroke, or established peripheral arterial
disease, by mouth, ADULT, 75 mg daily [NOTE:
Recommended as alternative to aspirin, or
concomitantly with aspirin if patient is not at increased
risk for bleeding but at high risk for cardiovascular
disease].
52
BLOOD AND BLOOD FORMING ORGANS
Transient ischemic attack, early specific treatment), by
mouth, ADULT, 75 mg once daily.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate impairment, dose adjustment is not
required.
For severe impairment, refer patient to a specialist.
Precautions:
WARNING: CYP2C19 Inhibition and Poor Metabolizers:
Effectiveness depends on activation to active
metabolite by cytochrome P450 system, principally
CYP2C19. May be less effective in poor metabolizers
lacking CYP2C19. Poor metabolizers exhibit higher
cardiovascular event rates after acute coronary
syndrome or percutaneous coronary intervention at
recommended doses. >50% of Asians have CYP2C19
genetic variants that inhibit Clopidogrel metabolism.
Use of CYP2C19 inhibitors (Proton Pump Inhibitors)
or use in poor metabolizers may decrease
antiplatelet effect.
Patients at risk of increased bleeding from trauma,
surgery, or other pathological conditions;
patients taking medications that increase
risk of bleeding; patients allergic to aspirin
who are undergoing PCI; History of bleeding or
hemostatic disorders; bleeding diathesis; ulcers; renal
impairment; hepatic impairment; Surgery (may need to
discontinue 5-10 days before surgical procedure);
Pregnancy (avoid use if possible).
Adverse Drug Reactions:
Common: Abdominal pain, bleeding, chest pain,
depression, diarrhea, dyspepsia, flu-like syndrome,
hemorrhage, rhinitis, upper respiratory tract infection,
urinary tract infection, urticaria.
Less Common: Constipation, dizziness, flatulence, gastritis,
GI ulcer, headache, leukopenia, nausea, paresthesia,
pruritus, rash, vomiting
Rare: Acute liver failure, agranulocytosis, angioedema,
aplastic anemia, bronchospasm, colitis, confusion,
exfoliative dermatitis, hallucinations, hepatitis,
hypersensitivity-like reactions, hypotension, interstitial
pneumonitis, lichen, myalgia, neutropenia, pancreatitis,
Stevens-Johnson syndrome (SJS), stomatitis,
thrombocytopenia, thrombotic thrombocytopenic
purpura, vasculitis
Drug Interactions:
NOTE: CYP2C19 enzyme metabolizes Clopidogrel to its
active metabolite. Combining Clopidogrel with CYP2C19
Inhibitors (e.g. Omeprazole) of may decrease its efficacy.
Monitor closely with:
Enhances therapeutic effect of Clopidogrel:
Carbamazepine. Rifampin
Increases risk of adverse or toxic effects when used in
combination with the following drugs:
Anticoagulants, e.g., Warfarin (bleeding); Aspirin
(unusual bleeding, severe abdominal pain, weakness,
black stools); drugs which can affect the clotting process,
e.g. NSAIDs, other Antiplatelets (bleeding; inhibits
platelet aggregation)
BLOOD AND BLOOD FORMING ORGANS
Reduces therapeutic effect of Clopidogrel:
Atorvastatin (blood clotting), Clarithromycin,
Erythromycin, Isoniazid
Avoid concomitant use with:
Reduces antiplatelet effect of Clopidogrel by reducing
formation of its active metabolite:
Proton Pump Inhibitors, e.g., Omeprazole, Esomeprazole
Administration: May be taken with or without food.
Pregnancy Category: B
ATC Code: B01AC04
Rx DIPYRIDAMOLE
Oral: 25 mg tablet
A non-nitrate coronary vasodilator that inhibits platelet
aggregation. It inhibits phosphodiesterase and
adenosine reuptake.
Indications: Secondary prevention of stroke in patients with
a history of non-cardioembolic ischemic stroke or TIA
(preferably with aspirin); to decrease thrombosis after
artificial heart valve replacement (with warfarin).
Dose:
Adjunctive therapy for prophylaxis of thromboembolism with
cardiac valve replacement, by mouth, ADULT, 75–200
mg 4 times daily.
Dose Adjustment:
Geriatric:
Avoid use due to risk of orthostatic hypotension.
Precautions:
Cardiovascular disease (use with caution in patients with
hypotension, unstable angina, and/or recent MI); hepatic
impairment; Elderly (use with caution); Lactation (use
with caution).
Adverse Drug Reactions:
Common: Dizziness, headache, skin rash, pruritus,
abdominal distress, diarrhea, vomiting, hepatic
insufficiency.
Less Common: Alopecia, arthritis, cholelithiasis, dyspepsia,
fatigue, hepatitis, hypersensitivity reaction, hypotension,
laryngeal edema, malaise, myalgia, nausea, palpitations,
paresthesia, tachycardia, thrombocytopenia.
Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Dipyridamole:
Other Anticoagulants e.g., Warfarin, Heparin;
Thrombolytic Agents e.g., Streptokinase
Enhances antiplatelet effect of Dipyridamole:
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs; Glucosamine; Multivitamins/
Fluoride with Vitamins ADE; Multivitamins/ Minerals with
Vitamins ADEK, Folate, Iron; Multivitamins/ Minerals
with Vitamins AE, no Iron; Omega­3 Fatty Acids;
Pentoxifylline; Prostacyclin Analogues; Vitamin E
Enhances therapeutic effect of Dipyridamole:
Hypotensive effect: Barbiturates e.g., Phenobarbital;
B
Nicorandil; Risperidone
Enhances therapeutic effect of Beta Blockers (bradycardic
effect) [except Levobunolol, Metipranolol]
Increases risk of adverse or toxic effects of Dipyridamole:
Ibrutinib; Other Hypotensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Bleeding: Deoxycholic Acid; Obinutuzumab; Salicylates
e.g. Aspirin; Iodine 131; Ibritumab
Orthostatic hypotensive effect: Duloxetine
Levodopa
Reduces therapeutic effect of Acetylcholinesterase
Inhibitors e.g. Physiostigmine
Avoid concomitant use with:
Enhances therapeutic effect of Rivaroxaban (anticoagulant
effect)
Increases risk of adverse or toxic effects of Adenosine
(cardiovascular effects; Apixaban (bleeding)
Increases risk of adverse or toxic effects of Dipyridamole:
Herbs with anticoagulant or antiplatelet properties, e.g.,
Alfalfa, Anise, Bilberry (bleeding)
Increases serum concentration of the following drugs:
Afatinib (reduce Afatinib by 10mg if not tolerated);
Colchicine (increase distribution into certain tissues,
e.g., brain); Dabigatran Etexilate [active metabolites];
Doxorubicin (conventional); Everolimus [reduce doses if
used for subependymal giant cell astrocytoma or renal
cell carcinoma]; Pazopanib; Silodosin; Topotecan;
Vincristine (liposomal)
Administration: Administer with water 1 hour before meals.
NOTE: Preferably used in combination with aspirin. When
used concomitantly with aspirin, consider the cautions,
precautions, and contraindications associated with
aspirin.
Pregnancy Category: B
ATC Code: B01AC07
53

ENZYMES
HUMAN RECOMBINANT TISSUE
Rx TYPE PLASMINOGEN ACTIVATOR
(ALTEPLASE)
B
Inj.: 50 mg powder (IV infusion)
A recombinant DNA-derived form of human tissue-type
plasminogen activator (t-PA) used as a thrombolytic
agent. The agent t-PA promotes thrombolysis by forming
the active proteolytic enzyme plasmin, which is capable
of degrading fibrin, fibrinogen, and factors V, VIII, and XII.
Indication: Management of acute ischemic stroke (within 0–
4.5 hours of symptom onset).
Contraindications: Active internal bleeding; history of
cerebrovascular accident; recent (within 2 months)
intracranial or interspinal surgery or trauma; intracranial
neoplasm; arteriovenous malformation; bleeding
disorders; severe uncontrolled hypertension; likelihood
of left heart thrombus; acute pericarditis; bacterial
endocarditis; severe liver dysfunction; age >75;
pregnancy; septic thrombophlebitis; concomitant use of
oral anticoagulants.
Dose:
NOTE: Each 1 mg of Alteplase provides 580,000 units of
human recombinant tissue plasminogen activator
activity.
Acute ischemic stroke or thrombotic stroke, by IV infusion,
ADULT, 0.9 mg/kg over 60 minutes with 10% of dose as
an initial bolus over 1 minute (maximum, 90 mg).
Precautions:
WARNING: Avoid administration of Aspirin or IV
Heparin within the first 24 hours after treatment. if
heparin is required for other indications, do NOT
exceed 10,000 units per day (SC).
If bleeding occurs, stop the infusion, then resume
when bleeding stops. Report any signs of bleeding.
Stop therapy immediately if dysrhythmias occur.
Recent major surgery (within 10 days); risk of bleeding from
venipuncture or invasive procedures; cerebral vascular
disease; acute stroke; recent GI or GU bleeding; recent
trauma; Conditions in which thrombolysis might give rise
to embolic complications such as enlarged left atrium
with atrial fibrillation; Hypertension; Hemorrhagic
ophthalmic conditions; External chest compression;
Recent or concurrent use of drugs that increase risk of
bleeding; Elderly; Children; Lactation.
Adverse Drug Reactions:
Common: Internal and superficial bleeding (cerebral,
retroperitoneal, GU, GI), hemorrhage at injection site,
increased blood pressure, decreased pulse, coronary
artery reperfusion events (e.g., rhythm disorders,
nausea, vomiting, headache, muscle pain, fever.
54
BLOOD AND BLOOD FORMING ORGANS
Rare: Anaphylaxis, other hypersensitivity reactions.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Alteplase:
Orolingual angioedema: ACE Inhibitors e.g. Enalapril
Hemorrhage: Anticoagulants e.g., Warfarin; Antiplatelet
Agents, e.g., Aspirin; Clopidogrel; Dipyridamole, GP
IIb/IIIa Inhibitors e.g. Abciximab
Administration:
Reconstitution of 50-mg vial:
Use a large-bore needle, e.g., 18-gauge. Do NOT prime
needle with air. Dilute contents of vial with SWFI supplied
by manufacturer. Direct the stream of sterile water into
the lyophilized cake. Slight foaming is normal. Allow to
stand until bubbles dissipate. The resulting
concentration is 1 mg/mL.
Start IV infusion as soon as possible after the
thrombolytic event, preferably within 6 hours. Administer
drug as reconstituted or further diluted with an equal
volume of NS or D5W to yield 0.5 mg/mL. Administer 5
mg as an initial bolus over 1 minute, then give the
remainder of the 0.75 mg/kg dose over 60 minutes.
Follow infusion with an IV flush of 30–50 mL of NS or
D5W.
Do NOT exceed a total dose of 100 mg (higher doses
have been associated with intracranial bleeding).
Do NOT use if vacuum in vial has been broken.
NOTE: Spontaneous bleeding occurs twice as often with
Alteplase than Heparin. Avoid invasive procedures. IM
injections are contraindicated. Avoid physical
manipulation of patient during thrombolytic therapy to
prevent bruising.
Pregnancy Category: C
ATC Code: B01AD02
Rx STREPTOKINASE
Inj.: 1,500,000 IU powder, vial (IV infusion)
A derivative of the beta-hemolytic streptococci. It promotes
thrombolysis by activating the conversion of
plasminogen to plasmin, the enzyme that degrades
fibrin, fibrinogen, and other procoagulant proteins. It
decreases blood and plasma viscosity and erythrocyte
aggregation tendency, thus increasing perfusion of
collateral blood vessels.
Indications: Management of acute myocardial infarction
(within 12 hours of onset) with persistent ST-segment
elevation or left bundle-branch block; for the lysis of
acute arterial thrombi or emboli; management of
extensive acute proximal deep vein thrombosis (DVT)
and acute massive pulmonary embolism (PE).
Contraindications: Hypersensitivity to Anistreplase aside
from Streptokinase; recent internal bleeding; recent
stroke, intracranial or intraspinal surgery or head trauma
BLOOD AND BLOOD FORMING ORGANS
(within 2 months); recent major or invasive operation
(within 6–10 days); intracranial neoplasm or other
neoplasm with risk of hemorrhage, arteriovenous
malformation, or aneurysm; known bleeding diathesis;
spontaneous fibrinolysis and extensive clotting
disorders; severe uncontrolled hypertension (systolic BP
>200 mmHg and/or diastolic BP >100 mmHg);
hypertensive retinopathy (grade III or IV); acute
pancreatitis; severe renal impairment; severe hepatic
impairment; endocarditis or pericarditis; concurrent oral
anticoagulant therapy (INR >1.3).
Dose:
ST-elevation myocardial infarction (STEMI), by IV infusion,
ADULT, 1.5 million units over 1 hour; may administer
second dose if re-occlusion occurs within 5 days of initial
dose.
Deep vein thrombosis, by IV infusion, ADULT, 250,000 units
over 30 minutes, followed by 100,000 units/hour for
24–72 hours;
alternative (high-dose) regimen, day 1, initially 250,000
units over 30 minutes followed by 1.5 million units/hour
for up to a maximum of 6 hours; days 2 and 3, if needed,
may repeat infusion of 1.5 million units/hour for 6 hours
once daily.
Pulmonary embolism, by IV infusion, ADULT, initially
250,000 units over 30 minutes, followed by 100,000
units/hour for 24–72 hours;
alternative accelerated regimen, 1.5 million units
administered over 2 hours.
Peripheral arterial thrombosis or embolism, by IV infusion,
ADULT, initially, 250,000 units over 30 minutes, followed
by 100,000 units/hour for 24 to 72 hours.
Dose Adjustment:
Renal and Hepatic Impairment:
For patients with severe impairment, use is contraindicated.
Precautions:
Recent intubation; Previous puncture of non-compressible
vessels; cerebrovascular disease; Recent
gastrointestinal or genitourinary bleeding (within 10
days); Recent trauma (within 10 days), including CPR;
High likelihood of left heart thrombus, e.g., mitral
stenosis with atrial fibrillation; Undergoing trans-lumbar
aortography; Subacute bacterial endocarditis; Active
tuberculosis or severe bronchitis; Hemostatic defects
including ones caused by renal or hepatic dysfunction;
Diabetic hemorrhagic retinopathy or other hemorrhagic
ophthalmic conditions; With indwelling urethral catheter;
Septic thrombophlebitis or occluded AV cannula at
seriously infected site any condition where bleeding
constitutes a significant hazard or would be particularly
difficult to manage because of location; Anaphylaxis;
Arrhythmias; Bleeding (discontinue if serious bleeding
occurs; hold heparin therapy prior to initiation of
streptokinase until aPTT is <2 times the normal control
value); Hypotension; Elderly (use with caution in patients
>75 years; may increase bleeding risk); Pregnancy;
obstetrical delivery or abortion.
Adverse Drug Reactions:
Common: Angina pectoris, arrhythmias, development of
anti-streptokinase antibodies, bradycardia, cardiogenic
shock, CHF, flushing, hypotension, myocardial
reinfarction, pericarditis, recurrent ischemia,
tachycardia, chills, fever, headache, malaise,
ecchymoses, pruritus, rash, urticaria, diarrhea, epigastric
pain, gastrointestinal hemorrhage, nausea, vomiting,
genitourinary hemorrhage, angioedema, bleeding at
injection site, back pain, muscle pain, weakness, eye
hemorrhage, periorbital edema, bronchospasm,
B
dyspnea, epistaxis, pulmonary edema.
Less Common: Agitation, allergic reactions, anaphylactic
shock, anaphylactoid reactions, anaphylaxis, arthritis,
cardiac arrest, cardiac tamponade, confusion, dizziness,
embolism, erysipelas-like rash, Guillain-Barré syndrome,
hemarthrosis, hemiparesis, intracranial hemorrhage,
iridocyclitis, iritis, laryngeal edema, major hemorrhage,
mitral valve insufficiency, myocardial rupture,
noncardiogenic pulmonary edema, paralysis, pericardial
effusion, pericardial epistaxis, polyneuropathy,
pulmonary embolism, respiratory arrest, respiratory
depression, retroperitoneal hemorrhage, serum
sickness, shock, splenic rupture, thrombolytic drug-
induced cholesterol embolism, uveitis, vasculitis.
Drug Interactions:
Monitor closely with:
Enhance therapeutic effect of Streptokinase:
Anticoagulant effect: Agents with antiplatelet properties,
e.g., P2Y12 inhibitors, NSAIDs, SSRIs; Other
Anticoagulants
Hypotensive effect: Barbiturates e.g. Phenobarbital;
Nicorandil
Enhances therapeutic effect of the following drugs:
Dabigatran Etexilate (anticoagulant effect); Risperidone
(hypotensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Orthostatic hypotensive effect: Duloxetine; Hypotensive
Agents
Bleeding: Levodopa, Prostacyclin Analogues, Salicylates
e.g. Aspirin
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Streptokinase:
Herbs with anticoagulant or antiplatelet properties, e.g.,
Alfalfa, Anise, Bilberry (bleeding)
Reduces therapeutic effect of Streptokinase:
Aprotinin
Reduces therapeutic effect of the following drugs:
Aprotinin; Heparin (anticoagulant effect); Vitamin K
Antagonists, e.g., Warfarin (anticoagulant effect)
Administration: Temporarily loosen the needle from syringe
to remove any residual vacuum while adding the diluent
to ensure powder is completely dissolved. After
reconstitution withdraw entire contents of vial and add to
appropriate diluent for infusion.
May have a slight yellow color in solution due to the
presence of albumin.
Pregnancy Category: C
ATC Code: B01AD01
55

OTHER ANTITHROMBOTIC AGENTS
Rx FONDAPARINUX
Inj.: 2.5 mg/0.5 mL solution (as sodium salt)
B
A synthetic activated factor X (Xa) inhibitor used as an
anticoagulant. It increases the affinity of antithrombin III
for factor Xa, a key enzyme in the coagulation cascade.
Indications: Management of unstable angina (UA) or non-ST
segment elevation myocardial infarction (NSTEMI);
management of ST segment elevation myocardial
infarction (STEMI).
Contraindications: Severe renal impairment; body weight
<50 kg; active major bleeding; bacterial endocarditis;
Thrombocytopenia associated with a positive in vitro test
for antiplatelet antibodies in the presence of
Fondaparinux.
Dose:
NOTE: PT and aPTT are insensitive measures of
Fondaparinux activity. If unexpected changes in
coagulation parameters or major bleeding occur,
discontinue fondaparinux.
UA or NSTEMI, by SC injection, ADULT, 2.5 mg once daily for
the duration of hospitalization or up to 8 days, initiate as
soon as possible after presentation.
STEMI, by IV injection, ADULT, 2.5 mg once;
for subsequent doses, starting the following day, by SC
injection, 2.5 mg once daily for the duration of the
hospitalization up to 8 days, or until revascularization
[NOTE: Discontinue Fondaparinux 24 hours prior to
CABG surgery and administer UFH instead, as per
institutional practice].
Dose Adjustment:
Renal Impairment:
For CrCl >50 mL/minute, no dose adjustment is necessary,
however, total clearance is reduced ~25%.
For CrCl of 30–50 mL/minute, use with caution. Total
clearance ~40% lower compared to normal renal
function. When used for thromboprophylaxis, reduce
dose 50% or use low-dose heparin.
For CrCl <30 mL/minute, use is contraindicated.
Hepatic Impairment:
For severe impairment, use with caution. Monitor closely for
signs of bleeding.
Precautions:
WARNING: Epidural or spinal hematomas may occur in
patients who are anticoagulated with low molecular
weight heparins, heparinoids, or fondaparinux and
are receiving neuraxial anesthesia or undergoing
spinal puncture. This may result in long­term or
permanent paralysis. Monitor patients frequently for
signs and symptoms of neurologic impairment. If
neurologic compromise is noted, urgent treatment is
necessary.
56
BLOOD AND BLOOD FORMING ORGANS
Hemorrhage may occur at any site. Risk appears
increased by several factors including renal
dysfunction, age (>75 years), and weight (<50 kg).
Bleeding; thrombocytopenia; Hepatic impairment; Renal
impairment; Patients <50 kg (use with caution; dose
reduction recommended); Elderly (use with caution ;
increased risk of bleeding in patients >75 years of age);
Lactation (use with caution).
Adverse Drug Reactions:
Common: Anemia, hypotension, insomnia, dizziness,
confusion, increased wound secretion, skin blister,
hypokalemia, thrombocytopenia, purpura, hematoma,
minor or major hemorrhage, postoperative hemorrhage,
postoperative wound infection, epistaxis.
Less Common: Anaphylactoid reaction, anaphylaxis,
angioedema, catheter site thrombosis, elevated aPTT
associated with bleeding, epidural hematoma,
hemorrhagic death, injection site reaction (bleeding, skin
rash, pruritus), intracranial hemorrhage, reoperation due
to bleeding, spinal hematoma, thrombocytopenia,
severe thrombocytopenia (<50,000/mm3).
Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Fondaparinux:
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs; Omega-3 Fatty Acids; Other
Anticoagulants; Salicylates e.g. Aspirin; Sugammadex;
Thrombolytic Agents; Tibolone; Vitamin E (increases
overall risk for bleeding)
Increases risk of adverse or toxic effects of Fondaparinux:
Ibrutinib; Prostacyclin Analogues
Increases risk of adverse or toxic effects of the following
drugs:
Deferasirox (GI ulceration or irritation; GI bleeding;);
Deoxycholic Acid (bleeding or bruising in the treatment
area)
Increases risk of adverse or toxic effects of the following
drugs:
Bleeding: Nintedanib; Obinutuzumab; Iodine I131
Avoid concomitant use with:
Enhances anticoagulant effect of the following drugs:
Apixaban; Dabigatran Etexilate; Rivaroxaban
Increases risk of bleeding of Fondaparinux:
Herbs with anticoagulant or antiplatelet properties, e.g.,
Alfalfa, Anise, Bilberry;
Reduces anticoagulant effect of Fondaparinux:
Estrogen Derivatives, Progestins [except Tibolone]
Administration: Initiate therapy 6–8 hours following surgery.
When used for DVT prophylaxis, early initiation (before 6
hours after orthopedic surgery) has been associated with
increased bleeding.
For STEMI, administer via IV route. Administer initial dose
as IV push or mix in NS and infuse over 1–2 minutes.
BLOOD AND BLOOD FORMING ORGANS

Flush tubing with NS after infusion to ensure complete Hematuria, by mouth, ADULT, 1–1.5 g every 8–12 hours
administration. daily until macroscopic
hematuria is no longer present.
If to be administered via SC route, alternate injection
sites. Administer according to recommended regimen. Dose Adjustment:
Do NOT expel air bubble from syringe before injection. Pediatric:

B
Limited data suggest that dosing instructions for adults can
Do NOT administer with other agents that increase the be used for children.
risk of hemorrhage unless they are essential for the Geriatric:
management of the underlying condition. No dose reduction necessary, unless there is
evidence of renal failure.
Do NOT administer via IM route.
Renal Impairment:
CONVERSION. To convert from IV UFH infusion to SC Fondparinux, Reduce doses because of risk of drug accumulation.
calculate specific dose for Fondaparinux based on indication.
Discontinue UFH and begin Fondaparinux within 1 hour.
To convert from SC Fondaparinux to IV UFH infusion, discontinue Precautions:
Fondaparinux, calculate specific dose for IV UFH infusion based on For prolonged treatment, perform an ophthalmological
indication. Omit Heparin loading dose. examination, including visual acuity, color vision,
eyeground, and visual fields, before and at regular
For SC Fondaparinux dosed every 24 hours, start IV UFH infusion intervals during treatment; Hematuria caused by
22–23 hours after last Fondaparinux dose.
diseases of the renal parenchyma; High risk for
thrombosis; Genitourinary effect; Irregular menstrual
Pregnancy Category: B bleeding (use is not recommended); Indissoluble clots
may develop in body cavities,
ATC Code: B01AX05 such as pleural space, joint spaces and urinary tract
(e.g., renal pelvis, bladder) due to
extravascular clots, which may be resistant to physiologic
ANTIHEMORRHAGICS fibrinolysis; Children (limited use in children, principally
in tooth extraction); Pregnancy (use only if clearly
needed); Lactation (exercise caution when administering
ANTIFIBRINOLYTICS to breastfeeding women).

Adverse Drug Reactions:

Rx TRANEXAMIC ACID Common: Abdominal pain, anemia, arthralgia, back pain,
diarrhea, fatigue, headache, muscle cramps and
spasms, nausea, nasal and sinus symptoms, vomiting.
Oral: 250 mg and 500 mg capsule
Rare: Allergic skin reactions, diarrhea, hypersensitivity
500 mg tablet
reactions, hypotension, thrombosis, thromboembolic
Inj.: 100 mg/mL, 2.5 mL and 5 mL ampule (IM, IV)
events (e.g., deep vein thrombosis, pulmonary
embolism); transient disturbance of color vision.
A competitive inhibitor of plasminogen activity used as an
anti-fibrinolytic agent
Drug Interactions:
Monitor closely with:
Indication: Treatment and control of excessive bleeding in
Enhances therapeutic effect of Tranexamic Acid:
various surgical and medical, obstetric and gynecologic,
Tretinoin (systemic) (thrombogenic effect)
and dental
conditions.
Reduces therapeutic effect of the following drugs:
Fibrinolytic Preparations e.g., Streptokinase (counteracts
Contraindications: History or risk of thrombosis, unless
thrombolytic effect)
concomitant treatment with anticoagulants; active
thromboembolic disease (e.g., deep vein thrombosis,
Avoid concomitant use with:
pulmonary embolism, cerebral thrombosis); acquired
Enhances therapeutic effect of Tranexamic Acid:
disturbances of color vision; subarachnoid hemorrhage.
Contraceptives, e.g., Estrogens, Progestins
(thrombogenic effect)
Dose:
Menorrhagia or menometrorrhagia, by mouth, ADULT,
Enhances therapeutic effect of the following drugs:
1–1.5 g every 6–8 hours for 3–4 days (maximum, 4 g
Anti-Inhibitor Coagulant Complex, human (thrombogenic
daily).
effect)
Dental surgery, by mouth, ADULT, 25 mg/kg 2
hours before surgery, then 25 mg/kg 3 or 4 times daily
Administration:
for 6–8 days.
For oral route, may be taken with or without food.
Epistaxis, by mouth, ADULT, 1.5 g every 8 hours for 4–10
Capsules must be swallowed whole. Do NOT chew,
days.
break, or crush.
Gastrointestinal hemorrhage, by IV injection, ADULT, initially
1 g every 4 hours for a maximum of 3 days, followed by
For intravenous route, administer by direct IV injection at
an oral dose of 1.5 g every 6 hours for a maximum of 4
a maximum rate of 100 mg/minute. Use plastic syringe
days.

57

only for IV push. Dilute loading doses in 50–250 mL and
administer over 5–30 minutes.
Pregnancy Category: B
ATC Code: B02AA02
B
VITAMIN K AND OTHE RHEMOSTATICS
BLOOD COAGULATION FACTORS
Rx FACTOR VIII CONCENTRATE
Inj.: 100 IU/g lyophilized powder, vial + diluent (IV)
A plasma protein fraction that contains the glycoprotein
coagulation factor VIII together with varying amounts of
von Willebrand factor. Factor VIII is required for clot
formation and maintenance of hemostasis. It acts by
activating factor X, a coagulation factor necessary in
thrombin and eventual fibrin formation.
Indication: Treatment of bleeding episodes in adults with
acquired hemophilia A.
NOTE: Not indicated for the treatment of congenital
hemophilia A or von Willebrand disease.
Contraindication: Life-threatening hypersensitivity reactions
to antihemophilic factor or any component of the
formulation (including traces of hamster proteins).
Dose:
NOTE: Individualize dose, dosing frequency, and duration
based on location and severity of bleeding, target factor
VIII levels, and clinical condition of the patient. Plasma
levels of factor VIII should not exceed 200% of normal or
200 units/dL.
Acquired hemophilia A, mild to moderate hemorrhage, by IV
injection, ADULT, initially 200 units/kg to achieve factor
VIII plasma level 50–100% of normal; titrate subsequent
doses to maintain recommended factor VIII trough levels
and individual clinical response; dose every 4–12 hours;
adjust frequency based on clinical response or factor VIII
levels.
Acquired hemophilia A, major hemorrhage, by IV injection,
ADULT, initially 200 units/kg to achieve factor VIII
plasma level 100–200% of normal for acute bleed or
50–100% of normal after acute bleed is controlled, if
required of normal; titrate subsequent doses to maintain
recommended factor VIII trough levels and individual
clinical response; dose every 4–12 hours; adjust
frequency based on clinical response or factor VIII levels.
Precautions:
Antibody formation (suspect an anti-porcine factor VIII
antibody if the plasma factor VIII level does not increase
as expected or if bleeding is not controlled after
administration); Hypersensitivity reactions (discontinue
immediately if allergic or anaphylactic-type reactions
occur); Lactation (use with caution).
58
BLOOD AND BLOOD FORMING ORGANS
Adverse Drug Reactions:
Common: Antibody development
Less Common: Hypersensitivity reaction
Drug Interactions: No known significant interactions
Administration: Administer via IV route at a rate of 1–2
mL/minute.
Prior to reconstitution, warm vial and diluent to room
temperature. Gently swirl vial in a circular motion after
adding diluent until dissolved.
Do NOT administer in the same tubing or container with
other medicinal products.
Pregnancy Category: C
ATC Code: B02BD02
FACTOR IX COMPLEX CONCENTRATE
Rx (COAGULATION
FACTORS II, VII, IX, X)
Inj.: 100 IU/mL, 5 mL and 10 mL vial (IV)
500 IU lyophilized powder vial + diluent (IV)
A sterile lyophilized concentrate derived from human
plasma. It is also known as prothrombin complex
concentrate and is composed of several Vitamin K-
dependent clotting factors including factor IX, factor II
(prothrombin), factor X, and low levels of factor VII.
Indication: Prevention and control of bleeding in patients
with factor IX deficiency (hemophilia B).
NOTE: NOT indicated for the treatment of other factor
deficiencies, hemophilia A patient with inhibitors to
factor VIII, or bleeding caused by low levels of liver-
dependent coagulation factors.
Contraindications: Hypersensitivity reactions to factor IX
complex or any component of the formulation; known
allergy to heparin; history of heparin-induced
thrombocytopenia.
Dose:
NOTE: Dosage is expressed in units of factor IX activity.
Individualize doses based on severity of factor IX
deficiency, extent and location of bleeding, and clinical
status of patient. Closely monitor factor IX level to
determine proper dosage.
When multiple doses are required, administer at 24-hour
intervals unless otherwise specified.
Control or prevention of bleeding in patients with factor IX
deficiency, by IV injection, ADULT and CHILD,
BLOOD AND BLOOD FORMING ORGANS

Indication Bebulin Profilnine or until healing

has been
Usually 50–75 Maintenance achieved
units/kg as a dose, 30–50
single infusion units/kg every
1 hour prior to 16–24 hours
Dental surgery,
surgery [raise for 7–10 days

B
single tooth
factor IX level following
to 40–60% of surgery or until
normal on day healing has
of surgery] been achieved
[raise factor IX
Replacement
level to 50% of
therapy may be
normal
required for up
immediately
to 1 week
Dental surgery, prior to
[raise factor IX
multiple teeth procedure; Typical dose,
level to 40–
maintain factor 50–75
60% of normal
IX levels at 30 units/kg [raise
on day of
to 50% of factor IX level
surgery]
normal] to 40–60% of
Initially 30–50
Indication Bebulin Profilnine normal on day
units/kg prior
Initially 20–30 of surgery]
Initially 25–35 to surgery
units/kg every Then lower
units/kg for 1 [raise factor IX
16–24 hours dose to usually
Minor day [raise level to 30–
for 1–2 days 26–65
bleeding, e.g., factor IX level 50% of normal]
for minor units/kg for 1–
early to 20% of Maintenance
hemorrhage or 2 weeks or
hemarthrosis, normal] dose, 30–50
until until adequate
minor units/kg every
hemorrhage Minor surgical wound healing
epistaxis, [NOTE: A single 16–24 hours
stops and procedures [decrease
gingival dose is usually for 7–10 days
healing has factor IX level
bleeding, mild sufficient, but following
been achieved to 20 to 40% of
hematuria a second dose surgery or until
[raise factor IX normal during
healing is
may be given initial postop
level to 20– achieved
after 24 hours] period]
30% of normal] [maintain
Give preop
Initially, 20–30 factor IX levels
Moderate dose 1 hour
units/kg every at 30 to 50% of
bleeding, e.g., prior to
16–24 hours normal]
severe joint surgery,
Initially 50–65 for 2–7 days
bleeding, early initially every
units/kg for 2 for moderate
hematoma, 12 hours, then
days, or until hemorrhage,
major open every 24 hours
adequate or until
bleeding, postop
wound healing hemorrhage
minor trauma,
[raise factor IX stops and
minor
level to 40% of healing has
hemoptysis,
normal] been achieved
hematemesis,
[raise factor IX
melena, major
level to 20–
hematuria
30% of normal]
Initially 30–50
units/kg every
16–24 hours
(maintenance
Major
Initially 75–90 dose, 20
bleeding, e.g.,
units/kg for 2– units/kg) [raise
severe
3 days or until factor IX level
hematoma,
adequate to 30–50% of
major trauma,
wound healing normal]
severe
[raise factor IX Following this
hemoptysis,
level to ≥60% treatment
hematemesis,
of normal] period,
melena
maintain factor
IX levels at
20% of normal
for 3–10 days,

59
 BLOOD AND BLOOD FORMING ORGANS

Indication Bebulin Profilnine Precautions:

Typical initial WARNING: Factor IX complex (factors II, IX, X) contains
dose, 75–90 low or nontherapeutic levels of factor VII component.
units/kg [raise Do NOT confuse with prothrombin complex
factor IX level concentrate (factors II, VII, IX, X, protein C, protein S),
to ≥60% of which contains therapeutic levels of factor VII.
B

normal on day
of surgery]
Antibody formation; Thrombotic events; Hepatic impairment
Adjust dose to
(use with caution)
typically 25–
75 units/kg for
Adverse Drug Reactions:
1–2 weeks
Common: Flushing, thrombosis, chills, fever, headache,
[decrease Initially 30–50
lethargy, somnolence, rash, urticaria, nausea, vomiting,
factor IX level units/kg prior
disseminated intravascular coagulation, paresthesia,
to 20–60% of to surgery
dyspnea, anaphylactic shock, development of clotting
normal during [raise factor IX
factor antibodies, heparin-induced thrombocytopenia.
initial postop level to 30–
period] 50% of normal]
Administration: Administer by IV infusion. Infuse solution at
Adjust dose to Maintenance
room temperature at 2 mL/minute for Bebulin or 10
typically 25– dose, 30–50
mL/minute for Profilnine.
35 units/kg units/kg every
Major surgical
during late 16–24 hours
procedures Prior to reconstitution, bring diluent (SWFI) and Factor IX
postop period for 7–10 days
Concentrate to room temperature. Do NOT exceed 37°C
(≥3 weeks) and following
[98.6°F]. Gently rotate or agitate to dissolve. Do NOT
continue until surgery or until
shake. Use reconstituted solution within 3 hours. Do NOT
adequate healing is
refrigerate. Vials are intended for single use. Discard
wound healing achieved
unused portion.
is achieved [maintain
[further factor IX levels
Do NOT mix with other drugs or solvents.
decrease to at 30–50% of
maintain a normal]
Do NOT exceed the recommended infusion rates to
factor IX level
prevent vasomotor reactions due to rapid administration.
of 20% of
Slowing the rate of infusion, changing the lot of
normal]
medication, or administering antihistamines may relieve
Give preop
some adverse reactions.
dose 1 hour
prior to
NOTE: [Bebulin] Reconstituted product should be a
surgery,
colorless to slightly yellowish and clear to slightly turbid
initially every
solution.
12 hours, then
every 24 hours
[Profilnine] A few particles may remain in solution
postop
following reconstitution. The Mix2Vial set will remove the
particles and the labeled potency will not be reduced.
Formula for units required to raise blood level %:
NOTE: Larger doses may be required, especially if treatment Pregnancy Category: C
is delayed.
ATC Code: B02BD04
[Bebulin] factor IX 1 unit/kg will increase the plasma factor
IX level by 0.8%
Number of Factor IX units required =
body weight (kg) x desired factor IX increase (as % of
normal) x 1.2 units/kg
[Profilnine] factor IX 1 unit/kg will increase the plasma
factor IX level by 1%
Number of factor IX units required =
bodyweight (kg) x desired factor IX increase (as % of
normal) x 1 unit/kg

Dose Adjustment:
Hepatic Impairment:
No dose adjustment required. Monitor factor IX levels.

60
BLOOD AND BLOOD FORMING ORGANS
ANTIANEMIC PREPARATIONS
IRON PREPARATIONS
OTC FERROUS SALT
Oral: Tablet (equivalent to 60 mg elemental iron)
Oral drops, 15 mL and 30 mL (equivalent to 15 mg
elemental iron/0.6 mL)
Syrup, 60 mL (equivalent to 30 mg elemental iron/5
mL)
NOTE: The elemental iron content of a ferrous salt depends
on the type of preparation as follows:
Ferrous fumarate 33%
Ferrous gluconate 12%
Ferrous lactate 19%
Ferrous sulfate, hydrated 20%
Ferrous sulfate, desiccated 32%
An essential trace element required for the formation of
hemoglobin and for the efficient oxygen transport in the
blood.
Indications: Treatment of iron-deficiency anemia and in
people on hemodialysis who are receiving erythropoietin
(supplement and prophylaxis); hematinic.
Dose:
Iron-deficiency anemia, by mouth, ADULT, elemental iron,
100–200 mg daily in divided doses.
Prevention of iron-deficiency anemia (in at risk population),
by mouth, ADULT (female), elemental iron 60 mg daily;
CHILD >5 years, elemental iron, 30 mg daily; CHILD <5
years, elemental iron, 2 mg/kg daily (maximum, 30 mg).
NOTE: May also administer Folic Acid in women and children
>5 years.
See Ferrous Salts under Mineral Supplements in Chapter 1:
Alimentary Tract and Metabolism for other information.
ATC Code: B03AA02, B03AA03, B03AA07
Rx IRON SUCROSE
Inj.: 20 mg/mL, 5 mL ampule (contains 100 mg elemental
iron)
Indication: Management of iron-deficiency anemia in non-
dialysis-dependent chronic kidney disease (NDD-CKD)
patients, rhemodialysis dependent chronic kidney
disease (HDD-CKD) patients receiving erythropoietin,
and peritoneal dialysis dependent chronic kidney
disease (PDD-CKD) patients receiving erythropoietin.
Contraindications: Iron overload; anemia not caused by iron
deficiency.
Dose:
NOTE: Dose is expressed in terms of mg of elemental iron.
Each 5-mL vial contains 100 mg elemental iron (20
mg/mL). Most CKD patients require a minimum
cumulative dose of 1,000 mg elemental iron
administered over sequential sessions to achieve a
B
favorable hemoglobin or hematocrit response. Patients
may then continue to require therapy at the lowest dose
necessary to maintain target levels of hemoglobin,
hematocrit, and iron storage parameters within
acceptable limits.
NDD-CKD, by slow IV injection, ADULT, 200 mg undiluted
over 2–5 minutes on 5 different occasions within a 14-
day period for a total cumulative dose of 1,000 mg;
patients weighing less than 70 kg may require a longer
infusion time.
HDD-CKD, by slow IV injection, ADULT, 100 mg undiluted
over 2–5 minutes; or
by IV infusion, ADULT, 100 mg diluted in a maximum of
100 mL of 0.9% NaCl over a period of at least 15 minutes
per consecutive hemodialysis session for a total
cumulative dose of 1,000 mg.
PDD-CKD, by IV injection, ADULT, 2 infusions of 300 mg over
1.5 hours 14 days apart followed by one 400 mg infusion
over 2.5 hours 14 days later for a total cumulative dose
of 1,000 mg in 3 divided doses within a 28-day period
(dilute each dose in a maximum of 250 mL of 0.9%
NaCl).
Precautions:
WARNING: Iron sucrose should only be administered
when personnel and resuscitative interventions are
immediately available for the treatment of
anaphylaxis and other serious hypersensitivity
reactions.
Hypersensitivity reactions; hypotension; Children; Lactation
(use with caution).
Adverse Drug Reactions:
Common: Dysgeusia, hypotension, nausea, dizziness,
diarrhea, vomiting, headache, pruritus, extremity pain,
arthralgia, back pain, muscle cramp, injection site
reactions, chest pain, peripheral edema.
Rare: Severe, life-threatening allergic reactions (loss of
consciousness, collapse, difficulty breathing or
convulsions), severe hypotension.
Drug Interactions:
Avoid concomitant use with:
Reduces absorption of the following drugs:
Oral Iron Preparations, concomitantly administered
Administration: Administered only by slow IV injection or IV
infusion. Discard unused portion
Inspect visually for clarity, particulate matter, precipitate,
discoloration and leakage prior to administration.
When prepared as an infusion, use immediately. Do NOT
store.
Do NOT mix iron sucrose with other medications or add
to parenteral nutrient solutions for IV infusion.
61
 BLOOD AND BLOOD FORMING ORGANS

NOTE: Administer with caution due to limited excretion. VITAMIN B12 AND FOLIC ACID
Excess tissue iron can be hazardous. Withhold
administration of IV iron formulations if patients VITAMIN B12 (CYANOCOBALAMIN AND ANALOGUES)
demonstrate transferrin saturation >50% and/or serum
ferritin >800 nanograms/mL.
Rx MECOBALAMIN
B

Avoid paravenous infiltration. If this occurs, discontinue

infusion immediately. Apply ice to cause local
vasoconstriction and decrease fluid absorption. Do NOT Oral: 500 micrograms tablet
massage area. Inj.: 500 micrograms/mL, 1mL ampule (IM, IV)

Monitor patients for signs and symptoms of A form of Vitamin B12, a water-soluble vitamin It acts as
hypersensitivity during and after administration for at coenzymes in nucleic acid synthesis.
least 30 minutes and until clinically stable following
completion of the infusion. Indications: Symptomatic treatment of peripheral
neuropathy associated with vitamin B12 deficiency (e.g.,
Guide for Dilution: numbness, pain, paralysis), including diabetic
Nominal Volume neuropathy and polyneuropathy; management of
Dose Volume of megaloblastic anemia associated with vitamin B12
concentration of iron
(mg Fe) diluent deficiency.
per mL sucrose
Hemodialysis-Dependent Chronic Kidney Disease
Patients (HDD-CKD) Dose:
Peripheral neuropathy, by mouth, ADULT, 500 micrograms
1 mg/mL (when
3 times daily;
maximum Maximum:
by IV or IM injection, ADULT, 500 micrograms 3 times
100 mg volume of 5 mL 100 mL
weekly.
diluent is used) 0.9% NaCl
Megaloblastic anemia, by IV or IM injection, ADULT, initially
500 micrograms 3 times weekly; 500 micrograms every
Non-Dialysis-Dependent Chronic Kidney Disease 1–3 months as maintenance dose after approximately 2
Patients (NDD-CKD) months of treatment).
2 mg/mL (when Administration: For IM or IV use. Administer immediately
Maximum:
maximum after removing from package to limit direct exposure to
500 mg 25 mL 250 mL
volume of light.
0.9% NaCl
diluent is used)
Peritoneal Dialysis-Dependent Chronic Kidney Disease For IM route, avoid multiple injections at the same site.
Patients (PDD-CKD) Do NOT inject near highly innervated regions.
1.2 mg/mL
(when NOTE: Do NOT use for more than 1 month without clear
300 mg maximum 15 mL signs of clinical improvement. Avoid long term use in
volume of patients regularly exposed to mercury or mercury
Maximum:
diluent is used) compounds.
250 mL
1.6 mg/mL
0.9% NaCl
(when See Mecobalamin under Vitamins in Chapter 1: Alimentary
400 mg maximum 20 mL Tract and Metabolism for other information.
volume of
diluent is used) Pregnancy Category: C

Pregnancy Category: B ATC Code: B03BA05

ATC Code: B03AE10

FOLIC ACID AND DERIVATIVES

Rx FOLIC ACID

Oral: 400 micrograms, 800 micrograms, 1 mg, and 5 mg

tablet/capsule
2.5 mg/mL pediatric drops
5 mg/5mL syrup

Also known as Vitamin B9, it is reduced in the body to

tetrahydrofolate, which is a coenzyme for various
metabolic processes, including the synthesis of purine
and pyrimidine nucleotides needed in DNA synthesis. It
is also involved in some amino acid conversions, and in
the formation and utilization of formate.

62
BLOOD AND BLOOD FORMING ORGANS
Indications: Treatment of megaloblastic and macrocytic
anemias due to folate deficiency; used in diarrhea in
pediatric patients.
Dose:
Anemia, by mouth, ADULT, 0.4 mg daily; PREGNANT and
LACTATING WOMEN, 0.8 mg daily; CHILD <4 years, up to
0.3 mg daily; INFANT, 0.1 mg daily.
Administration: May be administered by deep IM injection,
IV injection, or IV infusion.
For IV injection or infusion, administer ≤5 mg undiluted
over ≥1 minute; or dilute ≤5 mg in 50 mL of NS or D5W
and infuse over 30 minutes. May be added to IV
maintenance solutions and given as an infusion.
See Folic Acid under Vitamins in Chapter 1: Alimentary Tract
and Metabolism for other information.
Pregnancy Category: A
ATC Code: B03BB01
Rx FOLIC ACID + FERROUS SALT
Oral: 400 micrograms folic acid + 60 mg elemental iron per
tablet / capsule / FC tablet
A two-component, nutritional supplement of iron and folic
acid given during pregnancy.
Indication: Prevention of iron and folic acid deficiencies,
especially in pregnancy.
Dose:
Prevention of iron and folate deficiencies in pregnancy, by
mouth, ADULT, 100 mg elemental iron + 350 to 400
micrograms folic acid daily throughout pregnancy.
Administration: To be taken on an empty stomach, at least
1 hour before or 2 hours after meal. Avoid taking
antacids or antibiotics within 2 hours before or after
taking it.
See Ferrous Salt + Folic Acid under Mineral Supplements in
Chapter 1: Alimentary Tract and Metabolism for other
information.
Pregnancy Category: A
ATC Code: B03BB51
OTHER ANTIANEMIC PREPARATIONS
EPOETIN ALFA (RECOMBINANT
Rx
HUMAN ERYTHROPOIETIN)
Inj.: 2,000 IU/0.5 mL, pre-filled syringe (IV, SC)
B
4,000 IU/0.4 mL, pre-filled syringe (IV, SC)
4,000 IU/mL, 1 mL vial (IV, SC)
10,000 IU/mL, pre-filled syringe (IV, SC)
A glycosylated protein hormone and a hematopoietic growth
factor that regulates erythropoiesis by stimulating the
differentiation and proliferation of erythroid precursors,
the release of reticulocytes into the circulation, and the
synthesis of cellular hemoglobin. It has the same
pharmacological actions as endogenous erythropoietin.
Indications: Treatment of anemia due to concurrent
myelosuppressive chemotherapy, chronic kidney
disease (CKD), or associated with HIV (zidovudine)
therapy; reduction of allogeneic RBC transfusion for
elective, noncardiac, nonvascular surgery.
NOTE: NOT indicated for use in cancer patients receiving
hormonal therapy, therapeutic biologic products, or
radiation therapy unless also receiving concurrent
myelosuppressive chemotherapy.
Contraindications: Serious allergic reactions to epoetin alfa
or any component of the formulation; uncontrolled
hypertension; pure red cell aplasia (PRCA) that begins
after treatment with epoetin alfa or other epoetin protein
drugs; neonates, infants, pregnant women, and nursing
women (multi-dose vials).
Dose:
NOTE: Initiate treatment when hemoglobin is <10 g/dL.
Reduce dose or interrupt treatment if hemoglobin
approaches or exceeds 11 g/dL.
Anemia associated with CKD patients on dialysis, by IV or SC
injection, ADULT, initially 50–100 units/kg 3 times a
week; CHILD 1 month–16 years, initially 50 units/kg 3
times a week; if hemoglobin does not increase by >1
g/dL after 4 weeks, increase dose by 25%; if hemoglobin
increases >1 g/dL in any 2-week period, reduce dose by
≥25%.
Anemia associated with CKD patients not on dialysis, by IV
or SC injection, ADULT, initially 50–100 units/kg 3 times
a week (use only if rate of hemoglobin decline would
likely result in RBC transfusion and desire is to reduce
risk of alloimmunization and/or other RBC transfusion-
related risks); reduce dose or interrupt treatment if
hemoglobin exceeds 10 g/dL; if hemoglobin does not
increase by >1 g/dL after 4 weeks, increase dose by
25%; if hemoglobin increases >1 g/dL in any 2-week
period, reduce dose by ≥25%.
Anemia due to chemotherapy in cancer patients (only if
anticipated duration of myelosuppressive chemotherapy
is at least 2 additional months), by SC injection, ADULT,
initially 150 units/kg 3 times a week or 40,000 units
once weekly until completion of chemotherapy; titrate
dose to use the minimum effective dose that will
maintain a hemoglobin level sufficient to avoid RBC
transfusions; discontinue erythropoietin following
completion of chemotherapy; ADOLESCENT and CHILD
≥5 years, initially 600 units/kg once weekly until
63

completion of chemotherapy; titrate dosage to use the
minimum effective dose that will maintain hemoglobin
level sufficient to avoid RBC transfusions; discontinue
erythropoietin following completion of chemotherapy.
Anemia due to Zidovudine in HIV-infected patients (serum
erythropoietin levels ≤500 milliunits/mL and zidovudine
B
doses ≤4200 mg/week), by IV or SC injection, ADULT,
initially 100 units/kg 3 times a week; if hemoglobin does
not increase after 8 weeks, increase dose by 50–100
units/kg at 4– to 8-week intervals until hemoglobin
reaches a level sufficient to avoid RBC transfusion
(maximum dose, 300 units/kg); withhold dose if
hemoglobin exceeds 12 g/dL, may resume treatment
with a 25% dose reduction once hemoglobin <11 g/dL;
discontinue if hemoglobin increase is not achieved with
300 units/kg for 8 weeks; titrate dose to use the
minimum effective dose that will maintain a hemoglobin
level sufficient to avoid RBC transfusions; hemoglobin
levels should not exceed 12 g/dL); CHILD 8 months to
17 years, 50–400 units/kg 2–3 times a week; titrate
dosage to use the minimum effective dose that will
maintain a hemoglobin level sufficient to avoid RBC
transfusions; hemoglobin levels should not exceed 12
g/dL).
Surgery patients (perioperative hemoglobin should be >10
g/dL and ≤13 g/dL), by SC injection, ADULT, initially 300
units/kg daily for 15 days (10 days before surgery, the
day of surgery, and 4 days after surgery); or
600 units/kg once weekly for 4 doses (21, 14, and 7
days before surgery, and on the day of surgery).
Dose Adjustment:
Renal Impairment:
For CKD patients, use the minimum effective dose that will
maintain a hemoglobin level sufficient to avoid RBC
transfusions and evaluate patient for other causes of
anemia.
Dose reduction is recommended. Do NOT increase dose
more frequently than every 4 weeks. Dose decreases
may occur more frequently. Avoid frequent dosage
adjustments. Discontinue therapy if responsiveness
does not improve.
Adjustments in dialysis parameters may be needed.
Oncology:
Use lowest dose needed to avoid RBC transfusions. Use
ESAs only for treatment of anemia from concomitant
myelosuppressive chemotherapy.
Precautions:
WARNING: Erythropoiesis-stimulating Agents (ESAs)
increase the risk of death, myocardial infarction
(MI), stroke, venous thromboembolism, thrombosis
of vascular access.
Cardiovascular events; hypertension (use with caution);
Perisurgery patients; Pure red cell aplasia or PRCA
(discontinue treatment in patients with PRCA secondary
to neutralizing antibodies to erythropoietin; do not switch
to another ESA in patients who develop antibody-
mediated anemia); Severe anemia or acute blood loss;
Hypersensitivity; Chronic kidney disease; Seizures;
Elderly (decreased endogenous erythropoietin in elderly
with normocytic or iron deficiency anemias or those with
a serum hemoglobin concentration <12 g/dL);
64
BLOOD AND BLOOD FORMING ORGANS
Pregnancy (does not cross human placenta;
polyhydramnios and intrauterine growth retardation
have been reported; hypospadias and pectus excavatum
have been reported with first trimester exposure;
menstruation may resume following treatment with
recombinant erythropoietin in amenorrheic
premenopausal women; if needed, only use single dose
preparations); Lactation (use with caution).
Adverse Drug Reactions:
Common: Hypertension, fever, headache, pruritus, rash,
nausea, vomiting, injection site reactions, arthralgia,
cough, deep vein thrombosis, edema, thrombosis, chills,
depression, dizziness, insomnia, dysphagia, urticaria,
hyperglycemia, hypokalemia, stomatitis, weight loss,
leukopenia, clotted vascular access, muscle spasm,
myalgia, pulmonary embolism, bone pain, respiratory
congestion, upper respiratory infection.
Less Common: Anaphylactic reaction, angioedema,
bronchospasm, erythema, hypersensitivity reactions,
hypertensive encephalopathy, MI, microvascular
thrombosis, neutralizing antibodies, porphyria, pure red
cell aplasia (PRCA), renal vein thrombosis, retinal artery
thrombosis, seizure, stroke, tachycardia, temporal vein
thrombosis, thrombophlebitis, transient ischemic attack,
tumor progression.
Drug Interactions:
Monitor closely with:
Decreases bleeding time:
Desmopressin
Increases sensitivity of erythroid progenitors:
Androgens e.g. testosterone
Administration: For IV or SC administration. Do NOT shake.
For patients with CKD on hemodialysis, IV route is
preferred. May be administered into the venous line at
the end of the dialysis procedure.
For other patient populations, SC route is preferred.
Usually administered undiluted, although may use a 1:1
dilution with bacteriostatic NS (contains benzyl alcohol).
Pregnancy Category: C
ATC Code: B03XA01
EPOETIN BETA
Rx
(RECOMBINANT ERYTHROPOIETIN)
Inj.: 2,000 IU/0.3 mL, pre-filled syringe with needle (IV,
SC)
5,000 IU/0.3 mL, pre-filled syringe with needle (IV,
SC)
10,000 IU/0.6 mL, pre-filled syringe (IV, SC)
A glycosylated protein hormone and a hematopoietic growth
factor that regulates erythropoiesis by stimulating the
differentiation and proliferation of erythroid precursors,
the release of reticulocytes into the circulation, and the
synthesis of cellular hemoglobin. It has the same
pharmacological actions as endogenous erythropoietin.
BLOOD AND BLOOD FORMING ORGANS

Indication: Treatment of symptomatic anemia associated

with chemotherapy in patients treated for non-myeloid Based on Response to Therapy:
malignancies and anemia associated with chronic renal HEMOGLOBIN
failure (CRF). DOSE ADJUSTMENT
INCREASE
≥1 g/dL but <2 g/dL
Contraindications: Hypersensitivity to Epoetin beta or any (hemoglobin ≤12 Continue initial dose

component of the formulation; uncontrolled
hypertension; use in autologous blood donors with MI or
stroke in the past month, with unstable angina, or with
increased deep venous thrombosis (DVT) risk factors.
Dose:
Note: Individualize dose and use the lowest dose necessary
to control symptoms of anemia and avoid hemoglobin
>12 g/dL. Hemoglobin target range is 10–12 g/dL.
Anemia associated with CRF, by IV injection, ADULT, initially
40 units/kg 3 times per week; may increase dose to 80
units/kg 3 times per week based on hemoglobin
response after 4 weeks; may further increase dose by 20
units/kg 3 times per week every 4 weeks, if necessary
(maximum dose, 720 units/kg per week);
by SC injection, ADULT, 20 units/kg 3 times per week or
60 units/kg per week divided into 7 daily doses; may
increase dose every 4 weeks by 60 units/kg per week if
hemoglobin response is <0.25 g/dL per week (maximum
dose, 720 units/kg per week); maintenance, after
reaching hemoglobin target, reduce weekly dose to ½ of
the previously administered dose and titrate every 12
weeks as needed until stable hemoglobin response is
achieved.
Anemia associated with chemotherapy in cancer patients,
by SC injection, ADULT, initially 30,000 units/week or
450 units/kg per week given once weekly or in divided
doses administered 3 times weekly or once daily for 7
days (maximum dose, 60,000 units/week); after 4
weeks, adjust initial dose based on change in
hemoglobin.
Treatment for increasing yield of autologous blood, by IV
injection, ADULT, 200–800 units/kg twice weekly
(maximum, 1,600 units/kg per week);
by SC injection, ADULT, 150–600 units/kg twice per
week (maximum, 1,200 units/kg per week).
Dose Adjustment:
Renal Impairment:
Use with caution in patients with nephrosclerosis who have
not initiated dialysis. Avoid concomitant therapy with
aluminum-containing products.
Oncology:
Use lowest dose needed to avoid symptoms of anemia and
RBC transfusions.
B
g/dL)
Consider doubling initial
<1 g/dL dose (maximum dose:
60,000 units weekly)
<1 g/dL after 8
Discontinue therapy
weeks of therapy
>2 g/dL in 4 weeks
Reduce dose by 25% to
>12 g/dL and ≤13
50%
g/dL
Temporarily discontinue
therapy; once hemoglobin
>13 g/dL
≤12 g/dL, reinitiate at
25% of previous dose
Precautions:
WARNING: Avoid all admixtures. Compatibility has not
been studied.
Cardiovascular events; electrolyte disturbance; Pure red cell
aplasia (patients with a sudden loss of response should
be evaluated for PRCA with associated neutralizing
antibodies to erythropoietin); Hypertension or
cardiovascular disease (use with caution; rapid rise of
hemoglobin is associated with development or
exacerbation of hypertension; hypertensive
encephalopathy, e.g. sudden headache, confusion, gait
instability, or seizure has been reported and requires
immediate intervention); Cancer; Chronic hepatic failure;
chronic renal failure; Myelodysplastic syndromes (MDS)
(use caution in patients with refractory anemia with
excess blasts in transformation); Seizures (use with
caution); Severe anemia or acute blood loss;
Thrombocytosis (use with caution); Pregnancy (does not
cross placenta; polyhydramnios and intrauterine growth
retardation have been reported with use in women with
chronic kidney disease; hypospadias and pectus
excavatum have been reported with first trimester
exposure; menstruation may resume in amenorrheic
premenopausal women; multi-dose formulations
containing benzyl alcohol are contraindicated for use in
pregnant women, use single dose preparations);
Lactation (use with caution).
Adverse Drug Reactions:
Common: hypertension, thromboembolism, headache.
Less Common: Hypertensive crisis, hypertensive
encephalopathy, injection site reaction, iron deficiency,
non-immunologic anaphylaxis or anaphylactoid reaction,
pruritus, pure red cell aplasia (PRCA), rash, seizure,
thrombocytosis, thrombosis of dialysis shunt, urticaria.

Drug Interactions:
Monitor closely with:
Enhance therapeutic effect of Epoetin Beta:
Nandrolone (erythropoiesis-stimulating effect)

Enhance therapeutic effect of the following drugs:

65

Thrombogenic effect: Lenalidomide Thalidomide
(thrombogenic effect)
Administration: May be administered by IV or SC route.
Dissolve powder with full contents in accompanying
solvent ampule. Swirl vial gently until dissolved. Do NOT
B
shake. Solution should be clear, colorless, and
practically free of particles. Use a 26-gauge needle to
withdraw appropriate amount for a single injection.
Replace needle before injection. Use appropriate size for
injection.
SC route is the preferred route of administration except
in patients with CRF on hemodialysis.
For IV route, administer over a period of 2 minutes. IV is
the preferred route in CRF patients on hemodialysis. May
be injected into the venous line at the end of the dialysis
procedure. In patients treated for increasing autologous
blood, administer after blood is donated.
NOTE: Multi-dose vials contain preservative.
Pregnancy Category: Not available
ATC Code: B03XA01
BLOOD SUBSTITUTES AND PERFUSION
SOLUTIONS
NOTE: All plasma fractions should comply with the WHO
requirements for the Collection, Processing and
Quality Control of Human Blood and Blood Products)
BLOOD AND RELATED PRODUCTS
Rx ALBUMIN, HUMAN
Inj.: 20%, 50 mL and 100 mL bottle (IV, IV infusion)
25%, 50 mL and 100 mL bottle (IV, IV infusion)
25%, 50 mL plastic bag (IV, IV infusion)
A protein colloid prepared as a sterile solution of serum
albumin by fractionating pooled plasma from healthy
human donors. Albumin is the major protein involved in
maintaining colloid osmotic pressure in the blood. It is
used to restore effective plasma circulating volume and
colloid osmotic pressure.
Indication: Management of neonatal hyperbilirubinemia
associated with hemolytic disease of the newborn.
Contraindications: Patients at risk of volume overload (e.g.,
patients with renal impairment, severe anemia, heart
failure); dilution with sterile water for injection.
Dose:
NOTE: Dose depends on the size of the patient, the severity
of trauma or illness, and on continuing fluid and protein
losses. Determine dose required based on measures of
adequacy of circulating volume and NOT plasma albumin
levels.
66
BLOOD AND BLOOD FORMING ORGANS
Hemolytic disease of the newborn, by IV infusion, INFANT, 1
g/kg per dose of 25% albumin prior to or during
exchange transfusion.
Dose Adjustment:
Renal Impairment:
In chronic renal insufficiency, receiving albumin solution
may be at risk for accumulation of aluminum and
potential toxicities.
Precautions:
WARNING: Parenteral product may contain aluminum.
Toxic aluminum concentrations may be seen with
high doses, prolonged use, or renal dysfunction.
Monitor for adequate hydration electrolytes level in patients
receiving hyperosmotic solutions of albumin; Anaphylaxis
(discontinue immediately if allergic or anaphylactic
reactions are suspected); Hemodynamic effects (closely
monitor hemodynamic parameters); Hypervolemia or
hemodilution (use with caution; adjust rate of
administration per hemodynamic status and solution
concentration; observe for signs of hypervolemia, such
as pulmonary edema); Cardiovascular disease (avoid
rapid infusions; may cause circulatory overload and
pulmonary edema; discontinue at first signs of
cardiovascular overload); Hepatic impairment; Renal
impairment; Critical illness; sodium restricted patients
(use with caution); Premature neonates; Lactation (use
with caution).
Adverse Drug Reactions:
Common: Anaphylactoid reactions, fever, chills, rash,
nausea, vomiting, tachycardia, hypotension.
Less Common: Anaphylaxis, urticaria, pruritus,
angioneurotic edema, erythema or flushing, dysguesia,
increased salivation, hyperhidrosis, headache,
confusion, loss of consciousness, pulmonary edema,
dyspnea, bronchospasm.
Rare: Hemolysis
Drug Interactions:
Monitor closely with:
Increase risk of adverse or toxic reactions of the following
drugs:
ACE Inhibitors (flushing, hypotension) [for patients
undergoing therapeutic plasma exchange with human
albumin replacement, withhold ACE inhibitors at least 24
hours prior to plasma exchange]
Administration: For IV administration only. Use within 4
hours after entering package. Discard unused portion. In
emergencies, may administer as rapidly as necessary to
improve clinical condition.
Do NOT use sterile water to dilute albumin solutions, as
this has been associated with hypotonic-associated
hemolysis. Do NOT use with ethanol or protein
hydrolysates as precipitation may form.
Do NOT use solution if it is turbid or contains a deposit.
Use within 4 hours after opening vial. Discard unused
portion.
BLOOD AND BLOOD FORMING ORGANS
After initial volume replacement:
5% albumin: Do not exceed 2–4 mL/minute in patients
with normal plasma volume or 5–10 mL/minute in
patients with hypoproteinemia. If unavailable, it may be
prepared by diluting 25% human albumin with NS or
D5W.
25% albumin: Do not exceed 1 mL/minute in patients
with normal plasma volume or 2–3 mL/minute in
patients with hypoproteinemia. May by diluted with NS or
D5W.
NOTE: Rapid infusion may cause vascular overload.
Pregnancy Category: C
ATC Code: B05AA01
DEXTRAN, HIGH MOLECULAR
Rx
WEIGHT (DEXTRAN 70)
Inj.: 6% dextran 70 in 0.9% sodium chloride, 500 mL
bottle (IV infusion)
6% dextran 70 in 5% dextrose, 500 mL bottle (IV
infusion)
A nonprotein colloid and plasma volume expander used in
the management of hypovolemic shock. It reduces blood
viscosity, interferes with fibrin polymerization, has an
antiplatelet effect, and inhibits sludging or aggregation
of red blood cells.
Indication: Blood volume expander used in treatment of
shock or impending shock when blood or blood products
are not available.
NOTE: NOT a substitute for blood or blood components.
Contraindications: Hypersensitivity with dextran or any
component of the formulation; severe heart failure;
bleeding disorders; renal failure
Dose:
Volume expansion or shock, by IV infusion, ADULT, initially
500–1,000 mL at a rate of 20–40 mL/minute for not
longer than 3 days (maximum dose, 20 mL/kg during the
first 24-hour period and 10 mL/kg daily thereafter).
Precautions:
Renal impairment; hemorrhage; chronic liver disease;
patients at risk of developing pulmonary edema or heart
failure; Lactation (use with caution).
Adverse Drug Reactions:
Common: Hypersensitivity reactions (fever, nasal
congestion, joint pains, urticaria, hypotension,
bronchospasm)
Less Common: Nausea, vomiting
Rare: Severe anaphylactic reactions
Drug Interactions:
Monitor closely with:
Enhances anticoagulant effect of Heparin
Administration: For IV infusion only.
Do NOT use if crystalline precipitate forms. Discard
partially used containers. Do NOT add any drugs to
dextran solution. Flush tubing well or change IV tubing
before infusing blood after dextran to prevent blood
coagulation.
B
Monitor central venous pressure during the initial period
of infusion to detect fluid overload. Stop immediately if
signs of anaphylactic reactions, or oliguria, or renal
failure appear. Maintain hematocrit at 30% or higher and
observe for signs of bleeding complications.
Pregnancy Category: C
ATC Code: B05AA05
Rx HYDROXYETHYL STARCH
Inj.: 6% solution, 250 mL and 500 mL bottle (IV infusion)
A nonprotein synthetic colloid used for the prevention or
treatment of hypovolemia. Derived from corn starch
composed it expand circulating blood volume by an
amount approximately equal to the volume infused.
Indication: Blood volume expander used in treatment of
hypovolemia.
Contraindications: Renal failure with oliguria or anuria (not
related to hypovolemia) ; any fluid overload condition
(e.g., pulmonary edema, CHF) ; pre­existing coagulation
or bleeding disorders; critically ill adult patients,
including patients with sepsis or burns; severe liver
disease; lactic acidosis; leukapheresis.
Dose:
NOTE: Determine daily dose and rate of infusion based on
the amount of blood lost, maintenance or restoration of
hemodynamics, and amount of hemodilution.
Administer lowest effective dose for the shortest period
possible. Do NOT administer etherified starches for more
than 24 hours. With severe dehydration, administer
crystalloid first.
Plasma volume expansion, by IV infusion, ADULT, 500–
1,000 mL or 20 mL/kg daily (maximum, 1,500 mL or 50
mL/kg daily); titrate to individual colloid needs,
hemodynamics, and hydration status.
Dose Adjustment:
Renal Impairment:
Avoid use in patients with pre­existing renal dysfunction.
Discontinue use at the first sign of renal injury.
Hepatic Impairment:
Use with caution.
67

Precautions:
WARNING: Etherified starches are associated with
increased bleeding. Avoid in patients with
coagulation disorders.
Hydroxyethyl starch (HES) solutions have been
associated with mortality and renal injury requiring
B
renal replacement therapy in critically ill patients.
Avoid use in critically ill adult patients, including those
with sepsis or burns, as well as patients admitted to
the ICU.
Anaphylactoid reactions (patients allergic to corn may be
allergic to hetastarch); Bleeding (not recommended as a
cardiac bypass pump prime; monitor the coagulation
status in patients undergoing open heart surgery in
association with cardiopulmonary bypass; may cause
coagulation abnormalities in conjunction with a
reversible, acquired von Willebrand-like syndrome
and/or factor VIII deficiency when used over a period of
days); Fluid overload; Hematologic reactions; Hepatic
impairment; Renal impairment; Critically-ill patients
(avoid use in patients with pre­existing renal dysfunction
and discontinue use at the first sign of renal injury;
monitor renal function in all patients for at least 90 days);
Lactation (use with caution).
Adverse Drug Reactions:
Common: Hypersensitivity reactions (including anaphylactic
reactions), pruritus, hemodilution, decreased plasma
proteins and hematocrit.
Drug Interactions: Incompatibilities can occur on mixing with
other medicaments.
Administration: Administer by IV infusion only.
Administration rates vary depending on the extent of
blood loss, age, and clinical condition of patient. Do NOT
exceed 1.2 g/kg per hour (20 mL/kg per hour).
Do NOT use if crystalline precipitate forms or appears as
a turbid deep brown solution.
May be administered via infusion pump or pressure
infusion. If administered by pressure infusion, air should
be withdrawn or expelled from bag prior to infusion to
prevent air embolus.
Do NOT administer with blood through the same
administration set. Change IV tubing or flush copiously
with NS before administering blood through the same
line. Change IV tubing at least every 24 hours.
Pregnancy Category: C
ATC Code: B05AA07
MODIFIED FLUID GELATIN
Rx (POLYMERISATE OF DEGRADED
SUCCINYLATED GELATIN)
Inj.: 3% and 4% solution, 500 mL bottle (IV infusion)
A sterile non-pyrogenic solution for infusion of succinylated
gelatin used as colloidal plasma substitutes. They
contain large molecules that do not readily leave the
68
BLOOD AND BLOOD FORMING ORGANS
intravascular space where they exert osmotic pressure to
maintain circulatory volume.
Indications: Prophylaxis and treatment of absolute and
relative hypovolemia (e.g., following shock due to
hemorrhage or trauma, perioperative blood losses,
burns, sepsis); prophylaxis of hypotension (e.g., with
induction of epidural or spinal anesthesia);
hemodilution; extracorporeal circulation (heart-lung
machine, hemodialysis).
Contraindications: Hypervolemia; hyperhydration; severe
cardiac insufficiency; severe disturbance of blood
coagulation.
Dose:
NOTE: Determine infusion rate and duration of
administration based on individual requirements. Adjust
rate and duration to the current requirement by
monitoring the usual circulation parameters.
Hypovolemia or hypotension, prophylaxis, by IV infusion,
ADULT, 500–1,000 mL.
Mild hypovolemia, treatment, by IV infusion, ADULT, 500–
1,000 mL.
Hypovolemia, by IV infusion, ADULT, 500–1000 mL.
Severe hypovolemia, treatment, by IV infusion, ADULT,
1,000–2,000 mL;
Severe hypovolemia, emergencies with vital indications, by
rapid IV infusion, ADULT, 500 mL.
Hemodilution, isovolemic, by IV infusion, ADULT, not more
than 20 mL/kg body weight daily.
Extracorporeal circulation, by IV infusion, ADULT, 500–
1,500 mL.
NOTE: Infuse the first 20–30 mL slowly under close
observation to allow early recognition of allergic
reactions (e.g., anaphylactic, anaphylactoid).
Precautions:
Hypernatremia (use with great caution; additional sodium is
administered with modified fluid gelatin); States of
dehydration; Disturbance of blood coagulation; Renal
insufficiency; Hepatic impairment
.
Adverse Drug Reactions:
Less Common: Transient mild nausea or abdominal pain,
transient mild rise of body temperature.
Rare: Anaphylactoid reactions, tremor, hypotension,
hypertension, wheezing, dyspnea, hypoxia, urticarial
reactions, sweating, chills, pyrexia.
Drug Interactions: Incompatibilities can occur on mixing with
other medicaments.
Administration: Administer by IV route. Warm solution to
body temperature prior to administration by pressure
infusion.
Administer by rapid IV infusion under external pressure
in emergency situations. Remove all air from containers
with air space before starting the infusion to prevent air
embolism during infusion.
Do NOT use if solution is not clear or the container or its
closure show visible signs of damage.
BLOOD AND BLOOD FORMING ORGANS
Pregnancy Category: No information available
ATC Code: B05AA06
I.V. SOLUTIONS FOR PARENTERAL NUTRITION
ALL-IN-ONE ADMIXTURES
Rx (3 IN 1 SOLUTIONS /
DUAL ENERGY SOLUTIONS)
Solution: Volume 400 – 2500 mL
Concentration Variable
Protein 3-6 g/100 mL
Carbohydrates 6–15 g/100 mL
Lipid 2–5 g/100 mL
Calories Variable
Electrolytes Variable
A sterile, nonpyrogenic emulsion of essential amino acids,
electrolytes, dextrose, and lipid for central venous
administration, in a three-chamber bag.
Indications: Supply of water, proteins, electrolytes, essential
amino acids & calories to patients by TPN when oral or
enteral nutrition is unfeasible, insufficient, or
contraindicated; prevention of essential fatty acid
deficiency; treatment of negative nitrogen balance in
adult patients.
Contraindications: Hypersensitivity to eggs, soy protein, fat
emulsion, amino acids, or glucose; hyperlipemia; severe
liver insufficiency; blood coagulation disorders;
congenital disorder of amino acid metabolism; severe
renal insufficiency without hemofiltration or dialysis;
acute shock; hyperglycemia requiring insulin over 6 units
hourly; elevated serum levels including electrolytes.
Dose:
NOTE: Individualize dose and infusion rate based on the
ability to eliminate fat and metabolize glucose.
Determine bag size with regard to the clinical condition
of the patient, the body weight and the nutritional
requirements.
Normal nutritional state or under mild catabolic stresses, by
IV drip infusion, ADULT, 0.7–1 g/kg (nitrogen 0.1–0.15
g/kg) daily of amino acids.
Moderate to high catabolic stresses, by IV drip infusion,
ADULT, 1–2 g/kg (nitrogen 0.15–0.3 g/kg); generally,
0.7–1 g/kg daily of total amino acid (nitrogen 0.1–0.15
g/kg) into peripheral or central veins; do not exceed a
rate of 3.7 mL/kg per hour (equivalent to 0.25 g glucose,
0.09 g amino acids, and 0.13 g lipids per kg);
recommended infusion period is 12–24 hours or as
prescribed by the physician.
Dose Adjustment:
Geriatric:
Administer more slowly or at reduced dose.
Precautions:
WARNING: Preterm infants and low birth weight
infants have poor clearance of IV lipid emulsion
and increased free fatty acid plasma levels
following lipid emulsion infusion. Deaths in preterm
infants after infusion of IV lipid emulsions have
B
been reported.
Special clinical monitoring is required at the beginning of IV
infusion (serum triglyceride level should not exceed 2
mmoL/L in 5–6 hours after the administration). Carefully
monitor serum glucose level, electrolytes, osmolarity,
fluid balance, acid-base status, liver enzyme level
[alkaline phosphatase, alanine aminotransferase (ALT),
and aspartate aminotransferase (AST) during
administration. Should any abnormal sign occur, the
infusion must be stopped.
For long-term administration, consider additional
administration of trace elements (e.g., copper, zinc) due
to increased urinary excretion accompanying IV
administration of amino acids. Monitor blood cell count
and coagulation during long-term administration.
Disorders of lipid metabolism (induced by renal failure,
pancreatitis, impaired liver function, hypothyroidism
accompanied by hypertriglyceridemia); sepsis; lactic
acidosis, insufficient cellular oxygen supply, increased
serum osmolarity; patients who need a fluid
resuscitation; patients with a tendency toward electrolyte
retention.
Renal failure (carefully monitor phosphate and potassium
intake to prevent hyperphosphatemia or hyperkalemia).
Patients under malnutrition state (monitor patients carefully
and fine tune of the amount of additional solutions,
electrolytes, vitamins, and minerals required).
Elderly (adjust dose; reduced physiological activities).
Adverse Drug Reactions:
Common: Transient increase in body temperature.
Less Common: Shivering, chillness, nausea, vomiting.
Rare: Thrombophlebitis, hypersensitivity reactions (e.g.,
anaphylactic reaction, rash, urticaria), respiratory
symptoms (hyperventilation), hypertension or
hypotension, hemolysis, increased reticulocytes,
abdominal pain, headache, fatigue, penile stiffness.
Drug Interactions:
Monitor closely with:
Interferes with lipase system:
Heparin (increases plasma lipolysis due to transient
release of lipoprotein lipase; transient decrease of
triglyceride clearance rate at initial administration),
Insulin
General incompatibilities:
Glucose in solution (may form precipitates)
Reduces therapeutic effect of Coumarin Derivatives:
Vitamin K1 [in soybean oil]
Administration: The solution is for IV infusion ONLY into a
central vein.
Correct any state of electrolyte imbalance prior to initial
administration. Observe strict aseptic procedures during
insertion and manipulation to catheters to avoid
contamination.
69

Inspect the bag prior to activation. Use only if glucose
solution and amino acid solution with electrolytes are
transparent, and fat emulsion is homogeneous. Discard
the bag if there is evidence of damage to the bag, if more
than one chamber is white, if the solution is yellow, or if
any seal is broken.
B
Mix the contents of each chamber thoroughly right
before use by inverting the bag upside down to ensure a
homogenous admixture. Ensure the vertical seals
between chambers are broken and the contents of all
three chambers are mixed together prior to infusion.
Ensure that precipitates have not formed during the
mixing or addition of additives and that the emulsion has
not separated. Separation of the emulsion can be visibly
identified by a yellowish streaking or the accumulation of
yellowish droplets in the mixed emulsion. If any of those
mentioned are observed, discard the admixture.
Consume solution within 24 hours unless specifically
stated that it is stable for a longer time. Discard any
remaining mixture after administration.
Do NOT inject with same syringe containing blood at the
same time to minimize risk of false coagulation reaction.
Use a dedicated line without any connections. Multiple
connections could result in air embolism due to residual
air being drawn from the primary container before
administration of the fluid from the secondary container
is completed.
NOTE: Use of a vented IV administration set with the vent in
the open position could result in air embolism.
Do NOT use administration sets and lines that contain di-
2-ethylhexyl phthalate (DEHP) or administration sets that
contain polyvinyl chloride (PVC) components as these
contain DEHP as a plasticizer.
Pregnancy Category: Not available
ATC Code: B05BA10
AMINO ACID + CARBOHYDRATE +
Rx
MULTIVITAMINS + ELECTROLYTES
Inj: Solution for IV injection/infusion set, 1000 mL
Indications: Provision of water, electrolytes, calories, amino
acids and vitamin in patients who require central venous
nutrition because oral or enteral nutrition is inadequate
or not possible.
Contraindications: Abnormal electrolyte metabolism;
hepatic dysfunction; serious renal dysfunction; abnormal
amino acid metabolism; hemophilia; hypersensitivity to
any component of the formulation.
Dose:
Parenteral nutrition, by IV infusion, ADULT, 2000 mL via
central vein over 24 hours.
70
BLOOD AND BLOOD FORMING ORGANS
Dose Adjustment:
The dosage should be adjusted according to patient’s
clinical condition, body weight, and age.
Use in Elderly:
Reduce the dose by decreasing the infusion rate.
Precautions:
Use in caution in patients with bacteremia, dehydration,
hepatic dysfunction, renal failure, severe burns, cardiac
failure, reduced urine output due to obstructive
uropathy, diabetes mellitus, diabetes insipidus, severe
acidosis, pancreatic disorders, history of allergic
reactions and known hypersensitivity to any component
of the formulation.
Adverse Drug Reactions:
Clinically Significant: Acidosis, shock and anaphylactoid
reactions, and hyperglycemia.
Less Common: Rash, pruritus, hyperkalemia,
hyperglycemia, nausea, and vomiting.
Frequency Unknown: Facial flushing, hypernatremia,
hypercalcemia, abdominal pain, diarrhea, anorexia,
abnormal liver function tests, chest discomfort,
palpitation, cerebral edema, pulmonary edema,
peripheral edema, water intoxication, chills, fever, feeling
of warmth, headache.
Drug Interactions:
Reduces the effects of the following:
Antiparkinsonian agents e.g. Levodopa, Warfarin
Enhances the effects of:
Digitalis agents
Administration: Infuse via central vein; do not infuse via
peripheral vein.
Pregnancy Category: C
ATC Code: B05BA
AMINO ACID + GLUCOSE +
Rx
ELECTROLYTES + VITAMIN B1
Inj: Solution for peripheral venous infusion, 500 mL and
1000 mL
The upper chamber contains an amino acid solution with
electrolytes and the lower chamber contains a glucose
solution with electrolytes and vitamin B1.
Indications: Provision of amino acids, electrolytes, vitamin
B1 and water via peripheral vein to patients with mild
hypoproteinemia or mild malnutrition due to inadequate
oral intake, before and after surgery.
Contraindications: Hepatic coma or at risk of developing
hepatic coma; serious renal dysfunction or azotemia;
congestive heart failure; severe acidosis; abnormal
electrolyte metabolism; reduced urine output due to
obstructive uropathy; abnormal amino acid metabolism;
known hypersensitivity to thiamine chloride
hydrochloride.
BLOOD AND BLOOD FORMING ORGANS

Dose:
Mild hypoproteinemia or mild malnutrition, by IV infusion,
ADULT, 500 mL per dose infused via peripheral vein at
infusion rate of 500 mL administered over 120 minutes.
Maximum dose: 2500 mL per day.
Precautions:
Exercise caution against volume overload; Monitor
periodically for signs of hyperosmolarity, hyperglycemia,
glycosuria, and hypertriglyceridemia; Essential fatty acid
deficiency syndrome (may be prevented or corrected by
appropriate treatment with IV fat emulsions).

Dose Adjustment:
Use in Elderly:
Reduce the dose by decreasing the infusion rate under
careful supervision.
Precautions:
Use in caution in patients with hepatic dysfunction, renal
dysfunction, cardiovascular dysfunction, acidosis, and
diabetes mellitus.
Adverse Drug Reactions:
Common: Vascular pain and phlebitis.
Less Common: Nausea, vomiting, chest discomfort
Rare: Rash, palpitations, cerebral, pulmonary, and
peripheral edema, hyperkalemia, water intoxication,
acidosis, chills, fever, sensation of warmth, and fever.
Drug Interactions:
No information provided in the manufacturer’s labeling.
B
Adverse Drug Reactions:
Common: Acidosis, alkalosis, hypophosphatemia,
hypocalcemia, rebound hypoglycemia, electrolyte
imbalance, hyperammonemia, nausea, vomiting, chills,
flushing, sensation of warmth, headache, dizziness.
Drug Interactions: No information available
Administration: To be administered by IV route.
Use only if bottle and seal are undamaged and solution
is clear with vacuum present. Do NOT expose to light
before using. Once closure is penetrated, transfer
contents promptly, total time not to exceed 4 hours.
Initiation and termination of infusions of TPN fluids must
be gradual to permit adjustment of endogenous insulin
release.

Administration: Immediately before use, break the center NOTE: Dose on the first day should be approximately half
seal between the two chambers and mix solutions the anticipated optimal dose and increased gradually to
thoroughly. The usual infusion rate in adults is 500 mL minimize glycosuria.
administered over 120 minutes.
Withdraw administration gradually to avoid rebound
Pregnancy Category: C hypoglycemia.

ATC Code: B05BA Pregnancy Category: Not available

ATC Code: B05BA01

AMINO ACIDS,
Rx
CRYSTALLINE STANDARD
COMBINED GLUCOSE-AMINO
Rx
Inj.: 3.5%, 500 mL bottle (IV infusion) ACID SOLUTIONS
5%, 100 mL, 250 mL, and 500 mL bottle (IV infusion)
6%, 100 mL and 250 mL bottle (IV infusion) Inj.:
7%, 8.5%, 10%, and 11.4%, 100 mL, 500 mL, and 1 Volume 100 mL and 500 mL
L bottle (IV infusion) Concentration variable
8% (as branched chain), 500 mL bottle (IV infusion) Glucose (sorbitol) 25-50 g
9.12%, 20 mL ampule and 200 mL bottle (IV infusion) Protein 20-30 g
10%, 100 mL and 500 mL bottle (IV infusion) Calories 300-450 kcal
Electrolytes variable
A sterile, clear, nonpyrogenic solution of essential and
nonessential amino acids for intravenous infusion in The solution provides carbohydrate calories and crystalline
parenteral nutrition following appropriate dilution. amino acids to stimulate protein synthesis, limit protein
catabolism, minimize liver glycogen depletion, and
Indications: Treatment of negative nitrogen balance when promote wound healing.
adequate nutrition by mouth or gastroduodenal tube is
impossible or undesirable; prevention of nitrogen loss. Indication: IV nutritional therapy to prevent nitrogen loss or
treat negative nitrogen balance in patients with
Contraindications: Hepatic coma; severe renal failure; adequate stores of body fat, in whom, for short periods
metabolic disorders involving impaired nitrogen of time, oral nutrition cannot be tolerated, is undesirable,
utilization. or inadequate.

Dose: Dose depends on metabolic status and clinical
response of the patient as therapy proceeds. Accompany
administration with other calorie sources in the form of
carbohydrate or fat to ensure protein is utilized for
protein synthesis. Doses which achieve nitrogen
equilibrium or positive balance are the most desirable.
Contraindications: Hypersensitivity to one or more amino
acids in the solution; allergy to corn or corn products;
hepatic coma; metabolic disorders involving impaired
nitrogen utilization; intracranial or intraspinal
hemorrhage; severe dehydration; severe liver disease.

71
 BLOOD AND BLOOD FORMING ORGANS

Dose: Total daily dose depends on the daily protein SOYA BEAN + MEDIUM CHAIN
requirements and on the patient’s metabolic and clinical Rx TRIGLYCERIDES + OLIVE OIL +
response. Providing adequate calories in the form of
hypertonic dextrose may require the administration of PURIFIED FISH OIL
exogenous insulin to prevent hyperglycemia and
glycosuria. Administer 5% dextrose solution when Inj: 20 mg/mL (20%) emulsion for IV infusion, 250 mL
B

hypertonic dextrose infusions are abruptly discontinued

to prevent rebound hypoglycemia. A sterile, non-pyrogenic, white, homogenous lipid emulsion
consists of a mixture of soybean oil, medium-chain
Precautions: triglycerides, olive oil, and fish oil.

WARNING: Administration by central venous catheter Indications: Used for parenteral nutrition when oral or
should be used only by those familiar with this enteral nutrition is impossible, insufficient or
technique and its complications. contraindicated.

Contraindications: Known hypersensitivity to fish, egg,

Renal impairment (may induce a rise in BUN; perform
soybean, or peanut protein, or to any active ingredients
appropriate laboratory tests periodically; a modest rise in
or excipients of the product; severe hyperlipidemia or
BUN normally occurs as a result of increased protein
severe disorders of lipid metabolism characterized by
intake; discontinue infusion if BUN levels exceed normal
hypertriglyceridemia.
postprandial limits); Hepatic insufficiency; Diabetic or
prediabetic patients (take special care when
Dose:
administering glucose); Pulmonary disease, or with
The dose depends on the patient’s individual energy
cardiac insufficiency (use with caution to avoid excessive
requirements influenced by age, body weight, tolerance,
fluid accumulation); Severe renal failure and in
clinical status, and the ability to eliminate and
conditions where potassium retention is present (use
metabolize lipids.
with great care); Metabolic or respiratory alkalosis;
Increased level or impaired utilization of acetate (e.g.,
Dose Adjustment:
severe hepatic insufficiency) (use with great care);
Hepatic Impairment
Hyperammonemia.
Use in caution in patients with hepatic impairment.
Adverse Drug Reactions: Nausea, erythema, extravasation,
Precautions:
infection at the injection site, phlebitis extending from
May cause death after infusion in preterm infants,
the injection site, venous thrombosis, warm sensation,
hypersensitivity reactions, increased risk of catheter-
hyperglycemia, hyperosmolar syndrome, hypervolemia,
related infections, fat overload syndrome, refeeding
diuresis, fever, flushing, glycosuria.
syndrome, aluminum toxicity, parenteral nutrition-
associated liver disease, and hypertriglyceridemia.
Drug Interactions:
Monitor closely with:
Adverse Drug Reactions:
Reduces nitrogen-sparing effects of amino acids:
Common: Nausea.
Tetracycline.
Less Common: Vomiting, hyperglycemia, flatulence, pyrexia,
abdominal pain, increased blood triglycerides,
Administration: Administer by IV route. Hypertonic
hypertension, sepsis, dyspepsia, UTI, anemia, and
admixtures may be administered by continuous IV
device-related infection.
infusion through a central venous catheter with the tip
Rare: Dyspnea, leukocytosis, diarrhea, pneumonia,
located in the superior vena cava.
cholestasis, dysgeusia, increased blood alkaline
phosphatase, tachycardia, headache, pruritus, dizziness,
Inspect visually for particulate matter and discoloration
rash and thrombophlebitis.
prior to administration.
Drug Interactions:
Administration time for a single bottle and set should
No drug interaction studies have been performed. However,
NEVER exceed 24 hours.
vitamin K1 content of soybean oil and olive oil may
counteract the anticoagulant activity coumarin and
Solutions administrated to children by peripheral vein
coumarin derivatives including warfarin.
should NOT exceed twice the normal serum osmolarity
(718 mOsmol/L).
Administration: For central or peripheral intravenous
infusion.
Pregnancy Category: C
Pregnancy Category: C
ATC Code: B05BA10
ATC Code: B05BA02

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BLOOD AND BLOOD FORMING ORGANS

I.V. SOLUTIONS AFFECTING THE ELECTROLYTE 5% DEXTROSE

BALANCE Rx
IN 0.3% SODIUM CHLORIDE
DEXTROSE PREPARATIONS IN SODIUM CHLORIDE Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)

General Information Composition:

B
Dextrose 50 g/L
Sterile preparations containing dextrose for IV Na+ 51 mmol/L
administration. Cl- 51 mmol/L

Contraindications: Known hypersensitivity to corn or corn
products; where the administration of sodium or chloride
could be clinically detrimental.
Dose:
Dose is dependent on age, weight, and clinical condition of
patient. Select dose and constant infusion rate with
caution in pediatric patients, particularly neonates and
low birth weight infants, because of the increased risk of
hyperglycemia or hypoglycemia.
Dose of sodium chloride is dependent on degree of sodium
depletion (e.g., moderately severe hyponatremia (serum
sodium, 125–129 mmol/L) or profound hyponatremia
(serum sodium <125 mmol/L); on severity of symptoms
(e.g., moderate or severe); and time of development of
hyponatremia (acute, where hyponatremia is
documented to exist <48 hours).
A sterile, non-pyrogenic, large-volume parenteral solution,
which contains 0.3% of sodium chloride and 5% dextrose
in water for injection; a source of electrolytes, water, and
calories for patients.
Indication: Initial fluid replacement therapy for patients
having elevated serum sodium and conditions where
fluid loss exceeds electrolyte loss.
Adverse Drug Reactions:
Rare: Sodium accumulation, water retention
See General Information on Dextrose Preparations in
Sodium Chloride under Blood Substitutes and Perfusion
Solutions – I.V. Solutions affecting the Electrolyte
Balance in Chapter 02: Blood and Blood Forming Organs
for other information.

Dose Adjustment: Pregnancy Category: C

Renal Impairment:
Take care in dose selection due to an increased risk of ATC Code: B05BB02
adverse effects.

Precautions: 5% DEXTROSE
Rx
IN 0.45% SODIUM CHLORIDE
WARNING: Mix infusion solutions thoroughly after
adding concentrated electrolytes to avoid possible
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)
toxicity.
Composition:
Cardiovascular condition, cirrhotic disease, and nephrotic Dextrose 50 g/L
disease, and in patients receiving corticosteroid therapy; Na+ 77 mmol/L
Solutions containing dextrose should be used with Cl- 77 mmol/L
caution in patients with overt or known diabetes mellitus
and carbohydrate intolerance for any reason; clinical A sterile, non-pyrogenic, large-volume parenteral solution,
evaluation and periodic laboratory examinations are which contains 0.45% of sodium chloride and 5%
necessary; Cardiovascular effects. dextrose in water for injection, intended for intravenous
administration.
Drug Interactions:
Monitor closely with: Indications: For parenteral replenishment of fluid, minimal
Increases risk of hypertension and edema of the following carbohydrate calories, and sodium chloride as required
drugs due to sodium and water retention: by the clinical condition of the patient.
Corticosteroids
Adverse Drug Reactions: Febrile response, infection at the
Administration: Adjust rate of administration according to site of injection, venous thrombosis or phlebitis
tolerance. Too rapid infusion of hypertonic solutions may extending from the site of injection, extravasation,
cause local pain and venous irritation. hypervolemia.

Inspect visually for particulate matter and discoloration Administration: Intended only as a single-dose injection.
prior to administration. Do NOT administer unless Contains no bacteriostatic agent, antimicrobial agent, or
solution is clear, and container is undamaged. added buffer. Discard unused portion.

See General Information on Dextrose Preparations in

Sodium Chloride under Blood Substitutes and Perfusion
Solutions – I.V. Solutions affecting the Electrolyte

73
 BLOOD AND BLOOD FORMING ORGANS

Balance in Chapter 02: Blood and Blood Forming Organs NOT for use the treatment of severe potassium
for other information. deficiency, lactic acidosis, or severe metabolic acidosis.

Pregnancy Category: C Contraindications: Known hypersensitivity to sodium

lactate; allergy to corn or corn products.
ATC Code: B05BB02
B

Dose: Dose is dependent on age, weight, and clinical

condition of patient.
5% DEXTROSE
Rx Dose Adjustment:
IN 0.9% SODIUM CHLORIDE
Geriatric:
Start at the low end of the dosing range, reflecting the
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)
greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease or drug therapy.
Composition:
Dextrose 50 g/L
Renal and Hepatic Impairment:
Na+ 154 mmol/L
Select dose with care due to increased risk of adverse
Cl- 154 mmol/L
effects, e.g., sodium and potassium retention.
A sterile, non-pyrogenic, large-volume parenteral solution,
Precautions:
which contains 0.9% of sodium chloride and 5% dextrose
in water for injection; a source of electrolytes, water, and WARNING: Mix infusion solutions thoroughly after adding
calories for patients. concentrated electrolytes to avoid possible toxicity.

Indications: Initial fluid and electrolyte replacement therapy Hypersensitivity (immediately stop infusion if any signs or
in conditions with combined water and sodium depletion; symptoms of a suspected hypersensitivity reaction
vehicle for IV drug administration. develop); Electrolyte imbalance; Hyperkalemia or
conditions predisposing to hyperkalemia; alkalosis or
Adverse Drug Reactions: risk for alkalosis; Conditions that may cause sodium
Rare: Sodium accumulation, water retention and/or potassium retention, fluid overload, or edema;
Cardiac disease; hypervolemia; overhydration; Impaired
See General Information on Dextrose Preparations in glucose tolerance or diabetes mellitus; Severe renal
Sodium Chloride under Blood Substitutes and Perfusion impairment; Conditions associated with increased
Solutions – I.V. Solutions affecting the Electrolyte lactate levels or impaired lactate utilization, such as
Balance in Chapter 02: Blood and Blood Forming Organs severe hepatic insufficiency; Substantially hypertonic
for other information. solutions (administer hyperosmolar solutions with
caution, if at all, to patients with hyperosmolar states);
Pregnancy Category: C Solutions containing calcium salts should be used with
caution in patients with hypercalcemia or conditions
ATC Code: B05BB02 predisposing to hypercalcemia, such as severe renal
impairment and granulomatous diseases associated
with increased calcitriol synthesis such as sarcoidosis,
5% DEXTROSE calcium renal calculi; Elderly; children and newborns
Rx
IN LACTATED RINGER’S
Adverse Drug Reactions:
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion) Less Common: Pain and inflammation at the injection site,
phlebitis, tissue necrosis, venous irritation, venous
Composition: thrombosis.
Dextrose 50 g/L Rare: Angioedema, anxiety, blood pressure decreased,
Na+ 130 mmol/L bronchospasm, chest discomfort and pain, cough,
K+ 4 mmol/L decreased heart rate, dysgeusia, dyspnea, edema,
Ca++ 1.22 – 1.5 mmol/L erythema, flushing, headache, hyperkalemia,
Cl- 109 mmol/L hypersensitivity reactions, including anaphylactic and
Lactate 28 mmol/L anaphylactoid reactions; hypesthesia, nausea,
A sterile, non-pyrogenic solution, which contains 5% paresthesia, pruritus, pyrexia, rash, respiratory distress,
dextrose and lactated ringer’s solution, in a single-dose tachycardia, throat irritation, urticaria.
container for IV administration and can produce a
metabolic alkalinizing effect. Drug Interactions:
Monitor closely with:
Indications: Source of water, electrolytes, and calories; Alters renal clearance of the following drugs:
alkalinizing effect. Acidic Drugs, e.g., Salicylates, Barbiturates (increased
renal clearance)
NOTE: Capable of inducing diuresis depending on the Basic Drugs, e.g., Sympathomimetics (decreased renal
clinical condition of the patient. clearance)
Lithium (increased renal clearance)

74
BLOOD AND BLOOD FORMING ORGANS
Increases risk of adverse or toxic effects of the following
drugs:
Corticosteroids (sodium and fluid retention)
Increases risk of adverse or toxic effects of the following
drugs:
Drugs which can cause hyperkalemia, e.g., Potassium-
sparing Diuretics, Angiotensin II Receptor Antagonists,
ACE Inhibitors, Immunosuppressants (hyperkalemia)
Thiazide Diuretics (hypercalcemia)
Vitamin D (hypercalcemia)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Ceftriaxone
(Ceftriaxone-Calcium Salt precipitation in the
bloodstream)
Administration: Administer via IV route.
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
solution is clear, and container is undamaged.
Do NOT connect flexible plastic containers in series to
avoid air embolism due to possible residual air contained
in the primary container. Pressurizing IV solutions
contained in flexible plastic containers to increase flow
rates can result in air embolism if the residual air in the
container is not fully evacuated prior to administration.
Do NOT administer simultaneously with citrate
anticoagulated or preserved blood through the same
administration set to prevent likelihood of coagulation.
Pregnancy Category: C
ATC Code: B05BB02
Rx ACETATED RINGER’S SOLUTION
Inj.: 500 mL and 1 L bottle / bag (IV infusion)
Composition:
Na+ 130 mmol/L
K+ 4 mmol/L
Ca++ 3 mmol/L
Cl- 109 mmol/L
Acetate 28 mmol/L
A sterile, non-pyrogenic, lactate-containing solution,
which serves as a source of water and electrolytes.
Indication: For fluid and electrolyte replacement therapy.
Contraindications: Extracellular hyperhydration;
hypervolemia.
Dose: Dose is dependent on age, weight, and
clinical and biological (acid-base balance) conditions of
patient and concomitant therapy.
Dose Adjustment:
Renal Impairment:
Select doses with care due to an increased
risk of adverse effects, e.g., sodium and potassium
retention.
B
Precautions:
WARNING: Mix infusion solutions thoroughly after
adding concentrated electrolytes to avoid possible
toxicity.
High volume infusion must be used under specific
monitoring in patients with cardiac or pulmonary failure,
in patients presenting edema, ascitic cirrhosis or renal
insufficiency; Closely monitor patient’s clinical status
and laboratory parameters, including plasma electrolyte
levels of sodium, chloride, potassium, magnesium and
calcium; Sodium content (administer carefully to
patients with hypertension, heart failure, peripheral or
pulmonary edema, impaired renal function, pre-
eclampsia, aldosteronism, or other conditions
associated with sodium retention); Potassium content
(administer with caution to patients with cardiac
diseases or conditions that can lead to hyperkalemia
such as renal or adrenocortical insufficiency, acute
dehydration, or extensive tissue destruction as occurs
with severe burns); Calcium content (Calcium Chloride is
an irritant; administer with caution to prevent
extravasation; administer with caution to patients with
impaired renal function, or disease associated with
elevated Vitamin D concentrations, such as sarcoidosis
or to patients receiving Digitalis therapy); Magnesium
content (use with caution in patients with renal
impairment, severe heart rate disorders, and myasthenia
gravis; monitor for clinical signs of excess magnesium,
particularly when being treated for eclampsia; use with
caution when administered after neuromuscular block
during the postoperative period since magnesium salts
can lead to a recurarisation effect); Acetate content (may
cause metabolic alkalosis; not suitable as treatment for
severe metabolic or respiratory acidosis).
Adverse Drug Reactions:
Common: Overhydration, heart failure in patient with
cardiac disorder, pulmonary edema, febrile reaction,
infection at the site of injection, local pain or reaction,
vein irritation, venous thrombosis or phlebitis extending
from the site of injection, extravasation.
Rare: Hypersensitivity reactions, allergic reactions or
anaphylactic or anaphylactoid symptoms, tachycardia,
bradycardia, chest tightness, chest pain, localized or
generalized urticaria, pruritus.
Drug Interactions:
Monitor closely with:
Alters renal clearance of the following drugs:
Bicarbonates (increased renal elimination of certain
drugs, e.g., quinidine, salicylates, lithium; decreased
elimination of sympathomimetics).
Increases risk of adverse or toxic effects of the following
drugs:
Potassium and or sodium retention: ACE Inhibitors e.g.,
Captopril; Cyclosporine; Corticosteroids e.g. Prednisone;
Digitalis Glycosides e.g. Digoxin; Potassium-sparing
Diuretics e.g. Spironolactone
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 BLOOD AND BLOOD FORMING ORGANS

Tacrolimus BALANCED MULTIPLE

Rx
MAINTENANCE SOLUTON
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Inj.: with 5% dextrose, 250 mL and 500 mL (infants) and
drugs:
1 L (children and adults), bottle / bag (IV infusion)
Suxamethonium (hyperkalemia; intensifies negative
B

effect on cardiac rhythm); Potassium (hyperkalemia;

Composition:
intensifies negative effect on cardiac rhythm)
INFANTS CHILDREN
& ADULTS
Potentiates therapeutic effects of Neuromuscular Blockers,
Dextrose 50 g/L 50 g/L
e.g., Suxamethonium, Vecuronium, Tubocurarine:
Na+ 25-30 mmol/L 40-50 mmol/L
Magnesium Salts
K+ 20-25 mmol/L 13-30 mmol/L
Mg++ 1.35-1.65 mmol/L 1.65 mmol/L
Administration: Administer via IV route.
Cl- 22 mmol/L 40 mmol/L
Acetate 23 mmol/L 16 mmol/L
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
A sterile, nonpyrogenic, hypertonic solution of balanced
solution is clear, and container is undamaged.
maintenance electrolytes and 5% dextrose injection in
water for injection.
Administer with sterile equipment using aseptic
technique. Prime equipment with the solution to prevent
Indication: Fluid and electrolyte maintenance therapy.
air entering the system.
Contraindications: Hyperkalemia; oligo-anuric renal failure.
Do NOT connect flexible plastic containers in series to
avoid air embolism due to possible residual air contained
Dose: Dose is dependent on age, weight, and degree of fluid
in the primary container before the administration of the
and electrolyte loss.
fluid from the secondary container is completed.
Pressurizing IV solutions contained in flexible plastic
Dose Adjustment:
containers to increase flow rates can result in air
Renal Impairment:
embolism if the residual air in the container is not fully
Select doses with care due to an increased risk of adverse
evacuated prior to administration. Avoid using a vented
effects, e.g., sodium and potassium retention.
IV administration set with the vent in the open position
to prevent air embolism.
Precautions:
Do NOT administer simultaneously with citrate WARNING: Mix infusion solutions thoroughly after
anticoagulated or preserved blood through the same adding concentrated electrolytes to avoid possible
administration set to prevent likelihood of coagulation. toxicity.

Do NOT administer via the same infusion system as
concomitant blood transfusion because of the risk of
coagulation
Due to its iso-osmolality, this solution can be
administered through a peripheral vein. Use only if the
solution is clear, without visible particles and if the
container is undamaged. Administer immediately
following the insertion of infusion set. Do NOT remove
unit from overwrap until ready for use. The inner bag
maintains the sterility of the product. Discard after single
use. Discard any unused portion. Do not reconnect
partially used bags.
NOTE: Additives may be introduced before or during infusion
through the injection site. When additive is used, verify
isotonicity prior to administration. Thorough and careful
aseptic mixing of any additive is mandatory. Solutions
containing additives should be used immediately and not
stored. Adding other medication or using an incorrect
administration technique might cause fever reactions
due to the possible introduction of pyrogens. Stop
infusion immediately in case of adverse reaction.
Pregnancy Category: C
ATC Code: B05BB01
Hypersensitivity reactions; CHF; renal insufficiency; clinical
states with edema with sodium retention.
Administration of the solution can cause fluid and/or solute
overloading resulting in dilution of serum electrolyte
concentration, overhydration, congested states or
pulmonary edema; Clinical evaluation and periodical
laboratory determinations are necessary to monitor
changes in fluid balance, electrolyte concentration, and
acid-base balance during prolonged therapy or whenever
the patient’s condition warrants such evaluation.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis
extending from the site of injection, extravasation,
hypervolemia
NOTE: May occur because of the solution or the technique
during administration.
Drug Interactions: No information available
NOTE: Additives may be incompatible. Consult with
pharmacist.
Administration: Administer by IV infusion. Contains no
bacteriostat, antimicrobial agent, or added buffer and is
intended only for use as a single-dose injection. Discard
unused portion.

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BLOOD AND BLOOD FORMING ORGANS

When introducing additives, use aseptic technique, mix Drug Interactions:

thoroughly, and do not store.
Select dose and constant infusion rate of IV dextrose with
caution in pediatric patients, particularly neonates and
low birth weight infants, because of the increased risk of
Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Corticosteroids e.g. prednisone

B
hyperglycemia or hypoglycemia. Administration: Administer via IV infusion.

Pregnancy Category: C Inspect visually for particulate matter and discoloration

prior to administration. Do NOT administer unless
ATC Code: B05BB02 solution is clear, and container is undamaged.

Pregnancy Category: C
BALANCED MULTIPLE
Rx ATC Code: B05BB02
REPLACEMENT SOLUTON
Inj.: 500 mL and 1 L bottle / bag (IV infusion)
BALANCED MULTIPLE
Composition: Rx REPLACEMENT SOLUTION
Na+ 140-145 mmol/L WITH pH 7.4
K+ 4-5 mmol/L
Mg++ 1-1.65 mmol/L Inj.: 500 mL and 1 L bottle / bag (IV infusion)
Cl- 98-127 mmol/L
Acetate 24-50 mmol/L Composition:
Plus 5% dextrose (50 g/L) Na+ 140 mmol/L
K+ 5 mmol/L
A sterile, non-pyrogenic solution consisting of balanced Mg++ 3 mmol/L
electrolytes with 5% dextrose in water for injection. Cl- 98 mmol/L
Acetate 50 mmol/L
Indications: Acute fluid and electrolyte replacement therapy;
fluid replacement in hyperchloremic acidosis. A sterile, nonpyrogenic, isotonic solution of balanced
Contraindications: Not to be used for fluid and electrolyte electrolytes in water for injection, administered by IV
maintenance therapy; hyperkalemia, hypermagnesemia; infusion for parenteral replacement of acute losses of
metabolic alkalosis. extracellular fluid.

Dose: Dose is dependent on age, weight, and degree of fluid
and electrolyte loss.
Dose Adjustment:
Renal Impairment:
Select doses with care due to an increased risk of adverse
effects, e.g., sodium and potassium retention.
Precautions:
WARNING: Mix infusion solutions thoroughly after
adding concentrated electrolytes to avoid possible
toxicity.
Indications: Replacement of acute losses of extracellular
fluid volume in surgery, trauma, burns, or shock; adjunct
to restore a decrease in circulatory volume in patients
with moderate blood loss.
NOTE: NOT intended to supplant transfusion of whole blood
or packed red cells in the presence of uncontrolled
hemorrhage or severe reductions of red cell volume.
NOT intended to correct acidosis or large deficits of
individual electrolytes, nor to replace blood or plasma
expanders when these are indicated.

Hypersensitivity reactions; CHF; renal insufficiency; clinical Contraindications: Hypernatremia or hyperchloremia and
states with edema with sodium retention; Administration related conditions (hypermagnesemia,
of the solution can cause fluid and/or solute overloading hyperphosphatemia, edema, certain cardiac diseases).
resulting in dilution of serum electrolyte concentration,
overhydration, congested states or pulmonary edema; Dose: Dose is dependent on age, weight, and degree of fluid
Clinical evaluation and periodical laboratory and electrolyte loss.
determinations are necessary to monitor changes in fluid
balance, electrolyte concentration, and acid-base Dose Adjustment:
balance during prolonged therapy or whenever the Geriatric:
patient’s condition warrants such evaluation. Select doses with caution. Begin at the low end of the dosing
range.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis Precautions:
extending from the site of injection, extravasation, Can cause fluid and/or solute overloading resulting in
hypervolemia. dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema;
NOTE: May occur because of the solution or the technique Clinical evaluation and periodic laboratory
during administration.

77
 BLOOD AND BLOOD FORMING ORGANS

determinations are necessary to monitor changes in fluid ISOTONIC ELECTROLYTE SOLUTION

balance, electrolyte concentrations and acid-base Rx
FOR IV INFUSION
balance during prolonged parenteral therapy or
whenever the condition of the patient warrants such
Inj: 1 L bottle
evaluation; Sodium content (use with caution in CHF,
concomitant corticosteroid use, severe renal
Composition:
B

insufficiency, and clinical states with edema with sodium

retention); Potassium content (use with caution in
hyperkalemia, severe renal failure, and potassium
retention); Acetate content (use with caution in
metabolic or respiratory alkalosis and severe hepatic
insufficiency); Renal impairment (monitor renal function
during fluid replacement); Elderly (have been shown to
secrete higher levels of ADH; increased risk for
developing fluid overload and dilutional hyponatremia).
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis
extending from the site of injection, extravasation,
hypervolemia
NOTE: May occur because of the solution or the technique
during administration.
If an adverse reaction occurs, discontinue the infusion,
evaluate the patient, institute appropriate therapeutic
countermeasures, and save the remainder of the fluid for
examination, if deemed necessary.
Drug Interactions:
Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Corticosteroids e.g. Prednisone
NOTE: Additives may be incompatible. Consult with pharmacist.
Administration: Administer by IV infusion. Contains no
bacteriostat, antimicrobial agent, or added buffer
(except for pH adjustment) and is intended only for use
as a single-dose injection. Discard unused portion.
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
solution is clear, and container is undamaged.
Determine the amount to be infused based on
replacement of losses of extracellular fluid volume in the
individual patient. Up to 3 times the volume of estimated
blood loss during and after surgery can be given to
correct circulatory volume when there is only a moderate
loss of blood.
Pregnancy Category: C
ATC Code: B05BB02
Sodium chloride - 6.80 g
Potassium chloride - 0.30 g
Calcium chloride dehydrate - 0.37 g
Magnesium chloride hexahydrate - 0.20 g
Sodium acetate trihydrate - 3.27 g
Malic acid - 0.67 g
An isotonic electrolyte solution resembling human plasma.
Indications: Use in the replacement of extracellular fluid
losses in the case of isotonic dehydration, where acidosis
is present or imminent.
Contraindications: Hypervolemia; severe congestive heart
failure, renal failure with oliguria or anuria; severe
general edema; hyperkalemia; hypercalcemia; metabolic
alkalosis.
Dose:
The dosage depends on the age, weight, clinical and
biological conditions of the patient and concomitant
therapy.
Dose Adjustment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
Use in caution in patients with mild to moderate cardiac
insufficiency, peripheral or pulmonary edema or
extracellular hyperhydration, hypernatremia,
hyperchloremia, hypertonic dehydration, hypertension,
impaired renal function, present or imminent eclampsia,
aldosteronism or other conditions or treatment
associated with sodium retention;
Use in caution in patients with cardiac disease, or conditions
predisposing to hyperkalemia such as renal or
adrenocortical insufficiency, acute dehydration, or
extensive tissue destruction as occurs with severe burns;
May cause extravasation due to calcium content and should
be given cautiously in patients with impaired renal
function or diseases associated with elevated vitamin D
concentrations such as sarcoidosis.
Adverse Drug Reactions:
Less Common: Adverse reactions associated to the
technique of administration including febrile response,
infection at the injection site, local pain or reaction, vein
irritation, vein irritation, venous thrombosis or phlebitis
extending from the site of injection and extravasation.
Rare: Urticaria due to intravenous administration of
magnesium salts.

Drug Interactions:
Monitor closely with:
Corticosteroids- may be associated with sodium and water
retention, with increased risk of edema and
hypertension.
Digoxin- enhanced hypercalcemia, which can lead to cardiac
arrhythmia.

78
BLOOD AND BLOOD FORMING ORGANS
Drugs that can cause hyperkalemia (e.g., suxamethonium,
potassium-sparing diuretics or tacrolimus) - increased
risk of hyperkalemia.
Vitamin D- may induce hypercalcemia.
Administration: The solution is administered IV; do not
administer unless the solution is clear and container is
undamaged.
Pregnancy Category: C
ATC Code: B05BB01
I.V. SOLUTIONS PRODUCING OSMOTIC DIURESIS
Rx MANNITOL
Inj.: 20%, 250 mL and 500 mL bottle (IV)
A hexahydric alcohol related to mannose that acts as an
osmotic agent with little energy value. When given
parenterally, it raises the osmotic pressure of the
plasma, thus drawing water out of body tissues and
producing an osmotic diuresis.
Indications: To reduce cerebral edema; to reduce increased
intraocular pressure; to promote urinary excretion of
toxic substances.
NOTE: NOT recommended to be used for the prevention of
acute renal failure and/or promotion of diuresis.
Contraindications: Hypersensitivity to mannitol or any
component of the formulation; severe renal disease
(anuria); severe dehydration; active intracranial bleeding
except during craniotomy; progressive heart failure,
pulmonary congestion, or renal dysfunction after
administration; severe pulmonary edema or congestion.
Dose:
Increased intracranial pressure, cerebral edema, by IV
injection, ADULT, 0.25–2 g/kg per dose, may repeat
every 6–8 hours, as needed to maintain a serum
osmolality <300-320 mOsm/kg; CHILD, 0.25–1 g/kg per
dose administered over 30–60 minutes, repeat as
needed to maintain a serum osmolality <300–320
mOsm/kg.
Reduction of intraocular pressure, by IV injection, ADULT,
0.25–2 g/kg administered over 30–60 minutes 1–1.5
hours prior to surgery; CHILD, 1 to 2 g/kg or 30–60 g/m2
administered over 30–60 minutes 1–1.5 hours prior to
surgery.
Reduction of intraocular pressure, traumatic hyphema, by IV
injection, ADULT, 1.5 g/kg administered over 45 minutes
twice daily for IOP >35 mmHg; may administer every 8
hours; CHILD, 1.5 g/kg administered over 45 minutes
twice daily for IOP >35 mmHg; may administer every 8
hours in patients with extremely high pressure.
Dose Adjustment:
Geriatric:
Consider initiation at lower end of dosing range.
Small and/ or debilitated patients:
Consider giving 500 mg/kg.
Precautions:
WARNING: Use caution in patients with underlying
renal disease. May be used to reduce the incidence
B
of acute tubular necrosis when administered prior
to revascularization during kidney transplantation.
Carefully monitor fluid balance, electrolytes, renal function,
and vital signs during infusion to prevent fluid and
electrolyte imbalance, including circulatory overload and
tissue dehydration; Extravasation (vesicant at
concentrations >5%; ensure proper catheter or needle
position prior to and during IV infusion); fluid or
electrolyte loss (close medical supervision and dose
evaluation are required; adjust dose to avoid
dehydration); Nephrotoxicity (use caution in patients
taking other nephrotoxic agents, with sepsis or
pre­existing renal disease; maintain serum osmolality
less than 320 mOsm/L to minimize adverse effects;
discontinue if evidence of acute tubular necrosis occurs);
Cerebral edema; cardiovascular status should also be
evaluated; Lactation (use with caution).
Adverse Drug Reactions:
Common: Fluid and electrolyte imbalance including
circulatory overload and acidosis (large doses), nausea,
vomiting, thirst, headache, dizziness, chills, fever,
tachycardia, chest pain, hyponatremia, dehydration,
blurred vision, urticaria, hypotension or hypertension,
hypersensitivity reactions, extravasation (leading to
edema and skin necrosis), thrombophlebitis.
Rare: Acute renal failure (large doses)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Mannitol:
Barbiturates (hypotensive effect)
Brimonidine, topical (hypotensive effect)
MAO Inhibitors (hypotensive effect)
Nicorandil (hypotensive effect)
Pentoxifylline (antihypertensive effect)
Phosphodiesterase-5 Inhibitors (antihypertensive effect)
Prostacyclin Analogues (hypotensive effect)
Enhances therapeutic effect of the following drugs:
Alfuzosin (hypotensive effect), Other Antihypertensives
(hypotensive effect), Herbs with hypertensive properties
(hypotensive effect), Risperidone (hypotensive effect)
Increases risk of adverse or toxic effects of Mannitol:
Opioid Analgesics, Other Hypotensive Agents, MAO
Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Duloxetine (orthostatic hypotensive effect)
Levodopa (orthostatic hypotensive effect)
Reduces therapeutic effect of Mannitol:
Herbs with hypertensive properties (antihypertensive
effect)
Methylphenidate (antihypertensive effect)
79
 BLOOD AND BLOOD FORMING ORGANS

Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Aminoglycosides (nephrotoxic effect)
Obinutuzumab [withhold Mannitol 12 hours prior to
Obinutuzumab infusion until 1 hour after the end of the
B
Dose: For use as an irrigant during ocular surgery, consult
specialized references for proper use during various
ocular surgery types.
Precautions:
WARNING: Open under aseptic conditions only.

infusion] (hypotensive effect)

Rituximab (hypotensive effect)
Sodium Phosphates (nephrotoxic effect; risk of acute
phosphate nephropathy)
Administration: For IV administration. Determine
concentration and rate of administration based on
indication or severity or adjust to urine flow.
Inspect for crystals prior to administration. If crystals are
present, re-dissolve by warming solution. Use filter type
administration set for infusion solutions containing
≥20% Mannitol.
Do NOT administer until adequacy of renal function and
urine flow is established. Use 1–2 test doses to assess
renal response.
Do NOT administer electrolyte-free mannitol solutions
with blood. NEVER add to whole blood for transfusion or
administer through the same set by which blood is being
infused to prevent crenation and agglutination of RBC.
Pregnancy Category: C
ATC Code: B05BC01
IRRIGATING SOLUTIONS
INTRAOCULAR IRRIGATING
Rx SOLUTION
(BALANCED SALT SOLUTION)
Solution: 15 mL, 250 mL, and 500 mL bottle
Corneal clouding and edema; Diabetes (use with caution in
patients undergoing vitrectomy).
Adverse Drug Reactions: Corneal swelling or bullous
keratopathy (prolonged procedures), inflammatory
reactions (post-operative), corneal edema (post-
operative), corneal decompensation (post-operative)
NOTE: Use proper solution in accordance to the surgical
procedure to prevent cytotoxic effects.
Drug Interactions: No information found
Administration: Use according to standard format for each
surgical procedure. For single patient use only. This
solution contains no preservative. Discard unused
portion.
Use an administration set with an air-inlet in the plastic
spike since the bottle does not contain a separate airway
tube. Follow directions of the administration set to be
used. Remove blue flip-off cap. Clean and disinfect the
rubber stopper using a sterile alcohol wipe. Insert the
spike aseptically into the bottle through the target area
of the rubber stopper. Allow the fluid to flow and remove
air from the tubing before irrigation.
Do NOT use unless product is clear, seal is intact,
vacuum is present, and container is undamaged. Do NOT
use if product is discolored or contains a precipitate.
Pregnancy Category: C
ATC Code: B05CX10

Composition:
Sodium chloride 0.64% PERITONEAL DIALYTICS
Potassium chloride 0.075%
Calcium chloride 0.048%
Magnesium chloride
Rx PERITONEAL DIALYSIS SOLUTION
(hexahydrate) 0.03%
Sodium acetate 0.39% Solution: Sterile with 1.5%, 2.3%, 2.5% and 4.25%
Sodium citrate 0.17% dextrose, 2 L and 5 L bottle/bag
Water for injection to make 100%
Content per liter:
A sterile, isotonic, balanced salt solution for use in irrigating Glucose monohydrate 16.5 g
tissues of the eyes. (equivalent to 15.0 g glucose)
Fructose up to 0.75 g
Indications: Extraocular and intraocular irrigating solution Sodium chloride 5.786 g
during ocular surgical procedure involving the anterior Sodium (S) – lactate solution 7.85 g
chamber (e.g., cataract and glaucoma surgeries) and (equivalent to 3.925 g sodium (S) – lactate)
vitreous cavity (e.g., vitrectomy); for perfusion of the eye Calcium chloride dihydrate 183.8 mg
with an expected maximum duration of <60 minutes. Magnesium chloride hexahydrate 101.7 mg

Contraindications: No information available A sterile, nonpyrogenic solution containing electrolytes at a

concentration close to the electrolytic composition of
plasma and glucose in varying concentrations or other
suitable osmotic agents. It is used for peritoneal dialysis,

80
BLOOD AND BLOOD FORMING ORGANS

a procedure for removing toxic substances and
metabolites normally excreted by the kidneys, and for
aiding in the regulation of fluid and electrolyte balance.
Indications: Correct acid and electrolyte imbalance, and
fluid overload; remove metabolites in renal failure.
Administration: For intraperitoneal infusion only. Do NOT
administer by IV infusion.
Observe aseptic technique throughout the procedure.
The drained fluid should be inspected for the presence
of fibrin or cloudiness, which may indicate the presence

B
of peritonitis. Discard any unused solution.
Contraindications: Known hypersensitivity to corn or corn
products; abdominal sepsis; previous abdominal Prior to use, check for leaks by squeezing the inner bag
surgery; severe inflammatory bowel disease; presence of firmly. If leaks are found, do NOT use solution as sterility
abdominal devices; pre-existing severe lactic acidosis; may be impaired. Check to see that solution is clear and
uncorrectable mechanical defects that prevent effective free of foreign matter. Solutions that are cloudy,
peritoneal dialysis or increase the risk of infection; discolored, contain visible particulate matter, or show
documented loss of peritoneal function or extensive evidence of leakage should not be used or discarded.
adhesions that compromise peritoneal function.
Heating the dialysis solution to 37°C while in the over
Dose: Individualized according to clinical condition and pouch may decrease discomfort and heat loss and
based on blood chemistry results. increase urea clearance compared to solution at room
Precautions: temperature. Use only dry heat (e.g. heating pad,
Encapsulating Peritoneal Sclerosis; azotemic diabetics warming plate). Do NOT heat solutions in water or in a
(carefully monitor insulin requirements during and microwave oven due to the potential for patient injury or
following dialysis); Improper clamping or priming discomfort.
sequence may result in infusion of air into the peritoneal
cavity; Abdominal conditions, including disruption of the When introducing additives, refer to directions for use
peritoneal membrane and diaphragm by surgery or from accompanying drugs to obtain full information on
congenital anomalies or trauma until healing is additives, and use aseptic techniques. Mix thoroughly.
complete, abdominal tumors, extensive adhesions, Do NOT store.
bowel distension, undiagnosed abdominal disease,
abdominal wall infection, hernias or burns, fecal fistula, NOTE: 1,000–2,000 international units of heparin per liter
colostomy or ileostomy, frequent episodes of of solution may be added to the dialysis solution to
diverticulitis, inflammatory or ischemic bowel disease, prevent catheter blockage in patients with peritonitis, or
tense ascites, obesity, and large polycystic kidneys, or when the solution drainage contains fibrinous or
other conditions that compromise the integrity of the proteinaceous material.
abdominal wall, abdominal surface, or intra-abdominal
cavity (perform peritoneal dialysis with great care); Aortic Pregnancy Category: C
graft replacement and severe pulmonary disease
(perform peritoneal dialysis with caution); Protein, amino ATC Code: B05DA (isotonic), B05DB (hypertonic)
acids, water-soluble vitamins, and other medicines may
be lost during peritoneal dialysis and may require
replacement (carefully monitor patients to avoid over- I.V. SOLUTIONS ADDITIVES
and under-hydration); Routine periodic evaluation of
blood chemistries, serum electrolyte concentrations, and
hematologic factors, as well as other indicators of patient Rx 0.9% SODIUM CHLORIDE
status, should be performed for stable patients
undergoing maintenance peritoneal dialysis.
Inj.: 2 mL, 2.5 mL, 5 mL, 10 mL, and 20 mL ampule
50 mL, 100 mL, 200 mL, 500 mL, and 1 L bottle /
Adverse Drug Reactions: Abdominal pain, bleeding,
bag (IV infusion)
peritonitis, catheter blockage, difficulty in fluid removal,
ileus, electrolyte and fluid imbalances, hypovolemia,
Solution: 1 L bottle solution for irrigation
hypervolemia, hypertension, hypotension,
hyperphosphatemia, muscle cramping, fungal
Composition:
peritonitis, bacterial peritonitis, catheter-related
Na+ 154 mmol/L
infection, hypervolemia, fluid retention, hypokalemia,
Cl- 154 mmol/L
hyponatremia, dehydration, hypochloremia, dyspnea,
sclerosing encapsulating, peritonitis, peritoneal cloudy
A sterile, non-pyrogenic, isotonic solution of sodium chloride
effluent, vomiting, diarrhea, nausea, constipation,
in water for injection.
abdominal distension, abdominal discomfort, Stevens-
Johnson syndrome, urticaria, rash, pruritus, myalgia,
Indications: Fluid and electrolyte replacement
musculoskeletal pain, muscle spasms, generalized
therapy in conditions where water and sodium losses are
edema, pyrexia, malaise, infusion site pain, catheter-
in isotonic proportion; vehicle for IV
related complication.
drug administration; priming and rinsing fluid
for hemodialysis; lavage in surgical patients.
Drug Interactions:
NOTE: Additives may be incompatible. Consult with
Contraindication: Where the administration of
pharmacist familiar with peritoneal dialysis.
sodium or chloride could be clinically detrimental.

81
 BLOOD AND BLOOD FORMING ORGANS

Dose:
NOTE: Individualize fluid administration based on calculated Rx 5% DEXTROSE IN WATER
maintenance or replacement fluid requirements.
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion and
Fluid and electrolyte replacement, by IV infusion, as vehicle for IV medications)
ADULT and CHILD, determined based on clinical and,
B

whenever possible, electrolyte A sterile, non-pyrogenic solution of dextrose that is

monitoring. See under Sodium Chloride.
Dose of sodium chloride is dependent on degree of sodium
depletion (i.e., moderately severe hyponatremia where
serum sodium is between 125-129 mmol/L or profound
hyponatremia where serum sodium is <125 mmol/L); on
severity of symptoms (i.e., moderately or severely
symptomatic); and on time of development of
hyponatremia (acute, where hyponatremia is
documented to exist <48hrs).
IMPORTANT NOTE: Sodium deficit must be corrected
gradually in stages. Avoid overtly rapid correction to
prevent development of Osmotic Demyelination
Syndrome (previously named Central Pontine
Myelinosis). The rate of correction of hyponatremia
should not be more than 10 mmol/L (or 10 mEq/L) in
24 hours, or 18 mmol/L (or 10 mEq/L) in 48 hours.
Dose Adjustment:
Renal Impairment:
Select doses with care due to an increased risk of adverse
effects.
Precautions:
WARNING: Mix infusion solutions thoroughly after adding
concentrated electrolytes to avoid possible toxicity.
Impaired renal function, cardiac failure, hypertension,
peripheral and pulmonary edema, and toxemia during
pregnancy (restrict intake); Cardiac, cirrhotic, or
nephrotic patients.
Adverse Drug Reactions: Air embolization, febrile response,
local tenderness, tissue necrosis or infection at the site
of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation, hypervolemia
NOTE: May occur because of the solution, added drugs or
the technique of reconstitution or administration.
Rare: Edema, sodium accumulation
Drug Interactions:
Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Corticosteroids
Administration: For single use only. Contamination may lead
to injury, illness or death.
Inspect visually for particulate matter and discoloration
prior to administration.
indicated for use in adults and children as a
source of calories and water of hydration.
Indications: Replacement therapy in conditions
mainly due to water losses; elevated serum sodium; IV
infusion to keep vein open for IV drug administration.
Contraindication: Known hypersensitivity to corn
or corn products.
Dose:
For replacement therapy, by IV infusion, depending
on requirement, with average dose 1,000–2,000
mL/day (flow rate up to 120 drops/minute, 360
mL/hour).
Dose Adjustment:
Renal Impairment:
Select doses with care due to an increased risk of adverse
effects.
Precautions:
WARNING: Mix infusion solutions thoroughly after adding
concentrated electrolytes to avoid possible toxicity.
Fluid and/or solute overload; prolonged infusion of isotonic
or hypotonic dextrose in water; Hyponatremia; fluid
retention; DM or carbohydrate intolerance (use with
caution); Contains aluminum which may be toxic,
particularly in those with impaired kidney function, e.g.,
premature neonates.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis
extending from the sit
e of injection, extravasation, hypervolemia.
NOTE: may occur because of the solution or the technique
during administration.
Drug Interactions: No information found
Administration: Adjust rate of administration according to
tolerance. Too rapid infusion may cause local pain and
venous irritation. Use largest peripheral vein and a small-
bore needle.
Inspect visually for particulate matter and discoloration
prior to administration.
Pregnancy Category: C
ATC Code: Not available

Pregnancy Category: C

ATC Code: B05XA03

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BLOOD AND BLOOD FORMING ORGANS
Rx 10% DEXTROSE IN WATER
Inj.: 250 mL, 500 mL, and 1 L bottle / bag (IV infusion)
3 mL ampule (as solvent)
A sterile, non-pyrogenic, hypertonic solution of Dextrose,
USP in water for injection for intravenous administration
after appropriate admixture or dilution.
Indications: Source of water and calories; parenteral
nutrient, indicated as a caloric component in a
parenteral nutrition regimen; used with an appropriate
protein (nitrogen) source in the prevention of nitrogen
loss or in the treatment of negative nitrogen balance in
patients where:
(1) alimentary tract cannot or should not be used,
(2) GI absorption of protein is impaired, or
(3) metabolic requirements for protein are substantially
increased, as with extensive burns.
Contraindications: Intracranial or intraspinal hemorrhage;
severe dehydration; anuric; hepatic coma.
Dose: Dose is usually dependent upon the age, weight, and
clinical condition of the patient, as well as laboratory
determinations.
NOTE: Use with caution in infants of diabetic mothers,
except as may be indicated in hypoglycemic neonates.
Precautions:
WARNING: Contains aluminum that may be toxic. May
reach toxic aluminum levels with prolonged use if
kidney function is impaired.
Administration by central venous catheter should
be used only by those familiar with this technique
and its complications.
Overt or subclinical diabetes mellitus or carbohydrate
intolerance (use with caution); hyperglycemia and
glycosuria (slow the infusion rate to minimize these
conditions; monitor blood and urine glucose); vitamin B-
complex deficiency; Acute ischemic stroke (do not use
after acute ischemic strokes); cardiac insufficiency (use
with caution to avoid circulatory overload); Hypokalemia;
IV injections can cause fluid and/or solute overload
resulting in dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema;
Clinical evaluation and periodic laboratory
determinations are necessary to monitor changes in fluid
balance, electrolyte concentrations, and acid-base
balance during prolonged parenteral therapy, or
whenever the condition of the patient warrants such
evaluation; Elderly and children (administer with
caution); premature neonates.
Adverse Drug Reactions: Febrile response, infection at the
site of injection, venous thrombosis or phlebitis
extending from the site of injection, extravasation,
hypervolemia [NOTE: May occur because of the solution or the
technique of administration].
Hyperosmolar syndrome (excessively rapid
administration), hypovolemia, dehydration, mental
confusion, and/or loss of consciousness, diuresis (too
rapid infusion), hyperglycemia (too rapid infusion),
glycosuria (too rapid infusion), hyperosmolar coma (too
rapid infusion)
B
NOTE: If an adverse reaction occurs, discontinue the
infusion, evaluate the patient, institute appropriate
therapeutic countermeasures and save the remainder of
the fluid for examination, if deemed necessary.
Drug Interactions:
Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Corticosteroids
NOTE: Additives may be incompatible. Consult a pharmacist.
If additives are to be introduced, use aseptic technique.
Administration: For IV administration only. Contains no
bacteriostat, antimicrobial agent or added buffer. For
use only as a single-dose injection following admixture or
dilution.
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT administer unless
solution is clear and seal is intact.
Prior to administration, dilute to a concentration which,
when administered with an amino acid (nitrogen) source,
will result in an appropriate calorie-to-gram nitrogen
ratio, and which has an osmolarity consistent with the
route of administration.
NOTE: Unless appropriately diluted, hypertonic dextrose
infusion into a peripheral vein may result in vein
irritation, vein damage, and thrombosis. Strongly
hypertonic nutrient solutions should be administered
through an indwelling IV catheter with the tip located in
a large central vein such as the superior vena cava.
Use a final filter during administration. Slowly inject the
solution at a rate not exceeding 0.5 g/kg body weight per
hour.
NOTE: About 95% of the dextrose is retained when infused
at a rate of 0.8 g/kg/hour.
Do NOT administer by SC or IM route.
Do NOT administer simultaneously with blood through
the same administration set because of the possibility of
pseudo-agglutination or hemolysis.
NOTE: All injections in plastic containers are intended for IV
administration using sterile equipment. Replace IV
administration apparatus at least once every 24 hours.
Interruption or rapid cessation of hypertonic dextrose
therapy may result in a hypoglycemic reaction. Titrate
with a dilute dextrose solution until the patient has
reached glucose equilibrium.
Pregnancy Category: C
83

ATC Code: Not available
Rx CALCIUM GLUCONATE
B
Inj.: 10%, 10 mL ampule/vial (IV)
10%, 20 mL and 25 mL bottle (IV)
The calcium salt of gluconic acid, produced as an oxidation
product of glucose. Calcium is an essential element for
regulating the excitation threshold of nerves and
muscles, for blood clotting mechanisms, cardiac function
(rhythm, tonicity, contractility), maintenance of renal
function, for body skeleton and teeth, as well as in
regulating storage and release of neurotransmitters and
hormones, regulating amino acid uptake and absorption
of vitamin B12, gastrin secretion, and in maintaining
structural and functional integrity of cell membranes and
capillaries. Calcium gluconate increases cardiac muscle
tone and force of systolic contractions (positive inotropic
effect).
Indications: Treatment of conditions arising from calcium
deficiencies such as hypocalcemic tetany, hypocalcemia
related to hypoparathyroidism, and hypocalcemia due to
rapid growth or pregnancy; to antagonize cardiac toxicity
in patients not receiving digitalis.
Contraindications: Ventricular fibrillation; metastatic bone
disease; injection into myocardium; renal calculi;
hypercalcemia and predisposition to hypercalcemia (e.g.,
hyperparathyroidism, certain malignancies); above
normal serum calcium levels; concomitant
administration of ceftriaxone in neonates.
Dose: Dose depends on the individual requirements of the
patient.
NOTE: 1 g calcium gluconate = 90 mg (4.5 mEq, 9.3%)
elemental calcium.
Severe hypermagnesemia, severe hyperkalemia, by IV
administration, ADULT, 10 mL of 10% solution over 2
minutes, repeated every 10 minutes if needed.
Hypermagnesemia, by IV administration, ADULT, 1,000–
2,000 mg (10–20 mL) single dose at a rate not
exceeding 0.5–2 mL/min; CHILD and NEONATE, 0.5
mL/kg of 10% solution single dose.
Hyperkalemia, by IV administration, ADULT, 500 to 3,000
mg (5–30 mL) single dose at a rate not to exceed 0.5–2
mL/min; CHILD and NEONATE, 0.5 mL/kg of 10%
solution single dose.
Hypocalcemic tetany, severe acute hypocalcemia, by IV
administration, ADULT, 2.25 mmoL over 10 minutes by
slow IV injection, followed by 58–77 mL 10% solution in
0.5–1 L of 5% dextrose solution as continuous IV
infusion; CHILD and NEONATE, 0.5 mL/kg of 10%
solution as a single dose (maximum, 20 mL of 10%
solution).
Hypocalcemia secondary to citrated blood infusion, by IV
administration, ADULT, 0.45 mEq elemental calcium for
each 100 mL citrated blood infused
Tetany, by IV administration, CHILD and INFANT, 100–200
mg/kg per dose over 5–10 minutes; may repeat after 6
84
BLOOD AND BLOOD FORMING ORGANS
hours or follow with an infusion (maximum dose, 500
mg/kg daily).
Daily maintenance calcium, by IV administration, INFANT
and CHILD ≤25 kg, 1–2 mEq/kg daily, CHILD 25–45 kg,
0.5–1.5 mEq/kg daily; CHILD >45 kg, 0.2–0.3 mEq/kg
daily or 10–20 mEq daily.
Precautions:
WARNING: May cause asystole when given by rapid IV
administration.
Cardiovascular effects (monitor cardiac rate); Concomitant
digitalis therapy; Sarcoidosis or renal or cardiac disease
(use with caution); history of lithiasis; renal impairment;
Immobilized patients (use with caution); Premature
neonates; Lactation (use with caution).
NOTE: Supersaturated solutions are prone to precipitation.
If crystallization has occurred, warm in a 60°C water
bath for 15–30 minutes with occasional shaking. Cool to
body temperature before use.
Adverse Drug Reactions:
Common: Tingling sensation, sensations of heat waves
(peripheral vasodilation), fainting, constipation, chalky
taste, increased gastric acid secretion, hypotension,
bradycardia, cardiac arrhythmias, cardiac arrest, pain
and burning at IV site, severe venous thrombosis,
extravasation (with necrosis and sloughing)
Drug Interactions:
Monitor closely with:
Decreases absorption of the following drugs:
Magnesium, Quinolone
Avoid concomitant use with:
Decreases therapeutic effect of the following drugs:
Tetracycline (forms Tetracycline-Calcium complex),
Calcium Channel Blockers, e.g., Verapamil
Increases risk of adverse or toxic effects of the following
drugs:
Ceftriaxone Sodium Injection (may form precipitates),
Digitalis Glycosides e.g digoxin (arrhythmias)
Administration: For IV use only. No preservative added.
Discard unused portion.
Inspect visually for particulate matter and discoloration.
Use only if solution is clear and seal intact.
For direct IV administration, administer undiluted at a
rate of 0.5 mL or a fraction thereof over 1 minute. Do
NOT exceed 2 mL/minute.
For intermittent or continuous IV administration,
administer diluted in 1,000 mL of NS slowly. Do NOT
exceed 200 mg/minute, through a small-bore needle
into a large vein to avoid possibility of extravasation and
resultant necrosis.
Do NOT administer by SC or IM injection as this may
cause severe necrosis and sloughing. IM injection may
cause local necrosis and abscess formation.
BLOOD AND BLOOD FORMING ORGANS

NOTE: Injection should be stopped if patient complains of LACTATED RINGER’S SOLUTION

any discomfort. Patient should be advised to remain in Rx
(RINGER’S LACTATE)
bed for at least 15–30 minutes following injection,
depending on response.
Inj.: 500 mL and 1 L bottle / bag (IV infusion)
Avoid scalp veins in children. Avoid rapid infusion. High
Composition:

B
concentrations of calcium suddenly reaching the heart
Na+ 130 mmol/L
can cause fatal cardiac arrest.
K+ 4 mmol/L
Ca ++ 1.22 – 1.5 mmol/L
Pregnancy Category: B; C
Cl- 109 mmol/L
Lactate 28 mmol/L
ATC Code: Not available
A sterile, non-pyrogenic, lactate-containing solution, which
serves as a source of hydration and electrolytes and
produces a metabolic alkalinizing effect.
Rx GLUCOSE (DEXTROSE)
Indications: Fluid and electrolyte replacement
therapy in the presence of acidosis; IV infusion in the
Inj.: 50%, 50 mL vial (IV) initial management of the injured or wounded;
50%, 10 mL and 20 mL ampule (IV) hypovolemic shock
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV)
Contraindications: Metabolic and respiratory
A sterile, hypertonic solution of glucose, which provides alkalosis; hypocalcemia; hypochlorhydria; lactic acidosis;
calories in a minimal volume of water and is used in anuria; oliguria; hyperkalemia; increased BUN; cardiac
restoring blood glucose concentrations in the treatment failure.
of hypoglycemia.
Dose: Dose is dependent on age, weight, and
Indication: Fluid replacement without significant electrolyte clinical condition of patient.
deficit.
Dose Adjustment:
Contraindications: Hyperglycemia; diabetic coma; use of Renal Impairment:
hyperosmotic solutions in patients with anuria; glucose- Select dose with care due to an increased
galactose malabsorption syndrome; dehydrated patients risk of adverse effects, e.g., sodium and potassium
with delirium; intracranial or intraspinal hemorrhage; retention.
following ischemic attacks.
Precautions:
Dose:
Fluid replacement, by IV infusion, ADULT and CHILD, WARNING: Mix infusion solutions thoroughly after
determine dose based on clinical data and, whenever adding concentrated electrolytes to avoid possible
possible, electrolyte monitoring. toxicity.

Administration: Administer via a large vein (e.g., into a Avoid simultaneous administration with blood;
secure IV cannula in an antecubital vein). hyperkalemia; hypernatremia; hyperchloremia; cardiac
diseases; alkalosis; increased blood glucose; hepatic
Inspect visually for particulate matter and discoloration. impairment; conditions which may cause potassium or
Use only if solution is clear and seal intact. sodium retention, fluid overload or edema, e.g., renal
impairment, hypervolemia, overhydration; There is risk
See Glucose (Dextrose) under Antihypoglycemics in Chapter for hyponatremia due to lower sodium
01: Alimentary Tract and Metabolism for other content compared to 0.9% NaCl or Balanced
information. Multiple Replacement Solution.
Pregnancy Category: C Adverse Drug Reactions:
Less Common: Pain and inflammation at the injection site,
ATC Code: Not available phlebitis, tissue necrosis, venous irritation, venous
thrombosis.
Rare: Angioedema, anxiety, blood pressure decreased,
bronchospasm, chest discomfort and pain, cough,
decreased heart rate, dysgeusia, dyspnea, edema,
erythema, flushing, headache, hyperkalemia,
hypersensitivity reactions, including anaphylactic and
anaphylactoid reactions; hypesthesia, nausea,
paresthesia, pruritus, pyrexia, rash, respiratory distress,
tachycardia, throat irritation, urticaria.

85

Drug Interactions:
Monitor closely with:
Alters renal clearance of the following drugs:
Increased renal clearance: Acidic Drugs, e.g., Salicylates,
Barbiturates; Lithium
B
Decreased renal clearance: Basic Drugs, e.g.,
Sympathomimetics
Increases risk of adverse or toxic effects of the following
drugs:
Hyperkalemia: Drugs which can cause hyperkalemia,
e.g., Potassium-sparing Diuretics, Angiotensin II
Receptor Antagonists, ACE Inhibitors,
Immunosuppressants
Hypercalcemia; Thiazide Diuretics, Vitamin D
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Ceftriaxone (Ceftriaxone-Calcium salt precipitation in the
bloodstream)
Administration: For IV administration.
Inspect visually for particulate matter and discoloration.
Use only if solution is clear and seal intact.
Pregnancy Category: C
ATC Code: B05XA30
Rx LIPIDS
Inj.: 10%, 100 mL, 200 mL, and 500 mL bottle (IV
infusion)
20%, 100 mL, 250 mL, and 500 mL bottle (IV
infusion)
An isotonic nutrient containing emulsified fat particles used
as a source of calories and essential fatty acids.
Indications: Parenteral nutrition; prevention of essential
fatty acid deficiency; source of essential fatty acids and
additional calories in high-density form to patients
receiving prolonged TPN therapy who cannot tolerate
high dextrose concentrations or when fluid intake must
be restricted as in renal failure, CHF, and ascites.
Contraindications: Any condition that disturbs normal fat
metabolism (e.g., pathologic hyperlipemia, lipoid
nephrosis, acute pancreatitis with hyperlipemia); bone
marrow dyscrasias; allergy to egg yolk phospholipids.
Dose:
Prevention of essential fatty acid deficiency, by IV infusion,
ADULT, 500 mL 10% solution or 250 mL 20% solution
infused over 8–12 hours twice a week (maximum rate,
100 mL/hour); CHILD, 0.5–1 g/kg infused slowly over 8–
12 hours twice a week (maximum dose, 3–4 g/kg daily;
maximum rate, 0.25 g/kg per hour).
Calorie source in fluid-restricted patients, by IV infusion,
ADULT, up to 2.5 g/kg daily (60% of nonprotein calories)
86
BLOOD AND BLOOD FORMING ORGANS
infused over at least 8–12 hours (maximum rate, 100
mL per hour); CHILD, up to 4 g/kg daily (60% of
nonprotein calories) infused over at least 8–12 hours
(maximum rate, 100 mL/hour); PREMATURE NEONATE,
initially 0.25–0.5 g/kg daily; increase by 0.25–0.5 g/kg
daily (maximum dose, 3–4 g/kg daily; maximum rate,
0.15 g/kg per hour).
Dose Adjustment:
Renal Impairment:
Normal renal function required. Reduce dose.
Precautions:
Jaundice (use with caution); Pulmonary disease; Liver
disease; Anemia; blood coagulation disorders;
thrombocytopenia; Diabetes mellitus; History of gastric
ulcer or when there is any danger of fat embolism; Renal
impairment; Premature neonates (use with caution).
Adverse Drug Reactions:
Common: Hypersensitivity reactions, irritation at infusion
site, thrombocytopenia (neonates), hypercoagulability,
increased liver function tests (transient), hyperlipidemia,
sepsis, cholestatic jaundice, hepatomegaly, kernicterus
Rare: Shock
Drug Interactions: No information available
Administration: Do NOT use if oil appears to be separating
out of the emulsion.
Pregnancy Category: B (Soyacal®); C (others)
ATC Code: Not available
Rx MAGNESIUM SULFATE
Inj.: 250 mg/mL, 2 mL and 10 mL ampule (IM, IV) and 10
mL, 20 mL and 50 mL vial (IV) (as heptahydrate)
500 mg/mL, 2 mL and 10 mL ampule (IM, IV) (as
heptahydrate)
A sterile preparation that contains magnesium as
heptahydrate.
Indications: For parenteral nutrition; treatment and
prevention of hypomagnesemia; pediatric acute
nephritis; treatment of cardiac arrhythmias (VT/VF)
caused by hypomagnesemia; prevention and control of
seizures in women with severe preeclampsia.
Contraindications: Heart block; myocardial infarction;
hypermagnesemia; deranged
renal function; myasthenia gravis; IV use for
pre­eclampsia or eclampsia during the 2 hours prior to
delivery.
Dose:
NOTE: Individualize dose based on patient requirement and
response. Discontinue as soon as desired response is
obtained.
Total Parenteral Nutrition, by IV injection, ADULT, 0.5 to 3 g
daily.
BLOOD AND BLOOD FORMING ORGANS
Hypomagnesemia seizures, mild, by IV or IM injection,
ADULT, 1 g every 6 hours for 4 doses.
Hypomagnesemia seizures, mild, by IV or IM injection,
ADULT, 250 mg/kg infused over 4 hours.
Hypomagnesemia seizures, by IV injection, CHILD, 20–100
mg/kg every 4–6 hours, or as needed.
Hypomagnesemia seizures, severe, by IV or IM injection,
ADULT, 1–2 g/hour for 3–6 hours, then 0.5–1 g/hour as
needed based on serum magnesium levels.
Dose Adjustment:
Geriatric and Renal Impairment:
Reduce dose. Up to 50% of an IV dose may be eliminated in
the urine.
For patients with renal disease, Do NOT exceed 20 g every
48 hours for patients with renal disease.
Precautions:
WARNING: Toxicity causes loss of deep tendon
reflexes, followed by respiratory depression and
ultimately respiratory arrest. If deep tendon
reflexes are absent, withhold further doses until
reflexes return. Toxicity can be reversed with
calcium gluconate.
Magnesium is excreted by the kidney. Monitor
regularly serum levels in women with oliguria (urine
output <100 mL/4 hours). If repeated seizures
occur despite magnesium, other pre-hospital
options include administering diazepam.
Myasthenia gravis or other neuromuscular disease (use
with extreme caution); Renal impairment (use with
caution); Electrolyte abnormalities; Magnesium toxicity;
Pregnancy (monitor mother and fetus closely; do not use
for longer than 5–7 days to prevent adverse fetal
events).
Adverse Drug Reactions:
Common: Flushing, nausea, vomiting
Less Common: Dizziness, drowsiness, headache, thirst
Rare: Arrhythmias, cardiac arrest, coma, confusion,
loss of tendon reflexes, muscle weakness,
respiratory depression
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Magnesium Sulfate:
Aminoglycosides (additive neuromuscular blocking
effect)
Enhances therapeutic effect of the following drugs:
Calcium Channel Blockers (hypotensive effect)
CNS Depressants, e.g., Barbiturates, Opiates, General
Aesthetics (CNS depressant effects)
Neuromuscular Blocking Agents, e.g., Tubocurarine,
Vecuronium, Succinylcholine (neuromuscular blocking
effect)
Increases risk of adverse or toxic effects of Magnesium
Sulfate:
Calcium Channel Blockers
Avoid concomitant use with:
Decreases absorption of Magnesium Sulfate:
Alpha-Lipoic Acid
Decreases absorption of the following drugs:
Alpha-Lipoic Acid, Multivitamins / Fluoride with ADE
B
(fluoride absorption) [separate administration by at least
1 hour]
Decreases serum concentration of the following drugs:
Bisphosphonate Derivatives [except Pamidronate,
Zoledronic Acid], Deferiprone, Dolutegravir,
Eltrombopag, Gabapentin, Levothyroxine, Multivitamins
/ Fluoride with ADE, Quinolone Antibiotics, Raltegravir
Enhances therapeutic effect of the following drugs:
Gabapentin (CNS depressant effect)
Increases serum concentration of Magnesium Sulfate:
Alfacalcidol, Calcitriol (systemic)
Administration: Administer at a concentration not exceeding
20%. Dilute according to manufacturer’s instructions.
For IM route, solutions may need dilution prior to
administration. 25% or 50% for adults or ≤20% for
children.
For IV route, solutions must be diluted to ≤20% for IV
infusion and may be administered by IV push, IVPB, or
continuous IV infusion.
For IV push, dilute first and do not administer faster than
150 mg/minute.
May be administered over 1–2 minutes in patients with
persistent pulseless VT or VF with known
hypomagnesemia. Administer over 15 minutes in
patients with torsade de pointes.
Maximum rate of infusion is 1 g/hour in asymptomatic
patients. For doses <6 g, infuse over 8–12 hours. For
larger doses, infuse over 24 hours.
If patient is severely symptomatic or has conditions such
as preeclampsia or eclampsia, more aggressive therapy
(≤4 g over 4-5 minutes) may be required.
Pregnancy Category: A
ATC Code: B05XA05
Rx POTASSIUM CHLORIDE
Oral: 600 mg tablet
750 mg durules (equiv. to approximately 10 mEq
potassium)
1 mmol/mL syrup, 30 mL and 60 mL
Inj.: 2 mEq/mL, 2 mL and 5 mL ampule (IV infusion)
2 mEq/mL, 10 mL and 20 mL vial (IV infusion)
A sterile preparation that contains potassium chloride,
utilized for the treatment of hypokalemia.
87

Indications: Prophylaxis and treatment of potassium
deficiency states; for parenteral nutrition.
Contraindications: Any disease or condition in which high
potassium levels may occur through potassium retention
or other processes (e.g., acute dehydration,
B
adrenocortical insufficiency); adynamia episodica
hereditaria (periodic loss of strength or weakness);
anuria; azotemia; crush syndrome; heat cramps;
hyperkalemia from any cause; oliguria; patients taking
digoxin with severe or complete heart block;
postoperative oliguria; renal failure; severe hemolytic
reactions.
Dose:
NOTE: Dose and rate of administration are dependent on specific
patient condition.
IV additive solution, by IV injection, ADULT, 40–100 mEq/L
or more daily (maximum, 150 mEq/L daily); maintenance
dose, 20–30 mEq/L.
Replacement in hypokalemia, IV additive solution, by IV
injection, CHILD and INFANT, 40–50 mEq/L.
Severe acute hypokalemia, by IV injection, ADULT,
serum potassium level >2.5 mEq/L, 40 mEq/L for not
more than 10 mEq/hour (maximum dose, 200 mEq/24
hours);
serum potassium level <2 mEq/L, 40 mEq/L at a rate of
up to 40 mEq/hr (maximum dose, 400 mEq/24 hours).
Dose Adjustment:
Geriatric:
Initiate at the lower end of the dosing range based on
potential for decreased organ function and concomitant
disease or drug therapy.
Renal Impairment:
Reduce dose. Do NOT use in patients with kidney failure.
Precautions:
WARNING: Concentrated solutions must be diluted before
administration. Direct injection of concentrated solutions
can be instantly fatal. Too rapid infusion may cause fatal
hyperkalemia. Rapid IV infusion or bolus may cause fatal
arrhythmia and cardiac arrest.
Impaired renal function or adrenal insufficiency; severe
hepatic insufficiency and metabolic or respiratory
alkalosis (use with caution); cardiac disease (cardiac
monitoring recommended); Potassium depletion (treat
cause of potassium depletion in addition to giving
potassium); Alkalizing potassium, e.g., acetate, citrate
(preferred for potassium-deficient patients with renal
tubular acidosis); May contain aluminum (may reach
toxic levels in impaired kidney function); Administration
of IV solutions can cause fluid and/or solute overload,
resulting in dilution of serum electrolyte concentrations,
overhydration, congested states, or pulmonary edema;
Premature neonates.
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea, nausea, vomiting,
extravasation, fever, hyperkalemia, hypervolemia,
infection or pain at the site of injection, phlebitis, venous
thrombosis.
88
BLOOD AND BLOOD FORMING ORGANS
Potassium intoxication: Areflexia (absence of reflexes),
cardiac arrest, cardiac arrhythmias, ECG abnormalities,
heart block, hypotension, mental confusion, muscular or
respiratory paralysis, paresthesias of the extremities,
weakness; progression of side effects may cause death.
Potassium deficit: Disruption of neuromuscular function,
intestinal ileus, dilatation.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Hyperkalemia: ACE Inhibitors, e.g., Captopril, Enalapril,
Lisinopril; Angiotensin Receptor Blockers, e.g., Losartan,
Valsartan; Potassium-sparing Diuretics, e.g.,
Spironolactone
Administration: For IV infusion only. Infuse at a rate not
exceeding 10 mEq/hour. Adult patients with severe
potassium depletion may be able to tolerate 20
mEq/hour.
Each individual dose must be diluted in a larger volume
of suitable IV solution and given as an infusion. Add the
desired amount to 100–1,000 mL IV solution. 40 mEq/L
is preferred to lessen irritation to veins. Usual maximum
concentration is 80 mEq/1000 mL.
After adding potassium chloride, invert bag or bottle
several times to ensure even distribution and to avoid
layering of potassium. NEVER add potassium chloride to
an IV bag or bottle, which is hanging. Use only clear
solutions.
In severe hypokalemia, solutions without dextrose are
preferred.
NEVER administer by IV push or in concentrated
amounts by any route.
Take extreme care to prevent extravasation and
infiltration. At first sign, discontinue infusion and select
another site.
NOTE: Potassium phosphate is preferred for specific
intracellular deficiency not caused by alkalosis.
Pregnancy Category: C
ATC Code: B05XA01
Rx POTASSIUM PHOSPHATE
Inj.: 224 mg monobasic potassium phosphate equivalent
to 3 mmol phosphorus and 4.4 mEq potassium per
236 mg dibasic-potassium phosphate anhydrous per
mL in 5 mL vial (IV)
A sterile preparation that contains potassium phosphate,
utilized for the treatment of hypophosphatemia.
Indication: For parenteral nutrition to prevent or correct
hypophosphatemia in patients with restricted or no oral
intake.
BLOOD AND BLOOD FORMING ORGANS
Contraindications: Any disease with high phosphate or low
calcium levels; hyperkalemia; severe renal impairment;
infected phosphate renal calculi.
Dose:
NOTE: Dose is dependent on individual needs of the patient.
TPN, by IV injection, ADULT and CHILD, 10–15 mM (310–
465 mg) of phosphorus/liter of TPN solution to maintain
normal serum phosphate (1 mM equals 31 mg); INFANT,
1.5–2 mM/kg daily.
Acute hypophosphatemia, by IV injection, ADULT and CHILD,
0.08–0.32 mM/kg as loading dose, equally distributed
over 6 hour; maintain pediatric patients with 0.5–1.5
mM/kg every 24 hours and adults with 48.4–64.5 mM
every 24 hours.
Dose Adjustment:
Geriatric:
Initiate doses at the lower end of the dosing range based on
the potential for decreased organ function and
concomitant disease or drug therapy.
Precautions:
Rapid infusion may cause phosphate, sodium, or potassium
intoxication. Serum calcium may be reduced, rapidly
causing hypocalcemic tetany; Cardiac disease, renal
disease, and digitalized patients (use with caution).
Adverse Drug Reactions:
Common: Hyperphosphatemia, hypocalcemia, ectopic
calcification, hypotension, organ damage, acute renal
failure, tissue calcification, nausea, vomiting, diarrhea,
abdominal pain, flatulence, bradycardia, hyperkalemia,
weakness, dyspnea.
Potentially fatal: Acute renal failure, arrhythmia, chest
pain, decreased urine output, dyspnea, edema, mental
confusion, paralysis, paresthesias, phlebitis, tetany.
Drug Interactions:
Monitor closely with:
Alters absorption of the following drugs:
Aluminum, Calcium, or Magnesium Salts (decreased
absorption due to phosphate binding)
Increases risk of adverse or toxic effects of the following
drugs:
Hyperkalemia: ACE Inhibitors, e.g., Enalapril; Potassium-
sparing Diuretics
Hyperphosphatemia: Vitamin D (hyperphosphatemia)
Increases therapeutic effect of Digitalis
Administration: For IV infusion. Infuse slowly. Equally
distribute desired dose over 6 hours. May also
administer up to 15 mM over 2 hours, up to 30 mM over
4 hours, and up to 45 mM over 6 hours.
Dilute in a larger volume of suitable IV solution prior to
administration. Soluble in most commonly used IV
solutions except protein hydrolysate. Mix thoroughly.
When adding an additive, consult a pharmacist. Specific
conditions may apply. TPN solutions requiring the
addition of phosphates and calcium salts must be mixed
by the pharmacist to avoid a precipitate of calcium
phosphate.
NOTE: Rapid infusion may cause phosphate or potassium
intoxication. Serum calcium may be reduced rapidly,
causing hypocalcemic tetany.
B
Potassium phosphate will be further limited by the
maximum rate for potassium. Consider potassium
content.
Pregnancy Category: C
ATC Code: B05XA06
Rx SODIUM BICARBONATE
Oral: 325 mg and 650 mg tablet
Inj.: 1 mEq/mL, 10 mL vial (pediatric), 50 mL and 100 mL
ampule / vial (adult) (IV infusion)
A sterile preparation that contains sodium bicarbonate,
utilized as an alkalizing agent.
Indications: Systemic alkalinizer to correct metabolic
acidosis; buffer for acidic parenteral solutions to prevent
acidosis; for parenteral nutrition.
Contraindications: Diuretics known to produce
hypochloremic alkalosis; edema; hypertension;
hypocalcemia; hypochloremia; hypernatremia; impaired
renal function; metabolic alkalosis; respiratory alkalosis
or acidosis; any situation where administration of sodium
could be clinically detrimental.
Dose:
NOTE: Doses are adjusted according to pH, PaCO2,
calculated base deficit, clinical response, and fluid
limitations of the patient.
Cardiac arrest, by IV injection, ADULT, initially 1 mEq/kg of
7.5% or 8.4% solution initially, then 0.5 mEq/kg every 10
minutes, depending on arterial blood gas determinations
(8.4% solutions contain 50 mEq/50 mL), given over 1–2
minutes; CHILD, 0.5–1 mEq/kg of 4.2% solution every
10 minutes, depending on arterial blood gas
determinations, given over 1–2 minutes.
Metabolic acidosis, by IV infusion, ADULT, 2–5 mEq/kg over
4–8 hours; CHILD and INFANT, 2 to 3 mEq/kg daily of
4.2% solution over 4–8 hours.
Amount (mEq NaHCO3) = (base deficit)(0.3)(BW in kg)
Amount (mEq NaHCO3)=(27 mEq HCO3/L)(0.3)(BW in kg)
Dose Adjustment:
Geriatric, Renal and Hepatic Impairment:
Dose adjustment may be required.
Administration: Give 4.2% (0.5 mEq/mL) and 5% (0.595
mEq/mL) NaHCO3 solutions undiluted. Dilute 7.5%
(0.892 mEq/mL) and 8.4% (1 mEq/mL) solutions with
compatible IV solutions. Dilute to at least 4.2% for infants
and children. Give a bolus dose only in emergency
situations. The usual rate is 2–5 mEq/kg over 4–8 hours.
89

Do not exceed 50 mEq/hour. Stop infusion immediately
if extravasation occurs. Flush IV line thoroughly before
and after administration.
WARNING: Rapid or excessive administration may
produce alkalosis, hypokalemia, and hypocalcemia.
B
Cardiac arrhythmias may result from an intracellular
shift of potassium. Many other complications may
arise from electrolyte imbalance.
See Sodium Bicarbonate under Antacids in Chapter 1:
Alimentary Tract and Metabolism for other information.
Pregnancy Category: C
ATC Code: B05XA02
Rx SODIUM CHLORIDE
Inj.: 2.5 mEq/mL, 20 mL and 50 mL vial
A sterile, non-pyrogenic, concentrated solution of
sodium chloride administered to replenish electrolytes.
Indication: Hyponatremia with overt manifestations.
Contraindications: Where the administration of
sodium or chloride could be clinically detrimental (e.g.,
hypernatremia); fluid retention; hypertension; CHF.
Dose: Dose is dependent on degree of sodium depletion
(i.e., moderately severe hyponatremia where serum
sodium is between 125–129 mmol/L or profound
hyponatremia where serum sodium is <125 mmol/L); on
severity of symptoms (i.e., moderately or severely
symptomatic); and on time of development of
hyponatremia (acute, where hyponatremia is
documented to exist <48hrs).
IMPORTANT NOTE: Sodium deficit must be corrected
gradually in stages. Avoid overtly rapid correction to
prevent development of Osmotic Demyelination
Syndrome (previously named Central Pontine
Myelinosis). The rate of correction of hyponatremia
should not be more than 10 mmol/L (or 10 mEq/L) in 24
hours, or 18 mmol/L (or 10 mEq/L) in 48 hours.
Dose Adjustment:
Renal Impairment:
Select doses with caution due to potential to
result in sodium retention and increased risk
of adverse effects.
Precautions:
WARNING: Contains aluminum, which may be toxic. May
reach toxic aluminum levels with prolonged use,
especially if kidney function is impaired.
Monitor fluid balance, electrolyte concentration, and
acid-base balance; observe for hypernatremia, water
retention and pulmonary edema; restrict in patients with
renal insufficiency or failure, cardiac failure,
90
BLOOD AND BLOOD FORMING ORGANS
hypertension, peripheral and pulmonary edema, or
toxemia of pregnancy; Seizures or neurologic deficit
(requires aggressive therapy); IV administration can
cause fluid and/ or solute overloading resulting in
dilution of other electrolyte concentration, overhydration,
congested states or pulmonary edema; excessive
administration of potassium-free solutions may result in
significant hypokalemia; Premature neonates.
Adverse Drug Reactions: Air embolization, febrile response,
local tenderness, tissue necrosis or infection at the site
of injection, venous thrombosis or phlebitis extending
from the site of injection, extravasation [NOTE: May occur
because of the solution, added drugs or the technique of
reconstitution or administration].
Rare: Edema, sodium accumulation
Drug Interactions:
Monitor closely with:
Increases risk of hypertension and edema of the following
drugs due to sodium and water retention:
Corticosteroids e.g. Prednisone
Administration: Administer based on calculated dose
requirements for each patient. Must be diluted before
infusion to avoid a sudden increase in the plasma-
sodium level. Too rapid administration should be avoided
[see Important Note under Dose].
Inspect visually for particulate matter and discoloration
prior to administration. Do NOT use unless the solution
is clear, and seal is intact. Discard unused portion.
Pregnancy Category: C
ATC Code: B05XA03
Rx STERILE WATER FOR INJECTION
Inj.: 2 mL, 5 mL, 10 mL, and 20 mL ampule
50 mL, 100 mL, 500 mL, and 1 L bottle / bag (no
preservative)
A sterile, nonpyrogenic water for injection that does
not contain any antimicrobial agent or other
added substances, such as buffer, and is
supplied in single-dose containers to dilute or
dissolve drugs for injection.
Indication: For dissolving or diluting medicines that are
intended for parenteral injection.
NOTE: Use in accordance with the instructions set by the
manufacturer of the drug.
Contraindications: No information found
Dose: Volume to be used for any drug for injection is based
on the vehicle concentration, dose, and route of
administration as recommended by the drug
manufacturer.
BLOOD AND BLOOD FORMING ORGANS
Precautions:
WARNING: IV administration without a solute may
result in hemolysis.
Should be made isotonic prior to use; not for direct infusion;
not for non-automated admixture preparations;
Neonates and very small infants.
NOTE: Upon reconstitution of medicines, label to indicate
that no antimicrobial or other substance has been
added, and that it is not suitable for IV injection without
first having been made approximately isotonic by the
addition of a suitable solute.
Adverse Drug Reactions: Febrile response, local tenderness,
abscess, tissue necrosis or infection at the site of
injection, venous thrombosis or phlebitis extending from
the site of injection, extravasation.
NOTE: May occur because of the solution, added drugs, or
the technique reconstitution or administration
Drug Interactions: May be incompatible with some drugs for
injection in a given vehicle, or when combined in the
same vehicle.
Administration: Inspect reconstituted drugs for clarity and
freedom from unexpected precipitation or discoloration
prior to administration.
Do NOT use for IV injection unless the osmolar
concentration results in an isotonic admixture.
Do NOT use unless the solution is clear and intact. mix
thoroughly and use promptly after diluting or dissolving
drugs.
Do NOT store reconstituted solutions of drugs for
injection, unless otherwise directed. Do NOT reuse
single-dose containers.
Do NOT heat over 66°C (150°F).
Pregnancy Category: No information found
ATC Code: Not available
Rx TRACE ELEMENTS
Inj.: Contains Zn, Cu, Mn, Mg, Mb, etc., 10 mL ampule (IV
nutrition)
A sterile solution containing basic elements present in the
human body in specific amounts required to initiate,
facilitate, or maintain appropriate body systems. Trace
elements, or microminerals, are inorganic compounds
that aid physiological processes of the body such as
building and regulation.
Indication: Nutritional supplement to IV solutions given for
total parenteral or central nutrition.
Contraindications: Hypersensitivity to any component
(especially iodides); manganese contraindicated in
presence of high manganese levels; molybdenum
without copper supplementation contraindicated in
copper-deficient patients.
Dose: Dose is dependent on clinical condition of patient.
Dose Adjustment:
B
Geriatric:
Use with caution. Use lower end of the dosing range,
considering decreased organ function and concomitant
disease or drug therapy.
Renal Impairment:
Reduce or omit dose.
Precautions:
Assess possibility of diabetes mellitus when giving
chromium supplements to maintain normal glucose
metabolism; Selenium enhances vitamin E and
decreases the toxicity of mercury, cadmium, and arsenic;
Biliary tract obstruction; Wilson’s disease; Impaired
kidney function; Aluminum content; Premature
neonates; Lactation (use manganese with caution).
Adverse Drug Reactions:
Rare: Toxicity; anaphylaxis (due to iodine)
Drug Interactions:
NOTE: Therapeutic serum levels of copper and zinc will
decrease if not given together.
Administration: Must be added to daily volume of IV infusion
fluids including TPN. Administer properly diluted at rate
prescribed for IV infusion fluids or TPN.
Do NOT administer by direct IV.
If additives are to be added, consult with pharmacist;
specific conditions may apply.
Pregnancy Category: C
ATC Code: Not available
VITAMINS INTRAVENOUS (IV),
Rx
FAT-SOLUBLE
Inj.: Contains vitamins A, D, E, and K, 10 mL ampule (IV)
Organic substances that are essential for normal
metabolism and thus must be provided in the diet in
small quantities because these substances are not
synthesized in the human body.
Fat soluble vitamins include Vitamins A, D, E, and K. They
present a potential harm as they can be stored in
massive degree and many patients may take more than
the prescribed dose. Overdosing may cause toxic effects
because they are metabolized very slowly.
Indications: Daily multivitamin maintenance supplement for
patients receiving parenteral nutrition; situations, which
may provoke a stress response and alteration in the
body’s metabolic demands; dietary supplement when
oral administration is contraindicated, not possible, or
insufficient; treatment for specific deficiency states.
91

Contraindications: Hypersensitivity to any ingredient;
hypervitaminosis; pregnancy (vitamin A doses > RDA);
hypercalcemia; signs of vitamin D toxicity.
Dose: Dose is dependent on the clinical condition of the
patient. Multiples of the daily dose may be given for 2 or
B
more days in patients with multiple vitamin deficiencies
or markedly increased requirements. Individual
components may be indicated in specific or long-
standing deficiencies.
Precautions:
Do not wait for the development of clinical signs of vitamin
deficiency before initiating vitamin therapy; may contain
aluminum; Hypersensitivity reactions; elevated Vitamin E
blood levels; Renal failure or liver disease (use with
caution); Impaired kidney function; Premature neonates
Adverse Drug Reactions:
Rare: Agitation, allergic reactions, anxiety, diplopia,
dizziness, erythema, fainting, headache, pruritus, rash,
vitamin A and D hypervitaminosis
Drug Interactions:
Avoid concomitant use with:
Decreases therapeutic effect of Warfarin (anticoagulant
effect)
Administration: Most may be reconstituted with 5 mL of
SWFI or supplied diluent. All preparations must be
further diluted in at least 500 mL but preferably 1,000
mL of IV fluids.
Do NOT use if any crystals have formed. Vitamin A may
adhere to plastic, resulting in inadequate vitamin A
administration in the doses recommended.
If additives are to be added, consult with pharmacist.
Specific conditions may apply.
Pregnancy Category: C (product-specific)
ATC Code: B05XC
VITAMINS, INTRAVENOUS (IV),
Rx
WATER-SOLUBLE
Inj.: Contains vitamin B complex and vitamin C, 1 mL vial
and 2 mL ampule (IV)
Organic substances that are essential for normal
metabolism and thus must be provided in the diet in
small quantities because these substances are not
synthesized in the human body.
Water soluble vitamins include vitamins C, B1, B2, B6, B12,
biotin, folic acid, niacin, and pantothenic acid. Water-
soluble vitamins, are metabolized rapidly and any excess
is excreted in the urine. Except for niacin and pyridoxine,
overdosage seldom causes toxic effects in individuals
with normal renal function.
Indications: Daily multivitamin maintenance supplement for
patients receiving parenteral nutrition; dietary
supplement in a variety of circumstances where vitamin
deficiencies are likely to occur; for increased tissue
92
BLOOD AND BLOOD FORMING ORGANS
needs; for inborn errors of metabolism; treatment for
specific deficiency states.
Contraindications: Hypersensitivity to any ingredient;
hypervitaminosis; patients with hyperoxaluria; G6PD
deficiency; diabetes mellitus; hemochromatosis; renal
impairment; pregnancy; lactation.
Dose: Dose is dependent on the clinical condition of the
patient. Multiples of the daily dose may be given for 2 or
more days in patients with multiple vitamin deficiencies
or markedly increased requirements. Individual
components may be indicated in specific or long-
standing deficiencies.
Precautions:
Do not wait for the development of clinical signs of vitamin
deficiency before initiating vitamin therapy; may contain
aluminum; Preparations containing Vitamin C must be
protected from light; Hypersensitivity reactions;
Megaloblastic anemia (requires blood draws for the
detection of folic acid and cyanocobalamin deficiencies
prior to administration); pernicious anemia; diabetes
mellitus and hypoglycemic states; impaired kidney
function; Premature neonates.
Adverse Drug Reactions:
Rare: Agitation, allergic reactions, anxiety, diplopia,
dizziness, erythema, fainting, headache, pruritus, rash.
Drug Interactions:
Monitor closely with:
Bleomycin – inactivated in vitro by ascorbic acid (Vitamin C)
and riboflavin (Vitamin B2)
Chloramphenicol – hematologic response to vitamin B12
therapy in patients with pernicious anemia may be
inhibited
Erythromycin, kanamycin, streptomycin, doxycycline,
lincomycin – thiamine, riboflavin, pyridoxine,
niacinamide, and ascorbic acid may decrease their
antibiotic activity
Hydralazine, isoniazid (INH) – may increase pyridoxine
requirements
Levodopa – pyridoxine may reduce effectiveness of
levodopa
Methotrexate – folic acid may decrease the patient’s
response to methotrexate therapy
Phenytoin – folic acid may lower serum concentration of
phenytoin, resulting in increased seizure frequency;
monitor serum levels of both drugs; may decrease serum
folic acid concentrations; avoid during pregnancy
Administration: Most may be reconstituted with 5 mL of
SWFI or supplied diluent. All preparations must be
further diluted in at least 500 mL but preferably 1,000
mL of IV fluids. Do not use if any crystals have formed.
If additives are to be added, consult with pharmacist.
Specific conditions may apply.
Pregnancy Category: C
ATC Code: B05XC
BLOOD AND BLOOD FORMING ORGANS

HEMODIALYTICS AND HEMOFILTRATES

Rx HEMODIALYSIS SOLUTIONS
Preparations:
Acid Concentrate

B
Composition (g/L):
Glucose 0 – 49.50 g
Sodium chloride 216.19– 270.80 g
Potassium chloride 5.25 – 6.7 g
Calcium chloride 6.47 – 9.9 g
Magnesium chloride 3.58 – 4.75 g
Glacial acetic acid 8.1 – 8.46 g
Purified water 1,000 mL

Sodium bicarbonate for Hemodialysis

Sodium bicarbonate, 650 g powder

A clear, sterile solution of electrolytes with a concentration

close to the electrolytic composition of plasma.

Indications: Remove metabolites in renal failure; correct

electrolyte and acid-base abnormalities in End-Stage
Renal Disease (ESRD).

Dose: Dose depends on the clinical condition of the patient,

as well as the patient’s fluid, electrolyte, acid-base, and
glucose balance.

Precautions:
Monitor hemodynamic fluid, electrolyte and acid-base
balance throughout the procedure. Citrate, when used as
an anticoagulant, contributes to the base load, and can
reduce plasma calcium levels; Abnormalities in plasma
concentration of potassium, calcium, glucose, and
phosphate; Cardiovascular disease, especially those
using cardiac glycoside medications (carefully monitor
plasma levels of calcium, potassium, and magnesium).

Adverse Drug Reactions:

Common: Thrombophlebitis

Drug Interactions: No information found

NOTE: The blood concentrations of certain drugs may need

to be monitored and appropriate therapy implemented to
correct for removal during treatment.

Administration: Aseptic technique should be used

throughout administration. Take necessary precautions
during dilution and use to avoid microbial contamination.
Use diluted solutions immediately after preparation.
Discard any unused solution.
Hemodialysis solutions are usually prepared by diluting a
concentrated solution with water of suitable quality
because of the large volume used. In certain
circumstances, it may be necessary to use sterile
solutions.

Pregnancy Category: C

ATC Code: B05ZA

93

CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC GLYCOSIDES
C
Rx DIGOXIN
Oral: 250 micrograms tablet
50 micrograms/mL elixir, 60 mL
Inj.: 250 micrograms/mL, 2 mL ampule (IM, IV)
A cardiac glycoside obtained from the leaves of Digitalis
lanata. Digoxin inhibits the Na+-K+-ATPase pump and
consequently increases the force of cardiac contraction
and slows the heart rate.
Indication: For rate control in chronic atrial fibrillation and
atrial flutter.
Contraindications: Ventricular tachycardia or fibrillation;
hypertrophic obstructive cardiomyopathy (unless there is
concomitant atrial fibrillation and heart failure);
permanent or even intermittent second-degree and third-
degree atrioventricular block without a cardiac
pacemaker; pre-excited atrial fibrillation/atrial flutter or
antidromic atrioventricular reentrant tachycardia
associated with Wolff-Parkinson-White (WPW) syndrome;
arrhythmias caused by cardiac glycoside intoxication
Dose:
Atrial fibrillation or flutter, by mouth, ADULT,
Rapid Oral Loading: 750–1,500 micrograms as a single-
dose; where there is less urgency or greater risk of
toxicity, e.g., elderly, oral loading dose is given in divided
doses 6 hours apart, with half of the total dose given as
the first dose; assess clinical response before each
additional dose;
Slow Oral Loading: 250–750 micrograms daily for 1
week followed by appropriate maintenance dose;
Maintenance Dose: 3.4–5.1 micrograms/kg daily or
125–500 micrograms daily; increase dose gradually
every 2 weeks based on clinical responses, toxicity, and
serum drug levels.
Dose Adjustment:
Geriatric:
Use lower doses due to the tendency to develop impaired
renal function and lean body mass, which can lead to
digoxin toxicity.
Loading Dose: by mouth, 125–250 micrograms every 4–6
hours, to a maximum of 500 micrograms;
Maintenance Dose: by mouth, 62.5–125 micrograms once
daily.
Renal Impairment:
For mild-to-moderate renal impairment, reduce dose.
For severe impairment, refer patient to a specialist.
Hypomagnesemia, hypokalemia, hypercalcemia, hypoxia,
hypothyroidism: Reduce dose
94
CARDIOVASCULAR SYSTEM
Precautions:
WARNING: Fatal arrhythmia may follow overdose.
Maintain heart rate above 60 beats/minute and
early signs of toxicity should be carefully
monitored.
Acute myocarditis, such as rheumatic carditis; advanced
heart failure; severe pulmonary disease; sick sinus
syndrome; recent MI; Fever and hyperthyroidism;
Hypomagnesemia, hypokalemia;
hypercalcemia, hypoxia; Hypothyroidism; Renal impairment;
Elderly; Pregnancy (may need dose adjustment); lactation
(amount in breastmilk too small to be harmful)
Adverse Drug Reactions:
Common: Abdominal pain, agitation, anorexia, blurred
vision, confusion, depression, diarrhea, dizziness,
drowsiness, nausea, nightmares, visual disturbances,
vomiting
Less Common: Acute psychosis, amnesia, atrial or
ventricular extrasystoles, delirium, fatigue,
gynecomastia, hallucinations, headache, heart block,
intestinal ischemia, paroxysmal atrial tachycardia and
fibrillation; shortened QRS complex
Rare: Arrhythmias, rash, seizures, thrombocytopenia,
xanthopsia (yellow vision)
Drug Interactions:
Monitor closely with:
Alters absorption of Digoxin:
Acarbose (decreased absorption); Macrolides, e.g.,
Azithromycin, Clarithromycin, Erythromycin (increased
absorption)
Enhances therapeutic effect of Digoxin:
Amiodarone (slowing cardiac conduction), Beta
Blockers, e.g., Atenolol, Propranolol (slow
atrioventricular conduction), Diltiazem (additive negative
effects on heart rate and cardiac conduction)
Avoid concomitant use with:
Decreases serum concentration of Digoxin:
Antacids, e.g., Aluminum or Magnesium Hydroxide,
Rifampicin, Salbutamol
Reduces therapeutic effect of Digoxin by reducing its
absorption:
Bile Acid Binding Resins
Increases serum concentration of Digoxin, increasing its risk
of adverse or toxic effects:
Verapamil (additive negative effects on heart rate and
cardiac conduction)
Administration: To be taken 1 hour before or 2 hours after
eating food. For meals high in fiber, take it 2 hours before
or 2 hours after eating food.
IM route is generally not preferred due to severe injection
site pain.
Avoid rapid IV administration (increased risk of
arrhythmias);
Pregnancy Category: C
CARDIOVASCULAR SYSTEM
ATC Code: C01AA05
ANTIARRHYTHMICS
CLASS I ANTIARRHYTHMICS
Rx LIDOCAINE
Inj.: 20 mg/mL (as hydrochloride), 2 mL, 5 mL, 20 mL, and
50 mL ampule / vial (IM, IV)
A class IB antiarrhythmic agent that acts by blocking fast
sodium channels, thereby inhibiting the rapid
depolarization (phase 0) of fast response cardiac action
potentials while decreasing the effective refractory
period.
Indications: Management of pulseless ventricular fibrillation
or ventricular tachycardia; emergency treatment of
ventricular arrhythmia
Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy
with anticoagulants or an abnormal bleeding tendency;
severe anemia or heart disease; spinal/epidural
anesthesia in dehydrated or hypovolemic patients
Dose:
Pulseless ventricular fibrillation or ventricular tachycardia,
by IV injection, ADULT, 1–1.5 mg/kg repeated as
necessary (maximum dose, 3 mg/kg);
for ventricular arrhythmias in more stable patients, usual
loading dose, 50–100 mg at 25 to 50 mg/minute, may
repeat once or twice up to a maximum of 200–300 mg
in 1 hour, followed by 1–4 mg/minute via continuous IV
infusion, may need to reduce dose if the infusion is
longer than 24 hours.
Emergency treatment of ventricular arrhythmias, by IM
injection, ADULT, 300 mg injected into the deltoid
muscle, repeat after 60–90 minutes, if necessary.
Dose Adjustment:
Geriatric and Debilitated Patients:
Reduce doses commensurate with age and physical status.
Renal and Hepatic Impairment:
Reduce dose during prolonged infusion (>24 hours) or
repeated IV doses.
Precautions:
Severe bradycardia, heart block or impaired cardiac
conduction; severe shock; respiratory impairment; renal
impairment; hepatic impairment; epilepsy; porphyria;
neuromuscular diseases, e.g., myasthenia gravis;
neurological disease
Solutions containing epinephrine should be used with
caution for ring block of digits or appendages to prevent
risk of ischemic necrosis
Elderly (increased sensitivity); children <6 months (more
sensitive to toxic effects)
Pregnancy (avoid large doses during third trimester to
diminish risk of neonatal respiratory depression,
hypotonia and bradycardia after paracervical block);
lactation
Adverse Drug Reactions:
Common: Blurred vision, chest pain, confusion,
disturbances in vision, dizziness, drowsiness, dyspnea,
flushing, headache, lightheadedness, nausea,
paresthesia, tinnitus, tremors
Less Common: Arrhythmias, bradycardia, cardiac arrest,
C
coma, heart block, hypotension, muscle twitching,
recurrence of SVT, respiratory depression, restlessness,
seizures
Rare: Bronchospasm, convulsions, hypersensitivity
reactions, paraplegia, unconsciousness
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Lidocaine by
increasing its serum concentration:
Beta Blockers e.g., Metoprolol
Avoid concomitant use with:
Decreases therapeutic effect of Lidocaine:
Diuretics, e.g. Furosemide, Hydrochlorothiazide
Decreases therapeutic effect of the following drugs:
Antiarrhythmics, e.g., Amiodarone, Sotalol, Disopyramide
Increases risk of adverse or toxic effects of the following
drugs:
Bupivacaine (Bupivacaine toxicity), Drugs which
depresses cardiac contractility and conduction (heart
failure; significant bradyarrhythmia)
Administration: For IV or IM use only.
Pregnancy Category: B
ATC Code: C01BB01
CLASS II ANTIARRHYTHMICS
Rx ESMOLOL
Inj.: 10 mg/mL (as hydrochloride), 10 mL vial (IV)
100 mg/mL, 10 mL vial (IV)
A class II antiarrhythmic agent that competitively blocks
response to beta1-adrenergic stimulation with little or no
effect to beta2-receptors except at high doses. Esmolol
does not exhibit intrinsic sympathomimetic activity and
membrane stabilizing activity.
Indications: Treatment of supraventricular tachycardia
(SVT); treatment of atrial fibrillation or flutter; treatment
of intraoperative and postoperative tachycardia
Contraindications: Any supraventricular tachyarrhythmia
conducted across an accessory pathway (WPW
Syndrome-associated tachyarrhythmias including
preexcited atrial fibrillation/atrial flutter, antidromic
atrioventricular reentrant tachycardia).
95

Dose:
Intraoperative and postoperative tachycardia, immediate
control, by IV injection, ADULT, initially 1 mg/kg bolus
over 30 seconds, followed by 150 micrograms/kg per
minute, if necessary (maximum dose, 300
micrograms/kg per minute).
Intraoperative and postoperative tachycardia, gradual
control, by IV injection, ADULT, initially 0.5 mg/kg bolus
over 1 minute, followed by an infusion of 50
C
micrograms/kg per minute for 4 minutes, may be
continued at 50 micrograms/kg per minute (if response
is inadequate, titrate dose upward at 50 micrograms/kg
per minute increments, increase no more frequently than
every 4 minutes (maximum dose, 300 micrograms/kg
per minute); may administer an optional loading dose of
0.5 mg/kg over 1 minute prior to each increase in
infusion rate.
Supraventricular tachycardia, by IV injection, ADULT,
optional loading dose, 0.5 mg/kg over 1 minute, followed
by 50 micrograms/kg per minute infusion for 4 minutes;
continue infusion at 50 micrograms/kg per minute (if
response is inadequate, increase dose in 50
micrograms/kg per minute increments, for no more
frequently than every 4 minutes (maximum dose, 200
micrograms/kg per minute);
for a more rapid response, re-bolus with a second 0.5
mg/kg loading dose over 1 minute, and increase the
maintenance infusion to 100 micrograms/kg per minute
for 4 minutes;
a third, final 0.5 mg/kg loading dose may be
administered, if necessary, prior to increasing infusion
rate of 150 micrograms/kg per minute; after 4 minutes,
(maximum infusion rate, 200 micrograms/kg per
minute; usual dose, 50–200 micrograms/kg per minute;
maintenance infusions may be continued for up to 48
hours).
Perioperative tachycardia, by IV injection, ADULT, initially
1.5 mg/kg bolus (maximum dose, 100 mg) over 30
seconds, followed by 150 micrograms/kg per minute
infusion; adjust infusion rate as needed to maintain
desired heart rate (maximum rate, 300 micrograms/kg
per minute).
Atrial fibrillation or atrial flutter, by IV injection, ADULT, 0.5
mg/kg over 1 minute, followed by 50 micrograms/kg per
minute infusion for 4 minutes; continue infusion at 50
micrograms/kg per minute; if response is inadequate, re-
bolus with a second 0.5 mg/kg loading dose over 1
minute, and increase the maintenance infusion to 100
micrograms/kg per minute for 4 minutes; repeat if
necessary, until target heart rate or safety end point
begins to occur, then omit subsequent loading dose and
decrease dosing increment of maintenance infusion to
≤25 micrograms/kg per minute (usual effective dose is
50–200 micrograms/kg per minute; doses as low as 25
micrograms/kg per minute may be adequate).
Dose Adjustment:
Geriatric:
Dose reductions may be necessary.
Administration: For IV administration only. Administer
loading doses over 30 seconds to 1 minute depending
on how urgent the need for effect.
Avoid infusion into small veins or through a butterfly
catheter to prevent thrombophlebitis.
96
CARDIOVASCULAR SYSTEM
NOTE: Esmolol is a vesicant. Ensure proper needle or
catheter placement prior to and during infusion to avoid
extravasation. If extravasation occurs, stop infusion
immediately and disconnect (leave cannula or needle in
place) and gently aspirate extravasated solution then
elevate extremity. Do NOT flush the line.
See General Information on Beta Blocking Agents, Selective
under Beta Blocking Agents in Chapter 3: Cardiovascular
System for other information.
Pregnancy Category: C
ATC Code: C07AB09
Rx METOPROLOL
Oral: 50 mg and 100 mg tablet (as tartrate)
A selective inhibitor of beta1­adrenergic receptors that
competitively blocks beta1­receptors, with little or no
effect on beta2­receptors. Metoprolol does not exhibit
any membrane stabilizing activity or intrinsic
sympathomimetic activity.
Indications: Atrial fibrillation or flutter; supraventricular
tachycardia (SVT)
Contraindications: Any supraventricular tachyarrhythmia
conducted across an accessory pathway (WPW
Syndrome-associated tachyarrhythmias including
preexcited atrial fibrillation/atrial flutter, antidromic
atrioventricular reentrant tachycardia).
Dose:
Atrial fibrillation or flutter (ventricular rate control), and SVT,
maintenance, by mouth, ADULT, 25–100 mg twice daily.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate impairment, no dose adjustment
necessary.
For severe impairment, refer patient to a specialist.
Hepatic Impairment:
For mild-to-moderate impairment, dose reduction may be
warranted.
For severe impairment, refer patient to a specialist.
Precautions:
Major surgery. Do NOT routinely withdraw CHRONIC beta blocker
therapy prior to surgery. Use of high-dose extended-release
metoprolol in patients naive to beta blocker therapy undergoing
non-cardiac surgery has been associated with bradycardia,
hypotension, stroke, and death. Chronic beta-blocker therapy
should not be routinely withdrawn prior to major surgery.
See General Information on Beta Blocking Agents, Selective
under Beta Blocking Agents in Chapter 3: Cardiovascular
System for other information.
Pregnancy Category: C
ATC Code: C07AB02
CARDIOVASCULAR SYSTEM
Rx PROPRANOLOL
Oral: 10 mg and 40 mg tablet (as hydrochloride)
A non-selective beta-adrenergic blocker (class II
antiarrhythmic) that competitively blocks response to
beta1­ and beta2­adrenergic stimulation. It decreases
heart rate, myocardial contractility, blood pressure, and
myocardial oxygen demand.
Indication: Management of supraventricular
tachyarrhythmia
Contraindications: Uncompensated congestive heart failure
(unless the failure is due to tachyarrhythmias being
treated with propranolol); cardiogenic shock; severe
sinus bradycardia; sick sinus syndrome or heart block
greater than first degree (except in the presence of a
functioning artificial pacemaker); bronchial asthma; for
any supraventricular tachyarrhythmia conducted across
an accessory pathway (WPW Syndrome-associated
tachyarrhythmias including preexcited atrial
fibrillation/atrial flutter, antidromic atrioventricular
reentrant tachycardia).
Dose:
Tachyarrhythmias, by mouth, ADULT, 10–30 mg every 6–8
hours; usual maintenance dose, 10–40 mg 3 or 4 times
daily for rate control in patients with atrial fibrillation.
Dose Adjustment:
Geriatric:
Dose reduction may be necessary.
Administer 10 mg twice daily initially; increase dose every
3–7 days (usual dose range, 10–320 mg daily given in
1–2 divided doses).
Precautions:
WARNING: Exacerbations of angina pectoris and
myocardial infarction (MI) have occurred following
abrupt discontinuation of beta blockers. Gradually
reduce the dose over a period of 1–2 weeks and
monitor the patient. If angina or acute coronary
insufficiency develops, promptly resume therapy
temporarily, and take other measures appropriate
for the management of unstable angina. Avoid
abrupt discontinuation to prevent coronary artery
disease.
Anaphylactic reactions (patients may become more
sensitive to repeated challenges; treatment of
anaphylaxis, e.g., epinephrine, may be ineffective or
promote undesirable effects)
Bronchospastic disease (monitor closely)
Conduction abnormality (consider pre­existing conditions
such as sick sinus syndrome before initiating)
Heart failure (monitor for worsening of the condition);
Peripheral vascular disease (PVD) and Raynaud's disease
(can precipitate or aggravate symptoms of arterial
insufficiency);
Prinzmetal variant angina (unopposed alpha1-adrenergic
receptors mediate coronary vasoconstriction and can
worsen anginal symptoms; avoid beta­blockers without
alpha1­adrenergic receptor blocking activity)
Diabetes (may potentiate and/or mask signs and symptoms
of hypoglycemia); thyroid disease (may mask signs of
hyperthyroidism; carefully manage and monitor; abrupt
withdrawal may exacerbate symptoms of
hyperthyroidism or precipitate thyroid storm)
Pheochromocytoma (adequate alpha-blockade is required
prior to use of any beta blocker)
Hepatic impairment; renal impairment (may have increased
side effects)
C
Psoriasis; myasthenia gravis; psychiatric disease (may
cause or exacerbate CNS depression)
Smokers (may decrease plasma levels of propranolol by
increasing metabolism)
Elderly (bradycardia may be observed more frequently)
Pregnancy (may cause pharmacologic effects, such as
bradycardia, in the fetus and newborn infant)
NOTE: Do NOT withdraw abruptly. Gradually tapered over 1–
2 weeks to avoid acute tachycardia, hypertension,
and/or ischemia. Severe exacerbations of angina,
ventricular arrhythmias and myocardial infarction have
been reported following abrupt withdrawal of beta
blocker therapy. Temporary but prompt resumption of
beta blocker therapy may be indicated with worsening of
angina or acute coronary insufficiency.
Adverse Drug Reactions:
Common: Cold extremities, angina pectoris, AV conduction
disturbance, bradycardia, cardiogenic shock, congestive
heart failure, hypotension, ineffective myocardial
contractions, syncope, sleep disorder, agitation, fatigue,
dizziness, nightmares, irritability, drowsiness, amnesia,
catatonia, cognitive dysfunction, confusion,
hypersomnia, lethargy, paresthesia, psychosis, vertigo,
changes in nails, contact dermatitis, dermal ulcer,
eczematous rash, erosive lichen planus, hyperkeratosis,
pruritus, skin rash, hyperglycemia, hyperkalemia,
hyperlipidemia, diarrhea, abdominal pain, hypoglycemia,
decreased appetite, constipation, stomach discomfort,
immune thrombocytopenia, anorexia,
thrombocytopenia, oculomucocutaneous syndrome,
arthropathy, conjunctival hyperemia, decreased visual
acuity, polyarthritis, mydriasis, increased blood urea
nitrogen, bronchiolitis, bronchospasm, dyspnea,
bronchitis, pulmonary edema, wheezing, ulcer
Less Common: Abdominal cramps, agranulocytosis,
alopecia, arterial insufficiency, arterial mesenteric
thrombosis, decreased heart rate, depression, emotional
lability, epigastric distress, erythema multiforme,
erythematous rash, exfoliative dermatitis, fever,
hallucination, hypersensitivity reaction, impotence,
insomnia, ischemic colitis, lassitude, lupus-like
syndrome, myotonia, myopathy, nausea,
nonthrombocytopenic purpura, peripheral arterial
disease, Peyronie's disease, pharyngitis, psoriasiform
eruption, purpura, Raynaud's phenomenon, second-
degree atrioventricular block, slightly clouded
sensorium, Stevens-Johnson syndrome, systemic lupus
erythematosus, temporary amnesia, tingling of
extremities, toxic epidermal necrolysis, urticaria, visual
disturbance, vivid dream, vomiting, weakness,
xerophthalmia
Rare: Carpal tunnel syndrome, oliguria, proteinuria,
interstitial nephritis
97

Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Propranolol:
Bradycardic effect: Acetylcholinesterase Inhibitors e.g.
Neostigmine, Amiodarone (may induce cardiac arrest),
Bretylium, Dipyridamole, Disopyramide, Regorafenib,
Reserpine, Ruxolitinib, Tofacitinib, Other Bradycardia-
causing Agents
Antihypertensive effect: Phenothiazine Antipsychotic
C
Agents, Barbiturates e.g Phenobarbital, Brimonidine
(topical), Calcium Channel Blockers (Non-
Dihydropyridine e.g. Verapamil), Diazoxide, Lacidipine,
Molsidomine, Nicorandil, Nifedipine (also negative
inotropic effect), Pentoxifylline, Phosphodiesterase-5
Inhibitors, Prostacyclin Analogues e.g., Epoprostenol,
Propafenone (possesses independent beta-blocking
activity), Anilidopiperidine Opioids e.g., Fentanyl
(bradycardic and hypotensive effects),
Enhances therapeutic effect of the following drugs:
Bretylium (AV blockade), Cardiac Glycosides (bradycardic
effect), Disopyramide (negative inotropic effect),
Fingolimod (bradycardic effect), Insulin (hypoglycemic
effect), Ivabradine (bradycardic effect), Lacosamide (AV
blocking effect), Midodrine (bradycardic effect), Other
Antihypertensives (antihypertensive effect),
Sulfonylureas (hypoglycemic effect)
Increases metabolism of Propranolol:
CYP1A2 Inducers, CYP2D6 Inducers
Increases risk of adverse or toxic effects of Propranolol:
MAO Inhibitors (orthostatic hypotensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Cholinergic Agonists (potential for cardiac conduction
abnormalities and bronchoconstriction), Duloxetine
(orthostatic hypotensive effect), Levodopa (orthostatic
hypotensive effect), MAO Inhibitors [except Linezolid,
Tedizolid] (orthostatic hypotensive effect), Other
Antihypertensive Agents
Reduces therapeutic effect (anti-hypertensive effect) of
Propranolol:
Methylphenidate (antihypertensive effect), NSAIDS
(antihypertensive effect)
Avoid concomitant use with:
Enhances therapeutic effect of Propranolol:
Alpha2­agonists [except Apraclonidine] (AV blocking
effect), Dronedarone (bradycardic effect), Rivastigmine
(bradycardic effect)
Enhances therapeutic effect of the following drugs:
Alpha / Beta-Agonists, Direct-Acting (vasopressor effect)
Ceritinib (bradycardic effect), Ergot Derivatives e.g.,
Ergotamine (vasoconstricting effect)
Increases metabolism of Propranolol:
CYP1A2 Inducers, CYP2D6 Inducers
Increases risk of adverse or toxic effects of the following
drugs:
Alpha / Beta-Agonists, Direct-Acting (reduced beta-
adrenoceptor-mediated effects, including anaphylactic
98
CARDIOVASCULAR SYSTEM
effects of epinephrine), Alpha1 Blocker e.g. Tamsulosin
(orthostatic hypotensive effect), Alpha2­agonists [except
Apraclonidine] (rebound hypertension; may enhance
sinus node dysfunction), Amifostine (hypotensive
effect), Grass Pollen Allergen Extract / 5 Grass Extract
(may inhibit the ability to effectively treat severe allergic
reactions with epinephrine), Methacholine,
Obinutuzumab (hypotensive effect), Rituximab
(hypotensive effect)
Increases serum concentration of Propranolol:
Abiratone Acetate, Dronedarone, Fluvoxamine,
Panobinostat
Increases serum concentration of the following drugs:
Afatinib, Bosutinib, Colchicine (may increase distribution
to certain tissues, e.g., brain), Dabagitran Etexilate
[active metabolites], Doxorubicin (Conventional),
Edoxaban, Everolimus, Pazopanib, Rizatriptan [reduce
dose to 5 mg when used concomitantly], Silodosin,
Tizanidine, Topotecan, Vemurafenib, Vincristine
(Liposomal)
Reduces therapeutic effect of the following drugs:
Beta2­agonists e.g Salbutamol (bronchodilatory effect),
Theophylline Derivatives e.g., Aminophylline
(bronchodilatory effect)
Administration: To be taken on an empty stomach.
NOTE: Do NOT withdraw abruptly, particularly in patients
with CAD. Gradually taper dose to avoid acute
tachycardia, hypertension, and/or ischemia.
Pregnancy Category: C
ATC Code: C07AA05
CLASS III ANTIARRHYTHMICS
Rx AMIODARONE
Oral: 200 mg tablet (as hydrochloride)
Inj.: 50 mg/mL (as hydrochloride), 3 mL ampule (IV)
A class III antiarrhythmic agent with alpha- and beta-
blocking properties, that acts by inhibiting adrenergic
stimulation. Amiodarone affects sodium, potassium, and
calcium channels and prolongs the action potential
duration and refractory period in myocardial tissue. It
also decreases AV conduction and sinus node function.
Indications: Management of life-threatening recurrent
ventricular fibrillation (VF) or recurrent hemodynamically-
unstable ventricular tachycardia (VT); supraventricular
arrhythmias
Contraindications: Severe sinus-node dysfunction causing
marked sinus bradycardia; second- and third-degree
heart block; bradycardia causing syncope; cardiogenic
shock
CARDIOVASCULAR SYSTEM
Dose:
Recurrent life-threatening ventricular arrhythmias,
prevention, by mouth, ADULT, 800–1,600 mg daily in 1–
2 doses for 1–3 weeks; when adequate arrhythmia
control is achieved, decrease to 600–800 mg daily in 1–
2 doses for 1 month (maintenance, 300 mg daily).
Pulseless VT or VF, by IV push, I.O., ADULT, initially 300 mg
rapid bolus; if condition continues or recurs, administer
supplemental dose of 150 mg, preferably undiluted
(maximum recommended total daily dose, 2.2 g); once
spontaneous circulation returns, administer by IV
infusion of 1 mg/minute for 6 hours, then 0.5 mg/minute
for 18 hours); CHILD, 5 mg/kg rapid bolus (maximum,
300 mg per dose); may repeat twice up to a maximum
total dose of 15 mg/kg during acute treatment.
Stable VT, by IV infusion, ADULT, 150 mg over 10 minutes,
then 1 mg/minute for 6 hours, followed by 0.5
mg/minute; continue this rate for at least 18 hours or
until complete transition to oral (total infusion duration,
24 hours).
Breakthrough stable VT, by IV infusion, ADULT, 150 mg
supplemental doses in 100 mL D5W or NS over 10
minutes [NOTE: Mean daily doses >2.1 g/day have been
associated with hypotension.]
Atrial fibrillation, pharmacologic cardioversion, by mouth,
ADULT, 600–800 mg daily in divided doses to a total of
10 g, then 200 mg daily as maintenance dose (usual
maintenance dose, 100 mg daily); or
800 mg daily for 14 days, followed by 600 mg daily for
the next 14 days, then 300 mg daily for the remainder of
the first year, then 200 mg daily thereafter; or
10 mg/kg daily for 14 days, followed by 300 mg daily for
4 weeks, then 200 mg daily as maintenance dose;
by IV infusion, ADULT, 150 mg over 10 minutes, then 1
mg/minute for 6 hours, then 0.5 mg/minute for 18
hours, or change to oral dosing.
Maintenance of sinus rhythm, by mouth, ADULT, 400 to 600
mg daily in divided doses for 2–4 weeks followed by a
maintenance dose of 100–200 mg once daily.
Prevention of postoperative atrial fibrillation and atrial
flutter associated with cardiothoracic surgery, by mouth,
ADULT, 200 mg 3 times daily for 7 days prior to surgery,
followed by 200 mg daily until hospital discharge;
by IV injection, ADULT, 150 mg loading dose, followed by
0.4 mg/kg per hour for 3 days prior to surgery and for 5
days postoperative; after surgery, infuse 1,000 mg over
24 hours for 2 days.
Supraventricular tachycardia, pharmacologic cardioversion,
by mouth, ADULT, 600–800 mg daily in divided doses to
a total of 10 g, then 200 mg daily as maintenance;
by IV infusion, ADULT, 150 mg over 10 minutes, then 1
mg/minute for 6 hours, then 0.5 mg/minute for 18
hours, or change to oral dosing.
Dose Adjustment:
Geriatric:
Select doses with caution. Begin at low end of dosage range
and titrate slowly to evaluate response.
A maintenance dose of 100 mg daily is commonly used
especially for the elderly or patients with low body mass.
Hepatic Impairment:
Dose adjustment may be necessary. Decrease dose or
discontinue Amiodarone once hepatic enzymes exceed 3
times the normal or double in a patient with an elevated
baseline.
Precautions:
WARNING: For use only in patients with indicated life-
threatening arrhythmias due to the risk for
substantial, potentially fatal toxicity (e.g.,
pulmonary toxicity, overt liver disease).
Bradycardia or hypotension (infusion-rate related);
Proarrhythmic effects
C
Arrhythmias (hospitalize patients when amiodarone is
initiated), Wolff-Parkinson-White (WPW) syndrome
Cardiac devices, e.g., implantable defibrillators (chronic
therapy may increase defibrillation threshold)
Myocardial infarction
Dermatologic toxicity (may cause life-threatening or fatal
cutaneous reactions, including SJS and TEN)
photosensitivity (blue-gray discoloration of exposed skin
may occur during long-term treatment)
Hepatotoxicity
Neurotoxicity (peripheral neuropathy has been reported);
ocular effects (may cause optic neuropathy and/or optic
neuritis resulting in visual impairment; permanent
blindness has occurred; corneal microdeposits
commonly occur and may cause reversible visual
disturbances)
Pulmonary toxicity (hypersensitivity pneumonitis, or
interstitial or alveolar pneumonitis, and abnormal
diffusion capacity without symptoms may occur; acute-
onset pulmonary injury has occurred; most fatalities due
to sudden cardiac death occurred when amiodarone was
discontinued)
Thyroid effects (may cause hyper­ or hypothyroidism;
myxedema has been reported and may be fatal; thyroid
nodules and thyroid cancer have been reported)
Electrolyte imbalance (correct hypokalemia,
hypomagnesemia, or hypocalcemia prior to use and
throughout therapy)
Surgical patients (may enhance myocardial depressant and
conduction effects of halogenated inhalational
anesthetics; adult respiratory distress syndrome (ARDS)
has been reported postoperatively)
Elderly (use is associated with thyroid disease, pulmonary
abnormalities, and QT-interval prolongation)
Lactation (excreted in breastmilk; not recommended for
nursing mothers).
Adverse Drug Reactions:
Common: Hypotension, bradycardia, AV block, cardiac
arrest, cardiac arrhythmia, cardiac failure, ventricular
tachycardia, asystole, atrial fibrillation, cardiogenic
shock, torsade de pointes, ventricular fibrillation,
atrioventricular dissociation, cardiac conduction
disturbance, edema, flushing, peripheral
thrombophlebitis, pulseless electrical activity (PEA),
abnormal gait, ataxia, dizziness, fatigue, involuntary
body movements, malaise, peripheral neuropathy,
memory impairment, paresthesia, altered sense of
smell, headache, insomnia, sleep disorder, blue-gray
skin pigmentation, skin photosensitivity, hypothyroidism,
decreased libido, hyperthyroidism nausea, vomiting,
anorexia, constipation, altered salivation, dysgeusia,
abdominal pain, diarrhea, blood coagulation disorder,
hepatic disease, tremor, corneal deposits, visual halos,
visual disturbance, optic neuritis, photophobia,
pulmonary toxicity, pulmonary edema, hypersensitivity
99
 CARDIOVASCULAR SYSTEM

pneumonitis, interstitial pneumonitis, pulmonary Decreases metabolism of the following drugs:

fibrosis, fever Cyclosporine (Systemic), HMG-CoA Reductase Inhibitors
Less Common: Acute renal failure, adult respiratory distress [except Pitavastatin, Pravastatin; limit Simvastatin adult
syndrome, agranulocytosis, alopecia, anaphylactic maximum dose to 20 mg daily; limit Lovastatin adult
shock, anaphylactoid reaction, anaphylaxis, maximum dose to 40 mg daily], Tamoxifen, Tegafur
angioedema, aplastic anemia, back pain, bronchiolitis
obliterans organizing pneumonia, bronchospasm, Decreases serum concentration of Amiodarone:
bullous dermatitis, cholestasis, cholestatic hepatitis, Dabrafenib, Fosphenytoin, Mitotane, Rifampin [including
confusion, cough, delirium, demyelinating its active metabolite, desethylamiodarone],
C

polyneuropathy, disorientation, DRESS syndrome, drug-

induced Parkinson disease, dyspnea, eczema,
eosinophilic pneumonia, epididymitis, erythema
multiforme, exfoliation of skin, exfoliative dermatitis,
fever, hallucination, hemolytic anemia, hemoptysis,
hepatic cirrhosis, hepatic failure, hepatitis,
hepatotoxicity (idiosyncratic), hypoesthesia,
hypotension, hypoxia, impotence, increased intracranial
pressure, injection site reaction, jaundice,
leukocytoclastic vasculitis, malignant neoplasm of skin,
pulmonary mass, myasthenia, myopathy, neutropenia,
optic neuropathy, pancreatitis, pancytopenia, pleural
effusion, pleurisy, prolonged QT interval, pruritus,
pseudotumor cerebri, pulmonary alveolar hemorrhage,
pulmonary infiltrates, pulmonary phospholipidosis, renal
insufficiency, respiratory arrest, respiratory distress
syndrome, respiratory failure, rhabdomyolysis, SIADH,
sinoatrial arrest, sinus node dysfunction, skin carcinoma,
skin granuloma, skin rash, skin sclerosis, spontaneous
ecchymoses, Stevens-Johnson syndrome, superior vena
cava syndrome, thrombocytopenia, thyroid cancer,
thyroid nodule, thyrotoxicosis, tissue necrosis at injection
site, toxic epidermal necrolysis, urticaria, vasculitis,
vortex keratopathy, wheezing, xerostomia
Drug Interactions:
Monitor closely with:
Decreases absorption of Amiodarone:
Orlistat
Decreases metabolism of Tramadol
Decreases serum concentration of the following drugs:
Artesunate, Tamoxifen, Tegafur
Enhances therapeutic effect of Amiodarone:
QTc prolonging effect: Azithromycin (Systemic),
Fosphenytoin
Bradycardic effect: Non-Dihydropyrdine Calcium Channel
Blockers e.g., Diltiazem, Daclatasvir
Arrhythmogenic effect: Fingolimod
Enhances therapeutic effect of Amiodarone:
QTc prolonging effect: Ivabradine, Lopinavir,
Mifepristone, Other QTc-prolonging Agents, Saquinavir,
Bradycardic effect: Sofosbuvir
Enhances therapeutic effect of the following drugs:
Antiarrhythmic Agents, Class Ia (QTc prolonging effect),
Ceritinib (bradycardic effect), Flecainide [when used
concomitantly, decrease Flecainide dose by 50%] (QTc
prolonging effect), Vitamin K Antagonists, e.g., Warfarin
(anticoagulant effect)
Increases bioavailability of Amiodarone:
Grapefruit Juice
Increases risk of adverse or toxic effects of the following
drugs:
Loratadine (QT interval prolongation and torsade de
pointes), Propafenone (cardiac conduction and
repolarization)

Enhances therapeutic effect of Amiodarone: Increases serum concentration of Amiodarone:

Bretylium (bradycardic and AV blocking effects), Cimetidine, Fusidic Acid (Systemic) Idelalisib, Indinavir,
Lidocaine (arrhythmogenic effect), Ruxolitinib Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir
(bradycardic effect)
Tofacitinib (bradycardic effect) Increases serum concentration of the following drugs:
Afatinib [reduce Afatinib dose by 10 mg if not tolerated],
Enhances therapeutic effect of the following drugs: Antiarrhythmic Agents, Class Ia e.g. Procainamide,
Beta Blockers [except Levobunolol, Metipranolol] Artesunate, Bosutinib, Cardiac Glycosides e,g, Digoxin
(bradycardic effect), Bradycardia-causing Agents [when used concomitantly, reduce Cardiac Glycosides
(bradycardic effect), Lacosamide (AV blocking effect) dose by 30-50% or reduce frequency of administration],
Colchicine (may increase colchicine distribution into
Increases risk of adverse or toxic effects of Amiodarone: certain tissues, e.g., brain), Dabigatran Etexilate,
Cyclophosphamide (pulmonary toxicity), Porfimer Doxorubicin (Conventional), Everolimus, Flecainide
(photosensitizing effect), Telaprevir, Verteporfin [when used concomitantly, decrease Flecainide dose by
(photosensitizing effect) 50%], Lomitapide [limit maximum dose to 30 mg daily],
Loratadine, Metoprolol, Pazopanib, Pimozide,
Reduces therapeutic effect of the following drugs: Propafenone, Silodosin, Thioridazine, Tizanidine [if
Codeine, Tramadol (opioid-like effects) concomitant use cannot be avoided, initiate Tizanidine
at an adult dose of 2 mg and increase in 2–4 mg
Avoid concomitant use with: increments based on patient response], Topotecan,
Decreases bioavailability of Amiodarone: Vincristine (Liposomal), Vitamin K Antagonists, e.g.,
Bile acid sequestrants Warfarin

Decreases metabolism of Amiodarone: Reduces therapeutic effect of the following drugs:

Grapefruit Juice Agalsidase Alfa, Agalsidase Beta, Sodium Iodide I131

100
CARDIOVASCULAR SYSTEM
Administration:
For oral administration, administer consistently with
meals. Take in divided doses with meals if GI upset
occurs or if taking large daily doses. If GI intolerance
occurs with single-dose therapy, use twice daily dosing.
For IV infusions >1 hour, use concentrations ≤2 mg/mL
unless a central venous catheter is used. Use only
volumetric infusion pump to prevent underdosage.
Administer through an IV line located as centrally as
possible.
For IV infusions >2 hours, administer in a non-PVC
container (e.g., glass, polyolefin). PVC tubing is
recommended for administration regardless of infusion
duration. Flush with saline prior to and following infusion
to prevent incompatibilities with heparin.
For continuous IV infusions, use an in­line filter to reduce
the incidence of phlebitis. Adjust administration rate to
urgency. Give more slowly when perfusing arrhythmia is
present. Slow the infusion rate if hypotension or
bradycardia develops.
NOTE: IV administration at lower flow rates, i.e., pediatric
use, and higher concentrations than recommended may
result in leaching of plasticizers (DEHP) from IV tubing.
DEHP may adversely affect male reproductive tract
development.
Pregnancy Category: D
ATC Code: C01BD01
CLASS IV ANTIARRHYTHMICS
Rx VERAPAMIL
Oral: 80 mg tablet (as hydrochloride)
240 mg MR tablet (as hydrochloride) [for
maintenance therapy]
Inj.: 2.5 mg/mL (as hydrochloride), 2 mL ampule (IV)
A non-dihydropyridine calcium channel blocker that acts
during depolarization by inhibiting calcium ions from
entering “slow channels” or select voltage-sensitive
areas of vascular smooth muscle and myocardium.
Verapamil produces relaxation of coronary vascular
smooth muscle and coronary vasodilation, which
increases myocardial oxygen delivery in patients with
vasospastic angina and slows automaticity and
conduction of AV node.
Indications: Paroxysmal supraventricular tachycardia (PSVT)
prophylaxis; atrial fibrillation (rate control); ventricular
tachycardia
Contraindications: Severe left ventricular dysfunction;
hypotension (systolic pressure <90 mm Hg); cardiogenic
shock; sick sinus syndrome; second- or third-degree AV
block without a cardiac pacemaker; atrial flutter or
fibrillation; accessory bypass tract; any supraventricular
tachyarrhythmia conducted across an accessory
pathway (Wolff-Parkinson-White syndrome-associated
tachyarrhythmias including pre-excited atrial
fibrillation/atrial flutter, antidromic atrioventricular
reentrant tachycardia); Lown-Ganong-Levine syndrome);
concurrent use of IV beta-blocking agents; ventricular
tachycardia.
Dose:
PSVT prophylaxis, by mouth, ADULT, 240–480 mg daily in
3–4 divided doses.
Atrial fibrillation (rate control), by IV injection, ADULT, initially
C
0.075–0.15 mg/kg IV bolus over 2 minutes (usual dose,
5–10 mg) ; if no response, administer an additional 10
mg after 15–30 minutes; if patient responds to the initial
or repeat bolus dose, administer continuous infusion
initially at 5 mg/hour; titrate to goal heart rate;
by mouth, ADULT, as immediate-release tablet, 240-480
mg daily in 3–4 divided doses;
as MR tablet, 180–480 mg once daily.
SVT, by IV injection, ADULT, 2.5–5 mg over 2 minutes; a
second dose of 5–10 mg (approximately 0.15 mg/kg)
may be given 15–30 minutes after the initial dose if
patient tolerates, but does not respond to initial dose
(maximum total dose, 20–30 mg); CHILD 1–15 years,
0.1–0.3 mg/kg per dose over 2 minutes (maximum, 5
mg per dose); may repeat dose in 30 minutes if
inadequate response (maximum for second dose, 10
mg).
NOTE: Verapamil is NOT included in the Pediatric Advanced
Life Support (PALS) tachyarrhythmia algorithm.
Dose Adjustment:
Renal Impairment: Use with caution and monitor ECG.
Reduced renal clearance of verapamil and its
metabolite, norverapamil, in advanced renal failure.
Initiate at 100 mg daily at bedtime.
NOTE: NOT removed by hemodialysis.
Hepatic Impairment:
In patients with liver cirrhosis, administer 20% and 50%
of normal dose for oral and IV administration,
respectively. Initiate at 100 mg daily at bedtime. Monitor
ECG.
For patients with severe impairment, administer 30% of the
normal dose.
Precautions:
Conduction abnormalities (can cause first-degree AV block
or sinus bradycardia); hypotension or syncope
(symptomatic hypotension with or without syncope rarely
occur; blood pressure must be lowered at a rate
appropriate for the patient's clinical condition);
arrhythmia (severe hypotension likely to occur upon
administration); heart failure (avoid use; can exacerbate
condition); hypertrophic cardiomyopathy (use with
caution in patients with outflow tract obstruction)
Attenuated neuromuscular transmission (dose reduction
may be required); gastrointestinal effects (use MR
tablets with caution in patients with severe GI narrowing)
Hepatic impairment (monitor hemodynamics and ECG);
increased hepatic enzymes; renal impairment (monitor
hemodynamics and ECG, particularly if with concomitant
hepatic impairment)
Elderly (may experience a greater hypotensive response;
constipation may be more of a problem in the elderly;
101

may not be bioequivalent in the elderly); children (avoid
IV use in neonates and young infants due to severe
apnea, bradycardia, hypotensive reactions, and cardiac
arrest; use with caution in children as myocardial
depression and hypotension may occur)
Pregnancy (may cause adverse effects, including
bradycardia, heart block, and hypotension in fetus, and
maternal toxicity; crosses the placenta; fetal monitoring
is recommended); lactation excreted in breastmilk; not
C
recommended in nursing mothers)
Adverse Drug Reactions:
Common: Headache, gingival hyperplasia, constipation,
peripheral edema, hypotension, CHF, pulmonary edema,
AV block, bradycardia, flushing, fatigue, dizziness,
lethargy, pain, sleep disturbance, rash, dyspepsia,
nausea, diarrhea, myalgia, paresthesia, dyspnea, flu­like
syndrome, abdominal discomfort, alopecia, angina,
arthralgia, atrioventricular dissociation, blurred vision,
bruising, cerebrovascular accident, chest pain,
claudication, confusion, diaphoresis, ECG abnormal,
equilibrium disorders, erythema multiforme, exanthema,
extrapyramidal symptoms, galactorrhea,
hyperprolactinemia, gastrointestinal distress,
gynecomastia, hyperkeratosis, impotence, insomnia,
macules, MI, muscle cramps, palpitation, psychosis,
purpura (vasculitis), shakiness, somnolence, spotty
menstruation, Stevens-Johnson syndrome, syncope,
tinnitus, urination increased, urticaria, weakness,
xerostomia
Less Common: Bronchospasm, laryngeal spasm,
depression, diaphoresis, itching, muscle fatigue,
respiratory failure, rotary nystagmus, seizure, sleepiness,
urticaria, vertigo, asystole, eosinophilia, EPS, exfoliative
dermatitis, GI obstruction, hair color change, paralytic
ileus, Parkinsonian syndrome, pulseless electrical
activity, shock, ventricular fibrillation
Drug Interactions:
NOTE: Verapamil may inhibit CYP1A2 (weak), CYP2C9
(weak), CYP2D6 (weak), CYP3A4 (moderate), and P-
glycoprotein.
Monitor closely with:
Decreases metabolism of the following drugs:
Pimecrolimus, Tacrolimus
Enhances therapeutic effect of Verapamil:
Anti-hypertensive effect: Alpha1 Blockers e.g. Alfuzosin
Anilidopiperidine Opioids e.g., Fentanyl (bradycardic);
Barbiturates e.g. (antihypertensive effect), Bretylium
(bradycardic effect; AV blockade); Brimonidine, Topical
(antihypertensive effect); Clonidine (AV blocking effect);
Magnesium Salts (antihypertensive effect), Molsidomine
(antihypertensive effect); Nicorandil (antihypertensive
effect); Other Antihypertensives (antihypertensive
effect); Other Bradycardia-causing Agents (bradycardic
effect); Other Calcium Channel Blockers
(antihypertensive effect); Pentoxifylline
(antihypertensive effect); Phosphodiesterase-5
Inhibitors (antihypertensive effect); Prostacyclin
Analogues (antihypertensive effect); Quinidine
(antihypertensive effect); Regorafenib (bradycardic
effect); Ruxolitinib (bradycardic effect); Tofacitinib
(bradycardic effect)
102
CARDIOVASCULAR SYSTEM
Enhances therapeutic effect of the following drugs:
Beta Blockers [except Levobunolol] (antihypertensive
effect); Cardiac Glycosides (AV blocking effect);
Diazoxide (antihypertensive effect); Fingolimod
(bradycardic effect); Herbs with Hypotensive Properties
(antihypertensive effect); Lacosamide (AV blocking
effect); MAO Inhibitors [except Linezolid, Tedizolid]
(antihypertensive effect)
Enhances therapeutic effect of the following drugs:
Midodrine (bradycardic effect); Neuromuscular-blocking
Agents; Nondepolarizing (neuromuscular blocking
effect); Nitroprusside (antihypertensive effect);
Salicylates (anticoagulant effect)
Increases bioavailability of the following drugs:
Fexofenadine
Increases metabolism of Verapamil:
Barbiturates
Increases risk of adverse or toxic effects of Verapamil:
Clonidine (sinus node dysfunction)
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea); Beta
Blockers [except Levobunolol] (bradycardia; heart
failure); Duloxetine (orthostatic hypotensive effect);
Flecainide (impairment of myocardial contractility and
AV nodal conduction); Levodopa (orthostatic hypotensive
effect); Lithium (neurotoxic effect); Magnesium Salts;
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotensive effect)
Reduces therapeutic effect of Verapamil:
Calcium Salts; Herbs with Hypertensive Properties
(antihypertensive effect); Methylphenidate
(antihypertensive effect)
Reduces therapeutic effect of the following drugs:
Clopidogrel, Metformin
Avoid concomitant use with:
Decreases metabolism of Verapamil:
Cyclosporine, Systemic; Macrolide
Antibiotics [except Azithromycin, Fidaxomicin,
Spiramycin]; Protease Inhibitors; Antifungal Agents,
Systemic Azole Derivatives [except Fluconazole
Decreases metabolism of the following drugs:
Buspirone, Cyclosporine (Systemic)
Decreases serum concentration of Verapamil:
Carbamazepine, Dabrafenib, Mitotane, Phenytoin,
Rifamycin Derivatives, St John’s Wort
Enhances therapeutic effect of Verapamil:
Antifungal Agents, Systemic Azole Derivatives [except
Fluconazole, Isavuconazonium Sulfate] (negative
inotropic effect); Dantrolene (negative inotropic effect);
Ivabradine (QTc-prolonging effect); Telithromycin
(bradycardic and antihypertensive effects)
CARDIOVASCULAR SYSTEM

Enhances therapeutic effect of the following drugs: OTHER ANTIARRHYTHMIC AGENTS

Amiodarone (bradycardic effect); Ceritinib (bradycardic
effect); Dronedarone (AV-blocking and other
electrophysiologic effects); Ivabradine (bradycardic Rx ADENOSINE
effect)
Inj.: 3 mg/mL, 2 mL vial (IV)
Increases metabolism of Verapamil:
Nafcillin
A class V antiarrhythmic agent that slows conduction time
through the AV node, interrupting the re­entry pathways

C
Increases risk of adverse or toxic effects of Verapamil:
through the AV node, thus restoring normal sinus rhythm.
Dantrolene (hyperkalemic effect); Protease Inhibitors (AV
nodal blockade)
Indications: Treatment of paroxysmal supraventricular
tachycardia (PSVT), including accessory bypass tracts
Increases risk of adverse or toxic effects of the following
(Wolff-Parkinson-White syndrome); pharmacologic stress
drugs:
agent in myocardial perfusion thallium­201 scintigraphy.
Amifostine (hypotensive effect); Amiodarone (sinus
arrest); Antifungal Agents, Systemic Azole Derivatives
Contraindications: Patients with second- or third-degree AV
[except Fluconazole, Isavuconazonium Sulfate];
block, sick sinus syndrome, and symptomatic
Disopyramide (potential for profound depression of
bradycardia but without a cardiac pacemaker; known or
myocardial contractility); Obinutuzumab (hypotensive
suspected bronchoconstrictive or bronchospastic lung
effect); Oxycodone; Rituximab (hypotensive effect)
disease; asthma.
Increases serum concentration of Verapamil:
Dose:
Cimetidine, Conivaptan, CYP3A4 Inducers; Fusidic Acid,
PSVT, by rapid IV push, ADULT and CHILD ≥50 kg, initially 6
Systemic; Grapefruit Juice; Idelalisib; Mifepristone,
mg over 1–2 seconds via a peripheral line; if not effective
Protease Inhibitors; Stiripentol
within 1–2 minutes, administer 12 mg; may repeat 12
mg bolus if needed (maximum single dose, 12 mg);
Increases serum concentration of the following drugs:
follow each dose with 20 mL normal saline flush (reduce
Afatinib [reduce Afatinib by 10 mg if not tolerated];
initial dose to 3 mg if concomitantly on carbamazepine
Avanafil [when used concomitantly, limit Avanafil dose to
or dipyridamole, or has a transplanted heart, or if
50 mg per 24-hour period]; Budesonide (Systemic);
administered via central line); INFANT and CHILD
Carbamazepine; Cilostazol [reduce Cilostazol dose to 50
<50 kg, initially 0.05–0.1 mg/kg over 1–2 seconds via a
mg twice daily]; Colchicine (may increase colchicine
peripheral line (maximum initial dose, 6 mg); if
distribution into certain tissues, e.g., brain); Dabigatran
conversion of PSVT does not occur within 1–2 minutes,
Etexilate [active metabolites]; Dapoxetine (limit
increase dose by 0.05–0.1 mg/kg; repeat until sinus
Dapoxetine dose to 30 mg daily); Dofetilide,
rhythm is established or to a maximum single dose of 0.3
Domperidone; Doxorubicin, Conventional Dronedarone,
mg/kg or 12 mg; follow each dose with 20 mL normal
Eletriptan, Eplerenone, Everolimus, Fentanyl,
saline flush.
Fosphenytoin, Halofantrine, Ivabradine, Ivacaftor,
SVT treatment in pediatric advanced life support, by IV
Lovastatin [initiate Lovastatin at 10 mg daily; do not
injection, CHILD, initially 0.1 mg/kg (maximum initial
exceed 20 mg daily]; Oxycodone [including active
dose, 6 mg); if not effective within 1–2 minutes,
metabolite, Oxymorphone]; Pazopanib, Phenytoin,
administer 0.2 mg/kg (maximum single dose, 12 mg);
Pimozide; Ranolazine [limit Ranolazine dose to a
follow each dose with ≥5 mL normal saline flush.
maximum of 500 mg twice daily]; Rivaroxaban, Silodosin,
Pharmacologic stress testing, by continuous IV infusion,
Simeprevir; Simvastatin [if concomitant use cannot be
ADULT, 140 micrograms/kg per minute for 6 minutes
avoided, limit Simvastatin to 10 mg daily]; Suvorexant,
using syringe or volumetric infusion pump via peripheral
Tizanidine [if concomitant use cannot be avoided, initiate
line (total dose, 840 micrograms/kg); inject thallium–
Tizanidine at 2 mg and increase in 2–4 mg increments
201 at midpoint of infusion (3 minutes).
based on patient response]; Tolvaptan, Topotecan,
Ulipristal, Vindesine; Zopiclone [if concomitant use
Dose Adjustment:
cannot be avoided, initiate Zopiclone dose at not more
Heart Transplant Recipients:
than 3.75 mg]
Reduce dose.
Reduces therapeutic effect of Verapamil:
Yohimbine (antihypertensive effect)
Precautions:
Atrial fibrillation or flutter (especially in patients with PSVT
Administration:
and underlying Wolff-Parkinson-White syndrome);
For IV route, administer for over 2 minutes. Administer
Cardiovascular events (e.g. cardiac arrest, fatal and
for over 3 minutes in older patients.
nonfatal, myocardial infarction, cerebrovascular
accident, hemorrhagic and ischemic, and sustained
For oral route, take with food. Do NOT crush or chew MR
ventricular tachycardia requiring resuscitation;
tablets.
arrhythmia); conduction disturbances (may produce
first-, second-, or third-degree heart block; rare,
Pregnancy Category: C
prolonged episodes of asystole);
Hypertension; Hypotension; Pulmonary artery hypertension
ATC Code: C08DA01
Respiratory disease (dyspnea, bronchoconstriction, and
respiratory compromise have occurred)

103

Hypersensitivity (watch out for dyspnea, pharyngeal edema,
erythema, flushing, rash, or chest discomfort)
Seizures (new-onset or recurrent seizures)
Electrolyte imbalance (correct hypokalemia or
hypomagnesemia prior to use and throughout therapy)
Heart transplant recipients (use with extreme caution; may
cause prolonged asystole)
Elderly (may be at increased risk of hemodynamic effects,
bradycardia, and/or AV block; may be more sensitive to
C
the effects of Adenosine)
Lactation (not known if excreted in breastmilk; potential for
adverse reactions in the nursing infant)
Adverse Drug Reactions:
Common: Cardiac arrhythmia, chest pressure and
discomfort, atrioventricular block, depression of ST
segment on ECG, hypotension, chest pain, palpitations,
headache, dizziness, nervousness, paresthesia,
numbness, apprehension, facial flushing, diaphoresis,
gastrointestinal distress, nausea, neck discomfort, upper
extremity discomfort, dyspnea, hyperventilation
Less Common: Asystole (prolonged), atrial fibrillation,
blurred vision, bradycardia, bronchospasm, burning
sensation, cardiac arrest (fatal and nonfatal), increased
intracranial pressure, injection site reaction, loss of
consciousness, metallic taste, myocardial infarction,
respiratory arrest, seizure, torsade de pointes, transient
hypertension, ventricular arrhythmia, ventricular
fibrillation, ventricular tachycardia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Adenosine:
Nicotine (AV-blocking and tachycardic effects)
Increases risk for adverse or toxic effects of Adenosine:
Digoxin
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Adenosine:
Carbamazepine (risk of higher degree heart block),
Dipyridamole (cardiovascular effects)
Reduces therapeutic effect of Adenosine:
Caffeine and Caffeine-containing Products, Theophylline
Derivatives e.g Aminophylline
Administration: Administer via rapid bolus IV or IV infusion
only.
Administer IV push over 1–2 seconds via a peripheral IV
site as proximal as possible to trunk. Do NOT inject into
the lower arm, hand, lower leg, or foot. Follow each bolus
with a rapid normal saline flush. Use separate syringes
for Adenosine and NS flush, connected to a T-connector
or stopcock.
Pregnancy Category: C
ATC Code: C01EB10
104
CARDIOVASCULAR SYSTEM
Rx ATROPINE
Oral: 600 micrograms (as sulfate) (equivalent to 500 mcg
atropine)
Inj.: 1 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
An alkaloid from Atropa belladonna that competitively
blocks acetylcholine action in central and peripheral
muscarinic autonomic receptors.
Indications: Adjunct chronotropic agent; bradycardia
Dose:
Bradycardia, by IV injection, ADULT, 0.5 mg every 3-5
minutes (maximum dose, 3 mg or 0.04 mg/kg);
ADOLESCENT, CHILD, and INFANT, 0.02 mg/kg
(maximum single dose, 0.5 mg); may repeat once in 3-5
minutes (maximum total dose, 1 mg).
Stress echocardiography (adjunct chronotropic agent), by IV
injection, ADULT, 0.25–0.5 mg up to a total dose of 1–2
mg until 85% of target heart rate is achieved.
NOTE: May be ineffective in heart transplant recipients.
Use in children at doses <0.1 mg have been associated
with paradoxical bradycardia.
Administration: Administer undiluted by rapid IV injection.
Slow injection may result in paradoxical bradycardia.
See Atropine under Drugs for Functional Gastrointestinal
Disorders – Anticholinergics in Chapter 1: Alimentary
Tract and Metabolism for other information.
Pregnancy Category: B/C (product-specific)
ATC Code: Not available
Rx MAGNESIUM SULFATE
Inj.: 250 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IV)
250 mg/mL (as heptahydrate), 10 mL, 20 mL, and 50
mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IV)
Indication: Ventricular arrhythmia
Dose:
NOTE: Individualize dose based on patient requirement and
response. Discontinue as soon as desired response is
obtained.
Torsade de pointes, ventricular fibrillation, or pulseless
ventricular tachycardia associated with torsade de
pointes, by IV injection, ADULT, 1–2 g over 15 minutes.
Dose Adjustment:
Geriatric:
Use with caution. Reduce dose of magnesium sulfate.
Renal Impairment:
Use with caution. Up to 50% of an IV dose may be eliminated
in the urine.
CARDIOVASCULAR SYSTEM
Reduce dose. Do not exceed 20 g every 48 hours.
Administration: For intravenous use. May be administered
via IV push, IVPB, or continuous IV infusion.
Do NOT administer at doses exceeding 20%.
For IV push, do NOT administer faster than 150
mg/minute. Administer over 1–2 minutes in patients
with persistent pulseless VT or VF with known
hypomagnesemia. Administer over 15 minutes in
patients with torsade de pointes.
If patient is severely symptomatic, or has conditions such
as preeclampsia or eclampsia, more aggressive therapy
(≤4 g over 4–5 minutes) may be required.
See Magnesium Sulfate under I.V. Solutions Additives in
Chapter 2: Blood and Blood Forming Organs for other
information.
Pregnancy Category: D
ATC Code: Not available
CARDIAC STIMULANTS, EXCLUDING
CARDIAC GLYCOSIDES
Rx DOBUTAMINE
Inj.: 50 mg/mL (concentrate, as hydrochloride), 5 mL
ampule (IV infusion)
2 mg/mL (as hydrochloride), 250 mL D5W (pre-mixed)
(IV)
A racemic mixture of dobutamine. It stimulates myocardial
beta1­adrenergic receptors and some alpha1-receptors.
This results in increased contractility and heart rate, and
some peripheral vasodilation.
Indications: For management of cardiogenic or vascular
shock; inotropic agent; cardiac decompensation
Contraindications: Hypertrophic cardiomyopathy with
outflow tract obstruction (formerly known as idiopathic
hypertrophic subaortic stenosis [IHSS])
Dose:
Immediate post­cardiac arrest care setting, based on Adult
Advanced Cardiovascular Life Support (ACLS) guidelines,
by IV infusion, ADULT, initially 5–10 micrograms/kg per
minute; titrate to effect.
Cardiac output maintenance and post-resuscitation
stabilization, based on Pediatric Advanced Life Support
(PALS) guidelines, by IV injection, CHILD, 2–20
micrograms/kg per minute.
Cardiac decompensation, by IV infusion, ADULT, initially
0.5–1 micrograms/kg per minute; may initiate at higher
doses, e.g., 2.5 micrograms/kg per minute, depending
on severity of decompensation with titration to desired
response (maintenance dose, 2–20 micrograms/kg per
minute; maximum dose, 40 micrograms/kg per minute).
Dose Adjustment:
Heart Failure:
Reduce doses to minimize adverse effects (maximum dose,
20 micrograms/kg per minute).
Precautions:
Arrhythmias (e.g. ventricular arrhythmias and sudden
cardiac death; may increase ventricular response rate)
Blood pressure effects (increase in blood pressure is more
C
common due to augmented cardiac output; may also
cause hypotension due to peripheral vasodilation)
Heart failure complications (increased risk of hospitalization
and death with prolonged use)
Tachycardia and ventricular ectopy (dose-related)
Aortic stenosis (renders therapy ineffective); electrolyte
imbalance (correct hypokalemia or hypomagnesemia
prior to use and throughout therapy to minimize the risk
of arrhythmias); hypovolemia; active myocardial
ischemia or recent myocardial infarction (can increase
myocardial oxygen demand)
Lactation (not known if excreted in breastmilk; use with
caution in nursing women)
Adverse Drug Reactions:
Common: Ventricular premature contractions, angina
pectoris, chest pain, palpitations, hypotension,
increased blood pressure, increased heart rate, localized
phlebitis, ventricular ectopy (increased), headache,
paresthesia, nausea, local inflammation, local pain (from
infiltration), leg cramps, dyspnea, fever
Rare: Skin necrosis, thrombocytopenia
Drug Interactions:
Monitor closely with:
Decreases metabolism of Dobutamine:
COMT Inhibitors e.g. Entacapone
Enhances therapeutic effect (hypertensive and tachycardic
effects) of Dobutamine:
Atomoxetine, Tedizolid
Increases risk of adverse or toxic effects of the following
drugs:
Doxofylline, Other Sympathomimetics
Reduces therapeutic effect of Dobutamine:
Calcium Salts
Avoid concomitant use with:
Enhances therapeutic effect of Dobutamine:
Linezolid (hypertensive effect)
Administration: For IV administration. Always administer via
infusion device into a large vein.
Pregnancy Category: B
ATC Code: C01CA07
105

Rx DOPAMINE
Inj.: 40 mg/mL (as hydrochloride), 5 mL vial / ampule (IV)
800 micrograms/mL (as hydrochloride), 250 mL D5W
(pre-mixed) (IV)
1.6 mg/mL (as hydrochloride), 250 mL D5W (pre-
mixed) (IV)
C
A direct-acting sympathomimetic, which acts on beta1
receptors in cardiac muscles, leading to increased
contractility with little effect on rate. Dopamine may be
given for short periods in the treatment of severe heart
failure; it also causes renal vasodilation, thus preserving
renal perfusion and renal function. It also has peripheral
vasoconstricting properties when given at higher doses.
Indications: Hypovolemic shock and hemorrhagic shock as
adjuvant therapy to volume replacement; cardiogenic
shock (where systolic BP <90 in adults); septic shock
Contraindications: Ischemic heart disease;
tachyarrhythmias, ventricular fibrillation;
pheochromocytoma; hyperthyroidism
Dose:
Hypovolemic and hemorrhagic shock as adjuvant therapy to
volume replacement, by IV infusion into a large vein,
ADULT, initially 5 micrograms/kg per minute, gradually
increase by 5–10 micrograms/kg per minute according
to blood pressure, cardiac output, and urine output
(seriously-ill patients, up to 20 micrograms/kg per
minute); CHILD, 2–10 micrograms/kg per minute
depending on patient response.
Dose Adjustment:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose reduction may be
warranted. Use with caution
For severe impairment, refer patient to a specialist.
Precautions:
WARNING: This may cause peripheral ischemia in
patients with history of occlusive vascular disease
(e.g., atherosclerosis and Raynaud’s syndrome). In
case of extravasation causing peripheral ischemia,
use phentolamine for local infiltration.
NOTE: Dosage is critical – at low doses, it stimulates
myocardial contractility and increases cardiac output;
however, higher doses (more than 5 micrograms/kg per
minute) cause vasoconstriction, which increases blood
pressure and may also cause worsening of heart failure.
Close monitoring of arterial and venous pressure and
continuous ECG should be performed; treatment with
sympathomimetics should be guided by hemodynamic
monitoring (individualize treatment depending on clinical
response); use low dose in cardiogenic shock due to MI;
prolonged use of sympathomimetics may result in
diminution of therapeutic effect (downregulation of
receptors; disproportionate increase in diastolic
pressure)
Correct hypovolemia before treatment and maintain blood
volume during treatment; correct hypoxia, hypercapnia,
and metabolic acidosis before or at the start of treatment
106
CARDIOVASCULAR SYSTEM
(may reduce effectiveness and/or increase incidence of
adverse effects of dopamine)
Pulmonary hypertension (may be worsened due to
dopamine-induced pulmonary vasoconstriction);
suppresses pituitary secretion of thyroid-stimulating
hormone, growth hormone and prolactin
Elderly; Pregnancy (limited human data available)
Adverse Drug Reactions:
Common: Anginal pain, chest pain, dyspnea, ectopic beats,
flushing, headache, hypotension with dizziness, nausea,
palpitations, peripheral vasoconstriction, vomiting,
tachycardia
Less Common: Abnormal ventricular conduction,
bradycardia, extravasation (may cause necrosis and
sloughing of surrounding tissue), fainting, gangrene,
hypertension, mydriasis, piloerection, uremia
Rare: Allergic reactions, ventricular arrhythmia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Dopamine:
MAO Inhibitors, e.g., Linezolid, Phenelzine,
Tranylcypromine
Increases risk of adverse or toxic effects of Dopamine:
Phenytoin (hypotension; bradycardia)
Reduces therapeutic effect of Dopamine:
Alpha-adrenergic Blocking Agents
Avoid concomitant use with:
Decreases serum concentration of Dopamine:
Metoclopramide (inhibits GI absorption)
Increases risk of adverse or toxic effects of Dopamine:
Vasoconstrictors, e.g., Ergot Alkaloids (peripheral
ischemia)
Reduces therapeutic effect of Dopamine:
Beta-adrenergic Blocking Agents, e.g., Propranolol,
Metoprolol (cardiac effects); Chlorpromazine
(hypertensive effects); Fluphenazine (hypertensive
effects); Haloperidol (hypertensive effects);
Vasoconstrictors, e.g., Ergot Alkaloids (peripheral
vasoconstriction)
Administration: Administer via a large vein high up in the
limb, preferably the arm, to avoid tissue necrosis.
Dilute solution, usually to 1.6 or 3.2 mg/mL, in dextrose
5% or sodium chloride 0.9% before administration. Pre-
mixed dopamine solution is also available in
single/double concentration.
Do NOT admix with alkaline solutions, such as sodium
bicarbonate to prevent drug inactivation.
Pregnancy Category: C
ATC Code: C01CA04
CARDIOVASCULAR SYSTEM
Rx EPINEPHRINE (ADRENALINE)
Inj.: 1 mg/mL (as hydrochloride), 1 mL ampule (IV, IM, SC)
0.3 mg auto-injector (IM-preload), 0.3 mL preloaded
injection pen
A direct-acting, mixed alpha- and beta-adrenoceptor
agonist; a sympathomimetic catecholamine, which is a
potent cardiac stimulant, peripheral vasoconstrictor and
bronchodilator.
NOTE: Vasodilator at low dose (beta2-receptors).
Vasoconstrictor at high dose (alpha-receptors).
Indications: Management of anaphylactic shock; may be
used in cases of serious and fatal anaphylaxis; cardiac
arrest
Contraindications: Known hypersensitivity to epinephrine or
any of the excipients; pheochromocytoma; use in local
anesthesia of fingers, toes, ears, nose or genitalia;
shock; organic heart disease or cardiac dilatation;
closed-angle glaucoma; labor
NOTE: There are no absolute contraindications to the use of
epinephrine in life-threatening allergic reactions.
Dose:
Anaphylaxis, by IM or SC injection of 1:1,000 injection,
ADULT and ADOLESCENT, 500 micrograms (0.5 mL);
CHILD 6–12 years, 250 micrograms (0.25 mL); CHILD 6
months to 6 years, 120 micrograms (0.12 mL); INFANT
<6 months, 50 micrograms (0.05 mL); by SC injection of
1:1,000 injection, CHILD, 10 micrograms/kg (0.01
mL/kg), repeat if necessary at intervals of 20 minutes to
4 hours depending on the response of the patient and
the severity of the condition (maximum single dose, 500
micrograms).
Dose Adjustment: No information found
Precautions:
Cerebrovascular disease (increased risk of peripheral
ischemia or stroke); hypovolemia (correct before using
epinephrine); acidosis, hypercapnia, or hypoxia (may
reduce effectiveness and increase incidence of adverse
effects); heart diseases, e.g., ischemic heart disease,
heart failure, other arrhythmias (increased risk of
arrhythmias, angina, and myocardial ischemia); aortic
stenosis and hypertrophic cardiomyopathy (may
increase outflow obstruction); arrhythmias; pulmonary
hypertension (may worsen due to pulmonary
vasoconstriction).
Hyperthyroidism or diabetes mellitus (adverse reactions are
more likely to occur)
Elderly; Pregnancy (use with caution during second stage of
labor).
Adverse Drug Reactions:
Common: Anxiety, dizziness, dyspnea, fear, headache,
hyperglycemia, nausea, pallor, palpitations,
restlessness, sweating, tachycardia, tremor, vomiting,
weakness
Less Common: Angina, cerebral hemorrhage, excessive
increase in blood pressure, hypertension, peripheral
ischemia and necrosis (at infusion site), pulmonary
edema, ventricular arrhythmias
Rare: Allergic reactions
Drug Interactions:
NOTE: Alpha-adrenergic blockers antagonize
vasoconstricting and hypertensive effects of
epinephrine.
C
Monitor closely with:
Increases therapeutic effect of Epinephrine:
Tricyclic Antidepressants (blocks catecholamine uptake)
Increases risk of adverse or toxic effects of Epinephrine:
Drugs causing Potassium loss, [e.g., Corticosteroids,
Potassium-depleting Diuretics, Aminophylline,
Theophylline (hypokalemia)], Oxytocin (hypertension),
Tricyclic Antidepressants (arrhythmia)
Reverses therapeutic effect of Epinephrine:
Ergot Alkaloids (pressor effect)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Epinephrine:
Beta Blockers (hypertension followed by bradycardia)
Reduces therapeutic effect of Epinephrine:
Alpha Blockers (vasoconstricting and hypertensive
effects), Beta Blockers (prevents receptor activation)
Reduces therapeutic effect of Hypoglycemic Agents (loss of
blood sugar control)
Administration: Best administered by SC or IM injection into
the anterolateral aspect of the middle third of the thigh
for anaphylaxis or by IV injection for cardiac arrest or
emergency situations.
Administer by slow IV injection only in severely ill patients
when there is doubt about the adequacy of circulation
and absorption from the IM site.
Do NOT administer by intracardiac injection.
Do NOT mix with alkaline solutions. Discard after 24
hours or if solution is discolored or contains precipitate.
NOTE: If a central line is used, infusion pump is required. If
given through a peripheral line, each dose should be
followed by a flush of 20 mL of IV fluid to ensure delivery
of the drug to the central compartment.
Pregnancy Category: C
ATC Code: C01CA24
107

Rx NOREPINEPHRINE
Inj.: 1 mg/mL (as bitartrate), 2 mL and 4 mL ampule (IV
infusion)
1 mg/mL concentrate solution (as bitartrate), 10 mL
ampule (IV infusion)
2 mg/mL, solution for injection (as bitartrate), 4 mL
ampule
C
A direct-acting, mixed alpha- and beta-adrenoceptor agonist
that stimulates beta1-adrenergic receptors and alpha-
adrenergic receptors causing increased contractility and
heart rate, as well as peripheral vasoconstriction. This
results in an increased systemic blood pressure and
coronary blood flow. Vasoconstricting effects on alpha-
receptors are greater than the inotropic and chronotropic
effects on beta receptors.
Indications: For cardiogenic or vascular shock, persists after
adequate fluid volume replacement; severe hypotension;
first-choice vasopressor for the treatment of sepsis and
septic shock in adults
Contraindications: Hypotension from hypovolemia except as
an emergency measure to maintain coronary and
cerebral perfusion until volume could be replaced;
mesenteric or peripheral vascular thrombosis (unless
life-saving procedure); during anesthesia with
cyclopropane or halothane (risk of ventricular
arrhythmias)
Dose:
NOTE: Norepinephrine dose is stated in terms of its base
form.
Hypotension or shock, by continuous IV infusion, ADULT,
initially 8-12 micrograms/minute, titrate to desired
response (usual maintenance dose, 2–4
micrograms/minute); dosage range varies greatly
depending on clinical situation; CHILD, initially 0.05–0.1
micrograms/kg per minute; titrate to desired effect
(maximum dose, 2 micrograms/kg per minute) [NOTE: If
patient remains hypotensive despite large doses,
evaluate for occult hypovolemia, and provide fluid
resuscitation as appropriate.]
Post cardiac arrest care, by continuous IV infusion, ADULT,
initially 0.1–0.5 micrograms/kg per minute, titrate to
desired response.
Sepsis and septic shock, by continuous IV infusion, ADULT,
0.01–3 micrograms/kg per minute, titrate to desired
response.
Dose Adjustment: No information found
Precautions:
WARNING: If extravasation occurs, infiltrate the area
with 5–10 mg Phentolamine diluted in 10–15 mL
of saline using a fine hypodermic needle.
Administer Phentolamine within 12 hours after
extravasation is noted to prevent sloughing or
necrosis.
108
CARDIOVASCULAR SYSTEM
Extravasation (extravasation may cause severe ischemic
necrosis).
Pregnancy (animal reproduction studies have not been
conducted; norepinephrine is an endogenous
catecholamine and crosses the placenta);
Lactation (not known if excreted in breast milk; use with
caution when administering to nursing women).
Adverse Drug Reactions:
Common: Arrhythmias, bradycardia, peripheral ischemia,
anxiety, headache (transient), skin necrosis, dyspnea,
respiratory difficulty
Drug Interactions:
Monitor closely with:
Decreases metabolism of Norepinephrine:
COMT Inhibitors e.g., Entacapone
Enhances therapeutic effect of Norepinephrine:
MAO Inhibitors e.g., Selegeline (hypertensive effect;
tachycardia)
Enhances therapeutic effect of the following drugs:
Atomoxetine (hypertensive and tachycardic effects),
Droxidopa (hypertensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Doxofylline, Sympathomimetics
Reduces diagnostic effect of Ioflupane I123
Reduces therapeutic effect of Norepinephrine:
Alpha Blockers e.g., Phentolamine (vasodilating effect)],
Spironolactone (vasoconstricting effect)
Reduces therapeutic effect of Alpha Blockers e.g.,
Phentolamine (vasoconstricting effect)
Avoid concomitant use with:
Enhances therapeutic effect of Norepinephrine:
Beta Blockers (vasopressor effect), Ergot Derivatives
[except Ergoloid Mesylates] (hypertensive and
vasoconstricting effects), Hyaluronidase
(vasoconstricting effect), Linezolid (hypertensive effect)
[reduce initial dose], Serotonin / Norepinephrine
Reuptake Inhibitors (tachycardic and vasopressor
effects), Tricyclic Antidepressants e.g., Amitryptilline
(vasopressor effect)
Enhances therapeutic effect of Inhalational Anesthetics
e.g., Sevoflurane (arrhythmogenic effect)
Reduces therapeutic effect of Norepinephrine:
Beta Blockers e.g., Propranolol
Reduces therapeutic effect of Iobenguane I123
Administration: For IV route, administer as a continuous
infusion with the use of an infusion pump. Dilute prior to
use. Administer via a central line.
Do NOT administer alkaline solutions, i.e., sodium
bicarbonate, through the same IV line as norepinephrine.
Inactivation of norepinephrine may occur.
CARDIOVASCULAR SYSTEM

EXTRAVASATION MANAGEMENT: Norepinephrine is a Consider dose reduction. Significant accumulation of the

vesicant. Ensure proper needle or catheter placement
prior to and during infusion. Infuse into a large vein to
prevent extravasation. Avoid infusion into leg veins. If
extravasation occurs, stop infusion immediately and
disconnect. Leave cannula or needle in place then gently
aspirate extravasated solution. Do NOT flush the line.
Remove needle or cannula and elevate extremity. Initiate
phentolamine or alternative antidote. Apply dry warm
active metabolites may occur with chronic use.
Hepatic Impairment:
Consider dose reduction. Partially metabolized by the liver.
Precautions:
Long-term therapy (may develop nitrate tolerance;
administer nitrate-free interval daily to prevent
tolerance).

C
compresses. Severe hepatic impairment; renal impairment;
hypothyroidism; recent history of MI; malnutrition;
Pregnancy Category: C hypothermia.
Pregnancy (may cross placenta; avoid medication unless
ATC Code: C01CA03 potential benefit outweighs risk).

Adverse Drug Reactions:

VASODILATORS USED IN Common: Dizziness, fainting, flushing, hypotension
CARDIAC DISEASES (including orthostatic hypotension), palpitations,
peripheral edema, tachycardia, throbbing headache
Less Common: Heartburn, hypoxemia, nausea, rash,
Rx ISOSORBIDE DINITRATE (ISDN) rebound angina, syncope, vomiting
Rare: Angle-closure glaucoma
Oral: 10 mg and 20 mg tablet Drug Interactions:
20 mg MR tablet / capsule Monitor closely with:
Sublingual: 5 mg tablet Enhances therapeutic effect of ISDN:
Inj.: 1 mg/mL, 10 mL ampule (IV) Drugs which reduce blood pressure (hypotensive effects)
An organic nitrate vasodilator with better stability in storage Reduces therapeutic effect of ISDN:
than nitroglycerin. It is useful in patients who require Atropine (failure to dissolve under the tongue owing to
nitrates infrequently because of its slower onset of action dry mouth)
but longer duration. Commonly used as a PRN drug.
Avoid concomitant use with:
Indication: Prophylaxis and treatment of angina Increases risk of adverse or toxic effects of ISDN:
Phosphodiesterase Inhibitors [e.g., Sildenafil
Contraindications: Hypotension; hypovolemia; hypertrophic (hypotension; MI)]
obstructive cardiomyopathy; aortic stenosis; cardiac
tamponade; constrictive pericarditis; mitral stenosis; Reduces therapeutic effect of ISDN:
marked anemia; head trauma; cerebral hemorrhage; Antagonism of hypotensive effect: Dexamethasone,
angle-closure glaucoma; GI hypermotility; malabsorption Hydrocortisone Ibuprofen, Oral Contraceptives,
syndrome Prednisolone
Dose: Administration:
Angina, acute attack, by sublingual route, ADULT, 2.5–5 mg, For oral administration, take on an empty stomach ½
repeated every 5–10 minutes as required for 3 doses hour before meals.
[NOTE: Inability to relieve chest pain after 3 doses may signal
acute MI, which will need immediate hospitalization. IV infusion
may be started, while awaiting transfer to the hospital, at 1 For sublingual tablets, sit or lie down before use since
mg/hour and titrated upward to 4 mg/hour.] the tablet may cause dizziness. Place the appropriate
Angina prophylaxis, by mouth, ADULT, dose under the tongue. Do NOT swallow. After the pain
as regular release tablet, initially 5–20 mg 2–3 times has been relieved, the patient may spit out or swallow
daily (maintenance dose, 10–40 mg 2–3 times daily; what is left of the tablet to avoid adverse effects, such as
maximum dose, 240 mg); headache.
as MR tablet, 40–80 mg 1–2 times daily, space twice
daily dose 6 hours apart (maximum dose, 160 mg daily) For IV infusion, mix 10 mL (equivalent to 10 mg) in 90
[NOTE: Provide nitrate-free interval daily (14 hours for regular mL NSS.
release and 18 hours for extended release) to avoid development
of tolerance.] Pregnancy Category: C
Acute angina, prevention before a precipitating activity, by
sublingual route, ADULT, 5–10 mg taken 10 minutes ATC Code: C01DA08
before activity.
Chronic angina, prevention, by mouth, ADULT, 5-20mg
(maintenance 10–40 mg) up to 3 times daily.

Dose Adjustment:
Renal Impairment:

109
 CARDIOVASCULAR SYSTEM

ISOSORBIDE MONONITRATE Drug Interactions:

Rx Monitor closely with:
(ISMN)
Enhances therapeutic effect of ISMN:
Antihypertensive effect: Barbiturates e.g., Phenobarbital,
Oral: 40 mg tablet
Molsidomine, Nicorandil; Vasodilatory effect: Ethyl
30 mg and 60 mg MR tablet / capsule
alcohol
An antianginal agent that forms free radical nitric oxide.
Increases risk of adverse or toxic effects of ISMN:
Nitric oxide activates guanylate cyclase in smooth
Dapoxetine (orthostatic hypotension), Other
muscle which leads to smooth muscle relaxation and
C

Antihypertensive Agents
prominent vasodilator effect on the peripheral veins. It
also reduces cardiac oxygen demand by decreasing
Increases risk of adverse or toxic effects of the following
preload and afterload due to its vasodilatory effect. It
drugs:
likewise causes epicardial coronary arteries vasodilation.
Methemoglobinemia: Dapsone, (Topical), Nitric Oxide,
Prilocaine, Sodium Nitrite,
Indication: Prevention of angina pectoris
Orthostatic hypotension: Duloxetine, Levodopa,
Risperidone (hypotensive effect), Rosiglitazone
Contraindications: Hypersensitivity to organic nitrates;
(ischemia)
concurrent use with phosphodiesterase­5 inhibitors
Avoid concomitant use with:
Dose:
Decreases serum concentration of ISMN:
Angina, by mouth, ADULT,
CYP3A4 Inducers, Dabrafenib, Mitotane
as regular release tablet, initially 5–20 mg twice daily,
given 7 hours apart to decrease tolerance development;
Enhances therapeutic effect of ISMN:
patients initiating therapy with 5 mg twice daily should
Phosphodiesterase-5 Inhibitors e.g. Sildenafil
be titrated up to 10 mg twice daily in the first 2–3 days;
(vasodilatory effects)
as MR tablet, initially 30–60 mg once daily in the
morning; titrate upward as needed with at least 3 days
Enhances therapeutic effect of Riociguat (hypotensive
between increases (maximum single daily dose, 240
effect)
mg).
Increases serum concentration of ISMN:
Dose Adjustment:
CYP3A4 Inhibitors, Fusidic Acid (Systemic), Idelalisib,
Geriatric:
Mifepristone, Stiripentol
Start with lowest recommended adult dose. Administer first
dose in a physician's office to observe for maximal
Administration: Do NOT administer around-the-clock.
cardiovascular dynamic effects and adverse effects.
Adjust dose or change medication when reflux
For immediate release tablets, schedule twice daily
esophagitis occurs.
doses 7 hours apart (8 AM and 3 PM).
Precautions:
For MR tablets, administer once daily in the morning
Long-term therapy (may develop tolerance; administer
upon rising with a half-glassful of fluid. Do NOT chew or
nitrate-free interval daily to prevent tolerance)
crush MR tablets. MR tablets that are scored may be
Hypotension or bradycardia (may be accompanied by
split.
paradoxical bradycardia and increased angina pectoris;
increased risk of hypotension; orthostatic hypotension)
Pregnancy Category: B / C (product-specific)
Hypertrophic cardiomyopathy (may reduce preload,
exacerbate obstruction, and cause hypotension or
ATC Code: C01DA14
syncope and/or worsening of heart failure)
Increased intracranial pressure (may worsen clinical
outcomes in patients with neurologic injury)
Lactation (not known if excreted in breastmilk) NITROGLYCERIN
Rx
(GLYCERYL TRINITRATE)
Adverse Drug Reactions:
Common: Angina, flushing, headache, dizziness, fatigue, Inj.: 1 mg/mL, 10 mL and 25 mL ampule (IV infusion)
pain, emotional lability, pruritus, rash, nausea,
abdominal pain, diarrhea, upper respiratory infection, An antianginal agent which releases nitric oxide. Nitric oxide
cough, allergic reaction produces a more prominent vasodilator effect on the
Less Common: Amblyopia, anorexia, anxiety, apoplexy, peripheral veins than arteries. In turn, it reduces cardiac
arrhythmia, asthma, back pain, bradycardia, impaired oxygen demand by decreasing preload and afterload. It
concentration, depression, diaphoresis, dyspepsia, likewise causes epicardial coronary arteries vasodilation.
dyspnea, edema, hypertension or hypotension,
insomnia, MI, muscle cramps, neck pain, nervousness, Indication: Management of unstable angina
nightmares, orthostatic hypotension, pallor, palpitation,
paresthesia, prostatic disorder, restlessness, sinusitis, Contraindications: Concurrent use with PDE­5 Inhibitors or
susurrus aurium, tachycardia, taste disturbance, thirst, Riociguat; hypersensitivity to corn or corn products
tremor, vertigo, vomiting, xerostomia (solutions containing dextrose); constrictive pericarditis;
Rare: Methemoglobinemia pericardial tamponade; restrictive cardiomyopathy;

110
CARDIOVASCULAR SYSTEM
hypotension (SBP <90 mmHg or ≥30 mmHg below
baseline); marked bradycardia or tachycardia; right
ventricular infarction
Dose:
Angina, by IV infusion, ADULT, 5 micrograms/minute,
increase by 5 micrograms/minute every 3–5 minutes
until 20 micrograms/minute; if no response at 20
micrograms/minute, may increase dose by 10–20
micrograms/minute every 3–5 minutes (maximum dose,
400 micrograms/minute).
Unstable angina, management, by IV infusion, ADULT,
initially 10 micrograms/minute, increase by 10
micrograms/minute every 3–5 minutes until relief of
symptoms; if no response at 20 micrograms/minute,
may increase by 10 micrograms/minute and later by 20
micrograms/minute.
NOTE: If nitroglycerin is prescribed, advise the patient to
take 1 dose promptly in response to chest pain.
Dose Adjustment: No information found
Precautions:
Long-term therapy (may develop hemodynamic and
antianginal tolerance; administer 10–12 hours nitrate-
free interval daily to prevent tolerance; gradually
decrease dose to avoid withdrawal reaction).
Headache (dose-related; may occur during initial dosing);
increased intracranial pressure (may precipitate or
aggravate increased intracranial pressure; may worsen
clinical outcomes in patients with neurologic injury).
Hypotension or bradycardia (severe hypotension and
orthostatic hypotension can occur; paradoxical
bradycardia and increased angina pectoris can
accompany hypotension)
Hypertrophic cardiomyopathy (may reduce preload,
exacerbating obstruction and cause hypotension or
syncope and/or worsening of heart failure).
Elderly (hypotension is enhanced due to decreased
baroreceptor response, decreased venous tone,
hypovolemia, or other hypotensive drugs).
Lactation (not known if excreted in breastmilk; limited
information available; use with caution when
administering to nursing women).
Adverse Drug Reactions:
Common: Bradycardia, flushing, hypotension, orthostatic
hypotension, peripheral edema, syncope, tachycardia,
headache, dizziness, lightheadedness, nausea,
vomiting, xerostomia, paresthesia, weakness, dyspnea,
pharyngitis, rhinitis, diaphoresis
Less Common: Allergic reactions, anaphylactoid reaction,
blurred vision, cardiovascular collapse, crescendo
angina, exfoliative dermatitis, pallor, palpitation, rash,
rebound hypertension, restlessness, shock, vertigo
Rare: Methemoglobinemia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Nitroglycerin:
Antihypertensive effects: Alfuzosin, Barbiturates e.g.
Phenobarbital, Molsidomine, Nicorandil
Vasodilatory effect: Ethyl alcohol
Increases risk of adverse or toxic effects of Nitroglycerin:
Dapoxetine (orthostatic hypotension), Other
Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Methemoglobinemia: Dapsone, (Topical), Nitric Oxide,
Prilocaine, Sodium Nitrite,
Orthostatic hypotension: Duloxetine, Levodopa
C
Risperidone (hypotensive effect), Rosiglitazone
(ischemia)
Reduces therapeutic effect of Heparin (anticoagulant
effect)
Avoid concomitant use with:
Enhances therapeutic effect of ISMN:
Phosphodiesterase-5 Inhibitors e.g. Sildenafil
(vasodilatory effects), Ergot Derivatives (vasodilatory
effects)
Enhances therapeutic effect of Riociguat (antihypertensive
effects)
Increases serum concentration of Ergot Derivatives
Administration: For IV administration, administer via
infusion pumps.
Prepare in glass bottles, EXCEL, or PAB containers.
Adsorption occurs to soft plastic (e.g., PVC). Use
administration sets intended for nitroglycerin.
Prepare a 100 micrograms/mL solution by withdrawing
25 mL D5W from a 250-mL bottle of D5W and replace
this volume with 25 mg (25 mL) of nitroglycerin.
Prepare a 200 micrograms/mL solution by withdrawing
50 mL D5W from a 250-mL bottle of D5W and replace
volume with 50 mg (50 mL) of nitroglycerin.
Pregnancy Category: B / C (product-specific)
ATC Code: C01DA02
OTHER CARDIAC PREPARATIONS
Rx TRIMETAZIDINE
Oral: 35 mg tablet (as hydrochloride)
A fatty acid oxidation (pFOX) inhibitor that exerts antianginal
and anti-ischemic effects by altering metabolism to
maintain intracellular ATP levels in ischemic regions
without changing hemodynamic parameters.
Indication: Adjunctive treatment of symptomatic stable
angina
NOTE: NOT recommended as treatment for angina attacks
or for use as initial treatment during acute coronary
syndrome.
111

Contraindications: Parkinson disease; parkinsonian
symptoms; tremors, restless leg syndrome (RLS), or
other movement disorders; severe renal impairment
(CrCl <30 mL/minute)
Dose:
Adjunct in treatment of symptomatic stable angina, by
mouth, ADULT, initially 20 mg 3 times daily (maximum
dose, 20 mg 3 times daily).
C
NOTE: Discontinue treatment if lack of significant
antianginal response within 3 months of initiation.
Dose Adjustment:
Renal Impairment:
In patients with CrCl of 30–60 mL/minute, initial and
maximum dose is 20 mg twice daily.
In patients with CrCl <30 mL/minute, use is
contraindicated.
Hepatic Impairment:
Use in hepatic impairment has not been studied.
Precautions:
Extrapyramidal symptoms (new-onset or worsening of
parkinsonian symptoms have been reported)
Renal impairment (elimination is primarily renal; use with
caution in mild renal impairment).
Elderly (decreased renal function has been observed with
increased Trimetazidine exposure; induced gait
disturbances and/or hypotension may increase fall risk).
Lactation (not known if excreted in breastmilk;
breast­feeding is not recommended).
Adverse Drug Reactions:
Common: Dizziness, headache, pruritus, rash, urticaria,
abdominal pain, diarrhea, dyspepsia, nausea, vomiting,
weakness
Less Common: Acute generalized exanthematous
pustulosis (AGEP), agranulocytosis, angioedema,
constipation, drowsiness, flushing, gait instability,
extrasystoles, hepatitis, hypotension, insomnia,
movement disorders, palpitations, Parkinsonian
symptoms (tremor, akinesia, hypertonia), restless leg
syndrome (RLS), tachycardia, thrombocytopenia,
thrombocytopenic purpura
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Trimetazidine:
Metoclopramide (extrapyramidal symptoms)
Administration: To be taken with food.
Pregnancy Category: C
ATC Code: C01EB15
112
CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
AGENTS ACTING ON ARTERIOLAR
SMOOTH MUSCLE
Rx HYDRALAZINE
Oral: 25 mg and 50 mg tablet (as hydrochloride)
Inj.: 20 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
A direct vasodilator of arterioles with little effect on veins
and decreased systemic resistance.
Indication: Management of moderate to severe
hypertension
Contraindications: Mitral valve rheumatic heart disease
Dose:
Hypertension, by mouth, ADULT, initially 10 mg 4 times daily
for the first 2–4 days; increase to 25 mg 4 times daily for
the rest of the first week; further increase gradually by
10–25 mg/dose every 2–5 days to 50 mg 4 times daily
(maximum dose, 300 mg daily in divided doses); CHILD,
initially 0.75–1 mg/kg daily in 2–4 divided doses;
increase over 3–4 weeks up to 7.5 mg/kg daily in 2–4
divided doses (maximum daily dose, 200 mg daily).
Acute hypertension, by IM or IV injection, CHILD, 0.1 to 0.2
mg/kg per dose every 4–6 hours as needed (maximum
dose, 20 mg), up to 1.7–3.5 mg/kg daily in 4–6 divided
doses.
Hypertensive emergency, by IM or IV injection, ADULT, 10–
20 mg every 4–6 hours as needed. [NOTE: NOT
recommended due to unpredictable and prolonged
antihypertensive effects.]
Hypertensive emergency in pregnancy with systolic BP ≥160
mmHg or diastolic BP ≥110 mmHg, by IM or IV injection,
ADULT, initially 5 or 10 mg, may repeat dose in 20–40
minutes with 5–10 mg if blood pressure continues to
exceed thresholds (maximum total cumulative dose, 20
mg IV or 30 mg IM); after the initial dose, may initiate a
continuous infusion of 0.5–10 mg/hour instead of
intermittent dosing.
Perioperative hypertension, by IV injection, ADULT, 3 to 20
mg every 20–60 minutes as needed. [NOTE: Lower end of
dosing range is preferred in the immediate perioperative period
and in patients with renal failure. Avoid use in perioperative
hypertension, especially in patients with ischemic heart disease,
aortic dissection, or an intracranial process due to unpredictable
and prolonged antihypertensive effects.]
Dose Adjustment:
Geriatric:
Use lower initial doses within the recommended dosage
range.
Renal Impairment:
For patients with CrCl of 10–50 mL/minute, administer
every 8 hours.
For patients with CrCl <10 mL/minute, administer every 8–
16 hours in fast acetylators and every 12–24 hours in
slow acetylators.
CARDIOVASCULAR SYSTEM
Precautions:
Drug-induced lupus-like syndrome (dose-related); fluid or
sodium retention (drug-induced; may require addition or
increased dose of a diuretic); peripheral neuritis
(associated with paresthesia, numbness, and tingling,
possibly due to an anti-pyridoxine effect).
Cardiovascular disease (increase in tachycardia may
increase myocardial oxygen demand); pulmonary
hypertension (may cause hypotension); renal
impairment; hepatic impairment (undergoes extensive
hepatic metabolism).
Elderly.
Pregnancy (crosses the placenta; may cause adverse
events); lactation (excreted into breastmilk; use with
caution in nursing mothers).
Adverse Drug Reactions:
Common: Angina pectoris, flushing, orthostatic
hypotension, palpitations, paradoxical hypertension,
peripheral edema, tachycardia, vascular collapse,
anxiety, chills, depression, disorientation, dizziness,
fever, headache, increased intracranial pressure,
psychotic reaction, pruritus, rash, urticaria, anorexia,
constipation, diarrhea, nausea, paralytic ileus, vomiting,
dysuria, impotence, agranulocytosis, eosinophilia,
erythrocyte count reduced, hemoglobin decreased,
hemolytic anemia, leukopenia, muscle cramps,
peripheral neuritis, rheumatoid arthritis, tremor,
weakness, conjunctivitis, lacrimation, dyspnea, nasal
congestion
Less Common: Diaphoresis, drug-induced lupus-like
syndrome, fever, arthralgia, splenomegaly,
lymphadenopathy, asthenia, myalgia, malaise, pleuritic
chest pain, edema, positive ANA and LE cells,
maculopapular facial rash, positive direct Coombs' test,
pericarditis, pericardial tamponade
Rare: Thrombocytopenia
Drug Interactions:
Monitor closely with:
Enhances antihypertensive effect of Hydralazine:
Alfuzosin, Barbiturates, Brimonidine (Topical), Diazoxide,
Herbs with hypotensive properties, Other
Antihypertensive Agents, Molsidomine, Nicorandil,
Pentoxifylline, Phosphodiesterase-5 Inhibitors,
Prostacyclin Analogues
Increases risk of adverse or toxic effects of Hydralazine:
Orthostatic hypotension: Dapoxetine, Duloxetine, Other
Antihypertensive Agents, Levodopa, MAO Inhibitors
[except Linezolid, Tedizolid]
Increases risk of adverse or toxic effects of Risperidone
(hypotensive effect)
Reduces antihypertensive effect of Hydralazine:
Methylphenidate, Nonsteroidal Anti-Inflammatory Agents
e.g., Ibuprofen
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Hypotensive effect: Amifostine, Obinutuzumab,
Rituximab
TEST INTERACTION. Produces a positive direct Coombs’ Test,
interfering with blood cross-matching.
Administration: Food enhances bioavailability when taken
orally. Administer consistently with regard to meals.
For IV route, administer as a slow IV push with a
maximum rate of 5 mg/minute.
C
Pregnancy Category: C
ATC Code: C02DB02
NITROGLYCERIN
Rx
(GLYCERYL TRINITRATE)
Inj.: 1 mg/mL, 10 mL and 25 mL ampule (IV)
An antianginal agent that forms free radical nitric oxide,
which activates guanylate cyclase in smooth muscle,
increasing cGMP, leading to dephosphorylation of
myosin light chains and smooth muscle relaxation. It
produces a more prominent vasodilator effect on the
peripheral veins than arteries. It has blood pressure
lowering effects and also reduces cardiac oxygen
demand by decreasing preload and afterload.
Indication: For coronary artery disease
Dose:
Coronary artery disease, by IV injection, ADULT, 5
micrograms/minute, increase by 5 micrograms/minute
every 3–5 minutes until 20 micrograms/minute; if no
response at 20 micrograms/minute, may increase dose
by 10-20 micrograms/minute every 3–5 minutes
(maximum dose, 400 micrograms/minute).
See Nitroglycerin (Glyceryl Trinitrate) under Cardiac Therapy
– Vasodilators used in Cardiac Disease in Chapter 3:
Cardiovascular System for other information.
Pregnancy Category: B / C (product-specific)
ATC Code: Not available
Rx SODIUM NITROPRUSSIDE
Inj.: 50 mg powder, ampule (IV infusion)
A direct, short-acting vasodilating agent that acts directly on
the venous and arteriolar smooth muscle causing
peripheral vasodilation. It does not affect other smooth
muscle tissue, such as the uterus or duodenum, and has
no direct effect on vasomotor centers, sympathetic
nerves, or adrenergic receptors.
Indications: Management of hypertensive crisis; heart
failure and low-output syndromes; for controlled
hypotension during anesthesia
Contraindications: Inadequate cerebral circulation; use
during emergency surgery in patients near death;
113

compensatory hypertension; congenital (Leber’s) optic
atrophy; tobacco amblyopia
Dose:
Hypertensive crises, by IV infusion, ADULT and CHILD, 0.1–
10 micrograms/kg per minute (usual dose, 3
micrograms/kg per minute); start infusion at 0.25–0.3
micrograms/kg per minute and gradually increase every
few minutes until adequate blood pressure control is
C
achieved (maximum rate, 10 micrograms/kg per
minute); if well-tolerated, gradually reduce dose toward
normal in the next 24–48 hours.
Acute severe hypertension associated with preeclampsia,
by IV infusion, ADULT, 0.25 micrograms/kg per minute
(maximum dose, 5 micrograms/kg per minute)
NOTE: Do NOT exceed 10 micrograms/kg per minute to
avoid excessive thiocyanate accumulation and to
decrease the possibility of a precipitous drop in blood
pressure. Discontinue immediately if blood pressure is
not adequately controlled within 10 minutes following an
IV infusion of 10 micrograms/kg per minute.
Replace with longer-acting antihypertensive agents as
soon as possible to minimize the duration of sodium
nitroprusside therapy.
Dose Adjustment:
Renal Impairment:
For anuric patients, prolonged infusions should not exceed
1 microgram/kg per minute to maintain <60
micrograms/mL thiocyanate concentration.
Precautions:
WARNING: Infusions at rates exceeding 2
micrograms/kg per minute generate cyanogen
(cyanide radical) in amounts greater than can be
effectively buffered by normally present
methemoglobin, which can result to cyanogen
toxicity.
Hypotension; cyanogenic effects (toxic effects may be rapid,
serious, and possibly fatal; may manifest as venous
hyperoxemia, lactic acidosis, air hunger, confusion, and
death)
Methemoglobinemia; thiocyanate accumulation (monitor
for manifestations of thiocyanate).
Cyanogen or low plasma vitamin B12 concentrations
Renal and hepatic impairment (use with caution; cyanide
may accumulate); hypothyroidism; hyponatremia;
ischemic heart disease.
Increased intracranial pressure (use with extreme caution in
patients with preexisting increased intracranial
pressure); pulmonary disease (may reverse hypoxic
pulmonary vasoconstriction, which may exacerbate
intrapulmonary shunting, resulting in worsened
hypoxemia).
Pregnancy (effects are unknown); lactation (not known if
excreted in breastmilk; use with caution in nursing
mothers).
Adverse Drug Reactions:
Common: Profound hypotension, accumulation of cyanogen
(cyanide radical), metabolic acidosis
114
CARDIOVASCULAR SYSTEM
Less Common: Angina, myocardial infarction, ataxia,
seizures, stroke, tinnitus, miosis, confusion,
hyperreflexia, nausea, retching, vomiting, nasal
stuffiness, diaphoresis, apprehension, headache,
restlessness, muscle twitching, retrosternal discomfort,
palpitation, dizziness, abdominal pain or cramps,
bradycardia, tachycardia, ECG changes, rash, decreased
platelet aggregation, ileus, increased intracranial
pressure, flushing, venous streaking, irritation at the site
of injection
Rare: Methemoglobinemia, cyanosis, hyperthyroidism
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Alteplase (prolongs
fibrinolytic activity)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Sodium
Nitroprusside:
Phosphodiesterase Inhibitors e.g., Sildenafil (severe
hypertension)
Enhances therapeutic effect of Sodium Nitroprusside:
Additive hypotensive effects: Antihypertensives,
Circulatory Depressants, Ganglionic-blocking Agents,
General Anesthetics, Negative Inotropic Agents
Administration: Administer by IV infusion only using a
controlled-infusion device, micro-drip regulator, or
similar device that will allow precise measurement of the
flow rate.
Dilute concentrate prior to IV infusion. One vial
containing 50 mg of the drug should be diluted in 250–
1,000 mL of 5% dextrose injection.
Inspect visually for particulate matter and discoloration
prior to administration. The freshly prepared infusion
solution has a very faint brownish tint. Discard highly
colored solutions or solutions containing particulate
matter.
For single use only. Do NOT add other drugs to the
infusion fluid for simultaneous administration.
Sodium nitroprusside infusions at the maximum
recommended infusion rate of 10 micrograms/kg per
minute should NEVER last longer than 10 minutes.
Immediately discontinue infusion if blood pressure has
not been adequately controlled after 10 minutes.
Protect from light by promptly wrapping the containers in
aluminum foil or other opaque material. It is not
necessary to cover the infusion drip chamber or IV
tubing. If properly protected from light, diluted solutions
of the drug are stable for 24 hours.
Avoid extravasation. Adjust rate of administration to
maintain the desired hypotensive effect based on
continuous monitoring of blood pressure.
NOTE: Administer only when adequate facilities, equipment,
and personnel are available for close monitoring of blood
pressure. The hypotensive effect of sodium nitroprusside
occurs rapidly and can produce precipitous decreases in
CARDIOVASCULAR SYSTEM
blood pressure. The possible sequelae of profound,
prolonged hypotension are serious.
Pregnancy Category: C
ATC Code: C02DD01
AGENTS ACTING ON THE
RENIN-ANGIOTENSIN SYSTEM
ACE INHIBITORS, PLAIN
GENERAL INFORMATION
Mode of Action: This drug class acts by inhibiting the
Angiotensin-Converting Enzyme (ACE), which produces
two mechanisms to reduce blood pressure. First, by
inhibiting the conversion of Angiotensin I to Angiotensin
II, a potent vasoconstrictor that stimulates the release of
norepinephrine. Its other mechanism prevents the
breakdown of bradykinin, a vasodilator substance.
Precautions:
WARNING: Overzealous treatment with ACE inhibitors
may lead to sudden hypotension, renal
insufficiency or failure, or hyperkalemia with the
risk of arrhythmia.
Drugs acting directly on the renin-angiotensin
system can cause injury and death to a developing
fetus. When pregnancy is detected, discontinue as
soon as possible.
NOTE: ACE inhibitors should be initiated with careful clinical
monitoring in those with severe heart failure or those:
• Receiving multiple or high-dose diuretic therapy
• With hypovolemia
• With hyponatremia (plasma-sodium concentration <130
mmol/L)
• With hypotension (SBP <90 mmHg)
• With unstable heart failure
• Receiving high-dose vasodilator therapy
• Known vascular disease
Cough (dry, hacking, non-productive, which usually occurs
within the first few months of treatment and should
generally resolve within 1-4 weeks after discontinuation
of the ACE inhibitor).
Angioedema (may occur rarely; may involve head and neck,
or the intestine); Peripheral vascular disease or
generalized atherosclerosis (risk of renovascular
disease)
Collagen vascular disease (increased risk of
agranulocytosis)
Severe or symptomatic aortic stenosis (risk of hypotension);
Hypertrophic cardiomyopathy
Renal impairment (increased risk hyperkalemia; may affect
the excretion of ACE inhibitors); Hepatic impairment;
jaundice or marked elevations of hepatic enzymes
(discontinue use due to risk of hepatic necrosis); Renal
artery stenosis
Neutropenia and agranulocytosis
Obstructive sleep apnea
Surgery (excessive hypotension may occur during
anesthesia and after surgery)
Hypotension with the first dose, especially in patients on
diuretics, on a low-sodium diet, on dialysis, dehydrated,
or with heart failure.
Concomitant use of diuretics (see notes below)
Concomitant use of statins (increased risk of myopathy;
C
limit simvastatin dose to 20 mg daily if used
concurrently).
Elderly (may be more predisposed to first dose hypotension,
hyperkalemia, and renovascular disease)
Pregnancy (use in first trimester may cause major
congenital malformations; use in second and third
trimester may cause fetal renal dysfunction and
oligohydramnios, and subsequently fetal death);
lactation (avoid use in the first few weeks after delivery,
particularly in preterm infants; risk of profound neonatal
hypertension).
NOTE: Initiation of therapy in patients with ischemic heart
disease or cerebrovascular disease warrants close
observation due to the potential consequences posed by
falling blood pressure, e.g., MI, stroke. Fluid replacement
may restore blood pressure, if needed. Discontinue
therapy if hypotension recurs.
Concomitant use of ARB or renin inhibitor, e.g., Aliskiren,
is associated with an increased risk of hypotension,
hyperkalemia, and renal dysfunction.
USE WITH DIURETICS. Initiate at very low doses to
minimize the risk of very rapid fall in blood pressure in
volume-depleted patients. Discontinue or significantly
reduce high-dose diuretic therapy, e.g., with furosemide
at doses >80 mg daily, at least 24 hours before starting
enalapril (may not be possible in heart failure due to the
risk of pulmonary edema). If high-dose diuretic therapy
cannot be stopped, medical supervision is advised for at
least 2 hours after administration or until blood pressure
is stable.
Rx CAPTOPRIL
Oral: 25 mg and 50 mg tablet
An ACE inhibitor useful in treating hypertension, decreasing
morbidity and mortality in heart failure and left
ventricular dysfunction after myocardial infarction, and
delaying the progress of diabetic nephropathy.
Indications: Management of mild-to-moderate essential
hypertension (alone, or with thiazide-diuretic therapy)
and severe hypertension resistant to other treatment;
CHF with left ventricular dysfunction following MI;
diabetic nephropathy (microalbuminuria >30 mg/day) in
type 1 diabetes
Contraindications: Significant hyperkalemia; hypotension;
significant bilateral renal artery stenosis; angioedema;
pregnancy; concurrent use with Aliskiren in patients with
DM or renal impairment
115

Dose:
NOTE Titrate dose according to patient's response. Use
lowest effective dose.
Heart failure, by mouth, ADULT, initially 6.25–12.5 mg 3
times daily in conjunction with cardiac glycoside and
diuretic therapy (initial dose depends upon patient's fluid
or electrolyte status); increased at 2-week intervals to
25–75 mg twice daily (target dose, 50 mg 3 times daily).
C
Hypertension, by mouth, ADULT, initially 25 mg twice daily,
may increase by 12.5–25 mg per dose at 1- to 2-week
intervals up to a total dose of 150 to 200 mg daily in 2
divided doses.
Hypertensive urgencies, by mouth, ADULT, 25 mg, may
repeat as required.
LV dysfunction following MI, by mouth, ADULT, initially 6.25
mg; if tolerated, follow with 12.5 mg 3 times daily; then
increase to 25 mg 3 times daily during next several days
and then gradually increase over next several weeks to
target dose of 50 mg 3 times daily (some dose schedules
are more aggressive to achieve an increased goal dose
within the first few days of initiation).
Diabetic nephropathy, by mouth, ADULT, initially 25 mg 3
times daily; may be taken with other antihypertensive
therapy if required to further lower blood pressure.
Dose Adjustment:
Geriatric:
Start treatment with lower doses.
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Cough, dizziness, dysgeusia, fatigue, headache,
hyperkalemia, hypersensitivity reactions, hypertension,
malaise, nausea, rash
Less Common: Abnormal dreams, anaphylactoid reactions,
angina pectoris, anorexia, chest pain, congestive heart
failure, constipation, diarrhea, dry mouth, elevated
hepatic aminotransferases, alkaline phosphatase and
serum bilirubin; fever, flushing, hoarseness, itching,
muscle cramps, MI, pallor, palpitations, Raynaud’s
syndrome, sore throat, stomatitis, tachycardia, taste
disturbances, urticaria, vomiting
Rare: Acute renal failure, bronchospasm, cardiac arrest,
cerebrovascular insufficiency, dyspnea, angioedema,
erythema multiforme, exfoliative dermatitis,
gynecomastia, hepatitis, hemolytic anemia,
hyponatremia, impotence, neuropathy, myalgia, oliguria,
orthostatic hypotension, pancreatitis, pancytopenia,
polyuria, proteinuria, psoriasis, renal insufficiency,
serum sickness-like syndrome, rhythm disturbances,
Stevens-Johnson syndrome, syncope, toxic epidermal
necrolysis, visceral angioedema
Drug Interactions:
Monitor closely with:
Enhances antihypertensive effect of Captopril:
Other antihypertensive agents e.g. diuretics, other drugs
which reduce blood pressure
Increases risk of adverse or toxic effects of Captopril:
116
CARDIOVASCULAR SYSTEM
Angiotensin II Receptor Blockers e.g., Losartan, Loop
Diuretics e.g., Furosemide (severe hypotension with the
first ACE inhibitor dose), Drugs which reduce blood
pressure (ACE inhibitor-induced renal impairment),
Thiazide Diuretics (severe hypotension with the first ACE
inhibitor dose)
Avoid concomitant use with:
Decreases serum concentration of Captopril:
Antacids, e.g., Aluminum or Magnesium Hydroxide
Increases risk of adverse or toxic effects (hyperkalemia) of
Captopril:
Selective and Non-selective NSAIDs, (also renal
impairment); Potassium Supplements; Drugs that cause
Potassium retention, e.g., Potassium-sparing Diuretics
Reduces therapeutic effect of Captopril:
Indomethacin, Selective and Non-Selective NSAIDs,
Salicylates (other beneficial pharmacodynamic effects
desired for the treatment of CHF)
Administration: Take on an empty stomach.
Patient may feel dizzy when taking this medicine. Advise
the patient to get up gradually from sitting or lying
position to minimize this effect, and to sit or lie down if
the patient becomes dizzy or light-headed.
See General Information on Agents Acting on the Renin-
Angiotensin System – ACE Inhibitors, Plain in Chapter 3:
Cardiovascular System for information on Warnings and
Precautions.
Pregnancy Category: C in 1st trimester
D in 2nd & 3rd trimesters
ATC Code: C09AA01
Rx ENALAPRIL
Oral: 5 mg and 20 mg tablet (as maleate)
An oral ACE inhibitor, is converted by hydrolysis in the body
to enalaprilat. Its effects are similar with captopril.
Indications: Management of hypertension; heart failure;
acute coronary syndrome; post-myocardial infarction
maintenance
Contraindications: Significant bilateral renal artery stenosis;
renovascular disease; pregnancy; significant
hyperkalemia; hypotension; history of angioedema (ACEI-
induced, hereditary or idiopathic); concurrent use of
aliskiren in patients with DM or renal impairment
Dose:
Heart failure, adjunct or asymptomatic left ventricular
dysfunction, by mouth, ADULT, initially 2.5 mg once daily,
increased gradually over 2–4 weeks to 10–20 mg twice
daily if tolerated.
Hypertension, by mouth, ADULT, initially 5 mg once daily
(lower dose if used in addition to a diuretic); increased at
intervals of 1–2 weeks up to a total dose of 20 mg daily
in 1 or 2 divided doses; CHILD, refer to a specialist.
CARDIOVASCULAR SYSTEM
Dose Adjustment:
Renal Impairment:
For mild-to-moderate impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Hepatic Impairment:
For mild-to-moderate impairment, no dose adjustment is
needed.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Blurred vision, cough, depression, dizziness,
dyspnea, headache, hyperkalemia, hypertension
Less Common: Abnormal dreams, alopecia, anaphylactoid
reactions, angioedema, anorexia, chest pain, confusion,
diarrhea, drowsiness, dry cough, elevated hepatic
aminotransferases and bilirubin; dry mouth, fatigue,
fever, flushing, hoarseness, hypotension, impotence,
insomnia, muscle cramps, nausea, nervousness,
palpitations, rash, renal impairment, sweating, tinnitus,
urticaria, vertigo
Rare: Abdominal pain, agranulocytosis, allergic alveolitis,
aplastic anemia, arrhythmias, electrolyte disturbances,
exfoliative dermatitis, bronchospasm, GI angioedema,
gynecomastia, hepatitis, hemolytic anemia,
hypersensitivity-like reactions, hyponatremia, ileus, liver
damage, neuropathy, neutropenia, paresthesia, peptic
ulcer, pancreatitis, proteinuria, pulmonary infiltrates,
psoriasis, Raynaud’s syndrome, Stevens-Johnson
syndrome, thrombocytopenia, toxic epidermal necrolysis,
visceral angioedema, vomiting
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Enalapril:
Drugs which reduce blood pressure
Increases risk of adverse or toxic effects of Enalapril:
Digoxin (cardiac toxicity), Loop Diuretics (profound
diuresis; serious electrolyte disturbance), Potassium-
lowering Drugs (hypokalemia), Salbutamol
(hypokalemia)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Ibuprofen (nephrotoxicity)
Selective and Non- selective NSAIDs (nephrotoxicity)
Reduces therapeutic effect of the following drugs:
Lidocaine, Metformin (antagonism of hypoglycemic
effect), Selective and non-selective NSAIDs (renal
function, diuretic and hypotensive effect)
Administration: Take once daily in the morning. If to be
taken twice daily, take the first dose in the morning and
the second dose before 6 in the evening.
See General Information on Agents Acting on the Renin-
Angiotensin System – ACE Inhibitors, Plain in Chapter 3:
Cardiovascular System for information on Warnings and
Precautions.
Pregnancy Category: B
ATC Code: C09AA02
ACE INHIBITORS, COMBINATIONS
ENALAPRIL +
Rx
HYDROCHLOROTHIAZIDE
C
Oral: 20 mg enalapril + 12.5 mg hydrochlorothiazide tablet
Hydrochlorothiazide increases plasma renin activity,
increases aldosterone secretion, and decreases serum
potassium.
Enalapril blocks the renin-angiotensin-aldosterone axis and
reverses the potassium loss associated with the diuretic.
Indication: Treatment of hypertension
Contraindications: Hypersensitivity to other sulfonamide-
derived drugs; history of angioedema; idiopathic
angioedema; anuria; diabetes; co-administration with a
neprilysin inhibitor
Dose:
Hypertension, by mouth, ADULT, 10–25 mg enalapril with
12.5–50 mg hydrochlorothiazide daily as a single dose
or in 2 divided doses.
Dose Adjustment:
Renal Impairment:
In patients with severe impairment, use is not
recommended. Loop diuretics are preferred to thiazide
diuretics.
Precautions:
WARNING: Fetal Toxicity. Drugs acting directly on the
renin-angiotensin system can cause injury and
death to the developing fetus. When pregnancy is
detected, discontinue as soon as possible.
Hypotension (excessive hypotension and syncope has been
reported; in patients with CHF with or without associated
renal insufficiency, excessive hypotension may be
associated with oliguria and/or progressive azotemia).
Anaphylactoid and related reactions (exacerbation or
activation of systemic lupus erythematosus has been
reported; may be subject to a variety of adverse
reactions, some serious; have been reported in patients
undergoing low-density lipoprotein apheresis with
dextran sulfate absorption).
Angioedema (angioedema of the face, extremities, lips,
tongue, glottis, and/or larynx has been reported;
angioedema associated with laryngeal edema may be
fatal; intestinal angioedema has been reported
presenting with abdominal pain with or without nausea
or vomiting).
Neutropenia or agranulocytosis (agranulocytosis and bone
marrow depression has been reported; consider periodic
monitoring of WBC counts).
Hepatic impairment (associated with a syndrome that starts
with cholestatic jaundice and progresses to fulminant
hepatic necrosis, and sometimes, death; may precipitate
hepatic coma)
Renal disease (may precipitate azotemia).
117

Ophthalmic effects (can cause idiosyncratic reactions;
acute myopia and secondary angle-closure glaucoma
have been reported).
Adverse Drug Reactions:
Common: Dizziness, headache, fatigue, cough, muscle
cramps, nausea, asthenia, orthostatic effects,
impotence, diarrhea
Less Common: Syncope, chest pain, abdominal pain,
C
orthostatic hypotension, palpitation, tachycardia,
vomiting, dyspepsia, constipation, flatulence, dry mouth,
insomnia, nervousness, paresthesia, somnolence,
vertigo, pruritus, rash, dyspnea, gout, back pain,
arthralgia, diaphoresis, decreased libido, tinnitus,
urinary tract infection, angioedema, hypotension, cough
Administration: Take once daily in the morning. If to be
taken twice daily, take the first dose in the morning and
the second dose before 6 in the evening.
See individual monographs for Enalapril under Agents
Acting on the Renin-Angiotensin System – ACE
Inhibitors, Plain in Chapter 3: Cardiovascular System and
Hydrochlorothiazide under Diuretics – Thiazide Diuretics
in Chapter 3: Cardiovascular System for other
information.
Pregnancy Category: D
ATC Code: C09BA02; C03AX01
ANGIOTENSIN II ANTAGONISTS, PLAIN
GENERAL INFORMATION
Also known as Angiotensin Receptor Blockers (ARB), they
act by blocking the type 1 angiotensin II (AT1) receptors
on blood vessels and other tissues such as the heart,
which prevents the stimulation of vascular smooth
muscle contraction.
Precautions:
WARNING: Fetal Toxicity. Drugs acting directly on the
renin-angiotensin system can cause injury and
death to the developing fetus. When pregnancy is
detected, discontinue as soon as possible.
Peripheral vascular disease (patients may be more likely to
have renal artery stenosis)
Volume or sodium depletion (may activate the renin-
angiotensin system leading to excessive hypotension)
Aortic or mitral valve stenosis and hypertrophic
cardiomyopathy; angioedema (may occur rarely; may
involve head and neck or the intestine)
Hypotension (symptomatic hypotension may occur upon
initiation in patients who are salt- or volume-depleted);
Heart failure
Hyperkalemia; renal function deterioration (increased risk
of hyperkalemia);
Hepatic impairment
Renal artery stenosis (avoid use in patients with unstented
unilateral or bilateral renal artery stenosis).
Surgical patients (if on chronic ARB therapy, intraoperative
hypotension may occur with induction and maintenance
of general anesthesia).
118
CARDIOVASCULAR SYSTEM
Elderly (may be volume-depleted due to diuretic use and/or
blunted thirst reflex resulting in inadequate fluid intake).
Pregnancy (avoid use unless essential; may adversely affect
fetal and neonatal BP control and renal function)
Lactation (not known if excreted into breastmilk;
information is limited).
NOTE: Concomitant use of an ACE inhibitor or renin inhibitor,
e.g., Aliskiren, is associated with an increased risk of
hypotension, hyperkalemia, and renal dysfunction.
Drug Interactions:
Monitor closely with:
Decreases metabolism of ARB:
Antifungal Agents, e.g., Azole Derivatives, (Systemic),
CYP2C8 Substrates, CYP2C9 Substrates
Enhances therapeutic effect (antihypertensive effect) of
ARB:
Alfuzosin, Barbiturates e.g. Phenobarbital, Brimonidine
(Topical), Canagliflozin, Diazoxide, MAO Inhibitors
[except Linezolid, Tedizolid], Molsidomine, Nicorandil,
NSAIDs, Other Antihypertensive Agents, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
Prostacyclin Analogues e.g. Epoprostenol
Increases risk of adverse or toxic effects of ARB:
Antifungal Agents, e.g., Azole Derivatives, (Systemic)
Hyperkalemic effect: Canagliflozin, Heparin, Eplerenone,
Nicorandil NSAIDS (also acute renal failure), Tolvaptan,
Trimethoprim
Orthostatic hypotension: Dapoxetine, MAO Inhibitors
[except Linezolid, Tedizolid]
First ARB dose hypotension: Loop diuretics, Thiazide
diuretics
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Ciprofloxacin (systemic) (arrhythmogenic effect),
Cyclosporine (systemic) (hyperkalemic effect),
Drospirenone (hyperkalemic effect), Duloxetine
(orthostatic hypotension), Levodopa (orthostatic
hypotension), Risperidone (hypotensive effect)
Reduces therapeutic effect of ARB:
Methylphenidate, Rifampicin
Avoid concomitant use with:
Increases risk of adverse or toxic effects (hyperkalemia) of
ARB:
Aliskiren (also hypotensive, and nephrotoxic effects),
Potassium Supplements, Drugs that cause Potassium
retention, e.g., Potassium-sparing Diuretics,
Spironolactone
Increases risk of adverse or toxic effects (hypotensive
effect) of the following drugs:
ACE Inhibitors e.g. Enalapril, Amifostine [withhold ARB 24
hours prior to Amifostine administration], Obinutuzumab
[withhold ARB 12 hours prior to Obinutuzumab infusion
until 1 hour after the end of the infusion], Ramipril,
Rituximab, Sodium Phosphates (also nephrotoxic effect,
specifically acute phosphate nephropathy)
CARDIOVASCULAR SYSTEM
Increases serum concentration of the following drugs:
ACE Inhibitors e.g. Enalapril, Amodiaquine, Lithium,
Ramipril [Ramiprilat]
NOTE: Dual blockade of the Renin-Angiotensin-Aldosterone
system, i.e., ARB and ACEI combination, in patients with
established heart failure, atherosclerotic disease, or
diabetes with end-organ damage is associated with
higher risk for hypotension, syncope, hyperkalemia, and
disordered renal function, including acute renal failure.
Rx IRBESARTAN
Oral: 150 mg and 300 mg tablet
An angiotensin receptor antagonist that binds to the AT1
angiotensin II receptor. It blocks the vasoconstrictor
effect of angiotensin II, as well as sodium and water
reabsorption which results in a decrease in blood
pressure.
Indication: Treatment of hypertension alone or in
combination with other antihypertensive agents
Contraindication: Concomitant use with aliskiren in patients
with diabetes mellitus
Dose:
Hypertension, by mouth, ADULT, 150 mg once daily;
patients may be titrated to 300 mg once daily; usual
dosage range, 150–300 mg daily; target dose, 300 mg
once daily.
Dose Adjustment:
Renal Impairment
Use with caution. Dose adjustment is only required if patient
is volume-depleted.
Volume Depletion:
Start dose at 75 mg.
Adverse Drug Reactions:
Common: Fatigue, diarrhea, dyspepsia, upper respiratory
infection, cough
Less Common: Abdominal distension, abnormal urination,
angina, angioedema, arrhythmia, arthritis, bronchitis,
bursitis, cardiopulmonary arrest, cerebrovascular
accident, chest pain (noncardiac), chills, congestion,
conjunctivitis, constipation, depression, dermatitis,
dyspnea, ear infection, ear pain, ecchymosis, epistaxis,
erythema, facial edema, fever, flatulence, flushing,
gastroenteritis, gout, hearing abnormality, heart failure,
hepatitis, hypertension or hypotension, hypertensive
crisis, jaundice, decreased libido, MI, muscle aches,
muscle cramps, muscle weakness, numbness,
orthostatic hypotension, paresthesia, prostate disorder,
pruritus, pulmonary congestion, renal failure, impaired
renal function, sexual dysfunction, sleep disturbance,
somnolence, thrombocytopenia, TIA, tremor, upper
extremity edema, urticaria, vision disturbance, wheezing
Rare: Hyperkalemia, anemia, rhabdomyolysis
Administration: May be administered with or without food.
See for General Information on Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain in
Chapter 3: Cardiovascular System for other information.
Pregnancy Category: D
ATC Code: C09CA04
C
Rx LOSARTAN
Oral: 50 mg and 100 mg tablet (as potassium salt)
An angiotensin II type 1 (AT1) receptor blocker whose
efficacy in hypertension is similar to that of ACE
inhibitors, but is associated with a lower incidence of
side-effects, such as dry cough and angioedema.
Indications: Treatment of hypertension; treatment of
diabetic nephropathy in patients with type 2 diabetes
mellitus (noninsulin dependent, NIDDM) and a history of
hypertension; risk reduction of stroke in patients with
HTN and left ventricular hypertrophy (LVH)
Contraindication: Concomitant use with aliskiren in patients
with diabetes mellitus
Dose:
Hypertension, by mouth, ADULT, usual starting dose, 50 mg
once daily; can be administered once or twice daily with
a total daily dose ranging from 25–100 mg (usual initial
dose in patients receiving diuretics, or those with
intravascular volume depletion: 25 mg once daily).
Nephropathy in type 2 DM and hypertension, by mouth,
ADULT, initial dose, 50 mg once daily; can be increased
to 100 mg once daily based on BP response.
Stroke reduction, HTN with LVH, by mouth, ADULT, 50 mg
once daily (maximum daily dose, 100 mg); may be in
combination with a thiazide diuretic.
Dose Adjustment:
Renal Impairment:
For severe impairment, refer patient to a specialist.
Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Dizziness, fatigue, headache, hyperkalemia,
hypoglycemia, nausea, upper respiratory tract infections,
urinary tract infections
Less Common: Abnormal liver function, angina, back pain,
decreased hemoglobin, diarrhea, dyspepsia, dyspnea,
edema, hypotension (first-dose), insomnia, malaise,
muscle cramps, myalgia, nasal congestion, palpitation,
pharyngitis, pruritus, rash, sleep disorders
Rare: Anaphylaxis, anemia, angioedema, atrial fibrillation,
cerebrovascular accidents, cough, depression, erectile
dysfunction, hepatitis, hyponatremia, pancreatitis,
purpura, renal impairment, rhabdomyolysis, syncope,
thrombocytopenia, vasculitis
Administration: May be taken with or without food.
119

The patient may feel dizzy when taking this medicine.
Advise patient to get up gradually from sitting or lying
position to minimize this effect. and sit or lie down if the
patient becomes dizzy or light-headed.
See for General Information on Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain in
Chapter 3: Cardiovascular System for other information.
C
Pregnancy Category: C in 1st trimester; D in 2nd and 3rd
trimesters
ATC Code: C09CA01
Rx TELMISARTAN
Oral: 40 mg and 80 mg tablet
It blocks the vasoconstriction and the aldosterone secreting
effects of angiotensin II, resulting to a decrease in blood
pressure.
Indications: Cardiovascular risk reduction in patients ≥55
years of age unable to take ACE inhibitors and who are
at high risk of major cardiovascular events (e.g., MI,
stroke, death); treatment of hypertension, alone or in
combination with other antihypertensive agents
Contraindication: Concurrent use of aliskiren in patients
with diabetes
Dose:
Hypertension, by mouth, ADULT, initially 40 mg once daily;
usual dosage range, 40–80 mg daily.
Cardiovascular risk reduction, by mouth, ADULT, 80 mg
once daily.
Dose Adjustment:
Hepatic Impairment:
Initiate therapy at a low dose, then titrate slowly with close
monitoring.
Volume Depletion:
Initiate at a lower dose with close supervision.
Adverse Drug Reactions:
Common: Intermittent claudication, chest pain,
hypertension, peripheral edema, dizziness, fatigue,
headache, pain, skin ulcer, diarrhea, abdominal pain,
dyspepsia, nausea, urinary tract infection, back pain,
myalgia, upper respiratory infection, sinusitis, cough,
pharyngitis
Less Common: Abnormal ECG, abnormal vision, abscess,
allergic reaction, anaphylaxis, anemia, angina,
angioedema, anxiety, arthralgia, arthritis, asthma, atrial
fibrillation, bradycardia, bronchitis, cerebrovascular
disorder, CHF, conjunctivitis, constipation, cramps,
cystitis, depression, dermatitis, diabetes mellitus,
diaphoresis, dyspnea, earache, eczema, edema,
enteritis, epistaxis, erectile dysfunction, erythema, facial
edema, fever, fixed drug eruption, flatulence, flushing,
frequent urination, fungal infection, gastroenteritis, gout,
hemorrhoids, hepatic dysfunction, hyperkalemia,
hypersensitivity, hypoglycemia (diabetic patients),
120
CARDIOVASCULAR SYSTEM
hypotension, impotence, insomnia , malaise, MI,
migraine, muscle cramps, neoplasm, nervousness,
orthostatic hypotension, palpitation, paresthesia,
pruritus, otitis media, renal dysfunction, renal failure,
rhabdomyolysis, rash, reflux, rhinitis, somnolence,
tachycardia, syncope, tendon pain, tendonitis,
tenosynovitis, thrombocytopenia, tinnitus, toothache,
urticaria, vertigo, vomiting, weakness, xerostomia
Administration: May be administered without regard to
meals.
NOTE: May contain sorbitol (refer to product labelling prior
to administration in patients with fructose intolerance).
See for General Information on Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain in
Chapter 3: Cardiovascular System for other information.
Pregnancy Category: D
ATC Code: C09CA07
Rx VALSARTAN
Oral: 80 mg and 160 mg tablet / film coated tablet
A direct antagonist of the angiotensin II (AT2) receptors,
displacing angiotensin II from the AT1 receptor. It
produces its blood pressure lowering effects by
antagonizing AT1­induced vasoconstriction, aldosterone
release, catecholamine release, arginine vasopressin
release, water intake, and hypertrophic responses.
Indications: Treatment of primary hypertension, alone or in
combination with other antihypertensive agents;
reduction of cardiovascular mortality in left ventricular
dysfunction post-myocardial infarction; treatment of HF,
NYHA Class II–IV
Contraindication: Concomitant use with aliskiren in patients
with diabetes mellitus
Dose:
Hypertension, by mouth, ADULT, initially 80 mg or 160 mg
once daily if not volume-depleted; dose may be
increased to achieve desired effect; usual dosage range,
80–320 mg daily; target dose, 160–320 mg daily
(maximum recommended dose, 320 mg daily); CHILD 6–
16 years, initially 1.3 mg/kg once daily (maximum dose,
40 mg daily); may increase dose to achieve desired
effect.
Heart failure, by mouth, ADULT, initially 40 mg twice daily,
titrate dose to 80–160 mg twice daily, as tolerated
(maximum daily dose, 320 mg).
Left ventricular dysfunction after MI, by mouth, ADULT,
initially 20 mg twice daily, titrate dose to target of 160
mg twice daily as tolerated; may initiate ≥12 hours
following MI.
Dose Adjustment:
Renal Impairment:
Use with caution in patients with CrCl <30 mL/min. Safety
and efficacy have not been established.
CARDIOVASCULAR SYSTEM
Adverse Drug Reactions:
Common: Hypotension, orthostatic hypotension, syncope,
dizziness, fatigue, orthostatic dizziness, headache,
vertigo, hyperkalemia, diarrhea, abdominal pain,
nausea, neutropenia, viral infection, arthralgia, back
pain, blurred vision, renal insufficiency, cough
Less Common: Alopecia, anaphylaxis, anemia, angioedema,
anorexia, anxiety, bullous dermatitis, chest pain,
constipation, drowsiness, dyspepsia, flatulence,
hypersensitivity reaction, impotence, insomnia, muscle
cramps, myalgia, palpitation, photosensitivity, pruritus,
renal failure, rhabdomyolysis, skin rash, taste disorder,
paresthesia, vasculitis, vomiting, weakness, xerostomia
Rare: Hepatitis, thrombocytopenia
Administration: Administer consistently with regard to
meals. Food decreases peak plasma concentration by
50% and extent of absorption by 40%. Avoid salt
substitutes which contain potassium.
NOTE: May contain sorbitol (refer to product labelling prior
to administration in patients with fructose intolerance).
See for General Information on Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain in
Chapter 3: Cardiovascular System for other information.
Pregnancy Category: D
ATC Code: C09CA03
ANGIOTENSIN II ANTAGONISTS,
COMBINATIONS
IRBESARTAN +
Rx
HYDROCHLOROTHIAZIDE
Oral: 150 mg irbesartan + 12.5 mg hydrochlorothiazide
tablet
Irbesartan is an angiotensin receptor antagonist that binds
to the AT1 angiotensin II receptor, blocking the
vasoconstrictor effect of angiotensin II, as well as sodium
and water reabsorption, resulting in a decrease in blood
pressure
Hydrochlorothiazide inhibits sodium reabsorption in the
distal tubules causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Indication: Treatment of hypertension
Contraindications: Hypersensitivity to sulfonamide-derived
drugs concomitant use with aliskiren in patients with
diabetes mellitus; anuria
Dose:
NOTE: Maximum antihypertensive effects are attained
within 2 to 4 weeks after initiation or a change in dose;
however, if necessary, carefully titrate dose as soon as
after 1 week of treatment.
Hypertension, by mouth, ADULT, initially 1 tablet (150 mg
Irbesartan + 12.5 mg hydrochlorothiazide) once daily; if
initial response is inadequate, may titrate dose after 1–
2 weeks (maximum daily dose, 300 mg irbesartan + 25
mg hydrochlorothiazide).
Dose Adjustment:
Renal Impairment:
Use with caution in mild-to-moderate impairment.
Use is not recommended in severe impairment.
Adverse Drug Reactions:
C
Common: Edema, chest pain, tachycardia, dizziness,
fatigue, nausea, vomiting, abdominal pain, dyspepsia,
abnormal urination, musculoskeletal pain, flu-like
syndrome
Less Common: Angioedema, hepatitis, hyperkalemia,
urticaria
Administration: Administer with or without food.
See individual monographs for Irbesartan and
Hydrochlorothiazide under Agents Acting on the Renin-
Angiotensin System – Angiotensin II Antagonists, Plain
and under Diuretics – Thiazide Diuretics, respectively in
Chapter 3: Cardiovascular System for other information.
Pregnancy Category: D
ATC Code: C09DA04; C03AX01
LOSARTAN +
Rx
HYDROCHLOROTHIAZIDE
Oral: 50 mg losartan + 12.5 mg hydrochlorothiazide tablet
Losartan is an angiotensin II type 1 (AT1) receptor blocker
whose efficacy in hypertension is similar to that of ACE
inhibitors but is associated with a lower incidence of side
effects, such as dry cough and angioedema.
Hydrochlorothiazide inhibits sodium reabsorption in the
distal tubules causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Indications: Treatment of hypertension; to reduce the risk of
stroke in patients with hypertension and left ventricular
hypertrophy (LVH)
Contraindications: Hypersensitivity to sulfonamide-derived
drugs ; concomitant use with aliskiren in patients with
diabetes mellitus; anuria
Dose:
NOTE: Individualize doses. Combination product may be
substituted for individual components in patients
currently maintained on both agents separately or in
patients not adequately controlled with monotherapy.
Hypertension, replacement therapy, by mouth, ADULT, 1–2
tablets (50–100 mg losartan + 12.5–25 mg
hydrochlorothiazide) once daily, may titrate dose after
approximately 3 weeks of therapy as necessary until
maximum daily dose is reached (maximum daily dose,
100 mg losartan + 25 mg hydrochlorothiazide).
Severe hypertension, by mouth, ADULT, initially 1 tablet (50
mg losartan + 12.5 mg hydrochlorothiazide) once daily,
may titrate dose after 2–4 weeks of therapy as
necessary until maximum daily dose is reached
121

(maximum daily dose, 2 tablets: 100 mg losartan + 25
mg hydrochlorothiazide).
Hypertension with left ventricular hypertrophy, by mouth,
ADULT, 1 tablet (50 mg losartan + 12.5 mg
hydrochlorothiazide) once daily, may increase to 2
tablets (100 mg losartan + 12.5 mg hydrochlorothiazide
once daily).
NOTE: Initiate treatment with losartan monotherapy. If blood
C
pressure reduction is inadequate, initiate losartan +
hydrochlorothiazide combination.
Dose Adjustment:
Renal Impairment:
In severe impairment (CrCl ≤30 mL/min), use is not
recommended and is ineffective.
Hepatic Impairment:
Use is not recommended as initial therapy.
Adverse Drug Reactions:
Common: Edema, palpitation, dizziness, skin rash,
abdominal pain, back pain, upper respiratory infection,
cough, sinusitis
Less Common: hypertension or hypotension, hyponatremia,
rhabdomyolysis, thrombocytopenia
Administration: May be administered without regard to
meals.
See individual monographs for Losartan under Agents
Acting on the Renin-Angiotensin System – Angiotensin II
Antagonists, Plain in Chapter 3: Cardiovascular System
and Hydrochlorothiazide under Diuretics – Thiazide
Diuretics in Chapter 3: Cardiovascular System for other
information.
Pregnancy Category: D
ATC Code: C09DA01; C03AX01
Rx SACUBITRIL/VALSARTAN
Oral: 50 mg, 100 mg and 200 mg tablet
Sacubitril is a prodrug that inhibits neprilysin leading to
increased natriuretic peptides, which promotes excretion
of sodium by the kidneys; valsartan produces direct
antagonism of the angiotensin II receptors preventing
vasoconstriction, aldosterone release, arginine
vasopressin release, water intake, and hypertrophic
responses.
Indications: Reduce the risk of cardiovascular death and
hospitalization for heart failure in patients with chronic
heart failure (NYHA Class II-IV) and reduced ejection
fraction; usually administered in conjunction with other
heart failure therapies, in place of an angiotensin-
converting enzyme (ACE) inhibitor or other angiotensin II
receptor blocker (ARB).
Contraindications: Hypersensitivity to sacubitril, valsartan,
or any component of the formulation; history of
angioedema related to previous ACE inhibitor or ARB
therapy; concomitant use or use within 36 hours of ACE
122
CARDIOVASCULAR SYSTEM
inhibitors; concomitant use of aliskiren in patients with
diabetes.
Dose:
Heart failure, by mouth, ADULT, 100 mg tab twice daily
initially, double the dose after 2-4 weeks until target dose
of 200 mg twice daily as tolerated.
Dose Adjustment:
Renal impairment:
Mild to moderate- no dosage adjustment necessary.
Severe- reduce starting dose to 50 mg tab twice daily;
double the dose every 2-4 weeks to target maintenance
dose of 200 mg twice daily as tolerated.
Hepatic impairment:
Mild- no dosage adjustment necessary.
Moderate- reduce starting dose to 50 mg tab twice daily;
double the dose every 2-4 weeks to target maintenance
dose of 200 mg twice daily as tolerated.
Severe- use not recommended.
Precautions:
May cause angioedema, hyperkalemia, hypotension, renal
function deterioration; use in caution in patients with
aortic or mitral stenosis, heart failure, hepatic
impairment, renal artery stenosis, and renal impairment.
Adverse Drug Reactions:
Common: Hypotension and hyperkalemia.
Less Common: Cough, dizziness, orthostatic hypotension,
falls, decreased hematocrit and hemoglobin,
angioedema, and renal failure.
Rare: Anaphylaxis, hypersensitivity, pruritus, and skin rash.
Drug Interactions:
Monitor closely with:
Both drugs increase serum potassium:
Aspirin, Atenolol, Betaxolol, Bisoprolol, Candesartan,
Carvedilol, Celecoxib, Diclofenac, Digoxin, Esmolol,
Ibuprofen, Ketorolac, Losartan, Mefenamic Acid,
Naproxen, Potassium Chloride, Potassium Citrate,
Propranolol, Spironolactone, Succinylcholine,
Telmisartan
Decreases effects of sacubitril/valsartan:
Aspirin, Celecoxib, Diclofenac, Ibuprofen, Ketoprofen,
Ketorolac, Mefenamic Acid, Naproxen.
Either drug increases the toxicity of the other:
Aspirin, Celecoxib, Diclofenac, Ibuprofen, Ketorolac,
Mefenamic Acid, Naproxen
Increases effects of sacubitril/valsartan
Atorvastatin, Carbamazepine, Carbidopa,
Clarithromycin, Daclatasvir, Digoxin, Erythromycin,
Levodopa, Paclitaxel, Rifampin, Simvastatin, Tacrolimus
Increases toxicity of sacubitril/valsartan
Enoxaparin, Heparin
Increases the toxicity of the following:
Atorvastatin
Avoid concomitant use with:
Either increases the toxicity of the other:
CARDIOVASCULAR SYSTEM
Captopril, Enalapril, Lithium
Administration: Administer with or without food.
Pregnancy Category: D
ATC Code: C09DX04
TELMISARTAN +
Rx
HYDROCHLOROTHIAZIDE
Oral: 40 mg telmisartan + 12.5 mg hydrochlorothiazide
tablet
Telmisartan is a nonpeptide AT1 angiotensin II receptor
antagonist that binds to the AT1 angiotensin II receptor
preventing angiotensin II binding, thereby blocking the
vasoconstriction and the aldosterone secreting effects of
angiotensin II, resulting to a decrease in blood pressure.
Hydrochlorothiazide inhibits sodium reabsorption in the
distal tubules causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Indication: Treatment of hypertension
Contraindications: Hypersensitivity to sulfonamide-derived
drugs, or any component of the formulation; concomitant
use with aliskiren in patients with diabetes mellitus;
anuria
Dose:
NOTE: Combination product can be substituted for
individual titrated agents. Initiation of combination
therapy when monotherapy has failed to achieve desired
effects.
Do NOT use fixed-dose combination products as initial
therapy.
Hypertension, replacement therapy, by mouth, ADULT,
blood pressure not controlled by 80 mg telmisartan
monotherapy, 1 tablet (80 mg telmisartan + 12.5 mg
hydrochlorothiazide) once daily, may titrate dose up to 2
tablets (160 mg telmisartan + 25 mg
hydrochlorothiazide) if needed;
blood pressure not controlled by 25 mg
hydrochlorothiazide monotherapy, 1 tablet (80 mg
telmisartan + 12.5 mg hydrochlorothiazide) once daily,
may titrate dose up to 2 tablets (160 mg telmisartan +
25 mg hydrochlorothiazide) if blood pressure remains
uncontrolled after 2–4 weeks of therapy.
Dose Adjustment:
Renal Impairment:
If CrCl ≤30 mL/min, use is not recommended.
Hepatic Impairment:
In mild-to-moderate impairment or biliary obstructive
disorders, initiate at 40 mg telmisartan + 12.5 mg
hydrochlorothiazide.
In patients with severe hepatic impairment, use is not
recommended.
Adverse Drug Reactions:
Common: Dizziness, fatigue, diarrhea, nausea, upper
respiratory tract infection, sinusitis, flu-like syndrome
Less Common: Abdominal pain, back pain, increased
bilirubin, bronchitis, dyspepsia, decreased hematocrit
and hemoglobin, hypokalemia, orthostatic hypotension,
pharyngitis, rash, tachycardia, vomiting
Rare: Rhabdomyolysis
C
Administration: May be administered without regard to
meals.
See individual monographs for Telmisartan under Agents
Acting on the Renin-Angiotensin System – Angiotensin II
Antagonists, Plain in Chapter 3: Cardiovascular System
and Hydrochlorothiazide under Diuretics – Thiazide
Diuretics in Chapter 3: Cardiovascular System for other
information.
Pregnancy Category: D
ATC Code: C09DA07; C03AX01
VALSARTAN +
Rx
HYDROCHLOROTHIAZIDE
Oral: 80 mg valsartan + 12.5 mg hydrochlorothiazide tablet
Valsartan is a direct antagonist of the angiotensin II (AT1)
receptors, displacing angiotensin II from the AT1
receptor. It produces its blood pressure-lowering effects
by antagonizing AT1­induced vasoconstriction,
aldosterone release, catecholamine release, arginine
vasopressin release, water intake, and hypertrophic
responses.
Hydrochlorothiazide inhibits sodium reabsorption in the
distal tubule causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.
Indication: Treatment of hypertension
Contraindications: Hypersensitivity to valsartan,
hydrochlorothiazide, sulfonamide-derived drugs, or any
component of the formulation; concomitant use with
aliskiren in patients with diabetes mellitus; anuria
Dose:
NOTE: Combination product can be substituted for
individual titrated agents. Initiation of combination
therapy when monotherapy has failed to achieve desired
effects.
Do NOT use fixed-dose combination products as initial
therapy.
Hypertension, replacement therapy, by mouth, ADULT,
blood pressure not controlled by 80 mg valsartan
monotherapy, 1 tablet (80 mg valsartan + 12.5 mg
hydrochlorothiazide) once daily, may titrate dose up to 2
tablets (160 mg valsartan + 25 mg hydrochlorothiazide)
if needed;
blood pressure not controlled by 25 mg
hydrochlorothiazide monotherapy, 1 tablet (80 mg
valsartan + 12.5 mg hydrochlorothiazide) once daily,
123

may titrate dose up to 2 tablets (160 mg telmisartan +
25 mg hydrochlorothiazide) if blood pressure remains
uncontrolled after 2–4 weeks of therapy.
Dose Adjustment:
Geriatric:
Use with caution. Monitor renal function.
Renal Impairment:
C
If CrCl ≤30 mL/min, use is not recommended.
Hepatic Impairment:
In mild-to-moderate impairment or biliary obstructive
disorders, initiate at 40 mg valsartan + 12.5 mg
hydrochlorothiazide.
In severe hepatic impairment, use is not recommended.
Adverse Drug Reactions:
Common: Hypotension, dizziness, hypokalemia,
nasopharyngitis
Less Common: Anaphylaxis, increased appetite,
bronchospasm, constipation, dehydration, depression,
dysuria, epistaxis, flushing, gout, decreased hematocrit
or hemoglobin, decreased libido, hyperkalemia,
neutropenia, orthostatic hypotension, photosensitivity,
pruritus, syncope, vasculitis, abnormal vision, abdominal
pain, anxiety, arthralgia, chest pain, cough, diarrhea,
dyspepsia, dyspnea, fatigue, fever, flatulence,
hyperhidrosis, infection, insomnia, myalgia, nausea,
palpitation, paresthesia, peripheral edema, pollakiuria,
postural dizziness, rash, somnolence, tachycardia,
tinnitus, vertigo, vomiting, weakness, xerostomia
Rare: Rhabdomyolysis
Administration: Administer with or without food.
See individual monographs for Valsartan under Agents
Acting on the Renin-Angiotensin System – Angiotensin II
Antagonists, Plain in Chapter 3: Cardiovascular System
and Hydrochlorothiazide under Diuretics – Thiazide
Diuretics in Chapter 3: Cardiovascular System for other
information.
Pregnancy Category: D
ATC Code: C09DA03; C03AX01
124
CARDIOVASCULAR SYSTEM
BETA-BLOCKING AGENTS
ALPHA AND BETA BLOCKING AGENTS
Rx CARVEDILOL
Oral: 6.25 mg and 25 mg tablet
A racemic mixture, carvedilol has non-selective beta-
adrenoreceptor and alpha-adrenergic blocking activity. It
causes exercise-induced or beta-agonist-induced
tachycardia, a reduction of cardiac output and reflex
orthostatic tachycardia, vasodilation, decreased
peripheral and renal vascular resistance, reduced
plasma renin activity, and increased levels of atrial
natriuretic peptide
Indication: Management of heart failure
Contraindications: Decompensated cardiac failure requiring
intravenous inotropic therapy; bronchial asthma or
related bronchospastic conditions; second­ or third-
degree AV block, sick sinus syndrome, and severe
bradycardia (except in patients with a functioning
artificial pacemaker) ; cardiogenic shock; severe hepatic
impairment
Dose:
Heart failure, by mouth, ADULT, 3.125 mg twice daily for 2
weeks; if tolerated, may increase to 6.25 mg twice daily;
double the dose every 2 weeks to the highest dose
tolerated by patient.
Mild-to-moderate heart failure, by mouth, ADULT >85 kg,
maximum dose, 50 mg twice daily; ADULT <85 kg,
maximum dose, 25 mg twice daily.
Severe heart failure, by mouth, ADULT, 25 mg twice daily
(maximum dose, 80 mg once daily).
Left ventricular dysfunction following MI, by mouth, ADULT,
initially 3.125–6.25 mg twice daily; increase dose
incrementally at intervals of 3–10 days, based on
tolerance, to a target dose of 25 mg twice daily
(maximum dose, 50 mg twice daily).
NOTE: Use with caution in patients who require inotropes
during their hospital course. Increase dose gradually and
monitor for congestive signs and symptoms of HF making
every effort to achieve target.
Dose Adjustment:
Geriatric:
Lower initial dose and titrate to response. Dose reductions
may be necessary.
Patients with Hypotension or Syncope:
Lower initial dose and titrate to response. Lower blood
pressure at a rate appropriate for the patient's clinical
condition.
Precautions:
Anaphylactic reactions
Diabetes (may potentiate and/or mask signs and symptoms
of hypoglycemia)
Pheochromocytoma (adequate alpha-blockade should be
initiated prior to use of any beta­blocker).
CARDIOVASCULAR SYSTEM
Bradycardia (may occur; reduce dose if heart rate drops to
<55 beats/minute); Hypotension or syncope (may occur
within the first 30 days of therapy); Angina
Heart failure (may experience a worsening of renal function;
worsening heart failure or fluid retention may occur
during upward titration).
Floppy iris syndrome (has been observed in cataract surgery
patients who were on or were previously treated with
alpha1 blockers);
Myasthenia gravis; peripheral vascular disease (may
precipitate or aggravate symptoms of arterial
insufficiency).
Bronchospastic disease (use with caution and close
monitoring)
Hepatic impairment
Psoriasis (associated with induction or exacerbation of
psoriasis)
Thyroid disease (may mask signs of hyperthyroidism; abrupt
withdrawal may exacerbate symptoms of
hyperthyroidism or precipitate thyroid storm)
Abrupt withdrawal (may cause acute tachycardia,
hypertension, and/or ischemia; severe exacerbation of
angina, ventricular arrhythmias, and myocardial
infarction have been reported; chronic beta­blocker
therapy should not be routinely withdrawn prior to major
surgery)
Elderly (bradycardia may be observed more frequently).
Pregnancy (increased risk of cardiovascular defects was
observed); lactation (not known if excreted in breastmilk;
may cause serious adverse reactions in the nursing
infant).
Adverse Drug Reactions:
Common: Hypotension, bradycardia, syncope, peripheral
edema, generalized edema, angina, dependent edema,
AV block, cerebrovascular accident, hypertension,
hypervolemia or hypovolemia, orthostatic hypotension,
palpitation, dizziness, fatigue, headache, depression,
fever, hypoesthesia, hypotonia, insomnia, malaise,
somnolence, vertigo, hyperglycemia,
hypercholesterolemia, hypertriglyceridemia, diabetes
mellitus, gout, hyperkalemia, hyperuricemia,
hypoglycemia, hyponatremia, weight gain, diarrhea,
nausea, vomiting, abdominal pain, melena, periodontitis,
weight loss, impotence, anemia, decreased prothrombin,
purpura, thrombocytopenia, weakness, back pain,
arthralgia, arthritis, muscle cramps, paresthesia, blurred
vision, glycosuria, hematuria, renal insufficiency, cough,
nasopharyngitis, rales, dyspnea, pulmonary edema,
rhinitis, nasal congestion, sinus congestion, injury,
allergy, flu­like syndrome, sudden death
Less Common: Anaphylactoid reaction, alopecia,
angioedema, aplastic anemia, amnesia, asthma,
bronchospasm, bundle branch block, cholestatic
jaundice, concentration decreased, diaphoresis,
erythema multiforme, exfoliative dermatitis, GI
hemorrhage, decreased hearing, hypersensitivity
reaction, hypokalemia, hypokinesia, interstitial
pneumonitis, leukopenia, libido decreased, migraine,
myocardial ischemia, nervousness, neuralgia,
nightmares, pancytopenia, paresis, peripheral ischemia,
photosensitivity, pruritus, rash, respiratory alkalosis,
seizure, Stevens-Johnson syndrome, tachycardia,
tinnitus, toxic epidermal necrolysis, urinary incontinence,
urticaria, xerostomia
Drug Interactions:
Monitor closely with:
Decreases metabolism of Carvedilol:
Aminoquinolines e.g. Antimalarial drugs; Phenothiazine
Antipsychotic Agents, CYP2D6 Inhibitors (Moderate)
Decreases metabolism of Phenothiazine Antipsychotic
Agents
C
Enhances therapeutic effect of Carvedilol:
Bradycardic effect: Acetylcholinesterase Inhibitors e.g.,
Neostigmine, Amiodarone, Anilidopiperidine Opioids e.g.,
Fentanyl (bradycardic effect; antihypertensive effect),
Bretylium (also AV blockade), Cardiac Glycosides e.g.,
Digoxin, Dipyridamole, Disopyramide, Other Bradycardia-
causing Agents, Regorafenib, Ruxolitinib, Tofacitinib
Antihypertensive effect: Anilidopiperidine Opioids e.g.
Fentanyl, Phenothiazine Antipsychotic Agents,
Barbiturates e.g. Phenobarbital, Brimonidine (Topical),
Calcium Channel Blockers, Non-Dihydropyridine [except
Bepridil], Diazoxide, MAO Inhibitors [except Linezolid,
Tedizolid], Molsidomine, Nicardipine, Nicorandil,
Nifedipine (also inotropic effects), Other
Antihypertensive Agents , Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sidenafil,
Prostacyclin Analogues e.g. Epoporestenol, Reserpine;
Propafenone (possesses independent beta blocking
activity)
Enhances therapeutic effect of the following drugs:
Bradycardic effect: Fingolimod, Ivabradine, Midodrine
Hypoglycemic effect: Insulin, Sulfonylureas e.g.,
Gliclazide
Disopyramide (negative inotropic effect)
Lacosamide (AV blocking effect)
Increases risk of adverse or toxic effects of Carvedilol:
Amiodarone (cardiac arrest), Calcium Channel Blockers,
Non-Dihydropyridine [except Bepridil] (bradycardia; signs
of heart failure), MAO Inhibitors [except Linezolid,
Tedizolid] (orthostatic hypotension), Nicardipine (may
precipitate signs of heart failure), Other Antihypertensive
Agent
Increases risk of adverse or toxic effects of the following
drugs:
Cholinergic Agonists e.g., Betanechol (cardiac
conduction abnormalities; bronchoconstriction),
Duloxetine (orthostatic hypotension), Levodopa
(orthostatic hypotension), Risperidone (hypotensive
effect)
Reduces therapeutic effect of Carvedilol:
Antihypertensive effect: Methylphenidate, Nonsteroidal
Anti-Inflammatory Agents
Avoid concomitant use with:
Decreases metabolism of Carvedilol:
CYP2D6 Inhibitors
Enhances therapeutic effect of Carvedilol:
Bradycardic effect: Dronedarone, Rivastigmine
Enhances therapeutic effect of the following drugs:
125

Alpha / Beta Agonists, Direct-Acting [except Dipivefrin]
(vasopressor effect), Ceritinib (bradycardic effect), Ergot
Derivatives e.g., Ergotamine (vasoconstricting effect)
Increases risk of adverse or toxic effects of Carvedilol:
Alpha2 Agonists e.g., Clonidine (AV-blocking and sinus
node dysfunction effects; rebound hypertension),
Floctafenine
C
Increases risk of adverse or toxic effects of the following
drugs:
Alpha1 Blockers e.g. Tamsulosin (orthostatic
hypotension), Amifostine (hypotensive effect), Grass
Pollen Allergen Extract / 5 Grass Extract (inhibits the
ability to effectively treat severe allergic reactions with
Epinephrine), Methacholine, Obinutuzumab
(hypotensive effect), Rituximab (hypotensive effect)
Increases serum concentration of Carvedilol:
Abiraterone Acetate, Dronedarone, Panobinostat
Increases serum concentration of the following drugs:
Afatinib [reduce Afatinib by 10 mg], Bosutinib, Colchicine
(increase distribution into certain tissues, e.g., brain),
Cyclosporine (Systemic), Dabigatran Etexilate,
Doxorubicin (Conventional), Edoxaban, Everolimus.
Pazopanib, Silodosin, Topotecan, Vincristine (Liposomal)
Reduces therapeutic effect of the following drugs:
Alpha / Beta Agonists, Direct-Acting [except Dipivefrin]
(beta-adrenoceptor-mediated effects, including anti-
anaphylactic effects of epinephrine), Beta2 Agonists
(bronchodilatory effect), Theophylline Derivatives
(bronchodilatory effect)
Administration: Administer with food to minimize the risk of
orthostatic hypotension.
Initiate only in stable patients or hospitalized patients
after volume status has been optimized and IV diuretics,
vasodilators, and inotropic agents have all been
successfully discontinued. Stabilize other heart failure
medications and minimize fluid retention prior to
initiating therapy.
Pregnancy Category: C
ATC Code: C07AG02
BETA-BLOCKING AGENTS,
NON-SELECTIVE
Rx PROPRANOLOL
Oral: 10 mg and 40 mg tablet (as hydrochloride)
A non-selective beta-adrenergic blocker that competitively
blocks responses to beta1­ and beta2­adrenergic
stimulation, which results in decreases in heart rate,
myocardial contractility, blood pressure, and myocardial
oxygen demand. Propranolol exhibits no intrinsic
sympathomimetic activity (ISA).
126
CARDIOVASCULAR SYSTEM
Indications: Antianginal; Management of acute coronary
syndrome; post-myocardial infarction (MI) maintenance;
antihypertensive
Dose:
Hypertension, by mouth, ADULT, 40 mg twice daily; increase
dosage every 3–7 days; usual dosage range, 40–160 mg
twice daily; usual dose, 120 to 240 mg divided in 2–3
doses daily (maximum daily dose, 640 mg);
ADOLESCENT and CHILD, initially 1–2 mg/kg daily
divided in 2–3 doses daily; titrate dose to effect
(maximum dose, 4 mg/kg daily up to 640 mg daily).
Obstructive hypertrophic cardiomyopathy, by mouth, ADULT,
20–40 mg 3–4 times daily.
Post-MI mortality reduction, by mouth, ADULT, initially 40
mg 3 times daily; usual dosage range, 180 to 240 mg
daily in 3–4 divided doses.
Stable angina, by mouth, ADULT, 80–320 mg daily in
divided doses 2–4 times daily.
Dose Adjustment:
Geriatric:
For use in hypertension, consider lower initial doses and
titrate to response.
Renal and Hepatic Impairment:
Use with caution. Renal and/or hepatic impairment
increases systemic exposure to propranolol.
Administration: To be taken on an empty stomach.
See Propranolol under Cardiac Therapy – Antiarrhythmics
(Class II Antiarrhythmics) in Chapter 3: Cardiovascular
System for other information.
Pregnancy Category: C
ATC Code: C07AA05
BETA-BLOCKING AGENTS, SELECTIVE
GENERAL INFORMATION
Selective beta-blockers (cardio-selective) exhibit a
competitive inhibitory effect on beta1­adrenergic
receptors, with little or no effect on beta2­receptors,
except at high doses.
Mode of Action: Competitively inhibits beta1­adrenergic
receptors, preventing the action of norepinephrine and
epinephrine on these receptors. Beta1-adrenergic
receptors are primarily located in the heart. Their activity
causes a reduction in sympathetic influences, including
chronotropy (heart rate), inotropy (contractility),
dromotropy (electrical conduction), and lusitropy
(relaxation).
Contraindications: Reversible airway diseases; second- or
third-degree heart block (except in patients with
functioning artificial pacemaker); shock (cardiogenic and
hypovolemic); bradycardia (45 to 50 beats/minute); sick
sinus syndrome (except in the presence of a pacemaker);
severe hypotension; uncontrolled heart failure;
concomitant IV administration of calcium channel
blockers; pulmonary hypertension
CARDIOVASCULAR SYSTEM
Precautions:
WARNING: Do NOT withdraw beta blocker therapy
abruptly. Gradually taper over 1–2 weeks to avoid
acute tachycardia, hypertension, and/or ischemia.
Abrupt withdrawal may exacerbate angina and, in
some cases, cause myocardial infarction, ventricular
arrhythmias, and rebound hypertension. Temporary
but prompt resumption of beta-blocker therapy may
be indicated with worsening of angina or acute
coronary insufficiency.
Major surgery: Do NOT withdraw chronic beta blocker
therapy prior to major surgery.
Atrial fibrillation; Atrioventricular block (commonly produces
mild first-degree heart block; may also produce severe
first- (P-R interval ≥0.26 sec), second-, or third-degree
heart block; patients with acute myocardial infarction
have a high risk of developing heart block of varying
degrees)
Hypotension (symptomatic hypotension may occur with use)
Anaphylactic reactions (may become more sensitive to
repeated challenges; treatment of anaphylaxis, e.g.,
epinephrine, may be ineffective or even promote
undesirable effects)
Extravasation (can lead to skin necrosis and sloughing)
Hyperkalemia (associated with elevations in serum
potassium and development of hyperkalemia; monitor
serum potassium during therapy); hepatic impairment.
Bronchospastic disease (may be exacerbated)
Conduction abnormality (can cause bradycardia, including
sinus pause, heart block, severe bradycardia, and
cardiac arrest)
Diabetes (may potentiate and/or mask signs and symptoms
of hypoglycemia)
Heart failure (monitor for worsening of condition).
Myasthenia gravis
Peripheral vascular disease and Raynaud’s disease (can
precipitate or aggravate symptoms or arterial
insufficiency)
Pheochromocytoma (may aggravate hypertension; requires
adequate alpha blockade prior to use of beta-blockers)
Prinzmetal variant angina (requires concomitant alpha1-
adrenergic receptor blockage, unopposed alpha1-
adrenergic receptors mediate coronary vasoconstriction
and can worsen angina symptoms).
Psoriasis (associated with induction or exacerbation of
psoriasis)
Psychiatric disease (may cause or exacerbate CNS
depression)
Renal impairment (active metabolite is retained); thyroid
disease (may mask signs of hyperthyroidism, e.g.,
tachycardia; abrupt withdrawal may exacerbate
symptoms of hyperthyroidism and precipitate thyroid
storm; may alter thyroid function tests).
Elderly (bradycardia may be observed more frequently in
patients >65 years).
Pregnancy (crosses the placenta; may cause intrauterine
growth restriction, small placenta, fetal or neonatal
bradycardia, hypoglycemia, respiratory depression);
lactation (excreted in breast milk and detected in the
serum and urine of nursing infants; use with caution).
Adverse Drug Reactions:
Common: Alteration of glucose and lipid metabolism,
bradycardia, bronchospasm, cold extremities,
depression, diarrhea, dizziness, dyspepsia, dyspnea,
exacerbation of Raynaud’s phenomenon, fatigue,
hallucinations, first-degree heart block (P-R interval
≥0.26 seconds), heart failure, hypotension, nausea,
pruritus, second- and third-degree heart block, shortness
of breath, tiredness, syncope, vomiting, wheezing
C
Less Common: Acute urinary retention, anxiety, cardiogenic
shock, chest pain, claudication, confusion, constipation,
flatulence, gastric pain, headache, heartburn,
hyperhidrosis, impaired concentration, impotence,
insomnia, muscle cramps, nasal congestion,
nervousness, nightmares, palpitations, peripheral
edema, Peyronie’s disease, rash, reduced libido, sleep
disturbances, somnolence, taste disturbance, urticaria,
visual disturbances, vertigo, xerostomia
Rare: Agranulocytosis, alopecia, arthritis, blurred vision,
cardiac arrest, catatonia, emotional lability, exacerbation
of psoriasis, gangrene, hepatitis, hypersensitivity
reaction, jaundice, laryngospasm, liver function
abnormality, respiratory distress, retroperitoneal fibrosis,
thrombocytopenia, thrombocytopenic purpura, tinnitus
Drug Interactions:
Monitor closely with:
Decreases metabolism of Beta Blockers:
Aminoquinolines e.g., Antimalarial drugs
Enhances therapeutic effect of Beta Blockers:
Bradycardic effect: Acetylcholinesterase Inhibitors e.g.,
Neostigmine, Amiodarone; Anilidopiperidine Opioids e.g.,
Fentanyl (bradycardic and antihypertensive effects),
Bretylium (also AV blockade), Dipyridamole,
Disopyramide (also negative inotropic effect),
Regorafenib, Tofacitinib, Other Bradycardia-causing
Agents
Antihypertensive effect: Barbiturates e.g., Phenobarbital,
Brimonidine (Topical), Calcium Channel Blockers, Non-
Dihydropyridine [except Bepridil] e.g., Verapamil,
Diazoxide, Molsidomine, Nicorandil, Nifedipine (also
negative inotropic effect), Other Antihypertensives,
Pentoxifylline, Phosphodiesterase-5 Inhibitors e.g.,
Sildenafil, Prostacyclin Analogues e.g., Epoprostenol,
Reserpine; Propafenone (possesses independent beta
blocking activity)
Enhances therapeutic effect of the following drugs:
Bradycardic effect: Fingolimod, Ivabradine, Midodrine
Hypoglycemic effect: Insulin, Sulfonylureas e.g.,
Gliclazide
Lacosamide (AV blocking effect)
Increases risk of adverse or toxic effects of Beta Blockers:
Amiodarone (cardiac arrest), Calcium Channel Blockers,
Non-Dihydropyridine [except Bepridil] (bradycardia; signs
of heart failure), MAO Inhibitors [except Linezolid,
Tedizolid] (orthostatic hypotension), Other
Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Cardiac Glycosides (bradycardic effect); Cholinergic
Agonists (cardiac conduction abnormalities;
127

bronchoconstriction); Duloxetine (orthostatic
hypotension)
Levodopa (orthostatic hypotension); MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension)
Risperidone (hypotensive effect)
Reduces therapeutic effect of Beta Blockers:
Methylphenidate (antihypertensive effect); Nonsteroidal
Anti-Inflammatory Agents (antihypertensive effect)
C
Reduces therapeutic effect of the following drugs:
Beta2 Agonists (bronchodilatory effect); Theophylline
Derivatives (bronchodilatory effect)
Avoid concomitant use with:
Enhances therapeutic effect of Beta Blockers:
Alpha2 Agonists (AV blocking effect),
Bradycardic effect: Dronedarone, Rivastigmine,
Ruxolitinib
Enhances therapeutic effect of the following drugs:
Alpha / Beta Agonists, Direct-Acting [except Dipivefrin]
(vasopressor effect); Ceritinib (bradycardic effect); Ergot
Derivatives (vasoconstricting effect)
Increases risk of adverse or toxic effects of Beta Blockers:
CYP2D6 Inhibitors (heart block)
Increases risk of adverse or toxic effects of the following
drugs:
Alpha1 Blockers (orthostatic hypotension), Alpha2
Agonists (rebound hypertension; sinus node
dysfunction), Amifostine (hypotensive effect),
Floctafenine, Grass Pollen Allergen Extract / 5 Grass
Extract (inhibits the ability to effectively treat severe
allergic reactions with Epinephrine)
Methacholine, Obinutuzumab (hypotensive effect),
Rituximab (hypotensive effect)
Increases serum concentration of Beta Blockers:
CYP2D6 Inhibitors, Dronedarone
Reduces therapeutic effect of the following drugs:
Alpha / Beta Agonists, Direct-Acting [except Dipivefrin]
(beta-adrenoceptor mediated effects, including anti-
anaphylactic effects of Epinephrine)
Rx ATENOLOL
Oral: 50 mg and 100 mg tablet
A beta1-selective antagonist that competitively blocks beta1-
adrenergic stimulation, with little or no effect on beta2-
receptors except at high doses. It exhibits no intrinsic
sympathomimetic activity (ISA).
Indications: Treatment of hypertension, alone or in
combination with other agents; management of angina
pectoris; secondary prevention post-myocardial
infarction; for acute coronary syndrome
128
CARDIOVASCULAR SYSTEM
Dose:
Hypertension, by mouth, ADULT, initially 25–50 mg once
daily, may increase to 100 mg once daily after 1–2
weeks (usual dose, 100 mg once daily; target dose, 100
mg once daily); CHILD, 0.5–1 mg/kg per dose daily;
usual dosage range, 0.5 to 1.5 mg/kg daily (maximum
dose, 2 mg/kg daily for up to 100 mg daily).
Angina pectoris, by mouth, ADULT, 50 mg once daily; may
increase to 100 mg daily; some patients may require 200
mg daily.
Post-myocardial infarction, by mouth, ADULT, 100 mg daily
or 50 mg twice daily for 6–9 days post-myocardial
infarction.
Dose Adjustment:
Geriatric:
In the management of hypertension, consider lower initial
doses and titrate to response.
Renal Impairment:
If CrCl is 15–35 mL/minute per 1.73m2, maximum dose is
50 mg daily.
If CrCl is <15 mL/minute per 1.73m2, maximum dose is 25
mg daily.
For patients on hemodialysis, administer dose post-dialysis
or administer 25–50 mg supplemental dose. Atenolol is
moderately dialyzable (20% to 50%) via hemodialysis.
Administration: May be taken without regard to meals.
NOTE: When administered acutely, monitor ECG and blood
pressure.
See General Information on Beta Blocking Agents, Selective
listed above for other information.
Pregnancy Category: D
ATC Code: C07AB03
Rx BISOPROLOL
Oral: 2.5 mg and 5 mg tablet (as fumarate)
A beta1-selective antagonist that competitively blocks beta1
adrenergic stimulation, with little or no effect on beta2-
receptors at doses ≤20 mg.
Indication: Management of coronary heart failure
Dose:
Hypertension, by mouth, ADULT, initially 2.5–5 mg once
daily; may be increased to 10 mg and then up to 20 mg
once daily, if necessary; usual dose range 5–10 mg once
daily.
Heart failure, by mouth, ADULT, initially 1.25 mg once daily
(maximum dose, 10 mg once daily); increase dose
gradually and monitor for congestive signs and
symptoms of HF making every effort to achieve target
dose shown to be effective.
NOTE: Initiate only in stable patients or hospitalized patients
after volume status has been optimized and IV diuretics,
vasodilators, and inotropic agents have all been
CARDIOVASCULAR SYSTEM
successfully discontinued. Caution should be used when
initiating in patients who require inotropes during their
hospital course.
Dose Adjustment:
Renal Impairment:
For use in hypertension, if CrCl <40 mL/minute, initiate at
2.5 mg daily; increase cautiously.
Hepatic Impairment:
For patients with hepatitis or cirrhosis, initiate at 2.5 mg
daily; increase cautiously.
Administration: May be taken without regard to meals.
See General Information on Beta Blocking Agents, Selective
listed above for other information.
Pregnancy Category: C
ATC Code: C07AB07
Rx METOPROLOL
Oral: 50 mg and 100 mg tablet (as tartrate)
A beta1-adrenoceptor (cardio-selective) antagonist without
intrinsic sympathomimetic activity (ISA), which may be
advantageous in treating hypertensive patients who also
suffer from asthma, diabetes, or peripheral vascular
disease.
Indications: Management of hypertension; angina pectoris;
acute coronary syndrome; post-myocardial infarction
maintenance
Dose:
Angina, by mouth, ADULT, initially 50 mg twice daily; usual
dosage range is 50–200 mg twice daily (maximum dose,
400 mg daily); increase dose gradually at weekly
intervals to achieve desired effect.
Hypertension, by mouth, ADULT, initially 50 mg twice daily;
effective dosage range is 100–450 mg daily in 2–3
divided doses; increase dose at weekly intervals to
desired effect (maximum total daily dose, 450 mg; usual
dosage range, 50–100 mg twice daily; target dose, 100–
200 mg daily); CHILD 1–17 years, initially 1–2 mg/kg
daily (maximum dose, 6 mg/kg daily (≤200 mg daily) ;
administer in 2 divided doses.
Myocardial infarction, early treatment, by mouth, ADULT,
25–50 mg every 6–12 hours; transition over the next 2–
3 days to twice daily dosing and increase as tolerated to
a maximum daily dose of 200 mg. [NOTE: The ACCF/AHA
guidelines for the management of STEMI recommend initiation
within the first 24 hours. Do not initiate this regimen in those with
signs of heart failure, a low output state, increased risk of
cardiogenic shock, or other contraindications.]
Myocardial infarction, secondary prevention, by mouth,
ADULT, 25–100 mg twice daily; optimize dose based on
heart rate and blood pressure; continue indefinitely.
Dose Adjustment:
Geriaric:
In the management of hypertension, consider lower initial
doses and titrate to response.
Renal Impairment:
For mild-to-moderate impairment, no dose adjustment is
necessary.
For severe impairment, refer patient to a specialist.
Hepatic Impairment:
C
For mild-to-moderate impairment, dose reduction may be
warranted
For severe impairment, refer patient to a specialist.
Administration: To be taken with or immediately following
food.
See General Information on Beta Blocking Agents, Selective
listed above for other information.
Pregnancy Category: C
ATC Code: C07AB02
CALCIUM CHANNEL BLOCKERS
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH
MAINLY VASCULAR EFFECTS
Rx AMLODIPINE
Oral: 5 mg and 10 mg tablet (as besilate / camsylate)
A long-acting dihydropyridine, calcium channel blocker,
which is useful for hypertension and coronary artery
disease.
Indication: Management of hypertension
Contraindications: unstable angina; cardiogenic shock;
hypotension; significant aortic stenosis; in instances of
MI with heart failure or poor LV function
Dose:
Hypertension, by mouth, ADULT, initially 2.5 mg once daily,
increased if necessary (maximum dose, 10 mg once
daily); CHILD, refer to a specialist.
Dose Adjustment:
Hepatic Impairment:
In patients with hepatic insufficiency, consider dose
reduction, initiating with 2.5 mg daily.
In patients with severe impairment, titrate slowly.
Precautions:
Hypotension (poor cardiac function if given with other
cardiodepressant drugs); congestive heart failure; aortic
stenosis; pre-existing abnormalities in the sinoatrial
and/or atrioventricular node (increased angina or MI can
develop after starting or increasing the dose, particularly
in patients with severe obstructive coronary artery
disease).
Hepatic impairment (half-life prolonged); Acute porphyria
129

Increased intracranial pressure; Glaucoma
Pregnancy (limited information on use in humans; risk to
fetus should be balanced against the risk of uncontrolled
maternal hypertension); lactation (presence in milk is
possible; monitor infant).
Adverse Drug Reactions:
Common: Abdominal pain, dizziness, fatigue, flushing,
gingival hyperplasia, headache, nausea, palpitation,
C
peripheral edema, pulmonary edema, rash, sleep
disturbances
Less Common: Arthralgia, dryness of mouth, chest pain,
constipation, dyspepsia, dyspnea, GI disturbances,
gynecomastia, hypotension, impotence, myalgia,
paresthesia, polyuria, mood changes, pruritus,
pulmonary edema, sweating, syncope, tachycardia, taste
disturbances, tinnitus, tremor, urinary disturbances,
weight changes
Rare: Agitation, alopecia, amnesia, angioedema,
arrhythmias, ataxia, cardiac failure, cholestasis,
coughing, dermatitis, erythema multiforme, gastritis,
hepatitis, hyperglycemia, myocardial infarction,
pancreatitis, Parkinsonism, parosmia, jaundice,
peripheral neuropathy, purpura, thrombocytopenia,
twitching, vasculitis, abnormal visual accommodation,
xerophthalmia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Amlodipine:
Drugs that reduce blood pressure (enhanced
hypotensive effects)
Avoid concomitant use with:
Reduces therapeutic effect of Amlodipine:
Calcium Salts
Increases serum concentration of the following drugs,
increasing its risk of adverse or toxic effects:
Simvastatin [limit Simvastatin dose to 20 mg daily]
(myopathy)
Administration: May be taken with or without food.
Pregnancy Category: C
ATC Code: C08CA01
Rx FELODIPINE
Oral: 5 mg and 10 mg MR tablet
A dihydropyridine calcium channel blocker that inhibits
calcium ions from entering select voltage-sensitive areas
of vascular smooth muscle and myocardium during
depolarization, producing a relaxation of coronary
vascular smooth muscle and coronary vasodilation.
Indication: Management of hypertension
Dose:
Hypertension, by mouth, ADULT, 5 mg once daily; adjust
dose as needed at no less than 2-week intervals; usual
dose range, 5–10 once daily; ADOLESCENT and CHILD
130
CARDIOVASCULAR SYSTEM
≥6 years, initially 2.5 mg once daily; may increase as
needed at no less than 2-week intervals (maximum dose,
10 mg once daily).
Dose Adjustment:
Geriatric:
Consider lower initial doses and titrate at no less than 2-
week intervals to response.
Hepatic Impairment:
Initially administer 2.5 mg once daily. Monitor blood
pressure closely during titration.
Precautions:
Angina or myocardial infarction (reflex tachycardia may
occur)
Hypotension or syncope (symptomatic hypotension with or
without syncope rarely occur)
Peripheral edema (dose-dependent)
Aortic stenosis (may reduce coronary perfusion resulting in
ischemia); Heart failure (avoid use)
Hepatic impairment (may require lower starting dose)
Hypertrophic cardiomyopathy (reduction in afterload may
worsen symptoms associated with this condition)
Elderly (may experience a greater hypotensive response;
constipation may be more of a problem)
Pregnancy (untreated chronic maternal hypertension is
associated with adverse events in the fetus, infant, and
mother); lactation (not known if excreted in breastmilk)
Adverse Drug Reactions:
Common: Headache, peripheral edema, flushing,
tachycardia
Less Common: Abdominal pain, acid regurgitation, anemia,
angioedema, angina pectoris, anxiety disorders, arm
pain, arrhythmia, arthralgia, back pain, bronchitis, chest
pain, CHF, constipation, contusion, CVA, decreased
libido, depression, diarrhea, dizziness, dry mouth,
dyspnea, dysuria, epistaxis, erythema, facial edema,
flatulence, flu­like illness, flushing, foot pain, gingival
hyperplasia, gynecomastia, hip pain, hypotension,
impotence, influenza, insomnia, irritability, knee pain, leg
pain, leukocytoclastic vasculitis, MI, muscle cramps,
myalgia, nausea, nervousness, palpitation, paresthesia,
pharyngitis, polyuria, premature beats, respiratory
infection, sinusitis, somnolence, syncope, urinary
frequency, urinary urgency, urticaria, visual
disturbances, vomiting
NOTE: Doses >10 mg daily are associated with greater
antihypertensive effects but also with a large increase in
the incidence of peripheral edema and other
vasodilatory adverse effects.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Felodipine:
Cyclosporine (Systemic), CYP2C8 Substrates, CYP3A4
Inhibitors (Moderate)
Enhances antihypertensive effect of Felodipine:
Alfuzosin, Alpha1 Blockers, Barbiturates e.g.,
Phenobarbital, Brimonidine (Topical); Non-
Dihydropyridine Calcium Channel Blockers e.g.,
Verapamil, Diazoxide, Magnesium Salts, MAO Inhibitors
[except Linezolid, Tedizolid], Molsidomine, Nicorandil,
CARDIOVASCULAR SYSTEM
Other Antihypertensive Agents; Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g., Sildenafil,
Prostacyclin Analogues e.g., Epoprostenol
Enhances therapeutic effect of the following drugs:
Nondepolarizing neuromuscular-blocking Agents e.g.,
Vecuronium (neuromuscular-blocking effect),
Nitroprusside (hypotensive effect)
Increases absorption of Felodipine:
Ethyl Alcohol
Increases metabolism of Felodipine:
Barbiturates e.g., Phenobarbital
Increases risk of adverse or toxic effects of Felodipine:
Dapoxetine (orthostatic hypotension), MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension),
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea),
Duloxetine (orthostatic hypotension), Levodopa
(orthostatic hypotension), Magnesium Salts, Risperidone
(hypotensive effect)
Reduces antihypertensive effect of Felodipine:
Calcium Salts, Methylphenidate
Reduces therapeutic effect of Clopidogrel
Avoid concomitant use with:
Decreases metabolism of Felodipine:
Antifungal Agents, Azole Derivatives, (Systemic) [except
Fluconazole, Isavuconazonium Sulfate], CYP3A4
Inhibitors (Strong), Macrolide Antibiotics [except
Azithromycin, Fidaxomicin, Spiramycin]
Decreases serum concentration of Felodipine:
Dabrafenib, Mitotane, Phenytoin, Rifamycin Derivatives
Increases metabolism of Felodipine:
Carbamazepine, CYP3A4 Inducers (Strong), Nafcillin
Increases risk of adverse or toxic effects of Felodipine:
Antifungal Agents, Azole Derivatives, Systemic [except
Fluconazole] (negative inotropic effects), Mifepristone,
Stiripentol
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine (hypotensive effect), Obinutuzumab [withhold
Felodipine 12 hours prior to Obinutuzumab infusion until
1 hour after the end of the infusion] (hypotensive effect),
Phenytoin, Rituximab (hypotensive effect)
Increases serum concentration of Felodipine:
Cimetidine, Fosphenytoin, Fusidic Acid (Systemic),
Grapefruit Juice, Idelalisib, Itraconazole, Ketoconazole
(Systemic), Mifepristone, Stiripentol
Increases serum concentration of the following drugs:
Amodiaquine, Phenytoin
Reduces therapeutic effect of Felodipine:
Phenytoin
Administration: May be administered without food or with a
small meal that is low in fat and carbohydrates. Avoid
grapefruit juice during therapy.
Swallow tablet whole. Do NOT divide, crush, or chew.
NOTE: Felodipine peak plasma concentrations are
C
increased up to two-fold when taken after a meal high in
fat or carbohydrates. Grapefruit juice similarly increases
felodipine Cmax by two-fold. Increased therapeutic and
vasodilator side effects, including severe hypotension
and myocardial ischemia, may occur.
Pregnancy Category: C
ATC Code: C08CA02
Rx NICARDIPINE
Inj.: 1 mg/mL (as hydrochloride), 2 mL and 10 mL ampule
(IV)
A calcium channel blocker that inhibits calcium ions from
entering select voltage-sensitive areas of vascular
smooth muscle and myocardium. It produces a
relaxation of coronary vascular smooth muscle and
coronary vasodilation, thus increasing myocardial oxygen
delivery in patients with vasospastic angina.
Indication: Management of acute hypertension
Contraindications: Advanced aortic stenosis
Dose:
Acute hypertension, by IV infusion, ADULT, 5 mg/ hour
initially, may increase by 2.5 mg/hour every 5 minutes
for rapid titration, to every 15 minutes for gradual
titration (maximum dose, 15 mg/hour); in rapidly titrated
patients, consider reduction to 3 mg/hour after response
is achieved
Dose Adjustment:
Geriatric:
Initiate at the low end of the dosage range. Monitor closely.
Renal and Hepatic Impairment:
Dose adjustment may be necessary. Titrate slowly with
careful monitoring. Consider lower starting dose and
closely monitor response.
Precautions:
WARNING: Significant differences exist between oral
and IV dosing. Use caution when converting from
one route of administration to another.
Angina, myocardial infarction (increased frequency,
duration, or severity of angina and/or MI has occurred
with initiation or dosage titration; reflex tachycardia may
occur);
Hypotension; Syncope (rarely occurs); Peripheral edema
(dose-dependent); Tachycardia (may occur).
131

Aortic stenosis (may reduce coronary perfusion resulting in
ischemia)
Heart failure (may worsen symptoms of HF due to mild
negative inotropic effects of nicardipine, particularly with
concomitant beta blockade)
Hypertrophic cardiomyopathy with outflow tract obstruction
(reduction in afterload may worsen symptoms
associated with this condition)
Hepatic impairment; Renal impairment
C
Abrupt withdrawal may cause rebound angina in patients
with CAD
Elderly (constipation may be more of a problem; may
experience greater hypotensive response)
Pregnancy (adverse events have been observed in some
animal reproduction studies; crosses the placenta;
changes in fetal heart rate, neonatal hypotension and
neonatal acidosis have been observed following
maternal use); lactation (minimally excreted in
breastmilk; breast­feeding is not recommended).
Adverse Drug Reactions:
Common: Flushing, pedal edema, exacerbation of angina
pectoris, hypotension, palpitations, tachycardia, chest
pain, extrasystoles, hemopericardium, supraventricular
tachycardia, hypertension, edema, headache, dizziness,
hypoesthesia, intracranial hemorrhage, pain,
somnolence, diaphoresis, skin rash, hypokalemia,
nausea, vomiting, dyspepsia, abdominal pain,
xerostomia, hematuria, injection site reaction, pain at
injection site, weakness, myalgia, paresthesia
Less Common: Abnormal dreams, abnormal vision, angina
pectoris, anxiety, atrial fibrillation, atrioventricular block,
arthralgia, atypical chest pain, blurred vision, cerebral
ischemia, confusion, conjunctivitis, constipation, deep
vein thrombophlebitis, depression, ST segment
depression, dyspnea, ear disease, fever, gingival
hyperplasia, heart block, hot flash, hyperkinesia,
hypersensitivity reaction, hypophosphatemia,
hypertonia, impotence, infection, insomnia, inversion T
wave on ECG, malaise, myocardial infarction, neck pain,
nervousness, nocturia, orthostatic hypotension,
parotitis, pericarditis, peripheral vascular disease,
respiratory tract disease, rhinitis, sinus node
dysfunction, sinusitis, sore throat, sustained tachycardia,
syncope, thrombocytopenia, tinnitus, tremor, urinary
frequency, ventricular extrasystoles, ventricular
tachycardia, vertigo, vomiting
Drug Interactions:
Monitor closely with:
Decreases metabolism of Nicardipine:
Cyclosporine (Systemic), CYP2C19 Substrates, CYP2D6
Substrates
Enhances therapeutic effects of Nicardipine:
Antihypertensive effect: Alpha1 Blockers e.g. Alfuzosin,
Barbiturates e.g. Phenobarbital, Brimonidine (Topical),
Non-Dihydropyridine Calcium Channel Blockers,
Diazoxide, Magnesium Salts, Molsidomine, Nicorandil,
Pentoxifylline, Phosphodiesterase-5 Inhibitors e.g.
Sildenafil, Prostacyclin Analogues e.g. Epoporestenol,
Other Antihypertensive Agents
Moderate Risk QTc-prolonging Agents, Indeterminate
Risk and Risk Modifying (QTc-prolonging agents)
Enhances therapeutic effect of the following drugs:
132
CARDIOVASCULAR SYSTEM
Aripiprazole, Carvedilol (hypotensive effect),
Nondepolarizing Neuromuscular-blocking Agents e.g.
Pancuronium (neuromuscular-blocking effect),
Nitroprusside (hypotensive effect)
Increases metabolism of Nicardipine:
Barbiturates e.g. Phenobarbital
Increases risk of adverse or toxic effects of Nicardipine:
Dapoxetine (orthostatic hypotension), MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension),
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea), Carvedilol
(may precipitate signs of heart failure), Duloxetine
(orthostatic hypotension), Levodopa (orthostatic
hypotension), Magnesium Salts, Risperidone
(hypotensive effect)
Reduces therapeutic effect of Nicardipine:
Barbiturates e.g Phenobarbital, Calcium Salts,
Methylphenidate
Reduces therapeutic effect of the following drugs:
Codeine (prevents metabolic conversion to its active
metabolite, morphine); Tramadol (prevents metabolic
conversion to its active metabolite)
Avoid concomitant use with:
Decreases metabolism of Nicardipine:
Antifungal Agents, Azole Derivatives, Systemic [except
Fluconazole], CYP2C9 Substrates, CYP3A4 Inhibitors;
Macrolide Antibiotics [except Azithromycin, Spiramycin]
Decreases serum concentration of Nicardipine:
Dabrafenib, Efavirenz, Mitotane, Phenytoin, Rifamycin
Derivatives, Siltuximab
Decreases serum concentration of the following drugs:
Clopidogrel, Tamoxifen
Enhances therapeutic effect of the following drugs:
Highest Risk QTc-prolonging Agents, Indeterminate Risk
and Risk Modifying (QTc-prolonging effect)
Enhances therapeutic effect of Nicardipine:
Mifepristone (QTc-prolonging effect)
Increases metabolism of Nicardipine:
Carbamazepine, CYP3A4 Inducers, Nafcillin
Increases risk of adverse or toxic effects of Nicardipine:
Azole Antifungal Agents (Systemic) [except Fluconazole,]
(negative inotropic effects), Grapefruit Juice,
Mifepristone, Stiripentol
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine [withhold Nicardipine 24 hours prior to
Amifostine administration] (hypotensive effect),
Citalopram (serotonin syndrome; QT prolongation),
Fosphenytoin, Highest Risk QTc-prolonging Agents,
Indeterminate Risk and Risk Modifying (alterations of
cardiac rhythm), Obinutuzumab [withhold Nicardipine 12
CARDIOVASCULAR SYSTEM
hours prior to Obinutuzumab infusion until 1 hour after
the end of the infusion] (hypotensive effect), Phenytoin,
Rituximab (hypotensive effect)
Increases serum concentration of Nicardipine:
Fosphenytoin, Fusidic Acid (Systemic), Grapefruit Juice,
Idelalisib, Mifepristone, Simeprevir, Stiripentol
Increases serum concentration of the following drugs:
Afatinib [reduce Afatinib dose by 10mg], Bosutinib,
Cilostazol [reduce Cilostazol dose to 50 mg twice daily],
Citalopram [limit Citalopram dose to a maximum of 20
mg daily], Colchicine (increases distribution into certain
tissues, e.g., brain), Dabigatran Etexilate, Diclofenac
(Systemic), Doxorubicin (Conventional), Edoxaban,
Eliglustat [reduce Eliglustat dose to 84 mg daily],
Everolimus, Lacosamide, Lomitapide [limit maximum
Lomitapide dose to 30 mg daily], Metoprolol, Pazopanib,
Phenytoin, Pimozide, Silodosin, Thioridazine, Topotecan,
Vincristine (Liposomal)
Reduces therapeutic effect of Nicardipine:
Phenytoin
Reduces therapeutic effect of the following drugs:
Clopidogrel, Fosphenytoin
Administration: Administer by slow continuous IV infusion
via a central line or through a large peripheral vein. Avoid
use of small peripheral veins to minimize infusion site
reactions.
Do NOT combine or run in the same line as other
medications.
Monitor infusion site closely to prevent extravasation.
Peripheral venous irritation may be minimized by
changing the site of infusion every 12 hours.
Evaluate cardiac status and blood pressure and monitor
for rash, hypotension, bradycardia, confusion, and
nausea when starting, adjusting dose, or discontinuing.
NOTE: Parenteral administration is indicated only for short-term use.
Teach patient orthostatic precautions.
Pregnancy Category: C
ATC Code: C08CA04
Rx NIFEDIPINE
Oral: 10 mg capsule
30 mg MR tablet
A calcium channel blocker that inhibits calcium ion from
entering select voltage-sensitive areas of vascular
smooth muscle and myocardium during depolarization.
It produces coronary vasodilation and reduces peripheral
vascular resistance and ultimately, arterial blood
pressure.
Indication: Treatment of hypertension
Contraindications: Concomitant use with strong CYP3A4
inducers (e.g., rifampin); cardiogenic shock; STEMI;
Heart failure
Dose:
Hypertension, by mouth, ADULT, initially 30–60 mg once
daily, titrate to 30–90 mg daily (maximum, 90–120 mg
daily).
C
NOTE: Adjust dose at 7– to 14–day intervals to allow for
adequate assessment of new dose. If clinically indicated,
titration may be done more rapidly with appropriate
monitoring.
Use same total daily dose when switching from
immediate-release
to sustained-release formulation.
Dose Adjustment:
Geriatric:
Consider lower initial doses and titrate to response. Half-life
is extended in elderly patients (6.7 hours) as compared
to younger subjects (3.8 hours).
Hepatic Impairment:
Use with caution. Clearance is reduced in cirrhotic patients,
which may lead to increased systemic exposure. Monitor
closely for adverse effects or toxicity and consider dose
adjustments.
Precautions:
WARNING: Use with extreme caution due to rapid and
prolonged fall in blood pressure.
Use is restricted for acute hypertensive emergencies in
patients less than 18 years old.
Abrupt withdrawal (may cause rebound angina in patients
with CAD).
Angina or MI (increased angina and/or MI have occurred;
reflex tachycardia may occur resulting in angina and/or
MI in patients with obstructive coronary disease)
Hypotension or syncope (rarely occurs; blood pressure must
be lowered at a rate appropriate for the patient's clinical
condition; death, cerebrovascular ischemia, syncope,
stroke, acute myocardial infarction, and fetal distress,
have been reported)
Peripheral edema (most common side effect).
Aortic stenosis (may reduce coronary perfusion resulting in
myocardial ischemia); Heart failure (avoid use)
Hypertrophic cardiomyopathy with outflow tract obstruction
(reduction in afterload may worsen symptoms
associated with this condition).
Gastrointestinal strictures (alterations in GI anatomy, e.g.,
severe GI narrowing, history of GI cancer, obstruction,
bowel resection, gastric bypass, vertical banded
gastroplasty, and underlying hypomotility disorders have
led to bezoar formation with extended release forms);
hepatic impairment.
Immediate-release formulations should not be used to
manage primary hypertension (adequate studies have
not been conducted)
May contain lactose (do not administer in patients with
galactose intolerance, Lapp lactase deficiency, or
glucose-galactose malabsorption syndromes).
133

Surgery (cardiopulmonary bypass, intraoperative blood loss
or vasodilating anesthesia may result in severe
hypotension and/or increased fluid requirements;
consider withdrawing nifedipine >36 hours before
surgery).
Elderly (immediate-release tablets may cause hypotension
and risk of precipitating myocardial ischemia; may
experience a greater hypotensive response; constipation
may be more of a problem).
C
Pregnancy (crosses the placenta and small amounts can be
detected in the urine of newborn infants; an increase in
perinatal asphyxia, cesarean delivery, prematurity, and
intrauterine growth retardation have been reported);
lactation (excreted in breast milk; breast­feeding is not
recommended).
Adverse Drug Reactions:
Common: Flushing, peripheral edema (dose-related),
palpitation, transient hypotension (dose-related),
coronary heart failure, lightheadedness, dizziness,
giddiness, nervousness, headache, mood changes,
fatigue, shakiness, jitteriness, sleep disturbances,
difficulties in balance, fever, chills, dermatitis, pruritus,
urticaria, sexual difficulties, nausea, heartburn,
constipation, diarrhea, cramps, flatulence, muscle
cramps or tremor, weakness, inflammation, joint
stiffness, gingival hyperplasia, blurred vision, coughing,
wheezing, nasal congestion, sore throat, chest
congestion, dyspnea, diaphoresis
Less Common: Agranulocytosis, allergic hepatitis, alopecia,
anemia, aplastic anemia, angina, angioedema,
arrhythmia, arthritis with positive ANA, bezoars, cerebral
ischemia, depression, dysosmia, epistaxis, EPS, erectile
dysfunction, erythromelalgia, exanthematous pustulosis,
erythema multiforme, exfoliative dermatitis, facial
edema, gastroesophageal reflux, gastrointestinal
obstruction, gastrointestinal ulceration, gynecomastia,
hematuria, ischemia, leukopenia, lip cancer, memory
dysfunction, migraine, myalgia, myoclonus, nocturia,
paranoid syndrome, parotitis, periorbital edema,
photosensitivity, polyuria, purpura, Stevens-Johnson
syndrome, syncope, tachycardia, taste perversion,
thrombocytopenia, tinnitus, toxic epidermal necrolysis,
transient blindness, ventricular arrhythm
Drug Interactions:
Monitor closely with:
Decreases metabolism of Nifedipine:
Cyclosporine (Systemic)
Enhances antihypertensive effect of Nifedipine:
Alpha1 Blockers e.g. Alfuzosin, Barbiturates e.g.
Phenobarbital, Brimonidine (Topical), Non-
dihydropyridine Calcium Channel Blockers, Diazoxide,
Magnesium Salts, Molsidomine, Nicorandil, Other
Antihypertensive Agents, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
Prostacyclin Analogues e.g. Epoprostenol
Enhances therapeutic effect of the following drugs:
Aripiprazole, Beta Blockers (hypotensive effect; negative
inotropic effect), Nondepolarizing Neuromuscular-
blocking Agents e.g. Pancuronium (neuromuscular-
blocking effect), Nitroprusside (hypotensive effect)
Increases metabolism of Nifedipine:
134
CARDIOVASCULAR SYSTEM
Barbiturates e.g. Phenobarbital
Increases risk of adverse or toxic effects of Nifedipine:
Dapoxetine (orthostatic hypotension), MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension),
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea),
Duloxetine (orthostatic hypotension), Fluoxetine,
Levodopa (orthostatic hypotension), Magnesium Salts,
Risperidone (hypotensive effect)
Reduces therapeutic effect of Nifedipine:
Calcium Salts, Melatonin (antihypertensive effect),
Methylphenidate (antihypertensive effect)
Reduces therapeutic effect of Clopidogrel
Avoid concomitant use with:
Decreases metabolism of Nifedipine:
CYP3A4 Inhibitors, Macrolide Antibiotics [except
Azithromycin, Spiramycin]
Decreases serum concentration of Nifedipine:
Dabrafenib, Phenytoin
Enhances therapeutic effect of Nifedipine:
Cimetidine, Grapefruit Juice
Enhances therapeutic effect of Tizanidine
Increases metabolism of Nifedipine:
CYP3A4 Inducers (Strong), Nafcillin
Increases risk of adverse or toxic effects of Nifedipine:
Azole Derivatives (Systemic) [except Fluconazole,
Isavuconazonium Sulfate], Grapefruit Juice (severe
hypotension; myocardial ischemia), Mifepristone,
Stiripentol
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine [withhold Nifedipine 24 hours prior to
Amifostine administration] (hypotensive effect),
Obinutuzumab [withhold Nifedipine 12 hours prior to
Obinutuzumab infusion until 1 hour after the end of the
infusion] (hypotensive effect), Rituximab (hypotensive
effect), Tizanidine
Increases serum concentration of Nifedipine:
Cimetidine, Conivaptan, Fusidic Acid (Systemic),
Idelalisib, Mifepristone, Stiripentol
Increases serum concentration of the following drugs:
Phenytoin, Tizanidine [initiate Tizanidine at 2 mg and
increase in 2–4 mg increments based on patient
response]
Reduces therapeutic effect of Nifedipine:
Dabrafenib
Administration: May be taken with or without food. Capsules
are rapidly absorbed orally if administered without food
but may result in vasodilator side effects. If flushing is
CARDIOVASCULAR SYSTEM
problematic, administer low-fat meals to decrease
flushing.
Swallow tablets whole. Do NOT crush, split, or chew.
Teach patient orthostatic precautions.
NOTE: For Adalat CC, Afeditab CR, Nifediac CC, administer
on an empty stomach (as per manufacturer labelling).
Other extended-release products may not have this
recommendation; consult product labeling.
Nifedipine serum levels may be decreased if taken with
food. Food may decrease the rate but not the extent of
absorption of Procardia XL®.
Pregnancy Category: C
ATC Code: C08CA05
Rx NIMODIPINE
Oral: 30 mg tablet
A calcium channel blocker that inhibits calcium ion from
entering select voltage-sensitive areas of vascular
smooth muscle and myocardium during depolarization.
Nimodipine has a greater effect on cerebral arterials
than other arterials due to the drug's increased
lipophilicity and cerebral distribution.
Indication: Prophylaxis and treatment of ischemic
neurologic deficits caused by cerebral vasospasms
following subarachnoid hemorrhage of aneurysmal origin
Contraindications: Concomitant use with phenobarbital,
phenytoin, carbamazepine, or rifampin; concomitant use
with strong CYP3A4 inhibitors (e.g., clarithromycin,
telithromycin, delaviridine, indinavir, nelfinavir, ritonavir,
saquinavir, ketoconazole, itraconazole, voriconazole,
and nefazodone)
Dose:
Subarachnoid hemorrhage: oral: 60 mg every 4 hours for 21
consecutive days (maximum total duration of therapy), or
until transitioning IV therapy is needed.
Dose Adjustment:
Renal Impairment:
Nimodipine undergoes minimal renal elimination. Dose
adjustment may not be necessary.
Not removed by hemodialysis or peritoneal dialysis.
Supplemental dose is not necessary.
Hepatic Impairment:
Use with caution in patients with cirrhosis. Reduce dose to
30 mg every 4 hours.
Precautions:
Angina or MI (increased angina and/or MI have occurred
with initiation or dosage titration CCBs; reflex
tachycardia may occur resulting in angina and/or MI in
patients with obstructive coronary disease)
Hypotension or syncope (symptomatic hypotension with or
without syncope can occur; monitor blood pressure
closely during treatment); Peripheral edema.
Gastrointestinal events (intestinal pseudo-obstruction and
ileus)
Hepatic impairment (monitor blood pressure and heart rate
closely)
Hypertrophic cardiomyopathy with outflow tract obstruction
Elderly (may experience a greater hypotensive response;
C
constipation may be more of a problem)
Pregnancy (crosses the placenta; adverse events have been
observed in animal reproduction studies); lactation
(excreted into breastmilk; breast-feeding is not
recommended).
Adverse Drug Reactions:
Common: Decreased blood pressure, bradycardia,
headache, nausea
Less Common: Anemia, decreased platelet count,
diaphoresis, edema, disseminated intravascular
coagulation, dizziness, flushing, gastrointestinal
hemorrhage, GI pseudo-obstruction, hematoma,
hepatitis, hypertension, intestinal obstruction, jaundice,
muscle cramps, palpitations, pruritus, rebound
vasospasm, thrombocytopenia, vomiting, wheezing
Drug Interactions:
Monitor closely with:
Decreases metabolism of Nimodipine:
Cyclosporine (Systemic)
Enhances antihypertensive effect of Nimodipine:
Alpha1 Blockers e.g. Alfuzosin, Barbiturates e.g.
Phenobarbital, Brimonidine (Topical), Non-
Dihydropyridine Calcium Channel Blockers e.g.
Verapamil, Diazoxide, Magnesium Salts, MAO Inhibitors
[except Linezolid, Tedizolid], Molsidomine, Nicorandil,
Other Antihypertensive Agents, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
Prostacyclin Analogues e.g. Epoprostenol
Enhances therapeutic effect of the following drugs:
Nondepolarizing Neuromuscular-blocking Agents e.g.
Pancuronium (neuromuscular-blocking effect),
Nitroprusside (hypotensive effect)
Increases metabolism of Nimodipine:
Barbiturates e.g. Phenobarbital, Nafcillin
Increases risk of adverse or toxic effects of Nimodipine:
Dapoxetine (orthostatic hypotension)
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotension)
Other Antihypertensive Agents
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea),
Duloxetine (orthostatic hypotension), Levodopa
(orthostatic hypotension), Magnesium Salts, Risperidone
(hypotensive effect)
Reduces antihypertensive effect of Nimodipine:
Methylphenidate
Reduces therapeutic effect of Clopidogrel
135

Avoid concomitant use with:
Decreases metabolism of Nimodipine:
Macrolide Antibiotics [except Azithromycin, Fidaxomicin,
Spiramycin]
Decreases serum concentration of Nimodipine:
CYP3A4 Inducers (Strong), Dabrafenib
Enhances therapeutic effect of Nimodipine:
C
Cimetidine
Increases risk of adverse or toxic effects of Nimodipine:
Mifepristone, Stiripentol
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine [withhold Nimodipine 24 hours prior to
Amifostine administration] (hypotensive effect);
Obinutuzumab [withhold Nifedipine 12 hours prior to
Obinutuzumab infusion until 1 hour after the end of the
infusion] (hypotensive effect); Rituximab (hypotensive
effect)
Increases serum concentration of Nimodipine:
Cimetidine, Conivaptan, CYP3A4 Inhibitors (Strong),
Fusidic Acid (Systemic), Idelalisib, Mifepristone,
Stiripentol
Reduces therapeutic effect of Nimodipine:
Dabrafenib
Administration: Administer consistently with or without
meals.
Swallow tablet whole with an adequate amount of fluid,
e.g., glass of water. Do NOT crush tablet.
Avoid alkaline mixtures for 2 hours before or after
administration. Patient should not be lying down during
administration.
Do NOT administer parenterally. Life-threatening
adverse events have occurred when contents of oral
formulation were administered parenterally.
Pregnancy Category: C
ATC Code: C08CA06
136
CARDIOVASCULAR SYSTEM
SELECTIVE CALCIUM CHANNEL
BLOCKERS WITH DIRECT
CARDIAC EFFECTS
GENERAL INFORMATION
Selective calcium-channel blockers (CCBs) exhibit an
inhibitory effect on L-type calcium channels. It is used for
the treatment of hypertension, angina, and arrhythmias.
Mode of Action: Binds to L-type calcium channels located on
the vascular smooth muscle, cardiac myocytes, and
cardiac nodal tissue, blocking entry of calcium into the
cell. This causes vascular smooth muscle relaxation,
decreased myocardial force generation, decreased heart
rate, and decreased conduction velocity within the heart.
Precautions:
WARNING: All CCBs have some degree of negative
inotropic effect and may, in excessive doses or in
combination with other drugs, produce myocardial
depression especially after MI.
Abrupt withdrawal and long-term use (has been associated
with severe angina).
Conduction abnormalities (may worsen first-degree AV
block and exacerbate bradycardia); arrhythmia (severe
hypotension likely to occur upon administration); heart
failure (can exacerbate condition); impaired left
ventricular function; hypotension or syncope
(symptomatic hypotension with or without syncope rarely
occur);
Hypertrophic cardiomyopathy [HCM] with outflow tract
obstruction.
Hepatic and renal impairment (in severe impairment,
monitor hemodynamics and ECG); Increased hepatic
enzymes (rarely observed)
Diabetes mellitus (affects insulin secretion and its
peripheral action).
Attenuated neuromuscular transmission (decreased
neuromuscular transmission has been reported).
Patients taking beta-blockers or digitalis (at risk of AV block,
bradycardia, asystole, or sinus arrest);
Patients at risk to develop intestinal obstruction (diltiazem
has an inhibitory effect on intestinal motility; may be
associated with mood changes).
Children (severe apnea, bradycardia, hypotensive
reactions, and cardiac arrest may occur).
Elderly (greater hypotensive response; constipation may be
more of a problem)
Pregnancy (crosses the placenta; adverse events were
observed in some animal reproduction studies); lactation
(excreted into breast milk; not recommended).
CARDIOVASCULAR SYSTEM
Rx DILTIAZEM
Oral: 60 mg tablet (as hydrochloride)
60 mg, 120 mg, 180 mg, and 240 mg MR capsule (as
hydrochloride)
120 mg and 180 mg MR tablet (as hydrochloride)
A non-dihydropyridine calcium channel blocker, which has a
negative chronotropic effect, thus decreasing the
workload of the heart, and consequently reducing its
oxygen requirements.
Indication: Prophylaxis and treatment of angina
Contraindications: Marked bradycardia (<40
beats/minute); sick sinus syndrome (without
pacemaker); severe hypotension (<90 mmHg systolic);
CHF; acute porphyria; second- or third-degree AV block
(without pacemaker); Wolff-Parkinson-White syndrome;
acute MI and pulmonary congestion; pregnancy
Dose:
Angina, by mouth, ADULT, initially 30 mg 3 or 4 times daily;
increase as required or at 1- to 2-day interval until
optimum response is obtained (maximum dose, 360 mg
daily in 3–4 divided doses); doses of up to 360 mg/day
may be needed in unstable angina;
controlled-release products, initially 180 mg once daily;
increase as required up to 360 mg once daily.
NOTE: Dose should not be increased if heart rate drops to
50 beats/minute.
Dose Adjustment:
Geriatric:
Start treatment at a lower dose.
Renal Impairment:
Start treatment at a lower dose. Use with caution.
Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction
may be warranted.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Abdominal pain, bradycardia, dizziness, dyspnea,
congestion, flushing, headache, fatigue, nausea,
nervousness, pain, palpitations, peripheral edema,
vasodilation, vomiting
Less Common: AV block, gout
Rare: Depression, EPS, gum hyperplasia, gynecomastia,
hepatitis, hypersensitivity reactions, photosensitivity
reactions, rash
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Diltiazem:
Drugs causing hypotension, bradycardia, or slow cardiac
conduction, e.g., Amlodipine, Diazepam, Methyldopa;
Hydrochlorothiazide (bradycardia; hypotension)
Increases risk of adverse or toxic effects of the following
drugs:
Carbamazepine, Digoxin, Midazolam (sedative and
respiratory depressant effects; due to decreased
metabolism), Phenytoin, Ritonavir (due to increased
serum concentration)
Reduces therapeutic effect of Rifampicin (due to increased
metabolism)
Avoid concomitant use with:
C
Increases risk of adverse or toxic effects of the following
drugs due to increased serum concentration:
Colchicine, HMG-CoA Reductase Inhibitors, e.g.,
Atorvastatin, Simvastatin (rhabdomyolysis; myopathy)
Administration: Normal release preparations may be taken
with or without food. Administer immediate-release
preparations before meals and at bedtime. For long-
acting dosage forms, swallow whole. Do NOT open, chew,
or crush.
NOTE: Serum levels may be elevated if taken with food.
See General Information on Calcium Channel Blockers –
Selective Calcium Channel Blockers with Direct Cardiac
Effects in Chapter 3: Cardiovascular System for other
information.
Pregnancy Category: C
ATC Code: C08DB01
Rx VERAPAMIL
Oral: 80 mg tablet (as hydrochloride)
240 mg MR tablet (as hydrochloride)
Inj.: 2.5 mg/mL (as hydrochloride), 2 mL ampule (IV)
A calcium channel blocker that inhibits calcium ion from
entering the “slow channels” or select voltage-sensitive
areas of vascular smooth muscle and myocardium
during depolarization, producing relaxation of coronary
vascular smooth muscle and coronary vasodilation.
Indication: Treatment of angina pectoris (vasospastic,
chronic stable, unstable), supraventricular arrhythmia,
and hypertension.
Contraindications: Severe left ventricular dysfunction;
hypotension (systolic pressure <90 mm Hg) or
cardiogenic shock; sick sinus syndrome (except in
patients with a functioning pacemaker) ; second- or third-
degree AV block (except in patients with a functioning
pacemaker) ; atrial flutter or fibrillation and an accessory
bypass tract (Wolff-Parkinson-White [WPW] syndrome,
Lown-Ganong-Levine syndrome)
Dose:
Angina, by mouth, ADULT, immediate-release tablets,
initially 80-120 mg 3 times daily; usual dose range, 80-
160 mg 3 times daily;
modified-release tablets, initially 180 mg once daily at
bedtime; if inadequate response, may increase dose at
weekly intervals to 240 mg once daily, then 360 mg once
137

daily, then 480 mg once daily (maximum dose, 480 mg
daily).
Hypertension, by mouth, ADULT, immediate-release tablets,
initially 80-120 mg 3 times daily; usual dose range, 80-
160 mg 3 times daily;
sustained-release tablets, initially 180-240 mg once
daily at bedtime.
C
Dose Adjustment:
Renal Impairment:
Use with caution. Monitor ECG.
Hepatic Impairment:
Dose reduction may be required.
In patients with cirrhosis, reduce dose to 20% of normal
dose. Monitor ECG.
Adverse Drug Reactions:
Common: Peripheral edema, hypotension, CHF, pulmonary
edema, AV block, bradycardia, flushing, headache,
fatigue, dizziness, lethargy, pain, sleep disturbance,
rash, gingival hyperplasia, constipation, dyspepsia,
nausea, diarrhea, myalgia, paresthesia, dyspnea, flu­like
syndrome
Less Common: Abdominal discomfort, alopecia, angina,
arthralgia, atrioventricular dissociation, blurred vision,
bruising, cerebrovascular accident, chest pain,
claudication, confusion, diaphoresis, ECG abnormal,
equilibrium disorders, erythema multiforme, exanthema,
extrapyramidal symptoms, galactorrhea or
hyperprolactinemia, gastrointestinal distress,
gynecomastia, hyperkeratosis, impotence, insomnia,
macules, MI, muscle cramps, palpitation, psychosis,
purpura (vasculitis), shakiness, somnolence, spotty
menstruation, SJS, syncope, tinnitus, urination
increased, urticaria, weakness, xerostomia, asystole,
eosinophilia, EPS, exfoliative dermatitis, GI obstruction,
hair color change, paralytic ileus, Parkinsonian
syndrome, pulseless electrical activity, shock, ventricular
fibrillation
Drug Interactions:
NOTE: Verapamil is a substrate of CYP1A2 (minor), CYP2B6
(minor), CYP2C9 (minor), CYP2E1 (minor), CYP3A4
(major), and P-glycoprotein.
Monitor closely with:
Decreases metabolism of the following drugs:
Pimecrolimus, Tacrolimus
Enhances antihypertensive effect of Verapamil:
Alfuzosin; Alpha1 Blockers e.g. Clonidine;
Anilidopiperidine Opioids e.g. Fentanyl; Barbiturates e.g.
Phenobarbital, Brimonidine (Topical); Diazoxide;
Magnesium Salts; MAO Inhibitors [except Linezolid,
Tedizolid]; Molsidomine; Nicorandil; Pentoxifylline;
Phosphodiesterase-5 Inhibitors e.g. Sildenafil;
Prostacyclin Analogues e.g. Epoprostenol; Quinidine,
Other Antihypertensive Agents
Enhances therapeutic effects of Verapamil:
Bradycardic effect: Anilidopiperidine Opioids, Bretylium
(AV blockade), Other Bradycardia-causing Agents,
Regorafenib, Ruxolitinib, Tofacitinib
AV blocking effect: Clonidine, Bretylium
138
CARDIOVASCULAR SYSTEM
Enhances therapeutic effect of the following drugs:
Aripiprazole, Beta Blockers [except Levobunolol,
Metipranolol] (hypotensive effect), Cardiac Glycosides
(AV blocking effect), Ethyl Alcohol, Fingolimod
(bradycardic effect), Lacosamide (AV blocking effect),
Midodrine (bradycardic effect), Non-depolarizing
Neuromuscular-blocking Agents e.g. Atracurium
(neuromuscular-blocking effect), Nitroprusside
(hypotensive effect), Salicylates (anticoagulant effect)
Increases risk of adverse or toxic effects of Verapamil:
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotension); Other Antihypertensive Agents
Avoid concomitant use with:
Decreases metabolism of Verapamil:
Azole Derivatives (Systemic) e.g. Ketoconazole,
Carbamazepine, Cyclosporine (Systemic), CYP3A4
Inhibitors (Strong), Macrolide Antibiotics [except
Azithromycin, Fidaxomicin, Spiramycin], Protease
Inhibitors e.g. Indinavir [reduce Verapamil dose by 50%]
Enhances therapeutic effect of Verapamil:
Cimetidine, Ivabradine (QTc-prolonging effect),
Telithromycin (bradycardic effect; antihypertensive
effect)
Enhances therapeutic effect of the following drugs:
Amiodarone (bradycardic effect) Ceritinib (bradycardic
effect), Dantrolene (negative inotropic effect),
Dronedarone (AV-blocking effect and other
electrophysiologic effects), Ivabradine (bradycardic
effect), Tizanidine
Increases metabolism of Verapamil:
CYP3A4 Inducers, Nafcillin
Increases risk of adverse or toxic effects of Verapamil:
Azole Derivatives e.g., Ketoconazole (Systemic) (negative
inotropic effects); Calcium Channel Blockers,
Dihydropyridine e.g. Amlodipine (hypotensive effect),
Dantrolene (hyperkalemic effect), Mifepristone,
Protease Inhibitors (AV nodal blockade), Stiripentol
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine [withhold Verapamil 24 hours prior to
Amifostine administration], Amiodarone (sinus arrest),
Avanafil, Budesonide (corticosteroid excess),
Carbamazepine, Ceritinib (symptomatic bradycardia),
Colchicine (Colchicine toxicity), Disopyramide (profound
depression of myocardial contractility), Fosphenytoin
(Phenytoin toxicity), Ibrutinib; Lovastatin [initiate
Lovastatin at 10 mg daily; do not exceed 20 mg daily]
(myositis; rhabdomyolysis), Obinutuzumab [withhold
Nicardipine 12 hours prior to Obinutuzumab infusion
until 1 hour after the end of the infusion] (hypotensive
effect), Oxycodone, Phenytoin, Rituximab (hypotensive
effect), Sonidegib (musculoskeletal adverse reactions),
Tizanidine, Ulipristal, Zopiclone
Increases serum concentration of Verapamil:
Atorvastatin, Cimetidine, Conivaptan, Fusidic Acid
(Systemic), Grapefruit Juice, Mifepristone, Protease
Inhibitors e.g. Indinavir [reduce Verapamil dose by 50%]
Stiripentol
CARDIOVASCULAR SYSTEM
Increases serum concentration of the following drugs:
Vincristine (Liposomal); Zopiclone [initial Zopiclone dose
should not exceed 3.75 mg]
Reduces therapeutic effect of Verapamil:
Carbamazepine, Phenytoin
TEST INTERACTION. May produce a false-positive result in the urine
detection of Methadone.
Administration: May be administered without regard to
meals. Do NOT crush or chew MR products.
For Calan SR, Isoptin SR, administer with food or milk.
Pregnancy Category: C
ATC Code: C08DA01
See Verapamil under Cardiac Therapy – Antiarrhythmics
(Class IV Antiarrhythmics) in Chapter 3: Cardiovascular
System for other information.
CENTRALLY ACTING
ANTIADRENERGIC AGENTS
Rx CLONIDINE
Oral: 75 micrograms and 150 micrograms tablet (as
hydrochloride)
Inj.: 150 micrograms/mL (as hydrochloride), 1 mL ampule
(IV)
An imidazoline-derived, centrally-acting agonist at alpha2-
adrenoceptors and imidazoline receptors, which acts by
reducing sympathetic tone resulting in BP lowering.
Indication: Hypertension (alone or used concomitantly with
other antihypertensive agents)
Contraindications: Bradyarrhythmia secondary to second- or
third-degree AV block or sick sinus syndrome.
Dose:
NOTE: Individualize dose based on patient’s BP response.
Hypertension, by mouth, ADULT, initially 75 micrograms 2–
3 times daily, increased by 75 micrograms daily every 2–
3 days (maximum dose, 1.2 mg daily; maintenance dose,
150–300 micrograms twice daily).
Hypertensive urgencies, by mouth, ADULT, 75 micrograms.
Dose Adjustment:
Renal Impairment:
Adjust dose according to the degree of impairment. Patients
may benefit from a lower initial dose.
For mild-to-moderate impairment, use with caution.
For severe impairment, refer to a specialist.
Precautions:
WARNING: Severe withdrawal syndrome (rebound
HTN) may occur after abrupt discontinuation.
Sudden cessation of treatment has, in some cases,
resulted in nervousness, agitation, headache, and
tremor accompanied or followed by a rapid rise in
BP and elevated catecholamine concentration in
the plasma.
C
Withdrawal syndrome (may be worsened by concomitant
administration of beta blockers; taper dose over 5–7
days before stopping the drug; excessive rise in BP
following discontinuation can be reversed by oral
administration).
Mild-to-moderate bradyarrhythmia, constipation, or
polyneuropathy (avoid use in patients with depression or
a history of it); coronary heart disease, severe coronary
insufficiency, conduction disturbances, recent MI,
cerebrovascular disease, Raynaud’s phenomenon or
other vasospastic peripheral vascular disease (may be
exacerbated).
CNS effects (may cause drowsiness; may increase effects
of alcohol); diabetes mellitus (may cause transient rise
in blood glucose); renal impairment (may worsen chronic
renal failure).
Surgery (stopping abruptly may precipitate a severe
withdrawal syndrome).
Elderly (can cause drowsiness); children (may be
particularly susceptible to hypertensive episodes
resulting from abrupt inability to take medication).
Pregnancy (may lower fetal heart rate; risk should be
balanced against the risk of uncontrolled maternal
hypertension; avoid IV injection); lactation (avoid use if
possible; limited data available; present in breastmilk;
may decrease prolactin secretion).
SKILLED TASKS. May impair ability to drive or operate machinery due
to drowsiness.
Adverse Drug Reactions:
Common: Constipation, depression, dizziness, drowsiness,
dry mouth, fatigue, headache, malaise, nausea,
orthostatic hypotension, salivary gland pain, sedation,
sexual dysfunction, sleep disturbances, vomiting.
Less Common: Bradycardia, confusion, delusion, disturbed
mental state, hallucination, itching, nightmare,
paresthesia, pruritus, rash, urticaria.
Rare: Alopecia, AV block, colonic pseudoobstruction,
decreased lacrimation, dry eyes, gynecomastia,
hepatitis, impaired visual accommodation, nasal
dryness, Raynaud’s phenomenon, urinary retention.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Clonidine:
CNS Depressants [e.g., Alcohol, Barbiturates, Other
Sedating Drugs], Drugs that affect sinus node function or
AV nodal conduction [e.g., Digitalis, CCB (AV block;
bradycardia)]
Increases risk of adverse or toxic effects of Clonidine:
CNS Depressants [e.g., Alcohol, Barbiturates, Other
Sedating Drugs (sedation; bradycardia; hypotension)],
Drugs that reduce blood pressure and slow heart rate
(bradycardia; hypotension)
139

Avoid concomitant use with:
Increases risk of adverse or toxic effects of Clonidine:
Beta Blockers e.g., Propranolol (bradycardia;
hypotension; paradoxical increase in BP), Drugs that
reduce blood pressure and slow heart rate (bradycardia;
hypotension)
Reduces therapeutic effect of Clonidine:
Tricyclic Antidepressants e.g. Amitryptilline
C
(antihypertensive effect)
Administration: If further increments are needed to produce
the desired response, take larger portion of the oral daily
dose at bedtime to minimize drowsiness and dry mouth.
Advise the patient to get up gradually from sitting or lying
to minimize this effect, and to sit or lie down if the patient
becomes dizzy or light-headed.
Pregnancy Category: C
ATC Code: C02AC01
Rx METHYLDOPA
Oral: 250 mg tablet
A centrally-acting, alpha2-adrenoceptor agonist that is
useful in the management of hypertension in pregnancy.
Indication: For gestational hypertension and chronic
hypertension in pregnant women.
Contraindications: Pheochromocytoma; active liver disease;
depression, porphyria; patients in whom previous
methyldopa treatment resulted in liver abnormalities, or
direct Coombs’ positive hemolytic anemia
Dose:
Hypertension in pregnancy, by mouth, ADULT, initially 250
mg 2–3 times daily; gradually increase at intervals of 2
or more days, if necessary; (maximum dose, 3 g daily).
Dose Adjustment:
Renal Impairment:
Start with a small dose or adjust dosage frequency. May
require only usual initial dose.
For severe impairment, refer patient to a specialist.
Precautions:
Avoid abrupt withdrawal; monitor blood count and liver
function before treatment and at intervals during first 6–
12 weeks, or if unexplained fever occurs.
History of depression (may be exacerbated).
Renal impairment (increased sensitivity to hypotensive and
sedative effects); Hepatic impairment (caution in history
of liver disease; avoid use if possible).
Lactation (amount in breastmilk is too small to be harmful).
SKILLED TASKS. May impair ability to perform skilled or
hazardous tasks, e.g., operating machinery or driving.
Adverse Drug Reactions:
140
CARDIOVASCULAR SYSTEM
Common: Diarrhea, dizziness, dryness of mouth, fatigue,
fever, headache, light-headedness, positive Coombs’
test, sedation, tiredness, weakness.
Less Common: Angina, bradycardia, constipation,
depression, edema, sodium and water or fluid retention,
hemolytic anemia, impaired concentration and memory,
decreased libido and impotence in men, nasal
congestion, orthostatic hypotension, psychosis, rash,
sleep disturbance, sore or “black” tongue.
Rare: Arthralgia, bone marrow depression, hepatotoxicity
with acute or chronic active hepatitis or hepatic necrosis,
hyperprolactinemia, hypersensitivity reactions, jaundice,
leukopenia, myocarditis, nausea, pancreatitis,
Parkinsonism, pericarditis, sialadenitis, stomatitis,
thrombocytopenia, toxic epidermal necrolysis, urine
darkens on standing, vomiting.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Methyldopa:
Antihypertensive effect: Chlorpromazine, Drugs that
reduce blood pressure
Increases risk of adverse or toxic effects of Methyldopa:
Chlorpromazine (extrapyramidal effects), Salbutamol
(acute hypotension)
Avoid concomitant use with:
Reduces therapeutic effect of Methyldopa:
Ibuprofen (antagonizes antihypertensive effect), Iron
Preparations {e.g., Ferrous Sulfate, Ferrous Gluconate
[due to reduced bioavailability] (antihypertensive
effect)}, Oral Contraceptives (Estrogen antagonizes
antihypertensive effect)
TEST INTERACTION. Produces a positive direct Coombs’
Test, interfering with blood cross-matching.
Administration: May be taken with or without food.
Advise the patient to get up gradually from sitting or lying
to minimize this effect, and to sit or lie down if the patient
becomes dizzy or light-headed.
Pregnancy Category: B
ATC Code: C02AB01 (levorotatory)
C02AB02 (racemic)
DIURETICS
LOW-CEILING DIURETICS
Rx HYDROCHLOROTHIAZIDE
Oral: 12.5 mg and 25 mg tablet
A moderately-potent, thiazide diuretic whose maximal
antihypertensive effect is usually observed at doses
lower than those that produce maximal diuretic effect. It
acts by blocking the reabsorption of sodium in the distal
convoluted tubules of the nephrons.
CARDIOVASCULAR SYSTEM
Indications: Management of mild hypertension (alone), or in
moderate or severe hypertension (in combination with
other drugs); edema.
Contraindications: Severe renal impairment or anuria;
severe hepatic impairment; hyponatremia;
hypercalcemia; refractory hypokalemia; symptomatic
hyperuricemia; Addison disease.
Dose:
Hypertension, by mouth, ADULT, 12.5–25 mg daily,
increase to 25–100 mg daily if necessary; CHILD, refer
to a specialist.
Dose Adjustment:
Renal Impairment:
Avoid use if creatinine clearance <10 mL/minute.
Precautions:
High doses (may cause hypokalemia; avoid use if there is
history of kidney stones).
Hypokalemia (may precipitate coma).
Gout (diuretic-induced rise in serum uric acid
concentration).
Heart failure with significant edema (hyponatremia may
occur).
Hepatic impairment (may precipitate hepatic coma or
encephalopathy).
Alcoholic cirrhosis (increased risk of hypomagnesemia).
Renal impairment (may aggravate diabetes mellitus, gout,
and systemic lupus erythematosus); porphyria.
Elderly (more susceptible to electrolyte imbalance and
orthostatic hypotension).
Pregnancy (avoid use; may cause electrolyte disturbances
and thrombocytopenia in neonates if used during third
trimester; reduction of maternal blood volume may
diminish uteroplacental perfusion); Lactation (may
inhibit lactation).
Adverse Drug Reactions:
Common: Dizziness, headache, hyperuricemia,
hypochloremic alkalosis, hypokalemia,
hypomagnesemia, hyponatremia, lethargy, muscle
cramps, orthostatic hypotension, polyuria, weakness
Less Common: Blurred vision, dyslipidemia, hypercalcemia,
hyperglycemia, impotence, rash
Rare: Agranulocytosis, aplastic anemia, cardiac
arrhythmias, cholecystitis, constipation, dermatitis,
diarrhea, hemolytic anemia, hypersensitivity reactions,
impotence, intrahepatic cholestatic jaundice,
leukopenia, nausea, necrotizing vasculitis, pancreatitis,
purpura, thrombocytopenia, toxic epidermal necrolysis,
visual disturbances, vomiting
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Hydrochlorothiazide:
Drugs that reduce blood pressure (additive hypotensive
effects), Loop Diuretics (synergistic effect; profound
diuresis and serious electrolyte disturbance)
Increases risk of adverse or toxic effects of
Hydrochlorothiazide:
Digoxin (cardiac toxicity due to hypokalemia), Potassium-
lowering Drugs (hypokalemia), Salbutamol (hypokalemia
with high doses)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of
Hydrochlorothiazide:
ACE Inhibitors (severe hypotension with the first ACEi
dose), Angiotensin II Receptor Blockers (excessive
hypotension with the first ARB dose due to volume
depletion), Hydrocortisone (hypokalemia), Ibuprofen
(nephrotoxicity), NSAIDs including Selective COX-2
Inhibitors (nephrotoxicity)
C
Reduces therapeutic effect of Hydrochlorothiazide:
Hydrocortisone (antagonism of diuretic effect), Ibuprofen
(antagonism of diuretic effect), NSAIDs including
Selective COX-2 Inhibitors (renal function; diuretic and
antihypertensive effect), Lidocaine, Metformin
(antagonism of hypoglycemic effect), Oral
Contraceptives (antagonism of antihypertensive effect)
Administration: Usually taken once daily in the morning. If
the patient is to take it twice a day, take the first dose in
the morning and the second dose before 6 in the
evening.
Pregnancy Category: B
ATC Code: C03AA03
Rx INDAPAMIDE
Oral: 1.5 mg MR tablet
A thiazide-related diuretic that exerts its diuretic effect at
the proximal segment of the distal tubule of the nephron
by enhancing sodium, chloride, and water excretion, thus
interfering with the transport of sodium ions across the
renal tubular epithelium. It does not appear to have
significant effect on glomerular filtration rate or renal
blood flow.
Indication: Management of mild-to-moderate hypertension
in combination with other anti-hypertensive agents.
Contraindication: Anuria
Dose:
Hypertension, by mouth, ADULT, 1.5 mg once daily; doses
>1.5 mg daily may increase saluretic effect.
Dose Adjustment:
Renal Impairment:
Do not use in patients with CrCl <30 mL/minute.
Hepatic Impairment:
Do not use in patients with severe hepatic impairment or
hepatic encephalopathy.
Precautions:
WARNING: Prolongs QT interval and is accepted as
having a risk of causing torsade de pointes. The
risk of drug-induced torsade de pointes is
extremely low with one QT interval prolonging drug.
141
 CARDIOVASCULAR SYSTEM

Electrolyte disturbances (severe hyponatremia with Barbiturates e.g. Phenobarbital (orthostatic

hypokalemia has been reported; dose-dependent; hypotension), Beta2 Agonists (hypokalemia), Calcium
hypochloremic alkalosis, hypomagnesemia, or Salts (metabolic alkalosis due to decreased excretion of
hypercalcemia may occur); photosensitivity; sulfonamide Calcium Salts), Corticosteroids (hypokalemia),
(potential for T-cell-mediated type IV reactions). Dexketoprofen, Ethyl Alcohol (orthostatic hypotension),
Diabetes (may alter glucose control); gout (can be Opioid Analgesics, Other Antihypertensive Agents,
precipitated). Licorice (hypokalemia), Multivitamins / Fluoride with ADE
Hypercholesterolemia (may increase cholesterol (hypercalcemic effect), Multivitamins / Minerals [with
concentration). ADEK, Folate, Iron (hypercalcemic effect)], Multivitamins
C

Hypokalemia (use with caution; correct before initiating
therapy).
Hepatic impairment (use with caution; undergoes extensive
hepatic metabolism; electrolyte and acid / base
imbalance in cirrhosis might lead to hepatic
encephalopathy).
Renal impairment (use with caution; approximately 70% is
excreted in the urine).
Systemic lupus erythematosus (can cause exacerbation or
activation).
Elderly (increased risk for severe hyponatremia with
hypokalemia in elderly women).
Pregnancy (crosses the placenta; found in cord blood; may
cause fetal or neonatal jaundice, thrombocytopenia, or
other adverse events); lactation (not known if excreted in
breast milk).
Adverse Drug Reactions:
Common: Agitation, anxiety, dizziness, fatigue, headache,
irritability, lethargy, malaise, nervousness, pain, tension,
tiredness, hypokalemia, back pain, muscle cramps or
spasm, paresthesia, weakness, rhinitis, infection,
arrhythmia, chest pain, flushing, orthostatic hypotension,
palpitation, peripheral edema, PVC, vasculitis,
depression, drowsiness, insomnia, lightheadedness,
vertigo, hives, pruritus, rash, hyperglycemia,
hyperuricemia, hypochloremia, hyponatremia,
decreased libido, abdominal pain, anorexia,
constipation, cramping, diarrhea, dyspepsia, gastric
irritation, nausea, vomiting, weight loss, xerostomia,
nocturia, polyuria, hypertonia, blurred vision,
conjunctivitis, glycosuria, cough, pharyngitis, rhinorrhea,
sinusitis, flu­like syndrome
Less Common: Agranulocytosis, anaphylactic reaction,
aplastic anemia, bullous eruptions, erythema
multiforme, fever, hepatitis, hypercalcemia, cholestatic
jaundice, leukopenia, pancreatitis, photosensitivity,
pneumonitis, purpura, Stevens-Johnson syndrome,
thrombocytopenia, torsade de pointes
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Indapamide:
Antihypertensive effects: ACE Inhibitors, Alfuzosin,
Brimonidine [Topical], Diazoxide, Ethyl Alcohol, Herbs
with hypotensive properties, MAO Inhibitors [except
Linezolid, Tedizolid], Methylphenidate, Molsidomine,
Nicorandil, Other Antihypertensives, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
Prostacyclin Analogues e.g. Epoprostenol
Enhances therapeutic effect of the following drugs:
QTc-prolonging Agents, Ivabradine (arrhythmogenic
effect)
Increases risk of adverse or toxic effects of Indapamide:
/ Minerals [with AE, no Iron
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors (nephrotoxicity), Allopurinol (allergic or
hypersensitivity reactions), Carbamazepine
(hyponatremia), Cardiac Glycosides (toxicity due to
hypokalemic and hypomagnesemic effects of
Indapamide), Cyclophosphamide (granulocytopenia),
Diazoxide, Duloxetine (orthostatic hypotension),
Levodopa (orthostatic hypotension), MAO Inhibitors
[except Linezolid, Tedizolid] (orthostatic hypotension),
Oxcarbazepine (hyponatremia), Porfimer
(photosensitizing effect)
Reduces therapeutic effect of Indapamide:
Herbs with hypertensive properties, NSAIDS
Reduces therapeutic effect of Antidiabetic Agents
Avoid concomitant use with:
Decreases absorption of Indapamide:
Bile Acid Sequestrants e.g. Cholestyramine
Decreases excretion of Lithium
Enhances therapeutic effect of the following drugs:
Dofetilide (QTc-prolonging effect), QTc-prolonging Agents
Increases risk of adverse or toxic effects of Indapamide:
Mifepristone (QTc-prolonging effect), SSRIs e.g.
Fluoxetine (hyponatremic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Amifostine (hypotensive effect), Levosulpiride, Rituximab
(hypotensive effect), Sodium Phosphates (nephrotoxic
effect, specifically the risk of acute phosphate
nephropathy), Topiramate (hypokalemic effect),
Risperidone (hypotensive effect), Verteporfin
(photosensitizing effect), Vitamin D Analogues
(hypercalcemic effect)
Increases serum concentration of the following drugs:
Dofetilide, Topiramate
Reduces therapeutic effect of Indapamide:
Bile Acid Sequestrants e.g. cholestyramine (diuretic
response)
Administration: May be administered without regard to
meals. Administer with food or milk to decrease GI
adverse effects.
Administer early in the day to avoid nocturia.
Swallow whole. Do NOT crush or chew.

142
CARDIOVASCULAR SYSTEM
Pregnancy Category: B
ATC Code: C03BA11
HIGH-CEILING DIURETICS
Rx BUMETANIDE
Oral: 1 mg tablet
Inj.: 500 micrograms/mL, 4 mL ampule (IM, IV)
A loop diuretic that inhibits reabsorption of sodium and
chloride in the ascending loop of Henle and proximal
renal tubule, interfering with the chloride-binding
cotransport system, thus causing increased excretion of
water, sodium, chloride, magnesium, phosphate, and
calcium.
Indications: Management of congestive heart failure;
management of edema secondary to heart failure or
hepatic or renal disease, including nephrotic syndrome
Contraindications: Anuria; hepatic coma or states of severe
electrolyte depletion until the condition improves or is
corrected
Dose:
Heart failure, by mouth, ADULT, 0.5–2 mg 1–2 times daily;
may repeat in 4–5 hours for up to 2 doses (maximum
dose, 10 mg daily);
by IM or IV injection, 0.5–1 mg per dose; may repeat in
2–3 hours for up to 2 doses (maximum dose, 10 mg
daily).
Edema, by mouth, ADULT, 0.5–2 mg 1–2 times daily; may
repeat in 4–5 hours for up to 2 doses (maximum dose,
10 mg daily);
by IM or IV injection, 0.5–1 mg per dose; may repeat in
2–3 hours for up to 2 doses (maximum dose, 10 mg
daily;
by mouth, IM or IV injection, CHILD and INFANT, 0.015–
0.1 mg/kg per dose every 6–24 hours (maximum dose,
10 mg daily).
NOTE: Adjust doses based on individual patient’s needs.
Dose equivalency for patients with normal renal function
(approximate): Furosemide 40 mg = Bumetanide 1 mg =
Torsemide 20 mg = Ethacrynic Acid 50 mg
Precautions:
WARNING: Bumetanide is a potent diuretic. If given in
excess, can lead to a profound diuresis with water
and electrolyte depletion. Careful medical
supervision is required.
Fluid or electrolyte loss (can lower serum calcium
concentrations; can predispose a patient to serious
cardiac arrhythmias),
Hyperuricemia; Nephrotoxicity (monitor fluid status and
renal function to prevent oliguria, azotemia, and
reversible increases in BUN and creatinine),
Ototoxicity (may occur with rapid IV administration, renal
impairment, excessive doses, and concurrent use of
other ototoxins),
Sulfonamide allergy (may stimulate T-cell-mediated type IV
reactions),
Cirrhosis and ascites (sudden changes in fluid and
electrolyte balance and acid / base status may lead to
hepatic encephalopathy; increased risk of precipitating
hepatic coma),
C
Renal impairment (may exhibit diminished effects;
increased risk of adverse effects).
Diuretic resistance (can be overcome by IV administration,
use of two diuretics together, or the use of a diuretic with
a positive inotropic agent; monitor serum electrolytes
very closely).
Surgical patients (may render the patient volume depleted
and blood pressure may be labile during general
anesthesia if given the morning of surgery),
Elderly (excess amounts can lead to profound diuresis with
fluid and electrolyte loss; severe loss of sodium and/or
increase in BUN can cause confusion); neonates (potent
displacer of bilirubin in critically ill patients),
Pregnancy (adverse events have been observed in animal
reproduction studies); lactation (not known if excreted in
breastmilk; can decrease milk volume and suppress
lactation; breast­feeding is not recommended),
Adverse Drug Reactions:
Common: Dizziness, hyperuricemia, hypochloremia,
hypokalemia, hyponatremia, hyperglycemia, phosphorus
change, variations in bicarbonate and CO2 content,
abnormal serum calcium, abnormal lactate
dehydrogenase, azotemia, and muscle cramps.
Less Common: Abdominal pain, arthritic pain, asterixis,
auditory impairment, brain disease (preexisting liver
disease), chest pain, dehydration, diaphoresis, diarrhea,
dyspepsia, ECG changes, erectile dysfunction, fatigue,
glycosuria, headache, hyperventilation, hypotension,
musculoskeletal pain, nausea, nipple tenderness,
orthostatic hypotension, otalgia, ototoxicity, premature
ejaculation, proteinuria, pruritus, renal failure, skin rash,
Stevens-Johnson syndrome, thrombocytopenia, toxic
epidermal necrolysis, urticaria, vertigo, vomiting,
weakness, xerostomia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Bumetanide:
Antihypertensive effect: Alfuzosin, Barbiturates e.g.
Phenobarbital, Brimonidine [Topical], Diazoxide, Herbs
with hypotensive properties, MAO Inhibitors [except
Linezolid, Tedizolid], Molsidomine, Nicorandil, Other
Antihypertensive Agents, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g. Sildenafil,
Prostacyclin Analogues e.g., Epoprostenol
Diuretic effect: Fosphenytoin
Enhances therapeutic effect of the following drugs:
Dofetilide (QTc-prolonging effect), Ivabradine
(arrhythmogenic effect), Neuromuscular-blocking Agents
(neuromuscular-blocking effect)
Increases risk of adverse or toxic effects of Bumetanide:
Beta2 Agonists (hypokalemic effect), Corticosteroids
(hypokalemic effect), Cyclosporine, Licorice
143

(hypokalemic effect), Opioid Analgesics, Other
Antihypertensive Agents, Probenecid
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors (hypotensive and nephrotoxic effects),
Allopurinol, Aminoglycosides (nephrotoxicity; ototoxicity),
Cardiac Glycosides (hypokalemia; hypomagnesemia),
Cisplatin (nephrotoxicity; ototoxicity), Duloxetine
C
(orthostatic hypotension), Levodopa (orthostatic
hypotension), MAO Inhibitors [except Linezolid, Tedizolid]
(orthostatic hypotension), Topiramate (hypokalemic
effect)
Reduces therapeutic effect of Bumetanide:
Methylphenidate (antihypertensive effect), Phenytoin
(diuretic effect), Probenecid, Salicylates (diuretic effect),
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Neuromuscular-blocking Agents
(neuromuscular-blocking effect)
Avoid concomitant use with:
Decreases absorption of Bumetamide:
Bile Acid Sequestrants e.g. Cholestryamine
Enhances therapeutic effect of Bumetanide:
Canagliflozin (antihypertensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Hypotensive effect: Amifostine, Levosulpiride,
Obinutuzumab, Risperidone, Rituximab
Sodium Phosphates (nephrotoxic effect, specifically,
acute phosphate nephropathy)
Increases serum concentration of Bumetanide:
Methotrexate
Increases serum concentration of the following drugs:
Foscarnet, Methotrexate
Reduces therapeutic effect of Bumetanide:
Methotrexate, NSAIDS (diuretic effect)
Administration:
For oral administration, take without food. Administering
with food slows the rate of absorption and reduces the
extent of absorption and may reduce diuretic efficacy.
May require increased intake of potassium-rich foods.
Administer an alternate-day schedule or a 3–4 daily
dosing regimen with rest periods of 1–2 days in between.
For IV administration, administer slowly, over 1–2
minutes.
Pregnancy Category: C
ATC Code: C03CA02
144
CARDIOVASCULAR SYSTEM
Rx FUROSEMIDE
Oral: 20 mg and 40 mg tablet
Inj.: 10 mg/mL, 2 mL ampule (IM, IV)
10 mg/mL, 25 mL ampule (IV infusion)
A potent, high-ceiling, sulfonamide loop diuretic, which
produces dose dependent diuresis of relatively short
duration.
Indications: Management of edema; pulmonary edema;
cerebral edema; hepatic cirrhosis; nephrotic syndrome;
oliguria due to renal failure; congestive heart failure
Contraindication: Severe fluid and sodium depletion
Dose:
Edema, by mouth, ADULT, 40 mg daily in divided doses, may
be increased gradually to 120 mg in resistant edema;
CHILD, 1–3 mg/kg daily (maximum, 40 mg daily);
INFANT, 1–6 mg/kg daily given in divided doses every 6–
12 hours; NEONATES or PREMATURE INFANTS, 1–4
mg/kg per dose once or twice daily due to poor
bioavailability;
by IV injection, NEONATES or PREMATURE INFANTS, 1–2
mg/kg per dose every 12–24 hours;
by continuous IV infusion, NEONATES or PREMATURE
INFANTS, 0.05 mg/kg per hour (maximum, 0.4 mg/kg
per hour).
Heart failure, by mouth, ADULT, initially 20–40 mg; may
repeat the same dose or increase dose in increments of
20–40 mg per dose at intervals of 6–8 hours (maximum
total daily dose, 600 mg); usual maintenance dose
interval is once or twice daily; adjust dosing frequency
based on patient-specific needs; CHILD and INFANT,
initially 2 mg/kg per dose, increased in increments of 1–
2 mg/kg per dose at intervals of 6–8 hours until a
satisfactory response is achieved (maximum dose, 6
mg/kg per dose);
by IM or IV injection, ADULT, initially 20–40 mg per dose,
may repeat the same dose or increase dose in
increments of 20 mg per dose and administer 1–2 hours
after previous dose (maximum dose, 200 mg per dose);
given once or twice daily; CHILD and INFANT, initially 1
mg/kg per dose, may increase dose in increments of 1
mg/kg per dose and administer not sooner than 2 hours
after previous dose, until a satisfactory response is
achieved; may administer maintenance dose at intervals
of every 6–12 hours (maximum dose, 6 mg/kg per dose);
by continuous IV infusion, ADULT, initially administer an
IV bolus dose 40–100 mg over 1 to 2 minutes, followed
by continuous IV infusion rate of 10–40 mg/hour; repeat
loading dose before increasing infusion rate.
Acute pulmonary edema, by slow IV injection, ADULT, 40 mg
initially, dose may be doubled every hour until a ceiling
dose of 160 mg; CHILD 1 mg/kg daily (maximum,
6mg/kg daily);
by slow IV drip or infusion, ADULT, 40 mg/hour.
Oliguria with glomerular filtration rate <20 mL/minute, by
slow IV infusion at a rate not exceeding 4 mg/minute,
ADULT, initially 250 mg over 1 hour; if urine output is not
satisfactory during the hour after the first dose, infuse
500 mg over 2 hours then, if there is no satisfactory
response during the hour after the second dose, infuse
1 g over 4 hours; if there still is no response after the
CARDIOVASCULAR SYSTEM
third dose, dialysis is probably necessary; may repeat
effective dose, up to 1 g, every 24 hours.
Dose Adjustment:
Geriatric:
Reduce dose.
Renal Impairment:
In acute renal failure, higher doses may be required to
initiate desired response. Avoid use in oliguric states.
Not removed by hemodialysis or peritoneal dialysis.
Supplemental dose is not necessary.
In CrCl <25 mL/minute, use upper end of the initial infusion
dosage range. If urine output is <1 mL/kg per hour,
double as necessary to a maximum of 80–160 mg/hour.
Monitor effects, particularly with high doses.
NOTE: Dose equivalency for patients with normal renal function
(approximate): Furosemide 40 mg = Bumetanide 1 mg =
Torsemide 20 mg = Ethacrynic Acid 50 mg
Precautions:
WARNING: Cases of tinnitus, hearing impairment,
and deafness have been reported. Ototoxicity is
related to rapid injection, severe renal impairment,
use of higher than recommended doses,
hyponatremia, or concomitant therapy with
aminoglycoside antibiotics or other ototoxic drugs.
If high doses are necessary, parenteral therapy
with controlled IV infusion is advisable.
Prostatic enlargement and/or obstruction (may precipitate
acute urinary retention).
Gout (may be aggravated by diuretic-induced
hyperuricemia).
Hypotension.
Diabetes (may see changes in glucose control); SLE (may
cause SLE exacerbation or activation).
Oliguria (correct hypovolemia before administration).
Renal impairment (monitor electrolytes particularly
potassium and sodium, as well as creatinine).
Hepatic impairment (hypokalemia may precipitate coma);
cirrhosis (diminished natriuretic effect with increased
sensitivity to hypokalemia and volume depletion);
alcoholic cirrhosis (increased risk of hypomagnesemia).
Severe urinary retention.
Patients at high risk for radiocontrast nephropathy (can lead
to higher incidence of deterioration in renal function).
Elderly (more susceptible to electrolyte imbalance and
orthostatic hypotension).
Pregnancy (avoid use; may cause electrolyte disturbance in
fetus; possible neonatal thrombocytopenia; monitor fetal
growth because of potential for higher fetal birth
weights); lactation (enters breastmilk; use with caution).
Adverse Drug Reactions:
Common: Dehydration, dizziness, gout, hyperuricemia,
hypokalemia, hypomagnesemia, hyponatremia,
orthostatic hypotension, syncope
Less Common: Dyslipidemia, hyperglycemia, hypocalcemia,
concentration, rash
Rare: Acute pancreatitis, agranulocytosis, bone marrow
depression, bullous eruptions, exfoliative dermatitis,
hemolytic anemia, interstitial nephritis, jaundice,
photosensitivity, Stevens-Johnson syndrome,
thrombocytopenia, tinnitus, vertigo
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Furosemide:
Alcohol (antihypertensive effect), Thiazide Diuretics [e.g.,
Hydrochlorothiazide (profound diuresis; serious
electrolyte disturbance)]
C
Increases risk of adverse or toxic effects of Furosemide:
Salbutamol (hypokalemia)
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors [e.g., Enalapril (severe hypotension with
the first ACEi dose; ACEi-induced renal impairment)],
ARBs (excessive hypotension with the first ARB dose due
to volume depletion), Drugs causing hypotension [e.g.,
Amlodipine, Diazepam, Hydrochlorothiazide, Methyldopa
(hypotension)], Digoxin (cardiac toxicity due to
hypokalemia), NSAIDs including COX-2 Inhibitors
(nephrotoxicity), Ototoxic Drugs [e.g., Gentamicin,
Streptomycin (ototoxicity)]
Reduces therapeutic effect of Furosemide:
Selective and non-selective NSAIDs
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Furosemide:
Hydrocortisone (hypokalemia)
Increases risk of adverse or toxic of Ibuprofen
(nephrotoxicity)
Reduces therapeutic effect of Furosemide:
Hydrocortisone (antagonism of diuretic effect), Ibuprofen
(antagonism of diuretic effect), Oral Contraceptives
(Estrogen antagonizes diuretic effect)
Reduces therapeutic effect of the following drugs:
Lidocaine (antagonized by hypokalemia), Metformin
(antagonism of hypoglycemic effect)
Administration:
For oral administration, take tablet once daily, in the
morning. If to be taken twice daily, take the first dose in
the morning and the second dose at lunchtime.
Advise the patient to get up gradually from sitting or lying
to minimize dizziness upon standing when taking the
medicine. The patient should sit or lie down if dizziness
occurs
For IV administration, administer no faster than 4
mg/minute to avoid ototoxicity. Dilute dose in a suitable
amount of infusion fluid, according to the hydration of
the patient.
Pregnancy Category: C
ATC Code: C03CA01
145

POTASSIUM-SPARING AGENTS
Rx SPIRONOLACTONE
Oral: 25 mg, 50 mg, and 100 mg tablet
A mineralocorticoid (aldosterone) receptor antagonist that
competes with aldosterone for receptor sites in the distal
C
renal tubules, increasing sodium chloride and water
excretion while conserving potassium and hydrogen ions.
Indications: Management of edema associated with
excessive aldosterone excretion or congestive heart
failure alone or in combination with other diuretics;
hypertension; primary hyperaldosteronism (establishing
diagnosis, short-term preoperative treatment, and long-
term maintenance therapy) ; hypokalemia; severe heart
failure (NYHA class III­IV)
Contraindications: Anuria; acute renal insufficiency;
significant impairment of renal excretory function;
hyperkalemia; Addison disease; concomitant use with
eplerenone.
Dose:
Edema, by mouth, ADULT, 25–200 mg daily in 1–2 divided
doses; CHILD 1–17 years, 1 mg/kg daily, divided every
12–24 hours (maximum dose: 3.3 mg/kg daily, up to
100 mg daily).
Hypokalemia, by mouth, ADULT, 25–100 mg once daily.
Hypertension, by mouth, ADULT, 50–100 mg in 1–2 divided
doses; may adjust dose after 2 weeks (usual dosage
range, 25–50 mg daily); CHILD 1 to 17 years, 1 mg/kg
daily, divided every 12–24 hours (maximum dose: 3.3
mg/kg daily, up to 100 mg daily).
Diagnosis of primary aldosteronism, by mouth, ADULT,
long test, 400 mg once daily for 3–4 weeks; short test,
400 mg once daily for 4 days (maintenance until surgical
correction: 100–400 mg once daily).
Severe heart failure, NYHA class III–IV, by mouth, ADULT,
initially 12.5–25 mg once daily (maximum daily dose, 50
mg); if 25 mg once daily is not tolerated, reduce to 25 mg
every other day.
NOTE: To reduce delay in onset of effect, a loading dose of
2 or 3 times the daily dose may be administered on the
first day of therapy.
Dose Adjustment:
Geriatric:
Use with caution and monitor potassium closely. Avoid using
doses >25 mg daily in heart failure or reduced renal
function.
Renal Impairment:
In patients with heart failure:
If eGFR ≥50 mL/minute/1.73 m2, administer an initial
dose of 12.5–25 mg once daily (maintenance dose, 25
mg once daily; after 4 weeks of treatment with potassium
≤5 mEq/L).
If eGFR 30–49 mL/minute/1.73 m2, administer an initial
dose of 12.5 mg once daily or every other day
(maintenance dose, 12.5–25 mg once daily; after 4
146
CARDIOVASCULAR SYSTEM
weeks of treatment with potassium ≤5 mEq/L); if eGFR
<30 mL/minute/1.73 m2, use is not recommended.
Discontinue therapy if potassium >5 mEq/L or serum
creatinine >4 mg/dL. Withhold treatment if potassium
>5.5 mEq/L or renal function worsens. Hold doses until
potassium is <5 mEq/L and consider restarting with a
reduced dose after confirming resolution of
hyperkalemia or renal insufficiency for at least 72 hours.
SKILLED TASKS. May cause drowsiness or blurred vision.
Avoid performing tasks, which require mental alertness,
e.g., operating machinery or driving.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Spironolactone has been shown to be tumorigenic
in chronic toxicity studies in rats. Avoid
unnecessary use of this drug.
CNS effects (somnolence and dizziness have been
reported); gynecomastia (dose-related).
Fluid or electrolyte loss (excess amounts can lead to
profound diuresis); hyperkalemia (dose-related; rates of
hyperkalemia increase with declining renal function;
concurrent use of large doses of ACE inhibitors increases
the risk of hyperkalemia).
Adrenal vein catheterization; cirrhosis (avoid electrolyte and
acid / base imbalances that may lead to hepatic
encephalopathy); heart failure (eGFR should be >30
mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL
(men) or ≤2 mg/dL (women) with no recent worsening,
and potassium should be <5 mEq/L with no history of
severe hyperkalemia; renal impairment (increased risk of
hyperkalemia).
Ethanol use (may increase risk of orthostasis).
Elderly (monitor patient for increased risk of hyperkalemia).
Pregnancy (crosses the placenta; have been shown to
cause feminization of the male fetus in animal studies;
avoid use during first trimester; avoid use in women of
reproductive potential); lactation (active metabolite,
canrenone, has been found in breastmilk; may decrease
milk volume and suppress lactation).
Adverse Drug Reactions:
Common: Vasculitis, ataxia, confusion, drowsiness,
headache, erythematous maculopapular rash, lethargy,
Stevens-Johnson syndrome, toxic epidermal necrolysis,
urticaria, amenorrhea, gynecomastia, hyperkalemia,
abdominal cramps, diarrhea, gastritis, gastrointestinal
hemorrhage, gastrointestinal ulcer, nausea, vomiting,
impotence, irregular menses, postmenopausal bleeding,
agranulocytosis, malignant neoplasm of breast,
hepatotoxicity, anaphylaxis, DRESS syndrome, increased
blood urea nitrogen, renal failure, renal insufficiency,
fever.
Drug Interactions:
Monitor closely with:
Enhances antihypertensive effect of Spironolactone:
Alfuzosin, Barbiturates, Brimonidine (Topical), Diazoxide,
Herbs with hypotensive properties, MAO Inhibitors
[except Linezolid, Tedizolid], Methylphenidate,
CARDIOVASCULAR SYSTEM

Molsidomine, Nicorandil, Other Antihypertensive Agents, OTHER DIURETICS

Pentoxifylline, Phosphodiesterase-5 Inhibitors,
Prostacyclin Analogues, Yohimbine
Enhances therapeutic effect of the following drugs: Rx MANNITOL
ACE Inhibitors (hyperkalemic effect), Neuromuscular-
blocking Agents [Non-Depolarizing (neuromuscular-
Inj.: 20%, 250 mL and 500 mL bottle (IV)
blocking effect)], Quinidine
A hexahydric alcohol related to mannose that acts as an
Increases risk of adverse or toxic effects of Spironolactone:
osmotic agent with little energy value. It is eliminated

C
Angiotensin II Receptor Blockers (hyperkalemia),
from the body before any metabolism can take place.
Atorvastatin (enhanced effects on reducing endogenous
When given parenterally, mannitol raises the osmotic
steroid activity), Canagliflozin (hyperkalemia;
pressure of the plasma, thus drawing water out of body
hypotension), Cholestyramine Resin (metabolic acidosis;
tissues and producing an osmotic diuresis.
hyperkalemia), Digoxin, Drospirenone (hyperkalemia),
Heparin (hyperkalemia), MAO Inhibitors [except
Indications: To reduce cerebral edema; to reduce increased
Linezolid, Tedizolid] (orthostatic hypotension), Nicorandil
intraocular pressure
(hyperkalemia), Nitrofurantoin (hyperkalemia),
Nonsteroidal Anti-Inflammatory Agents (hyperkalemia),
NOTE: NOT recommended for the prevention of acute renal
Opioid Analgesics, Other Antihypertensive Agents,
failure and/or promotion of diuresis.
Tolvaptan (hyperkalemia), Trimethoprim (hyperkalemia)
Dose:
Increases risk of adverse or toxic effects of the following
Increased intracranial pressure, cerebral edema, by IV
drugs:
injection, ADULT, 0.25–1 g/kg per dose; may repeat
Ciprofloxacin [Systemic (arrhythmogenic effect)],
every 6–8 hours, as needed; maintain serum osmolality
Duloxetine (orthostatic hypotension), Levodopa
<300–320 mOsm/kg; CHILD, 0.25–1 g/kg per dose;
(orthostatic hypotension), Risperidone (hypotensive
repeat as needed to maintain serum osmolality <300–
effect)
320 mOsm/kg; administer over 30–60 minutes.
Reduction of intraocular pressure, by IV injection, ADULT,
Reduces antihypertensive effect of Spironolactone:
0.25–2 g/kg administered over 30–60 minutes 1–1.5
Nonsteroidal Anti-Inflammatory Agents
hours prior to surgery; CHILD, 1 to 2 g/kg or 30–60 g/m2
administered over 30–60 minutes 1–1.5 hours prior to
Reduces therapeutic effect of the following drugs:
surgery.
Abiraterone acetate, Alpha / Beta Agonists
Reduction of intraocular pressure, traumatic hyphema, by IV
(vasoconstricting effect), Cardiac Glycosides (inotropic
injection, ADULT, 1.5 g/kg administered over 45 minutes
effects)
twice daily for IOP >35 mm Hg; may administer every 8
hours; CHILD, 1.5 g/kg administered over 45 minutes
Avoid concomitant use with:
twice daily for IOP >35 mm Hg; may administer every 8
Enhances therapeutic effect of the following drugs:
hours in patients with extremely high pressure.
Mitotane
Administration: Administer by intravenous route.
Increases risk of adverse or toxic effects of Spironolactone:
Concentration and rate of administration depends on
Hyperkalemia: Amiloride, Eplerenone, Potassium Salts,
indication, severity, or adjusted to urine flow.
Triamterene
Inspect for crystals prior to administration. If crystals are
Ammonium Chloride (systemic acidosis)
present, warm solution to re-dissolve crystals. Use filter
type administration set for infusion solutions greater
Increases risk of adverse or toxic effects of the following
than or equal to 20%.
drugs:
Amifostine (hypotensive effect), Cyclosporine [Systemic
Do NOT administer until adequacy of renal function and
(hyperkalemia)], Obinutuzumab (hypotensive effect),
urine flow is established. Use 1–2 test doses to assess
Rituximab (hypotensive effect), Sodium Phosphates
renal response.
(nephrotoxic effect, specifically, acute phosphate
nephropathy), Tacrolimus [Systemic (hyperkalemia)]
NEVER add to whole blood for transfusion or administer
through the same set by which blood is being infused to
TEST INTERACTIONS. Produces a false increase in assays
prevent crenation and agglutination of red blood cells.
used to determine digoxin concentrations.
See Mannitol under Blood Substitutes and Perfusion
Administration: Administer with food to increase absorption
Solutions – I.V. Solutions producing Osmotic Diuresis in
and decrease GI upset.
Chapter 2: Blood and Blood Forming Organs for other
information.
Pregnancy Category: C
Pregnancy Category: C
ATC Code: C03DA01
ATC Code: Not available

147

LIPID MODIFYING AGENTS
HMG CoA REDUCTASE INHIBITORS
Rx ATORVASTATIN
C
Oral: 10 mg, 20 mg, 40 mg, and 80 mg tablet (as calcium)
A selective, competitive inhibitor of 3-hydroxy-3-
methylglutaryl coenzyme A (HMG-CoA) reductase, which
prevents the conversion of HMG-CoA to mevalonate, an
early and rate-limiting step in cholesterol biosynthesis.
Indication: Adjunct to diet for the reduction of elevated total
cholesterol, LDL cholesterol, apolipoprotein B, and
triglycerides, and elevation HDL cholesterol in patients
with primary hypercholesterolemia and combined
hyperlipidemia
NOTE: Atorvastatin has not been studied in conditions
where the major lipoprotein abnormality is elevation of
chylomicrons (Fredrickson Types I and V).
Contraindications: Active liver disease, including
unexplained persistent elevations in hepatic
transaminase levels; pregnancy; breastfeeding
Dose:
NOTE: Individualize starting and maintenance doses
according to patient characteristics, such as goal of
therapy and response.
Hyperlipidemia, by mouth, ADULT, initially 10 or 20 mg once
daily; usual range, 10–80 mg once daily;
patients who require an LDL-C reduction of more than
45% may be started at 40 mg once daily.
Heterozygous Familial Hypercholesterolemia, by mouth,
CHILD 10–17 years, initially 10 mg daily (maximum
dose, 20 mg daily); adjust doses at intervals of 4 weeks
or more.
Homozygous Familial Hypercholesterolemia, by mouth,
ADULT, 10–80 mg daily.
Dose Adjustment:
Renal Impairment:
Hemodialysis does not have any significant effect on
atorvastatin clearance.
Hepatic Impairment:
In patients with active liver disease, use is contraindicated.
Precautions:
Skeletal muscle effects (rare cases of rhabdomyolysis with
acute renal failure secondary to myoglobinuria have
been reported; immune-mediated necrotizing myopathy,
IMNM, rarely occurs).
Liver dysfunction (jaundice has been reported; reversible
increases in liver function tests may occur); hepatic
impairment; endocrine function (increased HbA1c and
fasting serum glucose levels have been reported).
CNS toxicity (brain hemorrhage and CNS vascular lesions,
characterized by perivascular hemorrhages, edema, and
mononuclear cell infiltration of perivascular spaces have
148
CARDIOVASCULAR SYSTEM
been observed in animal studies); stroke or TIA (may
occur).
Elderly (use with caution; age ≥65 years is a predisposing
factor for myopathy); children (use of doses >20 mg has
not been studied).
Pregnancy (crosses the placenta; use with caution;
insufficient studies on use during pregnancy); lactation
(not known if excreted in breastmilk; use with caution).
Adverse Drug Reactions:
Common: Nasopharyngitis, arthralgia, diarrhea, pain in
extremity, urinary tract infection, dyspepsia, nausea,
musculoskeletal pain, muscle spasms, myalgia,
insomnia, pharyngolaryngeal pain
Less Common and Rare: Rhabdomyolysis, myopathy, liver
enzyme abnormalities, malaise, pyrexia, abdominal
discomfort, eructation, flatulence, hepatitis, cholestasis,
muscle fatigue, neck pain, joint swelling, hyperglycemia,
nightmare, epistaxis, urticaria, vision blurred, tinnitus,
positive WBC in urine, anaphylaxis, angioneurotic
edema, bullous rashes, fatigue, tendon rupture, fatal and
non-fatal hepatic failure, dizziness, depression,
peripheral neuropathy, pancreatitis
Drug Interactions:
Monitor closely with:
Increases distribution of the following drugs:
Oral Contraceptives [norethindrone; ethinyl estradiol]
Avoid concomitant use with:
Increases distribution of Atorvastatin:
Cyclosporine
Increases risk of adverse or toxic effects (myopathy) of
Atorvastatin:
Colchicine (including rhabdomyolysis), Cyclosporine,
CYP3A4 Inhibitors, i.e., Clarithromycin, HIV Protease
Inhibitors, Itraconazole, Fibric Acid Derivatives, Niacin
Increases serum concentration of Atorvastatin:
CYP3A4 Inhibitors (Strong) i.e., Clarithromycin, HIV
Protease Inhibitors, Itraconazole, Grapefruit Juice [avoid
excessive consumption, i.e., >1.2 L/day]
Administration: Administer as a single dose at any time of
the day, with or without food.
Pregnancy Category: X
ATC Code: C10AA05
Rx ROSUVASTATIN
Oral: 10 mg and 20 mg tablet (as calcium salt)
An active HMG-CoA reductase inhibitor, which is effective in
reducing LDL-cholesterol concentration and has been
efficacious in severe hypercholesterolemia.
Indications: Prevention of cardiovascular events in patients
at high risk of a first cardiovascular event; mixed
dyslipidemia, or homozygous familial
hypercholesterolemia in patients who have not
responded adequately to diet and other appropriate
CARDIOVASCULAR SYSTEM
measures; (adults) treatment of primary
hypercholesterolemia, e.g., heterozygous familial and
non-familial hypercholesterolemia; (children and
adolescents) treatment of heterozygous familial
hypercholesterolemia
Contraindications: Pregnancy; breastfeeding; women who
are planning to conceive or those using inadequate
contraception; severe renal impairment; active liver
disease; unexplained persistent elevation in serum
transaminases
Dose:
NOTE: Individualize doses based on baseline LDL-
cholesterol levels, recommended goal of therapy, and
patient response. Adjust doses at 4-week intervals or
more.
Reserve highest dose (40 mg) only for patients who fail
to achieve desired cholesterol level at 20 mg daily.
High cardiovascular risk, by mouth, ADULT MEN >50 years
and WOMEN >60 years, 20 mg once daily.
Hypercholesterolemia, by mouth, ADULT, initially 5 or 10 mg
once daily, may increase dose to 20 mg if necessary at
intervals of at least 4 weeks; usual range, 5–20 mg once
daily (maximum dose, 40 mg once daily); CHILD 10–18
years, initially 5 mg once daily (maximum dose, 20 mg
once daily).
Dose Adjustment:
Geriatric:
Start at low dose. Initiate dose at 5 mg once daily.
Renal Impairment:
For mild-to-moderate impairment, initiate dose at 5 mg once
daily with a maximum dose of 10 mg once daily.
Asian Ancestry:
Patients may build up higher drug levels and be at higher
risk to develop myopathy. Initiate dose at 5 mg. Do not
administer 40 mg dose.
Patients at Risk for Myopathy:
Consider lower initial dose, e.g., 5 mg daily in adults.
Precautions:
Renal impairment (may reduce elimination of rosuvastatin;
increases risk of myopathy); Hepatic effects (hepatic
impairment may impair elimination of rosuvastatin).
Myopathy (may occur with lipid lowering agent; monitor
creatine kinase (CK) levels and discontinue if these are
markedly elevated; increased risk for rhabdomyolysis);
immune-mediated necrotizing myopathy (have been
rarely reported)
Severe intercurrent illness, e.g., infection, trauma,
metabolic disorder, endocrine and electrolyte
disturbances, uncontrolled seizures (increases risk of
myopathy, rhabdomyolysis, and renal failure).
Diabetes mellitus (small increases in HbA1c and fasting
blood glucose have been reported); hematuria and
proteinuria; hypothyroidism (should be managed
adequately before starting treatment with a statin)
Treatment with systemic Sodium Fusidate (may increase
the risk of rhabdomyolysis)
Elderly (risk of myopathy is higher); children (safety and
efficacy have not been established in children <10 years;
establish a healthy lifestyle to reduce cardiovascular
risk)
Pregnancy (use during first trimester has been associated
with fetal malformation; decreased synthesis of
cholesterol may possibly affect fetal development);
lactation
C
Adverse Drug Reactions:
Common: Abdominal pain, arthralgia, constipation, diabetes
mellitus, dizziness, headache, flu-like illness, insomnia,
mild GI symptoms, myalgia, nausea, UTI, weakness
Less Common: Pruritus, rash, urticaria
Rare: Myopathy (including myositis), angioedema, alopecia,
amnesia, anaphylaxis, gynecomastia, hematuria,
hepatitis, hypersensitivity (rash, pruritus, urticaria),
impotence, interstitial lung disease, jaundice, liver
failure, pancreatitis, paresthesia, peripheral neuropathy,
proteinuria, rhabdomyolysis, renal failure, toxic
epidermal necrolysis
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Rosuvastatin:
Fibrates e.g. Fenofibrate (myopathy; rhabdomyolysis)
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:
Warfarin (increases INR)
Increases risk of adverse or toxic effects of Rosuvastatin:
Niacin (rhabdomyolysis; increased toxicity due to
pharmacodynamic synergism)
Increases risk of adverse or toxic effects of Warfarin
(bleeding)
Reduces absorption of Rosuvastatin:
Bile Acid Binding Resins [administer statin at least 1 hour
before, or 4 hours after, the resin]
Administration: May be taken with or without food. May be
taken at any time of the day.
Pregnancy Category: X
ATC Code: C10AA07
Rx SIMVASTATIN
Oral: 20 mg and 40 mg tablet
An HMG-CoA reductase inhibitor, which is effective in
reducing LDL cholesterol concentration, and has been
reported to reduce the incidence of fatal and non-fatal
MI, stroke and mortality, and the need for coronary and
non-coronary revascularization procedures.
Indications: For prevention of cardiovascular events in
patients with high cardiovascular risk due to
atherosclerotic cardiovascular disease or DM; primary
hypercholesterolemia; homozygous familial
hypercholesterolemia, or combined hyperlipidemia in
149

patients who have not yet responded adequately to diet
or other appropriate measures; (children and
adolescents) heterozygous familial
hypercholesterolemia
Contraindications: Known hypersensitivity to simvastatin or
any component of the formulation; active liver disease,
or persistently abnormal liver function tests; porphyria;
pregnancy (congenital anomalies reported; decreased
C
synthesis of cholesterol possibly affects fetal
development); breastfeeding
Dose:
Homozygous familial hypercholesterolemia, by mouth,
ADULT, initially 40 mg daily at night, adjusted at intervals
of at least 4 weeks (see restricted dosing with 80 mg
once daily at night).
Prevention of cardiovascular events, by mouth, ADULT,
initially 10–40 mg once daily at night, adjusted at
intervals of at least 4 weeks with recommended starting
dose of 40 mg for those at high risk of cardiovascular
events.
Primary hypercholesterolemia or combined hyperlipidemia,
by mouth, ADULT, 10–20 mg daily at night, adjusted at
intervals of at least 4 weeks (see restricted dosing with
80 mg once daily at night).
Heterozygous familial hypercholesterolemia, by mouth,
ADOLESCENT 10–18 years, initially 10 mg at night, may
increase if necessary, at intervals of at least 4 weeks to
a maximum of 40 mg at night.
NOTE: Maximum simvastatin dose:
with concomitant and diltiazem, 10 mg daily;
with concomitant amiodarone or amlodipine, 20 mg
daily. Contraindicated with erythromycin, clarithromycin,
ketoconazole, HIV protease inhibitors, and gemfibrozil.
Dose Adjustment:
Geriatric:
Use with caution. Start at low dose.
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Hepatic Impairment:
Use with caution. Start at low dose. Contraindicated in
active liver disease or persistent abnormal liver function
tests.
Restricted Dosing for 80 mg:
Restrict use of 80-mg dose to patients who have been
taking Simvastatin 80 mg chronically, e.g., for 12 months
or more, without evidence of muscle toxicity, to minimize
the risk of myopathy, including rhabdomyolysis,
particularly during the first year of treatment.
Precautions:
Muscle effects (do not start simvastatin if creatine kinase
[CK] is elevated in patients at high risk of muscle effects;
risk of myopathy is increased if simvastatin is given at
high doses or with a fibrate, with lipid-lowering doses of
nicotinic acid, or with immunosuppressants; monitor
liver function and creatine kinase). Rhabdomyolysis
150
CARDIOVASCULAR SYSTEM
(rarely occurs; risk may be increased in renal impairment
and hypothyroidism).
Severe intercurrent illness, e.g., infection, trauma, or
metabolic disorder (increased risk of myopathy,
rhabdomyolysis, and renal failure;); hypothyroidism
(should be managed before starting treatment with a
statin); surgery (increased risk of acute renal
impairment, which increases the likelihood of myopathy
and rhabdomyolysis).
History of liver disease, or high alcohol intake (monitor liver
function at initiation of treatment, after 4 to 12 weeks
and periodically thereafter, e.g., at 6-month intervals or
when clinically indicated; discontinue if serum
transaminase concentration rises to, and persists at, 3
times the upper limit of the reference range); renal
impairment).
Elderly (increased risk of myopathy); Children (safety and
efficacy have not been established in children <10
years).
Adverse Drug Reactions:
Common: Abdominal pain, atrial fibrillation, constipation,
diabetes mellitus, dizziness, eczema, edema, elevated
CK and serum transaminase level, flatulence, gastritis,
headache, insomnia, myalgia, nausea, upper respiratory
infection, urinary tract infection, vertigo, vomiting
Less Common: Mild GI symptoms
Rare: Anaphylaxis, anemia, angioedema, gynecomastia,
hepatitis, hypersensitivity, impotence, interstitial lung
disease, jaundice, liver failure, myopathy, pancreatitis,
peripheral neuropathy, pruritus, rash, renal failure,
rhabdomyolysis, toxic epidermal necrolysis
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Simvastatin:
Carbamazepine
Avoid concomitant use with:
Increases risk of adverse or toxic effects of simvastatin:
Clotrimazole (myopathy), CYP3A4 Inhibitors, e.g.,
Clarithromycin, Erythromycin, Ketoconazole, Diltiazem
(myopathy; rhabdomyolysis)
Increases serum concentration of the following drugs:
CYP3A4 Inhibitors, e.g., Clarithromycin, Erythromycin,
Ketoconazole, Diltiazem
Reduces absorption of simvastatin:
Bile Acid Binding Resins [administer statin at least 1 hour
before, or 4 hours after, the resin]
Administration: May be taken with or without food.
Avoid excessive consumption, i.e., >1 L daily of grapefruit
juice.
Pregnancy Category: X
ATC Code: C10AA01
CARDIOVASCULAR SYSTEM

FIBRATES Elderly (higher incident of renal impairment)

Pregnancy (embryotoxicity in animal studies); lactation.

Rx FENOFIBRATE Adverse Drug Reactions:

Common: Arthralgia, bronchitis, cough, dizziness, fatigue,
headache, insomnia, GI disturbances (e.g., dyspepsia,
Oral: 200 mg capsule
abdominal pain); hypertension, nausea, rhinitis,
160 mg tablet
infections (e.g., urinary tract, respiratory tract)
Less Common: Pancreatitis, photosensitivity, pulmonary
A peroxisome proliferator receptor alpha (PPARα) activator,

C
embolism, VTE
which modulates lipoprotein synthesis and catabolism. It
Rare: Agranulocytosis, anemia, arrhythmias, hepatitis,
reduces plasma triglyceride, moderately increases high-
cholestatic jaundice, gallstones, hypersensitivity
density lipoprotein (HDL) and has a variable effect on
reactions (e.g., angioedema, anaphylaxis, exfoliative
LDL concentrations.
dermatitis), hypokalemia, leukopenia, myopathy,
rhabdomyolysis, thrombocytopenia
Indications: Hypertriglyceridemia; dyslipidemia associated
with type 2 diabetes; second-line treatment in
Drug Interactions:
hypercholesterolemia
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Contraindications: Photosensitivity to ketoprofen;
Insulins, Sulfonylureas e.g. Gliclazide (hypoglycemic
pancreatitis, unless due to hypertriglyceridemia; severe
effect)
renal impairment, including patients receiving dialysis;
hepatic impairment; primary biliary cirrhosis; gallstones;
Increases risk of adverse or toxic effects of Statins e.g.
gall bladder disease; unexplained, persistent liver
Atorvastatin (myopathy; rhabdomyolysis)
function abnormality; pregnancy; lactation
Avoid concomitant use with:
Dose:
Enhances therapeutic effect of Anticoagulants, e.g.,
NOTE: At least 2-3 months of therapy is required to
Warfarin (anticoagulant effect)
determine efficacy.
Increases risk of adverse or toxic effects of Anticoagulants,
Hyperlipidemias, by mouth, ADULT, 200–300 mg once daily
e.g., Warfarin (bleeding)
in divided doses; usual range, 200–400 mg daily; CHILD
>10 years old, up to maximum of 5 mg/kg daily.
Reduces absorption of Fenofibrate:
Bile Acid Sequestrants
Dose Adjustment:
Geriatric:
Administration: Best taken with food as food increases the
Use with caution. May need dose adjustment.
bioavailability of fenofibrate.
Renal Impairment:
Pregnancy Category: C
For mild-to-moderate impairment, dose reduction is
warranted. Initiate dose at 40–50 mg once daily in
ATC Code: C10AB05
adults. Refer child to pediatrician.
For severe impairment, fenofibrate is contraindicated.

Precautions:
NOTE: Fenofibrate has a uricosuric effect, which may reduce
uric acid concentrations by about 25%.

Hyperlipidemia; myopathy, myositis, and rhabdomyolysis

(have been reported; concomitant HMG-CoA reductase
inhibitor may potentiate rhabdomyolysis and lead to
acute renal failure).
Increase in hepatic transaminases (monitor regularly and
discontinue if enzyme levels persist 3 times above the
upper limit of normal); increase in serum creatinine (may
occur; monitor renal function).
Avoid exposure of skin to sun, wear protective clothing and
use sunscreen
Lack of optimal response (withdraw therapy if an adequate
response is not obtained after 2–3 months of therapy at
the maximal daily dose).
Women and obese individuals (at high risk for biliary tract
disease; modest increase in the risk of cholesterol
gallstones, reflecting an increase in the cholesterol
content of bile; may cause cholelithiasis)
Patients at risk for venous thromboembolism (associated
with pulmonary embolism and deep venous thrombosis).

151

DERMATOLOGICALS
ANTIFUNGALS FOR
DERMATOLOGICAL USE
ANTIFUNGALS FOR TOPICAL USE
IMIDAZOLE AND TRIAZOLE DERIVATIVES
D
Rx CLOTRIMAZOLE
Topical: 1% (10 mg/g) cream, 3 g, 10 g, and 20 g
2% (20 mg/g) cream, 30 g
Vaginal: 1% 10 g (vaginal cream)
A broad-spectrum imidazole active against fungi, (both
dermatophytes and yeasts) and gram-positive cocci
(Staphylococcus and Streptococcus spp.)
Indications: Management of anogenital and vulvovaginal
candidiasis; ringworm; skin infections, including
pityriasis versicolor and dermatophytosis (e.g., tinea
corporis, tinea pedis, tinea cruris); protozoal infections
(e.g. trichomoniasis)
Contraindication: Severe liver impairment
Dose:
Anogenital candidiasis, by topical use, ADULT, apply 1%
cream to anogenital area 2–3 times daily.
Skin infections, including pityriasis versicolor and
dermatophytosis, by topical use, ADULT, apply cream 2–
3 times daily for 1–2 weeks.
Vulvovaginal candidiasis, by vaginal administration, ADULT,
apply 5 g of 10% vaginal cream as a single dose at night,
repeated once if necessary 1% is to 6 doses; 2% is to 3
doses).
Dose Adjustment:
Vulvovaginal candidiasis in pregnancy:
Requires a longer duration of treatment, about 7 days, to
clear the infection. Avoid oral antifungals.
Precautions:
Discontinue if irritation or sensitivity occurs; Damages latex
condoms and diaphragms; Pregnancy (safety in the first
trimester has not been established)
Adverse Drug Reactions:
Common: Local pain or discomfort
Less Common: Blistering, burning, edema, erythema,
general skin irritation, itch, peeling, pruritus, stinging
Rare: Allergic reactions
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effect of Simvastatin
(myopathy)
152
DERMATOLOGICALS
Administration: For topical application, gently massage
sufficient amount into the affected and surrounding skin
areas twice daily, in the morning and evening.
If the feet are infected, wash and dry feet, especially
between the toes, before applying the cream.
Pregnancy Category: B
ATC Code: D01AC01
Rx KETOCONAZOLE
Topical: 2% (20mg/g) cream 3.5 g and 15 g
2% (20mg/g) shampoo 6 mL, 10 mL, 60 mL,
100 mL
Imidazole derivate that exerts its antifungal effects by
altering the permeability of the cell wall by blocking
fungal cytochrome P450. This inhibits the biosynthesis
of triglycerides and phospholipids in the fungal cell,
inhibiting several fungal enzymes that results in a build-
up of toxic concentrations of hydrogen peroxide.
Indications: Treatment of tinea corporis, tinea cruris, tinea
pedis, tinea versicolor, cutaneous candidiasis,
seborrheic dermatitis, pityriasis capitis; treatment and
prophylaxis of pityriasis versicolor
Dose:
Tinea corporis and tinea cruris, by topical application, rub
gently onto the affected area once daily for 2 weeks.
Tinea versicolor and cutaneous candidiasis, by topical
application, apply once daily to cover affected and
immediate surrounding area for 2 weeks.
Tinea pedis, by topical application, rub gently onto the
affected area once daily for 6 weeks.
As shampoo, massage onto scalp. Leave on for 3-5 minutes
then rinse.
Seborrheic dermatitis and pityriasis capitis, treatment,
apply shampoo twice weekly for 2-4 weeks
Seborrheic dermatitis and pityriasis capitis, prophylaxis,
apply shampoo once every 1 or 2 weeks
Pityriasis versicolor, treatment, apply once daily for 5 days.
Pityriasis versicolor, prophylaxis, once daily for 3 days during
a single treatment course.
Dose Adjustment: No information found
Precautions:
Hypersensitivity reactions; Irritation; Lactation (do not apply
to breast area of breastfeeding mothers).
Adverse Drug Reactions:
Common: Stinging, local burning, acne, allergic reaction,
contact dermatitis, discharge, dizziness, dryness,
erythema, facial swelling, headache, impetigo,
keratoconjunctivitis sicca, nail discoloration, ocular
irritation or swelling, pain, paresthesia, pruritus,
pustules, pyogenic granuloma, severe irritation
Drug Interactions: No known significant interactions
Administration: For external use only. Do NOT administer
intravaginally.
DERMATOLOGICALS
Do NOT apply directly to hands. Do NOT apply to the eyes.
If contact with eyes, mouth, or vagina occurs, rinse the
exposed areas thoroughly with water.
Pregnancy Category: C
ATC Code: D01AC08
Rx MICONAZOLE
Topical: 2% cream, 5 g
Oral gel: 20 mg, 3.5 g
A synthetic imidazole derivative that inhibits 14-α-
demethylase, a microsomal cytochrome P450-
dependent enzyme system critical to sterol synthesis,
causing membrane defects, reducing growth rate of the
fungal cell.
Indications: Treatment of tinea pedis, tinea cruris, tinea
capitis, oropharyngeal candidiasis, and GIT candidiasis
Contraindication: Self-administration of intravaginal
miconazole for longer than 7 days
Dose:
Tinea pedis, by topical application, ADULT, apply to the
cleansed, dry infected area twice daily for 4 weeks; pay
special attention to the areas between the toes.
Tinea capitis, by topical application, ADULT, apply to the
cleansed, dry infected area twice daily for 4 weeks.
Tinea cruris, by topical application, ADULT, apply to the
cleansed, dry infected area twice daily for 2 weeks.
Oropharyngeal candidiasis, oral gel, ADULT and CHILD ≥2 yr,
2.5 mL (½ measuring spoon) four times daily; INFANT 6-
24 months, 1.25 mL (¼ measuring spoon) four times
daily
GIT candidiasis, oral gel, CHILD ≥6 months, 20 mg/kg body
weight per day in 4 divided doses. (Maximum dose, 250
mg four times daily.
Precautions:
WARNING: Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center immediately.
Avoid continuous and long-term use particularly on large
skin area; Avoid contact with eyes and moist membranes
lining the inside of mouth and nasal passages; Children;
Lactation.
Adverse Drug Reactions: Local sensitization or irritation
Drug Interactions: No known significant interactions
Administration: For external use only. Supervise children in
the use of this product.
Do NOT use if the safety-sealed tube is punctured or
damaged.
Clean the affected area and dry thoroughly. Apply a thin
layer of the product over the affected area twice daily
(morning and night) or as directed by a healthcare
professional. Prolong treatment for 10 days after all
lesions have disappeared to prevent relapse.
Avoid contact with the eyes. If contact with eyes occurs,
rinse the exposed areas thoroughly with water.
NOTE: For tinea pedis, instruct patients to wear well-fitting
ventilated shoes, and to change socks at least once
daily.
Do NOT use on children under 2 years of age unless
directed by a healthcare professional.
D
Pregnancy Category: C
ATC Code: D01AC02
OTHER ANTIFUNGALS FOR TOPICAL USE
Rx SALICYLIC ACID
Topical: 5% solution, 30 mL and 60 mL bottle
2-hydroxy derivative of benzoic acid that produces
desquamation of the horny layer of skin while not
effecting qualitative or quantitative changes in the
structure of the viable epidermis.
Indications: Keratolytic; management of keratosis in arsenic
poisoning; removal of excessive keratin in hyperkeratotic
skin disorders; acne
Contraindications: Prolonged use or application to large
areas; impaired circulation; warts with hair growth or on
face; birthmarks; moles
Dose:
Plantar warts, calluses, corns, by topical application, ADULT,
apply to affected area; repeat until condition clears;
occasional use will maintain remission.
Acne, by topical application, ADULT, as 0.5 to 2%
preparation, apply thinly to the affected area 1–3 times
daily, reduce to once daily or every other day if dryness
or peeling occurs.
NOTE: Safety and efficacy in children is not yet established.
Precautions:
Renal or hepatic impairment (monitor for signs of salicylate
toxicity, i.e., nausea, vomiting, dizziness, loss of hearing,
tinnitus, lethargy, hyperpnea, diarrhea, psychic
disturbances); Impaired peripheral circulation; Diabetes;
Significant peripheral neuropathy; Children (monitor for
signs of salicylate toxicity, listed above; avoid use in
children with varicella or influenza due to potential risk
of developing Reye’s Syndrome); Lactation.
Adverse Drug Reactions:
Common: Dermatitis, skin peeling, discomfort, irritation,
dryness, ulceration, erosion, salicylate toxicity (systemic),
toxic inner ear damage, excessive erythema and scaling
(when used on open skin lesions)
Rare: Hypersensitivity reactions (potentially fatal e.g.
anaphylactic reaction)
153

Drug Interactions:
Increases risk of adverse or toxic effects of the following
drugs:
Oral Anticoagulants (bleeding); Pyrazinamide
(pyrazinamide-induced uricemia); Sulfonylureas
(hypoglycemia)
Increases serum concentration of Salicylic Acid:
Aspirin, Other salicylate-containing Medications
Reduces therapeutic effect of Heparin (interferes with
heparin hemostasis due to decreased platelet
D
adhesiveness)
Administration: For external use only. Avoid contact with
eyes or mucous membrane.
NOTE. Excessive application of the product other than is
needed to cover the affected area will not result in more
therapeutic benefit.
Pregnancy Category: C
ATC Code: D01AE12
Rx SELENIUM SULFIDE
Topical: 2.5% lotion, 100 mL bottle
An anti-seborrheic and antifungal preparation for topical
application. It has a cytostatic effect on cells of the
epidermis and follicular epithelium, reducing corneocyte
production.
Indications: For treatment of tinea versicolor; seborrheic
dermatitis or dandruff
Contraindications: Broken or severely inflamed skin
Dose:
Tinea versicolor, by topical application, ADULT, apply to
affected areas and lather with a small amount of water;
leave on skin for 10 minutes; rinse body thoroughly;
repeat once daily for 7 days.
Seborrheic dermatitis, by topical application, ADULT,
massage 1 or 2 teaspoonfuls of shampoo into wet scalp;
leave on scalp for 2–3 minutes; rinse thoroughly; repeat
application and rinse thoroughly; apply 1 to 2 times
weekly; may repeat at less frequent intervals
subsequently.
NOTE: After treatment, wash hands well. Do NOT apply more
frequently than required to maintain control.
Precautions:
WARNING: Do NOT use on broken skin or inflamed areas. If
allergic reactions occur, discontinue use.
Do not use when acute inflammation or exudation is present
as increased absorption may occur; Children.
Adverse Drug Reactions: Skin irritation, hair loss, hair
discoloration, oiliness and dryness of scalp
154
DERMATOLOGICALS
Drug Interactions: No known significant interactions
Administration: For external use only. Protect from heat.
Shake well before use. Keep tightly capped. Keep out of
reach of children.
Avoid getting shampoo in eyes or in contact with genital
area as it may cause irritation and burning.
Avoid use within 48 hours of applying hair dye,
straightening, or waving preparations.
Pregnancy Category: C
ATC Code: D01AE13
OTC TERBINAFINE
Topical: 1% cream (as hydrochloride), 3 g, 5 g, 10 g, and
15 g tube
An allylamine derivative with a wide spectrum of antifungal
activity against pathogens of the skin, hair, and nails. It
inhibits squalene epoxidase, preventing fungal sterol
synthesis, resulting in ergosterol deficiency. This causes
membrane disruption and cell death.
Indications: Dermatophytosis (tinea corporis, tinea cruris,
tinea pedis, cutaneous candidiasis, and pityriasis)
Dose:
Tinea corporis and tinea cruris, by topical application,
ADULT, apply once daily for 1 week or as directed by a
doctor.
Tinea pedis, by topical application, ADULT, apply 1–2 times
for 1 week; apply twice daily between the toes for 1 week
or as directed by a doctor; apply twice daily on the bottom
or sides of the foot for 2 weeks or as directed by a doctor
(wear well-fitting, ventilated shoes; change shoes and
socks at least once daily).
Cutaneous candidiasis and pityriasis, by topical application,
ADULT, apply 1–2 times daily to affected area(s) for 2
weeks.
NOTE: NOT for vaginal yeast infections.
Precautions:
Do not use on nails or scalp, in or near the mouth or the
eyes; Presence of lesions.
NOTE: Stop use and ask a doctor if too much irritation
occurs or gets worse.
Adverse Drug Reactions:
Common: Psoriasis exacerbation, rash, pruritus, urticaria,
skin exfoliation, application site reaction
Rare: Serious skin reaction (potentially fatal)
Drug Interactions: No known significant interactions
Administration: For external use only. Do NOT use if seal on
tube is broken or is not visible.
DERMATOLOGICALS
Wash hands after each use.
Avoid contact with eyes. If contact with eyes occur, rinse
thoroughly with water.
Pregnancy Category: B/C
ATC Code: D01AE15
OTC SODIUM THIOSULFATE
Topical: 2.5% and 5% solution
A solution containing sodium thiosulfate, used topically for
fungal infections of the skin.
Indication: Treatment of pityriasis versicolor caused by
Malassezia furfur
Dose:
Fungal infections, by topical application, ADULT, thoroughly
clean affected area and dry well, apply a thin layer on the
affected and other susceptible areas and rub in gently;
apply twice daily; treatment usually lasts several weeks
to months.
NOTE: Evidence of infection may disappear within a few
days. Continue treatment as directed by physician
despite lack of signs or symptoms.
Precautions:
Do not put on irritated skin or healthy skin; Use only as
directed; Children; Lactation.
Adverse Drug Reactions:
Common: Skin irritation
Rare: Allergic reactions (e.g., rash, hives, itching, red,
swollen, blistered, or peeling skin with or without fever,
wheezing, tightness in the chest or throat, trouble
breathing or talking, unusual hoarseness, swelling of the
mouth, face, lips, tongue, or throat)
Drug Interactions: No known significant interactions
Administration: For external use only. Shake well before use.
Keep out of mouth, nose, and eyes. Contact may cause
a burning sensation.
Do NOT use coverings, e.g., bandages, dressings, unless
told to do so by the doctor.
Wash your hands before and after use. Do NOT wash
your hands after use if putting this on your hand.
Pregnancy Category: C
ATC Code: Not available
ANTIFUNGALS FOR SYSTEMIC USE
Rx TERBINAFINE
Oral: 250 mg tablet
An allylamine derivative with a wide spectrum of antifungal
activity against pathogens of the skin, hair, and nails. It
inhibits squalene epoxidase, preventing fungal sterol
synthesis, resulting in ergosterol deficiency and causes
D
membrane disruption and cell death.
Indications: Treatment of oncychomycosis of the toenail or
fingernail due to dermatophytes; dermatophytosis (tinea
corporis, tinea cruris, tinea pedis)
Contraindications: Chronic or active hepatic disease;
Lactation
Dose:
Fingernail onychomycosis, by mouth, ADULT, 250 mg once
daily for 6 weeks.
Toenail onychomycosis, by mouth, ADULT, 250 mg once
daily for 12 weeks.
Tinea cruris, by mouth, ADULT, 250 mg once daily for 2–4
weeks.
Tinea corporis, by mouth, ADULT, 250 mg once daily for 4
weeks.
Tinea pedis, by mouth, ADULT, 250 mg once daily for 2–6
weeks.
Dose Adjustment:
Geriatric:
Start at the low end of dosing range, increasing frequency
for decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy.
Renal Impairment:
For patients with CrCl <50 mL/minute, reduce dose to 50%
of usual dose.
Precautions:
Immunosuppression; Psoriasis; Autoimmune disease;
Renal impairment; Hepatotoxicity; Hematologic effects;
Thrombotic microangiopathy; Elderly; Children;
Lactation.
Adverse Drug Reactions:
Common: Headache, diarrhea, dyspepsia, abdominal pain,
nausea, flatulence, rash, pruritus, urticaria, liver enzyme
abnormalities, decreased appetite, feeling of fullness,
visual disturbance, application site reactions (redness,
itching, stinging)
Less Common: Pancytopenia, agranulocytosis, severe
neutropenia, anemia, thrombotic microangiopathy,
hemolytic uremic syndrome, anxiety, depression, weight
loss, smell disturbances, paresthesia, hypoesthesia,
ocular lens and retina changes, vision color changes,
color confusion, decreased visual acuity, hearing
impairment, vertigo, tinnitus, vasculitis, psoriasis
exacerbation, photosensitivity, hair loss, rhabdomyolysis,
arthralgia, myalgia, malaise, fatigue, influenza-like
illness, pyrexia
Rare: Systemic lupus erythematosus, serious skin and
hypersensitivity reaction (potentially fatal), taste
155
 DERMATOLOGICALS

disturbance, hepatic failure (potentially fatal), Indications: Symptomatic treatment of mild pruritus and
hepatobiliary dysfunction insect stings

Drug Interactions: Contraindication: Avoid application prior to x-ray (zinc oxide

Monitor closely with: may affect outcomes)
Increases risk of adverse or toxic effects of Oral
Contraceptives (menstrual disturbances) Dose:
Mild pruritus, ADULT and CHILD, apply liberally to the entire
Avoid concomitant use with: affected area 3–4 times daily, or as often as needed.
Increases risk of adverse or toxic effects of Warfarin
(increases blood creatine phosphokinase)
Precautions:
D

Administration: May be taken with or without food. If condition worsens or if rash develops, stop the medication
immediately.
Pregnancy Category: B
Adverse Drug Reactions:
ATC Code: D01AE15 Rare: Irritation, rash

Drug Interactions: No known significant interactions

EMOLLIENTS AND PROTECTIVES Administration: Shake well prior to use. Apply gently with a
pad of cotton wool to the affected parts as required.

OTC PETROLATUM (PETROLEUM) Do NOT use on open wounds or burns. Avoid contact with
the eyes and the mucous membranes of the mouth,
nose, and anogenital area.
Topical: USP grade jelly, 25 g, 100 g, and 200 g jar
Pregnancy Category: No information found
An emollient used to soothe, smooth, and hydrate the skin.
ATC Code: Not available
Indications: Skin emollient; protectant

Contraindication: No information found

ANTIPSORIATICS
Dose:
Apply topically to affected area(s) as needed.
ANTIPSORIATICS FOR TOPICAL USE
Precautions:
Do not use in eyes, on puncture wounds, animal bites, or
serious burns or for more than one week unless directed Rx CALCIPOTRIOL
by a doctor; Do not use in nose to avoid lipid aspiration;
Breastfeeding. Topical: 50 micrograms per g ointment, 30 g tube or
bottle
Adverse Drug Reaction: Hypersensitivity
A synthetic vitamin D3 derivative that binds to vitamin D
Drug Interactions: No known significant interactions receptors to induce differentiation and suppress
proliferation of keratocytes.
Administration: For external use only.
Indication: Management of mild-to-moderate plaque
Pregnancy Category: A psoriasis
ATC Code: D02AX Contraindications: Severe renal or hepatic impairment;
Hypercalcemia; Calcium metabolism disorder; Acute
psoriatic eruptions
ANTIPRURITICS, INCLUDING
ANTIHISTAMINES, ANESTHETICS, ETC. Dose:
Mild-to-moderate plaque psoriasis, by topical application,
ADULT, apply a thin layer and rub in gently and
OTC CALAMINE, PLAIN completely to the affected area 1–2 times daily
(maximum, 100 g per week); CHILD >12 years, apply
2 times daily (maximum, 75 g per week); CHILD 6-12
Topical: 8% lotion, 60 mL and 120 mL bottle years, apply 2 times daily (maximum, 50 g per week).

A topical antipruritic substance, which contains basic zinc Precautions:

oxide with about 0.5% colored ferric oxide. Erythrodermic exfoliative psoriasis; Generalized pustular
psoriasis; Lactation.

156
DERMATOLOGICALS

Adverse Drug Reactions: hypothalamic-pituitary-adrenal (HPA) axis suppression,

Common and Less Common: Skin irritation, burning, itching, manifestations of Cushing’s syndrome, hyperglycemia,
erythema, dryness, eczema, contact dermatitis, glucosuria
aggravated psoriasis, hypercalcemia, hypercalciuria Rare: Hypercalcemia, hypercalciuria, angioedema, facial
Rare: Skin atrophy, hyperpigmentation, photosensitivity edema

Drug Interactions: Administration: For external use only.

Avoid concomitant use with:
Reduces therapeutic effect of Calcipotriol: Avoid exposure to natural or artificial sunlight. Avoid
Salicylic Acid (Topical) (inactivates Calcipotriol) application under occlusive dressings.

Administration: For external use only. Pregnancy Category: C

D
Avoid application to the face, eyes, or mucous ATC Code: D05AX52
membranes. Avoid exposure to natural or artificial
sunlight.
Rx SALICYLIC ACID
Pregnancy Category: C
Topical: 5% solution, 30 mL and 60 mL bottle
ATC Code: D05AX02
2-hydroxy derivative of benzoic acid that has been shown to
produce desquamation of the horny layer of skin while
CALCIPOTRIOL + not effecting qualitative or quantitative changes in the
Rx
BETAMETHASONE structure of the viable epidermis.

Topical: 50 micrograms calcipotriol (as hydrate) + 500
micrograms betamethasone (as dipropionate)
per gram ointment, 30 g tube
Calcipotriol is a synthetic vitamin D3 derivative that binds to
vitamin D receptors to induce differentiation and
suppress proliferation of keratocytes. Betamethasone is
a topical corticosteroid with anti-inflammatory,
antipruritic, and vasoconstrictive properties. It depresses
the formation, release, and activity of endogenous
chemical mediators of inflammation through the
induction of phospholipase A2 inhibitory proteins
(lipocortins) and subsequent inhibition of the release of
arachidonic acid.
Indication: Psoriasis vulgaris
Indications: Management of hyperkeratotic and scaling skin
conditions
Dose:
Hyperkeratotic and scaling skin conditions, by topical
application, ADULT, apply as 1.8 to 3% preparation to
affected area of the skin and/or scalp 1–4 times daily.
NOTE: Safety and efficacy in children is not yet established.
Administration: For external use only. Avoid contact with
eyes or mucous membrane.
NOTE. Excessive application of the product other than is
needed to cover the affected area will not result in more
therapeutic benefit.

Contraindications: Known or suspected disorder of calcium
metabolism; erythrodermic, exfoliative and pustular
psoriasis; viral lesions of the skin, fungal or bacterial skin
infections, parasitic infections, skin manifestations in
relation to TB, perioral dermatitis, atrophic skin, striae
atrophicae, fragility of skin veins, ichthyosis, acne
vulgaris, rosacea, ulcers and wounds
See Salicylic Acid under Antifungals for Dermatological Use
– Other Antifungals for Topical Use in Chapter 4:
Dermatologicals for other information.
Pregnancy Category: C
ATC Code: Not available

Dose:
Psoriasis vulgaris, by topical application, ADULT, apply to
affected area once daily for up to 4 weeks for scalp
areas, or 8 weeks for non-scalp areas (maximum, 15 g
daily or 30% of body surface).

Dose Adjustment: No information found

Precautions:
Diabetes mellitus; Lactation.

Adverse Drug Reactions:

Common and Less Common: Allergic contact dermatitis,
pruritus, headache, nasopharyngitis, psoriasis, rash,
influenza, erythema, pain, burning sensation, eye
irritation, dry skin, skin atrophy, folliculitis, reversible

157
 DERMATOLOGICALS

Dose:
ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR Secondary skin infection, by topical application, ADULT and
DERMATOLOGICAL USE CHILD ≥3 months, as cream, apply to affected area 3
times daily for up to 10 days; re-evaluate within 7 days if
no clinical response.
ANTIBIOTICS FOR TOPICAL USE Impetigo, by topical application, ADULT and CHILD ≥2
months, as ointment, apply to affected area 3 times daily
for up to 5–10 days; re-evaluate after 3–5 days if no
FUSIDATE SODIUM clinical response.
OTC
(FUSIDIC ACID)
Dose Adjustment:
Topical: 2% cream, 5 g tube Renal Impairment:
D

2% ointment, 15 g tube Use with caution. Some products contain polyethylene

An antibiotic derived from Fusidium coccineum, which is
active against several gram-positive organisms and can
penetrate intact skin. It acts by disrupting translocation
of peptide subunits and elongating the peptide chain of
susceptible bacteria, inhibiting protein synthesis.
glycol, which may be absorbed from open wounds and
damaged skin and secreted by the kidneys.
Precautions:
WARNING: Prolonged use may result in overgrowth of non-
susceptible microorganisms, including fungi.

Indications: Treatment of skin infections caused by

staphylococci, streptococci and Corynebacterium
minutissimum; impetigo; infected wounds; folliculitis;
boils; sycosis barbae; carbuncles; hidradenitis;
paronychia; erythrasma
Dose:
Skin infection, by topical application, ADULT, apply to the
affected area 2–3 times daily for 7 days; may be used
with or without covering dressing.
Precautions:
Hepatic disease (monitor liver function); Neonates;
Lactation.
Adverse Drug Reactions:
Common: Rashes, irritation
Less Common: Hypersensitivity reactions
Drug Interaction:
Avoid concomitant use with:
Ciprofloxacin (antagonistic activity)
Extensive burns and wounds; Renal impairment; Local
irritation (discontinue use when sensitization or severe
local irritation occurs); Lactation (not known if present in
breastmilk, has effects on breastfed child and milk
production).
Adverse Drug Reactions:
Common and Less Common: Burning, stinging, pruritus,
pain, rash, erythema, dry skin, tenderness, cellulitis, pain
or bleeding secondary to eczema, secondary wound
infection, urticaria, swelling, increased exudates, contact
dermatitis, furunculosis, exfoliative dermatitis
Rare: Systemic reactions (e.g., nausea, headache,
dizziness, abdominal pain, ulcerative stomatitis,
systemic allergic reactions)
Drug Interaction:
Avoid concomitant use with:
Reduces therapeutic effect of Mupirocin:
Chloramphenicol (interferes with antibacterial action of
Mupirocin in RNA synthesis)

Administration: For external use only. Observe caution when Administration: For external use only. NOT for intranasal,
applying in the eye region; may cause eye irritation. ophthalmic, or other mucosal use.

Pregnancy Category: Not available Avoid contact with eyes. In case of accidental contact,
rinse well with water.
ATC Code: D06AX01
Apply a small amount to the affected area using a cotton
swab or gauze pad. If desired, cover the treated area with
gauze dressing.
Rx MUPIROCIN
Do NOT apply concurrently with any other lotions,
creams, or ointments.
Topical: 2% cream, 5 g sachet and 15 g tube
2% ointment, 5 g and 15 g tube Pregnancy Category: C
A bacteriostatic that inhibits protein synthesis of the ATC Code: D06AX09
bacteria by binding to isoleucyl transfer RNA synthetase

Indications: Management of impetigo; secondary skin

infections (up to 10 cm in length or 100 cm2 in area) due
to susceptible Staphylococcus aureus and
Streptococcus pyogenes.

158
DERMATOLOGICALS
CHEMOTHERAPEUTICS FOR TOPICAL USE
Rx IMIQUIMOD
Cream: 5%, aluminum foil sachet
Imiquimod, an immune response modifier, is a Toll-like
receptor 7 agonist that activates immune cells. Topical
application to the skin is associated with increases in
markers for cytokines and immune cells.
Indications: Treatment of external genital and perianal
warts.
Dose:
External genital warts, by topical use, ADULT and CHILD,
apply 3 times a week on alternate days until total
clearance of warts or for a maximum of 16 weeks.
Dose Adjustment:
Renal and Hepatic impairment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
Avoid or minimize exposure to sunlight;
Local inflammatory reactions, flu-like symptoms, and vulvar
swelling;
Patients with actinic keratosis, autoimmune disorders, and
basal cell carcinoma;
Not recommended for oral, ophthalmic, urethral,
intravaginal, cervical, rectal, or intra-anal human
papilloma viral disease.
Adverse Drug Reactions:
Common: Application site reaction, URTI, erythema, erosion,
excoriation, edema, and itching.
Less Common: Sinusitis, burning sensation, headache,
squamous carcinoma, diarrhea, bleeding, stinging, pain,
eczema, induration, tenderness, irritation, back pain,
fatigue, atrial fibrillation, viral infection, dizziness,
vomiting, UTI, fever, rigor, and alopecia.
Rare: Headache, flu-like symptoms, and myalgia.
Drug Interactions:
Monitor closely with:
Increases levels or effects of Imiquimod: Trastuzumab
Avoid concomitant use with:
Decreases levels or effects of imiquimod: BCG
Increases levels or effects of imiquimod: Tacrolimus
Administration: Wash hands prior to and following
application. For topical use only. Apply a thin layer prior
to normal sleeping hours and leave on skin for
approximately 6-10 hours, then remove with mild soap
and water. Non-occlusive dressings may be used in the
management of skin reactions.
Pregnancy Category: C
ATC Code: D06BB10
Rx SILVER SULFADIAZINE
Topical: 1% cream, 15 g and 25 g tube
1% cream, 500 g jar (micronized)
A bactericidal agent with a broad spectrum of activity
against gram-negative and gram-positive bacterial, as
well as yeast.
Indications: Adjunct for the prevention and treatment of
wound sepsis in patients with second- and third-degree
D
burns
Contraindications: Pregnancy approaching or at term;
Lactation; Premature infants; Newborns ≤2 months;
Porphyria
Dose:
Condition, by topical administration, ADULT, apply 1 to 2
times daily to a thickness of approximately one-sixteenth
of an inch; reapply as needed.
Dose Adjustment:
Renal Impairment:
Use with caution. Some products contain polyethylene
glycol, which may be absorbed from open wounds and
damaged skin and secreted by the kidneys.
Precautions:
Maintain adequate fluid intake; Prolonged application over
a large area may result in argyria; Sulfonamides; G6PD
deficiency; Renal and hepatic impairment; Children;
Lactation (use with caution).
Adverse Drug Reactions:
Common: Leukopenia, nausea, vomiting, diarrhea,
hypersensitivity, skin reactions, hematuria, crystalluria,
thrombocytopenia, leucopenia, eosinophilia, Stevens-
Johnson syndrome (potentially fatal), agranulocytosis
(potentially fatal), jaundice (potentially fatal), hepatitis
(potentially fatal)
Less Common: Skin necrosis, erythema multiforme, skin
discoloration, burning sensation, rashes, and interstitial
nephritis
Rare: Skin rash
Drug Interaction: No known significant interactions
Administration: For external use only. Dressings may or may
not be used.
Clean and debride burn wounds, then apply to affected
area under sterile conditions. Burn areas should always
be well covered by the cream.
Reapply immediately after hydrotherapy. Continue
treatment until satisfactory healing has occurred or until
the burn site is ready for grafting.
Do NOT withdraw from the therapeutic regimen while
there remains the possibility of infection except if a
significant adverse reaction occurs.
Pregnancy Category: B
159
 DERMATOLOGICALS

ATC Code: D06BA01 Drug Interactions:

Monitor closely with:
Enhances therapeutic effect of Ceritinib (hyperglycemic
effect)
CORTICOSTEROIDS,
DERMATOLOGICAL PREPARATIONS Increases risk of adverse or toxic effects of Deferasirox (GI
ulceration, irritation, or bleeding)
CORTICOSTEROIDS
Reduces therapeutic effect of Corticorelin (plasma ACTH
GENERAL INFORMATION response)

Avoid concomitant use with:

D

Corticosteroids are group of natural and synthetic

analogues of the hormones secreted by the Reduces therapeutic effect of the following drugs:
hypothalamic-anterior pituitary-adrenocortical (HPA) Aldesleukin (antineoplastic effect)
axis. Corticosteroids are classified as glucocorticoids, Hyaluronidase
mineralocorticoids, and corticotropins.
Fingertip units (FTU) for Topical Steroids:
Glucocorticoids are potent anti-inflammatory agents that One FTU is the amount of topical steroid that is squeezed
affect glucose utilization, fat metabolism, and bone out from a standard tube (5 mm nozzle) along an adult's
development. fingertip, from the very end of the finger to the first
Mineralocorticoids control the retention of sodium and crease in the finger. Two FTUs are about the same as 1
water in the kidneys. g of topical steroid. One FTU is enough to treat an area
Corticotropins, also known as adrenocorticotropic hormone of skin twice the size of the flat of an adult's hand with
(ACTH), control the secretion of hormones by the pituitary the fingers together.
gland. Area of skin to be
FTU per dose
treated (average adult)
Precautions:
Hand and fingers (front
1 FTU
WARNING: NOT for use in children under 2 years of and back)
age.
Front of chest and
7 FTU
abdomen
NOT for diaper dermatitis, ocular herpes simplex,
cerebral malaria, fungal infections, or viral Back and buttocks 7 FTU
hepatitis.
Face and neck 2.5 FTU
Application under occlusion may result to increased
incidence of adverse effects. Entire arm and hand 4 FTU
Entire leg and foot 8 FTU
Adrenal suppression; Anaphylactoid reactions; contact
dermatitis; Eczema; Irritation (discontinue immediately); NOTE: Above measurements are approximated on an
Skin infections (use appropriate antifungal or average adult. Values may differ based on patient
antibacterial agent; discontinue use until the infection size.
has been adequately controlled); Fungal or bacterial
dermatologic infection (institute appropriate antifungal
or antibacterial therapy; if the infection does not resolve
promptly, discontinue use until the infection has been Rx BETAMETHASONE
adequately controlled); Immunosuppression (observe
closely patients with latent tuberculosis and/or Topical: 0.05% cream / ointment (as dipropionate), 5 g
tuberculosis reactivity); Kaposi sarcoma; Myopathy; and 10 g tube
Myasthenia gravis; Psychiatric disturbances; 0.1% cream / ointment (as valerate), 5 g tube
Sensitization; Skin reactions (discontinue if skin irritation
or contact dermatitis occurs; do not use in patients with A topical corticosteroid with intermediate to very high range
decreased skin circulation); Systemic effects; Diabetes potency. It exerts its anti-inflammatory, antipruritic, and
mellitus; Gastrointestinal disease; Ulcerative colitis; vasoconstrictive properties by depressing the formation,
Osteoporosis; Hepatic impairment; Renal impairment; release, and activity of endogenous chemical mediators
Cardiovascular disease; Myocardial infarction; Ocular of inflammation through the induction of phospholipase
disease; Thyroid disease (dose adjustment may be A2.
required); Stress due to trauma, surgery, or severe
infection (may require higher doses); Some dosage forms Indications: Relief of inflammatory and pruritic
may contain benzyl alcohol and/or sodium benzoate or manifestations of corticosteroid-responsive dermatoses
benzoic acid; Elderly; Children; Lactation

160
DERMATOLOGICALS
Dose:
NOTE: Base dosage on severity of disease and patient
response. Therapy should be discontinued when control
is achieved. Reassess if no improvement after 2 weeks
of treatment.
Corticosteroid-responsive dermatoses, by topical
application, ADULT, as 0.05% dipropionate salt, apply 1–
2 times daily (maximum, 50 g weekly); as 0.1% valerate
salt, apply 1–3 times daily.
Dose Adjustment:
Geriatric and Pediatric:
Use lowest effective dose for the shortest possible duration.
Adverse Drug Reactions: Acneiform eruptions, allergic
dermatitis, burning, dry skin, erythema, folliculitis,
hypertrichosis, irritation, miliaria, pruritus, skin atrophy,
striae, vesiculation
Administration: For external use only. NOT for oral,
ophthalmic, or intravaginal use.
Apply sparingly to affected areas.
Do NOT use with occlusive dressings or on weeping or
exudative lesions.
Do NOT use on broken skin or in areas of infection.
Do NOT apply to wet skin unless directed.
Do NOT apply very high potency agents to face, groin,
axillae, or diaper area.
Do NOT apply on breasts when breastfeeding.
NOTE: Withdraw therapy with gradual tapering of dose by
reducing the frequency of application or substitution of a
less potent steroid.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information.
Pregnancy Category: C
ATC Code: D07AC01
Rx CLOBETASOL
Topical: 0.05% cream / ointment (as propionate), 5 g
and 15 g tube
0.05% shampoo (as propionate), 25 mL bottle
An analogue of prednisolone with a high degree of
glucocorticoid activity and a slight degree of
mineralocorticoid activity. It has anti-inflammatory,
antipruritic, and vasoconstrictive properties by the
induction of phospholipase A2.
Indication: For the relief of inflammatory and pruritic
manifestations of corticosteroid-responsive dermatoses
Contraindications: Untreated bacteria, fungal, or viral skin
lesions; rosacea; perioral dermatitis; acne; plaque
psoriasis; (ointment / cream) children <1 year;
(shampoo) children <2 years
Dose:
NOTE: Use should be limited to small areas at any one time.
Do NOT use for more than 2 weeks at a time.
Discontinue use once control has been achieved.
Dermatoses, by topical application,
as ointment, ADULT, apply to affected area 1–2 times
daily, reduce if necessary (maximum, 50 g weekly for 2
weeks); CHILD >1 year, apply to affected area 1–2 times
D
daily, reduce if necessary (maximum, 50 g weekly for 5
days);
as shampoo, ADULT, apply directly to scalp once daily,
leave for 15 minutes; do not cover with shower cap
(maximum duration, 4 weeks).
Dose Adjustment: No information found
Adverse Drug Reactions:
Common and Less Common: Hypothalamic-pituitary-
adrenal (HPA) axis suppression or hypercorticism,
Cushing’s syndrome (prolonged use), contact dermatitis,
skin irritation, numbness of fingers, intracranial
hypertension, burning and stinging sensation, tingling,
cracking, irritation, itching, dryness, hypopigmentation,
maceration, erythema, folliculitis, perioral dermatitis,
skin atrophy, hypertrichosis, tenderness, telangiectasia,
striae, miliaria, alopecia, pustules, tightening of the
scalp, acneiform eruptions, allergic contact dermatitis,
secondary infection
Administration: For external use only. NOT for oral,
ophthalmic, or intravaginal use.
Apply thinly and rub gently and completely to the affected
area.
Do NOT use on the face, groin, or axillae.
Do NOT cover with occlusive dressing.
NOTE: Withdraw therapy with gradual tapering of dose by reducing the
frequency of application or substitution of a less potent steroid.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information.
Pregnancy Category: C
ATC Code: D07AD01
Rx FLUOCINONIDE
Topical: 0.05% cream / ointment, 5 g and 15 g tube
A topical corticosteroid with anti-inflammatory, antipruritic,
and vasoconstrictive properties. It has glucocorticoid
activity, used in the treatment of various skin disorders.
Indications: For the relief of inflammatory and pruritic
manifestations of corticosteroid-responsive dermatoses
161

Contraindications: Infection at treatment site; drug
intolerance; preexisting skin atrophy
Dose:
Dermatoses, by topical application, ADULT, apply on
affected area(s) 1–4 times daily; reduce dose as
condition improves.
Dose Adjustment: No information found
Adverse Drug Reactions:
Common: Burning, itching, irritation, dryness, folliculitis,
D
hypertrichosis, acneiform eruptions, hypopigmentation,
perioral dermatitis, allergic contact dermatitis,
maceration of the skin, secondary infection, skin
atrophy, striae, miliaria
Administration: For external use only.
Avoid contact with eyes and prolonged facial application.
Do NOT cover with occlusive dressing. Do NOT use more
than instructed.
Do NOT apply on breasts when breastfeeding.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information.
Pregnancy Category: C
ATC Code: D07AC08
OTC HYDROCORTISONE
Topical: 1% cream / ointment, 5 g and 10 g tube
1% and 2.5% lotion, 25 mL bottle
A topical corticosteroid with anti-inflammatory, antipruritic,
and vasoconstrictive properties by depressing the
formation, release, and activity of endogenous chemical
mediators of inflammation through the induction of
phospholipase A2.
Indications: Dermatosis; anal and genital itching (external)
Dose:
Dermatosis, by topical application, ADULT and CHILD, apply
a thin film to the affected area 2–4 times daily.
Anal and external genital itching, by topical application,
ADULT and CHILD, apply to the affected area 3–4 times
daily.
Atopic dermatitis, by topical application, ADOLESCENT,
CHILD, and INFANT ≥3 months, apply thin film to affected
area twice daily.
Dose Adjustment:
Geriatric:
Use in the smallest possible effective dose for the shortest
duration. Limit use due to age-related changes in the
skin.
Adverse Drug Reactions: Acneiform eruptions, burning,
dryness, folliculitis, hypertrichosis, hypopigmentation,
162
DERMATOLOGICALS
irritation, itching, maceration of skin, miliaria, perioral
dermatitis, secondary infection, skin atrophy, striae
Administration: For external use only. Shake lotion well
before use.
Apply a thin film to clean, dry skin and rub in gently.
Do NOT use with occlusive dressings or on weeping or
exudative lesions.
Do NOT apply on breasts when breastfeeding.
NOTE: After long-term use, withdraw therapy with gradual
tapering of dose.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for other information.
Pregnancy Category: C
ATC Code: D07AA02
ANTISEPTICS AND DISINFECTANTS
BIGUANIDES AND AMIDINES
Rx (0.12% preparation)
OTC (4% preparation)
CHLORHEXIDINE
Topical: 0.12% and 4% solution (as gluconate), 50 mL,
120 mL, 380 mL, 500 mL, 4 L, and 5 L
A very potent cationic chemoprophylactic agent with broad-
spectrum of activity against gram-positive and gram-
negative bacteria. It is bactericidal at high
concentrations by altering the bacterial cell osmotic
equilibrium and leakage of potassium and phosphorus.
Indications: Treatment of gingivitis; surgical hand scrub;
health care personnel hand wash; preoperative skin
preparation; skin wound and general cleansing
Dose:
Gingivitis, by mouth, ADULT, as 0.12% preparation, swish 1
tablespoon (15 mL) in mouth undiluted for 30 seconds,
then spit out; rinse twice daily, morning and evening,
after tooth brushing
Surgical hand scrub, by topical application, ADULT, as 4%
preparation, wet hands and forearms under running
water for 30 seconds; scrub hands and forearms with 5
mL of product with or without wet brush for 3 minutes;
pay close attention to the nails, cuticles, and interdigital
spaces; rinse thoroughly under running water for 30
seconds; dry thoroughly.
Health care personnel hand wash, by topical application,
ADULT, as 4% preparation, wet hands with water; wash
hands with 5 mL of product in a vigorous manner for 15
seconds; rinse and dry thoroughly.
Preoperative skin preparation, by topical application,
ADULT, as 4% preparation, apply liberally to surgical site
and swab for at least 2 minutes; dry with a sterile towel;
DERMATOLOGICALS
repeat cleansing for an additional 2 minutes and dry with
a sterile towel.
Skin wound and general cleansing, by topical application,
ADULT, as 4% preparation, thoroughly rinse with water
the area to be cleansed; apply the minimum amount of
product necessary to cover the skin or wound area and
wash gently; rinse thoroughly.
Precautions:
Gingivitis and periodontitis; Staining of oral surfaces;
Alteration in taste perception; Children; Lactation.
Adverse Drug Reactions:
Common: Reversible brown staining of teeth and other oral
surfaces, increased calculus formation, transient taste
disturbance, skin sensitivity, irritation of conjunctiva,
mucosal irritation, burning sensation of tongue,
anaphylaxis
Less Common: Aphthous ulcer, grossly obvious gingivitis,
trauma, ulceration, erythema, desquamation, coated
tongue, keratinization, geographic tongue, mucocele,
short frenum, stomatitis, glossitis, dry mouth,
hypesthesia, glossal edema, paresthesia, parotid gland
swelling, sialadenitis
Drug Interactions: No known significant interactions
Administration: Avoid contact w/ brain, meninges, middle
ear or sensitive tissues and eyes. Do NOT inject or use in
body cavities.
For 0.12% preparation: NOT intended for ingestion.
Should be expectorated after rinsing. Do NOT rinse with
water, or other mouthwashes, brush teeth, or eat
immediately after. Initiate oral rinse therapy directly
following a dental prophylaxis. Reevaluate patients and
give a thorough prophylaxis at intervals no longer than 6
months.
For 4% preparation: For external use only. Do NOT use in
the genital area. Do NOT use as a preoperative skin
preparation on the head or face.
Keep out of reach of children. If swallowed, get medical
help or contact a poison control center immediately
Pregnancy Category: B (0.12%; mouth or throat);
C (periodontal)
ATC Code: D08AC02
IODINE PRODUCTS
OTC IODINE
Topical: 1% and 2% tincture
2% and 5% solution
A nonmetallic element with germicidal activity.
Indications: First aid to prevent infection in minor cuts,
scrapes, and burns
Contraindication: Hypersensitivity to iodine or any
component in the formulation
Dose:
Clean the affected area; apply a small amount 1–3 times
daily; if to be bandaged, allow sufficient time for the
iodine to dry completely.
Precautions:
Stains skin and clothing.
Adverse Drug Reaction:
D
Common: Skin irritation
Drug Interactions: No information found.
Administration: For external use only. Apply topically to the
affected areas as necessary.
Do NOT cover iodine-treated wounds to avoid irritation.
Do NOT apply over large areas of the body.
Avoid contact with eyes. If contact occurs, flush with large
amounts of water while lifting upper and lower lids.
Pregnancy Category: Not available
ATC Code: D08AG03
OTC POVIDONE-IODINE
Topical: 10% ointment, 5 g, 15 g, and 30 g tube
10% paint, 10 mL bottle
10% solution, 15 mL, 30 mL, 60 mL, 120 mL, 1
L, and 1-gallon bottle
7.5% surgical cleanser, 60 mL, 120 mL, 480
mL, 1 L, and 1-gallon bottle
An antiseptic preparation of a soluble form of iodine used
for the disinfection of minor skin infections.
Indications: Skin disinfection; antiseptic; treatment of
common skin infections; prevention of infection in minor
burns, lacerations, cuts, and abrasions; infection control
during insertion and care of urinary catheters,
circumcision, suture removal, and dressing changes;
degerming care of stasis ulcers and umbilical area;
degerming during use of IV devices in blood transfusions,
hyperalimentation, cutdowns, central venous pressure
(CVP) catheterization, and in other procedures;
treatment of mouth sores (aphthous ulcers), herpes
simplex, herpes zoster (shingles), herpes labialis (cold
sores), grazes abrasions, cuts and wounds, or any break
in the skin which requires protection from infection;
maximum degerming of skin as preoperative preparation
Contraindications: Postmenstrual age of 32 weeks; regular
or prolonged use in patients with thyroid disorders, or
those taking lithium; regular use in neonates; in very low-
birthweight infants (e.g., <1.5 kg); hyperthyroidism
Dose:
Prevention and treatment of infections, by topical
application, ADULT and CHILD, as 10% ointment, clean
163

and dry affected area; apply liberally and cover with a
dressing or bandage; may be used as often as required;
use only as prescribed.
Mouth sores, herpes simplex, herpes zoster, herpes labialis,
grazes abrasions, cuts and wounds, by topical
application, ADULT and CHILD, as 10% paint, apply
undiluted to affected area and allow to dry; use twice
daily and cover with a dressing if desired.
Pre-operative and post-operative skin disinfection, by
topical application, ADULT and CHILD, as 10% solution,
apply an appropriate volume of solution directly to the
skin area.
D
Antiseptic (minor wounds and burns), by topical application,
ADULT and CHILD, as 10% solution, apply an appropriate
volume of solution to the affected area, twice daily (see
Precautions below).
Degerming of skin on patients, by topical application,
ADULT, as 7.5% surgical cleanser, apply necessary
quantity on area to wash, thoroughly distribute while
rubbing for at least 5 minutes; rinse off with a sterile
gauze saturated with water.
Degerming of skin on health care personnel, by topical
application, ADULT, as 7.5% surgical cleanser, apply
necessary quantity on area to wash, thoroughly distribute
while rubbing for at least 5 minutes; clean under
fingernails using a brush if desired; rinse under running
water.
Precautions:
WARNING: Do NOT use 10% paint preparation in
children <3 years.
Broken skin; Renal impairment (avoid regular application to
inflamed or broken mucosa); Pregnancy (second and
third trimesters: sufficient iodine may be absorbed to
affect the fetal thyroid).
Adverse Drug Reactions:
Rare: local irritation of the skin and mucous membranes
Drug Interactions: No information found.
TEST INTERACTION. May interfere with thyroid function tests
due to systemic effects.
Administration: For external use only. Apply locally as
needed.
Pregnancy Category: D
ATC Code: D08AG02
OTHER ANTISEPTICS AND DISINFECTANTS
OTC ALCOHOL, ETHYL
Topical: 95% solution, for dilution to 70%
(with BIR seal)
A clear, aqueous solution of ethyl alcohol which is used as a
disinfectant and skin antiseptic.
164
DERMATOLOGICALS
Indications: Disinfection of skin prior to injection,
venipuncture, or surgical procedures
Contraindications: Management of broken skin; patients
who have suffered severe burns when diathermy has
been preceded by application of alcoholic skin
disinfectants
Dose:
Disinfection of skin, by topical application, ADULT and
CHILD, apply an appropriate volume of solution directly
to the skin area.
Precautions:
Avoid heat, sparks and open flame and temperatures above
30°C; Emission of toxic fumes of carbon monoxide and
carbon dioxide, if exposed to fire.
Adverse Drug Reaction: Skin dryness and irritation with
frequent application of the aqueous solution
Drug Interactions: No information found
Administration: For external use only. Apply locally as
needed.
Pregnancy Category: No information found
ATC Code: D08AX08
OTC HYDROGEN PEROXIDE
Topical: 3% solution, 60 mL and 120 mL bottle
A clear, colorless solution of hydrogen peroxide, which is a
powerful oxidizing agent, and is used as a disinfectant.
Indications: Mild disinfectant for minor cuts, skin ulcers, and
wounds
Contraindication: Injection or instillation into closed body
cavities for which the released oxygen has no free exit
Dose:
Disinfection, by topical application, ADULT and CHILD, dress
the wound with cotton wool soaked in an appropriate
volume of hydrogen peroxide.
Precautions:
Use with caution in large or deep wounds; Avoid contact with
healthy skin, eyes and clothes.
Adverse Drug Reactions:
Rare: Hypersensitivity reactions, irritating burns on the skin
and mucous membranes with a white eschar (strong
solution)
Drug Interactions:
Avoid concomitant use with:
Incompatible with the following products:
Preparations containing Iodine,
Preparations containing Potassium Permanganate
DERMATOLOGICALS

Administration: For external use only. Apply locally as

needed. SODIUM DICHLOROISOCYANURATE

Pregnancy Category: No information found Solution: 3.5 mg tablet (2 mg free available chlorine)
8.68 mg tablet (5 mg free available chlorine)
ATC Code: D08AX01 12.5 mg tablet (8 mg free available chlorine)
17 mg tablet (10 mg free available chlorine)
67 mg tablet (40 mg free available chlorine)
OTC SODIUM HYPOCHLORITE The sodium salt of a chlorinated hydroxytriazine used as a
source of free available chlorine, in the form of
Solution: 1.25% available chlorine hypochlorous acid, for the disinfection of water.

A strong oxidizing agent that can be used for water
purification by producing chlorine when dissolved in
water.
Indications: To prevent and treat infections of the skin
tissue; pre- and post-surgery antiseptic; for cuts,
abrasions, and skin ulcers; for water purification
D
Indication: For water purification used in cleaning hospital
facilities, washing of hands, gloves, and other daily use
articles, and sterilizing of items used in hospitals;
disinfection of water in the prevention of water-borne
diseases

Contraindication: Sensitivity to chlorine compounds Appropriate use:

Approximate
Dose: Approximate
Tablet Volume of
Available
Management of lightly or moderately exudative wounds, by Strength Water to be
Chlorine
topical application, ADULT and CHILD, pour on or apply Treated
to affected area once daily; protect intact skin with a 8.68 mg 5 mg 1L
moisture barrier ointment or skin sealant as needed. 17 mg 10 mg 4L
Management of highly exudative or highly contaminated 75 mg 45 mg 10–20 L
wounds, by topical application, ADULT and CHILD, pour
on or apply to affected area twice daily; protect intact Precautions:
skin with a moisture barrier ointment or skin sealant as
WARNING: Not for consumption. Do NOT ingest
needed.
tablet.
Water purification
Approximate Volume of Approximate Volume of Ensure that use of tablets, especially for large volume
Sodium Hypochlorite Water to be Treated waters, is conducted in a well-ventilated area.
2.5 mL (½ teaspoon) 22.5 L (5 gallons)
Adverse Drug Reactions:
5 mL (1 teaspoon) 45 L (10 gallons) Rare: Cough, sore throat, redness, skin burns, pain
25 mL (5 teaspoons) 227 L (50 gallons) Pregnancy Category: Not applicable
ATC Code: Not applicable
Precautions:
WARNING: Not for consumption. Do NOT ingest tablet.

Ensure that use of tablets, especially for large volume ANTI-ACNE PREPARATIONS
waters, is conducted in a well-ventilated area; Stop use
and ask a doctor if redness, irritation, swelling or pain
persists or increases. OTC BENZOYL PEROXIDE
Adverse Drug Reactions: Cough, sore throat
Topical: 5% gel, 20 g tube
Administration: For external use only.
A topical peroxide preparation used in the treatment of
Keep out of reach of children. If swallowed, get medical help acne.
or contact a Poison Control Center immediately.
Indication: Treatment of acne vulgaris
Keep container closed when not using.
Contraindication: Sensitive skin
Pregnancy Category: C
Dose:
ATC Code: D10AE01 Acne vulgaris, by topical application, ADULT, initially, cover
the entire affected area with a thin layer once daily;
gradually increase to 2–3 times daily if needed or as
directed by a doctor

165
 DERMATOLOGICALS

Precautions:
Skin irritation and dryness; On initial application, a mild
burning sensation may be felt, and redness and peeling
may occur (reversible when drug is discontinued).

Adverse Drug Reactions: Allergic contact dermatitis, dryness

Drug Interactions: No information found

Administration: For external use only. Apply as directed after

thoroughly cleaning the affected area with a mild
cleanser and water.
D

Avoid contact with the eyes, lips, mouth, and mucous

membranes. Avoid unnecessary sun exposure and use
sunscreen. Avoid contact with hair and dyed fabrics
which may be bleached by this product.
Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center right away.

Pregnancy Category: C

ATC Code: D10AE01

166
GENITO URINARY SYSTEM AND SEX HORMONES
GENITO URINARY SYSTEM
AND SEX HORMONES
ANTIINFECTIVES AND ANTISEPTICS,
EXCLUDING COMBINATIONS WITH
CORTICOSTEROIDS
Rx NYSTATIN
Vaginal: 100,000 units per tablet
A polyene antifungal obtained from Streptomyces noursei
that interfere with the permeability of cell membrane of
fungi, particularly Candida.
Indications: Used in the prophylaxis and treatment of
infections caused by Candida, including vulvovaginal
candidiasis
NOTE: Diagnosis should be confirmed by KOH smears
and/or cultures prior to treatment. Some pathogens that
are also commonly associated with vulvovaginitis like
Trichomonas and Haemophilus vaginalis should be ruled
out through adequate laboratory procedures.
Dose:
Vaginal candidiasis, by vaginal insertion, ADULT, 100,000–
200,000 units daily for 14 days or longer.
NOTE: For cutaneous lesions, ointment, gel, cream, or
dusting powder having 100,000 units per gram can be
applied 2 to 4 times daily.
Precautions:
Intravaginal preparations may damage latex contraceptives
(an additional contraceptive method is recommended
during treatment);
Pregnancy (check first with a health care professional if
pregnant or trying to get pregnant).
Adverse Drug Reactions:
Contact dermatitis, ashes, including urticaria, irritation,
sensitization, generalized pustular eruptions
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects:
Other vaginal products [consult health care professional]
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Progesterone
(Intravaginal gel) (alters progesterone release)
Administration: For use in the vagina only. Do NOT take by
mouth.
Wash hands first before and after use. Insert 1 tablet in the
applicator tip. Lie on the back then gently insert
applicator high in the vagina and push plunger to release
the tablet. Gently remove the applicator. Wash it well with
warm water and soap.
Follow course of medication. Do NOT use in amounts other
than what is directed.
Pregnancy Category: A
ATC Code: G01AA01
OTHER GYNECOLOGICALS
UTEROTONICS
ERGOT ALKALOIDS
METHYLERGOMETRINE
Rx
G
(METHYLERGONOVINE)
Inj.: 200 micrograms/mL (as hydrogen maleate or
maleate), 1 mL ampule (IM, IV)
Methylergometrine is an amine ergot alkaloid that increases
tone, rate, and amplitude of contractions on the smooth
muscles of the uterus.
Indications: For management of third stage labor; routine
management after delivery of the placenta;
management of postpartum hemorrhage, uterine
subinvolution, and postpartum atony
Contraindications: Hypertension; toxemia; pregnancy or
patients with threatened spontaneous abortion
Dose:
Management of postpartum hemorrhage, by IM or IV
injection, ADULT, 0.2 mg after delivery of anterior
shoulder, after delivery of placenta, or during
puerperium, may be repeated every 24 hours as needed.
Management of postpartum hemorrhage, severe
hemorrhage, by IM or IV injection, ADULT, 0.2 mg after
delivery of anterior shoulder, after delivery of placenta,
or during puerperium, may be repeated as required at 2-
to 4-hour intervals.
NOTE: IV administration must only be considered during life-
threatening situations due to the possibility of inducing
sudden hypertension and cerebrovascular incident.
Dose Adjustment:
Renal and Hepatic Impairment:
Use with caution.
Precautions:
WARNING: Do NOT exceed dosing guidelines and
avoid prolonged administration. Ergot alkaloids
use may result in ergotism or intense
vasoconstriction resulting in peripheral vascular
ischemia and possible gangrene, usually
associated with overdose or prolonged chronic use.
Coronary heart disease; Hypertension; Heart disease;
Venoatrial shunts;
Mitral valve stenosis;
Sepsis;
Obliterative vascular disease;
Ergotism;
167

Pleural and/or retroperitoneal fibrosis;
Hepatic and renal impairment;
Pregnancy (use with caution in women in second stage of
labor).
Adverse Drug Reactions: Acute MI, angina pectoris, arterial
spasm, atrioventricular block, bradycardia,
cerebrovascular accident, chest pain,
hyper/hypotension, palpitation, tachycardia, vasospasm,
ventricular fibrillation, dizziness, hallucinations,
headache, seizure, rash, water intoxication, abdominal
pain, diarrhea, foul taste, nausea, vomiting,
thrombophlebitis, leg cramps, paresthesia, tinnitus,
hematuria, dyspnea, nasal congestion, anaphylaxis, and
diaphoresis
G
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Methylergometrine:
Metoclopramide, Tedizolid (serotonergic effects)
Enhances therapeutic effect of Anti-emetics e.g., 5-HT3
Antagonists, Anti-psychotic Agents (dopamine blockade)
Increases risk of adverse or toxic effects of
Methylergometrine:
Anti-psychotic Agents, Tedizolid (serotonin syndrome),
CYP3A4 Inhibitors (ergotism), Metoclopramide
(serotonin syndrome; neuroleptic malignant syndrome)
Increases risk of adverse or toxic effects of the following
drugs:
Anti-emetics, e.g., 5-HT3 Antagonists (serotonin
syndrome), Anti-psychotic Agents (neuroleptic malignant
syndrome)
Avoid concomitant use with:
Enhances therapeutic effect of Methylergometrine:
Beta Blockers, Serotonin 5-HT1 Receptor Agonists
(vasoconstricting effects).
Enhances therapeutic effect of the following drugs:
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive
effects), Serotonin 5-HT1 Receptor Agonists
(vasoconstricting effects)
Increases risk of adverse or toxic effects of
Methylergometrine:
Azole Antifungals, CYP3A4 Inhibitors, Dapoxetine,
Protease Inhibitors (ergotism), Serotonin Modulators
[except Tedizolid] (serotonin syndrome)
Increases serum concentration of Methylergometrine:
Anti-hepaciviral Combination Products, Boceprevir,
Fusidic Acid, Macrolide Antibiotics [except Azithromycin],
Mifepristone, Nitroglycerin
Reduces therapeutic effect of Nitroglycerin (vasodilatory
effect)
Administration: May be administered by IM or IV injection.
Limit IV use to patients with severe uterine bleeding or other
life-threatening emergency situations with doses given
over a period of not less than 1 minute. NOT for routine
IV administration due to risk of inducing sudden
hypertensive and cerebrovascular accidents. Some
168
GENITO URINARY SYSTEM AND SEX HORMONES
clinicians recommend diluting the IV dose to a volume of
5 mL with 0.9% sodium chloride injection before
administration. Monitor blood pressure, CNS status, and
vaginal bleeding regularly.
Pregnancy Category: C
ATC Code: G02AB01
PROSTAGLANDINS
Rx CARBOPROST
Inj.: 125 micrograms/0.5 mL, 250 micrograms/mL
solution and 1 mL ampule/vial
Carboprost is a synthetic derivative of prostaglandin that
stimulates uterine smooth muscle, increasing uterine
tone.
Indication: For the treatment of post-partum hemorrhage
after failure of treatment with oxytocin therapy or if the
use of methylergometrine is contraindicated (pre-
eclampsia, hypertension, cardiovascular disease)
Contraindications: Acute pelvic inflammatory disease;
active cardiac, pulmonary, renal or hepatic disease
Dose:
NOTE: Ask clinician regarding the need for additional doses
and adequate dosing interval based on clinical events of
the patient.
Post-partum hemorrhage, by deep IM injection, ADULT, 250
micrograms/mL, then repeat every 15–90 minutes, if
needed (maximum total dose, 2 mg or 8 doses).
Dose Adjustment:
Renal and Hepatic Impairment:
Use with caution.
Precautions:
WARNING: A potent oxytocic agent. Strictly adhere to
recommended dosing. Use should only be under
the direct supervision of medically trained
personnel in a hospital that can immediately
provide intensive care unit and surgical facilities.
Glaucoma or raised intraocular pressure;
Asthma;
Hypertension, Hypotension, or any cardiovascular disease;
Anemia;
Jaundice;
Hepatic and renal impairment;
Diabetes;
Epilepsy
Adverse Drug Reactions:
Common: Diarrhea, nausea, vomiting, increase in body
temperature, flushing/hot flashes, chills, endometritis,
uterine hemorrhage, retained placenta or membranes,
headaches, cough
GENITO URINARY SYSTEM AND SEX HORMONES
Less Common / Rare: Nervousness, epistaxis, sleep
disorder, asthma, wheezing, chest pain, hypertension,
syncope, palpation, tachycardia, chest tightness, anxiety,
dizziness, drowsiness, dystonia, faintness, lethargy, light-
headedness, nervousness, sleep disturbance, vasovagal
syndrome, vertigo, rash, breast tenderness,
dysmenorrhea-like pain, thyroid storm, gagging/retching,
drowsiness, dry throat, choking sensation, thirst, taste
alterations, perforated uterus, posterior cervical
perforation, urinary tract infection, excessive uterine
bleeding, uterine rupture, uterine sacculation, pain at the
injection site, backache, leg cramps, muscular pain,
parethesia, torticollis, weakness, blurred vision, eye
pain, eyelid twitching, tinnitus, coughing, bronchospasm,
hyperventilation, pulmonary edema, respiratory distress,
upper respiratory tract infection, wheezing, diaphoresis,
hiccups, retained placental fragment, septic shock
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Carboprost:
Oxytocic agents
Administration: Administer by deep IM injection directly to
the uterine corpus. Do NOT administer intravenously.
Consider administration of anti-emetic and anti-diarrheal
drugs prior to therapy to decrease incidence of GI effects.
Pregnancy Category: C
ATC Code: G02AD04
Rx ISOXSUPRINE
Oral: 10 mg and 40 mg tablet (as hydrochloride)
Inj.: 5 mg/mL (as hydrochloride), 2 mL ampule (IM, IV
infusion)
A beta-adrenergic agonist that stimulates the beta2
receptors, causing direct relaxation of vascular and
uterine smooth muscle.
Indications: For management of uncomplicated premature
labor; uterine hypermotility disorder; threatened
abortion; dysmenorrhea
Contraindications: Recent arterial hemorrhage or bleeding;
immediately postpartum; infection
Dose:
Premature labor, treatment, IV infusion, ADULT, 200 to 500
micrograms/minute, adjusted according to the response
of the patient until control is achieved; once labor has
been arrested, by IM injection, ADULT, 10 mg every 3–8
hours.
Premature labor, prophylaxis, by mouth, ADULT, 30 to 90
mg daily after parental therapy.
NOTE: Oral therapy is no longer recommended because of
lack of reported evidence of benefit from this route.
Precautions:
WARNING: Extreme caution is required for risk of maternal
pulmonary edema or respiratory distress syndrome.
Elderly (avoid use due to its lack of reported efficacy in this
age group); Pregnancy (monitor maternal blood pressure
and hydration, as well as maternal and fetal heart rates
all throughout infusion).
Adverse Drug Reactions: Chest pain, hypotension,
tachycardia, dizziness, rash, abdominal distress,
nausea, vomiting, transient flushing, maternal
pulmonary edema, fetal tachycardia, trembling,
nervousness, weakness, transient palpitation
G
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Isoxsuprine:
Barbiturates, Nicorandil (hypotensive effect)
Enhances therapeutic effect of Risperidone (hypotensive
effect)
Increases risk of adverse or toxic effects of Isoxsuprine:
Hypotensive Agents (orthostatic hypotension)
Increases risk of adverse or toxic effects of the following
drugs:
Duloxetine, Levodopa (orthostatic hypotension)
Administration:
For parenteral administration, may be administered by
syringe pump. Limit therapy to a maximum of 48 hours.
For oral administration, may be taken with meals, milk, or
antacids to minimize GI discomfort.
Pregnancy Category: C
ATC Code: Not available
Rx MAGNESIUM SULFATE
Inj.: 250 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IM, IV)
250 mg/mL, 10 mL, 20 mL and 50 mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IM, IV)
A sterile preparation that contains magnesium salt as
heptahydrate.
Indications: Drug of choice for the prevention of seizures in
women with severe preeclampsia; control of seizures or
prevention of recurrence among eclamptic patients
Contraindications: Heart block; myocardial infarction;
hypermagnesemia; deranged renal function; myasthenia
gravis
Dose:
Prevention of recurrent seizures, by IV injection, ADULT, 4 g
as loading dose over 5–15 minutes followed by IV
infusion of maintenance dose of 1 g/hour for at least 24
169

hours after the last seizure or delivery, whichever occurs
later;
by deep IM injection (used when IV lines are not
available), ADULT, 5 g into each buttock, then 5 g every
4 hours into alternate buttocks for at least 24 hours after
the last seizure or delivery; treat recurrent seizure by
further IV bolus of 2 g or 4 g if body weight is over 70 kg.
Dose Adjustment:
Renal Impairment:
Dose should not exceed 20 g in 48 hours. Use with caution
and monitor for hypermagnesemia.
Precautions:
G
WARNING: Magnesium toxicity can cause loss of deep
tendon reflexes, followed by respiratory depression
and ultimately respiratory arrest. If deep tendon
reflexes are absent, withhold further doses of
magnesium sulfate until reflexes return. If
repeated seizures occur despite magnesium, other
pre-hospital options include administering
diazepam.
Magnesium toxicity can be reversed with
administration of calcium gluconate, administered
as a 10–20 mL IV of 10% solution, as an antidote
for problematic signs associated with
hypermagnesemia.
Magnesium is excreted by the kidney. Monitor
serum levels regularly in women with oliguria (urine
output <100 mL/4 hours).
Myasthenia gravis;
Hepatic impairment (avoid in hepatic coma if there is a risk
of renal failure);
Renal impairment;
Magnesium toxicity can lead to fatal cardiovascular arrest
and/or respiratory failure or paralysis;
Pregnancy.
Adverse Drug Reactions:
Common: Flushing, nausea, vomiting
Less Common: Dizziness, drowsiness, headache, thirst
Rare: Arrhythmias, cardiac arrest, coma, confusion, loss of
tendon reflexes, muscle weakness, respiratory
depression
Drug Interactions:
Monitor closely when used with drugs that:
Enhance the therapeutic effect of Mg Sulfate:
Aminoglycosides e.g. Streptomycin (additive
neuromuscular blocking effect), CNS Depressants, e.g.,
Barbiturates, Opiates, General Anesthetics, Gabapentin
(additive central depressant effects), Neuromuscular
Blockers e.g., Tubocurarine, Succinylcholine,
Vecuronium (potentiates neuromuscular blockade),
Nifedipine (Parenteral)
Increases risk of adverse or toxic effects of Magnesium
Sulfate:
Nifedipine (hypotension)
170
GENITO URINARY SYSTEM AND SEX HORMONES
Administration: For IV administration, do not exceed the rate
of 150 mg/minute. See manufacturer’s directions for
instructions on dilution and administration.
NOTE: Should NOT be used via IV route for pre-eclampsia or
eclampsia during 2 hours prior to delivery.
Do NOT freeze since it may result in precipitation or
crystallization.
Route Preparation
Concentration should NOT exceed 20% (200
mg/mL). Dilute 1 part magnesium sulfate,
IV
50%, with at least 1.5 parts of water for
injection)
Adult: Concentrations of 25% (250 mg/mL)
or 50% (500 mg/mL). Mix magnesium
IM sulfate, 50%, with 1 mL lidocaine injection,
2%
Child: Should not exceed 20% (200 mg/mL)
Pregnancy Category: D
ATC Code: Not available
SEX HORMONES AND MODULATORS OF
THE GENITAL SYSTEM
HORMONAL CONTRACEPTIVES
FOR SYSTEMIC USE
PROGESTINS AND ESTROGENS,
FIXED COMBINATIONS
General Information
Combination of hormonal contraceptives that inhibit
ovulation via a negative feedback mechanism involving
the hypothalamus. These modify the normal pattern of
gonadotropin secretion of the follicle stimulating
hormone (FSH) and luteinizing hormone by the anterior
pituitary. Thus, inhibiting the follicular phase FSH and
midcycle surge of gonadotropins. These contraceptives
also produce alterations in the genital tract, including
changes in the cervical mucus, making it unfavorable for
sperm penetration.
Indication: Contraception
Contraindications: Breast cancer (current or recent); risk
factors for venous thromboembolism and arterial
disease; heart disease associated with pulmonary
hypertension or risk of embolism; migraine; history of
subacute bacterial endocarditis; ischemic
cerebrovascular disease; liver disease, including
disorders of hepatic secretion; porphyria; systemic lupus
erythematosus (SLE); history of hemolytic uremic
syndrome; liver adenoma; gallstones; estrogen-
dependent neoplasm; neoplasm of genital tract;
GENITO URINARY SYSTEM AND SEX HORMONES
undiagnosed vaginal bleeding; history of pruritus during
pregnancy, chorea, deteriorating otosclerosis,
cholestatic jaundice, or pemphigoid gestationis; after
evacuation of hydatidiform mole; smokers >35 years
Dose:
ADMINISTRATION. Each tablet (“pill”) should be taken at
approximately the same time each day. If one or more
tablets are forgotten for more than 12 hours,
contraceptive protection will be reduced.
For Schedule 1:
Begins dose on first Sunday after onset of
menstruation. If the menstrual period
starts on a Sunday, take first tablet that
Sunday
very same day. With a Sunday start, an
Starter
additional method of contraception should
be used until after the first 7 days of
consecutive administration.
Take 1 tablet daily for 21 consecutive
21- days, followed by 7 days off the
tablet medication.
package Start new course on the 8th day after the
last tablet is taken.
28-
tablet Take 1 tablet daily without interruption.
package
For Schedule 2:
Day 1 Take 1 tablet daily starting on the first day
Starter of the menstrual cycle.
Take 1 tablet daily for 21 consecutive
days, followed by 7 days off the
21-
medication (during which withdrawal
tablet
bleeding occurs).
package
Start new course on the 8th day after the
last tablet is taken.
28- Take 1 tablet daily without interruption
tablet (withdrawal bleeding occurs when inactive
package tablets are being taken).
NOTE: If all doses have not been taken on schedule and one
menstrual period is missed, the possibility of pregnancy
should be considered. If 2 consecutive menstrual
periods are missed, pregnancy test is required before
starting a new dosing cycle.
MISSED PILL. The critical time for loss of contraception
protection is when a pill is omitted either at the beginning
or at the end of a cycle (as this lengthens the pill free
interval). If a woman forgets to take a pill, she should
take it as soon as she remembers, and take the next one
at the normal time. If the delay with any pill is 24 hours
or longer, the pill may not work. Continue taking the pill
normally but be aware that contraception may not work
for the next 7 days. If these 7 days run beyond the end
of the packet, the next packet should be started at once,
omitting the 7 inactive tablets or the pill-free interval.
Emergency contraception is recommended if more than
2 combined oral contraceptive tablets are missed from
the first 7 tablets in a packet.
DIARRHEA AND VOMITING. Vomiting within 2 hours of taking
an oral contraceptive or very severe diarrhea can
interfere with the absorption of the drug. Additional
precautions should be used during, and for 7 days after,
recovery. If vomiting and diarrhea occur during the last 7
pills, omit inactive pills or next pill-free period.
Dose Adjustment:
Renal Impairment
In mild-to-moderate impairment, use with caution.
In severe impairment, refer patient to a specialist.
Precautions:
WARNING: Increased risk of cardiovascular side
effects in women who smoke cigarettes
(especially heavy smokers with ≥15 cigarettes
per day). Strongly advise women who use
G
combination hormonal contraceptives to stop
use of oral contraceptives or not to smoke.
Unexplained vaginal bleeding (investigate cause before
starting contraceptive);
Risk factors for venous thromboembolism and arterial
disease;
Migraine without focal aura or controlled with 5HT1 agonist;
Hyperprolactinemia;
Gallbladder disease;
Some types of hyperlipidemia;
History of severe depression especially if induced by
hormonal contraception;
Long-term immobilization [see Travel below];
Sickle-cell disease;
Inflammatory bowel disease, including Crohn’s disease;
Diabetes;
Smoking;
BMI >30;
Malabsorption syndromes;
Surgery;
Systemic Lupus Erythematosus (SLE);
Pregnancy (epidemiological evidence suggests no harmful
effects on fetus; use within 3 weeks of birth);
Breastfeeding (combined oral contraceptives may inhibit
lactation; use alternative method of contraception until
weaning or for 6 months after birth).
MIGRAINE. Report any increase in headache frequency or
onset of focal symptoms. Discontinue immediately and
refer urgently to a neurologist if focal neurological
symptoms not typical of aura persist for more than 1
hour.
TRAVEL. Women may be at an increased risk of deep-vein
thrombosis during travel involving long periods of
immobility (over 5 hours). The risk may be reduced by
appropriate exercise during the journey, and possibly by
wearing elastic hosiery.
Adverse Drug Reactions:
Common: Acne, breakthrough bleeding, breast enlargement
and tenderness, changes in libido, chloasma, fluid
retention, headache, hypertension, mood changes (e.g.,
depression), nausea, thrush, vomiting
Less Common: Alopecia, amenorrhea, contact lens
intolerance, hirsutism, hyperinsulinemia, insulin
resistance, rash
Rare: Allergy, breast cancer, cervical cancer, hypertension,
jaundice, liver cancer, pancreatitis, photosensitivity,
stroke, VTE
171
 GENITO URINARY SYSTEM AND SEX HORMONES

Drug Interactions: ETHINYLESTRADIOL +

NOTE: Combined oral contraceptives are metabolized by Rx
DESOGESTREL
CYP3A4.
Oral: 30 micrograms ethinylestradiol + 150 micrograms
Monitor closely with:
desogestrel per tablet as 21 active tablets or 28-day
Enhances therapeutic effect of Fixed Combinations of
tablet with 21 active and 7 inactive pills
Progestins and Estrogens:
NSAIDs including COX-2 Inhibitors (thrombogenic effect)
A combined oral contraceptive, which contains estrogen as
ethinylestradiol, and progesterone as desogestrel. It
Enhances therapeutic effect of Immune Globulin
inhibits ovulation, reduces receptivity of the
(thrombogenic effect)
endometrium for implantation, and thickens cervical
mucus that serves as a barrier to sperm.
Reduces contraceptive effect of Fixed Combinations of
Progestins and Estrogens:
Indication: Contraception
G

Cephalosporins e.g. Ceftriaxone, Macrolide Antibiotics

e.g., Azithromycin, Erythromycin, Metronidazole,
Dose:
Penicillins e.g., Benzylpenicillin, Amoxicillin,
Contraception, by mouth, ADULT (female), 1 tablet (30
Phenoxymethylpenicillin, Ampicillin, Quinolones e.g.,
micrograms ethinylestradiol + 150 micrograms
Ciprofloxacin, Levofloxacin, Tetracyclines e.g.
desogestrel) daily for 21 days, followed by 7 days of
Doxycycline
inactive pills.
Reduces therapeutic effect of the following drugs:
Administration: Administer at the same time each day at
Anti-diabetic Agents, Thyroid Products
intervals not more than 24 hours. If 1 or more tablets are
forgotten for more than 12 hours, contraceptive
Avoid concomitant use with:
protection will be reduced.
Decreases serum concentration of Fixed Combinations of
Progestins and Estrogens:
Take 1 tab daily starting the 1st pack on the 1st day of
Bile Acid Sequestrants [administer oral contraceptives at
menstruation, without interruption for 22 days, followed
least 1-4 hours prior to or 4-6 hours after a Bile Acid
by 6 tab-free days. Start with the blue tablets and follow
Sequestrant], Dabrafenib, Efavirenz, Exemestane,
the directional arrows on the pack. For missed doses,
Griseofulvin, Lamotrigine, Topiramate
take as soon as remembered. If remembered >12 hours
than intended, risk of becoming pregnant increases.
Enhances therapeutic effect of Tranexamic Acid
(thrombogenic effect)
See General Information on Progestins and Estrogens,
Fixed Combinations listed above for further information.
Increases metabolism of Fixed Combinations of Progestins
and Estrogens:
Pregnancy Category: X
Carbamazepine, CYP2C19 Inducers, CYP3A4 Inducers,
Phenobarbital, Rifampicin
ATC Code: G03AA09
Increases risk of adverse or toxic effects of the following
drugs:
Anti-hepaciviral Combination Products (hepatotoxic ETHINYLESTRADIOL +
Rx
effect), Vitamin K Antagonists, e.g., Warfarin LEVONORGESTREL
(thromboembolic disorders)
Oral: 30 micrograms ethinylestradiol + 150 micrograms
Reduces therapeutic effect of Fixed Combinations of levonorgestrel per tablet as 21 active tablets or 28-
Progestins and Estrogens, leading to contraceptive day tablet with 21 active and 7 inactive pills
failure:
Artemether, Barbiturates e.g. Phenobarbital, A combined, oral contraceptive, which contains estrogen as
Carbamazepine, CYP2C19 Inducers, CYP3A4 Inducers, ethinylestradiol and progesterone as levonorgestrel. It
Fosphenytoin, Mifepristone, Mycophenolate, inhibits ovulation, reduces receptivity of the
Phenobarbital, Phenytoin, Protease Inhibitor [except endometrium for implantation, and thickens cervical
Indinavir], Retinoic Acid Derivatives [except Adapalene, mucus that serves as a barrier to sperm.
Tretinoin (topical)], Rifamycin Derivatives, Rifampicin
Indication: Contraception
Reduces therapeutic effect of the following drugs:
Amlodipine, Enalapril, Isosorbide Dinitrate, Methyldopa Dose:
(antagonizes hypotensive effect), Anastrozole, Anti- Contraception, by mouth, 1 tablet daily for 21 days starting
coagulants e.g. Warfarin, Heparin (counteracts on day 1 of the menstrual cycle; repeat subsequent
anticoagulant effects), Furosemide, Hyaluronidase, courses after a 7-day tablet-free interval (during which
Hydrochlorothiazide (antagonizes diuretic effect), withdrawal bleeding occurs); or
Metformin (antagonizes hypoglycemic effect) 28 tablets of everyday (ED) preparations, take 1 active
tablet daily starting on D1 of the cycle up to D21; repeat
subsequent courses without interval (withdrawal
bleeding occurs when inactive tablets are being taken).

172
GENITO URINARY SYSTEM AND SEX HORMONES
Administration: Take each pill at approximately the same
time each day. If delayed by longer than 24 hours,
contraceptive protection may be lost.
See General Information on Progestins and Estrogens,
Fixed Combinations listed above for further information.
Pregnancy Category: X
ATC Code: G03AA07
ETHINYLESTRADIOL +
Rx
NORETHISTERONE
Oral: 35 micrograms ethinylestradiol + 400 micrograms
norethisterone acetate per tablet as 21 active tablets
or 28-day tablet with 21 active and 7 inactive pills
A combined oral contraceptive, which contains estrogen as
ethinylestradiol and progesterone as norethisterone. It
inhibits ovulation, reduces the receptivity of the
endometrium for implantation, and thickens cervical
mucus that serves as a barrier to sperm.
Indication: Contraception
Dose:
Contraception, by mouth, ADULT (female), 1 tablet (35
micrograms ethinylestradiol + 400 micrograms
norethisterone acetate) daily beginning on the 5th day of
menstrual cycle for 21 days, followed by 7 tab-free days.
Precautions:
WARNING: NOT for use as prophylaxis of dementia. An increased
incidence of dementia was observed in women ≥65 years of
age taking conjugated estrogens alone or in combination with
medroxyprogesterone acetate.
NOT for use in the prevention of cardiovascular disease. An
increased risk of deep vein thrombosis (DVT), stroke,
pulmonary emboli (PE), and myocardial infarction (MI) was
observed in postmenopausal women.
The use of unopposed estrogen in women with an intact uterus
is associated with an increased risk of endometrial cancer.
Combination or inclusion of a progestin to estrogen treatment
may decrease the risk of endometrial hyperplasia, a precursor
to endometrial cancer.
Administration: Administer at the same time each day at
intervals for not more than 24 hours. If one or more
tablets are forgotten for more than 12 hours,
contraceptive protection will be reduced.
Use for the shortest duration possible at the lowest
effective dose in accordance with treatment goals.
See General Information on Progestins and Estrogens,
Fixed Combinations listed above for further information.
Pregnancy Category: X
ATC Code: G03AA05
ETHINYLESTRADIOL +
Rx
NORGESTREL
Oral: 30 micrograms ethinylestradiol + 300 micrograms
norgestrel per tablet as 21 active tablets or 28-day
tablet with 21 active and 7 inactive pills
A combined oral contraceptive, which contains estrogen as
ethinylestradiol and progesterone as norgestrel. It
inhibits ovulation, reduces receptivity of the
endometrium for implantation, and thickens cervical
mucus that serves as a barrier to sperm.
Indication: Contraception
G
Dose:
Contraception, by mouth, ADULT (female), 1 tablet (30
micrograms ethinylestradiol + 300 micrograms
norgestrel) daily.
Administration: Administer at the same time each day at
intervals for not more than 24 hours. If one or more
tablets are forgotten for more than 12 hours,
contraceptive protection will be reduced.
See General Information on Progestins and Estrogens,
Fixed Combinations listed above for further information.
Pregnancy Category: X
ATC Code: G03AA06
PROGESTINS
Rx ETONOGESTREL
Subdermal: 68 mg subdermal implant
Etonogestrel is a hormone that prevents ovulation by
reducing reception of endometrium to implantation and
thickening of the cervical mucus that serves as a barrier
to sperm.
Indication: Contraception
Contraindications: Breast cancer or other estrogen-
dependent or progestin-dependent neoplasms (current
or a history of); hepatic impairment; hepatic tumors or
disease; pregnancy; thrombosis or thromboembolic
disorders (current or history of); undiagnosed abnormal
genital bleeding
Dose:
Contraception, by subdermal implant, ADULT, 68 mg
implant under the skin at the inner side of the non-
dominant upper arm (therapy can be started at any time
in the menstrual cycle once it is determined that the
woman is not pregnant); back-up contraception is not
needed if started within 5 days of onset of menstruation;
if started >5 days after the onset of menstruation or at
any time in a woman experiencing amenorrhea (not
postpartum), back-up contraception should be used for
7 days.
173
 GENITO URINARY SYSTEM AND SEX HORMONES

Remove no later than the end of the third year. This can be
replaced with a new implant at time of removal if
continued contraception is needed, after ruling out
possibility of pregnancy. Insertion can be done as
follows:
No hormonal
Insert between days 1 through 5 of
contraceptives
within past month
menstruation, even if still bleeding
Transdermal system or vaginal ring
Switching from
Insert on the day of the removal of the
combination
transdermal system or vaginal ring or on
hormonal
the day following the transdermal-free or
contraceptive
G
Adverse Drug Reactions:
Common: Headache, acne vulgaris, menstrual disease (<3
episodes or 90 days; prolonged menstrual bleeding
lasting >14 days: >5 episodes in 90 days) amenorrhea
(no bleeding in 90 days); weight gain, abdominal pain,
vaginitis, mastalgia, pharyngitis
Less Common: Dizziness, emotional lability, depression,
nervousness, pain, localized erythema, dysmenorrhea,
nausea, leukorrhea, hypersensitivity, application site
reaction, local pain, hematoma at injection site, bruising
at injection site, back pain, flu-like symptoms
Rare: Alopecia, angioedema (including exacerbation of
hereditary angioedema), cerebrovascular accident,
anaphylaxis, convulsions, migraine, hypertension,

ring-free interval myocardial infarction, ovarian cyst, pulmonary embolism,

seizure
Implant or intrauterine device (IUD)
Insert on same day as removal of implant
Switching from a Drug Interactions:
or IUD
progestin-only Monitor closely with:
contraceptive
Injection Enhances therapeutic effect of C1 Inhibitors (thrombogenic
Insert on day next injection is due effect)
First trimester
Insert within first 5 days following first Reduces therapeutic effect of Antidiabetic Agents
abortion or
trimester abortion or miscarriage.
miscarriage
Avoid concomitant use with drugs that
Second trimester Decrease serum concentration of Etonogestrel:
Insert between 21 and 28 days following
abortion or
miscarriage
second trimester abortion or miscarriage. Acitretin, Aprepitant, Artemether, Bile Acid Sequestrants
[administer Etonogestrel at least 1–4 hours prior to or
If not breast-feeding, insert between 21 to 4–6 hours after Bile Acid Sequestrants], Bosentan,
28 days postpartum. Carbamazepine, Dabrafenib, Exenatide, Lixisenatide
[administer Etonogestrel 1 hour before or 11 hours after
Postpartum If breast-feeding, insert after the fourth Lixisenatide], Lumacaftor, Mycophenolate, Nelfinavir,
post-partum week and use a second non- Nevirapine, Oxcarbazepine, Perampanel, Prucalopride,
hormonal form of contraception for the Rifamycin Derivatives, Saquinavir, Sugammadex,
first 7 days of insertion.
Telaprevir, Topiramate

Precautions: Enhance therapeutic effect of Etonogestrel:

Breast cancer; Tranexamic Acid (thrombogenic effect)
Carbohydrate intolerance and diabetes;
Ovarian cysts; Increase risk of adverse or toxic effects of Vitamin K
Retinal vascular thrombosis (discontinue if there is loss of Antagonists e.g. Warfarin (thromboembolic disorders)
vision, proptosis, diplopia, papilledema, or retinal
vascular lesions); Increases serum concentration of Etonogestrel:
Thromboembolism and other vascular events (e.g., deep Atazanavir
vein thrombosis, myocardial infarction, pulmonary
embolism); Reduces therapeutic effect of Etonogestrel, leading to
Changes in vaginal bleeding; contraceptive failure:
Cardiovascular diseases; Barbiturates, Efavirenz, Fosphenytoin, Griseofulvin,
Depression; Mifepristone, Phenytoin, Retinoic Acid Derivatives
Disease that may be exacerbated by fluid retention; [except Adapalene, Tretinoin (topical)], Ulipristal [for
Gallbladder disease; uterine fibroids, avoid Etonogestrel within 12 days of
Hepatic adenomas or carcinomas; stopping Ulipristal; for emergency contraceptive, avoid
Hepatic impairment; Etonogestrel within 5 days of stopping Ulipristal]
Hyperlipidemia;
Hypertension; Reduces therapeutic effect of Anticoagulants, Vitamin K
Renal impairment; Antagonists e.g. Warfarin (anticoagulant effect)
Overweight women;
Wearers of contact lens; Administration: Insert implant subdermally at the inner side
Increased risk of cervical or ovarian cancer; of the non-dominant upper arm approximately 8–10 cm
May change results of some laboratory tests (e.g., (3–4 inches) above the medial epicondyle of the
coagulation factors, lipids, glucose tolerance, binding humerus just under the skin. Implant must be palpable
proteins); after insertion.
Does not protect against HIV infection or other sexually
transmitted disease X-ray, CT scan, ultrasound scanning, or MRI can be used to
confirm the location of the implant if it is not palpable.

174
GENITO URINARY SYSTEM AND SEX HORMONES
Use of a non-hormonal contraceptive is required until the
verification of the presence of the implant.
Confirm first that the entire implant has been removed by
measuring its length (4 cm), when removing. Get rid of all
pieces if implant has broken. A new implant may be
inserted in the same arm through the same incision.
Pregnancy Category: X
ATC Code: G03AC08
Rx MEDROXYPROGESTERONE
Inj.: 50 mg/mL (as acetate), 3 mL vial + syringe (IM)
150 mg/mL (as enanthate), 1 mL vial (IM)
NOTE: Use one (1) inch long needle
A long-acting, progestin injectable contraceptive indicated
for the prevention of pregnancy.
Indication: Parenteral progestin-only contraception (short-
or long-term)
Contraindications: Pregnancy; undiagnosed vaginal
bleeding; history of pruritus during pregnancy; active liver
disease and history of pruritus during pregnancy; severe
arterial disease; porphyria
Dose:
Contraception, by deep IM injection, ADULT (female),
short-term, 150 mg within the first 7 days of cycle or
within the first 5 days after parturition, delay until 6
weeks after parturition if breastfeeding;
long-term, by deep IM injection, ADULT (female), as for
short-term, repeated every 3 months.
NOTE: If the interval between injections is >3 months and
14 days, exclude pregnancy before administering the
next injection and advise patient to use additional
contraceptive measures (e.g., a condom) for 7 days after
the injection.
PATIENT ADVICE. Women should receive full counseling on
the likelihood of menstrual irregularities and the
potential for a delay in return to full fertility with long-term
use before treatment.
Dose Adjustment:
Hepatic Impairment:
Use with caution. Avoid use in active or severe liver disease.
Precautions:
Unexplained vaginal bleeding (investigate cause before
starting treatment);
History of endometriosis;
Uterine fibroids;
Migraine;
Liver disease (avoid use in active liver disease);
Thromboembolic or coronary vascular disease;
Diabetes Mellitus (monitor and adjust dose of antidiabetic
drug if necessary);
Epilepsy;
Smoking;
Systemic Lupus Erythematosus (SLE);
Hypertension;
Renal disease;
Gall bladder disease;
Severe arterial disease (multiple risk factors for venous
thromboembolism and arterial disease);
History of breast cancer (may be used after 5 years if no
evidence of current disease);
Elderly; (increased risk of coronary heart disease, stroke,
VTE and breast cancer);
Pregnancy (genital malformations and cardiac defects have
been reported in male and female fetuses; inadvertent
use of depot contraceptive injection unlikely to harm
G
fetus; avoid use if there is history of pruritus during
pregnancy);
Lactation (present in breastmilk; no adverse effects
reported; preferably start injectable contraceptive 6
weeks after birth or later)
Adverse Drug Reactions:
Common: Breast enlargement and tenderness, change in
libido, depression, endometrial hyperplasia, headache,
irregular or breakthrough bleeding, leg cramps, spotting
Less Common: Acne, benign proliferative breast disease,
breast cancer, cardiovascular events, dementia, edema,
exacerbation or recurrence of endometriosis, fluid
retention, gall stones, itch, migraine, nausea,
premenstrual-like syndrome
Rare: Chloasma, cholestatic jaundice, endometrial cancer,
enlargement of hepatic hemangiomas, enlargement of
uterine fibroids, galactorrhea, glucose intolerance,
hypersensitivity reactions, ovarian cancer, pancreatitis,
visual changes
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Metformin (antagonizes
hypoglycemic effect)
Administration: If the interval between injections is >3
months and 14 days, exclude pregnancy before
administering the next injection and advise patient to
use additional contraceptive measures (e.g. condom) for
7 days after the injection.
Pregnancy Category: X
ATC Code: G03AC06
ANDROGENS
Rx TESTOSTERONE
Inj.: 250 mg/mL solution (as undecanoate), 4 mL
The principal endogenous androgen responsible for
promoting growth and development of the male sex
organs and maintaining secondary sex characteristics in
androgen-deficient males.
Indication: For use in men who lack or have low testosterone
levels in conjunction with an associated medical
condition
175

Contraindication: Known or suspected prostate cancer
Dose:
Hypogonadism, by IM injection, ADULT, 750 mg followed by
750 mg administered 4 weeks later, then 750 mg
administered every 10 weeks thereafter.
Dose Adjustment:
Renal and Hepatic Impairment:
May enhance edema formation. Contraindicated in serious
renal and hepatic disease.
Precautions:
WARNING: Serious pulmonary oil microembolism
G
(POME) reactions, involving urge to cough,
dyspnea, throat tightening, chest pain, dizziness,
syncope, and episodes of anaphylaxis, including
life-threatening reactions, have been observed
during or immediately after administration of
testosterone. Observe patients for 30 minutes
following each injection to provide adequate
medical treatment in the event of serious POME
reactions or anaphylaxis.
Caution must be performed for possible risk of developing
major adverse cardiovascular events such as MI, stroke,
or cardiovascular death;
Gynecomastia;
Hypercalcemia in patients with prolonged immobilization or
cancer;
Oligospermia;
Polycythemia priapism;
Venous thromboembolism;
Prostate cancer; Benign prostatic hyperplasia;
Diseases that may be exacerbated by fluid retention
including cardiac, hepatic, or renal dysfunction;
Sleep apnea.
Adverse Drug Reactions: Hypertension, hypotension, deep
vein thrombosis, edema, vasodilatation, headache,
fatigue, irritability, insomnia, mood swings, aggressive
behavior, taste disorder, altered sense of smell,
abnormal dreams, amnesia, anxiety, chills, depression,
dizziness, emotional lability, excitement, hostility,
malaise, nervousness, outbursts of anger, paresthesia,
seizure, sleep apnea, suicidal ideation, acne vulgaris,
hyperhidrosis, alopecia, contact dermatitis, diaphoresis,
erythema, folliculitis, hair discoloration, pruritus,
seborrhea, skin rash, xeroderma, increased plasma
estradiol concentration, weight gain, gynecomastia, hot
flash, change in libido, fluid retention, hirsutism
(increase in pubic hair growth), hypercalcemia,
hyperchloremia, hyperglycemia, hyperkalemia,
hypernatremia, hypoglycemia, hypokalemia, inorganic
phosphate retention, menstrual disease (including
amenorrhea), diarrhea, gastroesophageal reflux disease,
gastrointestinal hemorrhage, gastrointestinal irritation,
increased appetite, nausea, vomiting, prostatitis,
ejaculatory disorder, prostate induration, spontaneous
erections, benign prostatic hypertrophy, difficulty in
micturition, hematuria, impotence, irritable bladder,
mastalgia, oligospermia, priapism, testicular atrophy,
urinary tract infection, virilization, cholestatic hepatitis,
cholestatic jaundice, hepatic insufficiency, hepatic
176
GENITO URINARY SYSTEM AND SEX HORMONES
necrosis, hepatocellular neoplasms, peliosis hepatis,
malignant neoplasm of prostate, clotting factors
suppression, hemorrhage, carcinoma, anaphylactoid
reaction, hypersensitivity reaction (including pulmonary
oil microembolism), pain at injection site, erythema at
injection site, inflammation at injection site, arthralgia,
back pain, abnormal bone growth (accelerated),
hemarthrosis, hyperkinesia, increased lacrimation,
polyuria, bronchitis, nasopharyngitis, sinusitis, upper
respiratory tract infection, dyspnea
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Blood Glucose Lowering Agents (hypoglycemic effect),
C1 Inhibitors (thrombogenic effect)
Increases risk of adverse effects of Testosterone:
Corticosteroids (fluid-retaining effect)
Avoid concomitant use with:
Enhances therapeutic effect of Vitamin K Antagonists e.g.
Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Cyclosporine
(hepatotoxic effect)
Increases serum concentration of Cyclosporine
Administration: Inject 3 mL of air through the gray rubber
stopper into the vial to create positive pressure, then
withdraw 3 mL of solution (750 mg) from the vial. Expel
air bubbles from the syringe and change the syringe
needle to a new IM needle. Discard unused portion.
Pregnancy Category: X
ATC Code: G03BA03
ESTROGENS
Rx CONJUGATED ESTROGEN
Oral: 625 micrograms and 1.25 mg tablet
Conjugated estrogen is a mixture of estrogens that are
available either as preparations that meet current official
USP standards or as nonofficial preparations, which are
prepared synthetically from plant sources (e.g., synthetic
conjugated estrogens A, synthetic conjugated estrogens
B).
Estrogens modulate the pituitary secretion of
gonadotropins, luteinizing hormone, and follicle-
stimulating hormone through a negative feedback
system reducing elevated levels of these hormones
possible for symptoms experienced by postmenopausal
women.
Indications: For estrogen replacement therapy; prevention
of progression of osteoporosis associated with estrogen
deficiency in postmenopausal women; management of
moderate to severe vasomotor symptoms associated
GENITO URINARY SYSTEM AND SEX HORMONES
with menopause; management of vulvar and vaginal
atrophy (atrophic vaginitis); management of female
hypoestrogenism secondary to hypogonadism,
castration, or primary ovarian failure; palliative treatment
of advanced, inoperable, metastatic carcinoma of the
breast in postmenopausal women and in men; palliative
treatment of advanced carcinoma of the prostate in men
Contraindications: Angioedema or anaphylactic reaction to
estrogen or any component of the formulation;
undiagnosed abnormal genital bleeding; DVT or PE
(current or history of); active or history of arterial
thromboembolic disease (e.g., stroke, MI); breast cancer
(known, suspected or history of); estrogen-dependent
tumor (known or suspected); hepatic impairment or
disease; protein C, protein S, antithrombin deficiency, or
other known thrombophilic disorders; pregnancy
Dose:
Treatment of moderate to severe vasomotor symptoms due
to menopause, by mouth, ADULT, 300 micrograms once
daily then maintain using 450 micrograms to 1.25 mg
daily, continuous or in cyclical regimens (e.g., 25 days on
therapy then 5 days off).
Treatment of moderate to severe vaginal dryness and pain
with intercourse, symptoms of vulvar and vaginal atrophy
due to intercourse, by mouth, ADULT, 300 micrograms
once daily, continuous or in cyclical regimens (e.g., 25
days on therapy then 5 days off).
Female hypoestrogenism due to hypogonadism, by mouth,
ADULT, 300–625 micrograms once daily administered
cyclically (e.g., 3 weeks on therapy then 1 week off).
Palliative treatment of advanced androgen-dependent
carcinoma of prostate, by mouth, ADULT, 1.25 to 2.5 mg
3 times daily.
Female castration or primary ovarian failure, by mouth,
ADULT, 1.25 mg once daily administered cyclically (e.g.,
3 weeks on therapy then 1 week off).
Palliative treatment of breast cancer in appropriately
selected women and men with metastatic disease, by
mouth, ADULT, 10 mg 3 times daily for at least 3 months.
Precautions:
Warning: Do NOT use for prophylaxis of dementia. An
increased incidence of dementia was observed in
women ≥65 years of age taking conjugated
estrogens alone or in combination with
medroxyprogesterone acetate.
Do NOT use in the prevention of cardiovascular
disease. An increased risk of deep vein thrombosis
(DVT), stroke, pulmonary emboli (PE), and
myocardial infarction (MI) was observed with
conjugated estrogens with medroxyprogesterone
acetate in postmenopausal women.
Use of unopposed estrogen in women with an
intact uterus is associated with an increased risk
of endometrial cancer. Combination therapy of a
progestin to estrogen treatment may decrease the
risk of endometrial hyperplasia, a precursor to
endometrial cancer. Conduct appropriate
monitoring and diagnostic measures, including
endometrial sampling if indicated, to rule out
malignancy in postmenopausal women with
undiagnosed abnormal vaginal bleeding.
An increased risk of invasive breast cancer was
observed in postmenopausal women using
conjugated estrogens in combination with
medroxyprogesterone acetate. An increase in
abnormal mammogram findings has also been
reported with estrogen alone or in combination
with progestin therapy. Treatment may also lead to
severe hypercalcemia in patients with breast
cancer and bone metastases. Stop treatment of
estrogen if this occurs. Use is contraindicated in
patients with known or suspected breast cancer.
G
Endometriosis (consider adding a progestin with residual
endometriosis post-hysterectomy);
Venous thromboembolism in women with inherited
thrombophilias;
Ovarian cancer;
Retinal vascular thrombosis (discontinue if migraine, loss of
vision, proptosis, diplopia, or other visual disturbances
occur);
Asthma;
Diabetes;
Cardiovascular diseases (avoid use);
Diseases exacerbated by fluid retention;
Epilepsy;
Gallbladder disease requiring surgery;
History of cholestatic jaundice associated with prior
estrogen use or pregnancy (discontinue if jaundice
develops or acute or chronic hepatic disturbances
occur);
Hepatic hemangiomas;
Hereditary angioedema;
Hypoparathyroidism;
Migraine;
Porphyria;
Renal impairment;
Systemic lupus erythematosus;
Estrogens should also be stopped at least 4-6 weeks prior
to elective surgery or be subjected to prolonged
immobilization due to increased risk of
thromboembolism. The use of estrogens may also modify
results of some laboratory tests (e.g., coagulation
factors, lipids, glucose tolerance, binding proteins)
Elderly (higher incidence of stroke and breast cancer was
seen in women >75 years old).
Adverse Drug Reactions:
Common: Headache, paresthesia, dizziness, pain,
abdominal pain, nausea, mastalgia, endometrial
hyperplasia, uterine hemorrhage, infection, back pain,
upper respiratory tract infection
Less Common: Anxiety, hypertonia, weight gain, dyspepsia,
vomiting, constipation, diarrhea, vaginitis, leg cramps,
cough, rhinitis, fever
Drug Interactions:
Monitor closely with:
Enhances thrombogenic effect of Conjugated Estrogen:
C1 Inhibitors, NSAIDs including COX-2 Inhibitors
Enhances thrombogenic effect of the following drugs:
Anthrax Immune Globulin (Human), Immune Globulin
177
 GENITO URINARY SYSTEM AND SEX HORMONES

Do NOT use in the prevention of cardiovascular

Increases risk of adverse or toxic effects of Dantrolene
disease. An increased risk of deep vein
(hepatotoxic effect)
thrombosis, stroke, pulmonary emboli, and
myocardial infarction was observed in conjugated
Reduces therapeutic effect of Conjugated Estrogen:
estrogens with medroxyprogesterone acetate in
Tocilizumab
postmenopausal women.
Reduces therapeutic effect of the following drugs: An increased risk of invasive breast cancer was
Antidiabetic Agents, Thyroid Products observed in postmenopausal women using
conjugated estrogens in combination with
Avoid concomitant use with: medroxyprogesterone acetate. An increase in
Decreases serum concentration of Conjugated Estrogen: abnormal mammogram findings has also been
Dabrafenib, Enzalutamide observed with estrogen alone or in combination
with progestin therapy. Treatment may also lead to
G

Increases metabolism of Conjugated Estrogen: severe hypercalcemia in patients with breast

CYP1A2 Inducers, CYP3A4 Inducers cancer and bone metastases. Use is
contraindicated in patients with known or
Increases serum concentration of Tizanidine suspected breast cancer.
Reduces therapeutic effect of the following drugs:
Anastrozole, Anticoagulants, Exemestane, Breast, cervical or ovarian cancer; Ovarian cysts;
Hyaluronidase, Somatropin Retinal vascular thrombosis (discontinue if there is loss of
vision, proptosis, diplopia, papilledema, or retinal
Administration: May be taken without regard to meals. Use vascular lesions);
alone or in combination with progestin with the lowest Transient dizziness or drowsiness;
effective dose and for the shortest duration possible. Cardiovascular diseases;
Depression;
Consider adding progestin when prescribing estrogen for a Disease that may be exacerbated by fluid retention;
postmenopausal woman with a uterus to reduce the risk Thromboembolism and other vascular events, e.g., DVT, MI,
of endometrial cancer. PE;
Hypertension;
NOTE: Women without uterus do not need progestin, Changes in vaginal bleeding;
however, hysterectomized women with a history of Carbohydrate intolerance and diabetes;
endometriosis may need progestin. Gallbladder disease;
Hepatic tumor;
Pregnancy Category: X Hepatic impairment;
Hyperlipidemia;
ATC Code: G03CA57 Renal impairment;
Porphyria;
Does not protect against HIV infection or other sexually
PROGESTINS transmitted disease;
Laboratory tests (may alter results, e.g., coagulation factors,
lipids, glucose tolerance, binding proteins);
General Information Overweight women;
Progestins are synthetic forms of progesterone that Wearers of contact lens
suppresses ovulation, thickens cervical mucus, alters
follicle stimulating hormone (FSH) and luteinizing Drug Interactions:
hormone (LH) concentrations, slows the movement of Monitor closely with:
ovum through the fallopian tubes, and alters the Enhances therapeutic effect of C1 Inhibitors (thrombogenic
endometrium. effect)
Contraindications: Breast cancer or other estrogen- or Reduces therapeutic effect of Antidiabetic Agents
progestin-dependent neoplasms (current or a history of);
hepatic tumors or disease; thrombosis or Avoid concomitant use with:
thromboembolic disorders (current or history of); Decreases serum concentration of Progestins:
undiagnosed abnormal genital bleeding Acitretin, Aprepitant, Artemether, Bile Acid Sequestrants
[administer oral progestin-containing contraceptives at
Precautions: least 1-4 hours prior to or 4-6 hours after Bile Acid
Warning: Do NOT use for prophylaxis of dementia. An Sequestrants], Bosentan, Carbamazepine, Clobazam,
increased incidence of dementia was observed in Dabrafenib, Darunavir, Exenatide, Felbamate,
women ≥65 years of age taking conjugated Fosaprepitant, Lixisenatide [administer oral
estrogens alone or in combination with contraceptives 1 hour before or at least 11 hours after
medroxyprogesterone acetate. Lixisenatide], Lumacaftor, Mycophenolate, Nelfinavir,
Nevirapine, Oxcarbazepine, Prucalopride, Rifamycin
Derivatives, Saquinavir, Sugammadex, Telaprevir,
Topiramate

178
GENITO URINARY SYSTEM AND SEX HORMONES
Enhances therapeutic effect of Progestins:
Tranexamic Acid (thrombogenic effect)
Increases risk of adverse or toxic effects of Vitamin K
Antagonists e.g. Warfarin (thromboembolic disorders)
Reduces therapeutic effect of Progestins, leading to
contraceptive failure:
Barbiturates, Fosphenytoin, Griseofulvin, Mifepristone,
Phenytoin, Retinoic Acid Derivatives [except Adapalene,
Topical Bexarotene, Tretinoin (Topical)], Ulipristal [avoid
Progestins within 5 days of stopping Ulipristal]
Reduces therapeutic effect of the following drugs:
Anticoagulants, Vitamin K Antagonists e.g. Warfarin
(anticoagulant effect)
Administration: Use for the shortest duration possible at the
lowest effective dose in accordance with treatment
goals.
PREGNEN (4) DERIVATIVES
Rx MEDROXYPROGESTERONE
Oral: 5 mg and 10 mg tablet (as acetate)
Inj.: 50 mg/mL (as acetate), 3 mL vial + syringe (IM)
150 mg/mL (as acetate or enanthate), 1 mL vial (IM)
NOTE: Use one (1) inch long needle
Medroxyprogesterone transforms the endometrium from a
proliferative to a secretory state. If given parenterally, it
can inhibit gonadotropin production, preventing follicular
maturation and ovulation.
Indications: Prophylaxis for endometrial hyperplasia;
Management of abnormal uterine bleeding,
amenorrhea, renal cell carcinoma andendometrial
carcinoma; hormonal replacement therapy
Contraindications: Suspected or known pregnancy; hepatic
impairment or disease
Dose:
Prophylaxis for endometrial hyperplasia, by mouth, ADULT,
5–10 mg once a day, in combination with estrogen
replacement therapy beginning on day 1 or day 16 of
each cycle, continuing for 12 to 14 consecutive days per
month; or 2.5 mg once a day continuously with estrogen
replacement therapy.
Abnormal uterine bleeding, by IM injection, ADULT and
ADOLESCENT, 5–10 mg once a day starting on the 16th
day of the cycle and continue for 10 days; or begin on the
21st day of the cycle and continue for 5 days (withdrawal
bleeding usually occurs within 3–7 days after the
discontinuation).
Amenorrhea, by IM injection, ADULT and ADOLESCENT, 5–
10 mg once a day starting at any time and continuing for
5–10 days (withdrawal bleeding usually occurs within 3–
7 days after the discontinuation).
Renal cell carcinoma and endometrial carcinoma, by IM
injection, ADULT, 400–1,000 mg once a week; can be
reduced to 400 mg once a month; frequency of
administration can be reduced if improvement or
stabilization occurs.
Administration: Shake injectable suspension immediately
prior to use. Administer IM injection deeply into gluteal,
deltoid or anterior thigh muscle.
See Medroxyprogesterone under Hormonal Contraceptives
for Systemic Use for other information.
Pregnancy Category: X
ATC Code: G03DA02
G
PREGNADIEN DERIVATIVES
Rx DYDROGESTERONE
Oral: 10 mg tablet
A synthetic retroisomer of progesterone that lacks
androgenic, estrogenic, thermogenic, corticoid, and
anabolic properties. It induces secretory changes in the
endometrium.
Indications: Abnormal uterine bleeding; secondary
amenorrhea; dysmenorrhea; endometriosis; infertility;
irregular menstrual cycle; menopause; recurrent and
threated pregnancy loss; premenstrual syndrome;
severe hepatic impairment
Dose:
Abnormal uterine bleeding, by mouth, ADULT, 10 mg twice
daily for 5-7 days to stop bleeding. Then continue to 10
mg twice daily on days 11–25 of cycle for prevention.
Amenorrhea, secondary, by mouth, ADULT, 10 mg twice
daily on days 11–25 of cycle. [NOTE: Prime endometrium with
adequate estrogen, exogenous or endogenous, prior to
administration. A dose of 10 mg once daily for 14 consecutive days
of each 28-day cycle has shown efficacy in premenopausal women
with normal estrogen levels.]
Dysmenorrhea, by mouth, ADULT, 10 mg twice daily on days
5–25 of cycle.
Endometriosis, by mouth, ADULT, 10 mg 2 or 3 times daily
on days 5–25 of cycle, or continuously.
Infertility due to luteal insufficiency, by mouth, ADULT, 10
mg once daily on days 14–25 of cycle for ≥6 consecutive
cycles.
Irregular menstrual cycle, by mouth, ADULT, 10 mg twice
daily on days 11–25 of cycle.
Menopause, by mouth, ADULT, in combination with cyclic
estrogen therapy, 10 mg once daily for the last 12–14
days of cycle, may increase to 10 mg twice daily if
evidence of lack of response or withdrawal bleeding
occurs; in combination with continuous estrogen
therapy, 10 mg once daily for 14 consecutive days of a
28-day cycle.
Pregnancy loss, recurrent, by mouth, ADULT, 10 mg twice
daily; may be taken through week 20 of pregnancy.
Pregnancy loss, threatened, by mouth, ADULT, 40 mg
loading dose, followed by 10 mg every 8 hours until
symptoms resolve; or 10 mg twice daily, with or without
40 mg loading dose.
179

Premenstrual syndrome, by mouth, ADULT, 10 mg twice
daily on days 11 to 25 of cycle.
Adverse Drug Reactions:
Less Common: Headache, migraine, amenorrhea,
hypermenorrhea, oligomenorrhea, nausea, breast
tenderness, dysmenorrhea, mastalgia
Rare: Abdominal pain, allergic dermatitis, angioedema,
breast swelling, depressed mood, dizziness, drowsiness,
edema, exacerbation of porphyria, hemolytic anemia,
hypersensitivity, jaundice, malaise, pruritus, rash, tumor
growth (meningioma), urticaria, vomiting, weakness,
weight gain
G
Administration: May split tablet to facilitate swallowing.
Missed dose can be administered as soon as possible if
<12 hours have elapsed; otherwise, skip missed dose
and resume with next scheduled dose.
NOTE: May contain lactose. Use with caution in patients with
galactose intolerance.
See General Information on Progestins listed under Chapter
5: Genito Urinary System and Sex Hormones for further
information.
Pregnancy Category: B
ATC Code: G03DB01
ESTREN DERIVATIVES
Rx LYNESTRENOL
Oral: 500 mcg tablet
A progestin-only pill that contains very low doses of a
progestin similar to the natural hormone, progesterone,
in a woman’s body.
Indication: For contraception in cases of intolerance to
estrogen-progestogen combined pills or when estrogen
is contraindicated.
Contraindications: Pregnancy, possible pregnancy,
porphyria, severe arterial disease, undiagnosed vaginal
bleeding, hormone-dependent neoplasms, severe liver
disease such as hepatic adenoma, and after recent
evacuation of a hydatidiform mole.
Dose:
Contraceptive, by mouth, ADULT, one tablet daily.
Dose Adjustment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
Use in caution in patients with asthma, diabetes mellitus,
epilepsy, heart disease, hypertension, thromboembolic
disorders, history of depression, past ectopic pregnancy,
functional ovarian cysts, malabsorption syndromes,
migraine, renal impairment, liver dysfunction, and other
conditions which may be aggravated by fluid retention.
180
GENITO URINARY SYSTEM AND SEX HORMONES
Adverse Drug Reactions:
Common: Gastrointestinal disturbances, changes in
appetite or weight, fluid retention, edema, chloasma,
allergic skin rashes, urticarial, mental depression, breast
changes including discomfort or occasionally
gynecomastia, changes in libido, hair loss, hirsutism,
fatigue, drowsiness, insomnia, fever, headache,
premenstrual syndrome-like symptoms and altered
menstrual cycles or irregular menstrual bleeding.
Rare: Anaphylaxis or anaphylactoid reactions, serum lipid
profile and liver function test alterations, and jaundice.
Drug Interactions:
Decreases effects of Lynestrenol:
Carbamazepine, Nevirapine, Oxcarbazepine, Phenytoin,
Phenobarbital, Topiramate, Rifabutin, Rifampicin
Increases side effects of the following drugs:
Atorvastatin, Tacrolimus
May enhance or reduce anticoagulant effect of Coumarins
e.g. Warfarin
Antagonizes the effect of Antidiabetics (hypoglycemic
effect)
Administration: Take one pill daily beginning on the first day
of menstrual bleeding or any other day as long as not
pregnant. Breastfeeding women can start six weeks after
giving birth. The interval between two pills should be 24
hours. If a pill is missed, take within three hours after the
24-hour lapse to sustain its efficacy.
Pregnancy Category: D
ATC Code: G03DC03
Rx NORETHISTERONE
Oral: 5 mg tablet (as acetate and as base)
Progestin-only contraception that acts by inhibiting
ovulation through thickening of cervical mucus, inhibiting
sperm penetration; altering FSH and LH concentrations;
slowing the movement of ovum through the fallopian
tubes, and modifying the endometrium.
Indications: Management of abnormal uterine bleeding,
amenorrhea, and endometriosis; contraception;
Contraindications: Current or history of deep vein
thrombosis, active or recent history of arterial
thromboembolic disease (e.g., stroke, MI); as a
diagnostic test for pregnancy; suspected or known
pregnancy; hepatic impairment or tumors
Dose:
Abnormal uterine bleeding and amenorrhea, by mouth,
ADULT, 2.5–10 mg once a day for 5–10 days; withdrawal
bleeding usually occurs within 3–7 days after the last
dose.
Endometriosis, by mouth, ADULT, 5 mg once a day for 14
days; increase dose at increments of 2.5 mg per day
GENITO URINARY SYSTEM AND SEX HORMONES
every 2 weeks until reaching 15 mg daily, continue for 6–
9 months or until presence of breakthrough bleeding.
Contraception, by mouth, ADULT, 350 micrograms once
daily; start on the first day of menstruation or after
miscarriage or abortion; if switching from a combined
oral contraceptive, begin on the day after finishing the
last active pill if the patient is not pregnant; if switching
from an UID, continue this or abstain or use an
alternative emergency contraceptive for at least 2 days
after contraceptive is initiated; in case of missed dose,
take as soon as remembered; if ≥3 hours late, use a
backup method of contraception for 48 hours. [NOTE:
Back up contraception is needed if therapy is initiated within 5
days of onset of menstruation. If started >5 days or at any time
women experienced amenorrhea, back up contraception should
be used for 2 days.]
Adverse Drug Reactions: Cerebral embolism, cerebral
thrombosis, deep vein thrombosis, edema, pulmonary
embolism, retinal thrombosis, depression, dizziness,
fatigue, headache, insomnia, migraine, emotional
lability, nervousness, acne vulgaris, alopecia, chloasma,
pruritus, skin rash, urticarial, amenorrhea, hirsutism,
hypermenorrhea, menstrual disease, weight gain,
abdominal pain, nausea, vomiting, breakthrough
bleeding, breast hypertrophy, breast tenderness, cervical
erosion, change in cervical secretions, decreased
lactation, genital discharge, mastalgia, spotting, vaginal
hemorrhage, hypersensitivity, cholestatic jaundice,
hepatitis, arm pain, leg pain, optic neuritis (with or
without vision loss)
Drug Interactions: No information found
Administration: Administer tablets at the same time each
day. NOT used for emergency contraception.
Pregnancy Category: X
ATC Code: G03DC02
GONADOTROPINS AND OTHER
OVULATION STIMULANTS
OVULATION STIMULANTS, SYNTHETIC
Rx CLOMIFENE
Oral: 50 mg tablet (as citrate)
A racemic mixture that acts at the level of the hypothalamus,
occupying the cell surface and intracellular estrogen
receptors (ERs) for longer durations than estrogen. It
inhibits receptor recycling, depletes hypothalamic ERs,
and prevents normal estrogenic negative feedback.
Inhibition of the feedback signal results in increased
pulsatile secretion of GnRH from the hypothalamus and
release of pituitary gonadotropins (FSH, LH) causing
growth of the ovarian follicle, followed by follicular
rupture.
Indications: Treatment of anovulatory infertility and male
infertility due to oligospermia
Contraindications: Hepatic disease or history of hepatic
impairment; abnormal uterine bleeding; enlargement or
development of ovarian cyst not due to polycystic ovarian
syndrome; uncontrolled thyroid or adrenal dysfunction;
presence of an organic intracranial lesion such as
pituitary tumor; pregnancy
Dose:
NOTE: Schedule intercourse to coincide with the expected
time of ovulation, usually 5–10 days after taking
Clomifene.
Ovulation induction, by mouth, ADULT (female), 50 mg once
a day for 5 days. Begin on or about the fifth day of cycle
if progestin-induced bleeding is expected or
G
spontaneous uterine bleeding occurs before starting
therapy. Therapy can be started anytime if there is no
recent uterine bleeding. Subsequent doses may be
increased to 100 mg once daily for 5 days only if
ovulation does not occur at the initial dose. Maximum
dose is 100 mg once a day for 5 days for 6 cycles (150
mg for women with PCOS). Long-term therapy of >6
cycles is not recommended; lower doses (12.5 to 25 mg
daily) can be used in women sensitive to clomiphene or
who consistently develop large ovarian cysts.
NOTE: May repeat 5-day cycle if needed as early as 30 days
after the previous therapy, ruling out the possibility of
pregnancy and using the lowest effective dose.
Discontinue treatment if ovulation does not occur after 3
courses of treatment; or if 3 ovulatory responses already
occurred but pregnancy is still not achieved.
Precautions:
Ovarian enlargement (generally regresses after stopping
treatment);
Visual disturbances;
Ovarian hyperstimulation syndrome;
Ascitic, pleural or pericardial fluids can be removed if
necessary to lessen symptoms (women with OHSS
should avoid pelvic examination and/or intercourse);
Borderline or invasive ovarian cancer;
Polycystic ovarian syndrome;
Patients unusually sensitive to pituitary gonadotropins;
Uterine fibroids
Adverse Drug Reactions:
Common: Ovarian enlargement
Less Common: Headache, hot flashes, breast discomfort,
abnormal uterine bleeding, distention,
bloating/discomfort, nausea, vomiting, visual symptoms
including blurred vision, diplopia, floaters, lights,
phosphenes, photophobia, scotomata, waves
Rare: Acute abdomen, alopecia, appetite increased,
constipation, depression, dermatitis, diarrhea, dizziness,
dry hair, fatigue, insomnia, lightheadedness,
nervousness, rash, urinary frequency/volume increased,
vaginal dryness, vertigo, weight gain or loss
Administration: Total daily dose should only be taken one at
a time to maximize effectiveness.
Pregnancy Category: X
ATC Code: G03GB02
181

ANTI-ANDROGENS
Rx CYPROTERONE
Oral: 50 mg tablet (as acetate)
Inj.: 100 mg/mL (as acetate), 3 mL ampule, depot (IM)
A steroid possessing anti-androgenic, anti-gonadotropic,
and progestin-like activity. It blocks binding of
dihydrotestosterone (DHT) to prostatic cancer cells and
utilizes negative feedback on hypothalamic-pituitary axis
by inhibiting luteinizing hormone (LH) secretion, leading
to decreased testosterone production.
G
Indication: Palliative treatment for advanced prostate
cancer
Contraindications: Hepatic disease or dysfunction; Dubin-
Johnson syndrome; Rotor syndrome; previous or existing
hepatic tumors (if not due to metastases from prostate
cancer); presence or history of meningioma; wasting
diseases (except inoperable prostate cancer); severe
chronic depression; existing thromboembolic processes
Dose:
Palliative treatment of advanced prostate cancer, by mouth,
ADULT (males), 200–300 mg once daily in 2–3 divided
doses; if following orchiectomy, reduce to 100–200 mg
once daily (maximum dose, 300 mg daily);
by IM injection, ADULT, 300 mg equivalent to 3 mL once
a week; if following orchiectomy, reduce to 300 mg every
2 weeks.
NOTE: Oral and IM administration may be interchanged but
must remain in the usual ranges (100–300 mg once
daily for oral route and 300 mg every 1 or 2 weeks for IM
route).
Precautions:
WARNING: Use is associated with dose-dependent
hepatotoxicity (jaundice, hepatitis, acute hepatic
failure) including fatal case reports with doses
≥100 mg daily. Hepatotoxicity typically develops
after a few weeks to several months of treatment
initiation. Use caution with concurrent use of other
hepatotoxic drugs. Monitor hepatic function and
discontinue in patients with evidence of hepatic
injury.
Adrenal cortical function suppression may occur;
Hypochromic anemia (monitor CBC regularly);
Metastatic prostate cancer;
Benign and malignant hepatic tumors (rule out the presence
of tumor in patients presenting with severe upper
abdominal discomfort, hepatic enlargement, or signs of
intraabdominal hemorrhage);
CNS depression
Lassitude, weakness, and fatigue;
Gynecomastia;
Thromboembolism;
Existing pulmonary dysfunction;
Familial defects of lipoprotein metabolism;
182
GENITO URINARY SYSTEM AND SEX HORMONES
Diseases aggravated by fluid retention or cardiovascular
disease;
History of depression (contraindicated in severe chronic
depression);
Diabetes or impaired glucose tolerance;
Fertility effects;
Pregnancy.
SKILLED TASKS. May cause drowsiness or blurred vision.
Avoid performing tasks, which require mental alertness,
e.g., operating machinery or driving.
Adverse Drug Reactions: Edema, heart failure, hypotension,
myocardial infarction, phlebitis, shock, stroke, syncope,
tachycardia, thrombosis (DVT, embolus, superficial
venous thrombosis), aphasia, chills, coma, depression,
dizziness, encephalopathy, fatigue, headache,
hemiplegia, lassitude, personality disorder, meningioma
(chronic therapy), psychotic depression, restlessness,
vascular headache, vasovagal reactions, dry skin (sebum
reduction), malaise, eczema, erythema nodosum,
exfoliative dermatitis, hirsutism, maculopapular rash,
patchy loss of body hair, pruritus, rash, photosensitivity,
scleroderma, skin discoloration, urticaria, adrenal
suppression (dose-related), benign nodular breast
hyperplasia, diabetes mellitus, galactorrhea,
gynecomastia, decreased libido, hypercalcemia, hot
flashes, hypernatremia, impotence, inhibition of
spermatogenesis, negative nitrogen balance, anorexia,
constipation, diarrhea, dyspepsia, glossitis, nausea,
pancreatitis, vomiting, weight gain/loss, bladder
carcinoma, urinary frequency, uterine fibroids enlarged,
uterine hemorrhage, anemia crystalluria, ascites,
cholestatic jaundice, cirrhosis, hepatic coma, hepatic
carcinoma, hepatic dysfunction (dose related), hepatic
failure, hepatitis, hepatoma, hepatic necrosis,
hepatomegaly, injection site reaction, abnormal gait,
myasthenia, abnormal accommodation, osteoporosis,
weakness, blindness, abnormal vision, optic neuritis,
optic atrophy, retinal vascular disorder, retinal vein
thrombosis, asthma, hematuria, renal failure, pulmonary
embolism, cough, dyspnea, hyperventilation, pulmonary
fibrosis, pulmonary oil microembolism, allergic reaction,
diaphoresis
NOTE: Reduces sperm count and volume of ejaculate at oral
doses of 30–50 mg daily. Infertility may be noted after
approximately 2 months of treatment. Changes are
reversible upon discontinuation of therapy, usually within
3–5 months, up to 20 months.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Cyproterone:
CYP3A4 Inhibitors
Enhances therapeutic effect of C1 Inhibitors (thrombogenic
effect)
Reduces therapeutic effect of Cyproterone:
Ethyl Alcohol (androgenic effect)
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Choline C11
GENITO URINARY SYSTEM AND SEX HORMONES
Avoid concomitant use with:
Decreases metabolism of Cyproterone:
CYP3A4 Inhibitors
Decreases serum concentration of Cyproterone:
CYP3A4 Inducers, Dabrafenib
Increases serum concentration of Cyproterone:
Mifepristone
Increases serum concentration of the following drugs:
Amodiaquine, HMG-CoA Reductase Inhibitors [except
Pitavastatin, Pravastatin, Rosuvastatin]
Reduces therapeutic effect of Cyproterone:
Ulipristal [for uterine fibroids, avoid progestins within 12
days of stopping ulipristal; for emergency contraception,
avoid progestins within 5 days of stopping ulipristal]
Reduces therapeutic effect of Anticoagulants
Administration:
For oral administration, take tablets at the same time each
day, after meals and with liquids. May be divided into
equal halves to facilitate swallowing.
For IM injection, administer slowly. Avoid IV injection to
prevent pulmonary microembolism.
Pregnancy Category: X
ATC Code: G03HA01
OTHER SEX HORMONES AND MODULATORS OF THE
GENITAL SYSTEM
Rx DANAZOL
Oral: 200 mg capsule
A synthetic derivative of ethisterone with weak androgenic
and anabolic properties. It suppresses pituitary output of
FSH and LH resulting to the regression and atrophy of
normal and ectopic endometrial tissues.
Indications: Treatment of endometriosis, fibrocystic breast
diseases, and hereditary angioedema
Contraindications: Undiagnosed genital bleeding;
pregnancy; breastfeeding; porphyria; markedly impaired
hepatic, renal, or cardiac function; androgen-dependent
tumor; thrombosis or thromboembolic disease (active or
history)
Dose:
Endometriosis, by mouth, ADULT (female),
mild disease, 200–400 mg daily;
moderate-to-severe, 800 mg daily in 2 divided doses;
continue therapy uninterrupted for 3–6 months up to 9
months.
Fibrocystic breast disease, by mouth, ADULT (female), 100–
400 mg daily in 2 divided doses; pain and tenderness
may be eliminated in 2–3 months; elimination of
nodularity may require therapy for 4–6 months.
Hereditary angioedema, by mouth, ADULT, 200 mg 2 to 3
times daily; after favorable response, decrease the
dosage to ≤100 mg at 1–3 months interval or longer if
needed; if an attack occurs, increase dose by up to 200
mg daily.
Precautions:
WARNING: Thromboembolism, thrombotic, and
thrombophlebitic events, including sagittal sinus
thrombosis and life-threatening or fatal strokes,
have been reported.
G
Peliosis hepatis and benign hepatic adenoma have
been reported with long-term use of the drug.
Has been associated with pseudomotor cerebri, a
case of benign intracranial hypertension.
Androgenic effects;
Blood lipid changes;
Diabetes;
Edematous condition;
Fibrocystic disease;
Porphyria;
Pregnancy (if patient becomes pregnant during treatment,
discontinue the drug, and appraise patient on the
potential risk to the fetus).
Adverse Drug Reactions:
Common and Less Common: Edema, flushing,
hypertension, MI, palpitation, tachycardia, depression,
dizziness, emotional lability, fainting, fatigue, headache,
nervousness, sleep disorders, Acne, alopecia, mild
hirsutism, maculopapular rash, papular rash, petechial
rash, pruritus, purpuric rash, seborrhea, urticaria,
vesicular rash, amenorrhea (may continue post therapy),
breast size reduction, glucose intolerance or glucagon
changes, libido changes, menstrual disturbances
(spotting, altered timing of cycle), semen abnormalities
(changes in volume, viscosity, sperm count or motility),
sex hormone and thyroid binding globulin changes,
constipation, gastroenteritis, nausea, vomiting,
spermatogenesis reduction, weight gain, vaginal
dryness, vaginal irritation, cholestatic jaundice, hepatic
adenoma, jaundice, malignant tumors (prolonged use),
peliosis, hepatis, back pain, extremity pain, joint lockup,
joint pain, joint swelling, muscle cramps, paresthesia,
spasms, neck pain, tremor, visual disturbances,
weakness, hematuria, Interstitial pneumonitis,
diaphoresis, voice change (hoarseness, sore throat,
instability, deepening of pitch), hepatotoxicity
(idiosyncratic)
Rare: Benign intracranial hypertension, anxiety, chills,
convulsions, Guillain Barré syndrome, erythema
multiforme, fever, Stevens-Johnson syndrome,
photosensitivity, clitoris hypertrophy, nipple discharge,
appetite changes, bleeding gums, pancreatitis, splenic
peliosis, pelvic pain, carpal tunnel syndrome, cataracts,
nasal congestion
183
 GENITO URINARY SYSTEM AND SEX HORMONES

Drug Interactions: Drug Interactions:

Monitor closely with: Monitor closely with:
Enhances therapeutic effect of C1 Inhibitors (thrombogenic Enhances therapeutic effect of Alpha-adrenoceptor
effect) Antagonists:
Anti-hypertensives, Aprepitant, Calcium Channel
Increases risk of adverse or toxic effects of Vitamin D Blockers (hypotensive effect), Cimetidine, Dasatinib,
Analogues [except Calcipotriene] (hypercalcemic effect) Fosaprepitant, Ivacaftor, Luliconazole, Netupitant

Increases risk of adverse or toxic effects of Danazol: Enhances therapeutic effect of Alpha-adrenoceptor
Corticosteroids (Dofetilide) Antagonists:
Nitroglycerin (hypotensive effect), Palbociclib,
Reduces therapeutic effect of Antidiabetic Agents Phosphodiesterase Inhibitors (hypotensive effect),
Simeprevir
Avoid concomitant use with:
G

Decreases metabolism of Carbamazepine Increases risk of adverse or toxic effects of Alpha-

adrenoceptor Antagonists:
Enhances therapeutic effect of Vitamin K Antagonists e.g. Beta Blockers (orthostatic hypotension), CYP3A4
Warfarin (anticoagulant effect) Inhibitors, e.g., Ketoconazole, Itraconazole, Ritonavir,
Dapoxetine (orthostatic hypotension), MAO Inhibitors
Increases risk of adverse or toxic effects of Cyclosporine [except Linezolid, Tedizolid] (orthostatic hypotension)
(hepatotoxic effect)
Reduces therapeutic effect of Alpha-adrenoceptor
Increases serum concentration of the following drugs: Antagonists:
Cyclosporine, HMG-CoA Reductase Inhibitors [except Alpha / Beta Agonists (vasoconstricting effect),
Fluvastatin, Pravastatin, Rosuvastatin], Bosentan, CYP3A4 Inducers, Deferasirox, Siltuximab,
Toclizumab
Increases serum concentration of the following drugs:
Pimozide, Simvastatin Avoid concomitant use with:
Decreases serum concentration of Alpha-adrenoceptor
Pregnancy Category: X Antagonists:
CYP3A4 Inducers, Dabrafenib
ATC Code: G03XA01
Enhances therapeutic effect of Alpha-adrenoceptor
Antagonists:
Alpha1 Blockers (antihypertensive effect),
UROLOGICALS Phosphodiesterase-5 Inhibitors e.g. Sildenafil
(antihypertensive effect), Protease Inhibitors e.g.,
Indinavir, Telaprevir
DRUGS USED IN BENIGN PROSTATIC
HYPERTROPHY (BPH) Enhances therapeutic effect of QTc-prolonging Agents
(Highest Risk)
ALPHA-ADRENOCEPTOR ANTAGONISTS
General Information Increases risk of adverse or toxic effects of Alpha-
adrenoceptor Antagonists:
Beta Blockers [except Levobunolol, Metipranolol],
Alpha–adrenoceptor blockers act preferentially on the
Stiripentol (orthostatic hypotension), CYP3A4 Inhibitors,
receptors in the lower urinary tract resulting to relaxation
Fusidic Acid, Mifepristone (orthostatic hypotension),
in the muscles of bladder and prostate.
Increases serum concentration of Alpha-adrenoceptor
Indications: Treatment of signs and symptoms of benign
Antagonists:
prostatic hypertrophy and relief of symptoms of urinary
CYP3A4 Inhibitors, Fusidic Acid, Telaprevir
obstruction
Reduces therapeutic effect of Alpha-adrenoceptor
Precautions:
Antagonists:
Hypotension;
Dabrafenib
Volume depletion;
Renal impairment;
Hepatic impairment;
Patients who are receiving an antihypertensive treatment Rx ALFUZOSIN
may require dose reduction and supervision;
Monitor for an improved urine flow and for “first dose”
orthostatic hypotension, headache, or GI disturbances, Oral: 10 mg tablet (as hydrochloride)
e.g., nausea, vomiting, at the beginning of therapy and
on a regular basis; An alpha1-selective adrenoceptor antagonist used in Benign
Elderly and patients undergoing cataract surgery (risk of Prostatic Hypertrophy (BPH) to relieve symptoms of
intraoperative floppy iris syndrome) urinary obstruction, including acute urinary retention.

184
GENITO URINARY SYSTEM AND SEX HORMONES
Indication: Treatment of functional symptoms of benign
prostatic hypertrophy
Contraindications: Moderate or severe hepatic impairment
Dose:
Benign prostatic hypertrophy, by mouth, ADULT, 10 mg once
daily.
NOTE: Do NOT use as an antihypertensive.
Dose Adjustment:
Renal Impairment:
Use with caution in patients with creatinine clearance <30
mL/minute.
Hepatic Impairment:
Use with caution in patients with mild impairment.
Adverse Drug Reactions:
Less Common: Dizziness, fatigue, headache, pain,
constipation, dyspepsia, nausea, impotence, upper
respiratory tract infection, bronchitis, pharyngitis,
sinusitis
Rare: Angina pectoris, angioedema, atrial fibrillation, chest
pain, diarrhea, edema, flushing, hepatic injury,
orthostatic hypotension, intraoperative floppy iris
syndrome, jaundice, priapism, pruritus, rhinitis, skin
rash, syncope, tachycardia, toxic epidermal necrolysis,
urticaria
Administration: Administer immediately following a meal at
the same time each day. Swallow tablets whole. Do NOT
crush or chew.
NOTE: Food increases extent of absorption.
See General Information on Alpha-Adrenoceptor
Antagonists under Drugs used in Benign Prostatic
Hypertrophy listed above for further information.
Pregnancy Category: B
ATC Code: G04CA01
Rx TAMSULOSIN
Oral: 200 micrograms capsule (as hydrochloride)
200 micrograms orally disintegrating tablet
400 micrograms prolonged-release FC tablet
An alpha1-selective adrenoceptor antagonist that is used in
mediating smooth muscle tone in the prostate to relieve
symptoms of urinary obstruction caused by BPH.
Indications: Treatment of sign and symptoms of BPH; relief
of symptoms of obstruction in BPH
Contraindications: History of micturition, syncope, and
postural hypotension
Dose:
Benign prostatic hypertrophy, by mouth, ADULT, 400
micrograms once daily.
NOTE: Do NOT use as an antihypertensive.
Dose may be increased after 2-4 weeks to 800
micrograms once daily in patients who fail to respond. If
therapy is interrupted for several days, restart with 400
micrograms once daily.
Dose Adjustment:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, use with caution.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Abnormal ejaculation, chest pain, dizziness,
drowsiness, fatigue, headache, insomnia, nasal
congestion, rhinitis, urinary urgency, weakness
Less Common: Blurred vision, dryness of mouth, edema,
G
first-dose hypotension, orthostatic hypotension,
increased sweating, nausea, palpitations, syncope,
tachycardia, urinary incontinence, vomiting
Rare: Angioedema, depression, dyspnea, hypersensitivity
reactions, itch, mood changes, paresthesia, rash,
urticaria, vertigo
Administration: Administer 30 minutes after the same meal
each day. Swallow capsules whole. Do NOT crush, chew,
or open.
NOTE: The extent and rate of absorption are reduced by the
presence of food.
See General Information on Alpha-Adrenoceptor
Antagonists under Drugs used in Benign Prostatic
Hypertrophy listed above for further information.
Pregnancy Category: B
ATC Code: G04CA02
Rx TERAZOSIN
Oral: 1 mg, 2 mg, and 5 mg tablet (as hydrochloride)
An alpha1-selective adrenoceptor antagonist used in BPH to
relieve symptoms of urinary obstruction, including acute
urinary retention.
Indications: For hypertension and lower urinary tract
symptoms (LUTS) associated with BPH; treatment of
signs and symptoms of BPH and relief of symptoms of
urinary obstruction
Dose:
Benign prostatic hypertrophy, by mouth, ADULT, 1 mg every
bedtime; may gradually increase at 7-day intervals
according to response; (maintenance dose, 5–10 mg
once every bedtime).
Adverse Drug Reactions:
Common: Dizziness, asthenia
Less Common: Hypotension, rhinitis, light-headedness,
somnolence, palpitation, nausea, edema, sinusitis,
dyspnea, fatigue, headache, back pain, flu-like
syndrome, tachycardia, amblyopia, blurred vision,
impotence, syncope
185
 GENITO URINARY SYSTEM AND SEX HORMONES

Administration: Administer with or without food once daily at crushed or broken tablets can be absorbed through the
bedtime. Give first dose and subsequent increase at skin and may negatively impact fetal development).
bedtime to prevent syncope.

See General Information on Alpha-Adrenoceptor

Antagonists under Drugs used in Benign Prostatic Adverse Drug Reactions:
Hypertrophy listed above for further information. Common: Orthostatic hypotension, dizziness, decreased
libido, impotence, neuromuscular and skeletal
Pregnancy Category: C weakness
Less Common: Edema, drowsiness, skin rash,
ATC Code: G04CA03 gynecomastia, decreased ejaculate volume, breast
tenderness, dyspnea, rhinitis
Rare: Altered mental status; change in libido, decreased
TESTOSTERONE-5-ALPHA testicular size, depression, disturbed sleep,
G

REDUCTASE INHIBITORS hypersensitivity (angioedema, facial swelling, pharyngeal

Rx FINASTERIDE
Oral: 5 mg tablet
A type II 5-alpha reductase inhibitor with anti-androgenic
properties due to the conversion of testosterone to
dihydrotestosterone.
Indications: Management of BPH; reduction of incidence of
acute urinary retention and need for surgery
NOTE: Although effective in partially relieving lower urinary
tract symptoms, therapy with and alpha1-adrenergic
blocker appears to result in greater improvement in
symptoms.
edema, pruritus, skin rash, swelling of the lips, swollen
tongue, urticaria), male infertility (temporary), malignant
neoplasm of the male breast, prostate cancer high
grade, prostatitis, reduction in penile curvature,
reduction in penile size, sexual disorder (may not be
reversible with discontinuation), testicular pain
Drug Interactions: No known significant interactions
Administration: May be administered with or without meals.
Pregnancy Category: X
ATC Code: G04CB01

Contraindications: Pregnant or women of childbearing age

Dose:
Benign prostatic hypertrophy, by mouth, ADULT, initially 1
mg at bedtime, subsequently increase stepwise to 2, 5,
or 10 mg once daily, as single drug or in combination, at
7-day intervals.

NOTE: A minimum of 6 months of treatment may be

necessary to determine if an individual will respond to
finasteride.

Dose Adjustment:
Hepatic Impairment:
Use with caution. Finasteride is metabolized extensively in
the liver.

Precautions:
WARNING: Decreases concentration of serum
markers of prostate cancer such as the Prostate
Specific Antigen (PSA) by up to 50% even if cancer
is present. Adjust reference values accordingly.

Monitor patients carefully with severely diminished urinary

flow;
Hepatic impairment (metabolized extensively in the liver);
Men at risk of obstructive uropathy;
Rule out prostate cancer before initiating treatment;
Pregnancy (women of childbearing age should not touch or
handle crushed or broken tablets; active ingredient of

186
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment:
SYSTEMIC HORMONAL Renal Impairment:
PREPARATIONS, EXCLUDING SEX In CrCl <50 mL/minute, use is contraindicated.
HORMONES AND INSULINS
Precautions:
Allergic reactions;
Hyponatremia;
PITUITARY AND HYPOTHALAMIC Thrombotic events (use with caution in patients
HORMONES AND ANALOGUES predisposed to thrombus formation);
Von Willebrand disease type 2B; Habitual or psychogenic
polydipsia (use with caution);
POSTERIOR PITUITARY LOBE HORMONES Primary nocturnal enuresis (interrupt treatment if the
patient experiences an acute illness, e.g. fever,
VASOPRESSIN AND ANALOGUES recurrent vomiting, or diarrhea);
Vigorous exercise;
Any condition associated with increase in water
Rx DESMOPRESSIN consumption;

H
Elderly and children.
Oral: 100 micrograms and 200 micrograms tablet (as
Adverse Drug Reactions:
acetate)
Inj.: 15 micrograms/mL (as acetate), 1 mL ampule (IM,
Common: Flushing (facial), headache, skin rash,
hyponatremia, water intoxication, abdominal cramps,
SC)
burning sensation at injection site, sore throat, erythema
or swelling at injection site, cough, nasal congestion,
A synthetic analogue of the antidiuretic hormone arginine
upper respiratory tract infection
vasopressin. It increases cAMP in renal tubular cells in a
dose dependent manner. This increases water
Less Common: Abnormality in thinking, agitation, balanitis,
chest pain, diarrhea, drowsiness, pain, coma, dyspepsia,
permeability, resulting in decreased urine volume and
insomnia, edema, localized warm feeling, palpitations,
increased urine osmolality, as well as increases plasma
photophobia, seizure, eye pruritus, tachycardia,
levels of von Willebrand factor, factor VIII, and tPA
vomiting, vulvar pain
contributing to a shortened activated partial
thromboplastin time (aPTT) and bleeding time.
Rare: Anaphylaxis, hypersensitivity reaction

Indications: For the treatment of central diabetes insipidus Drug Interactions:

and primary nocturnal enuresis in children aged 5 years Monitor closely with:
and above Increases risk of adverse or toxic effects of Desmopressin:
Carbamazepine, Chlorpromazine, Chlorpropramide,
Contraindications: Hyponatremia (current or a history of), Lamotrigine, Nonsteroidal Anti-Inflammatory Agents,
CrCl <50 mL/minute), type 2B or platelet type (pseudo) Opioid Analgesics e.g., morphine, fentanyl, Selective
von Willebrand’s disease; habitual or psychogenic Serotonin Reuptake Inhibitors e.g. Fluoxetine, Sertraline,
polydipsia; cardiac insufficiency; conditions requiring Tricyclic Antidepressants e.g., Amitriptyline Imipramine,
diuretic therapy (sublingual); nephrosis, severe hepatic Urea
dysfunction (sublingual)
Reduces therapeutic effect of Desmopressin:
Dose: Demeclocycline, Epinephrine [large doses], Ethyl Alcohol,
Nocturnal emesis, by mouth, ADULT and CHILD ≥5 years, Heparin, Lithium
initially 0.2 mg at bedtime, may be titrated up to 0.6 mg.
[NOTE: Limit fluid intake 1 hour prior to dose until the Avoid concomitant use with:
next morning, or at least 8 hours after administration]. Reduces therapeutic effect of Desmopressin:
Diabetes insipidus, IM, SC, ADULT, 2–4 micrograms (0.5–1 Tolvaptan
mL) daily in 2 divided doses;
Administration: Restrict fluid intake from 1 hour before to 8
by mouth, ADULT and CHILD ≥4 years, 0.05 mg twice daily;
hours after taking desmopressin tablets to decrease the
total daily dose should be increased or decreased as
possibility of water intoxication and hyponatremia.
needed to obtain adequate anti-diuresis (range: 0.1 to 1.2
mg 2–3 divided doses). [NOTE: Observe fluid restriction].
Pregnancy Category: B
Initial Dose Range ATC Code: H01BA02
Age (years) (micrograms, 2- (micrograms
3 times daily) daily)
Neonate 1–4 None stated
1 month -
10 30 – 150
2 years
2 – 12 50 100 – 800
12 – 18 100 200 – 1,200

187
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS
OXYTOCIN AND ANALOGUES
Rx CARBETOCIN
Inj: 100 mcg/mL, 1 mL ampule/vial, solution for injection
(IV)
Carbetocin binds oxytocin receptors located in uterine
smooth muscle producing rhythmic uterine contractions
characteristic to deliver, as well as increasing both the
frequency of existing contractions and uterine tone. It
enhances uterine involution early in postpartum.
Indications: Prevention of uterine atony and postpartum
hemorrhage following cesarean section under epidural
or spinal anesthesia.
H
Contraindications: Hypersensitivity to carbetocin, oxytocin,
or any component of the formulation; administration
prior to delivery of infant for any reason (including
elective or medical induction of labor); serious
cardiovascular disorders; use in children.
Dose:
Prevention of uterine atony and postpartum hemorrhage, by
IV injection, ADULT, 100 mcg (single dose only).
Dose Adjustment:
Renal and Hepatic impairment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
Antidiuretic effect and bleeding;
Use in caution in patients with asthma, cardiovascular
disease, epilepsy, and migraines.
Adverse Drug Reactions:
Common: Flushing, hypotension, headache, pruritus,
abdominal pain, nausea, vomiting, tremor, and feeling of
warmth.
Less Common: Chest pain, tachycardia, anxiety, chills,
dizziness, metallic taste, anemia, back pain, dyspnea,
and diaphoresis.
Drug Interactions:
Monitor closely with:
Increased levels/effects by Carbetocin:
Antipsychotic Agents (Second Generation), Hypotension-
Associated Agents, Levodopa-Containing Products.
Increases levels/effects of Carbetocin:
Alfuzosin, Barbiturates, Blood Pressure Lowering Agent,
Brimonidine, Carboprost.
Administration: Administer as bolus IV injection over 1
minute only after delivery of infant has been completed
by cesarean section. May administer before or after
delivery of placenta.
Pregnancy Category: C
ATC Code: H01BB03
188
Rx OXYTOCIN (SYNTHETIC)
Inj.: 10 IU/mL, 1 mL ampule (IM, IV)
A synthetic nonapeptide identical with oxytocin, a peptide
hormone, which participates in labor or delivery and
stimulates uterine contraction.
Indications: Prevention and treatment of postpartum and
post-abortion hemorrhage; induction and augmentation
of labor
Contraindications: Hypertonic uterine contractions;
mechanical obstruction to delivery; fetal distress; any
condition where spontaneous labor or vaginal delivery is
inadvisable; major cephalopelvic disproportion
Dose:
Induction of labor, by IV infusion, ADULT and ADOLESCENT,
initially 0.0005–0.001 IU/minute increased in 0.001–
0.002 IU/minute increments at intervals of 30 minutes
until up to 3–4 contractions occur every 10 minutes
(maximum rate, 0.02 IU/minute).
NOTE: Careful monitoring of fetal heart rate and uterine
motility is essential for dose titration. Discontinue
immediately in uterine hyperactivity or fetal distress.
Prevention of postpartum hemorrhage, by IM injection,
ADULT and ADOLESCENT, 10 IU when the anterior
shoulder is delivered or immediately after birth.
Prevention of postpartum hemorrhage, by slow IM injection,
ADULT and ADOLESCENT, 5 IU when the anterior
shoulder is delivered or immediately after birth.
Treatment of postpartum hemorrhage, by slow IV injection,
ADULT, 10-40 IU in 1000 mL of IV fluid at a rate sufficient
to control uterine atony; ADOLESCENT, 5-10 IU;
by IM injection, ADULT and ADOLESCENT, 10 IU, followed
in severe cases by a total of 40 IU, by intravenous
infusion, at a rate of 0.02-0.04 IU/minute; this should be
started after the placenta is delivered.
Dose Adjustment:
Renal Impairment:
Use with caution (increased risk of water retention and
oxytocin accumulation).
Precautions:
Oxytocin-resistant uterine inertia (avoid prolonged
administration);
Severe pre-eclamptic toxemia;
Severe cardiovascular disease;
Previous uterine surgery, multiple pregnancy, or >4 previous
births;
Induction or enhancement of labor in the presence of
borderline cephalopelvic disproportion (avoid use if
significant);
Mild-to-moderate pregnancy-associated hypertension or
cardiovascular disease;
Age >35 years;
History of low-uterine segment caesarean section;
Caudal block anesthesia;
Avoid tumultuous labor if fetal death or meconium-stained
amniotic fluid
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Adverse Drug Reactions:
Less Common: Nausea, vomiting
Rare: Anaphylactoid reaction, arrhythmias, ECG changes,
flushing, prolonged QT interval, rash, reflex tachycardia,
severe (tetanic) uterine spasm and contraction leading
to uterine rupture or fetal distress, hypoxia and death,
seizures, transient hypotension, water intoxication
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs due to enhanced vasopressor effect:
Ephedrine, Epinephrine
Administration: For IV bolus injection, administer slowly.
Avoid rapid injection due to risk of cardiovascular effects.
Avoid bolus IV injection during labor.
Head injury (high doses should not be used for the
management of head injury);
Ocular disease;
Hepatic impairment i.e. cirrhosis and renal impairment;
Osteoporosis;
Thyroid disease;
Stress (may require higher doses when subject to stress,
i.e., trauma, surgery, severe infection);
Elderly;
Children;
Pregnancy (use in early pregnancy may slightly increase the
risk of orofacial clefts);
Lactation (allow a 4-hour interval between administration
and breastfeeding).
Administration: For IM, intraarticular or intralesional use
only. Do NOT administer by IV or epidural injection. Avoid

H
injection into the deltoid muscle due to high incidence of
For IV infusion, monitor fluid balance to prevent water SC atrophy.
intoxication.
Use caution when transferring from systemic to inhaled
Avoid large volume infusions and restrict fluid intake to corticosteroids due to possible adrenal insufficiency or
prevent water intoxication and hyponatremia. withdrawal from steroids, including an increase in
allergic symptoms.
Pregnancy Category: X
NOTE: Withdraw therapy with gradual tapering of dose.
ATC Code: H01BB02 Chronic use may result in hypothalamic-pituitary adrenal
axis suppression, Cushing’s syndrome, and
hyperglycemia

CORTICOSTEROIDS FOR
SYSTEMIC USE
Rx DEXAMETHASONE
GLUCOCORTICOIDS Oral: 500 micrograms, 750 micrograms, 3 mg, and 4 mg
tablet
GENERAL INFORMATION Inj.: 4 mg/mL (as sodium phosphate), 1 mL and 2 mL
ampule / vial (IM, IV)
Glucocorticoids act as an anti-inflammatory agent by 5 mg/mL (as sodium phosphate), 1 mL ampule (IM,
suppressing the release of inflammatory proteins. It also IV)
aids in the biological response to stress, which includes
mobilization of fat and sugar stores in the body. A corticosteroid with mainly glucocorticoid activity, but lacks
mineralocorticoid properties.
Mode of Action: Glucocorticoids mimic the actions of
corticosteroids produced in the adrenal cortex and Indications: Management of a wide variety of inflammation
naturally found in the human body. and allergic disorders responsive to corticosteroid
therapy; management of asthma and related
Dose Adjustment: bronchospastic disorders; treatment of cerebral edema
Geriatric: caused by malignancy in intensive therapy or in
Use in the smallest effective dose for the shortest duration emergencies; prevention of nausea and vomiting
possible. induced by the cancer chemotherapy; treatment of all
conditions for which corticosteroid therapy is indicated
Precautions: except adrenal deficiency states; replacement therapy in
Adrenal suppression; adrenal insufficiency
Anaphylactoid reactions;
Diabetes; Contraindications: Systemic fungal infections; cerebral
Immunosuppression; malaria.
Latent TB;
Kaposi sarcoma; Dose:
Myopathy; Anti-inflammatory, by mouth or by IM or IV injection, ADULT,
Myasthenia gravis; 0.75–9 mg daily in divided doses every 6–12 hours.
Psychiatric disturbances; Anti-inflammatory or immunosuppressant, by mouth or by
Seizure disorders; IM or IV injection, CHILD, 0.08–0.3 mg/kg daily or 2.5–
Cardiovascular disease; Myocardial infarction; 10 mg/m2 daily in divided doses every 6–12 hours.
GI disease (avoid ethanol since this may enhance gastric For extubation or airway edema, by mouth or by IM or IV
mucosal irritation); injection, ADULT and CHILD, 0.5–2 mg/kg daily in

189
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS
divided doses every 6 hours beginning 24 hours prior to
extubation and continuing for 4–6 doses afterwards
Antiemetic, by mouth or by IV injection, ADULT, 10 to 20 mg
15–30 minutes before treatment on each treatment day;
by IV injection, CHILD, 10 mg/m2 per dose every 12–24
hours on days of chemotherapy for severely emetogenic
chemotherapy courses.
Type of Therapy for
Route Dose
Adults
10 mg every 12
Continuous Oral or
hours on each
infusion regimen IV
treatment day
Mildly emetogenic Oral, IM, 4 mg every 46
therapy or IV hours
H
Delayed nausea and vomiting, by mouth, ADULT, 4 to 10 mg
1–2 times daily for 2–4 days.
Multiple myeloma, by mouth or by IV injection, ADULT, 40
mg daily, days 1 to 4, 9 to 12, and 17 to 20, repeated
every 4 weeks, alone or as part of a regimen.
Multiple sclerosis, by mouth, ADULT, 30 mg daily for 1 week,
followed by 4–12 mg daily for 1 month.
Treatment of Addisonian crisis or shock, by IV injection,
ADULT, 4–10 mg as a single dose, may be repeated if
necessary.
Treatment of unresponsive shock, by IV route, ADULT, 1-6
mg/kg as a single dose or up to 40 mg initially followed
by repeat doses every 2–6 hours while shock persists.
Physiological replacement, by mouth or by IM or IV injection,
ADULT, as sodium phosphate, 0.03–0.15 mg/kg daily or
0.6 to 0.75 mg/m2 daily in divided doses every 6–12
hours; CHILD, 0.03 to 0.15 mg/kg daily or 0.6–0.75
mg/m2 daily in divided doses every 6-12 hours.
Croup or laryngotracheobronchitis, by mouth or by IM or IV
injection, CHILD, 0.6 mg/kg once (usual maximum dose,
16 mg; doses as high as 20 mg have been used), a single
oral dose of 0.15 mg/kg has been shown effective in
children with mild-to-moderate croup.
Bacterial meningitis, by IV injection, INFANT and CHILD >6
weeks, 0.15 mg/kg per dose every 6 hours for the first
2–4 days of antibiotic treatment; initiate 10–20 minutes
before or with the first dose of antibiotic.
Cushing's syndrome, diagnosis, by mouth, ADULT, 1 mg at
11 PM, draw blood at 8 AM; greater accuracy for
Cushing's syndrome may be achieved by the following:
0.5 mg every 6 hours for 48 hours (with 24­hour urine
collection for 17­hydroxycorticosteroid excretion)
Differentiation of Cushing's syndrome due to ACTH
excess from Cushing's due to other causes, 2 mg every 6
hours for 48 hours (with 24­hour urine collection for
17­hydroxy-corticosteroid excretion).
Adverse Drug Reactions: Arrhythmia, bradycardia, cardiac
arrest, cardiomyopathy, CHF, circulatory collapse,
edema, hypertension, myocardial rupture (post-MI),
syncope, thromboembolism, vasculitis, depression,
euphoria, emotional instability, headache, increased
intracranial pressure, insomnia, malaise, neuritis, mood
swings, personality changes, pseudotumor cerebri
(following discontinuation), seizure, psychic disorders,
vertigo, allergic dermatitis, acne, alopecia, angioedema,
bruising, dry skin, erythema, fragile skin, hypertrichosis,
hirsutism, hyperpigmentation or hypopigmentation, rash,
perianal pruritus (following IV injection), petechiae, skin
190
atrophy, impaired skin test reaction, striae, urticaria,
impaired wound healing, adrenal suppression,
decreased carbohydrate tolerance and glucose
intolerance, Cushing's syndrome, diabetes mellitus,
growth suppression (children), hypokalemic alkalosis,
hyperglycemia, menstrual irregularities, negative
nitrogen balance, protein catabolism, pituitary-adrenal
axis suppression, sodium retention, abdominal
distention, increased appetite, GI hemorrhage, GI
perforation, pancreatitis, peptic ulcer, ulcerative
esophagitis, weight gain; altered spermatogenesis,
hepatomegaly, nausea, arthropathy, aseptic necrosis
(femoral and humoral heads), fractures, muscle mass
loss, myopathy (in conjunction with neuromuscular
disease or neuromuscular-blocking agents),
thrombophlebitis, neuropathy, osteoporosis,
paresthesia, tendon rupture, weakness, vertebral
compression fractures, cataracts, exophthalmos,
glaucoma, increased intraocular pressure, glucosuria,
pulmonary edema, abnormal fat deposition,
anaphylactoid reaction, anaphylaxis, avascular necrosis,
diaphoresis, hiccups, hypersensitivity, impaired wound
healing, infections, Kaposi sarcoma, moon face,
secondary malignancy
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Dexamethasone:
Trastuzumab (neutropenic effect)
Enhances therapeutic effect of Warfarin (anticoagulant
effect)
Increases risk of adverse or toxic effects of Dexamethasone:
Denosumab (serious infections), Salicylates (GI
ulceration and bleeding)
Increases risk of adverse or toxic effects of the following
drugs:
Acetylcholinesterase Inhibitors e.g. pyridostigmine
edrophonium (increased muscular weakness),
Amphotericin B, Thiazide Diuretics, Loop Diuretics
(hypokalemic effect), Androgens (fluid-retaining effect),
COX-2 Inhibitors e.g. Celecoxib, Deferasirox (GI
ulceration or irritation; GI bleeding), NSAID (Non-
selective), Quinolone Antibiotics e.g. Levofloxacin
(tendonitis; tendon rupture)
Reduces absorption of Dexamethasone:
Bile Acid Sequestrants
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Calcitriol, Corticorelin (blunts
plasma ACTH response to corticorelin), Urea Cycle
Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of
Urea Cycle Disorder Agents needed to maintain
concentrations in the target range)
Avoid concomitant use with:
Decreases bioavailability of Dexamethasone:
Antacids [separate doses by at least 2 hours]
Decreases serum concentration of Dexamethasone:
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Fosphenytoin, Phenytoin
Rx HYDROCORTISONE
Decreases serum concentration of the following drugs:
Dasatinib, Fosphenytoin, Imatinib [increase Imatinib Oral: 5 mg and 20 mg tablet
dose by at least 50%], Nilotinib, Phenytoin, Rilpivirine, Inj.: 100 mg and 250 mg (as sodium succinate), vial (IV)
Ticagrelor [including its active metabolites], Vincristine 50 mg/mL (as sodium succinate), 2 mL vial (IM, IV)
125 mg/mL powder (as sodium succinate), 2 mL vial
Enhances therapeutic effect of Dexamethasone: (IV)
Nondepolarazing Neuromuscular-Blocking Agents e.g.
Pancuronium, Atracurium (neuromuscular effect) A glucocorticoid used for replacement therapy in adrenal
insufficiency, management of autoimmune and
Enhances therapeutic effect of Thalidomide (thrombogenic inflammatory conditions, and as emergency
effect) management of anaphylaxis and severe systemic
allergies.
Increases risk of adverse or toxic effects of Dexamethasone:
Nondepolarizing Neuromuscular-Blocking Agents, Indications: Management of autoimmune or inflammatory
(increased muscle weakness, possibly progressing to conditions; endocrinal disorders; management of all

H
polyneuropathies and myopathies)], Pimecrolimus, conditions requiring corticosteroids; replacement
Tacrolimus (Topical) therapy in cases of adrenocortical insufficiency (usually
in combination with a more potent mineral corticoid);
Increases risk of adverse or toxic effects of the following hypersensitivity reactions, such as anaphylactic shock
drugs: and angioedema; bilateral adrenalectomy
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia), Contraindications: Systemic fungal infections; serious
Thalidomide (dermatologic adverse effect), Tofacitinib infections, except septic shock or tuberculous
(immunosuppressive effect), Vaccines (Live) meningitis; viral, fungal, or tubercular skin lesions;
infective arthritis, skin or soft tissue infections near joints
Increases serum concentration of Dexamethasone: or a prosthetic joint; concurrent administration of live
Mifepristone virus vaccines and immunosuppressive doses of
corticosteroids; IM administration in idiopathic
Increases serum concentration of the following drugs: thrombocytopenia purpura; intrathecal administration
Fosphenytoin, Phenytoin
Dose:
Reduces therapeutic effect of Dexamethasone: Anti-inflammatory, by IV or IM injection, ADULT, 100 to 500
Mifepristone mg 3 or 4 times daily; CHILD, 2–4 mg/kg every 6 hours
for 24 hours, reduce over subsequent 24 hours or
Reduces therapeutic effect of the following drugs: change to oral prednisone
Aldesleukin (antineoplastic effect), BCG, (boosting by mouth, ADULT, 20–240 mg once daily.
effects), Hyaluronidase, Vaccines (Inactivated) Initial control of autoimmune disease, by IV injection,
[complete all age-appropriate vaccinations at least 2 ADULT, 100–500 mg 3 or 4 times daily according to
weeks prior to starting Dexamethasone; if vaccinated severity of condition.
during Dexamethasone therapy, revaccinate at least 3 Status asthmaticus, by IV injection, ADULT and CHILD, 1–2
months after discontinuation], mg/kg per dose every 6 hours for 24 hours, then
maintenance of 0.5–1 mg/kg every 6 hours.
Unknown impact on the therapeutic effect of Budesonide EC Physiologic replacement, by mouth, CHILD, 0.4–0.8 mg/m2
Tablets (could dissolve prematurely if given with drugs daily divided in 2–3 divided doses.
that lower gastric acid) Stress dosing, surgery in patients who are adrenally-
suppressed or on chronic systemic steroids, by IV
Administration: For oral administration, take after meals or injection, ADULT:
with food or milk to decrease GI effects. Increased
dietary intake of pyridoxine, vitamins A, B6, C, D, folate, Level of
calcium, zinc, and phosphorus is also recommended. Conditions Dose
Stress
See General Information on Corticosteroids for Systemic Inguinal
Minor 25 mg for 1 day
Use – Glucocorticoids listed under Chapter 6: Systemic herniorrhaphy
Hormonal Preparations for further information. 50–75 mg daily
Joint replacement, (25 mg every 8–
Moderate
Pregnancy Category: C cholecystectomy 12 hours) for 1–2
days
ATC Code: H02AB02 Pancreatico- 100–150 mg
duodenectomey, daily
Major esophago- (50 mg every 8–
gastrectomy, 12 hours) for 2–3
cardiac surgery days

191
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment: Increases risk of adverse or toxic effects of the following

Renal and Hepatic Impairment: drugs:
For mild-to-moderate impairment, dose reduction is Diuretics e.g., Furosemide, Hydrochlorothiazide
warranted. (hypokalemia), Drugs controlling Blood Glucose
For severe impairment, refer patient to a specialist. Concentration (may increase blood glucose
concentration; may alter control of diabetes),
Adverse Drug Reactions: Leflunomide (hematologic toxicity such as pancytopenia,
Common: Acne, adrenal suppression, amenorrhea, agranulocytosis, and/or thrombocytopenia), Tofacitinib
bruising, delayed wound healing, dyslipidemia, (immunosuppressive effect), Vaccines (Live)
dyspepsia, edema, fat redistribution, fractures, growth
retardation, hirsutism, hyperglycemia, hypertension, Increases serum concentration of Hydrocortisone:
hypokalemia, increased appetite, increased Mifepristone
susceptibility to infection, masking of signs of infection,
muscle weakness and wasting, myopathy, osteoporosis, Reduces therapeutic effect of Hydrocortisone:
psychiatric effects, skin atrophy, sodium and water Mifepristone
retention, weight gain
Less Common: Glaucoma, ocular hypertension, Reduces therapeutic effect of the following drugs:
H

osteonecrosis (femoral and humeral heads) Aldesleukin (antineoplastic effect), Amlodipine,

Rare: Anaphylactoid reaction, chorioretinopathy (central), Antihypertensives (e.g., Enalapril, Isosorbide Dinitrate,
euphoria, hypersensitivity reactions, hypomania, peptic Methyldopa), Diuretics (e.g., Furosemide,
ulceration, tendon rupture Hydrochlorothiazide (antagonizes hypotensive effect),
BCG (Intravesical)
Drug Interactions:
Monitor closely with: Reduces therapeutic effect of the following drugs:
Enhances therapeutic effect of Hydrocortisone: Hyaluronidase, Vaccines (Inactivated [complete all age-
Trastuzumab (neutropenic effect) appropriate vaccinations at least 2 weeks prior to
starting Dexamethasone; if vaccinated during
Enhances therapeutic effect of the following drugs: Dexamethasone therapy, revaccinate at least 3 months
Warfarin (anticoagulant effect) after discontinuation]), Vaccines (Live)

Increases risk of adverse or toxic effects of Hydrocortisone:
Denosumab (serious infections), Salicylates (GI
ulceration and bleeding)
Increases risk of adverse or toxic effects of the following
drugs:
Acetylcholinesterase Inhibitors (increased muscular
weakness), Amphotericin B, Thiazide Diuretics, Loop
Diuretics (hypokalemic effect), Androgens (fluid-
retaining effect), COX-2 Inhibitors e.g. Celecoxib,
Deferasirox (GI ulceration or irritation; GI bleeding),
NSAID (Non-selective), Quinolone Antibiotics (tendonitis;
tendon rupture)
Reduces absorption of Hydrocortisone:
Bile Acid Sequestrants
Reduces absorption of Calcium Salts
Unknown impact on the therapeutic effect of Budesonide EC
Tablets (could dissolve prematurely if given with drugs
that lower gastric acid)
Administration: Give directly or dilute in normal saline or
D5W. Administer within 24 hours after diluting.
See General Information on Corticosteroids for Systemic
Use – Glucocorticoids listed under Chapter 6: Systemic
Hormonal Preparations for further information.
Pregnancy Category: C; D in the 1st trimester
ATC Code: H02AB09

Reduces therapeutic effect of the following drugs:

Antidiabetic Agents, Calcitriol, Corticorelin (blunts
plasma ACTH response to Corticorelin), Urea Cycle
Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of
Urea Cycle Disorder Agents needed to maintain
concentrations in target range)

Reduces diagnostic effect of Coccidioides immitis Skin Test

Avoid concomitant use with:

Decreases bioavailability of Hydrocortisone:
Antacids [separate doses by at least 2 hours]

Increases risk of adverse or toxic effects of Hydrocortisone:

Nondepolarazing Neuromuscular-Blocking Agents,
(increased muscle weakness, possibly progressing to
polyneuropathies and myopathies), Pimecrolimus,
Tacrolimus (Topical)

192
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS
Rx METHYLPREDNISOLONE
Oral: 4 mg and 16 mg tablet
Inj.: 500 mg lyophilized powder (as sodium succinate), vial
(IM, IV)
1 g lyophilized powder (as sodium succinate), vial (IM,
IV)
125 mg/mL powder (as sodium succinate), 2 mL vial
+ diluent vial (IM, IV, IV infusion)
500 mg/7.7 mL powder (as sodium succinate), vial +
diluent vial (IM, IV, IV infusion)
500 mg/8.0 mL powder (as sodium succinate), vial +
diluent vial (IM, IV, IV infusion)
1 g/16 mL powder (as sodium succinate), vial +
diluent vial (IM, IV, IV infusion)
40 mg solution (as sodium succinate), single-dose vial
(IV, IM)
A synthetic glucocorticoid used principally as an anti-
inflammatory or immunosuppressant agent.
Indications: For the suppression of inflammatory and
allergic disorders, rheumatic diseases, and various skin
disorders; emergency management of acute idiopathic
thrombocytopenic purpura (ITP); management of the
chronic form of ITP
Contraindications: Systemic fungal infection; formulations
containing benzyl alcohol preservative are
contraindicated in premature infants; IM administration
in idiopathic thrombocytopenic purpura; intrathecal
administration
Dose:
Anti-inflammatory or immunosuppressive,
by mouth, ADULT, initially mg daily in 1–4 divided doses,
followed by a gradual reduction in dose to the lowest
effective dose;
by IM injection, ADULT, as sodium succinate, 10–80 mg
once daily;
by IM injection, ADULT, as acetate, 10–80 mg every 1–2
weeks;
by IV injection, ADULT, as sodium succinate, 10 to 40 mg
over a period of several minutes and repeated IV or IM at
intervals depending on the clinical response; when high
doses are required, a 30 mg/kg dose over a period of at
least 30 minutes may be given and may be repeated
every 4–6 hours for 48 hours;
by mouth or by IM or IV injection, CHILD, as sodium
succinate, 0.5–1.7 mg/kg daily or 5–25 mg/m2 daily in
divided doses every 6–12 hours (“pulse” therapy may
also be given at 15–30 mg/kg per dose for at least 30
minutes given once daily for 3 days).
Allergic condition, by mouth, ADULT
Asthma exacerbations, including status asthmaticus,
emergency medical care or hospital doses, by mouth or
IV injection, ADULT, 32–64 mg daily in 1–2 divided doses
until peak expiratory flow is 70% of predicted or personal
best; CHILD ≥12 years, 32–48 mg/kg daily in 2 divided
doses until symptoms resolve and peak expiratory flow is
80% of predicted or personal best; CHILD <12 years,
0.8–1.6 mg/kg daily in 2 divided doses (maximum, 60
mg daily), until peak expiratory flow is 80% of predicted
or personal best.
Severe persistent asthma or long-term control, by mouth,
ADULT and CHILD ≥12 years, 6–48 mg once daily or
every other day as needed for asthma control; CHILD
<12 years, 0.2–1.6 mg/kg once daily or every other day
as needed for asthma control (maximum dose, 48 mg).
For acute gout, by IM injection, ADULT, 4–120 mg.
For dermatomyositis or polymyositis, by IV injection, ADULT,
as sodium succinate, 1 g daily for 3–5 days for severe
muscle weakness, followed by conversion to oral
prednisone.
Adverse Drug Reactions:
Common: Arrhythmias, bradycardia, cardiac arrest,
cardiomegaly, circulatory collapse, congestive heart
failure, edema, hypertension, hypertrophic
cardiomyopathy (premature infants), myocardial rupture
(post-MI), fat embolism, syncope, tachycardia,
H
thromboembolism, vasculitis, delirium, depression,
emotional instability, euphoria, hallucinations,
headache, increased intracranial pressure, insomnia,
malaise, mood swings, nervousness, neuritis, personality
changes, psychic disorders, pseudotumor cerebri
(following discontinuation), seizure, vertigo, acne,
allergic dermatitis, alopecia, dry scaly skin, ecchymoses,
edema, erythema, hyperpigmentation or
hypopigmentation, rash, hirsutism, hypertrichosis,
impaired wound healing, petechiae, skin atrophy, sterile
abscess, impaired skin test reaction, striae, urticaria,
adrenal suppression, amenorrhea, increased
carbohydrate intolerance, Cushing's syndrome, diabetes
mellitus, fluid retention, glucose intolerance, growth
suppression (children), hyperglycemia, hyperlipidemia,
hypokalemia, hypokalemic alkalosis, menstrual
irregularities, negative nitrogen balance, pituitary-
adrenal axis suppression, protein catabolism, sodium
and water retention, abdominal distention, increased
appetite, GI hemorrhage, GI perforation, nausea,
pancreatitis, peptic ulcer, perforation of the small and
large intestine, ulcerative esophagitis, vomiting, weight
gain, leukocytosis (transient); hepatomegaly,
thrombophlebitis, arthralgia, arthropathy, aseptic
necrosis (femoral and humoral heads), fractures, muscle
mass loss, muscle weakness, myopathy (in conjunction
with neuromuscular disease or neuromuscular-blocking
agents), neuropathy, osteoporosis, paresthesia, tendon
rupture, vertebral compression fractures, weakness,
cataracts, glaucoma, glycosuria, pulmonary edema,
abnormal fat disposition, anaphylactoid reaction,
angioedema, avascular necrosis, anaphylaxis, increased
intraocular pressure, diaphoresis, hiccups,
hypersensitivity reactions, infections, exophthalmoses,
secondary malignancy
Rare: Venous thrombosis
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Methylprednisolone:
Trastuzumab (neutropenic effect)
Enhances therapeutic effect of Warfarin (anticoagulant
effect)
Increases risk of adverse or toxic effects of
Methylprednisolone:
Denosumab (serious infections), Salicylates (GI
ulceration and bleeding)
193
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Increases risk of adverse or toxic effects of the following

drugs: Rx PREDNISOLONE
Acetylcholinesterase Inhibitors (increased muscular
weakness), Amphotericin B (hypokalemic effect), Oral: 15 mg/5 mL syrup (as sodium phosphate), 60 mL
Androgens (fluid-retaining effect), COX-2 Inhibitor,
Deferasirox (GI ulceration or irritation; GI bleeding), Loop A synthetic glucocorticoid, which can decrease
Diuretics (hypokalemic effect), NSAIDs (Non-selective), inflammation by suppressing migration of
Quinolone Antibiotics (tendonitis; tendon rupture), polymorphonuclear leukocytes and by the reversal of
Thiazide Diuretics (hypokalemic effect) increased capillary permeability. It also suppresses the
immune system by reducing activity and volume of the
Reduces absorption of Methylprednisolone: lymphatic system.
Bile Acid Sequestrants
Indications: Relief of severe asthma; suppression of
Reduces diagnostic effect of Coccidioides immitis Skin Test inflammatory and allergic disorder

Reduces therapeutic effect of the following drugs: Contraindications: Acute superficial herpes simplex
Antidiabetic Agents, Calcitriol (Systemic), Corticorelin keratitis; live or attenuated virus vaccines; systemic
H

(blunts plasma ACTH response to Corticorelin), Urea fungal infections; varicella

Cycle Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of Dose:
Urea Cycle Disorder Agents needed to maintain NOTE: Asthma Exacerbations. For the short course
concentrations in target range) outpatient “burst” type, continue burst until symptoms
resolve and the peak expiratory flow is at least 80% of
Avoid concomitant use with: personal best.
Decreases bioavailability of Methylprednisolone:
Antacids [separate doses by at least 2 hours] Asthma exacerbations, by mouth, ADULT and CHILD ≥12
years, dose will depend on the type of treatment:
Increases risk of adverse or toxic effects of
Methylprednisolone: Type of
Neuromuscular-blocking agents [Non-depolarizing Guideline Dose
Treatment
(increased muscle weakness, possibly progressing to Global 1mg/kg daily as a
polyneuropathies and myopathies)], Pimecrolimus, Management
Initiative for single daily dose
Tacrolimus in primary
Asthma usually given for 5–
care or acute
(GINA) 7 days (maximum,
Increases risk of adverse or toxic effects of the following care facility
2015 50 mg daily).
drugs: 40–80 mg daily in
Leflunomide (hematologic toxicity such as pancytopenia, Asthma a single dose or in
agranulocytosis, and/or thrombocytopenia), Tofacitinib exacerbation 2 divided doses
(immunosuppressive effect), Vaccines (Live) (emergency until peak
care or expiratory flow is
Increases serum concentration of Methylprednisolone: hospital 70% of the
Mifepristone National
doses) predicted or
Asthma personal best.
Reduces therapeutic effect of Methylprednisolone: Education
Short course 40–60 mg daily in
Mifepristone and
outpatient a single dose or in
Prevention
“burst” (acute 2 divided doses for
Reduces therapeutic effect of the following drugs: Program
asthma) 5 to 10 days.
Aldesleukin (antineoplastic effect), BCG (Intravesical), (NAEPP)
7.5–60 mg daily
Hyaluronidase, Vaccines (Inactivated [complete all age- 2007
given as a single
appropriate vaccinations at least 2 weeks prior to
dose in the
starting Dexamethasone; if vaccinated during Long-term
morning or every
Dexamethasone therapy, revaccinate at least 3 months treatment
other day as
after discontinuation]), Vaccines (Live)
needed for control
of asthma.
Unknown impact on the therapeutic effect of Budesonide EC
Tablets (could dissolve prematurely if given with drugs
that lower gastric acid) Asthma exacerbations, by mouth, CHILD <12 YEARS, dose
will depend on the age of the child,
See General Information on Corticosteroids for Systemic Based on the Global Initiative for Asthma (GINA)
Use – Glucocorticoids listed under Chapter 6: Systemic 2015:
Hormonal Preparations for further information. Age Maximum Dose
Dose
(Years) (mg daily)
Pregnancy Category: C 1–2 mg/kg daily for up
<3 20
to 5 days
ATC Code: H02AB04 1–2 mg/kg daily for up
3–5 30
to 5 days

194
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

1–2 mg/kg daily weakness, cataracts, exophthalmus, eyelid edema,

6–11 usually given for 3–5 40 glaucoma, increased intraocular pressure, epistaxis,
days increased diaphoresis, irritation, impaired wound healing
Rare: Venous thrombosis
Based on the National Asthma Education and
Prevention Program (NAEPP) 2007 Guidelines: Drug Interactions:
Type of Monitor closely with:
Dose Enhances therapeutic effect of Prednisolone:
Treatment
Asthma Trastuzumab (neutropenic effect)
1–2 mg/kg daily in 2 divided
exacerbation
doses (maximum, 60 mg daily) Enhances therapeutic effect of Warfarin (anticoagulant
(emergency
until peak expiratory flow is 70% effect)
care or hospital
of the predicted or personal best.
doses)
Short course 1–2 mg/kg daily as a single dose Increases risk of adverse or toxic effects of Prednisolone:
outpatient or in 2 divided doses for 3–10 Denosumab (serious infections), Salicylates (GI
“burst” (acute days (maximum dose, 60 mg ulceration and bleeding)
asthma) daily).

0.25–2 mg/kg daily as a single
dose in the morning or every
Long-term
other day as needed for control of
treatment
asthma (maximum dose, 60 mg
daily).
Rheumatoid arthritis, by mouth, ADULT, initially 5–7.5 mg
daily, then adjust dose as needed.
Multiple sclerosis, by mouth, ADULT, 200 mg daily for 1
week followed by 80 mg every other day for 1 month.
Anti-inflammatory or immunosuppressant, by mouth,
ADULT, 5–60 mg in 2–4 divided doses (maintenance,
2.5–15 mg daily); CHILD, 1–2 mg/kg once daily
(maximum, 60 mg daily).
Nephrotic syndrome, by mouth, CHILD, for the first 3
episodes, initially 2 mg/kg daily or 60 mg/m2 daily
(maximum, 80 mg daily) in 3–4 divided doses until urine
is protein-free for 3 consecutive days (maximum of 28
days), followed by 1–1.5 mg/kg per dose or 40 mg/m2
per dose given every other day for 4 weeks; for frequent
relapses, 0.5–1 mg/kg per dose as maintenance every
other day for 3–6 months.
Dose Adjustment:
Renal Impairment:
For patients undergoing hemodialysis, administer
appropriate dose post-hemodialysis since the drug is
slightly dialyzable.
Precautions:
Cataracts; Glaucoma
Adverse Drug Reactions:
Common: Cardiomyopathy, CHF, edema (including facial),
hypertension, headache, insomnia, malaise,
nervousness, pseudotumor cerebri, psychic disorders,
seizure, vertigo, bruising, facial erythema, hirsutism,
petechiae, skin test reaction suppression, thin fragile
skin, urticaria, decreased carbohydrate tolerance,
Cushing's syndrome, growth suppression,
hyperglycemia, diabetes mellitus, hypernatremia,
hypokalemia, hypokalemic alkalosis, menstrual
irregularities, negative nitrogen balance, pituitary-
adrenal axis suppression, abdominal distention,
increased appetite, indigestion, nausea, pancreatitis,
peptic ulcer, ulcerative esophagitis, weight gain,
arthralgia, aseptic necrosis (humeral or femoral heads),
fractures, tendon rupture, decreased muscle mass,
muscle weakness, osteoporosis, steroid myopathy,
H
Increases risk of adverse or toxic effects of the following
drugs:
Acetylcholinesterase Inhibitors e.g. Neostigmine,
Edrophonium (increased muscular weakness),
Amphotericin B (hypokalemic effect), Androgens e.g.
Testosterone (fluid-retaining effect), COX-2 Inhibitors,
Deferasirox (GI ulceration or irritation; GI bleeding), Loop
Diuretics, Thiazide Diuretics (hypokalemic effect),
NSAIDs (Non-selective), Quinolone Antibiotics e.g.
Levofloxacin (tendonitis; tendon rupture)
Reduces absorption of Prednisolone:
Bile Acid Sequestrants e.g. Cholestryramine
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Calcitriol (Systemic), Corticorelin
(blunts plasma ACTH response to Corticorelin), Urea
Cycle Disorder Agents (increases protein catabolism and
plasma ammonia concentrations, increasing doses of
Urea Cycle Disorder Agents needed to maintain
concentrations in target range)
Avoid concomitant use with:
Decreases bioavailability of Prednisolone:
Antacids [separate doses by at least 2 hours]
Increases risk of adverse or toxic effects of Prednisolone:
Nondepolarizing Neuromuscular-blocking Agents
(increased muscle weakness, possibly progressing to
polyneuropathies and myopathies), Pimecrolimus,
Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia), Tofacitinib
(immunosuppressive effect), Vaccines (Live)
Increases serum concentration of Prednisolone:
Mifepristone, Ritonavir
Reduces therapeutic effect of Prednisolone:
Mifepristone
Reduces therapeutic effect of the following drugs:
Aldesleukin (antineoplastic effect), BCG (Intravesical),
Hyaluronidase, Vaccines (Inactivated [complete all age-

195
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS
appropriate vaccinations at least 2 weeks prior to
starting Dexamethasone; if vaccinated during
Dexamethasone therapy, revaccinate at least 3 months
after discontinuation]), Vaccines (Live)
Unknown impact on the therapeutic effect of Budesonide EC
Tablets (could dissolve prematurely if given with drugs
that lower gastric acid)
Administration: Should be taken after meals or with food or
milk to decrease GI effects. Increased dietary intake of
pyridoxine, vitamins A, B6, C, D, folate, calcium, zinc, and
phosphorus is also recommended.
See General Information on Corticosteroids for Systemic
Use – Glucocorticoids listed under Chapter 6: Systemic
Hormonal Preparations for further information.
H
Pregnancy Category: C or D (product-specific)
ATC Code: H02AB06
Rx PREDNISONE
Oral: 5 mg, 10 mg, and 20 mg tablet
10 mg/5 mL suspension, 60 mL
A corticosteroid with glucocorticoid and anti-inflammatory
effects that can suppress adrenal function at high doses.
It is rapidly converted to the prednisolone in the body. Its
antitumor effects may be related to the inhibition of
glucose transport, phosphorylation, or induction of cell
death in immature lymphocytes. Its antiemetic effects
are thought to occur due to blockade of cerebral
innervations of the emetic center by inhibiting
prostaglandin synthesis.
Indications: Management of autoimmune disease; croup;
short-term suppression of inflammation in allergic
disorders; Pneumocystis carinii pneumonia; atopic
dermatitis; dermatomyositis or polymyositis; nephrotic
syndrome (idiopathic or related to lupus erythematosus);
immune-mediated thrombocytopenia; inflammatory
bowel disease; eye inflammation; rheumatic disease;
immunosuppression; acute severe asthma (reliever);
severe persistent asthma not responding to high-dose
inhaled steroids, long-acting agonists, and
methylxanthines (controller); adrenal insufficiency
Contraindications: Untreated systemic fungal infections;
administration of live attenuated virus vaccines with
immunosuppressive doses of prednisone
Dose:
NOTE: No definitive treatment guidelines exist. Dosing is
dependent on institution protocols and individual
response.
General dosing range, by mouth, initially 5–60 mg daily:
RECOMMENDATIONS ON APPROPRIATE USE:
Prior to use, dose and duration of treatment should be
based on the risk versus benefit for each individual
patient. Generally, use the smallest effective dose for the
196
shortest duration of time to minimize the adverse events.
Consider alternate day therapy for long-term therapy to
reduce adverse effects.
Dosage for infants and children should be based on severity
of the disease and response of the patient rather than
age, weight, or body surface area.
Gradually taper dose prior to discontinuing therapy,
especially long-term therapy. Abrupt withdrawal may
precipitate acute adrenal insufficiency.
Individualize tapering of dose based on the disease and
severity of condition. For example, the dose may be
tapered off by 10–20% every 3–5 days until a dose of 10
mg daily is reached. A slower weekly tapering is
recommended.
Autoimmune or inflammatory disease, by mouth, ADULT,
initially 5–60 mg once daily depending on the disease
and its severity, adjust dose according to response and
recommended guidelines; CHILD, initially 1–2 mg/kg
once daily (usual maximum dose, 60 mg) with dose
adjustments based on guidelines.
Croup, by mouth, CHILD, 1 mg/kg; repeat dose after 12–24
hours if necessary.
Pneumocystis carinii pneumonia, by mouth, ADULT, begin
within 72 hours of PCP therapy: 40 mg twice daily for 5
days, followed by 20 mg once daily for 11 days or until
antimicrobial regimen is completed; CHILD, 1 mg/kg
twice daily for 5 days, followed by 0.5–1 mg/kg twice
daily for 5 days, followed by 0.5 mg/kg once daily for 11–
21 days.
Acute asthma, by mouth, ADULT, 40–60 mg daily for 3–10
days as a single dose or in 2 divided doses; CHILD <12
years, 1–2 mg/kg daily for 3–10 days, with a maximum
of 60 mg daily.
Rheumatoid arthritis, by mouth, ADULT, ≤10 mg daily
[NOTE: Once the condition has stabilized, reduce to the
minimum required to maintain control of disorder.]
Acute gout, by mouth, ADULT, initially at least 0.5 mg/kg for
5–10 days.
Dermatomyositis/polymyositis, by mouth, ADULT, 1 mg/kg
daily (range of 0.5–1.5 mg/kg daily), often in conjunction
with steroid-sparing therapies.
Immune thrombocytopenia, by mouth, ADULT, 1–2 mg/kg
daily.
Nephrotic syndrome, by mouth, CHILD, initially 2 mg/kg
daily or 60 mg/m2 daily in 1–3 divided doses, with a
maximum of 80 mg daily until urine is protein free for 4–
6 weeks; followed by a maintenance dose of 2 mg/kgor
40 mg/m2every other day in the morning; discontinue
after 4–6 weeks by gradual tapering.
Lupus nephritis, induction, by mouth, ADULT, the following
doses apply:
Lupus
Nephritis Dose
Class
0.5–1 mg/kg daily (after glucocorticoid pulse)
III–IV
tapered, after a few weeks, to the lowest
effective dose, combined with an
immunosuppressive agent
0.5 mg/kg daily for 6 months combined with
mycophenolate mofetil and, if no improvement is
V seen after 6 months, use 0.5–1 mg/kg daily
(after glucocorticoid pulse) for an additional 6
months combined with cyclophosphamide
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Dose Adjustment: Dose:

Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted.
For severe impairment, refer patient to a specialist.
Adverse Drug Reactions:
Common: Acne, adrenal suppression, amenorrhea,
bruising, delayed wound healing, dyslipidemia,
dyspepsia, edema, fat redistribution, fractures, growth
retardation, hirsutism, hyperglycemia, hiccups,
hypertension, hypokalemia, increased appetite,
increased susceptibility to infections, malaise, masking
of signs of infection, muscle weakness and wasting,
myopathy, nausea, osteoporosis, psychiatric effects, skin
atrophy, sodium and water retention, weight gain
Less Common: Glaucoma, ocular hypertension,
Chronic hypothyroidism, by mouth, CHILD, initially 25
micrograms daily, adjust by 25 micrograms every 2–4
weeks.
Congenital hypothyroidism, juvenile myxedema, by mouth,
NEONATE ≤1 month, initially 5–10 micrograms/kg daily,
adjust by 25 micrograms every 2–4 weeks until mild
toxic symptoms appear, then reduce dose slightly;
INFANT and CHILD >1 month, 5 micrograms/kg daily,
adjust by 25 micrograms every 2–4 weeks until mild
toxic symptoms appear, then reduce dose slightly.
Severe hypothyroidism, by mouth, ADULT, initially 12.5–25
micrograms daily, adjust by 25 micrograms every 2–4
weeks, as appropriate; CHILD, initially 25 micrograms
daily, adjust by 25 micrograms every 2–4 weeks
Subclinical hypothyroidism, if treated, by mouth, ADULT, 1
microgram/kg daily.

H
Osteonecrosis or aseptic necrosis (femoral and humeral Hypothyroidism, by mouth, ADULT, usually 1.6–1.7
heads) micrograms/kg daily, may give full dose right away if
Rare: Anaphylactoid reaction, chorioretinopathy (central), without contraindications; for most, initially 50–100
euphoria, hypersensitivity reactions, hypomania, peptic micrograms daily before breakfast (25–50 micrograms
ulceration, tendon rupture for patients >50 years), increase by 25–50 micrograms
every 3 to 4 weeks until normal metabolism is
Drug Interactions: maintained (maintenance dose, 100–200 micrograms
NOTE: Prednisone is a substrate for CYP3A-based daily);
interaction. CHILD, dose would depend on the age:
Age Daily Dose (microgram/kg)
Please see Drug Interactions under Prednisolone
1–3
10–15
months*
Administration: Best taken with food. Taking it early in the
morning reduces possible side effects. 3–6 months 8–10
6–12
6–8
See General Information on Corticosteroids for Systemic months
Use – Glucocorticoids listed under Chapter 6: Systemic 1–5 years 5–6
Hormonal Preparations for further information. 6–12 years 4–5
>12 years 2–3
Pregnancy Category: C; D in the 1st trimester [NOTE: For infants 1-3 months at risk for developing
cardiac failure, administer a lower starting dose of 25
ATC Code: H02AB07 micrograms daily. If the initial serum thyroxine is
below 5 micrograms/dL, begin treatment at a higher
dose of 50 micrograms daily (12–17 micrograms/kg
daily).];
THYROID THERAPY
in cardiac disease, initially 25 micrograms daily or 50
THYROID PREPARATIONS micrograms on alternate days, adjusted by 25
micrograms every 4 weeks);
dosing for specific populations:
Rx LEVOTHYROXINE
Population Dose
Oral: 50, 100, and 150 micrograms tablet (as Adults <50 years;
1.6–1.7
sodium/anhydrous sodium) children in whom
micrograms/kg daily;
growth and puberty
usually ≤200
A synthetic form of thyroxine (T4), a thyroid hormone are complete; adults
micrograms daily;
involved in normal metabolism, growth, and >50 years recently
titrate dose every 6
development. It promotes gluconeogenesis, increase treated for
weeks; may give full
utilization of glycogen stores, stimulate synthesis of hyperthyroidism or
dose right away if
proteins, and increase basal metabolic rate. who have been
without
hypothyroid for only a
contraindications.
Indications: Management of hypothyroidism of any etiology; few months
TSH suppression Initially 25–50
Adults <50 years with micrograms daily,
Contraindications: Hyperthyroidism from any cause; acute or without cardiac adjust by 12.5–25
MI; untreated subclinical (suppressed serum TSH level disease microgram
with normal T3 and T4 levels); overt thyrotoxicosis of any increments at 6– to
etiology; uncorrected adrenal insufficiency

197
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS
8-week intervals, as
needed.
Initially 12.5–25
micrograms daily,
then adjusted by
Adults >50 years with
12.5–25 microgram
cardiac disease
increments at 4- to
6-week intervals, as
needed.
TSH suppression in well-differentiated thyroid cancer,
papillary and follicular, by mouth, ADULT, dose is highly
individualized; in general, more than 2 micrograms/kg
daily may be needed to suppress TSH to <0.1 mIU/L in
intermediate- to high-risk tumors; low-risk tumors may be
maintained at 0.1–0.5 mIU/L.
TSH suppression in benign nodules and nontoxic
H
multinodular goiter, by mouth, ADULT, initially 1.7–2
micrograms/kg daily may be used with a target TSH of
0.1–0.3 mIU/L [NOTE: Routine use is not recommended.
Avoid if TSH is already suppressed].
Dose Adjustment:
Geriatric:
Introduce gradually to avoid sudden increase in metabolic
demands. Maintenance replacement dose may be less
than in younger people.
The initial dose should not exceed 25–50 micrograms daily.
Maintain at intervals of at least 4 weeks.
Cardiovascular disorders (angina, heart failure, myocardial
infarction or insufficiency, hypertension):
Lower initial doses. Smaller increments and longer intervals
between increases could be necessary. Full replacement
dose may not be appropriate. Use with caution and
reduce dose as needed.
Long-standing Hypothyroidism:
Introduce gradually to avoid sudden increase in metabolic
demands. Maintenance replacement dose may be less
than in younger people.
Precautions:
WARNING: Use with caution in patients with underlying
coronary artery disease, previous MI, or acute coronary
syndromes and tachyarrhythmias.
Thyroid supplements are ineffective and potentially toxic
when used for the treatment of obesity or for weight
reduction, especially in euthyroid patients. High doses may
produce serious or even life-threatening toxic effects,
particularly when used with some anorectic.
Cardiovascular disorders, including angina, heart failure,
myocardial infarction or insufficiency, and hypertension;
Hypopituitarism or predisposition to adrenal insufficiency
(correct with a corticosteroid prior to treatment with
levothyroxine to prevent precipitation of an acute adrenal
crisis, e.g., panhypopituitarism);
Adrenal insufficiency (in uncorrected adrenal insufficiency,
glucocorticoid treatment should precede use of
levothyroxine);
Myxedema;
Diabetes insipidus or diabetes mellitus (may need to
increase dose of insulin or oral antidiabetic drug);
198
Myasthenic syndrome;
Osteoporosis;
Benign thyroid nodules (treatment should never be fully
repressive;
Avoid use in postmenopausal women, men more than 60
years of age, patients with cardiovascular disease,
osteoporosis, or systemic illness, and patients with large
thyroid nodules or long-standing goiters, or low-normal
TSH levels);
Elderly;
Pregnancy (monitor thyroid function each trimester;
reassess thyroxine maintenance dosage 6–8 weeks
post-partum);
Lactation (amount is too small to affect tests for neonatal
hypothyroidism).
Adverse Drug Reactions:
Common: Anginal pain, excitability, headache, flushing,
muscular weakness, restlessness, sweating, vomiting,
weight loss
Less Common: Cramps, diarrhea, nervousness, insomnia,
palpitations, tachycardia
Rare: Arrhythmias, decreased bone density (women),
papilledema, seizures, tremors
Drug Interactions:
Monitor closely with:
Decreases metabolism of Theophylline (hypothyroidism)
Enhances therapeutic effect of the following drugs:
Anticoagulants e.g. Warfarin, Tricyclic Antidepressants
e.g. (stimulatory effect)
Increases metabolism of Levothyroxine, increasing its
requirements in hypothyroidism:
Phenobarbital, Phenytoin, Rifampicin
Increases risk of adverse or toxic effects of Levothyroxine:
Piracetam (confusion, irritability, and sleep disorders)
Increases risk of adverse or toxic effects of the following
drugs:
Tricyclic Antidepressants (arrhythmogenic effect)
Reduces therapeutic effect of Levothyroxine:
Selective Serotonin Reuptake Inhibitors
Avoid concomitant use with:
Decreases serum concentration of Levothyroxine:
Aluminum Hydroxide [administer at least 4 hours apart],
Bile Acid Sequestrants [administer 4 hours prior to
Colesevelam; administer at least 1 hour before or 4–6
hours after Cholestyramine]
Decreases serum concentration of Levothyroxine:
Calcium Polystyrene Sulfonate [separate dosing or
administer Calcium Polystyrene Sulfonate rectally],
Lanthanum [administer at least 2 hours apart],
Magnesium Salts [administer at least 4 hours apart],
Multivitamins / Minerals (with ADEK, Folate, Iron)
[administer at least 4 hours apart], Sevelamer, Sodium
Polystyrene Sulfonate [separate dosing or administer
Sodium Polystyrene Sulfonate rectally], Sucroferric
Oxyhydroxide
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Reduces absorption of Levothyroxine, reducing its Hypothyroidism;

therapeutic effect, resulting to hypothyroidism: Lupus-like syndrome;
Calcium Salts [administer at least 4 hours apart], Nephritis;
Ciprofloxacin, Ferrous Salts [administer at least 4 hours Interstitial pneumonitis; Vasculitis
apart], Orlistat, Raloxifene, Simethicone
Adverse Drug Reactions: Allergy, periarteritis, edema,
Reduces therapeutic effect of Sodium Iodide I 131 vasculitis (ANCA-positive, cutaneous, leukocytoclastic),
drowsiness, headache, drug fever, neuritis, paresthesia,
Administration: Should be taken in the morning on an empty vertigo, alopecia, dermal ulcer, erythema nodosum,
stomach, at least 30–90 minutes before food intake. exfoliative dermatitis, pruritus, skin pigmentation, skin
rash, Stevens-Johnson syndrome, toxic epidermal
The tablet may be crushed and suspended in 5 to 10 mL necrolysis, urticaria, ageusia, dysgeusia, nausea, salivary
water, however, this must be used immediately. gland disease, stomach pain, vomiting, agranulocytosis,
aplastic anemia, granulocytopenia,
Pregnancy Category: A hypoprothrombinemia, acute hepatic failure,
hemorrhage, leukopenia, lymphadenopathy,
ATC Code: H03AA01 thrombocytopenia, hepatitis, hepatotoxicity, jaundice,

H
arthralgia, lupus-like syndrome, splenomegaly, myalgia,
acute renal failure, glomerulonephritis, nephritis;
ANTITHYROID PREPARATIONS interstitial pneumonitis, pulmonary alveolar hemorrhage;
fever

Rx PROPYLTHIOURACIL Drug Interactions:

Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Oral: 50 mg tablet drugs:
Clozapine (agranulocytosis), Dipyrone (agranulocytosis
An antithyroid agent derived from thiourea. It inhibits the and pancytopenia)
peripheral conversion of thyroxine to triiodothyronine in
the tissues. Reduces therapeutic effect of the following drugs:
BCG, Intravesical, Sodium Iodide I 131 [discontinue
Indication: Treatment of hyperthyroidism antithyroid therapy 3–4 days prior to sodium iodide I 131
administration], Vitamin K Antagonists [e.g. Warfarin
Contraindication: Breastfeeding patients (anticoagulant effect)]
Dose: Pregnancy Category: D
Hyperthyroidism, by mouth, ADULT, initially 300–400 mg
daily in 3 equally divided doses at 8-hour intervals; ATC Code: H03BA02
Severe hyperthyroidism and/or very large goiters, by mouth,
ADULT, 400 mg daily; some may require 600–900 mg
daily; maintenance dose is usually at 100–150 mg daily
SULFUR-CONTAINING IMIDAZOLE
in 3 equally divided doses; ADOLESCENT and CHILD >10
years, initially 150–300 mg daily in 3 equally divided DERIVATIVES
doses, then maintain at 50 mg twice daily when
euthyroid; CHILD 6–10 years, initially 50–150 mg daily
in 3 equally divided doses, then maintain at 50 mg twice
Rx METHIMAZOLE (THIAMAZOLE)
daily when euthyroid.
Oral: 5 mg and 10 mg tablet
Precautions:
WARNING: Severe liver injury and acute liver failure A thioamide used as an antithyroid agent that inhibits the
(sometimes fatal) were reported, requiring liver synthesis of thyroid hormones by blocking iodine
transplantation in some patients, including oxidation in the thyroid gland.
pregnant women. Reserve use of PTU for
patients who cannot tolerate methimazole or in Indications: For hyperthyroidism; for long-term use (1–2
whom radioactive iodine therapy or surgery are years) to induce remission in small goiters;
not appropriate. hyperthyroidism associated with Graves’ disease
Treatment of choice when antithyroid is
indicated during to or just prior to first trimester Contraindications: Previous agranulocytosis to
of pregnancy due to the risk of fetal methimazole; drug-induced nephritis or polyarteritis
abnormalities associated with the use of nodosa; liver disease; blood disorders, such as
methimazole. granulocytopenia and aplastic anemia

Bleeding; Bone marrow suppression (discontinue if Dose:

significant bone marrow suppression occurs, particularly Hyperthyroidism, by mouth, ADULT,
agranulocytosis or aplastic anemia); Mild hyperthyroidism, initially 15 mg daily in 3 divided
Dermatologic toxicity; doses, approximately every 8 hours;

199
 SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

Moderately severe hyperthyroidism, 30–40 mg daily; Anticoagulants e.g. Warfarin

Severe hyperthyroidism, 60 mg daily;
Maintenance, 5–15 mg daily as a single dose, continue Increases risk of adverse or toxic effects of Methimazole:
for 12–18 months to induce remission, or for 6–12 Macrolide Antibiotics e.g. Azithromycin (QT-prolongation)
months to prepare patients for definitive therapy in the
form of surgery or radioactive iodine therapy; Avoid concomitant use with:
CHILD, initially 0.4 mg/kg daily in 3 divided doses, Increases risk of adverse or toxic effects of the following
maintenance: 0.2 mg/kg daily in 3 divided doses; drugs:
suggested dosing based on the age: Clozapine (agranulocytosis), Dipyrone (agranulocytosis and
pancytopenia)
Population Daily Dose (mg)
Infants 1.25 Increases serum concentration of Tizanidine [initiate
Children 1–5 years 2.5–5 Tizanidine at 2 mg and increase in 24 mg increments
Children 5–10 years 5–10 based on patient response]
Children and Reduces therapeutic effect of the following drugs:
10–20
Adolescents 10–18 years BCG (Intravesical), Sodium Iodide I 131 [discontinue
H

Methimazole 3–4 days before Sodium Iodide I 131

Dose Adjustment: administration], Vitamin K Antagonists e.g. Warfarin
Renal Impairment: (anticoagulant effect)
For mild-to-moderate renal impairment, dose reduction is
warranted Administration: May be taken with food or milk to reduce
For severe impairment, refer patient to a specialist. stomach upset.

Hypothyroidism: Pregnancy Category: D

Adjust dose to maintain euthyroid state. Monitor THS and
free T4 levels. ATC Code: H03BB02

Precautions:
Hypoprothrombinemia; IODINE THERAPY
Bone marrow suppression;
Bleeding;
Aplastic anemia; Rx IODINE
Thrombocytopenia;
Leukopenia;
Leukocytoclastic vasculitis and positive vasculitis Oral: aqueous iodine solution (Lugol's solution)
(discontinuation immediately if vasculitis develops 5% iodine, 10% potassium iodide (total iodine = 130
during therapy); mg/mL), 30 mL
Dermatologic toxicity (discontinue if exfoliative dermatitis
develops); An anti-hyperthyroid agent that acts by reducing of the
Urticaria; thyroid gland through various mechanisms, such as the
Infection (discontinue at signs of infections, e.g., fever, sore reduction of vascularity, a firming of the glandular tissue,
throat, mouth ulcer, and clinical evidence of and shrinkage of the size of individual cells.
neutropenia;
Hepatic necrosis (hepatitis, fever); Indication: Antidote to thyroid block following radiation
Encephalopathy (discontinue in the presence of hepatitis; emergency
transaminase >3 times upper limit of normal);
Lupus-like syndrome; Contraindications: Dermatitis herpetiformis;
Pregnancy (first trimester: can cause fetal harm; high risk of hypocomplementemic vasculitis, nodular thyroid
agranulocytosis if doses >40 mg/day). condition with heart disease

Adverse Drug Reactions: Dose:

Common: Pruritus, rash Antidote, by mouth, ADULT (including pregnant and lactating
Less Common: Abnormal loss of hair, arthralgia, edema, women), 130 mg once daily for 10–14 days or until risk
epigastric distress, headache, loss of taste, of exposure is gone; CHILD, dose should continue for
lymphadenopathy, neuritis, paresthesia, pigmentation, 10–14 days or until risk of exposure has passed; dose
pruritus, sialadenopathy, urticaria, myalgia, nausea, based on age:
vertigo, vomiting Dose (mg
Population
Rare: Agranulocytosis, alopecia, aplastic anemia, drug once daily)
fever, granulocytopenia, hypoprothrombinemia, 1 month and below 16.25
hepatitis, jaundice, myopathy, nephritis, lupus-like >1 month – 3 years 32.5
syndrome, periarteritis, thrombocytopenia >3 years – 12 years 65
Drug Interactions: >12 years and adolescent
65
Monitor closely with: weighing less than 68 kg
Enhances therapeutic effect of Methimazole:

200
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULINS

>12 years and adolescent

weighing at least 68 kg
130 Rx PROPRANOLOL

Precautions: Oral: 10 mg and 40 mg tablet (as hydrochloride)

Allergy to iodine or potassium iodide;
Skin reactions; A non-selective beta-adrenergic blocker that competitively
Hypothyroidism; blocks response to beta adrenergic stimulation.
Adrenal insufficiency, including Addison disease; Indications for thyroid diseases are considered as off-
Bronchitis; label use.
Cardiac disease;
Myotonia congenital; Indications: Management of thyroid storm, thyrotoxicosis
Renal impairment tuberculosis.
Contraindications: Uncompensated congestive heart failure
Adverse Drug Reactions: Cardiac arrhythmia, confusion, (unless the failure is due to tachyarrhythmias being
fatigue, fever, numbness, tingling sensation, skin rash, treated with propranolol); cardiogenic shock; severe
urticaria, hyperthyroidism (prolonged use), sinus bradycardia; sick sinus syndrome or heart block
hypothyroidism (prolonged use), goiter, myxedema, greater than first degree (except in the presence of a

diarrhea, enlargement of salivary glands, gastric
distress, GI hemorrhage, metallic taste, nausea,
stomach pain, vomiting, lymphedema, thyroid adenoma,
weakness, dyspnea, hypersensitivity reaction
(angioedema, cutaneous and mucosal hemorrhage,
serum sickness-like symptoms), wheezing, iodine
poisoning (prolonged use, high doses)
H
functioning artificial pacemaker); bronchial asthma
Dose:
Thyroid storm, by mouth, ADULT, 60–80 mg every 4 hours.
Thyrotoxicosis, by mouth, ADULT, 10–40 mg/dose every 6–
8 hours; ADOLESCENT and NEONATE, 10–40 mg per
dose every 6 hours.

Drug Interactions: Administration: To be taken on an empty stomach.

Monitor closely with:
Increases risk of adverse or toxic effects of the following Do NOT withdraw abruptly, particularly in patients with CAD.
drugs: Gradually taper dose to avoid acute tachycardia,
ACE Inhibitors e.g., Enalapril, Aliskiren hypertension, and/or ischemia.
Angiotensin II Receptor Blockers e.g. Losartan, Heparin
(hyperkalemic effect) See individual entry for Propranolol under Cardiac Therapy
– Antiarrhythmics, Class II Antiarrhythmics in Chapter 3:
Increases risk of adverse or toxic effects of the following Cardiovascular System for further information.
drugs:
Lithium (hypothyroid effect), Nicorandil (hyperkalemic Pregnancy Category: C
effect)
ATC Code: Not available
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Eplerenone (hyperkalemic effect), Potassium-sparing
Diuretics (hyperkalemic effect)

Reduces therapeutic effect of the following drugs:

Sodium Iodide I 131 [discontinue Iodine 3 to 4 days prior
to Sodium Iodide I 131 administration], Vitamin K
Antagonists e.g. Warfarin (anticoagulant effect)

Administration: Administer with food or milk to decrease

gastric irritation. Dilute in a glassful of water, fruit juice,
or milk.

Pregnancy Category: D

ATC Code: H03CA

201

ANTI-INFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
Antibacterial Drug Classes
BETA- LACTAM, PENICILLINS
Penicillins with extended spectrum
The extended-spectrum penicillins are a group of semi-
synthetic penicillin antibiotics that have a wider
spectrum of activity than natural penicillins,
penicillinase-resistant penicillins, and aminopenicillins.
They are more active against gram-negative bacteria
because they are more resistant to inactivation by
extended-spectrum β-lactamases and/or because they
more readily penetrate the outer membranes of these
gram-negative organisms.
J
Beta-lactamase sensitive penicillins
This class of antibiotics binds to penicillin binding proteins
that catalyzes the synthesis of peptidoglycan and this
leads to the interruption of cell wall synthesis, leading to
bacterial cell growth inhibition and cell lysis
Beta-lactamase resistant penicillins
These semisynthetic penicillins are indicated for infection by
β-lactamase-producing staphylococci, although
penicillin-susceptible strains of streptococci and
pneumococci are also susceptible to these agents.
Listeria monocytogenes, Enterococci, and methicillin-
resistant strains of Staphylococci are resistant.
Beta-lactamase inhibitors
Commonly used for empirical therapy against a large
number of pathogens such as treatments for aerobic and
anaerobic infections. These class of drugs are potent
inhibitors of beta-lactamases and protects hydrolysable
penicillins from inactivation.
Beta-lactamase inhibitors in combination
The β-lactamase inhibitors bind to β-lactamases and
inactivate them. The β-lactamase inhibitors lack direct
antimicrobial activity but when combined with an
antibiotic, they extend the spectrum of activity and
increase stability against β-lactamases.
OTHER BETA-LACTAM ANTIBACTERIALS
Cephalosphorins (1st, 2nd, 3rd, 4th)
1st: First-generation cephalosporins include cefazolin,
cefadroxil, cephalexin, cephalothin, cephapirin, and
cephradine. These drugs are very active against gram-
positive cocci.
2 : Second-generation cephalosporins include cefaclor,
nd
cefamandole, cefonicid, cefuroxime, cefprozil,
loracarbef, and ceforanide; and the structurally related
cephamycins cefoxitin, cefmetazole, and cefotetan,
which have activity against anaerobes.
3 : Third-generation cephaosphorins include cefoperazone,
rd
cefotaxime, ceftazidime, ceftizoxime, ceftriaxone,
cefixime, cefpodoxime proxetil, cefdinir, cefditoren
pivoxil, ceftibuten, and moxalactam. They are active
against Citrobacter, S marcescens, and Providencia.
4th: Cefepime belongs to the fourth-generation
cephalosporin. It is more resistant to hydrolysis by
chromosomal β lactamases. Cefepime has good activity
202
ANTI-INFECTIVES FOR SYSTEMIC USE
against P aeruginosa, Enterobacteriaceae, S. aureus,
and S. pneumoniae. It is highly active against
Haemophilus and Neisseria sp.
Monobactams
They have a narrow and characteristic spectrum of activity
which acts by inhibiting bacterial cell wall synthesis due
to its high affinity for penicillin-binding protein 3 (PBP-3)
of gram-negative bacteria. It is also active against most
Enterobacteriaceae (including E. coli, Citrobacter,
Enterobacter, Klebsiella, Proteus, Providencia,
Salmonella, Serratia, Shigella, Yersinia spp. and
Morganella morganii).
Carbapenems
Carbapenems have an extremely broad spectrum of
antimicrobial activity and are highly resistant to a variety of
β-lactamases. They bind to penicillin-binding proteins and
inhibit bacterial cell wall synthesis.
Tetracyclines
Tetracycline are broad-spectrum antibiotics that inhibit
bacteriostatic action by reversibly binding to the 30S
subunits of the ribosome, thus preventing protein
synthesis and arresting cell growth. They are active
against many gram-positive and gram-negative bacteria
including Chlamydiaceae, Mycoplasma spp., Rickettsia
spp., spirochetes, and some protozoa.
Aminoglycosides
Aminoglycosides are used most widely in combination with
a β-lactam antibiotic in serious infections with gram-
negative bacteria, in combination with vancomycin or a
β-lactam antibiotic for gram-positive endocarditis, and
for treatment of tuberculosis. They are rapid bactericidal
irreversible inhibitors of protein synthesis by binding on
the 30S ribosome.
Lincosamides
Lincosamide is an antibiotic that binds to the 50S ribosomal
subunit at a site closely related to that at which
macrolides act resulting in bacteriostatic inhibition of
microbial protein synthesis.
Macrolides
Macrolides are bacteriostatic antibiotics with a broad
spectrum of activity against many gram-positive bacteria.
The antimicrobial activity of macrolides is exhibited by
the inhibition of bacterial protein biosynthesis after
binding of the macrolide, selectively and reversibly, to
the 50S ribosomal subunit.
Chloramphenicol
Chloramphenicol is a potent inhibitor of microbial protein
synthesis by reversibly binding to the 50S subunit of the
bacterial ribosome, thus preventing peptide bond
formation by peptidyl transferase. It has both
bacteriostatic and bactericidal action against H.
influenzae, N. meningitidis and S. pneumoniae.
Quinolones
Quinolones are broad-spectrum antibacterial agents. They
act by blocking bacterial DNA synthesis by inhibiting
bacterial topoisomerase II and topoisomerase IV.
Inhibition of topoisomerase II prevents the relaxation of
positively supercoiled DNA while inhibition of
ANTI-INFECTIVES FOR SYSTEMIC USE
topoisomerase IV interferes with separation of replicated
chromosomal DNA.
Glycopeptide antibiotics
It is a narrow-spectrum antibiotic which affects gram-
positive bacteria by interfering with the incorporation of
penicillin-binding protein enzymes into the cell wall by
binding to precursors of cell wall synthesis.
Polymyxins
Polymyxins are bactericidal drugs that bind to
lipopolysaccharides (LPS) and phospholipids in the outer
cell membrane of gram-negative bacteria. They
competitively displace divalent cations from the
phosphate groups of membrane lipids, which leads to
disruption of the outer cell membrane, leakage of
intracellular contents, and bacterial death.
Imidazole derivatives
These drugs inhibit the biosynthesis of ergosterol, the
main sterol in membranes of fungi. These agents also
affect the synthesis of triglycerides and phospholipids
leading to an intracellular buildup of toxic
concentrations of hydrogen peroxide, contributing to the
deterioration of subcellular organelles and to cell
necrosis.
Nitrofuran derivatives
Nitrofurans are bacteriostatic and bactericidal for many
gram-negative and gram-positive organisms but may not
affect P. aeruginosa and many strains of proteus.
Folic acid antagonists
Antifolate agents act at various steps in the folic acid
cycle. Antifolate agents are most commonly used in
combination to block sequential steps in the folic acid
metabolic pathway.
TETRACYCLINES
Rx DOXYCYCLINE
Oral: 100 mg capsule (as hyclate)
Indications: Treatment of leptospirosis; juvenile
periodontitis; gastroenteritis; acute bacterial
exacerbation of chronic bronchitis (ABECB); blepharitis
with associated acne rosacea; chlamydia and
mycoplasma infections; second-line treatment of acute
bacterial rhinosinusitis (ABRS) or for patients with severe
penicillin allergy; pneumonia due to Burkholderia
pseudomallei
Contraindications: Pregnancy; breastfeeding; porphyria;
SLE
Dose:
Acute bacterial exacerbation of chronic bronchitis ABECB,
mild-to-moderate, by mouth, ADULT, 100 mg twice daily.
Acute bacterial rhinosinusitis, ABRS, by mouth, ADULT, 100
mg every 12 hours for 5-7 days.
Blepharitis with associated acne rosacea, by mouth, ADULT,
100 mg twice daily for 2 weeks, then every 24 hours.
Chlamydia infections, by mouth, ADULT, 100 mg twice daily
for 7 days
Pneumonia due to Burkholderia pseudomallei, by mouth,
ADULT, 100 mg twice daily; CHILD, 4 mg/kg divided twice
daily with Trimethoprim-Sulfamethoxazole
Juvenile periodontitis, by mouth, CHILD ≥8 years, 200 mg
daily for 7 days.
Mycoplasma infections, by mouth, ADULT, 100 mg twice a
day for five to ten days
Leptospirosis a
Clinical manifestations that should lead a health
practitioner to consider suspected leptospirosis: any
individual with acute febrile illness of at least 2 days
duration and residing in a flooded area or has high-risk
exposure (defined as wading in floods and contaminated
water, contact with animal fluids, swimming in flood
water or ingestion of contaminated water, with or without
cuts or wounds) and with at least 2 of the following
symptoms: myalgia, calf tenderness, conjunctival
J
suffusion, chills, abdominal pain, headache, jaundice,
oliguria.
For mild leptospirosis (defined as acute febrile illness and
various manifestations BUT with stable vital signs,
anicteric sclera, good urine output and no evidence of
meningismus or meningeal irritation, sepsis or septic
shock, difficulty of breathing, and jaundice, that is able
to take oral medications) as first line agent to be started
as soon as the diagnosis is suspected regardless of the
phase of the disease or duration of symptoms, by mouth,
ADULT, 100 mg twice daily for 7 days; CHILD ≥8 years, 2-
4 mg/kg daily twice a day for 7 days (maximum dose,
200 mg daily).
For moderate to severe leptospirosis, refer immediately to a
higher level of healthcare facility or the hospital.
For pre-exposure and post-exposure prophylaxis: Pre-
exposure prophylaxis is not routinely recommended
except for travelers, soldiers, those engaged in water-
related recreational and occupational activities in high
endemic areas, by mouth, ADULT, 4 mg/kg single dose
(maximum dose, 200 mg regardless of age), take 100
mg twice daily if 200 mg daily is not tolerated.
For post-exposure prophylaxis:
Post-exposure prophylaxis depends on type of risk and
may be repeated once weekly if with continued exposure
to risk factors.
- Low-Risk Exposure (defined as single history of wading
in flood or contaminated water and the absence of
wounds, cuts, or open lesions of the skin), by mouth,
ADULT, 200 mg within 24-72 hours from exposure.
- Moderate-Risk Exposure (defined as single history of
wading in flood or contaminated water and the presence
of wounds, cuts, or open lesion in the skin, or the
accidental ingestion of contaminated water), by mouth,
ADULT, 200 mg once daily for 3-5 days to be started
immediately within 24-72 hours from exposure.
- High-Risk Exposure (defined as continuous exposure –
more than a single exposure or several days exposure –
of wading in flood or contaminated water with or without
the presence of wounds, cuts, or open lesions of the skin;
swimming in flooded waters especially in areas infested
with domestic / sewer rats and ingestion of
contaminated water), by mouth, ADULT, 200 mg once
weekly until the end of the exposure.
203

- For Pediatrics: by mouth, CHILD >8 years, 4 mg/kg as
single dose (maximum, 200 mg); if child is exposed for
more than 7 days, repeat the dose after one week.
NOTE: Antibiotic prophylaxis in the prevention of
leptospirosis is NOT 100% effective. Protective
measures should still be used. The most effective
preventive measure remains to be avoidance of high-risk
exposure. If unavoidable, use protective measures such
as boots, goggles, overalls, or rubber gloves.
WARNING: There is currently NO recommended pre-
exposure and post-exposute prophylaxis that is
safe for pregnant or lactating women.
a The Philippine Clinical Practice Guidelines on the
Diagnosis, Treatment and Prevention of Leptospirosis in
Adults 2010, PSMID, Quezon City.
Dose Adjustment:
J
Renal Impairment:
Doxycycline can be used without dose adjustment (does
NOT lead to excessive accumulation when used at the
usual recommended doses).
Hepatic Impairment:
Avoid high doses (hepatotoxicity more likely to occur in
hepatic impairment).
Precautions:
WARNING: Do not administer to pregnant women.
Avoid use in children less than 8 years of age.
Tetracyclines may increase muscle weakness in patients
with myasthenia gravis and may exacerbate SLE;
Overgrowth of non-susceptible organisms;
Hepatic impairment;
Photosensitivity (avoid exposure to sunlight or sunlamps);
tissue hyperpigmentation (skin, nail, eye, tooth, or gum
discoloration may occur);
Intracranial hypertension;
Autoimmune;
Possible interaction if co-administered with statins or
laxatives;
Breastfeeding (use alternative drugs if possible);
Probable absorption and discoloration of teeth in infants
may usually be prevented by chelation with calcium from
milk.
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea, enamel dysplasia,
epigastric burning, headache, nausea, photosensitivity,
reduced bone growth (in children <8 years), tooth
discoloration, vaginitis, vomiting
Less Common: Anorexia, bone deformity, dental hypoplasia,
flushing, fungal overgrowth, rash, stomatitis
Rare: Allergic reactions including SJS and anaphylaxis;
benign intracranial hypertension, blood disorders, C.
difficile-associated disease, esophageal ulcers,
hepatitis, hepatotoxicity, nail discoloration, pancreatitis,
serum sickness-like reactions, toxic epidermal
necrolysis, visual disturbances, tinnitus
204
ANTI-INFECTIVES FOR SYSTEMIC USE
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Contraceptives (oral)
Reduces therapeutic effect of Doxycycline:
Rifampicin
Avoid concomitant use with:
Reduces absorption of Doxycycline:
Aluminum, Magnesium or Calcium containing antacids
(separate administration by at least 2 hours), Calcium
salts (separate administration by at least 2 hours), Ferric
salts (separate administration by as long as possible, at
least 2 hours), Magnesium salts (separate
administration by at least 2 hours), Zinc salts (separate
administration by at least 2 hours)
Increases risk of adverse or toxic effects Doxycyline:
Oral retinoids (e.g., isotretinoin, acitretin)
Reduces therapeutic effect of Penicillin
Administration: To be taken with food or after a meal.
Capsules should be swallowed whole with plenty of fluid
(a full glass of water); remain sitting or standing (for at
least ½ hour) to prevent esophageal irritation or damage.
Do not give with milk.
Pregnancy Category: D
ATC Code: J01AA02
Rx TETRACYCLINE
Oral: 250 mg and 500 mg capsule
Indications: Treatment of susceptible bacterial infections of
both gram-positive and gram-negative organisms;
infections due to Mycoplasma, Chlamydia, and
Rickettsia; acute diarrhea (suspected cholera);
gastroenteritis; second-line treatment of malaria;
second-line treatment of trachoma; second-line
treatment of syphilis
Dose:
Bacterial infection, general dosing, by mouth, ADULT, 250-
500 mg every 6 hours; CHILD >8 years, 25 to 50 mg/kg
daily in divided doses every 6 hours.
Gastroenteritis due to Vibrio cholera, by mouth, ADULT, 500
mg 4 times daily for 3 days by mouth, CHILD 2 months to
5 years, 250 mg 4 times daily for 3 days.
Syphilis, primary, secondary, or latent, by mouth, ADULT,
500 mg 4 times daily for 14 days.
Syphilis, late latent, by mouth, ADULT, 500 mg 4 times daily
for 30 days.
Trachoma due to Chlamydia trachomatis, second-line, by
mouth, ADULT and CHILD, 250 mg 4 times daily for 14
days.
Dose Adjustment:
Renal Impairment:
For patients with CrCl of 50-80mL/minute, administer every
8-12 hours.
ANTI-INFECTIVES FOR SYSTEMIC USE
For patients with CrCl of 10-50mL/minute, administer every
12-24 hours.
For patients with CrCl <10mL/minute, administer every 24
hours
Tetracycline is slightly dialyzable (5-20%) via hemodialysis,
peritoneal dialysis, and continuous arteriovenous or
venous hemofiltration. Supplemental dose is not
necessary.
Precautions:
Do NOT administer to pregnant women.
Nephropathy;
Photosensitivity (discontinue if skin erythema occurs);
Superinfection;
Hepatic and renal impairment;
Pediatric (may cause tissue hyperpigmentation, enamel
hypoplasia, or permanent tooth discoloration; avoid use
in children <8 years);
Pregnancy (may affect fetal tooth development; associated
with retarded skeletal development and reduced bone
growth);
Lactation (excreted in breastmilk; binds to calcium in
maternal milk).
Adverse Drug Reactions: Pericarditis, bulging fontanels in
infants, increased intracranial pressure, paresthesia,
pseudotumor cerebri, exfoliative dermatitis,
photosensitivity, pigmentation of nails, pruritus,
abdominal cramps, anorexia, antibiotic-associated
pseudomembranous colitis, diarrhea, discoloration of
teeth (young children), enamel hypoplasia (young
children), esophagitis, nausea, pancreatitis,
staphylococcal enterocolitis, vomiting, thrombophlebitis,
hepatotoxicity, acute renal failure, azotemia, renal
damage, anaphylaxis, hypersensitivity reactions,
superinfection
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Neuromuscular-blocking agents e.g. Pancuronium
Vitamin K antagonists
Increases serum concentration of Quinine
Reduces therapeutic effect of BCG vaccine
Avoid concomitant use with:
Reduces absorption of Tetracycline:
Antacids, Bile acid sequestrants e.g. Colestipol
Magnesium salts, Sucralfate (if concomitant use cannot
be avoided, administer at least 2 hours apart), Zinc salts
(if concomitant use cannot be avoided, separate
administration by at least 2 hours; except: Zinc chloride)
Reduces absorption of Iron salts
Decreases serum concentration of Tetracycline:
Calcium salts, Dabrafenib, Dairy products, Iron salts
(except: ferric carboxymaltose, ferric gluconate, ferric
pyrophosphate citrate, ferumoxytol, iron dextran
complex, iron sucrose), Lanthanum (separate doses by
at least 2 hours), Multivitamins / Minerals (with ADEK,
folate, iron) (if concomitant use cannot be avoided,
separate administration by several hours), Multivitamins
/ Minerals (with AE, no iron) (if concomitant use cannot
be avoided, separate administration by several hours),
Quinapril (separate doses by at least 2 hours; if
concomitant use cannot be avoided, monitor for reduced
efficacy of tetracycline), Strontium ranelate
(discontinuation of strontium ranelate treatment during
tetracycline therapy is recommended)
Increases risk of adverse or toxic effects of the following
drugs:
Retinoic acid derivatives (pseudotumor cerebri) (except:
Adapalene), Tretinoin (Topical)
Increases metabolism of the Tetracycline:
CYP3A4 inducers (strong)
Reduces therapeutic effect of the following drugs:
BCG (intravesical), Penicillin, Sodium picosulfate,
Typhoid vaccine (postpone use of this vaccine until at
least 3 days after cessation of antibacterial agents)
J
Administration: Administer on an empty stomach (1 hour
before or 2 hours after meals) to increase total
absorption. Administer around-the-clock to promote less
variation in peak and trough serum levels.
Administer at least 1-2 hours prior to, or 4 hours after
antacid because aluminum and magnesium cations may
chelate with tetracycline and reduce its total absorption.
Do NOT administer to pregnant women.
Pregnancy Category: D
ATC Code: J01AA07
AMPHENICOLS
Rx CHLORAMPHENICOL
Oral: 500 mg capsule
125 mg/5 mL suspension (as palmitate), 60 mL
Inj.: 1 g vial (as sodium succinate) (IV, IM if recommended)
Indications: Treatment of brain abscess in the presence of
dental infection, meningitis, uncomplicated typhoid
fever, salmonella gastroenteritis. It is associated with
serious hematological side-effects when given
systemically and should therefore be reserved for the
treatment of life-threatening infections
Contraindications: Treatment of trivial or viral infections;
bacterial prophylaxis.
Dose:
Brain abscess, in the presence of dental infection, by IV or
IM injection, CHILD, 100 mg/kg in divided doses every 6
hours; ADULT, 1g every 6 hours.
Meningitis, by IV injection, CHILD and INFANT >2 months –
18 years old, 100 mg/kg in divided doses every 8 hours;
maximum daily dose: 4g.
Uncomplicated typhoid fever, by IV injection or by mouth
CHILD, 50-75 mg/kg in divided doses every 6 hours;
maximum daily dose: 500 mg 2 capsules every 6 hours;
by mouth, ADULT, 1 g every 6 hours for 14 days.
205

Salmonella gastroenteritis, by IV injection or by mouth,
CHILD, 50-75 mg/kg in divided doses every 6 hours for
7 days; maximum daily dose: 2-4 g.
Dose Adjustment:
Renal and Hepatic Impairment:
Use with caution; monitor serum concentrations.
Precautions:
WARNING: Serious and fatal blood dyscrasias (aplastic
anemia, hypoplastic anemia, thrombocytopenia, and
granulocytopenia) have occurred after both short-term
and prolonged therapy. Monitor CBC frequently in all
patients.
Characterized by circulatory collapse, cyanosis, acidosis,
abdominal distention, myocardial depression, coma, and
death. Reaction appears to be associated with serum
levels ≥50mcg/mL. May result from drug accumulation
J
in patients with impaired hepatic or renal function;
Prolonged use may result in fungal or bacterial
superinfections, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis;
Use with caution in patients with hepatic impairment
(reduced dosage recommended);
Use with caution in patients with renal impairment.
Adverse Drug Reactions:
Confusion, delirium, depression, fever, headache,
angioedema, rash, urticaria, diarrhea, enterocolitis,
glossitis, nausea, stomatitis, vomiting, aplastic anemia,
bone marrow suppression, granulocytopenia,
hypoplastic anemia, pancytopenia, thrombocytopenia,
optic neuritis, anaphylaxis, hypersensitivity reactions,
Gray baby syndrome.
Drug Interactions:
Decreases serum concentration of Chloramphenicol:
Anticonvulsants e.g. Phenytoin
Decreases metabolism of the following drugs:
Anticonvulsants e.g., Phenytoin, Barbiturates
Sulfonylureas
Increases serum concentration of Voriconazole
Increases metabolism of Chloramphenicol:
Barbiturates, Rifampin
Reduces therapeutic effect of the following drugs:
BCG, Cyanocobalamin, Typhoid Vaccine
Enhances therapeutic effect of Vitamin K Antagonists e.g.
Warfarin
Administration:
Do NOT administer IM; can be administered IV push over at
least 1 minute at a concentration of 100 mg/mL, or IV
intermittent infusion over 15-30 minutes at a final
concentration for administration of ≤20mg/mL.
Pregnancy Category: C
ATC Code: J01BA01
206
ANTI-INFECTIVES FOR SYSTEMIC USE
BETA-LACTAM ANTIBACTERIALS,
PENICILLINS
PENICILLINS WITH EXTENDED SPECTRUM
Rx AMOXICILLIN
WHO anti-biotic category: ACCESS
Oral: 250 mg and 500 mg capsule (as trihydrate)
100 mg/mL granules / powder for drops (as
trihydrate), 15 mL
250 mg/5 mL granules / powder for suspension (as
trihydrate), 60 mL
Indications: Treatment of acute bacterial exacerbation of
chronic bronchitis, acute otitis media, community
acquired pneumonia, eradication of H. pylori,
uncomplicated typhoid fever, mild leptospirosis,
pericoronitis and dental prophylaxis; second line
treatment for exudative tonsilitis
Contraindications: Hypersensitivity to amoxicillin, penicillin,
other beta-lactams, or any component of the formulation
Dose:
Acute bacterial exacerbation of chronic bronchitis (ABECB),
mild moderate infections, by mouth, ADULT, 500 mg
thrice a day for 5-10 days.
Acute otitis media, by mouth, CHILD <2 years old, 80-90
mg/kg in divided doses every 12 hours for 10 days;
CHILD 2-5 years old, 80-90 mg/kg in divided doses every
12 hours for 7 days; , CHILD >5 years old, 80-90 mg/kg
in divided doses every 12 hours for 5-7 days; ADULT, 1g
every 8 hours for 10 days.
Community Acquired Pneumonia with complete Hib
vaccination, by mouth, INFANT and CHILD up to 5 years
old, 80-90 mg/kg every 12 hours for 5 days.
Community Acquired Pneumonia, without co-morbid illness,
by mouth, ADULT, 1g thrice a day for 5-7 days.
Exudative tonsillitis, by mouth, ADULT and CHILD, 50 mg/kg
ever 8-12 hours for 10 days
Uncomplicated typhoid fever, by mouth, ADULT, 1g every 6
hours for 14 days; CHILD, 75-100 mg/kg in divided
doses every 8 hours; maximum daily dose: 500 mg, 2
capsules every 6 hours)
Leptospirosis, mild, by mouth, CHILD, 50 mg/kg every 8
hours for 7 days;
Pre-exposure prophylaxis, by mouth, 50 mg/kg every 8
hours for 3-5 days; maximum daily dose: 500 mg every 8
hours
Dental Prophylaxis, by mouth, ADULT, 2 g per day; CHILD,
50 mg/kg per day.
Pericoronitis, by mouth, ADULT, 500 mg every 8 hours for 7
days.
Dose Adjustment:
Renal Impairment:
Use of certain dosage forms (i.e. ER 775 mg tablet and IR
875 mg tablet) should be avoided in patients with CrCl
<30 mL/minute or patients requiring hemodialysis.
CrCl 10-30 mL/minute: 250-500 mg every 12 hours.
CrCl <10 mL/minute: 250-500 mg every 24 hours.
Moderately dialyzable (20% to 50%) by hemodialysis or
peritoneal dialysis; approximately 50 mg of amoxicillin
ANTI-INFECTIVES FOR SYSTEMIC USE
per liter of filtrate is removed by continuous
arteriovenous or venovenous hemofiltration.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy.
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis;
A high percentage of patients with infectious mononucleosis
have developed rash during therapy; (ampicillin-class
antibiotics not recommended in these patients);
Use with caution in patients with renal impairment (dosage
adjustment recommended).
Adverse Drug Reactions:
Agitation, anxiety, behavioral changes, confusion, dizziness,
headache, hyperactivity, insomnia, seizure, acute
exanthematous pustulosis, erythematous
maculopapular rash, erythema multiforme, exfoliative
dermatitis, hypersensitivity vasculitis, mucocutaneous
candidiasis, SJS, toxic epidermal necrolysis, urticaria,
black hairy tongue, diarrhea, hemorrhagic colitis,
nausea, pseudomembranous colitis, tooth discoloration,
vomiting, agranulocytosis, anemia, eosinophilia,
hemolytic anemia, leukopenia, thrombocytopenia, acute
cytolytic hepatitis, cholestatic jaundice, hepatic
cholestasis, crystalluria, anaphylaxis, serum sickness-
like reaction.
Drug Interactions:
Increases risk of adverse or toxic effects Amoxicillin:
Allopurinol
Reduces therapeutic effect of Amoxicillin:
Fusidic acid, Tetracycline derivatives
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine
Decreases excretion of Methotrexate
Decreases serum concentration of Mycophenolate
Increases serum concentration of Amoxicillin:
Probenecid
Administration:
May be taken with or without food. Best taken at the start of
meals for better absorption and reduction of GI
discomfort. Administer around-the-clock to promote less
variation in peak and trough serum levels. Appropriate
amount of suspension may be mixed with formula, milk,
fruit juice, water, ginger ale, or cold drinks; administer
dose immediately after mixing.
Pregnancy Category: B
ATC Code: J01CA04
AMPICILLIN
Rx
WHO anti-biotic category: ACCESS
Inj.: 250 mg, 500 mg, and 1 g vial (as sodium salt) (IM, IV)
Indications: Treatment of potential neonatal sepsis,
uncomplicated typhoid fever, chronic carrier, moderate
to severe leptospirosis, prosthetic joint infection, native
valve infective endocarditis, community acute bacterial
meningitis, community-acquired pneumonia, and dental
prophylaxis
Contraindications: Hypersensitivity to ampicillin, any
component of the formulation, or other penicillin.
Dose:
Potential neonatal sepsis, by IM injection or IV infusion,
NEONATE ≤7 days old ≤2kg, 50 mg/kg every 12 hours;
NEONATE 8-28 days old ≤2kg, 50 mg/kg every 8 hours;
NEONATE ≤7 days old >2kg, 50 mg/kg every 8 hours;
J
NEONATE 8-28 days old >2kg, 50 mg/kg every 6 hours;
with gentamicin or amikacin
Sepsis from intra-abdominal source, by IV infusion, CHILD,
200-400 mg/kg in divided doses every 8 hours;
maximum daily dose: 6-12 g.
Uncomplicated typhoid fever, by IV infusion, CHILD, 100-
200 mg/kg in divided doses every 6 hours for 14 days;
maximum daily dose: 12 g.
Chronic carrier, by IV infusion, CHILD, 100-200 mg/kg in
divided doses every 6 hours for 4 weeks; maximum daily
dose: 12 g.
Leptospirosis, moderate to severe, by IV infusion, CHILD,
100 mg/kg every 6 hours for 7 days; maximum daily
dose: 0.5-1 g every 6 hours.
Prosthetic joint infection, Enterococci (penicillin-
susceptible), by IV infusion, ADULT, 2 g every 4 hours for
4-6 weeks.
Native valve infective endocarditis, S. vidaris or S. bovis with
Penicillin G MIC >0.12 to ≤0.5mcg/mL, by IV infusion,
CHILD, 200-300 mg/kg in divided doses every 4-6 hours
for 6 weeks; maximum daily dose: 12 g; ADULT, 12 g in
divided doses every 4 hours for 4-6 weeks.
Native valve infective endocarditis, S. vidaris or S. bovis with
Penicillin G MIC >0.5 mcg/mL, by IV infusion, CHILD, 12
g in divided doses every 4 hours for 4-6 weeks with
gentamicin 1 mg/kg every 8 hours for 4-6 weeks.
Native valve infective endocarditis, Enterococci, penicillin-
susceptible, aminoglycoside-resistant, streptomycin
susceptible, by IV infusion, CHILD, 200–300 mg/kg IV
divided q4-6h daily (Max dose 12 g/d) with ceftriaxone
100 mg/kg IV/IM in divided doses every 12 hours or 80
mg/kg; maximum daily dose: 2 g every 12 hours for 6
weeks; ADULT, 12 g in divided doses every 4 hours with
ceftriaxone 2 g IV every 12 hours for 6 weeks.
Dental prophylaxis, by IM injection or IV infusion, CHILD, 50
mg/kg; ADULT, 2 g.
Community acute bacterial meningitis, by IM injection or IV
infusion, NEONATE <7 days old and <2kg, 50 mg/kg
every 12 hours; NEONATE <7 days old and ≥2kg, 50
mg/kg every 8 hours; NEONATE >7 days old and <2kg,
50 mg/kg every 8 hours; NEONATE >7 days old and
≥2kg, 50 mg/kg every 6 hours; with amikacin or
gentamicin; by IV infusion, ADULT >50 years old, 2 g
every 4 hours.
Community-acquired pneumonia, by IV infusion, NEONATE,
100-200 mg/kg in divided doses every 6 hours; INFANT
207

and CHILD up to 5 years old, 200 mg/kg in divided doses
every 6 hours.
Dose Adjustment:
Renal Impairment:
CrCl >50 mL/minute: Administer every 6 hours.
CrCl 10-50 mL/minute: Administer every 6-12 hours.
CrCl <10 mL/minute: Administer every 12-24 hours.
Intermittent hemodialysis (IHD) (administer after
hemodialysis on dialysis days): Dialyzable (20% to 50%):
IV: 1-2 g every 12-24 hours. Note: Dosing dependent on
the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): 250 mg every 12 hours.
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation
to target trough (if appropriate). The following are general
J
recommendations only (based on dialysate
flow/ultrafiltration rates of 1-2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment:
CVVH: Loading dose of 2 g followed by 1-2 g every 8-12
hours.
CVVHD: Loading dose of 2 g followed by 1-2 g every 8
hours.
CVVHDF: Loading dose of 2 g followed by 1-2 g every 6-8
hours.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a
history of beta-lactam hypersensitivity, history of
sensitivity to multiple allergens, or previous IgE-
mediated reactions. Use with caution in asthmatic
patients.
Appearance of a rash should be carefully evaluated to
differentiate a non-allergic ampicillin rash from a
hypersensitivity reaction; rash occurs in 5% to 10% of
children and is a generalized dull red, maculopapular
rash, generally appearing 3-14 days after the start of
therapy. It normally begins on the trunk and spreads over
most of the body. It may be most intense at pressure
areas, elbows and knees;
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis;
Use with caution in patients with renal impairment (dosage
adjustment recommended).
Adverse Drug Reactions:
Fever, penicillin encephalopathy, seizure, erythema
multiforme, exfoliative dermatitis, rash, urticaria, black
hairy tongue, diarrhea, enterocolitis, glossitis, nausea,
pseudomembranous colitis, sore mouth or tongue,
stomatitis, vomiting, oral candidiasis, agranulocytosis,
anemia, hemolytic anemia, eosinophilia, leukopenia,
thrombocytopenia purpura
Drug Interactions:
Decreases bioavailability of Atenolol
208
ANTI-INFECTIVES FOR SYSTEMIC USE
Reduces therapeutic effect of Ampicillin:
Fusidic acid, Tetracycline derivatives
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (only the live attenuated Ty21a
strain is affected)
Decreases serum concentration of Ampicillin:
Chloroquine, Lanthanum
Decreases serum concentration of Mycophenolate
Decreases excretion of Methotrexate
Increases serum concentration of Ampicillin:
Probenecid
Administration:
Administer around-the-clock to promote less variation in
peak and trough serum levels.
Administer over 3-5 minutes (125-500 mg) or over 10-15
minutes (1-2 g). More rapid infusion may cause seizures.
Ampicillin and gentamicin should not be mixed in the
same IV tubing.
Pregnancy Category: B
ATC Code: J01CA01
BETA-LACTAMASE SENSITIVE
PENICILLINS
PENICILLIN G BENZATHINE
Rx (BENZATHINE BENZYLPENICILLIN)
WHO anti-biotic category: ACCESS
Inj: 1,200,000 units vial (MR) (IM)
Indications: Secondary prevention for acute rheumatic fever
and treatment for pharyngitis or tonsilitis
Contraindications: Hypersensitivity to penicillin or any
component of the formulation.
Dose: Acute rheumatic fever, secondary prevention, by IM
injection, CHILD ≤27kg, 600,000 units every 3 weeks;
CHILD >27kg, 1,200,000 units every 3 weeks.
Pharyngitis or tonsillitis, by IM injection, ADULT, 1,200,000
units.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: Not for intravenous use; cardiopulmonary
arrest and death have occurred from inadvertent IV
administration.
Serious and occasionally severe or fatal hypersensitivity
reactions have been reported in patients on penicillin
therapy, especially a history of beta-lactam
ANTI-INFECTIVES FOR SYSTEMIC USE
hypersensitivity, history of sensitivity to multiple
allergens, or previous IgE-mediated reactions (Use with
caution in asthmatic patients);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
Adverse Drug Reactions:
Cerebral vascular accident, cyanosis, gangrene,
hypotension, pallor, palpitations, syncope, tachycardia,
vasodilation, vasospasm, vasovagal reaction, anxiety,
coma, confusion, dizziness, euphoria, fatigue, headache,
nervousness, pain, seizure, somnolence, bloody stool,
intestinal necrosis, nausea, vomiting, impotence,
priapism, arthritis, exacerbation, joint disorder,
neurovascular damage, numbness, periostitis,
rhabdomyolisis, transverse myelitis, tremor, weakness,
blindness, blurred vision, hematuria, myoglobinuria,
neurogenic bladder, proteinuria, renal failure,
diaphoresis, hypersensitivity reactions, Jarisch-
Herxheimer reaction, lymphadenopathy, mottling,
warmth
Drug Interactions:
Reduces therapeutic effect of Penicillin G benzathine:
Fusidic acid, Tetracycline derivatives
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (only the live attenuated Ty21a
strain is affected)
Decreases serum concentration of Mycophenolate
Decreases excretion of Methotrexate
Increases serum concentration of Penicillin G benzathine:
Probenecid
Administration: Warm to room temperature before
administration to lessen the pain associated with
injection. Administer by deep IM injection in the upper
outer quadrant of the buttock; in children <2 years of
age, IM injections should be made into the mid-lateral
muscle of the thigh, not the gluteal region. Do not inject
near an artery or a nerve; permanent neurological
damage or gangrene may result. When doses are
repeated, rotate the injection site. Do NOT administer by
IV, SC, or intra-arterially.
Pregnancy Category: B
ATC Code: J01CE08
PENICILLIN G CRYSTALLINE
Rx (BENZYLPENICILLIN)
WHO anti-biotic category: ACCESS
Inj.: 1,000,000 units vial (as sodium salt) (IM, IV)
5,000,000 units vial (as sodium salt) (IM, IV)
Indications: Treatment of native valve infective
endocarditis, membranous pharyngitis due to diphtheria,
streptococcal infections, and rat - bite fever severe
community acquired pneumonia in children with
complete Hib vaccination
Contraindications: Hypersensitivity to penicillin or any
component of the formulation.
Dose:
Native valve infective endocarditis, S. viridans or S. bovis (S.
gallolyticus) with Penicillin G MIC ≤0.12 mcg/mL, by IV
infusion, CHILD, 200,000-300,000 U/kg in divided
doses every 4 hours for 4 weeks.
Membranous pharyngitis due to diphtheria, by IV infusion,
CHILD, 100,000-150,000 U/kg every 6 hours; ADULT,
50,000 U/kg every 12 hours.
Rat-bite fever, for mild- moderate infections, by IV, 100,000-
150,000 U/kg/day in 4 doses, for severe infections, by
IV, 200,000-300,000 U/kg/day in 6 doses
Severe community acquired pneumonia, with complete Hib
vaccination, by IV, 200,000 U/kg every six hours daily
Neurosyphilis, by IV, 3-4 MU every four hours or continuous
infusion for 10- 14 days
Proven or highly probable congenital syphilis, by IV, 50,000
U/kg every 12 hours during the first 7 days of life and
J
every 8 hours thereafter for a total of 10- 15 days
Possible congenital syphilis, by IV, 50,000 U/kg every 12
hours during the first 7 days of life and every 8 hours
thereafter for a total of 10 days
Dose Adjustment:
Renal Impairment:
Uremic patients with CrCl >10 mL/minute/1.73m2:
Administer full loading dose followed by ½ of the loading
dose given every 4-5 hours.
CrCl <10 mL/minute/1.73m2: Administer full loading dose
followed by ½ of the loading dose given every 8-10
hours.
Intermittent hemodialysis (IHD) (administer after
hemodialysis on dialysis days): Administer normal
loading dose followed by either 25% to 50% of normal
dose every 4-6 hours or 50% to 100% of normal dose
every 8-12 hours. For mild-to-moderate infections,
administer 0.5-1 MU every 4-6 hours or 1-2 MU every 8-
12 hours. For neurosyphilis, endocarditis, or serious
infections, administer up to 2 MU every 4-6 hours;
administer after dialysis on dialysis days or supplement
with 500,000 units after dialysis. Note: Dosing
dependent on the assumption of 3 times/week,
complete IHD sessions.
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug relation
to target trough (if appropriate). The following are general
recommendations only (based on dialysate
flow/ultrafiltration rates of 1-2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment.
CVVH: Loading dose of 4 MU, followed by 2 MU every 4-6
hours.
CVVHD: Loading dose of 4 MU, followed by 2-3 MU every 4-
6 hours.
CVVHDF: Loading dose of 4 MU, followed by 2-4 MU every 4-
6 hours.
209

Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a history
of beta-lactam hypersensitivity, history of sensitivity to
multiple allergens, or previous IgE-mediated reactions.
Use with caution in asthmatic patients.
Avoid intra-arterial administration or injection into or near
major peripheral nerves or blood vessels; Prolonged use
may result in fungal or bacterial superinfection, including
C. difficile-associated diarrhea (CDAD) and
pseudomembranous colitis.
Adverse Drug Reactions:
Coma, hyper-reflexia, seizures, contact dermatitis, rash,
pseudomembranous colitis, neutropenia, positive
hemolytic anemia, phlebitis, thrombophlebitis,
myoclonus, acute interstitial nephritis, renal tubular
damage, anaphylaxis, hypersensitivity reactions, Jarisch-
J
Herxheimer reaction, serum sickness.
Drug Interactions:
Reduces therapeutic effect of Penicillin G crystalline:
Fusidic acid, Tetracycline derivatives
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (only the live attenuated Ty21a
strain is affected)
Decreases serum concentration of Mycophenolate
Decreases excretion of Methotrexate
Increases serum concentration of Penicillin G crystalline:
Probenecid
Administration:
For IM: Administer IM by deep injection in the upper outer
quadrant of the buttock.
For Intermittent IV: May be dissolved in small amounts of
SQFI, NS, D5W and administered peripherally as a
50,000-100,000 units/mL solution. In fluid-restricted
patients, 146,000 units/mL in SQ results in a maximum
recommended osmolality for peripheral infusion. Infused
over 15-30 minutes.
For Continuous IV infusion: Determine the volume of fluid
and rate of its administration required by the patient in a
24-hour period. Add the appropriate daily dosage of
penicillin to this fluid.
Pregnancy Category: B
ATC Code: J01CE01
210
ANTI-INFECTIVES FOR SYSTEMIC USE
PENICILLIN V
Rx (PHENOXYMETHYLPENICILLIN)
WHO anti-biotic category: ACCESS
Oral: 250 mg and 500 mg tablet / capsule (as potassium
salt)
250 mg/5 mL granules / powder for syrup /
suspension (as potassium salt), 60 mL
Indications: Treatment of acute rheumatic fever, acute
gingivitis, acute necrotizing ulcerative gingivitis,
pericoronitis, pharyngitis, erisipelas and tonsillitis.
Contraindications: Hypersensitivity to penicillin or any
component of the formulation.
Dose:
Acute rheumatic fever, by mouth, ADULT, 250mg twice daily
for 3 weeks.
Acute gingivitis, by mouth, ADULT, 500mg every 4 hours
with metronidazole 500mg every 8 hours.
Acute necrotizing ulcerative gingivitis, by mouth, ADULT,
500mg every 6 hours with metronidazole 500mg every 8
hours.
Pericoronitis, by mouth, ADULT, 500mg every 6 hours for 7
days.
Pharyngitis or tonsillitis, by mouth, CHILD, 25-50mg/kg
every 6 hours for 10 days; ADULT, 500mg every 12 hours
or 250mg every 6 hours for 10 days.
Recurrent pharyngitis, by mouth, CHILD, 25-50mg/kg in
divided doses every 6 hours for 10 days; ADULT, 500mg
every 12 hours or 250mg every 6 hours for 10 days.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
CrCl 10-50mL/minute: Administer every 8-12 hours.
CrCl <10mL/minute: Administer every 12-16 hours.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a history
of beta-lactam hypersensitivity, history of sensitivity to
multiple allergens, or previous IgE-mediated reactions.
Use with caution in asthmatic patients.
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis;
Use with caution in patients with severe renal impairment
(dosage adjustment necessary);
Use with caution in patients with a history of seizure
disorder; high levels, particularly in the presence of renal
impairment, may increase risk of seizures.
Adverse Drug Reactions:
Common: Mild diarrhea, vomiting, nausea, oral candidiasis.
Rare: Acute interstitial nephritis, convulsions, hemolytic
anemia, positive Coombs reaction.
Drug Interactions:
Reduces therapeutic effect of the following drugs:
ANTI-INFECTIVES FOR SYSTEMIC USE
BCG vaccine, Typhoid vaccine
Reduces therapeutic effect of Penicillin:
Fusidic acid, Tetracycline derivatives
Decreases excretion of Methotrexate
Decreases serum concentration of Mycophenolate
Increases serum concentration of Penicillin:
Probenecid
Administration:
Administer on an empty stomach to increase oral
absorption.
Pregnancy Category: B
ATC Code: J01CE02
BETA-LACTAMASE RESISTANT
PENICILLINS
Rx CLOXACILLIN
WHO anti-biotic category: ACCESS
Oral: 500 mg capsule (as sodium salt)
250 mg/5 mL powder for solution (as sodium salt),
60 mL
Indications: Treatment of bacterial infections caused by
susceptible strains of penicillinase-producing
staphylococci.
Contraindications: Hypersensitivity to cloxacillin, other
penicillins, cephalosporins, or any component of the
formulation.
Dose:
Internal hordeolum, by mouth, ADULT, for MSSA, 250-500
mg every 6 hours with hot packs; CHILD, 100-150 mg/kg
in divided doses every 6 hours.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a history
of beta-lactam hypersensitivity, history of sensitivity to
multiple allergens, or previous IgE-mediated reactions.
Use with caution in asthmatic patients.
Penicillin use has been associated with hematologic
disorders believed to be a hypersensitivity phenomenon.
Reactions are most often reversible upon discontinuing
therapy.
Adverse Drug Reactions:
Hypotension, confusion, fever, lethargy, seizure, pruritus,
rash, urticaria, abdominal pain, black or hairy tongue,
diarrhea, flatulence, nausea, oral candidiasis,
pseudomembranous colitis, stomatitis, vomiting,
agranulocytosis, bone marrow depression, eosinophilia,
granulocytopenia, hemolytic anemia, leukopenia,
neutropenia, thrombocytopenia, hepatotoxicity,
thrombophlembitis, arthralgia, myalgia, myoclonus,
hematuria, interstitial nephritis, proteinuria, renal
insufficiency, renal tubular damage, bronchospasm,
laryngeal edema, sneezing, wheezing, serum sickness-
like reaction.
Drug Interactions:
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)
Reduces therapeutic effect of Cloxacillin:
Fusidic acid, Tetracycline derivatives
Decreases excretion of Methotrexate
J
Decreases serum concentration of Mycophenolate
Increases serum concentration of Cloxacillin:
Probenecid
Administration:
Administer with water 1 hour before or 2 hours after meals.
Pregnancy Category: B
ATC Code: J01CF02
Rx OXACILLIN
Inj.: 250 mg and 500 mg vial (as sodium salt) (IM, IV)
Indications: Treatment of infections caused by susceptible
penicillinase­producing staphylococci.
Contraindications: Hypersensitivity to oxacillin, any penicillin
or any component of the formulation.
Dose:
Acute mastoiditis, by IV push, CHILD, 150-200 mg/kg in
divided doses every 6 hours.
Bacterial purulent pericarditis, MSSA, by IV push, CHILD,
200 mg/kg every 6 hours for 3-4 weeks.
Central-line associated bloodstream infection, MSSA, by IV
push, ADULT, 2 g every 4 hours.
Dacryocystitis, MSSA, by IV push, ADULT, 2 g every 6 hours
for 7-14 days.
Neonatal sepsis, by IM injection or IV push, NEONATE ≤7
days old ≤2 kg, 25 mg/kg every 12 hours; NEONATE 8-
28 days old ≤2 kg, 50 mg/kg every 8 hours; NEONATE ≤7
days old >2 kg, 50 mg/kg every 8 hours; NEONATE 8-28
days old >2 kg, 50 mg/kg every 6 hours.
Staphylococcal toxic shock syndrome, by IV push, CHILD,
150-200 mg/kg in divided doses 4-6 hours with
clindamycin or IVIG for 10-14 days; maximum daily dose:
4-12 g.
Osteomyelitis, contiguous focus, mild to moderate, by IV
push, CHILD, 100-150 mg/kg in 4 doses; maximum daily
dose: 4 g;
211

Severe, by IV push, CHILD, 150-200 mg/kg in 4-6 doses;
maximum daily dose: 12 g.
Osteomyelitis, hematogenous unlikely MRSA, long bones, by
IV push, ADULT, 2 g every 4 hours for 4-6 weeks;
Vertebral, by IV push, ADULT, 2 g every 4 hours with
ceftriaxone, piperacillin-tazobactam, OR levofloxacin for
6-12 weeks.
Septic bursitis, MSSA, by IV push, 2 g every 4 hours for 14-
21 days.
Prosthetic joint infection, MSSA, by IV push, ADULT, 2 g
every 4 hours with oral rifampin 300 mg twice daily for 2-
6 weeks.
Native valve infective endocarditis, MSSA, by IV push,
CHILD, 200 mg/kg in divided 4-6 doses for 6 weeks with
or without gentamicin; maximum daily dose: 12 g;
ADULT, 2 g every 4 hours for 4-6 weeks.
Prosthetic valve infective endocarditis, MSSA, by IV push,
CHILD, 200 mg/kg in divided 4-6 doses for 6 weeks with
rifampicin AND gentamicin; ADULT, 2 g every 4 hours
with rifampin and gentamicin.
J
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a
history of beta-lactam hypersensitivity, history of
sensitivity to multiple allergens, or previous IgE-
mediated reactions. Use with caution in asthmatic
patients.
Monitor patients for anaphylactic/hypersensitivity
reactions, hepatitis, superinfection;
Use with caution in patients with renal impairment;
Elderly;
Neonates.
Adverse Drug Reactions:
Fever, rash, diarrhea nausea and vomiting, agranulocytosis,
eosinophilia, leukopenia, neutropenia,
thrombocytopenia, hepatotoxicity, acute interstitial
nephritis, hematuria, serum sickness­like reactions
Drug Interactions:
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)
Reduces therapeutic effect of Oxacillin:
Fusidic acid, Tetracycline derivatives
Decreases excretion of Methotrexate
Decreases serum concentration of Mycophenolate
Increases serum concentration of Oxacillin:
Probenecid
Administration:
For IM: Administer into muscle; Avoid sciatic nerve injury.
For IV: Administer around-the-clock to promote less
variation in peak and trough serum levels. Administer IV
212
ANTI-INFECTIVES FOR SYSTEMIC USE
push over 10 minutes. Administer IV piggyback over 30
minutes.
Pregnancy Category: B
ATC Code: J01CF04
COMBINATIONS OF PENICILLINS,
INCLUDING BETA-LACTAMASE
INHIBITORS
PENICILLINS + BETA- LACTAMASE INHIBITORS
Rx AMPICILLIN + SULBACTAM
Inj.: 500 mg ampicillin + 250 mg sulbactam (as sodium
salt) per vial (IM, IV)
1000 mg ampicillin + 500 mg sulbactam (as sodium
salt) per vial (IM, IV)
2000 mg ampicillin + 1000 mg sulbactam (as sodium
salt) per vial (IM, IV)
Indications: Treatment of susceptible bacterial infections
involved with skin and skin structure, intra-abdominal
infections, Native valve infective endocarditis,
dentoalveolar infection or peri-apical abscess, Ludwig’s
angina, peritonsillar abscess, deep neck abscess/
retropharyngeal abscess, parapharyngeal space
infection, acute epiglottitis, severe community-acquired
pneumonia, acute emphysema, lung abscess
Dose:
Intra-abdominal source, by IM/IV injection, CHILD, 200
mg/kg in divided doses every 6 hours with or without
gentamicin/amikacin for 10-14 days or longer.
Native valve infective endocarditis, community-acquired, by
IV injection, CHILD, 200-300 mg/kg in 4-6 divided doses
with gentamicin; ADULT, 3 g every 6 hours with
gentamicin;
Haemophilus sp, Aggregatibacter sp, Cardiobacterium
hominis, Eikenella corrodens, and Kingella species
(HACEK), beta-lactamase producing, by IV injection,
CHILD, 200-300 mg/kg in 4-6 divided doses every 24
hours for 4 weeks; ADULT, 3 g every 6 hours for 4 weeks.
Dentoalveolar infection or peri-apical abscess, by IV
injection, CHILD, 200-400 mg every 6 hours for 7-14
days until local inflammation has resolved completely;
ADULT, 3 g every 6 hours for 7-14 days until local
inflammation has resolved completely.
Ludwig’s angina, by IV injection, CHILD, 200-400 mg every
6 hours with metronidazole or clindamycin for 2-3 weeks;
ADULT, 3 g every 6 hours with metronidazole or
clindamycin for 2-3 weeks.
Peritonsillar abscess, Deep neck abscess/ retropharyngeal
abscess, by IM/IV injection, CHILD, 100 mg/kg in divided
doses every 6 hours; ADULT, 6-12 g in divided doses
every 6 hours.
Parapharyngeal space infection, by IM/IV injection, CHILD,
100 mg/kg in divided doses every 6 hours; ADULT, 3 g in
divided doses every 6 hours.
Acute epiglottitis, by IV injection, CHILD, 100 mg/kg in
divided doses every 6 hours for 10 days.
ANTI-INFECTIVES FOR SYSTEMIC USE
Community-acquired pneumonia, severe, with no Hib
vaccination or incomplete or unknown vaccination
history, by IV injection, INFANT and CHILD up to 5 years,
100 mg/kg in divided doses every 6 hours;
Moderate-risk, by IV injection, ADULT, 1.5 g every 6 hours
with azithromycin OR clarithromycin OR levofloxacin for
7-28 days.
Acute emphysema, by IV injection, ADULT, 100 mg/kg in
divided doses every 6 hours for 2-4 weeks.
Lung abscess, by IV injection, ADULT, 3 g in divided doses
every 6 hours with metronidazole or piperacillin-
tazobactam for 4-6 weeks.
Pneumonia, anaerobic or aspiration with or without lung
abscess, by IV injection, ADULT, 3 g every 6 hours with
clindamycin for 3-4 weeks or longer.
Pathogen-specific treatment, Acinetobacter species, by IV
injection, ADULT, 3 g every 6 hours with meropenem;
Carbapenem resistant strains, by IV injection, CHILD,
100-200 mg/kg in divided doses every 6 hours with
amikacin OR gentamicin.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
CrCl 15-29 mL/minute/1.73m2: 1.5-3 g every 12 hours.
CrCl 5-14 mL/minute/1.73m2: 1.5-3 g every 24 hours.
Intermittent hemodialysis (IHD) (administer after
hemodialysis on dialysis days): 1.5-3 g every 12-24
hours. Note: Dosing dependent on the assumption of 3
times/week, complete IHD sessions.
Peritoneal dialysis (PD): 3 g every 24 hours.
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug levels in relation to target
trough (if appropriate). The following are general
recommendations only (based on dialysate
flow/ultrafiltration rates of 1-2L/hour and minimal
residual renal function) and should not supersede
clinical judgment:
CVVH: Initial: 3 g; maintenance: 1.5-3 g every 8-12 hours.
CVVHD: Initial: 3 g; maintenance: 1.5-3 g every 8 hours.
CVVHDF: Initial: 3 g; maintenance: 1.5-3 g every 6-8 hours.
Precautions:
WARNING: Serious and occasionally severe or fatal
hypersensitivity reactions have been reported in
patients on penicillin therapy, especially with a history
of beta-lactam hypersensitivity, history of sensitivity to
multiple allergens, or previous IgE-mediated reactions.
Use with caution in asthmatic patients.
Appearance of a rash should be carefully evaluated to
differentiate a non-allergic ampicillin rash from a
hypersensitivity reaction; rash occurs in 5% to 10% of
children and is a generalized dull, red maculopapular
rash, generally appearing 3-14 days after the start of
therapy;
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
Adverse Drug Reactions:
Common: Pain at injection site.
Less Common: Rash, diarrhea, thrombophlebitis, allergic
reaction.
Rare: Abdominal distention, candidiasis, chest pain, chills,
dysuria, edema, epistaxis, erythema, facial swelling,
fatigue, flatulence, glossitis, hairy tongue, headache,
interstitial nephritis, itching, malaise, mucosal bleeding,
nausea, pseudomembranous colitis, seizure, substernal
pain, throat tightness, thrombocytopenia, urine
retention, vomiting.
Drug Interactions:
Decreases bioavailability of Atenolol
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Live attenuated Ty21a strain)
Reduces therapeutic effect of Ampicillin + Sulbactam:
Fusidic acid, Tetracycline derivatives
J
Decreases excretion of Methotrexate
Decreases serum concentration of Mycophenolate
Increases serum concentration of Ampicillin + Sulbactam:
Probenecid
Decreases serum concentration of Ampicillin + Sulbactam:
Chloroquine, Lanthanum
Administration:
Administer around-the-clock to promote less variation in
peak and trough serum levels. Administer by slow
injection over 10-15 minutes or IV over 15-30 minutes.
Ampicillin and gentamicin should NOT be mixed in the same
IV tubing.
Pregnancy Category: B
ATC Code: J01CR01; J01CA51
CO-AMOXICLAV
(AMOXICILLIN +
Rx
POTASSIUM CLAVULANATE)
WHO anti-biotic category: ACCESS
Oral: 500 mg amoxicillin (as trihydrate) + 125 mg
potassium clavulanate per tablet
875 mg amoxicillin (as trihydrate) + 125 mg
potassium clavulanate per tablet
200 mg amoxicillin (as trihydrate) + 28.5 mg
potassium clavulanate per 5 mL granules / powder
for suspension, 70 mL
400 mg amoxicillin (as trihydrate) + 57 mg potassium
clavulanate per 5 mL granules / powder for
suspension, 70 mL
600 mg amoxicillin (as trihydrate) + 42.9 mg
potassium clavulanate per 5 mL granules / powder
for suspension
Indications: Upper respiratory tract infection: exudative or
diffuse erythematous, recurrent pharyngitis, peritonsillar
abscess (Quincy), deep neck abscess/retropharyngeal
abscess, parapharyngeal space infection, acute
213

bacterial rhinosinusitis (ABRS), acute otitis media, acute
otitis media (clinical failure after 3 days), second line
treatment for buccal cellulitis, severe lower respiratory
tract infection, community-acquired pneumonia, febrile
neutropenia
Contraindications: History of cholestatic jaundice or hepatic
dysfunction with amoxicillin/clavulanate potassium
therapy
Dose:
Recurrent pharyngitis, by mouth, ADULT, 500 mg/125 mg
every 12 hours for 10 days; CHILD <40 kg (second line
treatment), 25-45 mg/kg/day divided every 8 hours for
10 days; CHILD >40 kg (second line), 500 mg divided
every 12 hours or 250 mg every 8 hours (or more severe
infections, may increase the dose to 500 mg every 8
hours); INFANT >3 months old, 15-45 mg/kg/day divided
every 12 hours for 10 days.
Peritonsillar abscess (Quincy), by mouth, ADULT, 750 mg–
J
1.5 g per day every 8 hours (amoxicillin component) for
ten days; CHILD, 40 mg/kg per day divided every 8 hours
for 10 days.
Parapharyngeal space infection, by mouth, CHILD, 40
mg/kg per day divided every 8 hours for 10 days.
Acute bacterial rhinosinusitis, by mouth, ADULT (first line),
875/125 mg every 12 hours for 5-7 days; INFANT 1-3
months (first line), 30 mg/kg per day divided every 12
hours for 10-14 days; INFANT >3 months, 20-40 mg/kg
per day divided every 8 hours or 25-45 mg/ kg per day
divided every 12 hours for 10-14 days; For twice daily
dosing, use 200/28.5 mg or 400/57 mg, CHILD >3
months and greater than 40 kg (second line), 90 mg/kg
per day every 12 hours using 600/42.9 mg.
Acute otitis media, by mouth, ADULT with no penicillin
allergy (second line), 875/125 mg every 12 hours for 10
days.
Acute otitis media (clinical failure after 3 days), by mouth,
CHILD > 3 months and <40 kg (first line treatment), 90
mg/kg per day every 12 hours using 600/42.9 mg for 10
days (<2 years old) and for 5-7 days (> 2 years old).
Buccal cellulitis, by mouth, CHILD <5 years old, 45 mg/kg
per day divided every 12 hours for 7-14 days
Bite wounds, by mouth, CHILD and ADOLESCENT ≥40 kg,
875 mg every 12 hours.
Lower Respiratory Tract Infection, with severe infection, by
mouth, ADULT, 875/125 mg twice a day for 5-10 days.
Community-acquired pneumonia, PCAP A or B if with no Hib
vaccination or incomplete or unknown vaccination
history, by mouth, INFANT and CHILD up to 5 years old,
80-90 mg/kg per day (amoxicillin component) divided
every 8 hours (4:1 preparations) or divided every 12
hours (7:1 preparations), CHILD >40 kg, 500/125 mg
every 8 hours (Max 2 g/day of amoxicillin)
Low-risk CAP with stable co-morbid illness, by mouth,
ADULT, 1 g twice daily.
Pneumonia, anaerobic or aspiration with or without lung
abscess, by mouth, ADULT (first line or second line), 1 g
twice daily.
Febrile neutropenia, by mouth, ADULT, 625 mg three times
a day with ciprofloxacin or levofloxacin.
214
ANTI-INFECTIVES FOR SYSTEMIC USE
Dose Adjustment:
Renal Impairment:
Note: 875 mg tablet is not recommended for patients with
renal impairment. The extended-release formulation is
contraindicated in patients with a CrCl of 30mL/min.
Adult and pediatric patients weighing more than 40 kg:
CrCl 30 mL/min or more: No dosage adjustment necessary
CrCl 10-30 mL/min 250 to 500 mg (amoxicillin component)
every 12 hours, depending on the severity of the
infection
CrCl less than 10 mL/min 250-500 mg (amoxicillin
component) every 24 hours, depending on the severity
of the disease
Pediatric patients: dose adjustments are based on a usual
dose of 20-40 mg/kg per day (amoxicillin component)
divided every 8 hours, 25-45 mg/kg per day (amoxicillin
component) divided every 12 hours
CrCl 10-29 mL/min/1.73 m2: 8-20 mg/kg/dose amoxicillin
component (20 mg/kg/dose for high dose) every 12
hours
CrCl less than 10 ml/min/1.73 m2: 8-20 mg/kg/dose
amoxicillin component (20 mg/kg/dose for high dose)
every 24 hours
Precautions:
Monitor for anaphylactic or hypersensitivity reactions,
diarrhea, hepatic effects;
Monitor prolonged use for hepatic, renal and hematopoietic
functions and superinfection if used beyond
recommended duration of treatment;
Use with caution in patients with hepatic impairment
(monitor liver function tests at regular intervals);
Patients with infectious mononucleosis may develop rash
with this product;
Due to differing content of clavulanic acid, not all products
are interchangeable.
Adverse Drug Reactions:
Common: Diarrhea
Less Common: Diaper rash, skin rash, urticaria, abdominal
distress, vomiting, candidiasis, nausea, vaginal mycosis,
vaginitis, cholestatic jaundice, flatulence, headache,
hepatic insufficiency, vasculitis (hypersensitivity
Rare: Reversible leucopenia (including neutropenia),
erythema multiforme
Drug Interactions:
Monitor closely with:
Incompatible with Warfarin (unpredictable effects)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Methotrexate
Administration: Dosage depends on age, weight and renal
function of the patient and the severity of infection.
Dosages are expressed in terms of co-amoxiclav content
except when doses are stated in terms of an individual
component. Therapy can be started parenterally and
continued with an oral preparation.
Two co-amoxiclav 250/125 mg tablets should not be
substituted for one co-amoxiclav 500/125 mg tablet
since they are not equivalent.
Pregnancy Category: B
ANTI-INFECTIVES FOR SYSTEMIC USE
ATC Code: J01CR02
PIPERACILLIN + TAZOBACTAM
Rx
WHO anti-biotic category: WATCH
Inj.: 2 g piperacillin + 250 mg tazobactam (as sodium salt)
per vial (IV infusion)
4 g piperacillin + 500 mg tazobactam (as sodium salt)
per vial (IV infusion)
Indications: Blood-borne infections due to urinary source
(complicated UTI), blood-borne infections due to intra-
abdominal source, high risk blood-borne infection, health
care associated sepsis, severe sepsis and associated
shock, febrile neutropenia in children, non-neutropenic
sepsis, sepsis from suspect urinary tract infection, sepsis
from suspect intra-abdominal source, sepsis from
suspect illicit drug IV use source, osteomyelitis
(hematogenous), vertebral including disk space infection
and other sites, foot bone (calcaneus) following puncture
wound, long bone post-internal fixation of fracture, spinal
implant, acute bacterial arthritis, central line-associated
bloodstream infection (CLABSI) in children,
cardiovascular infection (impaired host, burn
neutropenic), primary spontaneous bacterial peritonitis,
secondary peritonitis, liver abscess, gallbladder
infection, biliary complicated intra-abdominal infection,
extra-biliary complicated intra-abdominal infection,
orbital cellulitis, jugular vein suppurative phlebitis
(Lemierre’s syndrome), necrotizing otitis externa, acute
mastoiditis, chronic or recurrent mastoiditis, high-risk
CAP, lung abscess, pneumonia (anaerobic or aspiration
with or without lung abscess)
Contraindications: History of acute, severe allergic reaction
to any other ß-lactam active substances (e.g.
cephalosporin, monobactam or carbapenem)
Dose:
Blood-borne infection due to intra-abdominal source, by IV
infusion, ADULT (second line), 300 mg (piperacillin
component) for 10-14 days or longer depending on
established foci of infection; (Max: 9-16 g per day)
Healthcare-associated shock, by IV infusion, ADULT, 300
mg/kg per day every 8 hours (piperacillin component)
(Max: 9-16 g per day) for a period of 10-14 days in the
absence of a complication.
Severe sepsis and aseptic shock, by IV infusion, CHILD, 300
mg/kg per day every 8 hours (piperacillin component)
(Max: 9-16 g per day) for a period of 10-14 days in the
absence of a complication.
Febrile neutropenia, by IV infusion, ADULT, 4.5 g every 6
hours, duration of treatment should be dictated by
organism or site; CHILD, 300 mg/kg per day divided
every 6 hours.
Sepsis, Non-neutropenic, by IV infusion, ADULT, (first line)
4.5 g every 6-8 hours.
Sepsis, Intra-abdominal suspect, by IV infusion, ADULT (first
line), 4.5 g every 6-8 hours.
Sepsis, Urinary tract infection suspect, by IV infusion, ADULT
(first line), 4.5 g every 6-8 hours.
Sepsis, Illegal drug IV use suspect, by IV infusion, ADULT,
4.5 g every 6-8 hours.
Osteomyelitis (hematogenous, long bone), by IV infusion,
ADULT, 4.5 g every 8 hours for 4-6 weeks.
Vertebral, including disk space infection and other sites, by
IV infusion, ADULT, (first and second line) 4.5 g every 8
hours, optimal duration of treatment is unknown, usually
6-12 weeks.
Foot bone (calcaneus), following puncture wound, by IV
infusion, ADULT, 4.5 g every 8 hours.
Long bone, post-internal fixation of fracture, by IV infusion,
ADULT, 4.5 g every 8 hours.
Spinal implant, by IV infusion, ADULT, 4.5 g every 8 hours
(within 30 days).
Acute bacterial arthritis, monoarticular, by IV infusion,
ADULT, (not at risk for STI) 4.5 g every 8 hours for 2-4
weeks.
CLABSI, by IV infusion, CHILD, 200-300 mg/kg per day every
8 hours (plus vancomycin and aminoglycoside) 5-7 days
or 10-14 days when catheter is retained or removed.
Cardiovascular infection (impaired host, neutropenic), by IV
infusion, ADULT, 4.5 g every 6-8 hours (plus
vancomycin).
Primary spontaneous bacterial peritonitis, by IV infusion,
J
ADULT (first line), 4.5 g every 6 hours or 4-hour infusion
of 4.5 g every 8 hours; CHILD, 300 mg/kg per day divided
3 doses (piperacillin component).
Secondary peritonitis, by IV infusion, CHILD, 300 mg/kg per
day divided 3 doses (piperacillin component) generally
given for 5-10 days but the primary basis for duration of
antibiotic treatment is the patient’s clinical course.
Liver abscess, by IV infusion, ADULT, 4.5 g every 4-6 hours
(with metronidazole); CHILD, 300 mg/kg per day divided
in 3 doses (piperacillin component) (plus metronidazole).
Gallbladder infection, by IV infusion, CHILD, 300 mg/kg per
day divided by 3 doses (piperacillin component).
Biliary complicated intra-abdominal infection (community-
acquired acute cholecystitis), by IV infusion, ADULT, (first
line) 4.5 g every 6 hours.
Extra-biliary complicated intra-abdominal infection (high
risk), by IV infusion, ADULT, (first line) 4.5 g every 6 hours.
Acute Peritonitis, by IV infusion, ADULT, (first line) 4.5 g
every 4-6 hours. (Maximum dose for children is 3000
mg/ dose)
Orbital Cellulitis, by IV infusion, ADULT, (if MRSA is not
considered) 4.5 g/kg every 8 hours; CHILD, (first line)
240-300 mg/kg per day in 3-4 doses (piperacillin
component) (max: 16 g/day).
Jugular vein suppurative phlebitis (Lemierre’s syndrome), by
IV infusion, ADULT/CHILD, (first line) 4.5 g every 8 hours.
Acute sinusitis in hospitalized patients with intubation, by IV
infusion, ADULT/CHILD, (first line) 4.5 g every 6-8 hours.
Necrotizing otitis externa, by IV infusion, ADULT, (first line)
4.5 g every 6 hours, (second line) 4.5 g every 6 hours +/-
gentamicin or amikacin per day; CHILD, (second line)
300 mg/kg per day every 8 hours.
Acute mastoiditis, by IV infusion, ADULT, (second line) 4.5 g
every 8 hours (plus vancomycin).
Chronic or recurrent mastoiditis, by IV infusion, CHILD, 300
mg/kg per day every 6 hours (plus gentamicin).
High-risk CAP (Risk for P. aeruginosa), by IV infusion, ADULT,
4.5 g every 6 hours (plus azithromycin and gentamicin or
levofloxacin or ciprofloxacin).
Lung abscess, by IV infusion, ADULT, 4.5 g every 8 hours (for
mixed infections with resistant gram-negative aerobes)
in combination with clindamycin or ampicillin-sulbactam
or ceftriaxone for 4-6 hours.
Pneumonia (anaerobic or aspiration with or without lung
abscess), by IV infusion, ADULT, (second line) 4.5 g every
8 hours.
215
 ANTI-INFECTIVES FOR SYSTEMIC USE

(HAP) Hospital-acquired pneumonia and Ventilator- Increases serum concentration of Piperacillin +

associated pneumonia (MDR pathogens), by IV infusion, Tazobactam:
ADULT/CHILD, 300 mg/kg/day every 6 hours. Probenecid
HAP with or without high risk of mortality and with or without
risk factor for MDR, by IV infusion, ADULT and CHILD, 4.5 Reduces therapeutic effect of Piperacillin + Tazobactam:
g every 6 hours. Tetracycline, Typhoid Vaccine (Only the live attenuated
Empiric treatment of Ventilation-acquired pneumonia, by IV Ty21a strain is affected)
infusion, ADULT and CHILD, 4.5 g every 6 hours.
Lower respiratory tract infection due to P. aeruginosa, by IV Administration:
infusion, ADULT, 4.5 g every 6 hours by extended Compatible diluents for reconstitution are 0.9% Sodium
infusion; CHILD (second line), 300 mg/kg/day divided Chloride for Injection, Sterile Water for Injection,
every 6 hours. Bacteriostatic Water for Injection, Bacteriostatic Water
for Injection with benzyl alcohol, Bacteriostatic water for
NOTE: Maximum dose for adults is 18 g daily unless injection with parabens.
specified Reconstitute vial with the right diluent. Shake well until
dissolved.
Dose Adjustment:
Renal Impairment: Pregnancy Category: C
CrCl 20 to 40 mL/min:
Nosocomial pneumonia: 3.375 g IV every 6 hours ATC Code: J01CR05
J

Other indications: 2.25 g IV every 6 hours

Precautions: OTHER BETA-LACTAM ANTIBACTERIALS

WARNING: Serious and occasional fatal hypersensitivity
(anaphylactic) reactions for people with hypersensitivity FIRST-GENERATION CEPHALOSPORINS
to multiple allergens.
Cross sensitivity reactions may happen with other CEFALEXIN (CEPHALEXIN)
lactam antibiotics such as cephalosporins. Rx
WHO anti-biotic category: ACCESS
In case of severe, persistent diarrhea, the possibility of
antibiotic -induced pseudomembranous colitis must be Oral: 500 mg capsule (as monohydrate)
taken into consideration. 100 mg/mL, granules / powder for drops (as
monohydrate), 10 mL
Patient with cystic fibrosis, history of seizure disorder, renal 125 mg/5 mL granules / powder for syrup /
impairment, children, pregnancy and lactation suspension (as monohydrate), 30 mL
250 mg/5 mL granules / powder for syrup /
Adverse Drug Reactions: suspension (as monohydrate), 60 mL
Common: Phlebitis, headache, insomnia, skin rash,
pruritus, electrolyte disturbance, hypokalemia, Indications: Treatment of dacryocystitis, mild methicillin
hyperglycemia, diarrhea, constipation, nausea, sensitive staphylococcus aureus infections, and dental
dyspepsia, vomiting, abdominal pain, eosinophilia, prophylaxis
positive direct Coombs test, leukopenia, neutropenia,
prolonged bleeding time, thrombocythemia, Dose:
thrombocytopenia, candidiasis, local irritation, fever Dental prophylaxis, allergic to penicillins or ampicillin, by
Less Common: Flushing, hypotension, rigors, mouth, CHILD, 50 mg/kg; ADULT, 2 g.
thrombophlebitis, purpura, pseudomembranous colitis, Dacryocystitis, by mouth, ADULT, 500 mg four times a day
hypoglycemia, anaphylaxis, injection site reaction, for 7-14 days.
arthralgia, myalgia, epistaxis Methicillin sensitive staphylococcus aureus, mild to
moderate infections, by mouth, 25- 50 mg/kg/day
Drug Interactions: divided in 3-4 doses, severe infections, by mouth, 75-
Monitor closely with: 100 mg/kg/day divided in 3- 4 doses
Reduces therapeutic effect of BCG Vaccine
Dose Adjustment:
Increases risk of adverse or toxic effects of Vancomycin Renal Impairment:
Adults: CrCl 10-50mL/min, 500 mg every 8-12 hours; CrCl
Enhances absorption of Vecuronium < 10 mL/min, 250-500 mg every 12-24 hours
Hemodialysis patients, 250 mg every 12-24 hours;
Enhances therapeutic effect of Vitamin K Antagonists e.g. moderately dialyzable (20-50%); give dose after dialysis
Warfarin session.

Avoid concomitant use with: Precautions:

Decreases serum concentration of Aminoglycosides e.g.
Streptomycin
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Sodium Picosulfate
Elevated INR especially with nutritionally-deficient patients,
prolonged treatment, hepatic or renal disease;
Penicillin allergy. Use with caution in patients with history of
penicillin allergy, especially IgE-mediated reactions (eg.
anaphylaxis, angioedema, urticaria);

216
ANTI-INFECTIVES FOR SYSTEMIC USE
Prolonged use may result in bacterial or fungal
superinfection including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis, CDAD has been
observed >2 months post-antibiotic treatment.
Adverse Drug Reactions:
Common and Less Common: Agitation, confusion,
dizziness, fatigue, hallucination, headache, genital
pruritus, skin rash, urticaria, abdominal pain, diarrhea,
dyspepsia, pseudomembranous colitis, gastritis, genital
candidiasis, vaginal discharge, vaginitis, eosinophilia,
hemolytic anemia, thrombocytopenia, neutropenia,
anaphylaxis, angioedema, arthralgia, arthritis,
arthropathy, hypersensitivity reactions
Rare: Erythema multiforme, Stevens Johnson syndrome,
toxic epidermal necrosis, nausea, vomiting, cholestatic
jaundice, hepatitis (transient), interstitial nephritis
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
BCG (intravesical), Sodium picosulfate, Typhoid vaccine
Enhances therapeutic effect of Vitamin K antagonists e.g.
Warfarin
Increases serum concentration of Cefalexin:
Metformin, Probenecid
Decreases serum concentration of Cefalexin:
Multivitamins/Minerals (with ADEK, folate, iron)
Reduces absorption of Cefalexin:
Zinc salts
Administration: Take without regard to food. If GI distress,
take with food. Give around­the­clock to promote less
variation in peak and trough serum levels.
Pregnancy Category: B
ATC Code: J01DB01
CEFAZOLIN
Rx
WHO anti-biotic category: ACCESS
Inj.: 500 mg and 1 g vial (as sodium salt) (IM, IV)
Indications: Treatment of staphylococcal toxic shock
syndrome, osteomyelitis, septic bursitis, prosthetic joint
infection, native valve infective endocarditis, central-line
associated bloodstream infection, dacryocystitis, and
dental prophylaxis
Contraindication: Known allergy to the cephalosporin group
of antibiotics.
Dose:
Staphylococcal toxic shock syndrome, by IV injection/
infusion, CHILD, 75-100 mg/kg in divided doses every 8
hours; maximum daily dose: 3-6 g.
Osteomyelitis, contiguous focus, MSSA, mild to moderate,
by IV injection/ infusion, CHILD, 50 mg/kg in 3 doses;
maximum daily dose: 4 g;
Severe, by IV injection/ infusion, CHILD, 100-150 mg/kg
in 3 doses; maximum daily dose: 6 g.
Septic bursitis, MSSA, by IV injection/ infusion, ADULT, 2 g
every 8 hours for 14-21 days.
Prosthetic joint infection, MSSA, by IV injection/ infusion,
ADULT, 2 g every 8 hours with rifampin for 2-6 weeks.
Native valve infective endocarditis, MSSA, by IV injection/
infusion, ADULT, 2 g every 8 hours for 6 weeks.
Dental prophylaxis, by deep IM injection or IV injection/
infusion, CHILD, 50 mg/kg; ADULT, 1 g.
Central-line associated bloodstream infection, MSSA, by IV
injection/ infusion, ADULT, 2 g every 8 hours.
Dacryocystitis, by IV injection/ infusion, ADULT, 2 g every 8
hours for 7-14 days.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
J
Adults:
CrCl 35-54 mL/minute or SrCr 1.6-3 mg%: Full dose every 8
hours or longer; ClCr 11-34 mL/minute or SrCr 3.1-4.5
mg%: 1/2 usual dose every 12 hours; CrCl ≤10
mL/minute or SrCr ≥4.6 mg%: 1/2 usual dose every 18-
24 hours.
Pediatrics:
CrCl 41-70 mL/minute: 60% of usual dose given in equally
divided doses every 12 hours; CrCl 21-40 mL/minute:
25% of usual dose given in equally divided doses every
12 hours; CrCl ≤5-20 mL/minute: 10% of usual dose
given in equally divided doses every 24 hours.
Precautions:
Monitor patients for: Elevated INR, Penicillin Allergy,
Superinfection;
Use with caution in patients with: Renal Impairment, Seizure
Disorders.
Adverse Drug Reactions: Diarrhea, oral candidiasis,
stomach cramps, anorexia, anaphylaxis, eosinophilia,
itching, skin rash, leukopenia, thrombocytopenia,
hepatitis, genital or anal pruritus
Drug Interactions:
Increases serum concentration of Cefazolin:
Probenecid
Increases risk of adverse or toxic effects of the following
drugs:
Fosphenytoin, Phenytoin, Vitamin K Antagonists e.g.
Warfarin
Reduces therapeutic effect of the following drugs:
BCG Vaccine (Immunization), Typhoid Vaccine
Administration:
For IM: Inject deep IM into large muscle mass.
For IV: Inject direct IV over 5 minutes or may infuse as an
intermittent infusion over 30­60 minutes.
Pregnancy Category: B
ATC Code: J01DB04
217
 ANTI-INFECTIVES FOR SYSTEMIC USE

SECOND-GENERATION CEPHALOSPORINS NOTE: Alternative recommendations: 2g within 60 minutes

prior to surgical incision; Doses may be repeated in 2
hours if procedure is lengthy or if there is excessive blood
Rx CEFOXITIN loss.

CHILD and INFANT >3 months old, 30-40 mg/kg 30-60

Inj.: 1 g vial (as sodium salt) (IM, IV)
minutes prior to surgical incision followed by 30-40
1 g powder for injection (as sodium) + 4% Dextrose
mg/kg/dose every 6 hours for no more than 24 hours
Solution for injection (IV infusion)
after surgery depending on the procedure.
Indications: Treatment of serious infections wherein
NOTE: Alternative recommendations: Children ≥1 years old:
anaerobes are suspected or documented including
40 mg/kg within 60 minutes prior to surgical incision
those of the lower respiratory tract, skin and skin
(maximum: 2000 mg/dose), doses may be repeated in 2
structure, bone and joint, and urinary tract; septicemia;
hours if procedure is lengthy or if there is excessive blood
Gynecologic infections; intra­abdominal infections
loss.
caused by susceptible bacteria; perioperative
prophylaxis
Dose Adjustment:
Renal Impairment:
Contraindications: Hypersensitivity to cefoxitin, any
IV: CrCl 30-50mL/minute: 1-2g every 8-12 hours; CrCl 10-
component of the formulation, or other cephalosporins.
29mL/minute: 1-2g every 12-24 hours; CrCl 5-9
J

mL/minute: 0.5-1g every 12-24 hours; CrCl

Dose:
<5mL/minute: 0.5-1g every 24-48 hours; Hemodialysis:
General dosing information, by IV push/ infusion,
Loading dose: 1-2g after each hemodialysis;
ADOLESCENT, CHILD, and INFANT >3 months, 80-160
Maintenance dose as noted above based on creatinine
mg/kg/day divided every 4-6 hours (max. daily dose: 12
clearance.
g).
Precautions:
NOTE: Alternative dose: Mild­to­moderate infection: Infants
Monitor patients for: Hypersensitivity, Superinfection; Use
>3 months old and Children, 80 mg/kg/day in divided
with caution in patients with: Gastrointestinal disease;
doses every 6-8 hours (maximum daily dose: 4000
renal impairment; seizure disorders; Discontinuation of
mg/day);
therapy: In pediatric patients ≥3 months old, higher
Severe infection: Infants >3 months old and Children, 160
doses have been associated with an increased incidence
mg/kg/day in divided doses every 4-6 hours (maximum
of eosinophilia and elevated AST.
dose: 12 g/day).
Adverse Drug Reactions:
Susceptible infections, by IV push/ infusion, ADULT, 1-2 g
Local reactions, rash, pruritus, fever, dyspnea, hypotension,
every 6-8 hours.
diarrhea, pseudomembranous colitis, exacerbation of
myasthenia gravis, eosinophilia, leukopenia,
NOTE: IM injection is painful
thrombocytopenia, bone marrow depression
Gas gangrene, by IV push/ infusion, ADULT, 2 g every 4
Drug Interactions:
hours or 3 g every 6 hours (max. daily dosage: 12 g).
Increases serum concentration of Cefoxitin:
Intra­abdominal infection, complicated community-
Probenecid
acquired, by IV push/ infusion, ADULT, Mild to moderate:
2 g every 6 hours for 4-7 days;
Increases risk of adverse or toxic effects of the following
Moderately severe or severe infections: 1 g every 4 hours or
drugs:
2 g every 6-8 hours (max. daily dosage: 8 g);
Aminoglycosides e.g. Streptomycin
Extra-biliary complicated intra- abdominal infections: 2 g
Vitamin K Antagonists e.g. Warfarin
every 6 hours.
Pelvic inflammatory disease for inpatients, by IV push/
Reduces therapeutic effect of the following drugs:
infusion, ADULT, 2 g every 6 hours plus doxycycline for at
BCG Vaccine, Typhoid Vaccine
least 24 hours after clinical improvement, followed by
doxycycline to complete 14 days;
Administration:
For outpatients, by IM injection, ADULT, 2 g with oral
For IM: Inject deep IM into large muscle mass.
probenecid, followed by doxycycline (with or without
For IV: Can be administered IVP over 3-5 minutes or by IV
concomitant metronidazole) for 14 days.
intermittent infusion over 10-60 minutes.
Surgical (perioperative) prophylaxis, by IV push/ infusion,
ADULT and ADOLESCENT, procedures other than
Pregnancy Category: B
Cesarean section, 2g 30-60 minutes prior to surgical
incision, followed by 2g every 6 hours for no more than
ATC Code: J01DC01
24 hours after surgery depending on the procedure;
Cesarean section: 2g as soon as umbilical cord is clamped
as a single dose or 2g as soon as umbilical cord is
clamped followed by 2g at 4 and 8 hours after the initial
dose;

218
ANTI-INFECTIVES FOR SYSTEMIC USE

Continuous renal replacement therapy (CRRT): 1 g every 12

Rx CEFUROXIME hours.

Oral: 500 mg tablet (as axetil) Precautions:

125 mg/5 mL granules for suspension (as axetil), 70
mL
250 mg/5 mL granules for suspension, 50 mL and
120 mL
Inj.: 250 mg and 750 mg vial (IM, IV)
1.5 g VIAL (as sodium salt) (IV infusion)
Indications: Treatment of infections caused by methicillin
sensitive staphylococci, group B. streptococcus, H.
influenzae (type A and B), E. coli, Enterobacter,
Salmonella, and Klebsiella; treatment of susceptible
infections of the upper and lower respiratory tract, otitis
media
Contraindications: Hypersensitivity to cefuroxime, any
component of the formulation, or other cephalosporins.
WARNING: Use with caution in patients with a history of
penicillin allergy.
May be associated with increased INR, especially in
nutritionally-deficient patients, prolonged treatment,
hepatic or renal disease; Prolonged use may result in
fungal or bacterial superinfection, including C. difficile-
associated diarrhea (CDAD) and pseudomembranous
colitis; CDAD has been observed >2 months post-
antibiotic treatment.
Adverse Drug Reactions:
Common: Diarrhea
Less Common: Diaper rash, nausea, vomiting, vaginitis,
eosinophilia

J
Rare: Anaphylaxis, angioedema, chest pain, cholestasis,
Dose: colitis, dyspnea, erythema multiforme, fever, GI bleeding,
Acute otitis media, no anaphylaxis, by mouth, CHILD, 30 hemolytic anemia, hepatitis, hives, hyperbilirubinemia,
mg/kg every 12 hours for 10 days (<2 years old), 7 days hypersensitivity, interstitial nephritis, jaundice,
(2-5 years old), 5-7 days (>5 years old); ADULT, 500 mg- leukopenia, neutropenia, pain at injection site,
1 g in divided doses every 12 hours for 7 days. pancytopenia, positive Coombs test,
Acute otitis media, clinical failure after 3 days, by mouth, pseudomembranous colitis, rash, renal dysfunction,
CHILD, 30 mg/kg in divided doses every 12 hours for 10 seizure, SJS, stomach cramps, tachycardia,
days (2yrs old OR severe symptoms regardless of age), thrombocytopenia, tongue swelling, toxic epidermal
5-7 days (>2yrs with mild or moderate disease). necrolysis, urticaria.
Acute bacterial exacerbation of chronic bronchitis (ABECB),
by mouth, ADULT, 500 mg twice a day for 5-10 days Drug Interactions:
Community-acquired pneumonia, non-severe, by mouth, Decreases serum concentration of Cefuroxime:
CHILD >40 kg, 20-30 mg/kg in divided doses every 12 Antacids
hours for 7 days;
Severe, with no Hib vaccination or incomplete or Reduces therapeutic effect of the following drugs:
unknown vaccination history, by mouth, CHILD, 100 BCG, Typhoid vaccine (Only the live attenuated Ty21a
mg/kg in divided doses every 8 hours. strain is affected.)
With stable co-morbid illness, by mouth, ADULT, 500 mg
twice a day for 5-7 days or 3-5 days if using with Increases serum concentration of Cefuroxime:
azithromycin. Probenecid
Recurrent pharyngitis, by mouth, CHILD, 20 mg/kg in
divided doses every 12 hours for 10 days; ADULT, 500 Reduces absorption of Cefuroxime:
mg-1 g every 12 hours for 10 days. H2-antagonists e.g. Cimetidine (Separate oral doses by
Deep neck abscess/ Retropharyngeal abscess, by mouth, at least 2 hours.)
CHILD, 20-30 mg/kg in divided doses every 12 hours
with metronidazole 10 mg/kg in divided doses every 6 Administration:
hours for at least 7 days; ADULT, 500 mg twice daily with For Oral suspension: Administer with food. Shake well
metronidazole 500 mg every 8 hours for at least 7 days. before use.
Acute bacterial rhinosinusitis, with severe penicillin allergy, For IM: Inject deep IM into large muscle mass.
by mouth, CHILD, 30 mg/kg in divided doses every 12 For IV: Inject direct IV over 3-5 minutes. Infuse intermittent
hours for 10 days; ADULT, 500 mg twice daily for 5-7 infusion over 15-30 minutes.
days.
Acute sinusitis (clinical failure after 3 days), by mouth, Pregnancy Category: B
ADULT, 500 mg twice daily for 7-10 days.
ATC Code: J01DC02
Dose Adjustment:
Geriatric:
Refer to adult dosing.

Renal Impairment:
CrCl 10-20mL/minute: Administer every 12 hours.
CrCl <10mL/minute: Administer every 24 hours.
Hemodialysis: Dialyzable (25%).
Peritoneal dialysis: Dose every 24 hours.

219

THIRD-GENERATION CEPHALOSPORINS
Rx CEFIXIME
WHO anti-biotic category: ACCESS and WATCH
Oral: 200 mg capsule and 400 mg capsule
20 mg/mL granules for drops (suspension), 10 mL
100 mg/5 mL granules for suspension, 60 mL
Indications: Second line therapy for uncomplicated typhoid
fever, salmonella gastroenteritis, uncomplicated
gonococcal infections of the cervix, urethras, rectum and
conjunctiva. Step down therapy for severe/complicated
typhoid fever
Dose:
Gonococcal conjunctivitis, CHILD, by mouth, 8 mg/kg/day
with 10- 12 mg/kg/day of azithromycin
Uncomplicated typhoid fever (second line), by mouth,
J
CHILD, 15-20 mg/kg/day every 12 hours for 7-10 days;
maximum daily dose: 12 g; ADULT, 200mg every 12
hours for 7-10 days.
Step down therapy, Severe complicated typhoid fever, by
mouth, CHILD, 15-20 mg/kg every 12 hours for 7-10
days; maximum daily dose: 200 mg 1 tablet every 12
hours; ADULT, 200 mg 1 tablet every 12 hours for 7-10
days.
Salmonella gastroenteritis, by mouth, CHILD, 15 mg/kg in
divided doses every 12 hours for 7-10 days; maximum
daily dose: 400 mg.
Uncomplicated gonococcal infections of the cervix, urethras
and rectum, ADULT, 400 mg per dose with 1g of
azithromycin per dose, CHILD, by mouth, 8 mg/kg/day
with 10-12 mg/kg/day of azithromycin
Dose Adjustment:
Renal Impairment:
CrCl 21-60 mL/ minute: Administer 75% of the standard
dose.
CrCl <20 mL/minute: Administer 50% of the standard dose.
10% removed by hemodialysis.
Precautions:
WARNING: Use with caution in patients with a history
of penicillin allergy, especially IgE-mediated
reactions.
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis. CDAD has been
observed >2 months post-antibiotic treatment; Use with
caution in patients with renal impairment; modify
dosage.
Adverse Drug Reactions:
Common: Diarrhea
Less Common: Abdominal pain, nausea, dyspepsia,
flatulence, loose stools.
Rare: Acute renal failure, anaphylactic reactions,
angioedema, candidiasis, dizziness, drug fever,
eosinophilia, erythema multiforme, facial edema, fever,
headache, hepatitis, hyperbilirubinemia, jaundice,
leukopenia, neutropenia, pseudomembranous colitis,
rash, seizure, serum sickness-like reaction, SJS,
220
ANTI-INFECTIVES FOR SYSTEMIC USE
thrombocytopenia, toxic epidermal necrolysis, urticaria,
vaginitis, vomiting.
Drug Interactions:
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a strain
is affected)
Increases serum concentration of Cefixime:
Probenecid
Administration:
May be administered with or without food; administer with
food to decrease GI distress.
Shake oral suspension well before use.
Pregnancy Category: B
ATC Code: J01DD08
Rx CEFOTAXIME
WHO anti-biotic category: ACCESS and WATCH
Inj.: 250 mg vial (as sodium salt) + 2 mL diluent (IM, IV)
500 mg vial (as sodium salt) + 2 mL diluent (IM, IV)
Indications: Treatment of serious bone and joint infections,
meningitis and other central nervous system infections,
serious lower respiratory tract infections (including
pneumonia), bacteremia/septicemia, serious skin and
skin structure infections, multi drug resistant or
complicated typhoid fever and other infections caused by
Salmonella, infections caused by Vibrio
parahaemolyticus or V. vulnificus.
Dose:
Bacterial purulent pericarditis, by IV bolus/ infusion, CHILD,
200-300 mg/kg in divided doses every 6 to 8 hours;
maximum daily dose: 12 g.
Community acute bacterial meningitis, by deep IM injection
or IV bolus/ infusion, NEONATE 0-7 days old and <2kg,
50 mg/kg every 12 hours; NEONATE 0-7 days old and
≥2kg, 50 mg/kg every 8 hours; NEONATE >7 days old
and <2kg, 50 mg/kg every 8 hours; NEONATE >7 days
old and ≥2kg, 50 mg/kg every 6 hours; duration
dependent on the etiology of bacterial meningitis.
Neonatal Sepsis, by deep IM injection or IV bolus/ infusion,
NEONATE ≤7 days old ≤2kg, 50 mg/kg every 12 hours;
NEONATE 8-28 days old ≤2kg, 50 mg/kg every 8-12
hours; NEONATE ≤7 days old >2kg, 50 mg/kg every 12
hours; NEONATE 8-28 days old >2kg, 50 mg/kg every 8
hours; with gentamicin OR amikacin with or without
oxacillin OR vancomycin.
Clinical sepsis without focus, by deep IM injection or IV
bolus/ infusion, CHILD, 200-225 mg/kg in divided doses
every 4-6 hours for 10-14 days or longer depending on
established foci of infection.
Immunocompetent children, Urinary source, by IV bolus/
infusion, CHILD, 200-225 mg/kg in divided doses every
4-6 hours; maximum daily dose: 8-12 g.
Immunocompetent children, Intra-abdominal source, by IV
bolus/ infusion, CHILD, 200-225 mg/kg in divided doses
every 4-6 hours; maximum daily dose: 8-12 g.
ANTI-INFECTIVES FOR SYSTEMIC USE
Post-splenectomy, by IV bolus/ infusion, CHILD, 200-225
mg/kg in divided doses every 4-6 hours; maximum daily
dose: 8-12 g.
Non-typhoidal salmonellosis, by IV bolus/ infusion, CHILD,
100-200 mg/kg in divided doses every 6 hours for 5-14
days; maximum daily dose: 8-12 g.
Leptospirosis, moderate to severe, by IV bolus/ infusion,
CHILD, 100-150 mg/kg every 6-8 hours for 7 days;
maximum daily dose: 1 g every 6 hours.
Orbital Cellulitis, by IV bolus/ infusion, CHILD, 100-200
mg/kg in 3-4 doses with linezolid for 7-14 days
depending on clinical response; maximum daily dose: 2g.
Osteomyelitis, hematogenous, by IV bolus/ infusion, INFANT
0-4 weeks and <1.2kg, 100 mg/kg in 2 doses; INFANT
<7 days old and 1.2-2kg, 100 mg/kg in 2 doses; INFANT
>7 days old and 1.2-2kg, 150 mg/kg in 3 doses; INFANT
<7 days old and >2kg, 100 mg/kg in 2 doses; INFANT >7
days old and >2kg, 150-200 mg/kg in 3-4 doses; CHILD,
100-200 mg/kg in 1-2 doses; maximum daily dose: 8 g.
Prosthetic valve infective endocarditis, gram negative
enteric bacilli, by IV bolus/ infusion, CHILD, 200 mg/kg
in divided doses every 6 hours daily for 6 weeks with
gentamicin; maximum daily dose: 12 g.
Suppurative arthritis, gram stain is negative OR if gram stain
is positive for gram-positive cocci, by IV bolus/ infusion,
CHILD, 100-200 mg/kg in 3-4 doses with vancomycin;
maximum daily dose: 12 g.
Suppurative arthritis, gram stain is positive for gram-
negative organisms, by IV bolus/ infusion, CHILD, 100-
200 mg/kg in 3-4 doses; maximum daily dose: 12 g.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Note: Renal function may be estimated using
Cockcroft­Gault formula for dosage adjustment
purposes.
CrCl <20mL/minute/1.73 m2: dose should be decreased by
50%.
Alternative recommendation:
Adults:
Glomerular Filtration Rate >50 mL/minute: Administer
every 6 hours; Glomerular Filtration Rate 10-50
mL/minute: Administer every 6-12 hours; Glomerular
Filtration Rate <10 mL/minute: Administer every 24
hours or decrease the dose by 50% (and administer at
usual intervals); Intermittent hemodialysis: Administer 1-
2 g every 24 hours (on dialysis days, administer after
hemodialysis).
NOTE: Dosing dependent on the assumption of 3 times a
week, complete intermittent hemodialysis sessions.
Peritoneal dialysis: 1 g every 24 hours
Continuous renal replacement therapy: Drug clearance is
highly dependent on the method of renal replacement,
filter type, and flow rate. Appropriate dosing requires
close monitoring of pharmacologic response, signs of
adverse reactions due to drug accumulation, as well as
drug concentrations in relation to target trough (if
appropriate). The following are general
recommendations only (based on dialysate flow
ultrafiltration rates of 1-2 L/h and minimal residual renal
function) and should not supersede clinical judgment:
Continuous veno-venous hemofiltration: 1-2 g every 8-12
hours; Continuous veno-venous hemodialysis: 1-2 g
every 8 hours; Continuous venovenous
hemodiafiltration: 1-2 g every 6-8 hours.
Children:
NOTE: Glomerular filtration rate should be estimated using
an acceptable pediatric method (eg, Schwartz equation,
Traub­Johnson equation, or a height/weight nomogram).
Dose Adjustment:
Glomerular filtration rate 30-50 mL/minute/1.73m2: 35-70
mg/kg/dose every 8-12 hours; Glomerular filtration rate
10 to 29 mL/minute/1.73m2: 35-70 mg/kg/dose every
12 hours; Glomerular filtration rate <10
mL/minute/1.73m2: 35 to 70 mg/kg/dose every 24
hours; Intermittent hemodialysis: 35-70 mg/kg/dose
every 24 hours; Peritoneal dialysis: 35-70 mg/kg/dose
every 24 hours; Continuous renal replacement therapy:
J
35-70 mg/kg/dose every 12 hours.
Precautions:
Monitor patients for: arrhythmia, granulocytopenia,
penicillin allergy, tissue inflammation, superinfection;
Use with caution in patients with colitis and renal
impairment.
Adverse Drug Reactions:
Injection-site reactions (e.g., pain, induration, tenderness,
inflammation)
Drug Interactions:
Increases serum concentration of Cefotaxime:
Probenecid
Increases risk of adverse or toxic effects of the following
drugs:
Aminoglycosides, Vitamin K Antagonists (e.g. Warfarin)
Reduces therapeutic effect of the following drugs:
BCG Vaccine (Immunization), Typhoid Vaccine
Administration:
For IM: Inject deep IM into large muscle mass. Individual
doses of 2 g may be given if the dose is divided and
administered in different IM sites.
For IV: Inject directly IV as a bolus over at least 3-5 minutes.
Infuse intermittent infusion over 15-30 minutes.
Pregnancy Category: B
ATC Code: J01DD01
221

CEFTAZIDIME
Rx
WHO anti-biotic category: WATCH
Inj.: 250 mg, 500 mg, and 1 g vial (as pentahydrate) (IM,
IV)
2 g vial (as pentahydrate) (IV infusion)
Indications: Treatment of documented susceptible
Pseudomonas aeruginosa infection and infections due
to other susceptible aerobic gram-negative organisms;
neonatal sepsis, osteomyelitis, bone and joint infections,
necrotizing otitis externa, dacryocystitis, acute sinusitis,
infective endocarditis.
Dose:
Neonatal Sepsis, by deep IM injection or IV push/ infusion,
NEONATE ≤7 days old ≤2 kg, 50 mg/kg every 12 hours;
NEONATE 8-28 days old ≤2 kg, 50 mg/kg every 8-12
hours; NEONATE ≤7 days old >2 kg, 50 mg/kg every 12
hours; NEONATE 8-28 days old >2 kg, 50 mg/kg every 8
J
hours; with gentamicin OR amikacin.
Healthcare-associated sepsis, by deep IM injection or IV
push/ infusion, CHILD, 150-200 mg/kg in divided doses
every 8 hours with or without amikacin OR vancomycin;
maximum daily dose: 6 g.
Osteomyelitis, hematogenous, long bones, by IV push/
infusion, ADULT, 2 g every 8 hours with vancomycin OR
oxacillin for 6-12 weeks.
Osteomyelitis, contiguous without vascular insufficiency,
foot bone, by IV push/ infusion, ADULT, 2 g every 8 hours.
Long bone or spinal implant, by IV push/ infusion, ADULT,
2 g every 8 hours with vancomycin 15-20 mg/kg every 8-
12 hours.
Acute bacterial arthritis (gram negative bacilli), by IV push/
infusion, ADULT, 2 g every 8 hours.
Bone and joint infections, by IV push/ infusion, ADULT, 2 g
every 12 hours for 4-6 weeks.
Native valve infective endocarditis, healthcare-associated,
by IV push/ infusion, CHILD, 100-150 mg/kg in divided
doses every 8 hours with vancomycin and gentamicin;
maximum daily dose: 2-4 g; ADULT, 2 g every 8 hours
with vancomycin and gentamicin.
Prosthetic valve infective endocarditis, gram-negative
enteric bacilli, by IV push/ infusion, CHILD, 100-150
mg/kg in divided doses every 8 hours for 6 weeks;
maximum daily dose: 2-4 g.
Impaired host, burn, neutropenic, by IV push/ infusion,
ADULT, 2 g every 8 hours with vancomycin.
Anatomic defects, neurological complications, open head
trauma, by deep IM injection or IV push/ infusion, CHILD,
150 mg/kg in divided doses every 8 hours with
vancomycin; ADULT, 2 g every 8 hours with vancomycin.
Brain abscess in the presence of chronic otitis media,
sinusitis, or mastoiditis, by deep IM injection or IV push/
infusion, CHILD, 150 mg/kg in divided doses every 8
hours with metronidazole; ADULT, 2 g every 8 hours with
metronidazole.
Dacryocystitis, by IV push/ infusion, CHILD, 100 mg/kg
divided in 3 doses for 7-14 days.
Acute sinusitis, by IV push/ infusion, ADULT, 2 g every 8
hours with vancomycin.
Necrotizing otitis externa, by IV push/ infusion, CHILD, 100-
150 mg/kg in divided doses every 8 hours.
Hospital-acquired and ventilator-associated pneumonia, by
IV infusion, CHILD, 100-150 mg/kg in divided doses
222
ANTI-INFECTIVES FOR SYSTEMIC USE
every 8 hours infused for 15-30 minutes with
vancomycin OR linezolid.
Pathogen-specific treatment, P. aeruginosa, by IV push/
infusion, CHILD, 100-150 mg/kg in divided doses every
8 hours with amikacin OR gentamicin; ADULT, 2 g every
8 hours with amikacin OR gentamicin OR aztreonam;
Achromobacter, by IV push/ infusion, CHILD, 100-150
mg/kg in divided doses every 8 hours with trimethoprim-
sulfamethoxazole;
Burkholderia pseudomallei, by IV push/ infusion, CHILD,
100-150 mg/kg in divided doses every 8 hours with
trimethoprim-sulfamethoxazole for 12-24 weeks; ADULT,
2 g every 6 hours for 10-14 days.
Dose Adjustment:
Geriatric:
IM, IV: Dosage should be based on renal function with a
dosing interval not more frequent than every 12 hours.
Renal Impairment:
CrCl 30-50mL/minute: Administer every 12 hours.
CrCl 10-30mL/minute: Administer every 24 hours.
CrCl <10mL/minute: Administer every 48-72 hours.
Intermittent hemodialysis (IHD) (administer after
hemodialysis on dialysis days): Dialyzable (50% to
100%): 0.5-1 g every 24 hours or 1-2 g every 48-72
hours. Note: Dosing dependent on the assumption of 3
times/week, complete IHD sessions.
Peritoneal dialysis (PD): Loading dose of 1 g, followed by
500 mg every 24 hours.
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation
to target trough (if appropriate). The following are general
recommendations only (based on dialysate
flow/ultrafiltration rates of 1-2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment:
CVVH: Loading dose of 2 g followed by 1-2 g every 12
hours.
CVVHD/CVVHDF: Loading dose of 2 g followed by either
1 g every 8 hours or 2 g every 12 hours. Note: Dosage of
1 g every 8 hours results in similar steady-state
concentrations as 2 g every 12 hours and is more cost
effective. Dosage of 2 g every 8 hours may be needed for
gram-negative rods with MIC ≥4 mg/L.
Note: For patients receiving CVVHDF, some recommend
giving a loading dose of 2 g followed by 3 g over 24 hours
as a continuous IV infusion to maintain concentrations
≥4 times the MIC for susceptible pathogens.
Precautions:
WARNING: Use with caution in patients with a history of
penicillin allergy, especially IgE-mediated reactions.
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months post-antibiotic treatment;
Use with caution in patients with renal impairment modify
dosage in severe impairment); Use with caution in
patients with a history of seizure disorder, high levels,
ANTI-INFECTIVES FOR SYSTEMIC USE
particularly in the presence of renal impairment, may
increase risk of seizures.
Adverse Drug Reactions:
Less Common: Diarrhea, pain at injection site,
hypersensitivity reactions.
Rare: Anaphylaxis, angioedema, asterixis, candidiasis,
dizziness, encephalopathy, eosinophilia, erythema
multiforme, hyperbilirubinemia, pruritus, toxic epidermal
necrolysis, vaginitis, vomiting.
Drug Interactions:
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)
Increases serum concentration of Ceftazidime:
Probenecid
Administration:
Any carbon dioxide bubbles that may be present in the
withdrawn solution should be expelled prior to injection.
Administer around the clock to promote less variation in
peak and trough serum levels.
Ceftazidime can be administered deep IM into large mass
muscle, IVP over 3-5 minutes, or IV intermittent infusion
over 15-30 minutes. Do not admix with aminoglycosides
in same bottle/bag. Final concentration for IV
administration should not exceed 100 mg/mL.
Pregnancy Category: B
ATC Code: J01DD02
CEFTRIAXONE
Rx
WHO anti-biotic category: ACCESS and WATCH
Inj.: 250 mg vial (as disodium / sodium salt) + 2 mL 1%
lidocaine solution (IM)
500 mg vial (as disodium / sodium salt) + 2 mL 1%
lidocaine solution (IM)
250 mg vial (as disodium / sodium salt), vial + 5 mL
diluent (IV)
1 g vial (as disodium / sodium salt) + 3.5 mL 1%
lidocaine solution (IM)
1 g vial (as disodium / sodium salt), vial + 10 mL
diluent (IV)
Indications: Treatment of lower respiratory tract infections,
acute bacterial otitis media, skin and skin structure
infections, bone and joint infections, intra-abdominal
and urinary tract infections, pelvic inflammatory disease
(PID), uncomplicated gonorrhea, bacterial septicemia,
and meningitis; used in surgical prophylaxis.
Contraindications: Do NOT use in hyperbilirubinemic
neonates, particularly those who are premature since
ceftriaxone is reported to displace bilirubin from albumin
binding sites; concomitant use with intravenous calcium-
containing solutions/products in neonates (≤28 days).
Dose:
Neonatal sepsis, by IM injection or IV infusion, CHILD, 50
mg/kg every 24 hours with gentamicin OR amikacin with
or without oxacillin OR vancomycin for 7-10 days or
approximately 5-7 days after clinical signs and symptoms
of infection have disappeared.
Clinical sepsis without focus, by IV infusion, CHILD, 100
mg/kg in divided doses every 12-24 hours with or
without oxacillin OR vancomycin for 10-14 days or longer
depending on foci of infection.
Immunocompetent children, urinary source, by IV infusion,
CHILD, 100 mg/kg in divided doses every 12-24 hours
with gentamicin OR amikacin.
Immunocompetent children, intra-abdominal source, by IV
infusion, CHILD, 100 mg/kg in divided doses every 12-
24 hours with metronidazole OR clindamycin.
Post-splenoctomy, by IV infusion, CHILD, 100 mg/kg in
divided doses every 12-24 hours.
Streptococcal toxic shock syndrome, by IV infusion, CHILD,
100 mg/kg in divided doses every 12-24 hours with
clindamycin and IVIG for 10-14 days or longer depending
on the infection.
Sepsis, suspect intra-abdominal source, by IV infusion,
ADULT, 2 g every12 hours with metronidazole.
J
Sepsis, suspect urinary tract infection, by IV infusion,
ADULT, 1 g every 24 hours.
Sepsis, suspect meningococcemia, by IV infusion, ADULT, 2
g every 12 hours.
Sepsis, post splenoctomy, by IV infusion, ADULT, 2 g every
12 hours.
Sepsis, Streptococcal toxic shock, by IV infusion, ADULT, 2 g
every 24 hours with clindamycin and IVIG for a minimum
of 14 day with bacteremia.
Complicated typhoid fever, by IV infusion, CHILD, 75 mg/kg
for 10-14 days; ADULT, 1-2 g for 10-14 days.
Non-typhoidal salmonellosis, Samonella gastroenteritis, by
IV infusion, CHILD, 75 mg/kg for 7 days;
Extra-intestinal infections, by IV infusion, CHILD, 100
mg/kg in divided doses every 6 hours for 10-14 days
(Bacteremia), 4 weeks (Meningitis), 4-6 weeks
(Osteomyelitis).
Leptospirosis, moderate to severe, by IV infusion, CHILD,
80-100 mg/kg every 24 hours for 7 days.
Osteomyelitis, hematogenous, by IV infusion, NEONATE 0-4
weeks and <2kg, 50 mg/kg in 1 dose; NEONATE 0-7 days
old and >2kg, 50 mg/kg in 1 dose; NEONATE >7 days old
and <1.2kg, 75 mg/kg in 1 dose; INFANT and CHILD,
100-200 mg/kg in 1-2 doses; for 3-6 weeks;
Long bones, gram-negative bacilli seen on gram stain, by
IV infusion, ADULT, 2 g every 24 hours with vancomycin
or oxacillin for 4-6 weeks.
Vertebral, by IV infusion, ADULT, 2 g every 24 hours with
vancomycin or oxacillin for 6-12 weeks.
Suppurative arthritis, gram stain is negative or if gram stain
is positive for gram-positive cocci, by IV infusion, CHILD,
100 mg/kg in 1-2 doses with vancomycin for 2-3 weeks.
Suppurative arthritis, gram stain is positive for gram-
negative organisms, by IV infusion, CHILD, 100 mg/kg in
1-2 doses for 2-3 weeks.
Acute bacterial arthritis, monoarticular, at risk for STI, by IV
infusion, ADULT, 1 g every 24 hours for 7 days minimum.
Acute bacterial arthritis, monoarticular, not at risk for STI, by
IV infusion, ADULT, 1 g every 24 hours for 2-4 weeks.
Acute bacterial arthritis, polyarticular, at risk for STI, by IV
infusion, ADULT, 1 g every 24 hours.
Prosthetic joint infections, P. acnes, by IV infusion, ADULT,
2 g every 24 hours for 4-6 weeks.
Native valve infective endocarditis, S. viridans or S. bovis,
with Penicillin G MIC ≤0.12 mcg/mL, by IM injection or IV
infusion, CHILD, 100 mg/kg in divided doses or 80
223

mg/kg for 4 weeks; by IV infusion, ADULT, 2 g every 24
hours for 4 weeks.
Native valve infective endocarditis, S. viridans or S. bovis,
with Penicillin G MIC >0.12 mcg/mL to ≤0.5 mcg/mL, by
IM injection or IV infusion, CHILD, 100 mg/kg in divided
doses or 80 mg/kg with gentamicin for 4 weeks; ADULT,
2 g every 24 hours for 4 weeks.
Native valve infective endocarditis, Enterococci, penicillin-
susceptible, aminoglycoside-resistant (Gentamicin MIC
>500 mcg/mL), streptomycin susceptible, by IM
injection or IV infusion, CHILD, 100 mg/kg in divided
dose every 12 hours or 80 mg/kg with ampicillin; by IV
infusion, ADULT, 2 g in divided doses every 12 hours with
ampicillin for 6 weeks.
Native valve infective endocarditis, Haemophilus sp,
Aggregatibacter sp, Cardiobacterium hominis, Eikenella
corrodens, and Kingella species (HACEK), by IM injection
or IV infusion, CHILD, 100 mg/kg in divided doses every
12 hours or 80 mg/kg for 4 weeks; by IV infusion, ADULT,
2 g every 24 hours for 4 weeks.
J
Prosthetic valve infective endocarditis, gram-negative
enteric bacilli, by IV infusion, CHILD, 100 mg/kg in
divided doses every 12 hours or 80 mg/kg in divided
doses every 12-24 hours for 6 weeks.
Dental prophylaxis, by IM injection or IV infusion, CHILD, 50
mg/kg; ADULT, 1 g.
Bacterial purulent pericarditis, S. aureus, Group A
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
IV infusion, CHILD, 100 mg/kg in divided doses every 12-
24 hours with vancomycin; ADULT, 2 g every 24 hours
with vancomycin.
Bacterial purulent pericarditis, S. pneumoniae (including
penicillin-resistant strains), N. meningitidis, H. influenzae
type B (for children who may be inadequately
immunized), by IV infusion, CHILD, 100 mg/kg in divided
doses every 12-24 hours.
Community acute bacterial meningitis, by IV infusion, CHILD
>2 months-5 years, 100 mg/kg in divided doses every
12-24 hours; by IV infusion, CHILD >5-18 years, 100
mg/kg in divided doses every 12 hours; add rifampin for
<10 years old with confirmed Hib meningitis; ADULT, 2g
every 12 hours; ADULT >50 years old, 2 g every 12 hours
with ampicillin.
Brain abscess in the presence of dental infection, by IM
injection or IV infusion, CHILD, 100 mg/kg in divided
doses every 12 hours with penicillin G; by IV infusion,
ADULT, 2 g every 12 hours with penicillin G.
Brain abscess in the presence of head trauma, by IM
injection or IV infusion, CHILD, 100 mg/kg in divided
doses every 12 hours with vancomycin; by IV infusion,
ADULT, 2 g every 12 hours with vancomycin.
Brain abscess in the presence of congenital heart disease,
by IM injection or IV infusion, CHILD, 100 mg/kg in
divided doses every 12 hours with metronidazole; by IV
infusion, ADULT, 2 g every 12 hours with metronidazole.
Buccal cellulitis, by IV infusion, CHILD, 50 mg/kg every 24
hours for 7-14 days.
Orbital cellulitis, by IV infusion, CHILD, 100 mg/kg in 1-2
doses with vancomycin for 7-14 days; ADULT, stage II-IV
MRSA considered, 1 g every 12 hours with vancomycin
for 10-21 days.
Conjunctivitis, N. gonorrhoeae, by IV infusion, NEONATE, 25-
50 mg/kg; maximum dose: 125 mg.
Gonococcal conjunctivitis, by IM injection or IV infusion,
ADULT, 1g with azithromycin and
levofloxacin/tobramycin/erythromycin.
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ANTI-INFECTIVES FOR SYSTEMIC USE
Peritonsillar abscess, by IV infusion, CHILD, 50-75 mg/kg
every 12-24 hours with metronidazole; ADULT, 2 g every
24 hours with metronidazole.
Deep neck abscess, by IV infusion, CHILD, 50-75 mg/kg
every 12-24 hours with metronidazole for at least 7 days;
ADULT, 2 g every 24 hours with metronidazolefor at least
7 days.
Gonococcal pharyngitis, by deep IM injection, CHILD <45 kg,
125mg; ADULT and CHILD >45 kg, 250 mg.
Jugular vein suppurative phlebitis, by IV infusion, ADULT, 2g
with metronidazole.
Acute epiglottitis, by IV infusion, CHILD, 50-100 mg/kg in
divided doses every 12-24 hours for 7-10 days; ADULT,
2 g every 24 hours for 7-10 days.
Acute mastoiditis, by IV infusion, CHILD, 100 mg/kg in
divided doses every 12 hours with oxacillin; ADULT, 2 g.
Community-acquired pneumonia, severe, with no Hib
vaccination or incomplete or unknown vaccination
history, by IV infusion, INFANT and CHILD up to 5 years,
100 mg/kg in divided doses every 12 hours;
Moderate risk, by IV infusion, ADULT, 2 g every 24 hours for
7-10 days;
High-risk, by IV infusion, ADULT, 2 g every 24 hours with
azithromycin or levofloxacin.
Acute emphysema, by IV infusion, CHILD, 50-100 mg/kg
every 24 hours for 10-30 minutes with clindamycin for 2-
4 weeks; ADULT, 2 g every 24 hours with vancomycin and
metronidazole for 2-4 weeks.
Lung abscess, by IV infusion, CHILD, 50-100 mg/kg every
24 hours for 10-30 minutes with clindamycin for 4-6
weeks; ADULT, 2g every 24 hours with
clindamycin/ampicillin sulbactam and
metronidazole/piperacillin tazobactam for 4-6 weeks.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
Severe cases (including some fatalities) of immune-related
hemolytic anemia have been reported in patients
receiving cephalosporins, including ceftriaxone;
Secondary to biliary obstruction, pancreatitis has been
reported rarely;
Use with caution in patients with a history of penicillin
allergy, especially IgE-mediated reactions;
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months post-antibiotic treatment.
Adverse Drug Reactions:
Common: Induration, tightness, warmth.
Less Common: Rash, diarrhea, eosinophilia,
thrombocytosis, leukopenia, tenderness at injection site,
pain.
Rare: Abdominal pain, agranulocytosis, allergic dermatitis,
allergic pneumonitis, anaphylaxis, anemia, basophilia,
biliary lithiasis, bronchospasm, chills, colitis,
diaphoresis, dizziness, dysgeusia, dyspepsia, edema,
epistaxis, erythema multiforme, exanthema, fever,
flatulence, flushing, gallbladder sludge, gallstones,
glossitis, hemolytic anemia, jaundice, Lyell’s syndrome,
monocytosis, oliguria, palpitation, renal and pulmonary
ceftriaxone-calcium precipitations, seizure, serum
ANTI-INFECTIVES FOR SYSTEMIC USE

sickness, Stevens-Johnson syndrome, stomatitis, toxic Pneumonia, nosocomial (HAP/VAP), by IV injection/

epidermal necrolysis, vaginitis, vomiting. infusion, ADULT, 2 g every 8-12 hours with azithromycin
and gentamicin/amikacin for 7-28 days;
Drug Interactions: Multi-drug resistant, by IV injection/ infusion, CHILD,
Reduces therapeutic effect of the following drugs: 100-150 mg/kg every 8 hours; ADULT, 2g every 8 hours
BCG, Typhoid vaccine (Only the live attenuated Ty21a with or without levofloxacin/ amikacin and
strain is affected.) vancomycin/linezolid.
Pathogen-specific treatment, P. aeruginosa, by IV injection/
Enhances therapeutic effect of Vitamin K antagonists e.g. infusion, CHILD, 150 mg/kg every 6 hours with
Warfarin ceftazidime; ADULT, 2g every 8-12 hours with
amikacin/gentamicin OR aztreonam;
Administration: Enterobacter, by IV injection/ infusion, CHILD, 100-150
Do not admix with aminoglycosides in same bottle/bag. Do mg/kg every 8-12 hours; ADULT, 2 g every 8 hours.
not reconstitute, admix, or co-administer with calcium-
containing solutions. Infuse intermittent infusion over 30 Dose Adjustment:
minutes. Geriatric:
Refer to adult dosing.
Pregnancy Category: B
Renal Impairment:
ATC Code: J01DD04 Intermittent hemodialysis (IHD) (administer after

J
hemodialysis on dialysis days): IV: Initial: 1 g (single dose)
on day 1. Maintenance: 0.5-1g every 24 hours or 1-2 g
FOURTH-GENERATION CEPHALOSPORINS every 48-72 hours. Note: Dosing dependent on the
assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): Removed to a lesser extent than
Rx CEFEPIME hemodialysis; administer normal recommended dose
WHO anti-biotic category: RESERVE
every 48 hours.
Continuous renal replacement therapy (CRRT): Drug
Inj.: 500 mg, 1 g, and 2 g vial (as hydrochloride) (IM, IV)
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
Indications: Treatment of complicated urinary tract
dosing requires close monitoring of pharmacologic
infections, including pyelonephritis caused by E. coli,
response, signs of adverse reaction due to drug
Klebsiella pneumoniae, or Proteus mirabilis;
accumulation, as well as drug concentrations in relation
monotherapy for febrile neutropenia; complicated skin
to target trough (if appropriate). The following are general
and skin structure infections caused by S. pyogenes or
recommendations only (based on dialysate
methicillin-susceptible staphylococci; moderate-to-
flow/ultrafiltration rates of 1-2 L/hour and minimal
severe pneumonia caused by S. pneumoniae, P.
residual renal function) and should not supersede
aeruginosa, Klebsiella pneumoniae, or Enterobacter
clinical judgment:
species; complicated intra-abdominal infections caused
CVVH: Loading dose of 2 g followed by 1-2 g every 12
by E.coli, P. aeruginosa, K. pneumoniae, Enterobacter
hours.
species against methicillin-susceptible staphylococci,
CVVHD/CVVHDF: Loading dose of 2 g followed by either
Enterobacter sp, and many other gram negative bacilli.
1 g every 8 hours or 2 g every 12 hours. Note: Dosage of
1 g every 8 hours results in similar steady-state
Dose:
concentrations as 2 g every 12 hours and is more cost
Healthcare-associated sepsis, by IV injection/ infusion,
effective.
CHILD, 100-150 mg/kg in divided doses every 8 hours
with or without amikacin/vancomycin.
Precautions:
Febrile neutropenia, monotherapy, by IV injection/ infusion,
Use with caution in patients with a history of penicillin
ADULT, 2 g every 8 hours for 7 days or until the
allergy, especially IgE- mediated reactions; Prolonged
neutropenia resolves; CHILD, 150 mg/kg in divided
use may result in fungal or bacterial superinfection,
doses every 8 hours for 7 days or until neutropenia
including C. difficile-associated diarrhea (CDAD) and
resolves.
pseudomembranous colitis, CDAD has been observed
Osteomyelitis, contiguous focus, by IV injection/ infusion,
>2 months post-antibiotic treatment; Use with caution in
CHILD, 100-150 mg/kg in 2-3 doses with clindamycin or
patients with a history of gastrointestinal disease,
vancomycin for 6 weeks.
especially colitis; Use with caution in patients with renal
Prosthetic joint infections, P. aeruginosa, by IV injection/
impairment; dosage adjustments recommended.
infusion, ADULT, 2 g every 12 hours for 4-6 weeks.
Native valve infective endocarditis, healthcare-associated,
Adverse Drug Reactions:
by IV injection/ infusion, CHILD, 100-150 mg/kg in
Common: Positive Coombs test without hemolysis.
divided doses every 8-12 hours with vancomycin and
Less Common: Fever, headache, rash, pruritus,
gentamicin; ADULT, 2 g every 8 hours with vancomycin
hypophosphatemia, diarrhea, nausea, vomiting,
and gentamicin.
inflammation, phlebitis.
Impaired host, neutropenic, by IV injection/ infusion, ADULT,
Rare: Agranulocytosis, anaphylactic shock, colitis, coma,
2 g every 8 hours with amikacin.
confusion, encephalopathy, hallucinations,
Chronic or recurrent mastoiditis, intracranial extension
hyper/hypocalcemia, hyperkalemia,
suspected, by IV injection/ infusion, CHILD, 150 mg/kg
every 8 hours.

225
 ANTI-INFECTIVES FOR SYSTEMIC USE

hyperphosphatemia, leucopenia, moniliasis, stupor, Precautions:

vaginitis. Rare cross-allergenicity to penicillins and cephalosporins
has been reported;
Drug Interactions: Prolonged use may result in fungal or bacterial
Reduces therapeutic effect of the following drugs: superinfection, including C. difficile-associated diarrhea
BCG, Typhoid vaccine (Only the live attenuated Ty21a (CDAD) and pseudomembranous colitis. CDAD has been
strain is affected.) observed >2 months post-antibiotic treatment;
Use the injectable formulation with caution in patients with
Increases serum concentration of Cefepime: renal impairment, dosing adjustment required.
Probenecid
Adverse Drug Reactions:
Administration: Rash, diarrhea, nausea, vomiting, thrombophlebitis, pain at
May be administered with IM or IV. injection site, abdominal cramps, abnormal taste,
Inject deep IM into large muscle mass. Inject direct IV over anaphylaxis, anemia, angioedema, breast tenderness,
5 minutes. Infuse intermittent infusion over 30 minutes. bronchospasm, chest pain, diaphoresis, dizziness,
dermatitis, fever, flushing, pancytopenia, paresthesia,
Pregnancy Category: B petechiae, pruritus, purpura, sneezing, tinnitus, urticaria,
vaginitis, vertigo, wheezing.
ATC Code: J01DE01
Drug Interactions:
J

Reduces therapeutic effect of the following drugs:

MONOBACTAMS BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)

Rx AZTREONAM Administration:
WHO anti-biotic category: RESERVE
For IM: Administer by deep injection into large muscle mass,
such as upper outer quadrant of gluteus maximus or the
Inj.: 1 g powder for injection
lateral part of the thigh.
For IV: Administer by slow IV push over 3-5 minutes or by
Indications: Treatment of hospital-acquired and ventilator-
intermittent infusion over 20-60 minutes.
associated pneumonia, and pathogen-specific infections
Pregnancy Category: B
Contraindications: Hypersensitivity to aztreonam or any
component of the formulation.
ATC Code: J01DF01
Dose:
Hospital-acquired and ventilator-associated pneumonia, not
at high risk of mortality but with factors increasing the CARBAPENEMS
likelihood of MRSA, by IV push/ infusion, ADULT, 2 g
every 8 hours with vancomycin OR linezolid;
Rx ERTAPENEM
High risk of mortality and with risk factor for MDR, by IV WHO anti-biotic category: WATCH
push/ infusion, ADULT, 2 g every 8 hours with
levofloxacin/amikacin and vancomycin/linezolid for 7 Inj.: 1 g powder, vial (as sodium salt)
days.
Community acute bacterial meningitis with severe penicillin Indications: Treatment of sepsis and pneumonia,
allergy, by IV push/ infusion, ADULT, 2 g every 6-8 hours community-acquired with or without lung abscess.
with vancomycin.
Contraindications: Anaphylactic reactions to beta-lactam
Pathogen-specific treatment, by IV push/ infusion, ADULT, antibiotics. If using intramuscularly, known
2g every 6 hours with piperacillin-tazobactam OR hypersensitivity to local anesthetics of the amide type
ceftazidime OR cefepime OR meropenem OR (lidocaine is the diluent).
levofloxacin OR ciprofloxacin.
Dose:
Dose Adjustment: NOTE: Children ≥13 years: Refer to adult dosing
Geriatric:
Refer to adult dosing. Sepsis, suspect urinary tract infection, by IV infusion,
ADULT, 1 g every 24 hours.
Renal Impairment: Community-acquired pneumonia, high risk, no risk for P.
IM, IV: Adults: Following initial dose, maintenance doses aeruginosa, by IV infusion, ADULT, 1 g every 24 hours
should be given as follows: with azithromycin OR levofloxacin for 10-14 days.
CrCl 10-30 mL/minute: 50% of usual dose at the usual Pneumonia, anaerobic or aspiration with or without lung
interval. abscess, by IV infusion, ADULT, 1 g every 24 hours with
CrCl <10 mL/minute: 25% of usual dosage at the usual piperacillin-tazobactam OR ceftriaxone.
interval.
Dose Adjustment:
Geriatric:
Refer to adult dosing.

226
ANTI-INFECTIVES FOR SYSTEMIC USE
Renal Impairment:
Adults: CrCl >30 mL/minute/1.73m2: No adjustment
required.
CrCl ≤30 mL/minute/1.73m2: and ESRD: 500 mg/day.
Hemodialysis: When the daily dose is given within 6 hours
prior to hemodialysis, a supplementary dose of 150 mg
is required following hemodialysis.
Precautions:
Serious hypersensitivity reactions, including anaphylaxis,
have been reported; Carbapenems have been
associated with CNS adverse effects, including
confusional states and seizures. Use caution with CNS
disorders and adjust dose in renal impairment to avoid
drug accumulation, which may increase seizure risk;
Prolonged use may result in fungal or bacterial
superinfection, include C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis. CDAD has been
observed >2 months post-antibiotic treatment.
Adverse Drug Reactions:
Less Common: Edema, chest pain, hypertension,
hypotension, tachycardia, headache, altered mental
status, decreased mental acuity, changed mental status,
fatigue, anxiety, rash, pruritus, diarrhea, vomiting,
dyspepsia, oral candidiasis.
Rare: Anaphylactoid reactions, arrhythmia, asthma,
asystole, atrial fibrillation, bradycardia, cholelithiasis,
delirium, DRESS syndrome, gout, facial edema, heart
failure, heart murmur, hemoptysis, hypoxemia, pleural
effusion, renal insufficiency, seizure, septicemia,
subdural hemorrhage, syncope, ventricular tachycardia.
Drug Interactions:
Reduces therapeutic effect of the following drugs:
BCG, Typhoid vaccine (Only the live attenuated Ty21a
strain is affected.)
Decreases serum concentration of the following drugs:
Divalproex, Valproic acid
Increases serum concentration of Ertapenem:
Probenecid
Administration:
For IM: Avoid injection into a blood vessel. Make sure
patient does not have an allergy to lidocaine or another
anesthetic of the amide type. Administer by deep IM
injection into a large muscle mass. Do not administer IM
preparation or drug reconstituted for IM administration
intravenously.
For IV: Infuse over 30 minutes.
Pregnancy Category: B
ATC Code: J01DH03
MEROPENEM
Rx
WHO anti-biotic category: WATCH
Inj.: 500 mg and 1 g powder, vial (as trihydrate)
Indications: Treatment of intra-abdominal infections,
meningitis, and skin and skin structure infections,
respiratory tract infections, septicemia, and urinary tract
infections caused by susceptible bacteria; empiric anti-
infective therapy in febrile neutropenic patients.
Contraindication: Patients who have experienced
anaphylactic reactions to beta-lactams.
Dose:
Healthcare-associated sepsis, by IV injection/ infusion,
CHILD, 60-120 mg/kg in divided doses every 8 hours
with or without amikacin OR vancomycin.
Severe sepsis and septic shock, by IV injection/ infusion,
CHILD, 60-120 mg/kg in divided doses every 8 hours
J
with vancomycin for 10-14 days.
Febrile neutropenia, by IV injection/ infusion, CHILD, 60-
120 mg/kg in divided doses every 8 hours; ADULT, 1-2 g
every 8 hours with aminoglycoside/
fluoroquinolone/vancomycin and antifungal treatment
for 4-6 weeks.
Sepsis, non-neutropenic, by IV injection/ infusion, ADULT,
1g every 8 hours with vancomycin.
Acute sinusitis, by IV injection/ infusion, ADULT, 1 g every 8
hours with or without vancomycin
Acute mastoiditis, caused by a multidrug-resistant
Pseudomonas sp, by IV injection/ infusion, ADULT, 1 g
every 8 hours.
Community-acquired pneumonia, multi-drug resistant
pathogens, by IV injection/ infusion, CHILD, 300 mg/kg
in divided does every 6 hours; 120 mg/kg/day every 8
hours if with meningitis.
Hospital-acquired pneumonia, Not at high risk of mortality
and no factors increasing the likelihood of MRSA, by IV
injection/ infusion, ADULT, 1 g every 8 hours;
Not at high risk of mortality but with factors increasing
the likelihood of MRSA, by IV injection/ infusion, ADULT,
1 g every 8 hours with vancomycin OR linezolid;
High risk of mortality and with risk factor for MDR; by IV
injection/ infusion, ADULT, 1 g every 8 hours with
vancomycin/ linezolid and levofloxacin/ amikacin;
Ventilator-associated pneumonia, No risk factors for MDR
VAP and no structural lung disease, by IV injection/
infusion, ADULT, 1 g every 8 hours;
With risk factors for MRD VAP and with structural lung
disease, by IV injection/ infusion, ADULT, 1 g every 8
hours with vancomycin/ linezolid and levofloxacin/
amikacin for 7 days or longer.
Pathogen-specific treatment, P. aeruginosa, by IV injection/
infusion, ADULT, 1 g every 8 hours with levofloxacin/
ciprofloxacin OR aztreonam;
Acinetobacter species, by IV injection/ infusion, CHILD,
60 mg/kg in divided doses every 8 hours with amikacin
OR gentamicin; ADULT, 1 g every 8 hours with ampicillin-
sulbactam;
Klebsiella pneumoniae, by IV injection/ infusion, CHILD,
60 mg/kg in divided doses every 8 hours;
Achromobacter, by IV injection/ infusion, CHILD, 60
mg/kg in divided doses every 8 hours with trimethoprim-
sulfamethoxazole; ADULT, 1 g every 8 hours;
227

Burkholderia cepacia, by IV injection/ infusion, CHILD,
60 mg/kg in divided doses every 8 hours with amikacin
or gentamicin; ADULT, 1 g every 8 hours;
Burkholderia pseudomallei, by IV injection/ infusion,
CHILD, 60 mg/kg in divided doses every 8 hours for 7-14
days with trimethoprim-sulfamethoxazole for 12-24
weeks;
Escherichia coli, by IV injection/ infusion, CHILD, 60
mg/kg in divided doses every 8 hours with amikacin or
gentamicin;
Enterobacter, by IV injection/ infusion, CHILD, 60 mg/kg
in divided doses every 8 hours with amikacin or
gentamicin; ADULT, 500 mg – 1 g every 8 hours.
Dose Adjustment:
Geriatric:
Dosage adjustment is not necessary for geriatric patients
with creatinine clearances >50 mL/minute; For geriatric
patients with reduced renal function, dosage should be
adjusted according to the guidelines for other adults with
J
renal impairment.
Renal Impairment:
Adults:
CrCl 26-50 mL/minute: Administer recommended dose
based on indication every 12 hours.
CrCl 10-25 mL/minute: Administer one­half recommended
dose based on indication every 12 hours.
CrCl <10 mL/minute: Administer one­half recommended
dose based on indication every 24 hours.
Children:
Glomerular Filtration Rate 30-50 mL/minute: Administer
20-40 mg/kg every 12 hours.
Glomerular Filtration Rate 10-29 mL/minute: Administer
10-20 mg/kg every 12 hours.
Glomerular Filtration Rate <10 mL/minute: Administer 10-
20 mg/kg every 24 hours. Intermittent hemodialysis
(IHD): 10-20 mg/kg every 24 hours administer after
hemodialysis on dialysis days).
Peritoneal dialysis: 10-20 mg/kg every 24 hours.
Continuous renal replacement therapy: 20-40 mg/kg every
12 hours.
Precautions:
Monitor patients for: anaphylaxis/hypersensitivity reactions,
central nervous system effects (including confusional
states and seizures), superinfection;
Use with caution in patients with renal Impairment, elderly,
pediatrics (Safety and efficacy not established in children
<3 months old).
Adverse Drug Reactions:
Peripheral vascular disease, shock, bradycardia, cardiac
arrest, cardiac failure, chest pain, hypertension,
hypotension, myocardial infarction, peripheral edema,
pulmonary embolism, syncope, tachycardia, headache,
convulsions, pain, agitation, anxiety, chills, confusion,
delirium, depression, dizziness, drowsiness,
hallucination, insomnia, nervousness, paresthesia,
seizure, skin rash, pruritus, dermal ulcer, diaphoresis,
urticaria, hypoglycemia, hypervolemia, nausea, diarrhea,
constipation, vomiting, oral candidiasis, gastrointestinal
disease, glossitis, abdominal pain, anorexia, dyspepsia,
enlargement of abdomen, flatulence, intestinal
obstruction, dysuria, pelvic pain, urinary incontinence,
vulvovaginal candidiasis, anemia, hypochromic anemia,
228
ANTI-INFECTIVES FOR SYSTEMIC USE
hyperbilirubinemia, cholestatic jaundice, hepatic failure,
jaundice, sepsis, inflammation at injection site, back
pain, weakness, renal failure, pharyngitis, pneumonia,
apnea, asthma, cough, dyspnea, hypoxia, pleural
effusion, pulmonary edema, respiratory tract disease,
fever
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Aminoglycosides e.g.
Streptomycin
Avoid concomitant use with:
Increases serum concentration of Meropenem:
Probenecid
Decreases serum concentration of Valproic acid
Administration:
For IV: injections of meropenem should be given over a 3-5
minutes period; infusions of meropenem should be given
over approximately 15–30 minutes.
Infants <3 months old: Administer as an IV infusion over 30
minutes;
Infants ≥3 months old, children, adolescents, and adults:
Administer IV infusion over 15-30 minutes; IV bolus
injection (5-20 mL) over 3-5 minutes; Extended infusion
administration:
Adults: Administer over 3 hours.
Note: Must consider meropenem’s limited room
temperature stability if using extended infusions.
Pregnancy Category: B
ATC Code: J01DH02
SULFONAMIDES AND TRIMETHOPRIM
COTRIMOXAZOLE
Rx (SULFAMETHOXAZOLE +
TRIMETHOPRIM)
WHO anti-biotic category: ACCESS
Oral: 400 mg sulfamethoxazole + 80 mg trimethoprim
tablet / capsule
800 mg sulfamethoxazole + 160 mg trimethoprim
tablet / capsule
200 mg sulfamethoxazole + 40 mg trimethoprim per
5 mL suspension, 70 mL and 120 mL
400 mg sulfamethoxazole + 80 mg trimethoprim per
5 mL suspension, 60 mL
Inj.: 400 mg sulfamethoxazole + 80 mg trimethoprim, 5
mL ampule (IV infusion)
Indications: Treatment of uncomplicated typhoid fever,
internal hordeolum, dacrocystitis, pertussis, and
pathogen-specific infections such Pneumocystis jirovecii
Contraindications: Infants <2 months of age; severe renal
or hepatic failure; megaloblastic anemia (due to folic
acid deficiency); blood dyscrasias; acute porphyria; late
pregnancy (due to risk of neonatal kernicterus, hemolytic
anemia and jaundice).
ANTI-INFECTIVES FOR SYSTEMIC USE

Dose: Rare: Arthralgia, aseptic meningitis, Clostridium difficile-

Uncomplicated typhoid fever, by mouth, ADULT, 800/180 associated disease, convulsions, depression, erythema,
mg every 12 hours for 14 days; CHILD, 8 mg/kg of hallucinations, hepatic necrosis, hepatitis,
Trimethoprim in 2 divided doses every 12 hours for 14 hypoglycemia, jaundice, lowered mental acuity,
days. megaloblastic anemia, myalgia, myocarditis,
Internal hordeolum, MRSA, by mouth, ADULT, 800/160 mg pancreatitis, peripheral neuropathy, pulmonary
every 12 hours. infiltrates, SJS, SLE, toxic epidermal necrolysis, urinary
Dacrocystitis, by mouth, ADULT, 2 double strenght tablets obstruction with anuria or oliguria, uveitis, vasculitis,
twice a day. vertigo.
Pertussis, by mouth, CHILD ≥ 2 months old, 8/40 mg/kg in
2 divided doses for 14 days; ADULT, 160/800 mg twice Drug Interactions:
daily for 14 days. Monitor closely with:
Pathogen-specific treatment, Achromobacter, by mouth, Drugs causing potassium retention e.g. ACE inhibitors,
CHILD, 8 mg/kg in divided doses every 12 hours with Other nephrotoxic drugs e.g., gentamicin and
ceftazidime; streptomycin
Burkholderia cepacia, by mouth, CHILD, 8 mg/kg in
divided doses every 12 hours; Administration:
Burkholderia pseudomallei, by mouth, CHILD, 8 mg/kg in Should be taken WITH food; this is best taken after meals
divided doses every 12 hours for 12-24 weeks. with an adequate amount of fluid.
Enterobacter, by mouth, CHILD, 8 mg/kg in divided

J
doses every 12 hours. Pregnancy Category: C

Dose Adjustment: ATC Code: J01EE01

Renal Impairment:
For mild to moderate renal impairment, dose reduction is
warranted; contraindicated for severe impairment.
Hepatic Impairment:
Contraindicated in significant hepatic impairment.
Precautions:
HIV infection;
Photosensitivity, slow acetylator phenotype;
Treatment with oral typhoid vaccine;
Systemic Lupus Erythematosus (SLE); Renal impairment
(avoid if severe and if plasma sulfamethoxazole
concentration cannot be monitored),
Low urine pH increases risk of crystalluria (maintain
adequate fluid intake to prevent crystalluria);
Hepatic impairment (avoid if severe);
Blood disorders (avoid unless under specialist supervision;
monitor blood count and discontinue immediately if
blood disorder develops);
Rash (discontinue treatment immediately);
Asthma;
G6PD deficiency;
Elderly (increased risk of blood dyscrasias and skin
disorders);
Pregnancy (first trimester: teratogenic effects which include
anencephaly, hypoplastic left heart syndrome, choanal
atresia, transverse limb defect, diaphragmatic hernia;
third trimester: neonatal hemolysis and
methemoglobinemia);
Breastfeeding (monitor infant for jaundice: small risk of
kernicterus in jaundiced infants);
G6PD-deficient infants (risk for hemolysis due to
sulfamethoxazole).
Caution in ill or premature infants and avoid in infants <6
weeks.
Adverse Drug Reactions:
Common: Anorexia, diarrhea, fever, hyperkalemia,
hyponatremia, itch, nausea, rash, sore mouth,
thrombocytopenia, vomiting.
Less Common: Drowsiness, headache, neutropenia,
photosensitivity.
MACROLIDES, LINCOSAMIDES, AND
STREPTOGRAMINS
MACROLIDES
Rx AZITHROMYCIN
WHO anti-biotic category: WATCH
Oral: 250 mg capsule (as base / as dihydrate)
250 mg and 500 mg tablet (as base / as dihydrate/as
monohydrate)
200 mg/5 mL powder for suspension (as base /as
dehydrate/as monohydrate), 15 mL and 60 mL
Inj.: 500 mg powder vial (as base / as dihydrate) (IV
infusion)
Indications: Suspected uncomplicated genital chlamydial
infections (e.g., urethritis, cervicitis, trachoma); low-risk
community-acquired pneumonia (CAP-LR) in adults,
when Legionella, Chlamydia or Mycoplasma is
suspected, or when there is hypersensitivity to the beta-
lactams; non-severe CAP in child with hypersensitivity to
amoxicillin.
Contraindications: With history of cholestatic jaundice or
hepatic impairment associated with prior azithromycin
use.
Dose:
Uncomplicated typhoid fever, by mouth, CHILD, 20 mg/kg
for 5-7 days; ADULT, 500 mg-1g for 5-7 days.
Complicated typhoid fever, by mouth, CHILD, 20 mg/kg for
5-7 days, ADULT, 500 mg 1-2 tablets for 5-7 days
Leptospirosis, mild, by mouth, CHILD, 1 g loading dose then
10 mg/kg for 2 days;
Moderate to severe, by mouth, CHILD, 500 mg for 5 days.
Prophylaxis, by mouth, CHILD, 10 mg/kg; If children are
exposed for more than 7 days, the dose should be
repeated after 1 week.

229

Acute bacterial arthritis, monoarticular, by mouth, ADULT,
1g for 7 days minimum.
Dental prophylaxis, allergic to penicillin or ampicillin, by
mouth, CHILD, 15 mg/kg; ADULT, 500 mg.
Conjunctivitis, Chlamydia trachomatis, by mouth, NEONATE
3-10 days, 20 mg/kg every 24 hours for 3 days.
Gonococcal conjunctivitis, for presumptive Chlamydia co-
infection, by mouth, ADULT, 1 g per day PLUS with topical
levofloxacin OR tobramycin OR erythromycin ointment
every 4 days for 2-3 weeks or until resolution of
symptoms.
Pharyngitis or tonsilitis, penicillin allergy, by mouth, CHILD,
12 mg/kg for 5 days; ADULT, 500 mg then 250 mg for 4
days or 500 mg for 3 days
Pertussis, by mouth, INFANT <1 month, 10 mg/kg every 24
hours for 5 days; INFANT >2 months, 10 mg/kg on day 1
then 5 mg/kg every 24 hours for 4 days; ADULT, 500 mg
on day 1 then 250 mg every 24 hours on day 2 to 5.
Acute bacterial exacerbation of chronic bronchitis (ABECB),
severe, by mouth, ADULT, 500 mg every 24 hours for 3
J
days.
Community-acquired pneumonia, by mouth, CHILD, 10
mg/kg for 3 days or 10 mg/kg on day 1 then 5 mg/kg on
day 2 to 5;
Low-risk, without co-morbid illness, by mouth, ADULT,
500 mg for 3-5 days;
Low-risk, with stable co-morbid illness, by mouth, ADULT,
500 mg with co-amoxiclav OR cefuroxime for 3-5 days;
Moderate-risk, by mouth, ADULT, 500 mg with ampicillin-
sulbactam or cefuroxime.
High-risk, risk for P. aeruginosa, by IV infusion, ADULT,
500 mg with piperacillin-tazobactam/
cefepime/meropenem and gentamicin/amikacin.
Dose Adjustment:
Renal Impairment:
For severe impairment – refer to specialist
Hepatic Impairment:
(except for Contraindications stated above):
For severe impairment – reduce dose
Precautions:
Cardiac conditions: congenital long QT syndrome and family
history of QT prolongation; torsades de pointes,
ventricular arrhythmia and other arrhythmias, congestive
heart failure, recent MI; Proarrhythmic conditions (e.g.,
hypokalemia, hypomagnesemia); Renal impairment
Exacerbations of myasthenia gravis
Elderly patients (may be more susceptible to drug-
associated QT prolongation);
Breastfeeding (limited drug information available – use only
if adequate alternatives are not available).
Adverse Drug Reactions:
Common: Abdominal pain, arthralgia, cramping, diarrhea,
dizziness, dyspepsia, flatulence, headache, malaise,
nausea, pruritic, rash, vaginitis, vomiting.
Less Common: Abnormal heart rhythm, allergic reaction,
anorexia, anxiety, chest pain, conjunctivitis, constipation,
drowsiness, edema, enteritis, fatigue, gastritis,
hyperkinesia, hypesthesia, hypotension, insomnia,
leukopenia, liver disorders, myasthenia gravis,
neutropenia, palpitations, pancreatitis, paresthesia,
photosensitivity, rash, sleep disturbances, somnolence,
thrombocytopenia, tinnitus, urticaria, vertigo.
230
ANTI-INFECTIVES FOR SYSTEMIC USE
Rare: Acute renal failure, agitation, angioedema, cholestatic
jaundice, convulsions, disturbances in taste and vision,
hemolytic anemia, hepatic necrosis and failure,
interstitial nephritis, seizures, syncope.
Drug Interactions:
NOTE: Macrolides inhibit P-glycoprotein, which may lead to
drug interactions.
Monitor closely with:
Reduces absorption of Azithromycin:
Antacids (e.g. aluminum or magnesium hydroxide)
Reduces therapeutic effect of Contraceptives (Oral)
Avoid concomitant use with:
Increases serum concentration of Digoxin
Increases risk of adverse or toxic effects of the following
drugs:
Amiodarone, Artemether + Lumefantrine
Administration:
Capsules should be taken at least 1 hour before, or 2 hours
after, food; oral suspension can be taken with food to
reduce GI discomfort and increase tolerability.
NOTE: Oral suspensions (100 mg/5 mL and 200 mg/5 mL)
may be stored for 10 days post-reconstitution and taken
without regard to food.
Pregnancy Category: B
ATC Code: J01FA10
CLARITHROMYCIN
Rx
WHO anti-biotic category: WATCH
Oral: 250 mg and 500 mg base tablet
125 mg/5 mL and 250 mg/5 mL granules / powder
for suspension, 50 mL
Indications: Management of low risk community-acquired
pneumonia in adults (CAP-LR) due to Legionella,
Chlamydia or Mycoplasma; non-severe PCAP with
hypersensitivity to amoxicillin; Helicobacter pylori
infection. In combination with other drugs. Alternative in
penicillin allergic patients.
Contraindications: Severe hepatic failure; hypokalemia;
patients with history of QT prolongation or ventricular
cardiac arrhythmias; cholestatic jaundice or hepatic
dysfunction with prior clarithromycin use.
Dose:
Dental prophylaxis, by mouth, CHILD, 15 mg/kg; ADULT,
500 mg.
Pharyngitis or tonsillitis, penicillin allergy, by mouth, CHILD,
15 mg/kg in divided doses every 12 hours for 10 days;
ADULT, 250 mg every 12 hours for 10 days.
Acute bacterial rhinosinusitis (ABRBS), severe penicillin
allergy, by mouth, CHILD, 15 mg/kg in divided doses
every 12 hours.
Acute otitis media (AOM), by mouth, CHILD, 15 mg/kg every
12 hours.
ANTI-INFECTIVES FOR SYSTEMIC USE
Pertussis, by mouth, INFANT >1 month, 7.5 mg/kg every 12
hours for 7 days; ADULT, 500 mg twice daily for 7 days.
Acute bacterial exacerbation of chronic bronchitis (ABECB),
severe, by mouth, ADULT, 500 mg twice daily for 5-10
days.
Community-acquired pneumonia, by mouth, CHILD >5 years
old, suspension 15 mg/kg in divided doses every 12
hours for 10 days.
Low-risk, without co-morbid illness, by mouth, ADULT,
500 mg twice daily for 5-7 days;
Low-risk, with stable co-morbid illness, by mouth, ADULT,
500 mg twice daily with co-amoxiclav OR cefuroxime for
5-7 days;
Moderate-risk, by mouth, ADULT, 500 mg twice daily with
ampicillin-sulbactam OR cefuroxime OR ceftriaxone for 7-
28 days;
Eradication of H. pylori, by mouth, ADULT, 500 mg twice
daily for 7 days in a combination treatment
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: Increased risk of cardiac deaths.
Patients with a predisposition to QT interval prolongation,
including electrolyte disturbances (e.g., uncorrected
hypokalemia or hypomagnesemia) and concomitant use
of drugs that prolong QT interval; History of ischemic
heart disease, severe cardiac insufficiency, ventricular
arrhythmia including torsades de pointes, bradycardia
(treatment risk-benefit should be considered);
Hepatic dysfunction (discontinue immediately if signs and
symptoms of hepatitis occur);
Antibiotic-associated colitis,
Myasthenia gravis (may be aggravated);
Elderly patients may be more susceptible to drug-associated
QT prolongation;
Breastfeeding (safety has not been established).
NOTE: Macrolides inhibit P-glycoprotein, which may lead to
drug interactions; CYP3A-based interactions
clarithromycin (a CYP3A inhibitor) may increase or
prolong both therapeutic and adverse effects of drugs
primarily metabolized by CYP3A enzymes.
Adverse Drug Reactions:
Common: Taste disturbance.
Less Common: Abdominal discomfort, diarrhea,
hepatotoxicity (including cholestatic jaundice), nausea,
rash, tinnitus, vomiting.
Rare: Antibiotic-associated colitis, arrhythmias,
pancreatitis, pulmonary infiltration with QT interval
prolongation, SJS, torsades de pointes, toxic epidermal
necrolysis.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Benzodiazepines e.g. Midazolam
Increases metabolism of Clarithromycin:
CYP3A4/5 inducers, Rifampicin
Increases risk of adverse or toxic effects Clarithromycin:
Class IA antiarrhythmics e.g. Procainamide
Class III antiarrhythmics e.g., Amiodarone, Sotalol or
drugs which prolong QT interval
Increases risk of adverse or toxic effects of Hypoglycemic
agents e.g. Insulin
Increases serum concentration of the following drugs:
Anticoagulants e.g. Warfarin, Phosphodiesterase
inhibitors e.g., Sildenafil, Theophylline
Avoid concomitant use with:
Decreases metabolism of Calcineurin inhibitors e.g.
Tacrolimus
Increases risk of adverse or toxic effects of the following
drugs:
Ergot alkaloids e.g. ergotamine, HMG-CoA reductase
J
inhibitors e.g. simvastatin (rhadomyolysis)
Increases serum concentration of the following drugs:
HMG-CoA reductase inhibitors e.g. simvastatin
Administration:
The regular tablet and liquid can be taken with or without
food; whereas, the long-acting tablet is usually taken with
food. Immediate release tablets are usually taken with or
without food. The tablet should be taken with a full glass
of water; while the long-acting tablet is swallowed whole
(do not split, chew or crush). Shake the suspension well
before use.
Pregnancy Category: C
ATC Code: J01FA09
ERYTHROMYCIN
Rx
WHO anti-biotic category: WATCH
Oral: 500 mg tablet (as stearate)
200 mg/5 mL granules / powder for suspension (as
ethyl succinate), 60 mL
400 mg/5 mL granules / powder for suspension (as
ethyl succinate), 50 mL and 60 mL
Indications: Alternative to penicillin in hypersensitive
patients such as in secondary prevention of rheumatic
fever and tonsillitis; conjunctivitis, pharyngitis, pertussis,
chlamydia infections and community-acquired
pneumonia.
Contraindications: Porphyria; severe hepatic impairment;
QT prolongation and ventricular cardiac arrhythmias.
Dose:
Conjunctivitis, Chlamydia trachomatis, by mouth, NEONATE,
12.5 mg/kg every 6 hours for 14 days.
Pharyngitis, penicillin allergy, by mouth, CHILD, 40 mg/kg in
divided doses every 6 hours for 10 days; ADULT, 400 mg
every 6-12 hours for 10 days.
Pertussis, by mouth, INFANT <1 month, 40 mg/kg in 4
divided doses for 14 days; ADULT, 500 mg four times
daily for 14 days.
231

Secondary prevention, acute rheumatic fever, ADULT, 20
mg/kg/day twice a day
Community-acquired pneumonia, by mouth, CHILD >5
years, 50 mg/kg in divided doses every 6-8 hours for 10-
14 days.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
Precautions:
Risk of sudden cardiac death from cardiac causes when oral
erythromycin used concomitantly with drugs that inhibit
CYP3A4;
Caution in ventricular cardiac arrhythmia and QT
prolongation;
Hepatic impairment (may cause idiosyncratic
hepatotoxicity), predisposition to QT interval
J
prolongation, including electrolyte disturbances and
concomitant use of drugs that prolong the QT interval;
Breastfeeding (small amounts found in milk – not known to
be harmful; may cause loose bowel in infants).
Adverse Drug Reactions:
Common: Abdominal pain, candida infections, cramps,
diarrhea, nausea, vomiting.
Less Common: Headache, rash, urticaria.
Rare: Blood dyscrasias, cardiac effects, cholestatic
jaundice, C. difficile-associated disease, hypersensitivity
reactions; anaphylaxis; infantile hypertrophic pyloric
stenosis, myasthenia-like syndrome, pancreatitis,
psychiatric disturbances, ototoxicity, toxic epidermal
necrolysis.
Frequency not defined: Torsades de pointes, ventricular
arrhythmias, ventricular tachycardia.
Drug Interactions:
NOTE: Macrolides inhibit P-glycoprotein, which may lead to
drug interactions.
Monitor closely with:
Reduces therapeutic effect of Contraceptives (Oral)
Avoid concomitant use with:
Increases serum concentration of Erythromycin:
CYP3A4 inhibitors, Verapamil
Increases serum concentration of HMG-CoA reductase
inhibitors e.g., Atorvastatin, Simvastatin
Increases risk of adverse or toxic effects of the following
drugs:
HMG-CoA reductase inhibitors (e.g. Atorvastatin,
Simvastatin) (myopathy and rhabdomyolysis) [stop
medication temporarily], Artemether + Lumefantrine
Decreases metabolism of Hydrocortisone
Administration:
Tablets and capsules should be swallowed WHOLE; best
taken on an empty stomach 1 hour before, or 2 hours,
after meals.
Pregnancy Category: B
232
ANTI-INFECTIVES FOR SYSTEMIC USE
ATC Code: J01FA01
LINCOSAMIDES
Rx CLINDAMYCIN
Oral: 150 and 300 mg capsule (as hydrochloride)
75 mg/5 mL granules for suspension (as palmitate
hydrochloride), 60 mL
Inj.: 150 mg/mL (as phosphate), 2 mL ampule / vial and
4 mL ampule (IM, IV)
Indications: Skin and soft tissue infections caused by
community-associated methicillin-resistant
Staphylococcus aureus (MRSA); alternative for
anaerobic infections. Alternative to macrolides for severe
penicillin allergy; recurrent pharyngitis
Contraindications: History of ulcerative or
pseudomembranous colitis.
Dose:
Immunocompetent children, intra-abdominal source, by IV
injection, CHILD, 20-40 mg/kg in divided doses every 6-
8 hours with ampicillin and gentamicin/amikacin for 10-
14 days.
Staphylococcal toxic shock syndrome, by IV injection, CHILD,
30-40 mg/kg in divided doses every 6-8 hours with
oxacillin/cefazolin/vancomycin and IVIG for 10-14 days.
Streptococcal toxic shock syndrome, by IV injection, CHILD,
30-40 mg/kg in divided doses every 6-8 hours with
penicillin G sodium/ceftriaxone and IVIG for 10-14 days.
Febrile neutropenia, low-risk, penicillin allergy, by mouth,
ADULT, 300 mg every 6 hours with
ciprofloxacin/levofloxacin until patient is afebrile and
absolute neutrophil count >500cells/μL.
Osteomyelitis, hematogenous, by IV injection, NEONATE 0-4
weeks old and <1.2kg, 10 mg/kg in 2 doses; NEONATE
0-7 days old and 1.2-2kg, 10 mg/kg in 2 doses;
NEONATE >7 days old and 1.2-2kg, 15 mg/kg in 3 doses;
NEONATE 0-7 days old and >2kg, 15 mg/kg in 3 doses;
NEONATE >7 days old and >2kg, 20 mg/kg in 4 doses;
CHILD and NEONATE >28 days old, 25-40 mg/kg in 3-4
doses; with cefotaxime OR ceftriaxone.
Osteomyelitis, contiguous focus, by IV injection, CHILD, 25-
40 mg/kg in 3-4 doses.
Suppurative arthritis, by IV injection, CHILD 3 months to 14
years, 25-40 mg/kg in 3-4 doses with cefotaxime OR
ceftriaxone for 3-6 weeks.
Dental prophylaxis, allergic to penicillin or ampicillin, by
mouth, CHILD, 20 mg/kg; ADULT, 500 mg; by IV IM/IV
injection, CHILD, 20 mg/kg; ADULT, 600 mg.
Dentoalveolar infection or peri-apical abscess, by mouth,
CHILD,10 mg/kg every 8 hours for 7-14 days; ADULT,
300mg every 8 hours for 7-14 days.
Acute gingivitis, by mouth, by IV injection, ADULT, 300 mg
with penicillin V potassium every 8 hours for 7-10 days.
Acute necrotizing ulcerative gingivitis, by mouth, by IV
injection, ADULT, 300 mg every 8 hours for 10 days.
Periodontal abscess, by mouth, CHILD, 10 mg/kg every 8
hours for 7 days; ADULT, 150-300 mg every 8 hours for
7 days.
ANTI-INFECTIVES FOR SYSTEMIC USE
Ludwig’s angina, by mouth, CHILD, 17-25 mg/kg in 3-4
equally divided doses for 2-3 weeks; by IV injection,
ADULT, 600 mg every 6-8 hours for 2-3 weeks.
Orbital cellulitis, stage II-IV, by IV injection, ADULT, 600 mg
every 8 hours with piperacillin-tazobactam OR
ciprofloxacin for 10-21 days.
Peritonsillar abscess, penicillin allergy, by IV injection,
CHILD, 40 mg/kg in divided doses every 6-8 hours;
ADULT, 600-900 mg every 6-8 hours.
Parapharyngeal space infection, by IV injection, ADULT,
600-900 mg every 8 hours with metronidazole.
Jugular vein suppurative phlebitis, by IV injection, ADULT,
600-900 mg every 8 hours.
Acute epiglottitis, by IV injection, ADULT, 600-900 mg every
6-8 hours with levofloxacin for 7-10 days.
Acute emphysema, by IV injection, CHILD, 25-40 mg/kg in
divided doses every 6-8 hours with ceftriaxone for 2-4
weeks; ADULT, 600 mg every 8 hours with ceftriaxone for
2-4 weeks.
Lung abscess, by IV injection, CHILD, 25-40 mg/kg in
divided doses every 6-8 hours with ceftriaxone for 4-6
weeks; ADULT, 600 mg every 8 hours for 4-6 weeks.
Pneumonia, anaerobic or aspiration with or without lung
abscess, by mouth, ADULT, 300-450 mg thrice a day for
3-4 weeks or longer; by IV injection, ADULT, 600 mg every
8 hours with ceftriaxone OR ampicillin-sulbactam for 3-4
weeks or longer.
Recurrent pharyngitis, ADULT, by mouth, 200 mg/kg/day
twice a day
Dose Adjustment:
Hepatic Impairment:
Use with caution in hepatic impairment, monitor for hepatic
abnormalities.
Precautions:
WARNING: Clostridium difficile-associated diarrhea
(CDAD) has been reported and may range in severity
from mild diarrhea to fatal colitis. This may occur during
treatment or for 2 months after discontinuation of
treatment. (more likely to be refractory to antimicrobial
therapy and may require colectomy).
Reserve clindamycin for serious infection where less toxic
antibiotics are inappropriate.
Avoid use for non-bacterial infection including most upper
respiratory tract infections.
Risk of potentially fatal pseudomembranous colitis, fungal
or bacterial superinfection on prolonged use,
discontinue therapy if significant abdominal cramps,
diarrhea or passage of blood and mucus occur;
Severe skin reactions (e.g. toxic epidermal necrolysis), some
with fatal outcome, have been reported, permanently
discontinue in these situations;
Parenteral product contains benzyl alcohol which may
cause “gasping syndrome” and death in newborn;
May increase the risk for antimicrobial-resistant bacteria if
used in the absence of proven or strongly suspected
susceptible bacteria;
Lactation: possibly unsafe.
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea, hypotension, jaundice,
nausea, pruritus, rash, urticaria, vomiting.
Frequency not defined: Agranulocytosis, C. difficile-
associated diarrhea, eosinophilia (transient),
esophagitis, fungal overgrowth, granulocytopenia,
hypersensitivity, neutropenia, polyarthritis,
pseudomembranous colitis, SJS, thrombocytopenia,
renal dysfunction.
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Conjugated estrogens or
estradiol or ethinylestradiol
Enhances therapeutic effect of the following drugs:
Digoxin, Warfarin (decreased vitamin-K producing
intestinal flora may increase INR after a few days)
Increases risk of adverse or toxic effects of Neuromuscular
blockers (e.g., pancuronium) (possible serious or life-
threatening interaction; risk of respiratory depression)
[use alternatives if possible]
J
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
Typhoid vaccine (Live) (antagonistic effects) (high
likelihood of serious or life-threatening interaction), BCG
vaccine (Live) (antagonistic effects) (high likelihood of
serious or life-threatening interaction), Erythromycin
(antagonistic effects)
Administration:
May be taken with food. Do not refrigerate reconstituted oral
solution since the solution will thicken; reconstituted
solution is stable for 2 weeks at room temperature.
Pregnancy Category: B
ATC Code: J01FF01
AMINOGLYCOSIDE ANTIBACTERIALS
Rx AMIKACIN
WHO anti-biotic category: ACCESS
Inj.: 50 mg/mL, 100 mg/mL, 125 mg/mL, and 250
mg/mL (as sulfate), 2 mL ampule / vial (IM, IV)
100 mg, 250 mg, 500 mg, and 1 g (as sulfate), vial
(IM, IV)
Indications:
Used in combination with beta lactams for the treatment of
potential and neonatal sepsis, bacterial purulent
pericarditis, acute bacterial meningitis in infants,
community-acquired pneumonia, hospital-acquired
pneumonia, ventilator-associated pneumonia, and
pathogen-specific infections
Dose:
Potential sepsis, by IM injection or IV infusion, NEONATE ≤7
days old ≤2 kg, 15 mg/kg every 48 hours; NEONATE 8-
28 days old ≤2 kg, 15 mg/kg every 24 hours; NEONATE
≤7 days old >2 kg, 15 mg/kg every 24 hours; NEONATE
8-28 days old >2 kg, 17.5 mg/kg every 24 hours; with
ampicillin
Neonatal sepsis, by deep IM injection or IV infusion,
NEONATE ≤7 days old ≤2kg, 15 mg/kg every 48 hours;
233

NEONATE 8-28 days old ≤2kg, 15 mg/kg every 24 hours;
NEONATE ≤7 days old >2kg, 15 mg/kg every 24 hours;
NEONATE 8-28 days old >2kg, 17.5 mg/kg every 24
hours; with cefotaxime/ceftriaxone with or without
oxacillin/vancomycin.
Immunocompetent children, intra-abdominal source, by IV
infusion, CHILD, 15-22.5 mg/kg in divided doses every
8-12 hours or 15-20 mg/kg daily with ampicillin and
metronidazole OR clindamycin for 10-14 days or longer.
Immunocompetent children, urinary source, by IV infusion,
CHILD, 15-22.5 mg/kg in divided doses every 8-12 hours
or 15-20 mg/kg daily with ceftriaxone OR cefotaxime for
10-14 days or longer.
Bacterial purulent pericarditis, S. aureus, Group A
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
IV infusion, CHILD, 15 mg/kg with vancomycin.
Impaired host, neutropenic, by IV infusion, CHILD, 15 mg/kg
with cefepime OR ceftazidime.
Community acute bacterial meningitis, by IM injection or IV
infusion, INFANT, 15 mg/kg with ampicillin OR
J
cefotaxime dependent on the etiology of bacterial
meningitis.
Community-acquired pneumonia, severe, by IV infusion,
NEONATE, 15 mg/kg with ampicillin OR penicillin G;
High-risk, risk for P. aeruginosa, by IV infusion, ADULT,
15 mg/kg with azithromycin and piperacillin-
tazobactam/cefepime/meropenem.
Hospital-acquired pneumonia, P. aeruginosa, A. baumanii,
K. pneumoniae; Klebsiella spp., E. coli, Enterobacter
spp.; Proteus spp.; Serratia marcesens, by IV infusion,
CHILD, 15 mg/kg with ceftazidime;
High risk of mortality and with risk factor for Multiple
Drug Resistance, by IV infusion, ADULT, 15-20 mg/kg
with vancomycin/linezolid AND piperacillin-tazobactam/
cefepime/ meropenem/ aztreonam for 7 days or longer.
Ventilator-associated pneumonia, with risk factors for Multi-
drug resistant VAP and with structural lung disease, by IV
infusion, ADULT, 15-20 mg/kg with vancomycin/linezolid
AND piperacillin-tazobactam/ cefepime/ meropenem/
aztreonam for 7 days or longer.
Pathogen—specific treatment, P. aeruginosa, by IV infusion,
CHILD, 15 mg/kg with ceftazidime; ADULT, 15 mg/kg
with levofloxacin OR ciprofloxacin;
Acinetobacter species, by IV infusion, CHILD, 15 mg/kg
in divided doses every 8 hours with meropenem;
Burkholderia cepacia, by IV infusion, CHILD, 15 mg/kg
with meropenem;
Escherichia coli, by IV infusion, CHILD, 15 mg/kg with
ceftriaxone;
Enterobacter, by IV infusion, CHILD, 15 mg/kg with
meropenem or cefepime.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Doses may be adjusted in patients with impaired renal
function either by administering normal doses at
prolonged intervals or by administering reduced doses at
fixed intervals. Neither method should be used when
dialysis is being performed.
Normal dose at prolonged intervals: If serum creatinine
concentration is 2mg/100mL, the recommended single
dose (7.5 mg/kg) should be administered every 18
hours.
234
ANTI-INFECTIVES FOR SYSTEMIC USE
Reduced dose at fixed interval; Serum amikacin should be
measured to avoid concentrations higher than 35
mcg/mL. If serum assay determinations are not available
and the patient’s condition is stable, serum creatinine
and clearance values are the most readily available
indicators of the degree of renal impairment.to use as
guide for dosage.
Precautions:
WARNING: Neurotoxicity, manifested as vestibular and
permanent bilateral auditory ototoxicity, can occur in
patients with preexisting renal damage in patients with
normal renal function treated at higher doses and/or
periods longer than those recommended.
Aminoglycosides are potentially nephrotoxic. The risk of
nephrotoxicity is greater in patients with impaired renal
function and in those who receive high doses or
prolonged therapy;
Neuromuscular blockade and respiratory paralysis have
been reported following parenteral injection, topical
instillation, and following oral use of aminoglycosides;
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months post-antibiotic treatment.
Adverse Drug Reactions:
Less Common: Neurotoxicity, nephrotoxicity, auditory
ototoxicity, vestibular ototoxicity.
Rare: Arthralgia, drowsiness, drug fever, dyspnea,
eosinophilia, headache, hypersensitivity reaction,
hypotension, nausea, paresthesia, skin rash, tremor,
vomiting, weakness
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects Amikacin:
Amphotericin B, Cephalosporins, Loop diuretics,
Vancomycin
Increases risk of adverse or toxic effects of the following
drugs:
Bisphosphonates e.g., Alendronate, Carboplatin
Neuromuscular-blocking agents
Reduces therapeutic effect of the following drugs:
BCG vaccine, Typhoid vaccine
Enhances therapeutic effect of Amikacin:
Capreomycin
Decreases excretion of Amikacin:
NSAIDs
Avoid concomitant use with:
Reduces therapeutic effect of Cholera vaccine
Increases risk of adverse or toxic effects Amikacin:
Foscarnet, Mannitol
Administration:
For IM: Administer IM injection in large muscle mass.
ANTI-INFECTIVES FOR SYSTEMIC USE
For IV: Infuse over 30 to 60 minutes (children, adolescents
and adults) or over 1 to 2 hours (infants).
Pregnancy Category: D
ATC Code: J01GB06
GENTAMICIN
Rx
WHO anti-biotic category: ACCESS
Inj.: 10 mg/mL (as sulfate), 2 mL ampule/vial (IM, IV)
40 mg/mL (as sulfate), 2 mL ampule / vial (IM, IV)
Indications: Used in combination with beta lactams for the
treatment of potential sepsis, sepsis neonatorum,
immunocompetent children due to specific sources,
native valve infective endocarditis, prosthetic valve
infective endocarditis, bacterial purulent pericarditis,
community acute bacterial meningitis, brain abscess in
the presence of endocarditis, chronic or recurrent
mastoiditis, community-acquired pneumonia, hospital-
acquired pneumonia, and pathogen-specific infections.
Contraindications: Perforated ear drum; hepatic
impairment; myasthenia gravis.
Dose:
Potential sepsis, by IV infusion, NEONATE ≤7 days old ≤2 kg,
5 mg/kg every 48 hours; NEONATE 8-28 days old ≤2 kg,
5 mg/kg every 36 hours; NEONATE ≤7 days old >2 kg, 4
mg/kg every 24 hours; NEONATE 8-28 days old >2 kg, 4-
5 mg/kg every 24 hours; with ampicillin.
Neonatal sepsis, by IV infusion, NEONATE ≤7 days old ≤2 kg,
5 mg/kg every 48 hours; NEONATE 8-28 days old ≤2 kg,
5 mg/kg every 36 hours; NEONATE ≤7 days old >2 kg, 4
mg/kg every 24 hours; NEONATE 8-28 days old >2 kg, 4-
5 mg/kg every 24 hours; with cefotaxime/ceftriaxone
with or without oxacillin/vancomycin.
Immunocompetent children, intra-abdominal source, by IV
infusion, CHILD, 6-7.5 mg/kg in divided doses every 8
hours or 5-7.5 mg/kg daily with ampicillin and
metronidazole OR clindamycin for 10-14 days or longer.
Immunocompetent children, urinary source, by IV infusion,
CHILD, 6-7.5 mg/kg in divided doses every 8 hours or 5-
7.5 mg/kg daily with ceftriaxone OR cefotaxime for 10-
14 days or longer.
Native valve infective endocarditis, community-acquired, by
IM injection or IV infusion, CHILD, 3-6 mg/kg in divided
doses every 8 hours with ampicillin-sulbactam; ADULT, 1
mg/kg every 8 hours with ampicillin-sulbactam;
Healthcare-associated, by IM injection or IV infusion,
CHILD, 3-6 mg/kg every 8 hours with vancomycin;
ADULT, 1 mg/kg every 8 hours with vancomycin and
cefepime/ceftazidime;
S. viridans or S. bovis (S. gallolyticus) with penicillin G
MIC ≤0.12 mcg/mL, by IV infusion, ADULT, 3 mg/kg with
penicillin G OR ceftriaxone for 2 weeks;
S. viridans or S. bovis (S. gallolyticus) with penicillin G
MIC >0.12 to ≤0.5mcg/mL, by IV infusion, CHILD, 3-6
mg/kg in divided doses every 8 hours with ampicillin OR
ceftriaxone for 2 weeks; ADULT, 3 mg/kg with penicillin
G for 2 weeks;
Enterococci, penicillin-resistant aminoglycoside-
sensitive, by IV infusion, CHILD, 3-6 mg/kg in divided
doses every 8 hours with vancomycin for 6 weeks;
ADULT, 1 mg/kg every 8 hours with vancomycin for 6
weeks.
Prosthetic valve infective endocarditis, by IV infusion,
CHILD, 3-6 mg/kg in divided doses every 8 hours with
vancomycin; ADULT, 1 mg/kg every 8 hours with
vancomycin and rifampin for 6 weeks;
MSSA, by IM injection or IV infusion, CHILD, 3-6 mg/kg in
3 divided doses with oxacillin and rifampin for 2 weeks;
ADULT, 1 mg/kg every 8 hours with oxacillin and rifampin
for 2 weeks;
Gram-negative enteric bacilli, by IV infusion, CHILD, 3-6
mg/kg in divided doses every 8 hours with
ceftazidime/cefotaxime/ceftriaxone.
Bacterial purulent pericarditis, S. aureus, Group A
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
IV infusion, ADULT, 5 mg/kg with vancomycin and
ceftriaxone/levofloxacin.
Community acute bacterial meningitis, by IM injection or IV
infusion, INFANT, 5 mg/kg with ampicillin OR cefotaxime
dependent on the etiology of bacterial meningitis.
J
Brain abscess in the presence of endocarditis, native valve,
by IM injection or IV infusion, ADULT and CHILD, 3-6
mg/kg with ceftriaxone.
Brain abscess in the presence of endocarditis, prosthetic
valve, by IM injection or IV infusion, ADULT and CHILD, 3-
6 mg/kg with vancomycin.
Chronic or recurrent mastoiditis, by IV infusion, CHILD, 7.5
mg/kg in divided doses every 8 hours with piperacillin-
tazobactam.
Community-acquired pneumonia, severe, by IV infusion,
NEONATE, 5 mg/kg with ampicillin OR penicillin G;
High-risk, risk for P. aeruginosa, by IV infusion, ADULT, 5-
7 mg/kg with azithromycin and piperacillin-
tazobactam/cefepime/meropenem.
Hospital-acquired pneumonia, P. aeruginosa, A. baumanii,
K. pneumoniae; Klebsiella spp., E. coli, Enterobacter
spp.; Proteus spp.; Serratia marcesens, by IV infusion,
CHILD, 5 mg/kg with ceftazidime;
Pathogen—specific treatment, P. aeruginosa, by IV infusion,
CHILD, 5-7 mg/kg with ceftazidime; ADULT, 5-7mg/kg
with levofloxacin OR ciprofloxacin;
Acinetobacter species, by IV infusion, CHILD, 5 mg/kg
with meropenem;
Burkholderia cepacia, by IV infusion, CHILD, 5-7 mg/kg
with meropenem;
Escherichia coli, by IV infusion, CHILD, 5 mg/kg with
ceftriaxone;
Enterobacter, by IV infusion, CHILD, 5-7 mg/kg with
meropenem or cefepime.
Dose Adjustment:
Neonates and Infants:
Adjust dosage; avoid prolonged use.
Geriatric:
For mild-to-moderate renal impairment, dose reduction or
dose interval extension is warranted; for severe
impairment, the patient should be referred to a
specialist.
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
235
 ANTI-INFECTIVES FOR SYSTEMIC USE

Precautions: QUINOLONE
WARNING: Neurotoxicity, manifested as both bilateral
auditory and vestibular ototoxicity, can occur in patients FIRST-GENERATION QUINOLONES
with pre-existing renal damage and in patients with (NON-FLUORINATED)
normal renal function treated at higher doses and/or
for periods longer than those recommended.
Aminoglycosides are potentially nephrotoxic. Risk is Rx NALIDIXIC ACID
greater in patients with impaired renal function and in
those who receive high doses or prolonged therapy. Oral: 500 mg tablet
Use with caution premature infants and neonates 250 mg/5 mL suspension, 60 mL
because of renal immaturity and the resulting
prolongation of serum half-life of the drug. Decrease Indications: Treatment of acute or chronic urinary tract and
dose. gastrointestinal tract infections caused by susceptible
Neuromuscular blockade and respiratory paralysis have gram-negative organisms.
been reported following parenteral injection of
aminoglycosides. Use with caution when giving in Contraindications: Hypersensitivity to any quinolones,
patients with neuromuscular diseases e.g. myasthenia children under 3 months old and pregnant women.
gravis.
Dose:
J

Obesity (use ideal body weight to calculate dose and
monitor serum gentamicin concentration closely);
Pregnancy (second and third trimesters: auditory or
vestibular nerve damage; reserve for severe or life-
threatening infections for which safer drugs are
inappropriate; if administered, monitor serum-
gentamicin concentration),
Breastfeeding (amount probably too small to be harmful;
monitor infant for thrush and diarrhea).
Adverse Drug Reactions:
Common: Edema, gait instability, ototoxicity (auditory and
vestibular damage), nephrotoxicity, reddening of the
skin, skin itching.
Less Common: Rash.
Rare: Anaphylaxis, antibiotic-associated colitis, blood
disorders, bronchospasm, CNS effects, electrolyte
disturbances, nausea, neuromuscular blockade, oliguria,
peripheral neuropathy, photosensitivity, stomatitis,
vomiting.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Gentamicin:
Ototoxic and nephrotoxic drugs e.g. Streptomycin
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Gentamicin:
Diuretics e.g. Furosemide
Administration:
Infuse gentamicin over 30-60 minutes; doses <120 mg may
be given as IV injection over 3-5 minutes. Final
concentration of IV infusion should not exceed 10
mg/mL.
Pregnancy Category: D
ATC Code: J01GB03
Shigellosis, by mouth, ADULT, 1 g every 6 hours for 5 days;
CHILD ≥3 months, 15 mg/kg (maximum 1 g) every 6
hours for 5 days.
Dose Adjustment:
Geriatric:
Risk of toxic reactions may be greater in patients with
impaired renal function.
Renal Impairment:
The normal dosage of nalidixic acid may be employed in
patients with creatinine clearance more than 20
mL/minute. Dosage should be halved in patients with
creatinine clearance 20 mL/minute or less.
Precautions:
WARNING: May cause toxic psychosis, convulsions,
increased intracranial pressure, or metabolic acidosis.
Use with caution in patients with known or suspected
CNS disorders e.g cerebral arteriosclerosis or epilepsy,
or other factors which predispose seizures
Serious and occasionally fatal hypersensitivity
(anaphylactoid) reactions, some following the first dose,
have been reported in patients receiving quinolone
therapy.
Adverse Drug Reactions:
Common: Nausea and vomiting.
Less Common: Visual disturbances, headache, rashes,
eosinophilia, and photosensitivity.
Rare: Hepatic and renal disturbances.
Drug Interactions:
Monitory closely with:
Enhances therapeutic effect of Warfarin
Reduces therapeutic effect of Nalidixic Acid:
Probenecid

Reduces absorption of Nalidixic Acid:

Antacids

Avoid concomitant use with:

Increases risk of adverse or toxic effects of Melphalan

236
ANTI-INFECTIVES FOR SYSTEMIC USE
Increases serum concentration of Cyclosporine
Administration: Can be taken with or without meals.
Patients should be advised to drink fluids liberally and
not take antacids.
Pregnancy Category: C
ATC Code: J01MB02
SECOND-GENERATION FLUOROQUINOLONES
Rx CIPROFLOXACIN
WHO anti-biotic category: WATCH
Oral: 250 mg and 500 mg tablet (as hydrochloride)
Inj.: 2 mg/mL (as lactate), 100 mL vial (IV infusion)
400 mg/200 mL (IV infusion)
Indications: Restricted use of treatment of severe infections
of the GI tract including MDR typhoid fever and Shigella
dysentery, chancroid; febrile neutropenia, alternative
treatment of acute uncomplicated cystitis;
meningococcal meningitis prophylaxis.
Contraindications: Known history of tendon disorders
related to quinolone use; children; concurrent tizanidine
use.
Dose:
Sepsis suspect intra-abdominal source, by IV infusion,
ADULT, 400 mg every 12 hours with metronidazole.
Febrile neutropenia, low risk, by mouth, Adult, 750 mg twice
daily with amoxicillin-clavulanic acid until patient is
afebrile and absolute neutrophil count >500cells/μL.
Antibacterial prophylaxis, by mouth, ADULT, 500-750 mg; by
IV infusion, ADULT, 400 mg every 12 hours.
Uncomplicated typhoid fever, by mouth, CHILD, 30 mg/kg in
divided doses every 12 hours for 7-10 days; ADULT, 500
mg 1 tablet every 12 horus for 7-10 days.
Complicated typhoid fever, by IV infusion, CHILD, 30 mg/kg
in divided doses every 12 hours for 7-10 days; ADULT,
400 mg every 12 hours for 7-10 days.
Chronic carrier, by IV infusion, CHILD, 30 mg/kg in divided
doses every 12 hours for 4 weeks; by mouth, ADULT,
500-750 mg every 12 hours for 28 days.
Non-typhoidal salmonellosis, Salmonella gastroenteritis, by
IV infusion, INFANT ≤3 months old, 10-20 mg/kg in
divided doses every 12 hours for 7-10 days.
Osteomyelitis, foot bone, by mouth, ADULT, 750 mg twice a
day,
Community acute bacterial meningitis, for severe penicillin
allergy, by IV infusion, ADULT, 400 mg with vancomycin;
For confirmed meningococcal meningitis and not treated
with Ceftriaxone, by mouth, ADULT, 500 mg.
Orbital cellulitis, with serious allergy to Penicillin and/or
cephalosporins, by mouth, CHILD, 20-30 mg/kg in 2
divided doses with vancomycin;
Stage II-IV MRSA not considered, by IV infusion, ADULT,
400 mg every 8-12 hours with clindamycin for 10-21
days;
Serious allergy to penicillin and/or cephalosphorin, by
mouth, ADULT, 500-750 mg twice a day with vancomycin
for 10-21 days; by IV infusion, ADULT, 400 mg every 12
hours with vancomycin for 10-21 days.
Community-acquired pneumonia, high risk, risk for P.
aeruginosa, by IV infusion, ADULT, 400 mg every 8-12
hours with azithromycin and gentamicin/ amikacin and
piperacillin-tazobactam /meropenem/ cefepime.
Pathogen-specific treatment, P. aeruginosa, by IV infusion,
CHILD, 20-30 mg/kg in divided doses every 12 hours
with amikacin/ gentamicin and piperacillin-tazobactam/
meropenem; ADULT, 400 mg every 8 hours with
amikacin/ gentamicin;
MDR Acinetobacter, by IV infusion, CHILD, 20-30 mg/kg
in divided doses every 12 hours;
Klebsiella pneumoniae, by IV infusion, CHILD, 20-30
mg/kg in divided doses every 12 hours;
Burkholderia cepacia, by IV infusion, CHILD, 20-30
mg/kg in divided doses every 12 hours; ADULT, 400 mg
every 12 hours;
Enterobacter, by IV infusion, CHILD, 20-30 mg/kg in
divided doses every 12 hours.
Dose Adjustment:
J
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
Hepatic Impairment:
Same dosage as in patients with normal hepatic function
may be used in patients with mild-to-moderate hepatic
impairment; for severe impairment, refer to a specialist.
Precautions:
WARNING: Associated with an increased risk of tendinitis
and tendon rupture; this risk is further increased in
older patients, usually those older than 60 years; in
kidney, heart, and lung transplant recipients; and with
the concomitant use of steroid therapy. If tendinitis is
suspected, the quinolone should be discontinued
immediately. Quinolones are contraindicated in
patients with a history of quinolone-related tendon
disorders.
May exacerbate muscle weakness in patients with
myasthenia gravis; avoid quinolones with known history
of myasthenia gravis.
History of epilepsy or conditions that predispose to seizures,
myasthenia gravis, G6PD deficiency (increased risk of
hemolytic anemia),
Risk of crystalluria (avoid excessive alkalinity of urine and
ensure adequate fluid intake)
Renal impairment;
photosensitivity (discontinue if photosensitivity occurs);
Pregnancy (avoid use; arthropathy reported in animal
studies; safer alternatives are available);
Breastfeeding (amount too small to be harmful; use
alternative drugs if possible).
USE IN CHILDREN: Ciprofloxacin causes arthropathy in
weight-bearing joints of immature animals, and is
therefore generally not recommended for use in children
and growing adolescents. However, the significance of
this effect in humans is uncertain and in some specific
circumstances, short-term use of ciprofloxacin in
children may be justified.
SKILLED TASKS: May impair ability to perform skilled tasks,
e.g., operating machinery or driving.
237

Adverse Drug Reactions:
Common: Abdominal pain, diarrhea, dyspepsia, flatulence,
itch, nausea, rash, vomiting.
Less Common: agitation, anorexia, arthralgia, arthritis,
confusion, decreased appetite and food intake,
depression, dizziness, drowsiness, hallucinations, fever,
headache, myalgia, superinfections, fever, headache,
myalgia, superinfections, restlessness, sleep and taste
disorders, urticaria.
Rare: Agranulocytosis, anaphylaxis, bone marrow
depression, C. difficile-associated disease, dyspnea,
edema, erythema multiforme, erythema, hematuria,
fixed drug eruptions, hearing loss, hemolytic anemia,
hepatitis, hyperglycemia, hypoglycemia, hypotension,
interstitial nephritis, jaundice, leukopenia, neutropenia,
pancreatitis, pancytopenia, petechiae, photosensitivity
reactions, psychotic reactions, renal impairment,
seizures, serum sickness-like reactions, SJS, syncope,
tachycardia, tendonitis, thrombocytopenia, toxic
epidermal necrolysis, vasculitis.
J
Drug Interactions:
NOTE: Ciprofloxacin inhibits CYP1A2, and may affect drugs
metabolized by this enzyme.
Monitor closely with:
Increases risk of adverse or toxic effects of Ciprofloxacin:
Ibuprofen
Reduces therapeutic effect of Phenytoin
Decreases metabolism of Theophylline
Enhances therapeutic effect of Warfarin
Increases risk of adverse or toxic effects of Warfarin (risk of
bleeding) [monitor INR]
Avoid concomitant use with:
Reduces absorption of Ciprofloxacin:
Antacids (e.g. aluminum or magnesium hydroxide) [give
it at least 2 hours, before, or 4-6 hours after, the antacid],
Calcium [separate doses by at least 2 hours], Iron
[separate doses by at least 2 hours], Sucralfate, Zinc
salts [separate doses by at least 2 hours]
Increases risk of adverse or toxic effects of Ciprofloxacin:
Seizure-inducing drugs, Artemether + Lumefantrine
Administration:
May be taken with or without food; do not take with
antacids, iron or dairy products.
Pregnancy Category: C
ATC Code: J01MA02
238
ANTI-INFECTIVES FOR SYSTEMIC USE
OFLOXACIN
Rx
WHO anti-biotic category: WATCH
Oral: 200 mg tablet
Indications: Treatment of acute exacerbations of chronic
bronchitis, community-acquired pneumonia, skin and
skin structure infections (uncomplicated), urethritis and
cervicitis (non-gonococcal) due to Chlamydia
trachomatis infection, mixed infections of the urethra
and cervix, pelvic inflammatory disease (acute), cystitis
(uncomplicated), urinary tract infections (complicated),
prostatitis.
Dose:
Cervicitis/urethritis, by mouth, non-gonococcal (due to
Chlamydia trachomatis), ADULT, 300 mg twice daily for
7 days
Chronic bronchitis (acute exacerbation), community-
acquired pneumonia, skin and skin structure infections
(uncomplicated), by mouth, ADULT, 400 mg every 12
hours for 10 days.
Pelvic inflammatory disease (acute), by mouth, ADULT, 400
mg every 12 hours for 10 to 14 days.
Prostatitis, by mouth, ADULT, 300 mg every 12 hours for 6
weeks.
Urinary tract infection, by mouth, ADULT, uncomplicated,
200 mg every 12 hours for 3 to 7 days; complicated, 200
mg every 12 hours for 10 days.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
After a normal initial dose, adjust as follows:
CrCl >20 mL/minute: Administer usual recommended dose
every 24 hours.
CrCl <20 mL/minute: Administer half the usual
recommended dose every 24 hours.
Intermittent hemodialysis (IHD): 100 to 200 mg after
dialysis.
Peritoneal dialysis: 200 mg every 24 hours.
Continuous renal replacement therapy (CRRT): 300 mg
every 24 hours.
Hepatic Impairment:
Use with caution for patients with severe impairment (e.g.,
cirrhosis with or without ascites).
Precautions:
WARNING: Significant hypoglycemia and certain mental
health side effects. Low blood sugar levels can lead to
coma; and the mental health side effects to be added
or updated across all fluoroquinolones are
disturbances in attention, disorientation, agitation,
nervousness, memory impairment, and serious
disturbances in mental abilities called delirium.
Associated with an increased risk of tendinitis and tendon
rupture in all ages. This risk is further increased in older
patients (usually older than 60 years), patients taking
corticosteroid drugs, and patients with kidney, heart, or
lung transplants.
ANTI-INFECTIVES FOR SYSTEMIC USE
May exacerbate muscle weakness in persons with
myasthenia gravis. Avoid ofloxacin in patients with a
known history of myasthenia gravis.
Fluoroquinolones may prolong QTc interval, avoid use in
patients with a history of QTc prolongation, uncorrected
hypokalemia, hypomagnesemia, or concurrent
administration of other medications known to prolong
the QT interval (including Class Ia and Class III
antiarrhythmics, cisapride, erythromycin, antipsychotics,
and tricyclic antidepressants);
Tremor, restlessness, confusion and very rare
hallucinations, increased intracranial pressure or
seizures may occur (use with caution in patients with
known or suspected CNS disorder. Discontinue in
patients who experience significant CNS adverse
effects);
Severe, sometimes, fatal, hypersensitivity reactions,
including anaphylaxis, have occurred with quinolone
therapy. (Prompt discontinuation of drug should occur if
skin rash or other symptoms arise);
Peripheral neuropathy (discontinue if symptoms of sensory
of sensorimotor neuropathy occur);
Photosensitivity (discontinue use if photosensitivity occurs);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
Adverse Drug Reactions:
Less Common: Chest pain, headache, insomnia, dizziness,
fatigue, drowsiness, sleep disorder, nervousness, trunk
pain, pruritus, skin rash, genital pruritus, nausea,
diarrhea, vomiting, abdominal cramps, constipation,
decreased appetite, dysgeusia, flatulence,
gastrointestinal distress, xerostomia, vaginitis, visual
disturbances, pharyngitis, fever.
Rare: Abnormal dreams, anaphylaxis, anxiety, auditory
disturbance, blurred vision, chills, cognitive dysfunction,
cough, depression, ecchymosis, edema, erythema
nodosum, euphoria, exacerbation of myasthenia gravis,
Gilles de la Tourette’s syndrome, hallucination, hepatic
insufficiency, hepatic failure, hepatitis, hepatotoxicity,
hyperglycemia, hypoglycemia, hypertension, increased
intracranial pressure, polydipsia, interstitial nephritis,
limb pain, malaise, palpitations, paresthesia, peripheral
neuropathy, photophobia, pneumonitis, pseudotumor
cerebri, psychotic reaction, rhabdomyolysis, rupture of
tendon, seizure, skin photosensitivity, SJS, syncope,
tendonitis, tinnitus, torsades de pointes, toxic epidermal
necrolysis, vasculitis, vasodilation, vertigo, weakness,
weight loss.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Glucose Lowering Agents e.g. Insulin
Delamanid, Fluoxetine, Porfimer, QTc-Prolonging
Agents, Tacrolimus, Vitamin K Antagonists e.g. Warfarin
Reduces absorption of Ofloxacin:
Antacids (except: sodium bicarbonate), Calcium Salts
(except: calcium chloride), Phosphate binder e.g.
Sevelamer
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Lactobacillus, Estriol, Sodium Picosulfate,
Typhoid Vaccine
Increases risk of adverse or toxic effects Ofloxacin:
Corticosteroids
Decreases excretion of Ofloxacin:
Probenecid
Avoid concomitant use with:
Increases risk of adverse or toxic effects Ofloxacin:
Nadifloxacin
Increases risk of adverse or toxic effects of Aminolevulinic
Acid
Reduces therapeutic effect of the following drugs:
BCG, Cholera Vaccine
Enhances therapeutic effect of the following drugs:
J
Hydroxychloroquine, Mifepristone, Probucol, QTc-
Prolonging Agents
Decreases serum concentration of Ofloxacin:
Strontium Ranelate
Administration: Administer with or without food; do not take
within 2 hours of sucralfate, didanosine, iron, zinc, or
antacids containing magnesium, calcium, or aluminum.
Pregnancy Category: C
ATC Code: J01MA01
THIRD-GENERATION FLUOROQUINOLONES
LEVOFLOXACIN
Rx
WHO anti-biotic category: WATCH
Oral: 250 mg, 500 mg, and 750 mg tablet
Inj.: 5 mg/mL solution for IV infusion, 100 mL and 150 mL
vial
Indications: Treatment of community-acquired pneumonia,
including multidrug resistant strains of S. pneumoniae;
nosocomial pneumonia; acute bacterial exacerbation of
chronic bronchitis; skin or skin structure infections
(uncomplicated or complicated); antibacterial
prophylaxis; pathogen-specific treatment
Dose:
Note: Sequential therapy (IV to oral) may be instituted based
on prescriber's discretion.
Sepsis, intra-abdominal source, by IV infusion, ADULT, 750
mg every 24 hours with metronidazole.
Febrile neutropenia, low risk, by mouth, ADULT, 750 mg with
amoxicillin-clavulanic acid until patient is afebrile and
absolute neutrophil count >500cells/μL.
Antibacterial prophylaxis, by mouth, by IV infusion, ADULT,
500-750 mg.
Osteomyelitis, hematogenous, vertebral, MRSA likely, by IV
infusion, ADULT, 750 mg every 24 hours with
vancomycin;
239

MRSA unlikely, by IV infusion, ADULT, 750 mg every 24
hours with oxacillin.
Osteomyelitis, foot bone, by mouth, ADULT, 750 mg every
24 hours.
Bacterial purulent pericarditis, S. aureus, Group A
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
IV infusion, ADULT, 750 mg every 24 hours with
vancomycin.
Acute epiglottitis, by IV infusion, ADULT, 750 mg every 24
hours with clindamycin.
Acute sinusitis, clinical failure after 3 days, by mouth,
ADULT, 500 mg for 5 days; by IV infusion, ADULT, 750
mg for 7-10 days.
Acute otitis media (AOM), with anaphylaxis, by mouth,
ADULT, 750 mg every 24 hours for 5 days.
Acute otitis media, clinical failure after 3 days, severe
penicillin allergy, by mouth, ADULT, 750 mg twice daily
for 5 days.
Acute mastoiditis, by IV infusion, ADULT, 750 mg daily.
Acute bacterial exacerbation of chronic bronchitis (ABECB),
J
severe, by mouth, ADULT, 500 mg every 24 hours for 5-
10 days.
Acute bacterial exacerbation (bronchiectasis), by mouth,
ADULT, 500 mg every 24 hours for 7-10 days.
Community-acquired pneumonia, moderate risk, by mouth,
ADULT, 750 mg with ampicillin-sulbactam/ cefuroxime
sodium/ ceftriaxone for 7-28 days;
High risk, no risk for P. aeruginosa, by IV infusion, ADULT,
750 mg with ceftriaxone or ertapenem;
High risk, risk for P. aeruginosa, by IV infusion, ADULT,
750 mg with gentamicin/amikacin and azithromycin and
piperacillin-tazobactam/ cefepime/ meropenem.
Hospital-acquired pneumonia, high risk of mortality and with
risk factor for MDR, by IV infusion, ADULT, 750 mg with
vancomycin/linezolid and piperacillin-tazobactam/
cefepime/ meropenem for 7 days or longer.
Ventilator-associated pneumonia, with risk factors for MRD
VAP and with structural lung disease, by IV infusion,
ADULT, 750 mg with vancomycin/linezolid and
piperacillin-tazobactam/ cefepime/ meropenem/
aztreonam for 7 days or longer.
Pathogen-specific treatment, P. aeruginosa, by IV infusion,
ADULT, 750 mg with amikacin OR gentamicin;
Klebsiella pneumoniae, by IV infusion, ADULT, 750 mg
every 24 hours.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Normal renal function dosing of 250 mg daily:
CrCl 20 to 49 mL/minute: No dosage adjustment required.
CrCl 10 to 19 mL/minute: Administer 250 mg every 48
hours (except in uncomplicated UTI, where no dosage
adjustment is required).
Normal renal function dosing of 500 mg daily:
CrCl 20 to 49 mL/minute: Administer 500 mg initial dose,
followed by 250 mg every 24 hours.
CrCl 10 to 19 mL/minute: Administer 500 mg initial dose,
followed by 250 mg every 48 hours.
Hemodialysis/chronic ambulatory peritoneal dialysis
(CAPD): Administer 500 mg initial dose, followed by 250
mg every 48 hours; supplemental doses are not required
following either hemodialysis or CAPD
Normal renal function dosing of 750 mg daily:
240
ANTI-INFECTIVES FOR SYSTEMIC USE
CrCl 20 to 49 mL/minute: Administer 750 mg every 48
hours.
CrCl 10 to 19 mL/minute: Administer 750 mg initial dose,
followed by 500 mg every 48 hours.
Hemodialysis/chronic ambulatory peritoneal dialysis
(CAPD): Administer 750 mg initial dose, followed by 500
mg every 48 hours; supplemental doses are not required
following either hemodialysis or CAPD.
Normal renal function dosing of 750 or 1,000 mg daily
(treatment of tuberculosis only) (CDC 2003): CrCl <30
mL/minute: Administer 750 or 1,000 mg 3 times per
week (in hemodialysis patients administer after dialysis
on dialysis days).
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation
to target trough (if appropriate). The following are general
recommendations only (based on dialysate
flow/ultrafiltration rates of 1 to 2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment:
CVVH: Loading dose of 500 to 750 mg followed by 250
mg every 24 hours.
CVVHD: Loading dose of 500 to 750 mg followed by 250
to 500 mg every 24 hours.
CVVHDF: Loading dose of 500 to 750 mg followed by
250 to 750 mg every 24 hours.
Precautions:
WARNING: Fluoroquinolones are associated with
disabling and potentially irreversible serious adverse
reactions that may occur together, including tendinitis
and tendon rupture, peripheral neuropathy, and CNS
effects. Discontinue levofloxacin immediately and
avoid use of fluoroquinolones in patients who
experience any of these serious adverse reactions.
Patients of any age or without preexisting risk factors
have experienced these reactions; may occur within
hours to weeks after initiation.
QTc prolongation (avoid use in patients with a history of QTc
prolongation, uncorrected hypokalemia,
hypomagnesemia, or concurrent administration of other
medications known to prolong the QT interval e.g, Class
Ia and Class III antiarrhythmics, cisapride, erythromycin,
antipsychotics, and tricyclic antidepressants;
Hypoglycemia/hyperglycemia (Patients should be
monitored closely for signs/symptoms of disordered
glucose regulation particularly severe hypoglycemia);
Severe hepatotoxicity (including acute hepatitis and
fatalities) has been reported. (Discontinue therapy
immediately if signs and symptoms of hepatitis occur);
Severe hypersensitivity reactions, including anaphylaxis
(Prompt discontinuation of drug should occur if skin rash
or other symptoms arise;
Photosensitivity (Discontinue use if photosensitivity occurs);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
ANTI-INFECTIVES FOR SYSTEMIC USE
Adverse Drug Reactions:
Less Common: Chest pain, edema, headache, insomnia,
dizziness, skin rash, pruritus, nausea, diarrhea,
constipation, abdominal pain, dyspepsia, vomiting,
vaginitis, candidiasis, injection site reaction, dyspnea
Rare: abnormal gait, acute generalized exanthematous
pustolosis, acute renal failure, ageusia, agitation,
agranulocytosis, altered sense of smell, anaphylactoid
reaction, aplastic and hemolytic anemia, anorexia,
anosmia, anxiety, arthralgia, blurred vision,
bronchospasm, cardiac arrest, cardiac arrhythmia
(including ventricular tachycardia/ fibrillation and
torsades de pointes), Clostridium difficile-associated
diarrhea, confusion, convulsions, crystalluria, decreased
visual acuity, depression, dermatological disease,
drowsiness, dysgeusia, epistaxis, erythema multiforme,
esophagitis, exacerbation of myasthenia gravis, fever,
gastritis (including gastroenteritis), glossitis,
granulocytopenia, hallucination, hepatic failure (some
fatal), hepatic insufficiency, hepatitis, hepatotoxicity
(idiosyncratic), hyperglycemia, hyperkalemia,
hyperkinesia, hypersensitivity pneumonitis,
hypersensitivity reaction (including anaphylaxis,
angioedema, rash, pneumonitis, and serum sickness),
hypertension, hypertonia, hypoacusis, hypoglycemia,
hypotension, increased intracranial pressure, interstitial
nephritis, intestinal obstruction, jaundice, leukocytosis,
leukopenia, leukorrhea, lymphadenopathy, multiorgan
failure, muscle injury, muscle spasm, myalgia,
palpitations, pancreatitis, pancytopenia, paralysis,
paranoia, paresthesia, peripheral neuropathy (may be
irreversible), phlebitis, phototoxicity, prolonged
prothrombin time, prolonged QT interval, pseudotumor
cerebri, psychosis, restlessness, rhabdomyolysis,
rupture of tendon, scotoma, seizure, skeletal pain, skin
photosensitivity, sleep disorder (including abnormal
dreams and nightmares), SJS, stomatitis, suicidal
ideation, syncope, tachycardia, tendonitis, tinnitus, toxic
epidermal necrolysis, toxic psychosis, thrombocytopenia
(including thrombotic thrombocytopenic purpura),
tremor, urticaria, uveitis, vasculitis, vasodilatation,
vertigo, visual disturbance (including diplopia), voice
disorder
Drug Interactions:
Monitory closely with:
Enhances therapeutic effect of the following drugs:
Blood Glucose Lowering Agents, Delamanid, Fluoxetine,
QTc-Prolonging Agents e.g. Tacrolimus, Vitamin K
Antagonists e.g. Warfarin
Reduces absorption of Levofloxacin:
Antacids (except: sodium bicarbonate), Calcium Salts
(except: calcium chloride), Sevelamer
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Lactobacillus, Estriol, Sodium Picosulfate,
Typhoid Vaccine
Increases risk of adverse or toxic effects Levofloxacin:
Corticosteroids
Decreases excretion of Levofloxacin:
Probenecid
Avoid concomitant use with:
Incrases risk of adverse or toxic effects Levofloxacin:
Nadifloxacin
Reduces therapeutic effect of the following drugs:
BCG, Cholera Vaccine
Enhances therapeutic effect of the following drugs:
Hydroxychloroquine, Macimorelin, Mifepristone,
Probucol, Promazine, QTc-Prolonging Agents
Decreases serum concentration of Levofloxacin:
Strontium Ranelate
Administration:
For oral: Tablets may be administered without regard to
meals. Oral solution should be administered at least 1
hour before or 2 hours after meals. Maintain adequate
hydration of patient to prevent crystalluria. Administer at
least 2 hours before or 2 hours after antacids containing
J
magnesium or aluminum, sucralfate, metal cations (e.g.
iron), multivitamin preparations with zinc, or didanosine
chewable/buffered tablets or the pediatric powder for
solution.
For IV: Infuse 250 to 500 mg IV solution over 60 minutes;
infuse 750 mg IV solution over 90 minutes. Too rapid of
infusion can lead to hypotension. Avoid administration
through an intravenous line with a solution containing
multivalent cations (eg, magnesium, calcium). Maintain
adequate hydration of patient to prevent crystalluria.
Pregnancy Category: C
ATC Code: J01MA12
FOURTH-GENERATION FLUOROQUINOLONES
Rx MOXIFLOXACIN
WHO anti-biotic category: WATCH
Oral: 400 mg film coated tablet
Indications: Treatment of multidrug resistant tuberculosis
(MDRTB); mild to moderate community-acquired
pneumonia, including multidrug-resistant Streptococcus
pneumoniae; acute bacterial exacerbation of chronic
bronchitis; acute bacterial sinusitis; complicated and
uncomplicated skin and skin structure infections;
complicated intra-abdominal infections; prophylaxis and
treatment of plague, including pneumonic and
septicemic plague, due to Yersinia pestis.
Dose:
Acute bacterial rhinosinusitis, by mouth, ADULT, 400 mg
every 24 hours for 10 days (manufacturer’s labeling) or
5 to 7 days. (Note: Recommended in patients with beta-
lactam allergy; may also be used if initial therapy fails, in
areas with high endemic rates of penicillin non
susceptible S. pneumoniae, those with severe infections,
age >65 years, recent hospitalization, antibiotic use
within the past month, or who are
immunocompromised).
Chronic bronchitis, acute bacterial exacerbation, by mouth,
ADULT, 400 mg every 24 hours for 5 days
241

Community-acquired pneumonia (CAP) (including MDRSP,
by mouth, ADULT, 400 mg every 24 hours for 7 to 14
days
Intra-abdominal infections, complicated, by mouth, ADULT,
400 mg every 24 hours for 5 to 14 days (initiate with IV);
Note: 2010 IDSA guidelines recommend a treatment
duration of 4 to 7 days (provided source controlled) for
community-acquired, mild to moderate IAI
Plague, by mouth, ADULT, 400 mg every 24 hours for 10 to
14 days
Skin and skin structure infections (Complicated), by mouth,
ADULT, 400 mg every 24 hours for 7 to 21 days
Skin and skin structure infections (Uncomplicated), by
mouth, ADULT, 400 mg every 24 hours for 7 days
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Hepatic Impairment:
J
No dosage adjustment necessary; however, use with
caution in this patient population secondary to the risk of
QT prolongation.
Precautions:
WARNING: Fluoroquinolones are associated with
disabling and potentially irreversible serious adverse
reactions that may occur together, including tendinitis
and tendon rupture, peripheral neuropathy, and CNS
effects. Discontinue moxifloxacin immediately and
avoid use of fluoroquinolones in patients who
experience any of these serious adverse reactions.
Patients of any age or without pre-existing risk factors
have experienced these reactions; may occur within
hours to weeks after initiation.
QTc prolongation (avoid use in patients with a history of QTc
prolongation, uncorrected hypokalemia,
hypomagnesemia, or concurrent administration of other
medications known to prolong the QT interval e.g. Class
Ia and Class III antiarrhythmics, cisapride, erythromycin,
antipsychotics, and tricyclic antidepressants;
Hypoglycemia/hyperglycemia (Patients should be
monitored closely for signs/symptoms of disordered
glucose regulation particularly severe hypoglycemia);
Severe hepatotoxicity (including acute hepatitis and
fatalities) has been reported. (Discontinue therapy
immediately if signs and symptoms of hepatitis occur);
Severe hypersensitivity reactions, including anaphylaxis
(Prompt discontinuation of drug should occur if skin rash
or other symptoms arise;
Photosensitivity (Discontinue use if photosensitivity occurs);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
Adverse Drug Reactions:
Common: headache, dizziness, insomnia, hyperchloremia,
nausea, diarrhea, constipation, vomiting, abdominal
pain, decreased hemoglobin, eosinopenia, leukocytosis,
hypoxia
Less Common: angina pectoris, atrial fibrillation,
bradycardia, cardiac arrest, cardiac failure, chest pain,
edema, hypertension, hypotension, palpitations,
peripheral edema, phlebitis, prolonged Q-T interval on
ECG, syncope, tachycardia, agitation, anxiety, chills,
242
ANTI-INFECTIVES FOR SYSTEMIC USE
confusion, depression, disorientation, drowsiness, facial
pain, fatigue, hallucination, hypoesthesia, lethargy,
malaise, nervousness, noncardiac chest pain, pain,
paresthesia, restlessness, vertigo, erythema,
hyperhidrosis, night sweats, pruritus, skin rash, urticaria,
hypokalemia, dehydration, hyperglycemia,
hyperlipidemia, abdominal discomfort, abdominal
distension, anorexia, decreased appetite, dysgeusia,
flatulence, gastritis, gastroenteritis, gastroesophageal
reflux disease, oral candidiasis, tinnitus, blurred vision,
fever, asthma, hypersensitivity reaction
Rare: agranulocytosis, anaphylactic shock, anaphylaxis,
angioedema, aplastic anemia, ataxia, auditory
impairment, cholestatic jaundice, Clostridium difficile
associated diarrhea, deafness (reversible), exacerbation
of myasthenia gravis, facial edema, hemolytic anemia,
hepatic failure, hepatic necrosis, hepatitis,
hypoglycemia, increased intracranial pressure,
interstitial nephritis, jaundice, laryngeal edema,
myasthenia, nightmares, pancytopenia, paranoia,
peripheral neuropathy (may be irreversible), pharyngeal
edema, phototoxicity, pneumonitis (allergic),
polyneuropathy, pseudomembranous colitis,
pseudotumor cerebri, psychotic reaction, renal
insufficiency, rupture of tendon, seizure, serum sickness,
skin photosensitivity, SJS, suicidal ideation, suicidal
tendencies, tendonitis, thrombotic thrombocytopenic
purpura, toxic epidermal necrolysis, ventricular
tachyarrhythmias (including torsades de pointes and
cardiac arrest
Drug Interactions:
Monitory closely with:
Enhances therapeutic effect of the following drugs:
Blood Glucose Lowering Agents, Fluoxetine, Porfimer,
QTc-Prolonging Agents, Tacrolimus, Verteporfin, Vitamin
K Antagonists (e.g. Warfarin)
Reduces absorption of Moxifloxacin:
Antacids (except: sodium bicarbonate), Calcium Salts
(except: calcium chloride), Sevelamer
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Lactobacillus and Estriol, Sodium
Picosulfate, Typhoid Vaccine
Increases risk of adverse or toxic effects Moxifloxacin:
Corticosteroids
Decreases excretion of Moxifloxacin:
Probenecid
Avoid concomitant use with:
Increases risk of adverse or toxic effects Moxifloxacin:
Nadifloxacin
Reduces therapeutic effect of the following drugs:
BCG, Cholera Vaccine
Enhances therapeutic effect of the following drugs:
Hydroxychloroquine, Macimorelin, Mifepristone,
Probucol, Promazine, QTc-Prolonging Agents, Vinflunine
Decreases serum concentration of Moxifloxacin:
Strontium Ranelate
ANTI-INFECTIVES FOR SYSTEMIC USE

Administration: Administer without regard to meals.
Administer at least 4 hours before or 8 hours after
products containing magnesium, aluminum, iron, or zinc,
including antacids, sucralfate, multivitamins, and
didanosine (buffered tablets for oral suspension or the
pediatric powder for oral solution).
Pregnancy Category: C
ATC Code: J01MA14
GLYCOPEPTIDE ANTIBACTERIALS
Rx VANCOMYCIN
WHO anti-biotic category: ACCESS and WATCH
Inj.: 500 mg and 1 g vial (as hydrochloride) (IV)
Indications: Treatment of early-onset prosthetic valve
Acute bacterial arthritis, monoarticular, not at risk for STI,
gram-positive cocci, by IV infusion, ADULT, 15-20 mg/kg
every 8-12 hours;
Negative on gram-stain, by IV infusion, ADULT, 15-20
mg/kg every 8-12 hours with ceftazidime OR piperacillin-
tazobactam.
Septic bursitis, MRSA, by IV infusion, ADULT, 15-20 mg/kg
every 8-12 hours for 14-21 days.
Prosthetic joint infections, Methicillin-resistant S. aureus or
epidermidis, by IV infusion, ADULT, 15-20 mg/kg every 8-
12 hours with rifampin and debridement, antibiotics and
implant retention (DAIR) followed by
levofloxacin/ciprofloxacin and rifampin for 3 months;
Enterococci (penicillin-resistant), by IV infusion, ADULT,
15 mg/kg every 12 hours for 4-6 weeks.
Native valve infective endocarditis, healthcare-associated,
by IV infusion, CHILD, 60 mg/kg in divided doses every 6
hours with gentamicin; ADULT, 15-20 mg/kg every 8-12
hours with gentamicin and cefepime/ceftazidime;
Enterococci, Penicillin-resistant aminoglycoside-

J
sensitive, by IV infusion, CHILD, 60 mg/kg in divided
diphtheroid endocarditis in combination; Treatment of
doses every 6 hours with gentamicin for 6 weeks; ADULT,
enterococci (e.g. Enterococcus faecalis) endocarditis, in
15-20 mg/kg every 8-12 hours with gentamicin for 6
combination; Treatment of staphylococcal endocarditis;
weeks.
Treatment of streptococcal endocarditis, as
MRSA, by IV infusion, CHILD, 60 mg/kg in divided doses
monotherapy or in combination; Treatment of serious or
every 6 hours; ADULT, 15-20 mg/kg every 8-12 hours for
severe infections (e.g. septicemia, bone infections, lower
6 weeks.
respiratory tract infections, skin and skin structure
Prosthetic valve infective endocarditis, empiric therapy, by
infections) caused by susceptible strains of methicillin-
IV infusion, CHILD, 40-60 mg/kg in divided doses every
resistant staphylococci; empiric therapy of suspected
6-8 hours with gentamicin and rifampin for 6 weeks;
methicillin-resistant staphylococci infections
ADULT, 15-20 mg/kg every 8-12 hours with gentamicin
Dose:
and rifampin for 6 weeks;
Severe sepsis and septic shock, by IV infusion, CHILD, 40-
MRSA, by IV infusion, CHILD, 40 mg/kg in 2-3 divided
60 mg/kg in divided doses every 6 hours for 10-14 days;
doses with gentamicin and rifampin for 6 weeks; ADULT,
meningitis, by IV infusion, NEONATE ≤28 days old, 15
15-20 mg/kg every 8-12 hours with gentamicin and
mg/kg with piperacillin-tazobactam OR meropenem for
rifampin for 6 weeks.
10-14 days;
Bacterial purulent pericarditis, S. aureus, Group A
Bacteremia, by IV infusion, NEONATE ≤28 days old, 10
Streptococcus, Enterobacteriaceae, S. pneumoniae, by
mg/kg with piperacillin-tazobactam OR meropenem for
IV infusion, CHILD, 60 mg/kg in divided doses every 6
10-14 days.
hours with ceftriaxone; ADULT, 15-20 mg/kg every 8-12
Staphylococcal toxic shock syndrome, MRSA, by IV infusion,
hours with ceftriaxone OR levofloxacin OR gentamicin OR
CHILD, 40-60 mg/kg in divided doses every 6 hours daily
amikacin.
drip for 1 hours with clindamycin and IV IG for 10-14
Methicillin-resistant S. aureus is isolated and/or with
days; ADULT, 25-30 mg/kg loading dose then 1 g every
history and clinical features for MRSA infection; S.
8 hours with clindamycin and IV IG for 2-3 days.
pneumoniae resistant to extended-spectrum
Sepsis, non-neutropenic and/or suspect illicit IV drug use
cephalosporins, or nosocomial infections, by IV infusion,
source, by IV infusion, ADULT, 25-30 mg/kg loading dose
CHILD, 60 mg/kg every 6 hours; empirical and
then 1 g every 8 hours with piperacillin-tazobactam.
determined partly by the nature of concomitant infection.
Osteomyelitis, hematogenous, MRSA likely, long bones, by
Once a pathogen is isolated and the antimicrobial
IV infusion, ADULT, 15-20 mg/kg every 8-12 hours for 4-
susceptibilities are known, the most specific
6 weeks;
antimicrobial agent is continued IV for 3-4 weeks.
Vertebral, by IV infusion, ADULT, 15-20 mg/kg every 8-
Central line-associated bloodstream infection (CLABSI), by
12 hours with ceftriaxone OR piperacillin-tazobactam,
IV infusion, CHILD, 60 mg/kg in divided doses every 6
OR levofloxacin.
hours with piperacillin-tazobactam and aminoglycoside;
Osteomyelitis, contiguous without vascular insufficiency,
ADULT, 15-20 mg/kg every 8-12 hours.
long bone or spinal implant, by IV infusion, ADULT, 15-20
Impaired host, neutropenic, by IV infusion, ADULT, 15-20
mg/kg every 8-12 hours with ceftazidime OR piperacillin-
mg/kg every 8-12 hours with cefepime OR ceftazidime
tazobactam;
OR piperacillin-tazobactam.
Sternum, post-surgery, by IV infusion, ADULT, 15-20
Community-acute bacterial meningitis, severe penicillin
mg/kg every 8-12 hours.
allergy, by IV infusion, ADULT, 15-20 mg/kg every 8-12
Osteomyelitis, contiguous focus, by IV infusion, CHILD, 45-
hours with aztreonam or ciprofloxacin.
60 mg/kg in 3-4 doses with ceftazidime OR cefepime.
Anatomic defects, neurosurgical complications, and open
Suppurative arthritis, gram stain is negative OR if gram stain
head trauma, by IM injection or IV infusion, CHILD, 60
is positive for gram-positive cocci, by IV infusion, CHILD
mg/kg in divided doses every 6 hours with ceftazidime;
3 months-14 years, 40-60 mg/kg in 3-4 doses with
ADULT, 15-20 mg/kg every 8-12 hours with ceftazidime.
cefotaxime OR ceftriaxone.

243

Brain abscess in the presence of head trauma, by IV
infusion, CHILD, 60 mg/kg in divided doses every 6 hours
with ceftriaxone; ADULT, 15-20 mg/kg every 8-12 hours
with ceftriaxone.
Brain abscess in the presence of endocarditis, by IV
infusion, CHILD, 60 mg/kg in divided doses every 6 hours
with gentamicin; ADULT, 15-20 mg/kg every 8-12 hours
with gentamicin.
Spinal abscess, by IV infusion, CHILD, 60 mg/kg in divided
doses every 6 hours; ADULT, 15-20 mg/kg every 8-12
hours.
Dacrocystitis, by IV infusion, CHILD, 40 mg/kg 3-4 in divided
doses with ceftazidime for 7-14 days;
With signs and symptoms of orbital cellulitis, ADULT, 15-
20 mg/kg every 8-12 hours with ceftriaxone or cefepime
for 7-14 days.
Acute mastoiditis, by IV infusion, CHILD, 45-60 mg/kg in
divided doses every 6 hours.
Acute emphysema, by IV infusion, ADULT, 40 mg/kg in
divided doses every 6 hours with ampicillin-sulbactam
J
for 2-4 weeks.
Lung abscess, by IV infusion, CHILD, 40 mg/kg in divided
doses every 6 hours with ceftriaxone and metronidazole
for 4 weeks.
Hospital-acquired pneumonia, not at high risk of mortality
but with factors increasing the likelihood of MRSA, by IV
infusion, ADULT, loading dose of 25-30 mg/kg then 15-
20 mg/kg every 8-12 hours with goal to target trough
level to 15-20 mg/mL with piperacillin-tazobactam/
cefepime/ meropenem/ aztreonam;
High risk of mortality and with risk factor for MDR, by IV
infusion, ADULT, loading dose of 25-30 mg/kg then 15-
20 mg/kg every 8-12 hours with goal to target trough
level to 15-20 mg/mL with piperacillin-tazobactam/
cefepime/ meropenem/ aztreonam and
levofloxacin/amikacin for 7 days.
Ventilator-associated pneumonia, with risk factors for MRD
VAP and with structural lung disease, by IV infusion,
ADULT, loading dose of 25-30mg/kg then 15-20 mg/kg
every 8-12 hours with goal to target trough level to 15-
20 mg/mL with piperacillin-tazobactam/ cefepime/
meropenem/ aztreonam and levofloxacin/ amikacin for
7 days.
Pathogen-specific treatment, by IV infusion, CHILD, 40-60
mg/kg in divided doses every 6 hours with goal to target
trough level to 15-20 mg/mL; ADULT, 15-20 mg/kg.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Poorly dialyzable by intermittent hemodialysis; however, use
of high-flux membranes and continuous renal
replacement therapy (CRRT) increases vancomycin
clearance, and generally requires replacement dosing
(Launay-Vacher 2002).
End-stage renal disease (ESRD) on intermittent
hemodialysis (IHD) (administer after hemodialysis on
dialysis days): Following loading dose of 15 to 25 mg/kg,
give either 500 to 1,000 mg or 5 to 10 mg/kg after each
dialysis session (Heintz 2009). Note: Dosing dependent
on the assumption of 3 times/week, complete IHD
sessions.
244
ANTI-INFECTIVES FOR SYSTEMIC USE
Redosing based on pre-HD concentrations:
<10 mg/L: Administer 1,000 mg after HD
10 to 25 mg/L: Administer 500 to 750 mg after HD
>25 mg/L: Hold vancomycin
Redosing based on post-HD concentrations: <10 to 15
mg/L: Administer 500 to 1,000 mg
Peritoneal dialysis (PD): 1 g every 4 to 7 days
Continuous renal replacement therapy (CRRT): Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation
to target trough (if appropriate). The following are general
recommendations only (based on dialysate
flow/ultrafiltration rates of 1 to 2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment:
CVVH: Loading dose of 15 to 25 mg/kg, followed by
either 1,000 mg every 48 hours or 10 to 15 mg/kg every
24 to 48 hours
CVVHD: Loading dose of 15 to 25 mg/kg, followed by
either 1,000 mg every 24 hours or 10 to 15 mg/kg every
24 hours
CVVHDF: Loading dose of 15 to 25 mg/kg, followed by
either 1,000 mg every 24 hours or 7.5 to 10 mg/kg every
12 hours
Note: Consider redosing patients receiving CRRT for
vancomycin concentrations <10 to 15 mg/L.
Precautions:
IV vancomycin is an irritant; ensure proper needle or
catheter placement prior to and during infusion; avoid
extravasation. If thrombophlebitis occurs, slow infusion
rates, dilute solution (eg, 2.5 to 5 g/L) and rotate infusion
sites;
May cause nephrotoxicity; usual risk factors include
preexisting renal impairment, concomitant nephrotoxic
medications, advanced age, and dehydration (If multiple
sequential (≥2) serum creatinine concentrations
demonstrate an increase of 0.5 mg/dL or ≥50% increase
from baseline (whichever is greater) in the absence of an
alternative explanation, the patient should be identified
as having vancomycin-induced nephrotoxicity);
Prolonged therapy and use of concomitant drugs that cause
neutropenia may increase the risk (monitor leukocyte
counts periodically in these patients. Prompt reversal of
neutropenia is expected after discontinuation of
therapy);
Ototoxicity is rarely associated with monotherapy (Serial
auditory function testing may be helpful to minimize risk.
Ototoxicity may be transient or permanent; discontinue
treatment if signs of ototoxicity occur);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile infection (CDI); CDI
has been observed >2 months post-antibiotic treatment.
Adverse Drug Reactions:
Common: Hypotension (accompanied by flushing)
Less Common: Local phlebitis, chills, drug fever, skin rash,
eosinophilia, neutropenia (reversible)
Rare: DRESS syndrome (drug rash with eosinophilia and
systemic symptoms), ototoxicity (use of other ototoxic
agents may increase risk), renal failure (limited data
ANTI-INFECTIVES FOR SYSTEMIC USE
suggesting direct relationship), SJS, thrombocytopenia,
vasculitis
Drug Interactions:
Monitory closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Aminoglycosides e.g. Streptomycin
Colistimethate
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Lactobacillus and Estriol
Sodium picosulfate, Typhoid Vaccine
Reduces therapeutic effect of Vancomycin:
Bile Acid Sequestrants
Enhances therapeutic effect of Neuromuscular-Blocking
Agents
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
BCG, Cholera Vaccine
Administration: Administer vancomycin with a final
concentration not to exceed 5 mg/mL by IV intermittent
infusion over at least 60 minutes (recommended
infusion period of ≥30 minutes for every 500 mg
administered; in adult patients in need of fluid
restriction, a concentration up to 10 mg/mL may be
used, but risk of infusion-related reactions is increased.
NOT for IM administration.
Pregnancy Category: B
ATC Code: J01XA01
POLYMYXINS
Rx COLISTIN
WHO anti-biotic category: RESERVE
Inj.: 2,000,000 IU lyophilized powder for injection (IV
infusion)
Indications: For extended-spectrum beta-lactamase (ESBL)
or carbapenemase-producing multidrug-resistant (MDR)
gram-negative bacillus; Treatment of acute or chronic
infections due to sensitive strains of certain gram-
negative bacilli (particularly Pseudomonas aeruginosa)
which are resistant to other antibacterials or in patients
allergic to other antibacterials
NOTE: Its use is restricted only to health facilities able to
satisfy the following criteria:
(1) Presence of an Infection Control Committee whose
chairperson is a physician and DOH-trained on
antimicrobial stewardship
(2) Presence of a board certified infectious disease
specialist who shall authorize the use of the drug as
clinically needed
Dose:
Susceptible infections, for IV injection, ADULT, 2.5 to 5 mg
CBA/kg/day in 2 to 4 divided doses; maximum: 5 mg
CBA/kg/day, CHILD, 2.5 to 5 mg CBA/kg/day in 2 to 4
divided doses; maximum: 5 mg CBA/kg/day
Dose Adjustment:
Geriatric:
Refer to adult dosing
Renal Impairment:
Note: Dosage expressed in terms of colistin base activity
(CBA); although reported conversions have varied slightly
in the literature, CBA 1 mg is defined to be equivalent to
colistimethate sodium (CMS) 30,000 units
CrCl ≥80 mL/minute: No dosage adjustment necessary;
maximum: 5 mg CBA/kg/day
CrCl 50 to 79 mL/minute: 2.5 to 3.8 mg CBA/kg/day in
2 divided doses
CrCl 30 to 49 mL/minute: 2.5 mg CBA/kg/day once daily
or in 2 divided doses
CrCl 10 to 29 mL/minute: 1.5 mg CBA/kg every 36 hours
Intermittent hemodialysis (IHD) (administer after
J
hemodialysis on dialysis days) - 1.5 mg CBA/kg every 24
to 48 hours
Continuous renal replacement therapy (CRRT) - Drug
clearance is highly dependent on the method of renal
replacement, filter type, and flow rate. Appropriate
dosing requires close monitoring of pharmacologic
response, signs of adverse reactions due to drug
accumulation, as well as drug concentrations in relation
to target trough (if appropriate).
CVVH/CVVHD/CVVHDF - 2.5 mg CBA/kg every 24 to 48
hours (frequency dependent upon site or severity of
infection or susceptibility of pathogen). Note: These are
general recommendations only (based on dialysate
flow/ultrafiltration rates of 1 to 2 L/hour and minimal
residual renal function) and should not supersede
clinical judgment. More recent data among patients
receiving CVVHDF suggest that the daily dose at least
equal or even exceed that of patients with normal renal
function.
Sustained low-efficiency dialysis (SLED): IV: May consider
using the following calculations; however, although
derived from critically ill patients, the use of this
algorithm has not been prospectively evaluated in the
critically ill (Nation 2017):
Loading dose of colistin base activity (mg) = Target
average colistin steady-state plasma concentration (in
mg/L) x 2 x weight (in kg) (maximum loading dose: 300
mg CBA). For patient weight, use the lower of ideal or
actual body weight expressed in kg. Application of these
equations has not been evaluated in obese patients.
Maintenance dose of colistin base activity (mg): Add 10%
per 1 hour of SLED replacement to the baseline daily
dose (refer to equation in IHD section above; administer
in 2 divided doses administered 12 hours apart). For
example, in a patient receiving 10 hours nocturnal SLED
session each day with a goal colistin steady-state
concentration of 2 mg/L, the suggested CBA dose is: 130
mg + 10 hours * 13 mg = 260 mg CBA/day. SLED
session should begin 1 to 2 hours after the
afternoon/evening dose.
Precautions:
Transient, reversible neurological disturbances (e.g.,
dizziness, numbness, paresthesia, generalized pruritus,
245
 ANTI-INFECTIVES FOR SYSTEMIC USE

slurred speech, tingling, vertigo) may occur. (Patients IMIDAZOLE DERIVATIVES

must be cautioned about performing tasks which require
mental alertness (e.g., operating machinery or driving).
Dose reduction may reduce neurologic symptoms; Rx METRONIDAZOLE
WHO anti-biotic category: ACCESS
monitor closely);
Dose-dependent nephrotoxicity has been reported,
Oral: 250 and 500 mg tablet
generally reversible upon discontinuation of treatment.
125 mg base/5 mL (200 mg/5 mL) (as benzoate)
Withhold treatment if signs of renal impairment occur
suspension, 60 mL
during treatment;
Inj.: 5 mg/mL, 100 mL vial (IV infusion)
Respiratory arrest has been reported with use; impaired
renal function may increase the risk for neuromuscular
Indications: Eradication of H. pylori; Treatment of acute
blockade and apnea;
intestinal amebiasis (amebic dysentery) and amebic liver
Prolonged use may result in fungal or bacterial
abscess; Treatment of bacterial septicemia; Treatment
superinfection, including C. difficile-associated diarrhea
(adjunctive therapy) of bone and joint infections;
(CDAD) and pseudomembranous colitis; CDAD has been
Treatment of CNS infections, including meningitis and
observed >2 months postantibiotic treatment.
brain abscess; Treatment of gynecologic infections
including endometritis, endomyometritis, tubo-ovarian
Adverse Drug Reactions:
abscess, or postsurgical vaginal cuff infection; Treatment
Common: Nephrotoxicity, acute, renal failure
of intra-abdominal infections, including peritonitis, intra-
Less Common: neurotoxicity
J

abdominal abscess and liver abscess; Treatment of

lower respiratory tract infections, including pneumonia,
Drug Interactions:
empyema and lung abscess
Monitory closely with:
Increases risk of adverse or toxic effects Colistin:
Dose:
Aminoglycosides e.g. Streptomycin; Amphotericin B
Sepsis, suspect intra-abdominal source, by IV infusion,
Cefazedone, Cephalothin, Vancomycin
ADULT, 1 g loading dose then 500 mg every 6 hours or 1
g every 12 hours. CHILD, 30-50 mg/kg every 6 hours with
Reduces therapeutic effect of the following drugs:
ampicillin and gentamicin/amikacin for 10-14 days.
BCG Vaccine, Lactobacillus and Estriol, Sodium
Brain abscess in the presence of chronic otitis media,
Picosulfate, Typhoid Vaccine
sinusitis, or mastoiditis, by IM injection or IV infusion,
CHILD and ADULT, 7.5 mg/kg every 6 hours or 15 mg/kg
Enhances therapeutic effect of Colistin:
every 12 hours with ceftazidime.
Capreomycin, Polymyxin B
Brain abscess, no focus or in the presence of congenital
heart disease, CHILD and ADULT, 7.5 mg/kg every 6
Enhances therapeutic effect of Neuromuscular-Blocking
hours or 15 mg/kg every 12 hours with ceftriaxone.
Agents
Acute gingivitis, oral anaerobes, by mouth, CHILD >12 years
old, 30 mg/kg in divided doses every 6 hours with
Avoid concomitant use with:
penicillin for 7-10 days; ADULT, 500 mg every 8 hours
Increases risk of adverse or toxic effects of the following
with penicillin V potassium for 7-10 days.
drugs:
Acute necrotizing ulcerative gingivitis, oral anaerobes, by
Bacitracin, Methoxyflurane
mouth, ADULT, 500 mg every 8 hours with penicillin V
potassium for 10 days.
Reduces therapeutic effect of the following drugs:
Juvenile periodontitis, by mouth, CHILD <8 years old, 50
BCG, Cholera Vaccine
mg/kg in divided doses every 8 hours for 7 days.
Ludwig’s angina, by IV infusion, CHILD, 22.5-40 mg/kg in 3
Administration: Administer by IM, direct IV injection over 3
divided doses with ampicillin-sulbactam OR penicillin G
to 5 minutes, intermittent infusion over 30 minutes or by
for 2-3 weeks; ADULT, 500 mg every 6-8 hours with
continuous IV infusion.
penicillin G for 2-3 weeks.
For continuous IV infusion, one-half of the total daily dose is
Jugular vein suppurative phlebitis (Lumierre’s syndrome), by
administered by direct IV injection over 3 to 5 minutes
mouth or IV infusion, ADULT, 500 mg every 8 hours with
followed 1 to 2 hours later by the remaining one-half of
ceftriaxone.
the total daily dose diluted in a compatible IV solution
infused over 22 to 23 hours. The final concentration for
Dose Adjustment:
continuous infusion administration should be based on
Geriatric:
the patient's fluid needs; infusion should be completed
Refer to adult dosing
within 24 hours of preparation.
Renal Impairment:
Pregnancy Category: C
Severe impairment: There are no dosage adjustments
provided in the manufacturer’s labeling; metronidazole
ATC Code: J01XB01
metabolites may accumulate; monitor for adverse
events.
ESRD requiring dialysis: Metronidazole metabolites may
accumulate; monitor for adverse events. Accumulated
metabolites may be rapidly removed by dialysis:

246
ANTI-INFECTIVES FOR SYSTEMIC USE
Intermittent hemodialysis (IHD): If administration cannot
be separated from hemodialysis, consider supplemental
dose following hemodialysis.
Peritoneal dialysis (PD): No dosage adjustment
necessary.
Hepatic Impairment:
Severe impairment (Child-Pugh class C):
Extended-release tablets: Use is not recommended.
Immediate-release capsules:
Amebiasis: 375 mg 3 times daily
Trichomoniasis: 375 mg once daily
Immediate-release tablets, injection:
Reduce dose by 50%
Precautions:
WARNING: Possibly carcinogenic based on animal
data. Unnecessary use should be avoided.
Clinical and laboratory monitoring recommended in course
lasting longer than 10 days;
Hepatic impairment and hepatic encephalopathy; Renal
impairment;
Congestive heart failure;
History of blood dyscrasias;
History of CNS disorders and seizures;
Severe neurological disturbances, including aseptic
meningitis (may occur within hours of a dose), cerebellar
symptoms, convulsive seizures, encephalopathy, optic
neuropathy, and peripheral neuropathy (usually
symmetric and of sensory type) have been reported;
CNS symptoms and CNS lesions are generally reversible
within days to weeks of discontinuation of therapy;
peripheral neuropathy symptoms may be prolonged after
discontinuation. (Monitor for neurologic symptoms and
discontinue therapy if any abnormal neurologic
symptoms occur);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months post-antibiotic treatment.
Candidiasis infection (known or unknown) may be more
prominent during metronidazole treatment, antifungal
treatment required.
Pregnancy (avoid use in early pregnancy); lactation
(significant amounts excereted in breastmilk; may cause
bitterness in milk)
Adverse Drug Reactions:
Common: Headache, nausea, vaginitis
Less Common: Metallic taste, dizziness, genital pruritus,
abdominal pain, diarrhea, xerostomia, dysmenorrhea,
urine abnormality, urinary tract infection, bacterial
infection, candidiasis, flu-like symptoms, upper
respiratory tract infection, pharyngitis, sinusitis
Drug Interactions:
Monitory closely with:
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Lactobacillus and Estriol, Sodium
Picosulfate, Typhoid Vaccine
Increases risk of adverse or toxic effects of the following
drugs:
Lithium, Lopinavir, Tipranavir
Enhances therapeutic effect of Vecuronium
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Alcohol (Ethyl), Carbocisteine, Products Containing
Propylene Glycol
Increases risk of adverse or toxic effects Metronidazole:
Disulfiram, Mebendazole, Ritonavir
Reduces therapeutic effect of the following drugs:
BCG, Cholera Vaccine
Administration:
For IV: Infuse intravenously over 30 to 60 minutes. Avoid
contact of drug solution with equipment containing
aluminum.
For oral: Immediate-release tablets and capsules may be
administered with food to minimize stomach upset.
J
Extended-release tablets should be administered on an
empty stomach (1 hour before or 2 hours after meals);
do not split, crush, or chew.
Pregnancy Category: B
ATC Code: J01XD01
NITROFURAN DERIVATIVES
Rx NITROFURANTOIN
WHO anti-biotic category: ACCESS
Oral: 50 mg and 100 mg capsule (as macrocrystals)
Indications: Treatment of acute, uncomplicated cystitis in
non-pregnant women, asymptomatic bacteruria;
recurrent urinary tract infection in non-pregnant women
(for asymptomatic bacteriuria in pregnancy, urine culture
is necessary).
Contraindications: Previous history of cholestatic jaundice
or hepatic dysfunction associated with prior
nitrofurantoin use; for infants <1 month of age
(increased risk of hemolytic anemia); G6PD-deficiency,
including breast-feeding of affected infants (only small
amounts in milk but may be enough to produce
hemolysis in G6PD-deficient infants); pregnancy at term
(third trimester: may produce neonatal hemolysis if used
at term); porphyria.
Dose:
Asymptomatic bacteriuria, by mouth, ADULT, in non-
pregnant patients 100 mg 4 times daily for 7-14 days; in
pregnant women, 100 mg 4 times daily for 7 days.
Acute uncomplicated cystitis in non-pregnant women, by
mouth, ADULT, 100 mg 4 times daily for 5 days; in
pregnant women, 100 mg 4 times daily for 7 days; CHILD
>1year, 5-7 mg/kg/day divided in 4 doses (maximum
dose, 400 mg).
Recurrent urinary tract infection in non-pregnant women, by
mouth, ADULT (women), 100 mg at bedtime for 6-12
months either continuously or as post-coital prophylaxis.
247

Dose Adjustment:
Renal Impairment:
Avoid use (peripheral neuropathy; ineffective because of
inadequate urinary concentrations).
Hepatic Impairment:
Avoid use (cholestatic jaundice and chronic active hepatitis
have been reported).
Precautions:
This is NOT indicated for the treatment of pyelonephritis; it
is ineffective in alkaline urine;
Pulmonary toxicity and disorders (monitor lung and liver
function on long-term therapy; discontinue use if the lung
function deteriorates; acute, subacute or chronic
pulmonary reactions have been observed);
Susceptibility to peripheral neuropathy (risk may be
increased in patients with anemia, renal impairment,
diabetes, vitamin B deficiency, debilitating disease, or
electrolyte disturbance);
J
Risk of optic neuritis;
Hepatic reactions (monitor liver function tests periodically);
Hemolytic anemia;
Neurological or allergic disorder;
folate deficiency; prolonged use may result in fungal or
bacterial superinfection; urine may be colored yellow or
brown.
Elderly (monitor closely for toxicities during use).
Pregnancy (when given during second trimester until 32
weeks age of gestation)
NOTE: During long-term treatment, monitor:
Pulmonary function; Liver function every month for 3
months, then every 3 months, since onset of
hepatotoxicity may be insidious; Renal function;
Development of paresthesia (withdraw to prevent severe
neuropathy).
Adverse Drug Reactions:
Common: Abdominal pain, allergic skin reactions, anorexia,
diarrhea, headache, nausea, vomiting.
Less Common: Dizziness, drowsiness, vertigo.
Rare: Alopecia, anaphylaxis, arthralgia, benign intracranial
hypertension; blood disorders, drug fever, cholestatic
jaundice, erythema multiforme, exfoliative dermatitis,
pancreatitis, peripheral neuropathy, pulmonary
reactions, SJS.
Drug Interactions:
NOTE: The bioavailability of nitrofurantoin is usually
increased by medicines that reduce gastric emptying
time, such as diphenoxylate and atropine.
Monitor closely with:
Increases risk of adverse or toxic effects of Aldosterone-
blocking agents e.g., eplerenone and spironolactone
(hyperkalemic effect)
Enhances therapeutic effect of Sedatives (e.g. alcohol)
(potentiative effect)
Avoid concomitant use with:
Reduces absorption of Nitrofurantoin:
Antacids
Administration:
Take with food or milk.
248
ANTI-INFECTIVES FOR SYSTEMIC USE
Pregnancy Category: B
ATC Code: J01XE01
FOSFOMYCIN
Rx
WHO anti-biotic category: RESERVE
Oral: 3 g granules for solution
Indication: First-line treatment for acute uncomplicated
cystitis
Dose:
Cystitis, acute uncomplicated, by mouth, ADULT, 3 g as a
single dose. Safety and effectiveness in the pediatric
population have not been established.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis; CDAD has been
observed >2 months post-antibiotic treatment;
Potentially significant interactions may exist, requiring dose
or frequency adjustment, additional monitoring, and/or
selection of alternative therapy.
Adverse Drug Reactions:
Common: None.
Less Common: Headache, pain, dizziness, skin rash,
diarrhea, nausea, abdominal pain, dyspepsia, vaginitis,
dysmenorrhea, back pain, weakness, rhinitis,
pharyngitis.
Rare: Abnormal stools, anaphylaxis, angioedema, anorexia,
aplastic anemia, cholestatic jaundice, constipation,
dermatological disease, drowsiness, dysuria, ear
disease, exacerbation of asthma, fatigue, fever,
flatulence, flu-like symptoms, hearing loss, hematuria,
hepatic necrosis, insomnia, lymphadenopathy,
menstrual disease, migraine, myalgia, nervousness,
optic neuritis, paresthesia, pruritus, toxic megacolon,
vomiting, xerostomia
Drug Interactions:
Monitory closely with:
Reduces therapeutic effect of the following drugs:
Sodium Picosulfate, Typhoid Vaccine
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
BCG Vaccine, Cholera Vaccine
Administration: Always mix with 3 to 4 oz (90 to 120 mL)
cool water before ingesting; do not administer in its dry
form or mix with hot water. May be administered without
regard to meals.
Pregnancy Category: C
ATC Code: J01XX01
ANTI-INFECTIVES FOR SYSTEMIC USE

SPECTINOMYCIN Staphylococcus aureus (MRSA) and complicated skin

Rx and soft tissue infections (cSSTI).
WHO anti-biotic category: ACCESS

Inj.: 2 g vial (IM) Contraindications: Concurrent or within 2 weeks of use of

Indications: Treatment of acute gonorrheal urethritis and
proctitis in the male and acute gonorrheal cervicitis and
proctitis in the female when due to susceptible strains of
Neisseria gonorrhoeae. Men and women with known
recent exposure to gonorrhea should be treated as those
known to have gonorrhea.
Contraindications: Hypersensitivity to spectinomycin or any
component of the formulation.
Dose:
Gonococcal infection, by IM injection, ADULT, 2 g as a single
dose. Max: 4 g, administer in two different injection sites;
CHILD, beyond newborn period and <45 kg: 40 mg/kg as
a single dose. Max: 2 g.
MAO inhibitors; Hypersensitivity to linezolid or any
component of the formulation
Dose:
Methicillin-resistant staphylococcal infections, by IV
injection or by mouth, ADULT, 600 mg every 12 hours.
Complicated skin and soft tissue infections, by IV injection
or by mouth, ADULT, 600 mg every 12 hours for 10-14
days; CHILD <12 years, 10 mg/kg every 8 hours for 10-
14 days; CHILD ≥12 years, 600 mg every 12 hours for
10-14 days.
Dose Adjustment:
Renal impairment:
Mild to severe impairment- no dosage adjustment
necessary.

Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
Ineffective in the treatment of syphilis and may mask or
delay symptoms of incubating syphilis.
Adverse Drug Reactions:
Common: Nausea, dizziness, fever and chills, insomnia,
urticaria, mild to moderate pain after IM injection,
alterations in kidney and liver function, decrease in Hb
and hematocrit.
Rare: Anaphylaxis or anaphylactoid reactions.
Drug Interactions:
Increases risk of adverse or toxic effects of Lithium
Administration: Given by deep intramuscular injection as a
single dose equivalent to 2 g of spectinomycin, although
a dose of 4 g may sometimes be required, divided
between two injection sites.
Pregnancy Category: B
ATC Code: J01XX04
J
End-stage renal disease on intermittent hemodialysis- no
dosage adjustment necessary; administer after
hemodialysis.
Hepatic impairment:
Mild to moderate impairment- no dosage adjustment
necessary.
Severe impairment- no dosage adjustments provided in the
manufacturer’s labeling.
Precautions:
May cause lactic acidosis, myelosuppression, peripheral
and optic neuropathy, serotonin syndrome, and
superinfection; use in caution in patients with carcinoid
syndrome, diabetes mellitus, hypertension,
hyperthyroidism, pheochromocytoma, and seizure
disorder.
Adverse Drug Reactions:
Common: Diarrhea.
Less Common: Headache, nausea, vomiting, dizziness,
rash, vaginal and oral moniliasis, taste alteration, fungal
infection, localized and generalized abdominal pain,
tongue discoloration, anemia, thrombocytopenia, loose
stools, eosinophilia, pruritus, and vertigo.
Rare: Lactic acidosis, myelosuppression, peripheral
neuropathy, optic nerve disorder, and serotonin
syndrome.

Drug Interactions:
Rx LINEZOLID Avoid concomitant use with:
WHO anti-biotic category: ACCESS
Both drugs increase serotonin levels:
Oral: 600 mg tablet/film-coated tablet Fluoxetine, Cocaine, Dextromethorphan, Ergotamine,
Inj: 2 mg/mL (600 mg/300 mL), solution for infusion (IV) Escitalopram, Isoniazid, Levodopa, Lithium, Morphine,
Selegiline, Sertraline, Tramadol
Linezolid inhibits bacterial protein synthesis by binding to
bacterial 23S ribosomal RNA of the 50S subunit. This Decreases effects of BCG vaccine
prevents the formation of a functional 70S initiation
complex that is essential for the bacterial translation Increases effects of the following:
process Linezolid is bacteriostatic against enterococci Caffeine, Dobutamine, Dopamine, Ephedrine,
and staphylococci and bactericidal against most strains Epinephrine, Formoterol, Norepinephrine,
of streptococci. Phenylephrine, Terbutaline

Indications: Treatment of serious life-threatening gram- Increases toxicity of the following:

positive infections including methicillin-resistant Butorphanol, Codeine, Nalbuphine, Oxycodone,
Tramadol, Fentanyl

249

Increases toxicity of Linezolid:
Carbamazepine
Administration: Oral: Administer with or without food.
IV: Administer intravenous infusion over 30-120 minutes.
Do not mix or infuse with other medications.
Pregnancy Category: C
ATC Code: J01XX08
ANTIFUNGALS FOR SYSTEMIC USE
POLYENE ANTIFUNGAL
Rx AMPHOTERICIN B
J
Inj.: Lipid Complex: 50 mg and 100 mg vial (as cholesteryl
complex, colloidal dispersion) (lipid complex) (IV
infusion)
Non-Lipid Complex: 50 mg vial lyophilized powder (as
deoxycholate) (non-lipid complex) (IV infusion)
Indications: Treatment of invasive fungal infection including
candidiasis, cryptococcus, and aspergillosis and
histoplasma infections. The lipid complex is only given in
patients who are refractory to or intolerant of
conventional amphotericin B (amphotericin B
deoxycholate) therapy.
Contraindications: Hypersensitivity to amphotericin or any
component of the formulation.
Dose:
For Non-lipid complex
CHILD, by IV, test dose: 0.1 mg/kg , not to exceed 1 mg,
administer over 20-60 min., initial dose, 0.25
mg/kg/dose daily, maintenance dose, increase by 0.25
mg/day increments as tolerated to 1-1.5 mg/kg/day
over 2-6 hrs, ADULT, by IV , test dose, 1 mg x 1 infused
over 20-30 min, loading dose, 0.25-0.5 mg/kg infused
over 2-6 hr , maintenance dose, 0.25-1 mg/kg daily OR
up to 1.5 mg/kg every other day (may increase gradually
by 0.25 mg-increments/day)
Lipid Complex
CHILD, by IV, 5 mg/kg daily, infuse IV at rate of 2.5 mg/hr,
ADULT, by IV, 5 mg/kg daily; infuse IV at rate of 2.5 mg/hr
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: This drug should be used for treatment of
patients with progressive and potentially life-
threatening fungal infections; it should not be used to
treat noninvasive forms of fungal disease such as oral
thrush, vaginal candidiasis, and esophageal
candidiasis in patients with normal neutrophil counts.
Monitor patients for anaphylaxis and infusion reactions.
250
ANTI-INFECTIVES FOR SYSTEMIC USE
Adverse Drug Reactions:
Chills, fever, multiple organ failure, nausea and vomiting,
hypotension, respiratory failure, dyspnea, sepsis,
diarrhea, headache, cardiac arrest, hypertension,
hypokalemia, kidney failure
Drug Interactions:
Increases risk of adverse or toxic effects of the following
drugs:
Antineoplastics, Nephrotoxic drugs
Corticosteroids, Foscarnet
Increases risk of adverse or toxic effects of Amphotericin B:
Aminoglycosides e.g Streptomycin; Cardiac glycosides
e.g. Digoxin; Colistimethate, Cyclosporine, Flucytosine
Reduces therapeutic effect of Antifungal Agents (Azole
Derivatives, Systemic)
Administration:
IV: For patients who experience non-anaphylactic infusion-
related reactions, premedicate 30-60 minutes prior to
drug administration with a NSAID ± diphenhydramine or
acetaminophen with diphenhydramine or
hydrocortisone. If the patient experiences rigors during
the infusion, meperidine may be administered.
Administer over 2-6 hours. Invert infusion container
several times prior to administration and every 2 hours
during infusion if it exceeds 2 hours. Do NOT use an in-
line filter during administration. Flush line with dextrose;
Normal saline may cause precipitate.
Pregnancy Category: B
ATC Code: J02AA01
TRIAZOLE DERIVATVES
Azoles are synthetic compounds that can be classified as
either imidazoles or triazoles according to the number of
nitrogen atoms. Azoles exhibit activity by reducing the
ergosterol synthesis through inhibition of fungal
cytochrome P450 enzymes.
Rx FLUCONAZOLE
Oral: 50 mg, 150 mg, and 200 mg capsule
Inj.: 2 mg/mL, 100 mL vial (IV infusion)
Indications: Treatment of candidiasis (esophageal,
oropharyngeal, peritoneal, urinary tract, vaginal);
Systemic candida infections (e.g., candidemia,
disseminated candidiasis, and pneumonia);
Cryptococcal meningitis; Antifungal prophylaxis in
allogeneic bone marrow transplant recipients.
Contraindications: Hypersensitivity to fluconazole or any
component of the formulation (crossreaction with other
azole antifungal agents may occur); Co-administration of
terfenadine in adult patients receiving multiple doses of
400mg or higher or with CYP3A4 substrates (e.g.,
ANTI-INFECTIVES FOR SYSTEMIC USE
astemizole, cisapride, erythromycin, pimozide, or
quinidine).
Dose:
Candiasis, prophylaxis, by mouth, by IV infusion, ADULT, 400
mg daily until recovery of neutropenia.
Central line-associated bloodstream infection (CLABSI),
Hyperalimentation, Candida spp., by mouth, by IV
infusion, CHILD, 12 mg/kg as loading dose, then 6
mg/kg as acceptable alternative if not critically ill and
unlikely to have fluconazole-resistant Candida spp; up to
2 weeks after clearance of candidemia.
Fungal meningitis, Cryptococcal meningitis, non-AIDS,
consolidation phase, by mouth, ADULT, 200 mg 4 times
a day for 10-12 weeks after CSF culture is negative;
Less severely ill, by mouth, by IV infusion, CHILD, 6-12
mg daily; ADULT, 400 mg; for 10-12 weeks after CSF
culture is negative.
Cryptococcal meningitis associated with HIV/AIDS,
induction phase, by IV infusion, CHILD, 6-12 mg/kg with
amphotericin B deoxycholate for at least 2 weeks; by
mouth, by IV infusion, ADULT, 800 mg with amphotericin
B deoxycholate for at least 2 weeks;
Consolidation phase, by IV infusion, CHILD, 6-12 mg/kg
for at least 8 weeks; by mouth, by IV infusion, ADULT,
400 mg for at least 8 weeks;
Suppression, by IV infusion, CHILD, 3 mg/kg for at least
1 year; by mouth, ADULT, 200 mg for at least 1 year.
Endophthalmitis, Candida sp., by mouth, ADULT, 800 mg
loading dose then 400-800 mg daily; CHILD, 12 mg/kg
loading dose then 6-12 mg/kg daily.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
NOTE: Renal function estimated using the Cockcroft-Gault
formula.
For multiple dosing in adults, administer loading dose of 50-
400 mg, then adjust daily doses as follows (dosage
reduction in children should parallel adult
recommendations):
CrCl >50 mL/minute: No dosage adjustment necessary
CrCl ≤50 mL/minute (no dialysis): Reduce dose by 50%
Endstage renal disease on intermittent hemodialysis: 100%
of daily dose (according to indication) after each dialysis
session; On nondialysis days, patient should receive a
reduced dose according to their CrCl; Alternate
recommendations: doses of 200-400 mg every 48-72
hours or 100-200 mg every 24 hours have been
recommended.
NOTE: Dosing dependent on the assumption of 3 times per
week, complete intermittent hemodialysis sessions.
Continuous renal replacement therapy: Drug clearance is
highly dependent on the method of renal replacement,
filter type, and flow rate. Appropriate dosing requires
close monitoring of pharmacologic response, signs of
adverse reactions due to drug accumulation, as well as
drug concentrations in relation to target trough (if
appropriate). The following are general
recommendations only (based on dialysate flow
ultrafiltration rates of 1 to 2 L/hour and minimal residual
renal function) and should not supersede clinical
judgment:
Continuous Veno-Venous Hemofiltration: Loading dose of
400-800 mg followed by 200-400 mg every 24 hours
Continuous venovenous hemodialysis / continuous veno-
venous hemodiafiltration: Loading dose of 400-800 mg
followed by 400-800 mg every 24 hours (Continuous
venovenous hemodialysis or continuous veno-venous
hemodiafiltration) or 800 mg every 24 hours (continuous
veno-venous hemodiafiltration).
NOTE: Higher maintenance doses of 400 mg every 24 hours
(Continuous veno-Venous Hemofiltration), 800 mg every
24 hours (continuous venovenous hemodialysis), and
500-600 mg every 12 hours (continuous veno-venous
hemodiafiltration) may be considered when treating
resistant organisms and/or when employing combined
ultrafiltration and dialysis flow rates of ≥2 L/hour for
continuous venovenous hemodialysis/ continuous veno-
venous hemodiafiltration.
J
Precautions:
WARNING: Serious hepatotoxicity has been reported in
patients with severe underlying disease such as AIDS
or malignancy.
Monitor patients for: arrhythmias; central nervous system
effects; hepatotoxicity, skin reaction. Use with caution in
patients with hepatic impairment. Formulation may
contain benzyl alcohol and derivatives.
Adverse Drug Reactions:
Common: gastrointestinal tract reactions such as
abdominal pain, diarrhea, flatulence, nausea and
vomiting, and taste disturbance.
Less Common: headache, dizziness, leukopenia,
thrombocytopenia, hyperlipidemia
Rare: anaphylaxis and angioedema.
Drug Interactions:
Increases serum concentration of Fluconazole:
Apixaban, Aripiprazole, Atorvastatin, Bosentan,
Budesonide, Busulfan, Calcium Channel Blocker e.g.
Amlodipine; Carbamazepine, Carvedilol, Cilostazol,
Colchicine, Cyclosporine, CYP2C9 Substrates, CYP3A4
Substrates, Domperidone, Doxorubicin, Dronabinol,
Fentanyl, Fosphenytoin, HMG-Coa Reductase Inhibitors
e.g. Simvastatin; Parecoxib, Phenytoin, Prednisone,
Propafenone, Proton Pump Inhibitors e.g. Omeprazole;
Rifamycin Derivatives; Ruxolitinib, Salmeterol, Sildenafil,
Sirolimus, Sulfonylureas e.g. Gliclazide; Tacrolimus,
Tipranavir, Tolvaptan, Vardenafil, Vitamin K Antagonists
e.g. Warfarin; Zidovudine, Zolpidem
Increases risk of adverse or toxic effects of Fluconazole:
Amitriptyline, Citalopram, Erythromycin, Qt-Prolonging
Agents, Methadone, Mifepristone, Oxycodone, Pimozide
Reduces therapeutic effect of Amphotericin B
Reduces therapeutic effect of Fluconazole:
Clopidogrel
Decreases serum concentration of Fluconazole:
Losartan
251
 ANTI-INFECTIVES FOR SYSTEMIC USE

Reduces absorption of Didanosine Use with caution in special population: Pediatric (the safety
and efficacy of itraconazole in children <18 years old
Decreases metabolism of Fluconazole: have not been established).
Buspirone, Quinidine, Solifenacin High potential for drug interactions: co-administration with
itraconazole can cause elevated plasma concentrations
Decreases active metabolite of Fluconazole: of certain drugs and can lead to QT prolongation and
Ifosfamide ventricular tachyarrhythmias, including torsades de
pointes.
Administration: Absorption of itraconazole capsules is reduced when gastric
For IV: Infuse over ~1-2 hours; Do not exceed 200 mg/hr; acidity is reduced (e.g., achlorhydria, acid suppressive
Do not add additional medication. therapy) administer with an acidic beverage (e.g. cola) in
For oral: May be administered without regard to meals. patients with reduced gastric acidity and separate
administration from acid suppressive therapy (refer to
Pregnancy Category: C (single 150 mg tablet use for vaginal drug interactions section). Monitor for response.
candidiasis) and D (all other indications) Appropriate use: Itraconazole should not be used for
voriconazole refractory aspergillosis because the same
ATC Code: J02AC01 antifungal and/or resistance mechanism(s) may be
shared by both agents.
Itraconazole capsule is not bioequivalent or
interchangeable to other oral itraconazole preparations.
J

Rx ITRACONAZOLE Due to variable bioavailability of oral preparations,

therapeutic drug monitoring is advisable.
Oral: 100 mg capsule
Adverse Drug Reactions:
Nausea and vomiting, edema, headache, rash, diarrhea,
Indications: Used in treatment of allergic bronchopulmonary
fatigue, fever, rhinitis, URTI, sinusitis, abdominal pain,
aspergillosis, second line treatment for cutaneous fungal
dizziness, hypertension, flatulence.
infections and prophylaxis of candidiasis
Drug Interactions:
Contraindications: Treatment of onychomycosis (or other
Avoid concurrent administration with astemizole, bepridil,
non-life-threatening indications) in patients with
colchicine, disopyramide, domperidone, dronedarone,
evidence of ventricular dysfunction, such as congestive
eplerenone, ergot derivatives, felodipine, fesoterodine,
heart failure (CHF) or a history of CHF; Treatment of
irinotecan, ivabradine, midazolam (oral), quinidine,
onychomycosis in women who are pregnant or intend to
ranolazine, simvastatin, solifenacin, ticagrelor,
become pregnant; Treatment of dermatomycosis (tinea
lercanidipine,
pedis, tinea cruris, tinea corporis, pityriasis versicolor) in
women who are pregnant or intend to become pregnant.
Increases serum concentration of Antiretroviral Agents
Dose:
Increases serum concentration of Itraconazole:
Prophylaxis of Candidiasis, by mouth, ADULT, 200 mg twice
Antiretroviral Agents, Aliskiren, Alprazolam
daily until recovery of neutropenia.
Aripiprazole, Benzodiazepines e.g. Diazepam; Bosentan,
Treatment of allergic bronchopulmonary aspergillosis, by
Budesonide, Calcium Channel Blocking Agents e.g.
mouth, ADULT, 200 mg twice daily for 16 weeks or
Amlodipine; Carbamazepine; Cardiac Glycoside e.g.
longer.
Digoxin; Cilostazol, Colchicine, Corticosteroids,
Tinea versicolor, by mouth, ADULT, 200 mg twice daily for 2-
Dabigatran etexilate, Disopyramide, Domperidone,
4 weeks, CHILD, by mouth, 5-10 mg/kg/day for 2-4
Doxorubicin, Dutasteride
weeks
Fexofenadine, Fluticasone, Fusidic Acid, Hydrocodone,
Medroxyprogesterone, Midazolam, Mifepristone,
Dose Adjustment:
Parecoxib, Propafenone, Repaglinide, Salmeterol,
Geriatric:
Saquinavir, Sildenafil, Tramadol, Vinblastine, Vitamin K
Refer to adult dosing.
Antagonists e.g. Warfarin; Zolpidem
Renal Impairment:
Increases risk of adverse or toxic effects of Calcium Channel
Use with caution in patients with renal impairment. Dosage
Blocking Agents e.g. Amlodipine
adjustment may be needed.
Increases risk of adverse or toxic effects of Itraconazole:
Precautions:
Antiarrhythmic Agents, Antilipidemic Agents,
WARNING: Congestive heart; High potential for drug Benzodiazepines e.g. Diazepam; Ergot Alkaloids e.g.
interactions. Ergotamine; Fentanyl, Pimozide, Phosphodiesterase
Type 5 Inhibitors e.g. Sildenafil; QT prolonging Agents,
Monitor patients for: Central Nervous System Depression; Oxycodone, Vincristine
Hearing Loss; Heart Failure; Hepatotoxicity;
Hypersensitivity; Neuropathy. Reduces therapeutic effect of Itraconazole:
Use with caution in patients with: Cystic Fibrosis; Amphotericin B
Dermatomycosis; Onychomycosis; Renal Impairment.
Increases serum concentration of the following drugs:

252
ANTI-INFECTIVES FOR SYSTEMIC USE
Antacids, Non-nucleoside Reverse Transcriptase
Inhibitors (NNRTIs), Carbamazepine, Isoniazid,
Nevirapine
Increases serum concentration of Itraconazole:
Meloxicam
Reduces absorption of Sucralfate
Decreases metabolism of Itraconazole:
Cyclosporine, Docetaxel
Administration:
Itraconazole capsules should be administered with a full
meal to ensure maximal absorption of the drug. Oral
doses >200 mg/day are given in 2 divided doses; Do not
administer with antacids. Take with food, it is best to
administer itraconazole after meals at the same time
each day.
The capsules should not be used for the treatment of
oropharyngeal or esophageal candidiasis; Efficacy has
not been established and this formulation may be less
effective than the oral solution for these infections.
Pregnancy Category: C
ATC Code: J02AC02
Rx VORICONAZOLE
Oral: 200 mg film-coated tablet
Inj.: 200 mg lyophilized powder for solution, 30 mL vial (IV
infusion)
Indications: Treatment of candida endophthalmitis, reserve
drug for the treatment of severe fungal infections;
prophylaxis for aspergillus in patients undergoing
chemotherapy for AML/MDS with neutropenia and
allogeneic HSCT recipients
Contraindications: Hypersensitivity. Concomitant use of
CYP3A4 substrates, terfenadine, astemizole, cisapride,
pimozide or quinidine; sirolimus, rifabutin, rifampicin,
carbamazepine, long-acting barbiturates, efavirenz,
ritonavir, ergot alkaloids
Dose:
Anti-aspergillus prophylaxis, by mouth, by IV infusion,
ADULT, 200 mg twice daily.
Endophthalmitis, Candida sp., by IV infusion, ADULT, 400
mg twice a day for 2 doses loading dose then 300 mg, by
mouth or IV infusion, twice a day; CHILD, 12 mg/kg twice
a day for 2 doses loading dose then 4 mg/kg, by mouth
or IV infusion, twice a day.
Dose Adjustment:
Geriatric:
Refer to adult dosing
Precautions:
Hypersensitivity to other azoles. Infusion-related reactions;
patients with potentially proarrhythmic conditions e.g.,
congenital or acquired QT prolongation, cardiomyopathy,
sinus bradycardia, existing symptomatic arrhythmias,
concomitant use w/ drugs known to prolong QT interval;
Monitor & correct electrolyte imbalances (hypokalemia,
hypomagnesemia and hypocalcemia) prior to and during
therapy. Monitor for hepatic toxicity and lab evaluation of
hepatic function (AST/ALT) at least weekly for the 1st
month of therapy;
Acute renal failure & visual adverse events in severely ill
patients with underlying conditions and/or concomitant
medications;
Adults and children with risk factors for acute pancreatitis.
Rare exfoliative cutaneous reaction, photosensitivity;
squamous cell carcinoma of the skin & melanoma,
periostitis on long-term therapy;
Pregnancy and lactation.
Adverse Drug Reactions:
Pseudomembranous colitis, sinusitis, bone marrow failure,
agranulocytosis, pancytopenia, thrombocytopenia,
leukopenia, anaemia, lymphadenopathy, eosinophilia,
J
anaphylactoid reaction, hypersensitivity, adrenal
insufficiency, hypothyroidism, hyperthyroidism,
hypoglycemia, hypokalemia, hyponatremia, peripheral
edema, depression, hallucination, anxiety, insomnia,
agitation, confusional state, hepatic encephalopathy,
brain edema, encephalopathy, syncope, extrapyramidal
disorder, tremor, hypertonia, Guillain-Barré syndrome,
peripheral neuropathy, ataxia, paresthesia,
hypoesthesia, nystagmus, dysgeusia, somnolence,
dizziness, headache, optic atrophy and nerve disorder,
papilloedema, retinal hemorrhage, oculogyric crisis,
corneal opacity, visual impairment, diplopia, scleritis,
blepharitis, hypoacusis, vertigo, tinnitus, torsades de
pointes, thrombophlebitis, hypotension, phlebitis,
lymphangitis, acute respiratory distress syndrome,
pulmonary edema, peritonitis, pancreatitis, swollen
tongue, diarrhea, vomiting, duodenitis, cheilitis,
gastroenteritis, dyspepsia, abdominal pain, glossitis,
constipation, gingivitis, nausea, hepatic failure, jaundice,
jaundice cholestatic, hepatitis, hepatomegaly,
cholecystitis, cholelithiasis, toxic epidermal necrolysis,
SJS, angioedema, pseudoporphyria, erythema
multiforme, dermatitis exfoliative, psoriasis, cutaneous
lupus erythematosus, drug eruption, alopecia,
photosensitivity reaction, purpura, rash maculopapular,
urticaria, rash, eczema, pruritus, back pain, arthritis,
renal failure acute, renal tubular necrosis, proteinuria,
nephritis, hematuria, chest pain, face edema, infusion
site reaction, flu like illness, asthenia, chills
Drug Interactions:
Decreases excretion of the following drugs:
Ergot alkaloids, Disopyramide
Simvastatin, Pimozide, Ranozaline, Sirolimus
Decreases excretion of Voriconazole:
Efavirenz, Rifabutin, Rifampin, Rionavir, Carbamazepine,
Phenobarbital
Administration: Should be taken on an empty stomach: Take
at least 1 hour before or after meals.
Pregnancy Category: D
ATC Code: J02AC03
253
 ANTI-INFECTIVES FOR SYSTEMIC USE

FLUCYTOSINE Drug Interactions:

Rx Increases risk of adverse or toxic effects of the following
(5-FLUOROCYTOSINE)
drugs:
Amphotericin B, Ganciclovir, Norfloxacin, Valganciclovir,
Oral: 250 mg tablet
Zidovudine
Indications: Adjunctive treatment of systemic fungal
Increases risk of adverse or toxic effects of Flucytosine:
infections (e.g., septicemia, endocarditis, urinary tract
Clozapine, Dipyrone, Hydroxyurea, Fluconazole,
infection, meningitis, or pulmonary) caused by
Itraconazole
susceptible strains of Candida or Cryptococcus.
Reduces therapeutic effect of Flucytosine:
Dose:
BCG Vaccine
Endocarditis, by mouth, CHILD, 100 mg/kg/day in 3 or 4
divided doses (with amphotericin B) for >4-6 weeks after
Reduces therapeutic effect of Cytarabine
valve replacement.
Administration:
Dose Adjustment:
Take orally; Administer around-the-clock to promote less
Geriatric:
variation in peak and trough serum levels.
Refer to adult dosing.
Pregnancy Category: C
Renal Impairment:
J

Adults (based upon dosing of 25 mg/kg every 6 hours):

ATC Code: J02AX01
CrCl >40 mL/minute: No dosage adjustment
recommended; CrCl 20-40 mL/minute: 50% of standard
dose every 6 hours; CrCl 10-20 mL/minute: 25% of
standard dose every 6 hours; End stage renal disease on Rx MICAFUNGIN
intermittent hemodialysis: 25-50 mg/kg every 48-72
hours, administer dose after hemodialysis.
Adults and Adolescents (HIV positive patients) (based upon Inj.: 50 mg lyophilized powder for infusion (IV)
dosing of 25 mg/kg every 6 hours): CrCl >40 mL/minute:
No dosage adjustment recommended; ClCr 20-40 Indications: For resistant candida and disseminated
mL/minute: 25 mg/kg every 12 hours; CrCl 10- ≤20 candidiasis
mL/minute: 25 mg/kg every 24 hours; CrCl <10
mL/minute: 25 mg/kg every 48 hours; End stage renal Contraindications: Hypersensitivity to micafungin, other
disease on intermittent hemodialysis: 25-50 mg/kg echincandins, or any component of the formulation.
every 48-72 hours, administer dose after hemodialysis.
Infants, Children, and non-HIV positive Adolescents (based Dose:
upon dosing of 100-150 mg/kg/day divided every 6 Anticandidal prophylaxis, by IV infusion, ADULT, 150 mg
hours): until recovery or neutropenia.

NOTE: Flucytosine should be avoided in children with severe Dose Adjustment:

renal impairment.
CrCl 30-50 mL/minute: 25-37.5 mg/kg every 8 hours;
CrCl 10-29 mL/minute: 25-37.5 mg/kg every 12 hours;
CrCl <10 mL/minute: 25-37.5 mg/kg every 24 hours;
Hemodialysis: 25-37.5 mg/kg every 24 hours;
Peritoneal dialysis: 25 to 37.5 mg/kg every 24 hours;
Continuous renal replement therapy: 25-37.5 mg/kg every
8 hours (monitor serum concentrations).
Precautions:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: Cases of hypersensitivity reactions including
anaphylactoid reactions and anaphylaxis with shock
have been reported in patients who receive micafungin.
Use with caution to avoid anaphylactic reactions, hemolytic
anemia, hepatic failure and renal impairment.

WARNING: Use with extreme caution in patients with renal Adverse Drug Reactions:
impairment. Close monitoring of hematologic, renal Common: Fever, headache, hypokalemia,
and hepatic status of all patients is essential. hypomagnesemia, diarrhea, nausea, vomiting, mucosal
inflammation, constipation.
Use with caution in patients with: Bone Marrow Depression; Less Common: Hypotension, tachycardia, hypertension,
Hematologic Disease; Patients who have been treated peripheral edema, edema, bradycardia, atrial fibrillation,
with radiation or drugs that suppress the bone marrow; insomnia, anxiety.
Hepatic Impairment; Renal Dysfunction.
Drug Interactions: No known significant interactions
Adverse Drug Reactions:
Myocardial toxicity, chest pain, dyspnea, rash, pruritus, Administration:
urticaria, nausea, jaundice, renal failure, azotemia, For IV use only; infuse over 1 hour. Flush line with NS prior
crystalluria, anemia, leukopenia, ataxia, confusion. to administration.

254
ANTI-INFECTIVES FOR SYSTEMIC USE
Pregnancy Category: C
ATC Code: J02AX05
Rx NYSTATIN
Oral: 100,000 units/mL suspension, 30 mL
Indication: Treatment of oral candidiasis
Contraindications: Hypersensitivity to nystatin or any
component of the formulation.
Dose:
Oral candidiasis, Candida albicans, by mouth, ADULT, oral
suspension 100,000 U/mL, 4mL 4 times daily for 7-14
days.
Precautions:
Not for use in systemic mycoses. Discontinue therapy if
irritation or sensitization observed during use.
Adverse Drug Reactions:
Localized sensitization; hypersensitivity reactions.
Drug Interactions:
Enhances erratic release of Nystatin:
Progesterone Intravaginal Gel
Administration:
Shake well before use. Swish about the mouth and retain in
the mouth for as long as possible (several minutes)
before swallowing. For neonates and infants, paint
nystatin suspension into recesses of the mouth.
Pregnancy Category: A
ATC Code: G01AA01
ANTIMYCOBACTERIALS
Antimycobacterial drugs are used in the treatment of
diseases caused by members of the Mycobacterium
genus, including tuberculosis (TB) and leprosy.
Combination chemotherapy is essential to kill
heterogeneous populations of bacterial cells located in
different conditions within the host, and to prevent drug
resistance.
DRUGS FOR TREATMENT
OF TUBERCULOSIS
DRUGS FOR TUBERCULOSIS
Rx ETHAMBUTOL
J
Oral: 200 mg and 400 mg tablet
100 mg tablet (pediatric)
Indication: Treatment of tuberculosis in combination with
isoniazid, rifampicin and pyrazinamide
Contraindications: Hypersensitivity to ethambutol or any
component of the formulation; optic neuritis; children <6
years
Dose:
NOTE: Doses may need adjustment if significant weight gain
occurs during treatment. Use doses below for the first 2
months of the 6-month multi-drug regimen.
Tuberculosis, by mouth, ADULT, 15 mg/kg (range: 15-20
mg/kg) daily, not to exceed 1.2 g daily; CHILD, 20 mg/kg
(range: 15-25 mg/kg) daily, not to exceed 1.2 g daily.
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance <30 mL/minute
or for adult patients receiving hemodialysis: 15-25
mg/kg dose three times per week (not daily).
Precautions:
Ocular examination is recommended before, and during,
treatment; warn patients to report visual changes;
elderly; young children; further deterioration in vision
may occur where there are visual defects (e.g. diabetic
retinopathy, cataract); renal impairment (monitor plasma
ethambutol concentration); gout (acute attack may
occur).
Pregnancy (not known to be harmful); breastfeeding
(amount too small to be harmful).
NOTE: Patients should report visual disturbances
immediately and discontinue treatment; children who
are incapable of reporting symptomatic visual changes
accurately should be given alternative therapy, as
should, if possible, any patients who cannot understand
warnings about visual adverse effects.
Adverse Drug Reactions:
Common: Retrobulbar neuritis (resulting in loss of visual
acuity and red-green color blindness).
255

Less Common: Abdominal pain, anorexia, confusion,
disorientation, hallucinations, headache, malaise,
nausea, vomiting.
Rare: Acute gout, hypersensitivity reaction, anaphylaxis,
hyperuricemia, neutropenia, peripheral neuritis, renal
failure, thrombocytopenia.
Drug Interactions:
Avoid concomitant use with:
Reduces absorption of Ethambutol:
Aluminum salts
Administration:
Tablets should be taken WITH food.
Pregnancy Category: C
ATC Code: J04AK02
J
Rx ISONIAZID
Oral: 300 mg and 400 mg tablet
200 mg/ 5 mL syrup, 120 mL
Indications: Treatment of tuberculosis in combination with
rifampicin, pyrazinamide and ethambutol; primary
regimen for latent tuberculosis.
Contraindications: Known hypersensitivity to isoniazid or
any component of the formulation; drug-induced hepatic
disease.
Dose:
Tuberculosis, treatment, by mouth, ADULT, 5 mg/kg (range:
4-6 mg/kg) daily, not to exceed 400 mg daily, not to
exceed 300 mg daily.
NOTE: Patients at risks of developing peripheral neuropathy
as a result of malnutrition, alcoholism or diabetes
mellitus should additionally receive pyridoxine, 10 mg
daily. Pregnant and patients with renal failure should
also receive pyridoxine while on isoniazid therapy.
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance <30 mL/min or
for adult patients receiving hemodialysis: 15-25 mg/kg
per dose three times per week.
Precautions:
WARNING: Severe and sometimes fatal hepatitis may be
associated with isoniazid therapy which is age-related.
Patients or their caregivers should be told how to
recognize signs of liver disorder, and advised to
discontinue treatment and seek immediate medical
attention if symptoms such as nausea, vomiting,
malaise or jaundice develop.
Very high doses can induce CNS adverse effects (e.g.,
seizures, ataxia, stupor, psychosis).
Malnutrition;
Chronic alcohol dependence;
Diabetes mellitus and HIV infection (risk of peripheral
neuritis);
256
ANTI-INFECTIVES FOR SYSTEMIC USE
Elderly patients;
Hepatic impairment (increased risk of hepatotoxicity,
monitor liver function regularly, and frequently in the first
2 months); Patients with liver disorder
Renal impairment (risk of ototoxicity and peripheral
neuropathy);
Epilepsy (isoniazid may cause seizures; ensure adequate
control);
Slow acetylator status (increased risk of adverse effects);
History of psychosis;
Porphyria;
Pregnancy (not known to be harmful);
Breasfeeding (monitor infant for possible toxicity;
theoretical risk of convulsions and neuropathy)
Adverse Drug Reactions:
Common: Acne, fever, GI disorders (e.g., nausea, vomiting,
diarrhea), hepatitis, rash, reduced alertness, skin
eruptions, tiredness.
Less Common: Atrophy, dryness of mouth, optic neuritis,
memory impairment, peripheral neuritis, seizures, toxic
encephalopathy, toxic psychosis.
Rare: Agranulocytosis, amenorrhea, aplastic anemia,
arthritic symptoms, convulsions, difficulty with
micturition, gynecomastia, hemolytic anemia,
hyperglycemia, hypersensitivity reactions, lupus-like
syndrome, pancreatitis, pellagra, pure red cell aplasia,
thrombocytopenia, urinary retention.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Carbamazepine
Reduces therapeutic effect of the following drugs:
Drug increasing blood glucose concentration (e.g.,
glucocorticoids, antipsychotics, calcineurin inhibitors,
and high-dose thiazide diuretics)
Oral contraceptives
Increases risk of adverse or toxic effects of Paracetamol
(more studies needed)
Increases risk of adverse or toxic effects of Isoniazid:
Rifampicin
Avoid concomitant use with:
Reduces absorption of Isoniazid:
Antacids (e.g., aluminum or magnesium hydroxide)
Decreases metabolism of Diazepam
Increases metabolism of Ketoconazole
Administration:
Absorbed best if taken on an empty stomach (1 hour before,
or 2 hours after a meal).
Pregnancy Category: C
ATC Code: J04AC01
ANTI-INFECTIVES FOR SYSTEMIC USE
Rx PYRAZINAMIDE
Oral: 500 mg tablet
250 mg/5 mL and 500 mg/5 mL suspension, 12O mL
Indication: Treatment of tuberculosis in combination with
isoniazid, rifampicin and ethambutol.
Contraindications: Severe hepatic impairment; porphyria;
acute gout.
Dose:
Tuberculosis, by mouth, ADULT, 25 mg/kg (range: 20-30
mg/kg) daily, not to exceed 2 g daily; CHILD, 30 mg/kg
(range: 20-40 mg/kg) daily, not to exceed 2 g daily.
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance <30 mL/minute
or for adult patients receiving hemodialysis: 25-35
mg/kg per dose three times per week. Monitor for gout.
Precautions:
Liver Disorders (Patients or their caregivers should be told
how to recognize signs of liver disorder, and advised to
discontinue treatment and seek immediate medical
attention if symptoms, such as persistent nausea,
vomiting, malaise or jaundice, develop.);
Acute gout;
Hepatic impairment (monitor hepatic function);
Renal impairment;
Diabetes mellitus (monitor blood glucose; may change
suddenly);
Pregnancy (use it only if potential benefits outweigh risks);
Breastfeeding (amount too small to be harmful).
Adverse Drug Reactions:
Common: Hyperuricemia, nausea, polyarthralgia, vomiting.
Less Common: Allergic reactions, anorexia, diarrhea, fever,
flushing, hepatotoxicity (including hepatomegaly,
jaundice, liver tenderness, liver failure, malaise, and
splenomegaly), itch, rash, urticaria
Rare: Acute gout, acute porphyric crisis, dysuria, pellagra,
photosensitivity, sideroblastic anemia,
thrombocytopenia.
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Anti-gout drugs e.g.,
allopurinol, colchicine
Increases risk of adverse or toxic effects of Rifampicin
(severe, or even fatal, liver injury has been reported in
patients using these two drugs as a 2-month treatment
regimen for latent TB infection).
Administration:
Should be taken with food.
Pregnancy Category: C
ATC Code: J04AK01
Rx RIFAMPICIN
Oral: 300 mg, 450 mg, and 600 mg tablet / capsule
200 mg/5 mL suspension, 120 mL
Indications: Treatment of tuberculosis in combination with
isoniazid, pyrazinamide and ethambutol, treatment of
leprosy using combination therapy
Contraindications: Hypersensitivity to rifamycins, or any
component of the formulation; jaundice.
Dose:
Tuberculosis, by mouth, ADULT, 10 mg/kg (range: 8-12
mg/kg) daily, not to exceed 600 mg daily; CHILD, 15
mg/kg (range: 10-20 mg/kg) daily; not to exceed 600 mg
daily.
Leprosy, by mouth, ADULT, 600 mg
J
Dose Adjustment:
Hepatic Impairment:
Dose reduction is warranted (maximum, 8 mg/kg/day).
Precautions:
Alcohol dependency, the elderly, and in prolonged therapy;
daily alcohol intake (may increase the risk of drug-
induced hepatotoxicity); renal impairment; hepatic
impairment (impaired elimination; monitor liver
function); porphyria; it discolors soft lenses.
IMPORTANT: Advise patient on hormonal contraceptives to
use additional means (effectiveness is reduced);
alternative family planning advice shall be offered.
LIVER DISORDERS: Monitor liver function and blood count
in liver disorder. Patients or their caregivers should be
told how to recognize signs of liver disorders and advised
to discontinue treatment and seek immediate medical
attention if symptoms such as persistent nausea,
vomiting, malaise, or jaundice develop.
Pregnancy (first trimester: very high doses are teratogenic
in animal studies; third trimester: risk of neonatal
bleeding may be increased); and breastfeeding (amount
too small to be harmful; may cause loose bowel
movement in babies).
NOTE: Resumption of rifampicin treatment after a long
interval may cause serious immunological reactions,
resulting in renal impairment, hemolysis, or
thrombocytopenia – discontinue permanently if serious
adverse effects occur.
Adverse Drug Reactions:
Common: Anorexia, cramps, diarrhea, epigastric distress,
flatulence, increased hepatic enzymes, nausea, orange-
red coloration of body fluids (urine, tears, saliva and
sputum), pancreatitis, rash, staining of soft contact
lenses, vomiting.
Less Common: Ataxia, behavioral changes, dizziness,
edema, fatigue, flu-like syndrome (characterized by
fever, chills, myalgia), flushing, headache, heartburn,
menstrual disturbances, numbness.
Rare: Acute renal failure, cerebral hemorrhage, C. difficile-
associated disease, collapse, exfoliative dermatitis,
hemolytic anemia, hepatitis, jaundice, leukopenia,
myopathy, pemphigoid reactions, psychosis, respiratory
symptoms, shock, thrombocytopenic purpura, toxic
epidermal necrolysis.
257

Drug Interactions:
NOTE: Enzyme induction: accelerates the metabolism of
various substrates, thus possibly decreasing their
effects.
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Azole antifungal e.g. ketoconazole
Beta blockers e.g., metoprolol, propranolol
Cotrimoxazole, Digoxin, Doxycycline, Theophylline
Increases metabolism of the following drugs:
Corticosteroids e.g., hydrocortisone, prednisone,
prednisolone; Thyroid hormones e.g. Thyroxine
Avoid concomitant use with:
Reduces absorption of Rifampicin:
Antacids (e.g., aluminum and magnesium hydroxide)
Reduces therapeutic effect of Oral Contraceptives
J
Increases metabolism of Praziquantel
Administration:
Take dose at least 30 minutes before a meal (absorption is
reduced when taken with food).
Pregnancy Category: C
ATC Code: J04AB02
Rx STREPTOMYCIN
Inj.: 1 g vial (as sulfate) (IM)
Indication: Treatment of tuberculosis, as an alternative to
ethambutol in combination with isoniazid, rifampicin and
pyrazinamide.
Contraindications: Hypersensitivity to streptomycin or any
component of the formulation; hearing disorders (e.g.,
vestibular disturbances and impaired hearing);
myasthenia gravis
Dose:
Tuberculosis, by deep IM injection, ADULT, 15 mg/kg
(range: 12-18 mg/kg) daily, not to exceed 1 g daily
(patients over 60 years, or those weighing <50 kg may
not tolerate doses above 500-750 mg daily); CHILD, 30
mg /kg (range: 20-40 mg/kg) daily, not to exceed 1 g
daily.
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance <30 mL/minute
or for adult patients receiving hemodialysis: 12-15
mg/kg per dose two or three times per week.
If possible, streptomycin should be avoided in patients with
renal failure.
258
ANTI-INFECTIVES FOR SYSTEMIC USE
Precautions:
WARNING: May cause nephrotoxicity and neurotoxicity.
Avoid concurrent use of nephrotoxic/neurotoxic drugs;
may cause neuromuscular blockade and respiratory
paralysis, especially when given after anesthesia or
muscle relaxants.
Children (painful injection, avoid use if possible);
Renal impairment (monitor plasma concentration);
Infants, and the elderly (adjust dose and monitor renal,
auditory, and vestibular function and plasma
streptomycin concentrations);
Pregnancy (second and third trimester: auditory and
vestibular damage in the fetus; avoid unless essential; if
given, serum-streptomycin concentration monitoring is
essential);
Breastfeeding (present in milk; continue breastfeeding and
monitor infant for thrush and diarrhea).
Adverse Drug Reactions:
Common: Fever, hearing loss, hypersensitivity reactions,
nausea, rash, sterile abscess and pain at injection site,
vertigo, vomiting.
Less Common: Albuminuria, high frequency range hearing
impairment, numbness around mouth, tinnitus, urinary
casts, vestibular damage and toxicity.
Rare: Agranulocytosis, anaphylactic shock, aplastic anemia,
C. difficile-associated disease, exfoliative dermatitis,
hemolytic anemia, hypomagnesemia, nephrotoxicity,
paresthesia, of the mouth, tubular necrosis,
thrombocytopenia.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Ototoxic and nephrotoxic drugs e.g., other
aminoglycoside antibiotics, furosemide, cephalosporins
and vancomycin
Enhances therapeutic effect of Streptomycin:
Magnesium sulfate
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Streptomycin:
H1 receptor blocker e.g. Diphenhyadramine
Administration:
Solutions retain their potency for 48 hours after
reconstitution at room temperature and for up to 14 days
when refrigerated.
Pregnancy Category: D
ATC Code: A07AA04; J01GA01
ANTI-INFECTIVES FOR SYSTEMIC USE

COMBINATIONS OF DRUGS FOR ATC Code: J04AM07

TREATMENT OF TUBERCULOSIS

ISONIAZID + RIFAMPICIN +
Rx ISONIAZID + RIFAMPICIN Rx
PYRAZINAMIDE

Oral: 75 mg isoniazid + 150 mg rifampicin tablet Oral: 50 mg isoniazid + 75 mg rifampicin + 150 mg

50 mg isoniazid + 75 mg rifampicin dispersible fixed- pyrazinamide dispersible fixed-dose
dose combination tablet (pediatric) combination tablets (pediatric)

Indication: Treatment of tuberculosis Indication: Treatment of tuberculosis

Contraindications: Combined preparations may not be
suitable for use in young children.
Dose:
Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for
Tuberculosis.
Contraindications: Combined preparations may not be
suitable for use in children; see under Single Dose
Formulation: Ethambutol, Isoniazid, Pyrazinamide and
Rifampicin.
Dose:
Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for

J
Dose Adjustments, Precautions, Adverse Drug Reactions, Tuberculosis.
and Drug Interactions:
Dose Adjustment, Precautions, Adverse Drug Reactions and
See under Single Dose Formulation: Isoniazid and Drug Interactions:
Rifampicin for other information.
See under Single Dose Formulation: Isoniazid, Rifampicin
Administration: and Ethambutol.
Take on an empty stomach with full glass of water.
Administration:
Pregnancy Category: C Take on an empty stomach with full glass of water.

ATC Code: J04AM02 Pregnancy Category: C

ATC Code: J04AM05

ISONIAZID + RIFAMPICIN +
Rx
ETHAMBUTOL
ISONIAZID + RIFAMPICIN +
Oral: 75 mg isoniazid + 150 mg rifampicin + 275 mg Rx PYRAZINAMIDE +
ethambutol tablet ETHAMBUTOL
Indication: Treatment of tuberculosis Oral: 75 mg isoniazid + 150 mg rifampicin + 400 mg
pyrazinamide + 275 mg ethambutol tablet
Contraindications:
Combined preparations may not be suitable for use in young Indications: Treatment of tuberculosis
children see under Single Dose Formulation: Isoniazid,
Rifampicin and Ethambutol. Contraindications: Combined preparations may not be
suitable for use in young children.
Dose:
Tuberculosis, by mouth, ADULT, refer to the section on Dose:
Recommended Treatment Regimen for Tuberculosis. Tuberculosis, by mouth, ADULT, refer to the Tables in the
section on Recommended Treatment Regimen for
Dose Adjustments, Precautions, Adverse Drug Reactions Tuberculosis.
and Drug Interactions:
Dose Adjustment:
See under Single Dose Formulation: Isoniazid, Rifampicin Renal and Hepatic Impairment:
and Ethambutol. For severe impairment, dose reduction may be warranted.

Drug Interactions: Precautions, Adverse Drug Reactions, and Drug

Refer to individual monographs of components. Interactions:

Administration: See under Ethambutol, Isoniazid, Pyrazinamide and

Take on an empty stomach with full glass of water. Rifampicin.
For more information, refer to individual monographs of
Pregnancy Category: C components.

259

Administration:
Should be taken on an empty stomach; take 1 hour before,
or 2 hours after meals.
Pregnancy Category: C
ATC Code: J04AM06
DRUGS FOR MULTIDRUG RESISTANT
TUBERCULOSIS (MDRTB)
Rx AMIKACIN
WHO anti-biotic category: ACCESS
Inj.: 50 mg/mL, 100 mg/mL, 125 mg/mL, and 250
mg/mL (as sulfate), 2 mL ampule / vial (IM, IV)
100 mg, 250 mg, 500 mg and 1 g vial (as sulfate) (IM,
IV)
J
Indication: Second line for the treatment of multi-drug
resistant tuberculosis in conjunction with at least
three other anti-tuberculosis agent.
Contraindications: Cross-sensitivity may exist with other
aminoglycosides.
Dose:
NOTE: Individualization is critical because of the low
therapeutic index.
Tuberculosis, by IM injection or IV infusion, ADULT and
CHILD, 5-7.5 mg/kg/dose every 8 hours.
See Amikacin under Aminoglycoside Antibacterials in
Chapter 07: Anti-infectives for other information.
Pregnancy Category: D
ATC Code: J01GB06
Rx CAPREOMYCIN
Inj.: 1 g powder for injection (IV, IM)
Indication: Second line treatment of multi-drug resistant
tuberculosis in conjunction with at least one three other
anti-tuberculosis agent
Contraindications: Hypersensitivity to capreomycin or any
component of the formulation.
Dose:
Tuberculosis, by deep IM injection or IV infusion, ADULT, 1
g/day (max: 20 mg/kg/day) for 60-120 days, followed by
1 g 2-3 times/week or 15 mg/kg/day (max: 1 g/dose) for
2-4 months, followed by 15 mg/kg (max: 1 g/dose) 2-3
times/week; CHILD <15 years and ≤40kg: 15-30
mg/kg/day (max: 1 g/day) for 2-4 months, followed by
15-30 mg/kg (max: 1 g/day) twice weekly; CHILD ≥15
years or >40kg: 15 mg/kg/day (max: 1 g/dose) for 2-4
months followed by 15 mg/kg (max: 1 g/dose) 2-3
times/week.
260
ANTI-INFECTIVES FOR SYSTEMIC USE
Dose Adjustment:
Geriatric:
Refer to adult dosing. Use with caution due to the increased
potential for pre-existing renal dysfunction or impaired
hearing.
Renal Impairment:
Adults (max: 1g/dose)
CrCl 110 mL/min: 13.9 mg/kg every 24 hours.
CrCl 100 mL/min: 12.7 mg/kg every 24 hours.
CrCl 80 mL/min: 10.4 mg/kg every 24 hours.
CrCl 60 mL/min: 8.2 mg/kg every 24 hours.
CrCl 50mL/min: 7mg/kg every 24 hours or 14 mg/kg every
48 hours.
CrCl 30 mL/min: 5.9 mg/kg every 24 hours or 11.7 mg/kg
every 48 hours.
CrCl 20 mL/min: 3.6 mg/kg every 24 hours or 7.2 mg/kg
every 48 hours or 10.7 mg/kg every 72 hours.
CrCl 10 mL/min:2.4mg/kg every 24 hours or 4.9 mg/kg
every 48 hours or 7.3 mg/kg every 72 hours.
CrCl 0mL/min: 1.3 mg/kg every 24 hours or 2.6 mg/kg
every 48 hours or 3.9 mg/kg every 72 hours.
Precautions:
WARNING: Use caution in patients with pre-existing
auditory impairment due to risk of additional eighth
nerve impairment and should be weighed against the
benefits. Use caution in patients with renal
impairment.
Other parenteral anti-tuberculosis agents (i.e. streptomycin)
also have similar and sometimes irreversible toxic
effects, particularly on the eighth cranial nerve and renal
function, simultaneous administration of these agents
with capreomycin is not recommended;
Safety has not been established in children and pregnant
women.
Adverse Drug Reactions:
Common: Ototoxicity and nephrotoxicity
Less Common: Eosinophilia
Rare: Acute tubular necrosis, Bartter syndrome,
hypersentivity, hypocalcemia, hypokalemia,
hypomagesemia, injection site reactions, leukocytosis,
leukopenia, renal injury, thrombocytopenia, tinnitus,
toxic nephritis, urinary sediment abnormal, vertigo.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Aminoglycosides e.g. Streptomycin; Neuromuscular-
blocking agents e.g. Pancuronium; Polymyxin B
Enhances toxic effect of Capreomycin:
Non-tuberculosis drugs (i.e. aminoglycosides) (ototoxic
or nephrotoxic effect)
Reduces therapeutic effect of BCG Vaccine
Administration:
Administer by deep IM injection into large muscle mass.
Infuse IV over 60 minutes.
Pregnancy Category: C
ANTI-INFECTIVES FOR SYSTEMIC USE

ATC Code: J04AB30

Rx KANAMYCIN

Inj.: 1 g vial (as sulfate) (IM)

Rx CYCLOSERINE
Indication: Second line treatment for Mycobacterium
Oral: 250 mg capsule tuberculosis in combination with atleast 3 other agents.

Indication: Secondline treatment for multidrug resistant Contraindications: Hypersensitivity to kanamycin, any
tuberculosis in combination with at least three other component of the formulation or other aminoglycosides;
agents. pregnancy.

Contraindications: Hypersensitivity to cycloserine or any Dose:

component of the formulation.
Dose:
NOTE: Some of the neurotoxic effects may be relieved or
prevented by the concomitant administration of
pyridoxine.
Tuberculosis, by mouth, ADULT, initial 250 mg every 12
NOTE: Dosing should be based on ideal body weight.
Tuberculosis, by IM injection or IV infusion, ADULT and
CHILD, 5-7.5 mg/kg/dose in divided doses every 8-12
hours (<15 mg/kg/day).
Dose Adjustment:
Geriatric:

J
hours for 14 days, then give 500 mg to 1 g/day in 2 Tuberculosis, by deep IM injection or IV infusion, initial dose
divided doses for 18-24 months (max daily dose: 1 g). should be 5-7.5 mg/kg based on ideal body weight;
CHILD, 10-20 mg/kg/day in 2 divided doses up to 1000 maintenance dose and interval should be adjusted for
mg/day for 18-24 months. estimated renal function; dosing interval in most older
patients is every 12-24 hours.
Dose Adjustment:
Geriatric: Renal Impairment:
Refer to adult dosing. CrCl 50-80 mL/minute: Administer 60% to 90% of dose or
administer every 8-12 hours.
Renal Impairment: CrCl 10-50 mL/minute: Administer 30% to 70% of dose or
CrCl 10-50mL/min: Administer every 12-24 hours. administer every 12 hours.
CrCl <10mL/min: Administer every 24 hours. CrCl <10 mL/minute: Administer 20% to 30% of dose or
administer every 24-48 hours.
Precautions:
WARNING: May cause CNS toxicity and Precautions:
superinfection. WARNING: May cause nephrotoxicity and
neurotoxicity.
Has been associated with CNS toxicity, including seizures,
psychosis, depression, and confusion; May cause neuromuscular blockade and respiratory
Decrease dosage or discontinue use if occurs; paralysis especially when given soon after anesthesia or
Prolonged use may result in fungal or bacterial muscle relaxants;
superinfection, including C. difficile-associated diarrhea Prolonged use may result in fungal or bacterial infection,
(CDAD) and pseudomembranous colitis; CDAD has been including C. difficile-associated diarrhea (CDAD) and
observed >2 months post-antibiotic treatment. pseudomembranous colitis; CDAD has been observed
>2 months post-antibiotic treatment;
Adverse Drug Reactions: Not intended for long-term therapy due to toxic hazards
Rare: Cardia arrhythmia, drowsiness, headache, dizziness, associated with extended administration.
vertigo, seizure, confusion, psychosis, paresis, coma,
rash, vitamin B12 deficiency, folate deficiency, tremor. Adverse Drug Reactions:
Rare: Edema, neurotoxicity, drowsiness, headache,
Drug Interactions: pseudomotor cerebri, skin itching, redness, rash,
Reduces therapeutic effect of the following drugs: photosensitivity, erythema, nausea, vomiting, diarrhea,
BCG, Typhoid vaccine malabsorption syndrome, anorexia, weight loss,
enterocolitis, burning weakness, tremor, muscle cramps.
Increases risk of adverse or toxic effects Cycloserine:
Isoniazid Drug Interactions:
Monitor closely with:
Administration: Enhances therapeutic effect of the following drugs:
Administer orally with meals. Botulinum toxin type A, RimabotulinumtoxinB,
Colistimethate
Pregnancy Category: C
Increases risk of adverse or toxic effects Kanamycin:
ATC Code: J04AB01 Amphotericin B, Vancomycin, Cisplatin

Enhances therapeutic effect of Kanamycin:

261
 ANTI-INFECTIVES FOR SYSTEMIC USE

Capreomycin
Rx OFLOXACIN
Decreases excretion of Kanamycon:
NSAIDs Oral: 200 mg tablet

Increases risk of adverse or toxic effects of Kanamycin: Indications: Quinolone antibiotic for the treatment of acute
Amphotericin B, Vancomycin, Cisplatin exacerbation of chronic bronchitis, community-acquired
Loop diuretics e.g. Furosemide pneumonia, skin and skin structure infections

Increases risk of adverse or toxic effects of the following Dose:

drugs: Tuberculosis, by mouth, ADULT and CHILD, 200–400 mg
Bisphosphonate derivatives e.g. Alendronate every 12 hours.
Carboplatin, Cyclosporine
Gallium nitrate Dose Adjustment:
Geriatric:
Avoid concomitant use with: Tuberculosis, by mouth, 200-400 mg per day (based on
Reduces therapeutic effect of the following drugs: estimated renal function) for 7 days to 6 weeks
BCG, Typhoid vaccine depending on indication.

Decreases serum concentration of Kanamycin: See Ofloxacin unde Second Generations Fluorquinolones in
J

Penicillins Chapter number 07: Anti-infectives title for other

information.
Administration:
Administer intramuscularly, deeply in upper outer quadrant Pregnancy Category: C
of the gluteal muscle. Infuse IV over 30-60 minutes.
ATC Code: J01MA01
Pregnancy Category: D

ATC Code: J01GB04

Rx PARA-AMINOSALICYLIC ACID

Rx LEVOFLOXACIN Oral: 4 g enteric-coated delayed-release granules, sachet

WHO anti-biotic category: WATCH
Indications: Adjunctive treatment of tuberculosis used in
Oral: 250 mg, 500 mg, and 750 mg tablet combination with other anti-tubercular agents.
Inj.: 5 mg/mL solution for IV infusion, 100 mL and 150 mL
vial Dose:
Tuberculosis, by mouth, ADULT, 150 mg/kg/day in 2-3
Indications: Used for drug-resistant tuberculosis or equally divided doses; CHILD, 200-300 mg/kg/day in 3-
intolerance to first-line agents in combination with other 4 equally divided doses.
agents.
Dose Adjustment:
Contraindications: Hypersensitivity to levofloxacin, any Geriatric:
component of the formulation, or other quinolones. Refer to adult dosing.

Dose: Renal Impairment:

Tuberculosis, by mouth, ADULT, 500-1000 mg daily; CHILD,
15-25 mg/kg daily (maximum dose of 1000 mg).
NOTE: Levofloxacin should be taken during the intensive (6
month) and continuation (12-18 months) phases of
treatment.
CrCl 10-50 mL/minute: Administer 50% to 75% of dose.
CrCl <10 mL/minute: Administer 50% of dose.
Administer after hemodialysis: Administer 50% of dose.
Continuous arteriovenous hemofiltration: Dose for CrCl <10
mL/minute.

See Levofloxacin under Third Generations Fluoroquinolones Precautions:

in Chapter 07: Anti-infectives for other information. Patients with sensitivity to tartrazine dyes, nasal polyps, and
asthma may have an increased risk of salicylate
Pregnancy Category: C sensitivity;
Use with caution in patients with gastric ulcer, hepatic
ATC Code: J01MA12 impairment, and renal impairment.

Adverse Drug Reactions:

Pericarditis, vasculitis, encephalopathy, fever, skin
eruptions, goiter, hypoglycemia, abdominal pain,
diarrhea, nausea, vomiting, agranulocytosis, anemia,
leukopenia, hepatitis, jaundice, optic neuritis,
eosinophilic pneumonia.

262
ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Isoniazid

Monitor closely with:
Reduces therapeutic effect of the following drugs: Administration:
ACE inhibitors e.g., Enalapril, Loop diuretics e.g., Administer WITH meals.
Furosemide, Probenecid
Pregnancy Category: D
Increases risk of adverse or toxic effects of Sulfonylureas
ATC Code: J04AD01
Enhances therapeutic effect of the following drugs:
Anticoagulants, Drotrecogin alfa, Corticosteroids,
Vitamin K antagonists
Rx RIFABUTIN
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following Oral: 150 mg capsule
drugs:
Carbonic anhydrase inhibitors, Thrombolytic agents, Indications: Alternative to the macrolides for the prophylaxis
NSAIDs of Mycobacterium avium complex (MAC) infection in
immunocompromised patients. Alternative to rifampicin
Increases risk of adverse or toxic effects of Para- in the treatment of tuberculosis in HIV patients in
aminosalicylic acid: combination with other mycobacterial agents.

Influenza virus vaccine
Administration:
May be administered orally with food. Do not use granules
if packet is swollen or if granules are discolored.
Granules may be sprinkled in applesauce or yogurt or
suspended in tomato or orange juice.
J
Dose:
Disseminated Mycobacterium Avium Complex in advanced
HIV infection, by mouth, ADULT, Prophylaxis: 300 mg
once a day or 150 mg 2 times a day; Treatment: 300
mg/day as an optional add-on to primary therapy of
clarithromycin and ethambutol.

Pregnancy Category: C Dose Adjustment:

Geriatric:
ATC Code: J04AA01 Refer to adult dosing.

Renal Impairment:
ClCr <30 mL/minute: Reduce dose by 50%.
Rx PROTHIONAMIDE
Precautions:
Oral: 250 mg film-coated tablet WARNING: Use with caution in patients with hepatic
impairment, renal impairment.
Indication: Treatment of multi-drug resistant tuberculosis
(MDRTB) Monitor patients for: Hematologic Toxicity, Hypersensitivity
Reactions, Superinfection; Uveitis, potentially significant
Contraindication: Severe liver disease due to risk of further interactions may exist, requiring dose or frequency
hepatotoxicity. adjustment, additional monitoring, and/or selection of
alternative therapy;
Dose: Must not be administered for Mycobacterium Avium
Tuberculosis, by mouth, ADULT/CHILD, 15-20 mg/kg Complex prophylaxis to patients with active tuberculosis
(maximum: 1 g) once daily. since its use may lead to the development of TB resistant
to both rifabutin and rifampin. Caution that active TB in
Dose Adjustment: the HIVpositive patient may present atypically (negative
Geriatric: PPD or extrapulmonary manifestations); Remove soft
Refer to adult dosing. contact lenses during therapy since permanent staining
may occur.
Adverse Drug Reactions: Urine, feces, saliva, sweat, tears, sputum, and skin may be
Common: Nausea, vomiting, diarrhea, anorexia, excessive discolored to brown/orange.
salivation, metallic test, stomatitis, and abdominal pain.
Less Common: dizziness, encephalopathy, peripheral Adverse Drug Reactions:
neuropathy, psychotic disturbances, depression, Rash, gastrointestinal disturbances, neutropenia,
hypoglycemia, hypothyroidism. polyarthralgia arthritis, uveitis, asymptomatic corneal
Rare: acute hepatitis, optic neuritis. opacities, orangetan skin pigmentation, discolored urine,
flulike syndrome in Crohn's disease, hepatitis,
Drug Interactions: leucopenia, neutropenia, epigastric pain, ageusia, fever,
Increases risk of adverse or toxic effects of the following vomiting.
drugs:
Cycloserine, P-aminosalicylic acid, Rifampicin Drug Interactions:
Increases serum concentration of the following drugs:
Increases serum concentration of Prothionamide:

263
 ANTI-INFECTIVES FOR SYSTEMIC USE

Antifungal Agents (Azole Derivatives), Voriconazole DRUGS FOR TREATMENT OF LEPRA

Increases risk of adverse or toxic effects Rifabutin:
Clarithromycin, Clopidogrel, Ifosfamide, Isoniazid Rx CLOFAZIMINE
Reduces therapeutic effect of Rifabutin:
Oral: 50 mg and 100 mg capsule (available under DOH
BCG (Intravesical), BCG Vaccine (Immunization), Sodium
program)
Picosulfate, Typhoid Vaccine
Indiations: Multibacillary leprosy; type 2 lepra reactions
Decreases serum concentration of Rifabutin:
(Erythema Nodosum Leprosum).
Abiraterone Acetate, Antihepaciviral Combination
Products, Apixaban, Aripiprazole, Axitinib, Bedaquiline,
Dose:
Boceprevir, Bortezomib, Bosentan, Bosutinib,
Multibacillary leprosy (in combination with dapsone and
Brentuximab Vedotin, Brexpiprazole, Buspirone,
rifampicin), by mouth, ADULT, 50 mg once daily and 300
Cabozantinib, Calcium Channel Blockers, Ceritinib,
mg once a month; CHILD 10-14 years, 50 mg on
Clozapine, Contraceptives (Estrogens), Contraceptives
alternate days, and 150 mg once a month; CHILD <10
(Progestins), Corticosteroids, Crizotinib, Cyclosporine,
years, required appropriate dosage adjustments (e.g., 50
CYP3A4 Substrates, Daclatasvir, Dapsone, Dasatinib,
mg twice a week and, 100 mg once a month); continue
Deferasirox, Dexamethasone, Doxorubicin, Dronabinol,
treatment for 12 months.
Dronedarone, Eliglustat, Enzalutamide, Erlotinib,
Type 2 lepra reactions, by mouth, ADULT and CHILD, 200-
J

Etoposide, Etravirine, Everolimus, Exemestane, Fentanyl,

300 mg daily in 2 or 3 divided doses for a maximum of 3
Gefitinib,, Guanfacine, HMG-CoA Reductase Inhibitors,
months; 4-6 weeks treatment may be required before
Hydrocodone, Hydrocortisone, Ibrutinib, Imatinib,
any effect is seen.
Irinotecan, Itraconazole, Ivabradine, Lapatinib,
Ledipasvir, Linagliptin, Lumefantrine,
Dose Adjustment:
Methylprednisolone, Mifepristone, Morphine,
Renal and Hepatic Impairment:
Mycophenolate, Netupitan, Nevirapine, Nifedipine,
Use drug with caution for mild-to-moderate impairment; for
Nilotinib, Nimodipine, Palbociclib, Pazopanib,
severe impairment, the patient should be referred to a
Perampanel, Praziquantel, Prednisolone, Prednisone,
specialist.
Propafenone, Quetiapine, Quinidine, Raltegravir,
Ramelteon, Ranolazine, Regorafenib, Rilpivirine,
Precautions:
Rivaroxaban, Roflumilast, Rolapitant, Saxagliptin,
Patients with pre-existing GI symptoms and problems
Siltuximab, Simeprevir, Sofosbuvir, Sorafenib, Sunitinib,
(reduce the dose, increase the dose interval or
Tacrolimus, Tadalafil, Tamoxifen, Telaprevir,
discontinue if symptoms develop during treatment);
Temsirolimus, Ticagrelor, Tocilizumab, Tofacitinib,
avoid use if abdominal pain and diarrhea persist; may
Tolvaptan, Ulipristal, Vincristine, Vitamin K Antagonists
discolor soft contact lenses; avoid treatment with daily
(e.g. Warfarin), Vortioxetine, Zolpidem
doses exceeding 100 mg; Pregnancy (use with caution
during first trimester); breastfeeding (crosses placental
Decreases serum concentration of Efavirenz
barrier and excreted in breast milk; can cause reversible
skin discoloration in nursing infant).
Decreases metabolism of Rifabutin:
Barbiturates
Adverse Drug Reactions:
Common: Abdominal pain, conjunctival discoloration,
Decreases metabolism of Macrolide Antibiotics
diarrhea, dryness of skin, eye irritation, ichthyosis, itch
nausea, pink to brownish-black discoloration of skin,
Administration:
rash, red-brown coloration of body fluids, vomiting.
Administer WITH meals.
Less Common: Constipation, dizziness, drowsiness,
eosinophilic enteritis, GI bleeding, splenic infarction,
Pregnancy Category: C
taste disturbances.
Rare: Enteropathy (due to the deposition of clofazimine
ATC Code: J04AB04
crystals in the GI mucosa and lymph nodes),
phototoxicity.

Drug Interactions:
Monitor closely with:
Reduces absorption of Rifampicin

Avoid concomitant use with:

Reduces therapeutic effect of Clofazimine:
Dapsone

Administration:
Medicines used in the treatment of leprosy should always
be used in combination (essential to prevent the
emergence of resistance); Clofazimine is best absorbed
when given right after a meal.

264
ANTI-INFECTIVES FOR SYSTEMIC USE
Pregnancy Category: C
ATC Code: J04BA01
Rx DAPSONE
Oral: 100 mg tablet
Indications: Paucibacillary and multibacillary leprosy;
dermatitis herpetiformis.
Contraindications: Severe anemia; porphyria.
Dose:
Dermatitis herpetiformis, by mouth, ADULT, start at 50 mg
daily, increase to 300 mg daily (or higher to achieve full
control).
NOTE: reduce dosage to minimum level as soon as possible.
Multibacillary leprosy (in combination with rifampicin and
clofazimine), by mouth, continued for 12 months, ADULT,
100 mg daily; CHILD 10-14 years, 50 mg daily; CHILD
<10 years, 50 mg every other day.
Paucibacillary leprosy (in combination with rifampicin), by
mouth, continued for 6 months, ADULT, 10-14 years, 50
mg daily; CHILD <10 years, 50 mg every other day.
Dose Adjustment:
Renal and Hepatic Impairment:
Use drug with caution for mild to moderate impairment; for
severe impairment, the patient should be referred to a
specialist.
Precautions:
Sulfonamide allergy (may predispose to dapsone allergy;
begin with low dose of dapsone and monitor closely for
adverse effects);
Cardiopulmonary disease or HIV and PCP (tolerate
hemolytic anemia and methemoglobinemia);
Susceptibility to hemolysis, including G6PD deficiency, or in
patients receiving drugs capable of inducing hemolysis
(including breastfeeding affected infants);
Hemoglobin M deficiency;
Methemoglobin reductase deficiency;
In patients with hepatic or renal disease; dermatologic
reactions (serious reactions are rare, but potentially
occurring);
Peripheral neuropathy (motor loss and muscle weakness
have been reported with use);
Prolonged use may result in fungal or bacterial
superinfection;
Pregnancy (supplementation with folic acid may be
necessary if use is warranted; possible risk of
hyperbilirubinemia in neonates);
Breastfeeding (avoid use)
BLOOD DISORDERS. On long-term treatment, patients and
their caregivers should be told how to recognize blood
disorders, and advised to seek immediate medical
attention of symptoms, such as fever, sore throat, rash,
mouth ulcers, purpura, bruising, or bleeding develop.
Adverse Drug Reactions:
Common: Asymptomatic methemoglobinemia, GI
symptoms, hemolytic anemia (occurs in most patients
taking more than 200 mg daily); rash (in HIV patients).
Less Common: Allergy, anorexia, fever, headache, insomnia,
nausea, nervousness, vomiting.
Rare: Agranulocytosis, albuminuria, aplastic anemia,
blurred vision, Dapsone syndrome (resembling
mononucleosis), hepatitis, Jarisch-Herxheimer reactions,
neutropenia, paresthesia, peripheral neuropathy (with
doses more than 200 mg daily); psychosis, severe skin
reactions (e.g. exfoliative dermatitis).
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects Dapsone:
Antimalarial agents (chloroquine and/or primaquine)
Reduces therapeutic effect of Clofazimine
J
Administration:
This may be administered with meals if GI upset occurs; do
NOT administer with antacids, alakine foods, or drugs.
NOTE: Stop dapsone if serious skin reaction or muscle
weakness occurs.
Pregnancy Category: C
ATC Code: J04BA02
Rx RIFAMPICIN
Oral: 300 mg, 450 mg, and 600 mg tablet / capsule
200 mg/5 mL suspension, 120 mL
Indications: First line of treatment for tuberculosis, in
combination with other drugs; treatment of leprosy, in
combination.
Dose:
Leprosy, Paucibacillary leprosy, by mouth, ADULT 50-70kg,
600mg/months with dapsone (100mg/ day); duration of
treatment: >6months;
Multibacillary leprosy, by mouth, ADULT 50- 70 kg, 600mg/
month with dapsone (100mg/day) and Clofazimine
(50mg/day + 300mg/month); Duration of treatment: >2
years and, when monitoring is feasible, until skin smears
are negative.
Note: Supervised use of Rifampicin.
See Rifampicin, in Drugs for Tuberculosis under Chapter 07
Pregnancy Category: C
ATC Code: J04AB02
265

ANTIVIRALS FOR SYSTEMIC USE
NUCLEOSIDES AND NUCLEOTIDES,
EXCLUDING REVERSE TRANSCRIPTASE
INHIBITORS
ANTIHERPES AGENTS
Rx ACICLOVIR (ACYCLOVIR)
Oral: 200 mg, 400 mg, and 800 mg tablet
200 mg/5 mL suspension, 60 mL and 120 mL
Inj.: 25 mg/mL, 10 mL vial (IV infusion)
An acyclic, purine nucleoside analogue, which has a high
degree of specificity, and is active against herpes
simplex virus and varicella-zoster virus.
J
Indications: Initial treatment and prophylaxis of recurrent
mucosal and cutaneous herpes (HSV1, HSV2) infections;
acute chickenpox (varicella zoster) in
immunocompromised patients; herpes zoster infections
(shingles).
Contraindications: Serious adverse reactions to individual
drug or metabolite; should not be used to treat severe
HSV infections in children with low resistance to disease.
Dose:
Antiviral prophylaxis, by mouth, ADULT, 800 mg twice a day
OR 400 mg 3-4 times a day.
Encephalitis, herpes simplex, by IV infusion, CHILD <12
years old, 20 mg/kg infused over 1 hour every 8 hours
for 14-21 days; ADULT, 10 mg/kg infused over 1 hour
every 8 hours for 14-21 days.
Herpes simplex virus gingivostomatitis, herpes simplex virus
1 and 2, by IV infusion, CHILD, 15 mg/kg every 8 hours
for 5-7 days.
Conjunctivitis, Herpes simplex types 1 and 2, by IV infusion,
NEONATE, 60 mg/kg in divided doses every 8 hours for
14 days.
Herpes keratitis, with recurrent infections, by mouth, ADULT
>12 years old, 400 mg twice a day for 2 months.
Varicella zoster ophthalmicus, by mouth, ADULT, 800 mg 5
times a day for 10 days.
Acute retinal necrosis, varicella zoster virus, by IV infusion,
ADULT, 10-12 mg/kg every 8 hours for 7-10 days until
disease stabilizes THEN by mouth, ADULT, 800 mg 5
times a day for a minimum of 6 weeks.
Vesicular, viral ulcerative pharyngitis, Coxsackie A9, B1-5;
ECHO viruses (multiple types); Enterovirus 71; Herpes
simplex virus (HSV) 1, 2, For HSV 1 and 2 in
immunocompromised host, by IV infusion, CHILD <12
years old, 10 mg/kg for 1-3 hours every 8 hours for 7-14;
CHILD >12 years old, 5 mg/kg for 1-3 hours every 8
hours for 7-14; by mouth, ADULT, 400 mg five times a
day for 5 days.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction is
warranted; for severe impairment, the patient should be
referred to a specialist.
266
ANTI-INFECTIVES FOR SYSTEMIC USE
Precautions:
WARNING: May aggravate renal sufficiency due to intra-
tubular obstruction with acyclovir microcrystals.
Use with caution in patients with dehydration, renal disease,
electrolyte abnormalities, underlying neurologic
diseases, hepatic dysfunction or renal impairment,
maintain adequate hydration (especially with infusion or
high doses, or during renal impairment) to minimize renal
adverse effects; Suppressive therapy of genital herpes
should be considered only if patient is severely affected
(periodic evaluation is recommended), and cross-
resistance may occur between agents due to their similar
mechanisms of action and activation pathways;
Prolonged or repeated courses of acyclovir in severely
immunocompromised patients may result in selection of
resistant viruses associated with infections which may
not respond, the elderly (at increased risk of neurological
adverse effects; likely to have reduced renal function),
pediatrics (safety and effectiveness in children <2 years
of age have not been adequately studied)
Adverse Drug Reactions:
Common: Diarrhea, hallucinations, headache, nausea,
vomiting.
Less Common: Abdominal pain, agitation, arthralgia,
confusion, constipation, dizziness, drowsiness, edema,
fatigue, pruritus, photosensitivity, rash, renal
impairment, sore throat, urticaria, vertigo, weakness.
Rare: Acute renal failure, anaphylaxis, anemia, anorexia,
coma, crystalluria, dyspnea, fatigue, fever, hepatitis,
jaundice, leukopenia, neutropenia, psychosis, seizures,
SJS, thrombocytopenia, toxic epidermal necrolysis,
tremor.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Acyclovir:
Probenecid
Increases risk of adverse or toxic effects of Theophylline
Enhances therapeutic effect of Zidovudine
Avoid concomitant use with:
Reduces therapeutic effect of Zoster vaccine
Administration:
For dosage taken 5 times daily, take every 4 hours during
waking hours. Make sure that the patient drinks plenty
of fluids (at least 1.5-2 L daily). This medication may
make the patient feel dizzy or confused; advise not to
drive or operate machinery if the patient is affected.
Pregnancy Category: B
ATC Code: J05AB01
ANTI-INFECTIVES FOR SYSTEMIC USE
Rx VALACICLOVIR (VALACYLOVIR)
Oral: 500 mg tablet (as hydrochloride)
Indications: Treatment of herpes zoster and herpes simplex
infections of the skin and mucous membranes, including
genital herpes.
Dose:
Herpes simplex virus gingivostomatitis, herpes simplex virus
1 and 2, by mouth, ADULT, 2 g every in 2 divided doses
every 12 hours for 7 days.
Varicella zoster ophthalmicus, by mouth, ADULT, 1g thrice a
day for 10 days.
Acute retinal necrosis, varicella zoster virus, by mouth,
ADULT, 1 g thrice a day.
Vesicular, viral ulcerative pharyngitis, Coxsackie A9, B1-5;
ECHO viruses (multiple types); Enterovirus 71; Herpes
simplex virus (HSV) 1, 2, For HSV 1 and 2 in
immunocompromised host, by IV infusion, CHILD> 12
years old, 4 g per day every 12 hours;
Recurrent herpes labialis, by IV infusion, CHILD >12
years old, 4g per day every 12 hours; by mouth, ADULT,
500 mg twice daily for 7 days.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
CrCl 30-49mL/minute: 1g every 12 hours;
CrCl 1029mL/minute: 1g every 24 hours;
CrCl <10mL/minute: 500mg every 24 hours.
Precautions:
WARNING: Monitor patients for CNS adverse effects and
thrombotic thrombocytopenic purpura/ hemolytic
uremic syndrome.
Use with caution in patients with renal impairment;
Adverse Drug Reactions:
Common: Diarrhea, hallucinations (high dose), headache,
nausea, vomiting.
Less Common: Abdominal pain, agitation, arthralgia,
confusion, constipation, dizziness, drowsiness, edema,
fatigue, pruritus, photosensitivity, rash, renal
impairment, sore throat, urticaria, vertigo, weakness.
Rare: Acute renal failure, anaphylaxis, anemia, anorexia,
coma, crystalluria, dyspnea, fatigue, fever, hepatitis,
jaundice, leukopenia, neutropenia, psychosis, seizures,
SJS, thrombocytopenia, toxic epidermal necrolysis,
tremor.
Drug Interactions:
Monitor closely with:
Decreases excretion of Tenofovir
Avoid concomitant use with:
Reduces therapeutic effect of Zoster vaccine
Administration:
If gastrointestinal upset occurs, administer with meals.
Pregnancy Category: B
ATC Code: J05AB11
ANTICYTOMEGALOVIRUS
Rx GANCICLOVIR
Inj.: 500 mg vial (as sodium) (IV infusion)
Indications: Treatment of CMV retinitis in
immunocompromised individuals, including patients
with acquired immunodeficiency syndrome; prophylaxis
of CMV infection in transplant patients.
Dose:
CMV Retinitis, by slow IV infusion, ADULT and CHILD,
induction therapy: 5mg/kg/dose every 12 hours for 14-
J
21 days followed by maintenance therapy of
5mg/kg/day as a single daily dose for 7 days/week or
6mg/kg/day for 5 days/week.
Prevention of CMV disease in transplant patients, by slow IV
infusion, ADULT and CHILD, same initial and
maintenance dose as CMV retinitis except duration of
initial course is 7-14 days, duration of maintenance
therapy is dependent on clinical condition and degree of
immunosuppression.
Dose Adjustment:
Geriatric:
Refer to adult dosing
Renal Impairment:
IV (induction):
CrCl 50-69mL/min: 2.5 mg/kg/dose every 12 hours.
CrCl 25-49mL/min: 2.5 mg/kg/dose every 24 hours.
CrCl 10-24mL/min: 1.25 mg/kg/dose every 24 hours.
CrCl <10mL/min: Administer 1.25mg/kg/dose
3 times/week following hemodialysis.
IV (maintenance):
CrCl 50-69mL/min: 2.5 mg/kg/dose every 24hours.
CrCl 25-49mL/min: 1.25 mg/kg/dose every 24 hours
CrCl 10-24mL/min: 0.625 mg/kg/dose every 24 hours.
CrCl >10mL/minute: 0.625 mg/kg/dose 3 times/week
following hemodialysis.
Precautions:
WARNING: Animal studies have demonstrated
carcinogenic and teratogenic effects, and
inhibition of spermatogenesis.
Granulocytopenia (neutropenia);
Anemia and thrombocytopenia may occur;
Use with caution in patients with renal impairment (dosage
adjustment or interruption of therapy may be necessary).
Adverse Drug Reactions:
Common: Fever, diarrhea, anorexia, vomiting,
thrombocytopenia, leukopenia, anemia, neutropenia,
retinal detachment, sepsis, diaphoresis.
Less Common: Chills, neuropathy, pruritus.
Rare: Anaphylaxis, alopecia, arrhythmia, bronchospasm,
cardiac arrest, cataracts, cholestasis, coma, dyspnea,
267

edema, encephalopathy, exfoliative dermatitis,
extrapyramidal symptoms, hepatitis, hepatic failure,
pancytopenia, pulmonary fibrosis, seizure, urticaria, SJS,
torsades de pointes, renal failure, visual loss.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Imipenem
Increases serum concentration of Mycophenolate
Increases serum concentration of Ganciclovir:
Probenecid
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse
Transcriptase Inhibitors
Increases serum concentration of Tenofovir
J
Administration:
Should NOT be administered by IM, subcutaneously, or
rapid IV push; administer by slow IV infusion over at least
1 hour. Too rapid infusion can cause increased toxicity
and excessive plasma levels.
Pregnancy Category: C
ATC Code: J05AB06
Rx VALGANCICLOVIR
Oral: 450 mg tablet
Indication: Treatment of cytomegalovirus (CMV) retinitis in
patients with acquired immunodeficiency syndrome
(AIDS).
Dose:
Cytomegalovirus Retinitis in Patients with AIDS, by mouth,
ADULT, induction dose 900 mg every 12 hours for 21
days. Maintenance dose 900 mg every day following
induction treatment, or in patients with inactive
Cytomegalovirus retinitis.
Cytomegalovirus prevention in solid organ transplant:
Kidney and kidney-pancreas transplantation, by mouth,
ADULT, 900 mg once a day; begin within 10 days of
transplant until 200 days post-transplant; INFANT, <4
months old: Safety and efficacy not established; CHILD,
4 months-16 years old, daily dose (mg) = 7 x BSA x CrCl;
not to exceed 900mg/day; begin within 10 days of
transplant and continue until 200 days post-transplant.
Heart transplantation, by mouth, ADULT, 900 mg once a
day. Begin within 10 days of transplant until 100 days
post transplant. CHILD, 1 month-16 years old, daily dose
(mg) = 7 x BSA x CrCl; not to exceed 900 mg/day; begin
within 10 days of transplant and continue until 100 days
post-transplant.
Dose Adjustment:
Geriatric:
Start at lower end of dosing range.
268
ANTI-INFECTIVES FOR SYSTEMIC USE
Renal Impairment:
CrCl 40-59mL/min: 450 mg every 12 hours (induction),
THEN 450mg/day.
CrCl 25-39mL/min: 450 mg daily (induction), THEN 450 mg
every 2 days.
CrCl 10-24mL/min: 450 mg every 2 days (induction), THEN
450 mg 2 times per week.
<10mL/minute (on hemodialysis): Not recommended.
Precautions:
WARNING: May cause dose- or therapy-limiting
granulocytopenia, anemia, and/or
thrombocytopenia. May be teratogenic,
carcinogenic and cause aspermatogenesis.
Monitor patients for hematologic toxicity; female infertility,
aspermatogenesis;
Use with caution in patients with preexisting cytopenias;
concomitant use nephrotoxic drugs;
May be teratogenic or embryotoxic;
Avoid pregnancy; male patients advised to use barrier
method during and for 90 days after treatment;
Maintain adequate hydration.
Adverse Drug Reactions:
Common: Fever, diarrhea, anorexia, vomiting,
thrombocytopenia, leukopenia, anemia, neutropenia,
retinal detachment, sepsis, diaphoresis.
Less Common: Chills, neuropathy, pruritus.
Rare: Anaphylaxis, alopecia, arrhythmia, bronchospasm,
cardiac arrest, cataracts, cholestasis, coma, dyspnea,
edema, encephalopathy, exfoliative dermatitis,
extrapyramidal symptoms, hepatitis, hepatic failure,
pancytopenia, pulmonary fibrosis, seizure, urticaria, SJS,
torsades de pointes, renal failure, visual loss.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Imipenem
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse
Transcriptase Inhibitors
Increases serum concentration of Tenofovir
Administration:
Administer orally with food. Do NOT break or crush the
tablets. Maintain adequate hydration.
Pregnancy Category: C
NOTE: Females of reproductive potential should use
effective contraception during treatment and for at least
30 days following treatment. Males should be advised to
practice barrier contraception during and for at least 90
days following treatment. Temporary or permanent
female and male infertility may occur.
ATC Code: J05AB14
ANTI-INFECTIVES FOR SYSTEMIC USE

NUCLEOSIDE AND NUCLEOTIDE Drug Interactions:

REVERSE TRANSCRIPTASE INHIBITORS Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse
NRTIs or nucleoside analogues act by competitive inhibition Transcriptase Inhibitors e.g. Lamivudine
of HIV-1 reverse transcriptase; incorporation into the
growing viral DNA chain causes premature chain Increases risk of adverse or toxic effects Abacavir:
termination due to inhibition of binding with the incoming Ribavirin
nucleotide.
Administration:
May be administered with or without food.
ANTIRETROVIRAL AGENTS
Pregnancy Category: C
Rx ABACAVIR ATC Code: J05AF06

Oral: 300 mg tablet (as sulfate)

Indication: First-line treatment for children with Human Rx ENTECAVIR

Immunodeficiency Virus (HIV) infection as combination
therapy. Oral: 500 micrograms and 1 mg tablet / film-coated tablet

Contraindications: Hypersensitivity to abacavir or any
component of the formulation; Moderate-to-severe
hepatic impairment.
Dose:
HIV treatment, by mouth, ADULT, 300 mg twice daily or 600
mg once daily in combination with other antiretroviral
agents.; CHILD 3 months to 16 years, 8 mg/kg twice daily
(maximum of 300 mg twice daily) in combination with
other antiretroviral agents.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Hepatic Impairment:
Mild hepatic dysfunction, 200 mg twice daily (oral solution
is recommended) while for moderate-to-severe
dysfunction, use is contraindicated.
Precautions:
WARNING: Serious and sometimes fatal hypersensitivity
reactions have occurred. Lactic acidosis and severe
hepatomegaly with steatosis have been reported with
nucleoside analogues, including fatal cases.)
May cause redistribution of fat (e.g., buffalo hump,
peripheral wasting with increased abdominal girth,
cushingoid appearance);
Patients may develop immune reconstitution syndrome
resulting in the occurrence of an inflammatory response
to an indolent or residual opportunistic infection (further
evaluation and treatment may be required).
J
0.05 mg/mL oral solution
Indications: Treatment of chronic hepatitis B infection, with
compensated or decompensated liver disease, in adults
with evidence of active viral replication.
Dose:
HIV/HBV coinfection, by mouth, ADULT and CHILD ≥16
years, recommended in patients who cannot take
tenofovir, 0.5 mg once daily.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Dosage adjustments depends on creatinine clearance of
patient.
Hepatic Impairment:
Decompensated liver disease, 1 mg once daily.
Precautions:
WARNING: Lactic acidosis and severe hepatomegaly with
steatosis. May cause development of HIV resistance in
chronic hepatitis B patients with unrecognized or
untreated HIV infection.
Use with caution in patients with renal impairment or
patients receiving concomitant therapy which may
reduce renal function, dose adjustment recommended
for ClCr <50mL/minute;
Cross-resistance may develop in patients failing previous
therapy with lamivudine.

Adverse Drug Reactions: Adverse Drug Reactions:

Common: Headache, nausea. Common: Peripheral edema, pyrexia, ascites
Less common: Depression, fever/chills, anxiety, rash, Less Common: Headache, fatigue, dizziness,
diarrhea, vomiting, and hypersensitivity reactions. hyperglycemia, diarrhea, dyspepsia, nausea, hepatic
Rare: Erythema multiforme, fat redistribution, hepatic encephalopathy, hematuria, glycosuria, upper
steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, respiratory tract infection.
pancreatitis, SJS, toxic epidermal necrolysis. Rare: Alopecia, anaphylactoid reaction, hepatomegaly,
hypoalbuminemia, insomnia, lactic acidosis, rash, renal
failure, somnolence, thrombocytopenia, vomiting.

269
 ANTI-INFECTIVES FOR SYSTEMIC USE

Drug Interactions: Administration:

Decreases serum concentration of Protease inhibitors e.g. Administer orally with no regard to meals.
Lopinavir
Pregnancy Category: C
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Reverse ATC Code: J05AF05
Transcriptase Inhibitors

Increases risk of adverse or toxic effects Abacavir: TENOFOVIR ALAFENAMIDE

Ribavirin (hepatotoxic) Rx
FUMARATE
Administration:
Oral: 25 mg tablet
Administer on an EMPTY stomach (2 hours before or after a
meal). Do not dilute or mix oral solution with water or
The active moiety of Tenofovir alafenamide inhibits
other beverages; use calibrated oral dosing syringe. Oral
replication of HBV by inhibiting HBV polymerase.
solution and tablet are bioequivalent on a mg-to-mg
basis.
Indication: Treatment of chronic hepatitis B
Pregnancy Category: C
Dose:
Chronic hepatitis B, by mouth, ADULT, 25 mg tab once daily.
J

ATC Code: J05AF10

Rx LAMIVUDINE
Oral: 100 mg tablet and 150 mg tablet / film-coated tablet
10 mg/mL suspension, 240 mL bottle
Indications: Treatment of HIV infection when antiretroviral
therapy is warranted; should always be used as part of a
multidrug regimen (at least three antiretroviral agents).
Dose:
HIV infection, ADULT, oral dose of 150 mg twice daily or 300
mg once daily. CHILD, 1-3 months, 4 mg/kg/dose twice
daily. 3 months to 16 years, 4 mg/kg/dose twice daily.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Precautions:
WARNING: Lactic acidosis and severe hepatomegaly
with steatosis.
Do not use as monotherapy in treatment of HIV. Lamivudine
combined with emtricitabine is not recommended as a
dual-NRTI combination due to similar resistance patterns
and negligible additive antiviral activity;
Use with caution in patients with renal impairment (dosage
reduction recommended).
Dose Adjustment:
Renal impairment:
CrCl >15 mL/min: no dosage adjustment necessary.
CrCl <15 mL/min: use is not recommnended.
Hepatic impairment:
Mild impairment: no dosage adjustment necessary.
Decompensated cirrhosis: use is not recommended.
Precautions:
May cause lactic acidosis, hepatomegaly, renal toxicity,
hepatitis B acute exacerbation;
Use is not recommended in patients with hepatic and renal
impairment, HIV-1 and HBV co-infection.
Adverse Drug Reactions:
Common: Headache and decreased bone mineral density.
Less Common: Fatigue, skin rash, glycosuria, abdominal
pain, nausea, diarrhea, dyspepsia, flatulence, vomiting,
back pain, arthralgia, cough
Drug Interactions:
Monitor closely with:
Increases the level or effect of Tenofovir:
Daclatasvir, Sofosbuvir/Velpatasvir
Administration: Administer with food.
Pregnancy Category: B
ATC Code: J05AF13

Adverse Drug Reactions:

Headache, nausea, malaise, fatigue, nasal signs and
symptoms, diarrhea, cough, fever

Drug Interactions:
Monitor closely with:
Decreases excretion of Lamivudine:
Trimethoprim

Avoid concomitant use with:

Enhances risk of adverse or toxic effects of Lamivudine:
Ganciclovir, Valganciclovir, Ribavirin

270
ANTI-INFECTIVES FOR SYSTEMIC USE

TENOFOVIR DISOPROXIL Stage Renal Disease on Intermittent Hemodialysis

Rx (admin dose after dialysis on dialysis days): 100mg every
FUMARATE
6-8 hours, alternate dosing: 100mg 3 times a day or
300mg/day. Peritoneal Dialysis: 100mg every 6-8 hours.
Oral: 300 mg tablet
Precautions:
Indications: First-line treatment for HIV infection; treatment
of chronic hepatitis B virus. WARNING: Hematologic toxicity; Lactic
acidosis/severe hepatomegaly.
Dose:
HIV infection, by mouth, ADULT, 300 mg once daily, in Monitor patients for: Fat Redistribution; Hematologic
combination with other antiretrovirals. CHILD, ≥12 years Toxicity, Immune Reconstitution Syndrome), Lactic
and ≥35 kg, 300 mg once daily. Acidosis, Severe Hepatomegaly with Steatosis,
Myopathy.
Precautions:
WARNING: Black box warning of chronic hepatitis B and Adverse Drug Reactions:
lactic acidosis or hepatomegaly. Common: Headache, malaise, nausea, anorexia, vomiting.
Less common: Constipation, anemia, muscle weakness.
Use with caution in patients with risk factors for liver disease Rare: Cardiomyopathy, rash, body fat redistribution,
(risk may be increased with female sex, obesity, abdominal pain, hepatitis, hearing loss.

J
pregnancy or prolonged exposure) and suspend
treatment in any patient who develops clinical or Drug Interactions:
laboratory findings suggestive of lactic acidosis or Monitor closely with:
hepatotoxicity. Increases risk of adverse or toxic effects of Zidovudine:
Aciclovir, Valaciclovir, Divalproex, Fluconazole,
Adverse Drug Reactions: Interferons, Protease inhibitors, Rifamycin
Common: Insomnia, abdominal pain, muscle weakness.
Less Common: Chest pain, fatigue, hyperglycemia. Avoid concomitant use with:
Rare: Neutropenia, diaphoresis. Reduces therapeutic effects of Stavudine

Drug Interactions: Increases risk of adverse or toxic effects of the following

Avoid concomitant use with: drugs:
Reduces therapeutic effect of Didanosine Ribavirin, Ganciclovir, Valganciclovir, Doxorubicin,
Clarithromycin
Administration: May be administered orally without meals.
Administration:
Pregnancy Category: B May be administered orally without regard to meals. Take
around the clock to promote less variation in peak and
ATC Code: J05AF07 trough serum levels.

Pregnancy Category: C

Rx ZIDOVUDINE ATC Code: J05AF01

Oral: 100 mg capsule

300 mg tablet, 60 per bottle NON-NUCLEOSIDE REVERSE
50 mg/5 mL suspension, 240 mL bottle TRANSCRIPTASE INHIBITORS (NNRTI)

Indication: Treatment of HIV-1 infection in combination with
at least two other antiretroviral agents.
Contraindications: Neutrophil count <750/mm3
hemoglobin <7.5g/dL (4.65mmol/L).
Dose:
HIV infection, by mouth, ADULT, 200 mg three times daily or
300 mg twice a day.
For treatment of HIV infection, by mouth, ADULT >18 years
old, dose calculated by body weight or body surface area:
240 mg/m2 every 12 hours or 160 mg/m2/dose every 8
hours, with a maximum dose of 200 mg every 8 hours.
Dose Adjustment:
Renal Impairment:
CrCl <15mL/minute: 100mg every 6-8 hours, alternate
dosing: 100mg 3 times a day or 300 mg once a day; End-
NNRTIs under Antiretroviral (ARV) HIV drug class act by
binding directly to HIV-1 reverse transcriptase, resulting
in allosteric inhibition of RNA- and DNA-dependent DNA
or polymerase activity.
ANTIRETROVIRAL AGENTS
Rx EFAVIRENZ
Oral: 50 mg, 100 mg, 200 mg and 600 mg tablet / capsule
Indications: First-line treatment for HIV infection; alternative
drug for patients who cannot tolerate nevirapine.
Contraindications: Concurrent use of bepridil, cisapride,
midazolam, pimozide, triazolam, voriconazole, or ergot
alkaloids.

271

Dose:
HIV infection, in combination with tenofovir and
emtricitabine, by mouth, ADULT, 600 mg once daily.
Dosage adjustment for concomitant use of voriconazole
to 300 mg once daily and increase voriconazole to 400
mg every 12 hours; CHILD ≥3 years and 10kg to <15kg,
200mg once daily; CHILD ≥3 years and 15kg to <20kg,
250mg once daily; CHILD ≥3 years and 20kg to <25kg,
300mg once daily; CHILD ≥3 years and 25kg to <32.5kg,
350mg once daily; CHILD ≥3 years and 32.5kg to <40kg,
400mg once daily; CHILD ≥3 years and ≥40kg, 600mg
once daily.
Dose Adjustment:
Hepatic Impairment:
Do not use for moderate-to-severe hepatic impairment.
Precautions:
May cause CNS depression; symptoms usually begin within
1-2 days after starting efavirenz, and generally resolve
J
within 2-4 weeks of continues therapy, avoid potentially
hazardous tasks such as driving or operating machinery;
Serious psychiatric side effects have been associated
with use, including severe depression, suicide, paranoia,
and mania, use with caution in patients with a history of
mental illness/drug abuse.
Not recommended in moderate-to-severe hepatic
impairment.
Adverse Drug Reactions:
Common: Dizziness, fever, depression, insomnia, anxiety,
pain, headache, rash, diarrhea, nausea, vomiting, cough.
Less Common: Impaired concentration, somnolence,
fatigue, abnormal dreams, nervousness, hallucinations,
pruritus, hyperglycemia, dyspepsia, abdominal pain,
anorexia
Rare: Allergic reaction, aggressive reaction, agitation,
arthralgia, ataxia, balance disturbances, body fat
accumulation/redistribution.
Drug Interactions:
Monitor closely with:
Increases metabolism of the following drugs:
CYP2B6 inducers, CYP3A4 inducers
Decreases metabolism of the following drugs:
CYP2C19 substrates, CYP3A4 substrates, CYP2B6
inhibitors
Administration:
Administer on an EMPTY stomach. Dosing at or before
bedtime is recommended to limit central nervous system
effects. Tablets should NOT be broken.
Pregnancy Category: D
ATC Code: J05AG03
272
ANTI-INFECTIVES FOR SYSTEMIC USE
Rx NEVIRAPINE
Oral: 200 mg tablet
50 mg dispersible tablet
50 mg/5 mL suspension, 240 mL
Indication: In combination therapy with other antiretroviral
agents for the treatment of HIV-1.
Contraindications: Moderate-to-severe hepatic impairment;
use in occupational or non-occupational post-exposure
prophylaxis regimen
Dose:
Treatment of HIV-1 infection, by mouth, ADULT, 200 mg
once daily for the first 14 days of therapy. Dose should
then be increased to 200 mg twice daily in patients who
do not experience rash or liver function test
abnormalities with the lower dosage; CHILD 15 days of
age or older, the usual initial dosage of nevirapine oral
suspension or immediate-release tablets is 150 mg/m2
once daily for the first 14 days of therapy. Dosage should
then be increased to 150 mg/m2 twice daily in patients
who do not experience rash or liver function test
abnormalities with the lower dosage. Dose should not
exceed 400 mg/day.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
Patients requiring dialysis: Administer additional 200 mg
dose after each dialysis treatment.
Hepatic Impairment:
Moderate to severe: Not recommended for use.
Precautions:
Patients taking nevirapine should be closely monitored for
adverse skin reactions and hepatotoxicity during the first
18 weeks of treatment, extra vigilance is advised during
the first 6 weeks of treatment. Use with extreme caution
in patients with moderate hepatic impairment,
contraindicated in those with severe hepatic impairment,
Treatment should be permanently stopped in patients
who suffer a severe rash, rash accompanied by
constitutional symptoms, hypersensitivity reactions or
clinical hepatitis.
Adverse Drug Reactions:
Common: Rash
Less common: Hypersensitivity reactions
Rare: Hepatitis, hepatic failure, SJS, and toxic epidermal
necrolysis.
Drug Interactions:
Avoid concomitant use with:
Decreases serum concentration of the following drugs:
Aripiprazole, Caspofungin, Contraceptives, Dolutegravir,
Fosamprenavir, Indinavir, Itraconazole, Ketoconazole,
Lopinavir, Voriconazole
Decreases serum concentration of Nevirapine:
Carbamazepine, Dabrafenib, Mitotane, Rifampin
ANTI-INFECTIVES FOR SYSTEMIC USE
Increases serum concentration of the following drugs:
Rilpivirine, Tizanidine
Increases risk of adverse or toxic effects of Efavirenz
Increases metabolism of Nevirapine:
CYP2B6 Inducers (Strong), CYP3A4 Inducers (Strong)
Increases metabolism of Methadone
Administration:
Administered orally without regard to food. Therapy is
initiated using a low dosage of immediate-release
nevirapine for the first 14 days since this appears to
reduce the frequency of rash.
Pregnancy Category: B
ATC Code: J05AG01
Rx RILPIVIRINE
Oral: 25 mg tablet (as hydrochloride)
Rilpivirine has activity against HIV-1 by binding to reverse
transcriptase. It consequently blocks the RNA-dependent
and DNA dependent DNA polymerase activities, including
HIV-1 replication.
Indications: Treatment of human immunodeficiency virus
type 1 (HIV 1) infection in combination with other
antiretroviral agents in treatment-naïve patients with
HIV-1 RNA <100,000 copies/mL.
Contraindications: Hypersensitivity to rilpivirine or any
component of the formulation.
Dose:
HIV-1 infection, by mouth, ADULT and CHILD ≥ 12 years, 25
mg once daily; CHILD <12 years, safety and efficacy not
established.
Dose Adjustment:
Dosage adjustment for concomitant therapy with rifabutin:
Increase to 50 mg once daily in patients on concomitant
rifabutin. Decrease to 25 mg once daily when rifabutin is
stopped.
Precautions:
Depressive disorders (may cause depression, mood
changes, negative thoughts, suicide attempts, or suicidal
ideation);
Fat redistribution (e.g., central obesity, buffalo hump, facial
wasting, peripheral wasting, breast enlargement, and
cushingoid appearance);
Hepatotoxicity (Patients with underlying hepatitis B or C, or
marked increased transaminases prior to treatment may
be at increased risk);
Immune reconstitution syndrome (During initial HIV
treatment, patient may develop immune reconstitution
syndrome resulting in the occurrence of an indolent or
residual opportunistic infection, or autoimmune
disorders later in therapy.)
Hypersensitivity (Severe skin and hypersensitivity reactions
reported, including cases of drug reaction with
eosinophilia and systemic symptoms (DRESS).
Adverse Drug Reactions:
Common: Depression, headache, drowsiness, nausea
Less Common: Dizziness, insomnia, abnormal dreams,
fatigue, skin rash, abdominal pain, vomiting
Rare: Angioedema, conjunctivitis, DRESS syndrome, facial
edema, fever, hepatitis, hypersensitivity reaction,
localized vesiculation, nephrotic syndrome, and suicidal
ideation.
Drug Interactions:
Monitor closely with:
Increased toxicity of the following drugs:
Amiodarone, Artemether/Lumefantrine, Azithromycin,
Chlorpromazine, Ciprofloxacin, Clarithromycin,
Erythromycin, Escotalopram, Fluconazole, Fluoxetine,
Haloperidol, Indapamide, Levofloxacin, Lopinavir,
J
Moxifloxacin, Octreotide, Ofloxacin, Paliperidone,
Quetiapine, Quinine, Risperidone, Tacrolimus,
Voriconazole
Avoid concomitant use with:
Decreases levels of Rilpivirine:
Carbamazepine, Dexamethasone, Efavirenz, Nevirapine,
Oxcarbazepine, Phenobarbital, Phenytoin, Rifampin,
Rifabutin
Administration: Must be taken with a normal to high calorie
meal. Taking with a protein supplement drink alone does
not increase absorption. Swallow tablet whole with
water.
Pregnancy Category: B
ATC Code: J05AG05
COMBINATIONS OF ANTIVIRALS FOR THE
TREATMENT OF HIV INFECTIONS
Rx LAMIVUDINE + TENOFOVIR
Oral: 300 mg lamivudine + 300 mg tenofovir tablet
Indication: First-line treatment for HIV infection which
consists of at least 3 agents
Contraindications: Hypersensitivity to tenofovir, lamivudine
or any excipient in the formulation
Dose:
Treatment of HIV-1 infection, by mouth, ADULT, one tablet
taken once daily
Dose Adjustment:
Renal Impairment:
Not recommended for patients with moderate or severe
renal impairment, may require dose interval adjustment
of lamivudine and tenofovir that cannot be achieved with
combination tablet.
273

Precautions:
WARNING: Chronic hepatitis B and lactic acidosis or
hepatomegaly may occur.
Should not be administered concomitantly with other
Cytidine analogues such as Emtricitabine.
Refer to individual drug monographs of lamivudine, and
tenofovir.
Adverse Drug Reactions:
Refer to individual drug monographs of lamivudine, and
tenofovir.
Drug Interactions:
Refer to individual drug monographs of lamivudine, and
tenofovir.
Administration: Tablet should be swallowed WHOLE with
J
water, taken on an empty stomach since food may
increase Efavirenz exposure and may lead to an increase
in the frequency of adverse reactions.
Not recommended for administration to CHILDREN.
Pregnancy Category: C
ATC Code: J05AR12
LAMIVUDINE + TENOFOVIR +
Rx
EFAVIRENZ
Oral: 300 mg lamivudine + 300 mg tenofovir + 600 mg
efavirenz
A combination of three antiviral drugs used to treat HIV
infection in adults and adolescents.
Indication: First-line treatment for HIV infection.
Contraindications: Patients with clinically significant
hypersensitivity to tenofovir, lamivudine, efavirenz or any
of the excipients contained in the formulation.
Dose:
Treatment of HIV-1 infection, by mouth, ADULT, one tablet
taken once daily
Dose Adjustment:
Geriatric:
Should be administered with caution.
Renal Impairment:
Not recommended for patients with moderate or severe
renal impairment, may require dose interval adjustment
of lamivudine and tenofovir that cannot be achieved with
combination tablet.
Hepatic Impairment:
Monitor closely for adverse reactions, especially nervous
system symptoms related to Efavirenz.
Precautions:
WARNING: Chronic hepatitis B and lactic acidosis or
hepatomegaly may occur.
274
ANTI-INFECTIVES FOR SYSTEMIC USE
Should not be administered concomitantly with other
cytidine analogues such as Emtricitabine.
Refer to individual drug monographs of Tenofovir,
Lamivudine and Efavirenz.
Adverse Drug Reactions:
Refer to individual drug monographs of Lamivudine,
Tenofovir, and Efavirenz.
Drug Interactions:
Refer to individual monographs of Lamivudine, Tenofovir,
and Efavirenz.
Administration: Tablet should be swallowed whole with
water, taken on an empty stomach since food may
increase efavirenz exposure and may lead to an increase
in the frequency of adverse reactions.
Not recommended for administration to CHILDREN.
Pregnancy Category: D
ATC Code: J05AR11
Rx LAMIVUDINE + ZIDOVUDINE
Oral: 30 mg lamivudine + 60 mg zidovudine dispersible
tablet
150 mg lamivudine + 300 mg zidovudine tablet
Indication: First-line treatment for HIV infection which
consists of at least 3 agents.
Dose:
Treatment of HIV infection, by mouth, ADULT and CHILD,
≥30 kg, 1 tablet twice daily (refer to adult dosing)
Dose Adjustment:
Renal Impairment:
Not recommended for use.
Hepatic Impairment:
Not recommended for use.
Precautions:
WARNING: Zidovudine is associated with hematologic
toxicity including neutropenia and severe anemia.
Lactic acidosis and severe hepatomegaly with
steatosis.
Prolonged use of Zidovudine has been associated with
symptomatic myopathy and myositis; Monitor closely for
chronic hepatitis B for several months following
discontinuation of therapy in patients co-infected with
HBV and HIV.
Refer to individual drug monographs of Lamivudine and
Zidovudine.
Adverse Drug Reactions:
Refer to individual drug monographs of Lamivudine and
Zidovudine.
ANTI-INFECTIVES FOR SYSTEMIC USE
Drug Interactions:
Refer to individual monographs of Lamivudine and
Zidovudine.
Administration:
May be taken with or without food
Pregnancy Category: C
ATC Code: J05AR01
LAMIVUDINE + ZIDOVUDINE +
Rx
NEVIRAPINE
Oral: 150 mg lamivudine + 300 mg zidovudine + 200 mg
nevirapine tablet
Indication: First-line treatment for HIV-1 infection
Contraindications: Severe Anemia (< 7.5 g/dL or 4.65
mmol/L); Neutropenia (< 0.75 x 109/L); Permanent liver
disease or marked changes in liver function; History of
liver inflammation; History of skin rash or liver injury
while on treatment with nevirapine-containing products;
Medication therapy with rifampicin; Children <25kg.
Dose:
NOTE: This fixed combination replaces the three
components (lamivudine, nevirapine and zidovudine)
used separately in similar dosages. Treatment must be
started with lamivudine, zidovudine, and nevirapine
separately for the first 6-8 weeks the patients is stable
on nevirapine 200mg 2 times a day and adequate
tolerability to lamivudine, zidovudine and nevirapine has
been demonstrated.
Treatment of HIV infection, by mouth, ADULT and CHILD,
>25kg: 1 tablet 2 times a day.
Dose Adjustment:
Renal Impairment:
It is recommended that separate preparations of
Lamivudine, Zidovudine and Nevirapine be
administered.
Hepatic Impairment:
Contraindicated in severe hepatic impairment.
Precautions:
Monitor patients for: liver damage, blood disorders (anemia
and neutropenia), hypersensitivity reactions, lactic
acidosis, immune reactivation syndrome, osteonecrosis;
It is recommended that separate preparations of
Lamivudine, Zidovudine and Nevirapine be administered
when any dosage adjustment is necessary.
Refer to individual drug monographs of Lamivudine,
Zidovudine and Nevirapine
Adverse Drug Reactions:
Refer to individual drug monographs of Lamivudine,
Zidovudine and Nevirapine
Drug Interactions:
Refer to individual drug monographs of Lamivudine,
Zidovudine and Nevirapine
Administration:
May be taken with or without food
Pregnancy Category: C
ATC Code: J05AR05
Rx LOPINAVIR + RITONAVIR
Oral: 40 mg lopinavir + 10 mg ritonavir oral pellets
contained in capsule
200 mg lopinavir + 50 mg ritonavir tablet / capsule
Indications: First-line treatment for HIV infection in children
less than 3 years; second-line treatment for HIV infection
J
in older children and adults
Contraindications: Co-administration with medications
highly dependent upon CYP3A4 for clearance.
Dose:
HIV infection, by mouth, ADULT, twice daily dosing lopinavir
400 mg/ ritonavir 100 mg. NOTE: This regimen is
preferred in pregnant therapy-naïve patients.
Once daily dosing for therapy-naïve or experience patients
with <3 lopinavir resistance-associated substitutions:
lopinavir 800 mg/ritonavir 200 mg once daily; by mouth,
CHILD <15 kg, 12 mg/kg twice daily; CHILD 15-40 kg, 10
mg/kg twice daily; CHILD >40 kg, lopinavir 400
mg/ritonavir 100 mg twice daily.
Dose Adjustment:
Geriatric:
Use with caution due to possible decreased hepatic, renal
and cardiac function.
Renal Impairment:
Decrease in clearance is not expected. Do not use once
daily dosing in hemodialysis patients.
Hepatic Impairment:
Use caution in hepatic impairment. AUC of lopinavir may be
increase ~30% in mild-to-moderate impairment.
Precautions:
May alter cardiac conduction and prolong the QT and/or PR
interval, second- and third-degree AV block and torsade
de pointes have been observed;
Patients may develop immune reconstitution syndrome
resulting in the occurrence of an inflammatory response
to an indolent or residual opportunistic infection, further
evaluation and treatment may be required;
Increases in total cholesterol and triglycerides have been
reported, screening should be done prior to therapy and
periodically throughout treatment.
Adverse Drug Reactions:
Common: Rash, hypercholesterolemia, diarrhea, abnormal
taste, vomiting, nausea, abdominal pain
275

Less Common: Vasodilation, insomnia, hyperglycemia,
hyperuricemia, dyspepsia, flatulence, weight loss,
muscular weakness,
Rare: Abdominal distention, Cushing’s syndrome, diabetes
mellitus, dry skin, dyskinesia, eczema, esophagitis,
exfoliative dermatitis, extrapyramidal symptoms, facial
paralysis, folliculitis, rhinitis, skin discoloration,
somnolence, splenomegaly, SJS, weight gain,
xerostomia.
Drug Interactions:
Monitor closely with:
Use with caution in patients taking CYP3A4 inhibitors,
inducers and substrates.
Avoid concomitant use with:
Incompatible with Colchicine
Increases risk of averse or toxic effects of Salmeterol
J
Administration:
May be taken with or without food. Swallow WHOLE; do NOT
break, crush or chew. May be taken with didanosine
when taken without food. Tablets are recommended in
patients <15kg.
Pregnancy Category: C
ATC Code: J05AR10
NEURAMINIDASE INHIBITORS
ANTI-INFLUENZA A AND B
Rx OSELTAMIVIR
Oral: 75 mg capsule (as phosphate)
Indications: Prophylaxis of influenza A and B (not a
substitute for flu vaccination); treatment of
uncomplicated acute illness due to influenza A and B
infection in patients who have been symptomatic for no
more than 2 days.
Dose:
Treatment of influenza (must be given within 2 days of onset
of flu symptoms), by mouth, ADULT, 75 mg every 12
hours for 5 days; INFANT 2 weeks-11 months old, 3
mg/kg twice a day for 5 days; CHILD ≤15kg, 30 mg twice
a day for 5 days; CHILD >15-23kg, 45 mg twice a day for
5 days; CHILD >23-40kg, 60 mg twice a day for 5 days;
CHILD>40kg and ADULT, 75 mg twice a day for 5 days;
Dose Adjustment:
Renal Impairment:
Administer with caution in moderate to severe renal
impairment.
Precautions:
WARNING: Severe hypersensitivity reactions have
been associated with use.
276
ANTI-INFECTIVES FOR SYSTEMIC USE
Most effective when used within 24-48 hours of onset of
symptoms; Age <1 year: safety and efficacy for
prophylaxis of influenza has not been established; Age
≤2 weeks: safety and efficacy for treatment of influenza
has not been established; Increased risk of serious skin
reactions; Reports of potentially fatal neuropsychiatric
adverse events in patients with flu.
Adverse Drug Reactions:
Common: Abdominal pain, conjunctivitis, ear disorder,
epistaxis, insomnia, nausea, vomiting, vertigo.
Less Common: Aggravation of diabetes, anemia,
arrhythmia, confusion, delirium, hemorrhagic colitis,
hepatitis, humerus fracture, peritonsillar abscess,
pneumonia, pseudomembranous colitis, pyrexia, rash,
seizure, increased transaminase, toxic epidermal
necrolysis, unstable angina, swelling of face or tongue.
Hypothermia also reported.
Administration:
May be taken with meals to reduce GI side effects. Capsule
may be opened and mixed with sweetened food
products. To prepare 100 mL of 6 mg/mL suspension,
put 7 mL of distilled water into a glass or
polyethyleneterephthalate (PET) bottle then empty
contents of eight 75 mg capsules (= 600 mg) into the
bottle. Swirl the suspension for at least 2 minutes then
slowly add 91 mL of syrup, sweetened condensed milk,
or yogurt. Shake well for 30 minutes. Instruct patient to
shake mixture well before using. Swallow mixture
immediately after preparation.
NOTE: Suspension can remain stable for 5 days at room
temperature or 5 weeks if refrigerated at 2-8 degrees
Centigrade.
Pregnancy Category: C
ATC Code: J05AH02
ANTIVIRALS FOR TREATMENT OF HCV INFECTIONS
Rx DACLATASVIR
Oral: 60 mg tablet
Daclatasvir binds to the N-terminus within Domain 1 of HCV
nonstructural protein 5A (NS5A) and inhibits viral RNA
replication and virion assembly.
Indications: Treatment of hepatitis C genotypes 1, 2, 3, and
4 in combination of sofosbuvir with or without ribavirin.
Contraindications: Concurrent use with strong inducers of
CYP3A4 and P-glycoprotein.
Dose:
Chronic hepatits C genotype 1a or 1b, by mouth, ADULT,
treatment-naïve without cirrhosis: 60 mg once daily with
concomitant sofosbuvir for 12 weeks;
peginterferon/ribavirin-experienced patients without
cirrhosis: 60 mg once daily with concomitant sofosbuvir
for 12 weeks; decompensated cirrhosis: 60 mg once
ANTI-INFECTIVES FOR SYSTEMIC USE

daily with concomitant sofosbuvir and ribavirin for 12 Etoposide, Everolimus, Fentanyl, Hydrocortisone,
weeks. Idarubicin, Imatinib, Irinotecan, Lansoprazole,
Chronic hepatits C genotype 2, by mouth, ADULT, treatment- Ledipasvir/Sofosbuvir, Levothyroxine, Lidocaine,
naïve without cirrhosis: 60 mg once daily with Loreramide, Loratadine, Methotrexate,
concomitant sofosbuvir for 12 weeks; treatment-naïve Methylprednisolone, Morphine, Nicardipine,
with compensated cirrhosis: 60 mg once daily with Nitrofurantoin, Omeprazole, Ondansetron, Paclitaxel,
concomitant sofosbuvir for 16-24 weeks; Paliperidone, Prednisone, Quinine, Ranitidine, Rifampin,
peginterferon/ribavirin-experienced without cirrhosis: 60 Rifaximin, Risperidone, Rosuvastatin,
mg once daily with concomitant sofosbuvir for 12 weeks; Sacubitril/Valsartan, Sertraline, Simvastatin,
peginterferon/ribavirin-experienced with compensated Tacrolimus, Telmisartan, Tenofovir, Testosterone,
cirrhosis: 60 mg once daily with concomitant sofosbuvir Valsartan, Verapamil, Vinblastine, Vincristine, Warfarin
for 16-24 weeks; patients with decompensated cirrhosis:
60 mg once daily with concomitant sofosbuvir and Increases the level or effect of Daclatasvir:
ribavirin for 12 weeks, and 24 weeks for patients not Ciprofloxacin, Fluconazole, Itraconazole, Verapamil
eligible for ribavirin; liver transplant recipients with or
without cirrhosis: 60 mg once daily with concomitant Increases toxicity of Amiodarone
sofosbuvir and ribavirin for 12 weeks; kidney transplant
recipients with or without compensated cirrhosis: 60 mg Avoid concomitant use with:
once daily with sofosbuvir and ribavirin for 12 weeks. Decreases the level or effect of Daclatasvir:
Carbamazepine, Oxcarbazepine, Phenobarbital,

J
Chronic hepatits C genotype 3, by mouth, ADULT, treatment- Phenytoin, Rifabutin, Rifampin, Dexamethasone,
naïve without cirrhosis: 60 mg once daily with Efavirenz
concomitant sofosbuvir for 12 weeks; treatment-naïve
with compensated cirrhosis: 60 mg once daily with Increases the level or effect of Daclatasvir:
concomitant sofosbuvir with or without ribavirin, for 24 Clarithromycin, Colchicine, Imatinib, Isoniazid,
weeks; peginterferon/ribavirin-experienced without Ketoconazole, Nicardipine, Voriconazole
cirrhosis: 60 mg once daily with concomitant sofosbuvir
for 12 weeks; patients with decompensated cirrhosis: 60 Increases the level or effect of Sofosbuvir
mg once daily with concomitant sofosbuvir and ribavirin
for 12 weeks, and 24 weeks for patients not eligible for Administration: May be taken with or without food.
ribavirin; liver transplant recipients with or without
cirrhosis: 60 mg once daily with concomitant sofosbuvir Pregnancy Category: C
and ribavirin for 12 weeks; kidney transplant recipients
with or without compensated cirrhosis: 60 mg once daily ATC Code: J05AP07
with sofosbuvir and ribavirin for 12 weeks.
Chronic hepatits C genotype 4, by mouth, ADULT, patients
with decompensated cirrhosis: 60 mg once daily with
concomitant sofosbuvir and ribavirin for 12 weeks, and Rx RIBAVIRIN
24 weeks for patients not eligible for ribavirin; liver
transplant recipients with or without cirrhosis: 60 mg Oral: 200 mg, 500 mg and 600 mg tablet
once daily with concomitant sofosbuvir and ribavirin for
12 weeks; kidney transplant recipients with or without Although not completely understood, Ribarivin appears to
compensated cirrhosis: 60 mg once daily with sofosbuvir interfere with RNA and DNA synthesis and subsequently
and ribavirin for 12 weeks. inhibit protein synthesis and viral replication.

Dose Adjustment: Indication: Treatment of chronic hepatitis C (HCV)

Renal and Hepatic impairment:
No dosage adjustment necessary.
Precautions:
May cause bradycardia; use in caution patients with
cardiovascular disease, hepatic disease, hepatitis B
virus reactivation; not to be used as monotherapy, use
only in combination with other antihepatitis C virus drugs.
Adverse Drug Reactions:
Common: Fatigue, headache, nausea, and anemia.
Less Common: Drowsiness, insomnia, skin rash, diarrhea
Rare: Reactivation of hepatitis B virus.
Drug Interactions:
Monitor closely with:
Increased level or effect due to Daclatasvir:
Atorvastatin, Azithromycin, Budesonide, Carvedilol,
Cetirizine, Ciprofloxacin, Cyclosporine, Dexamethasone,
Digoxin, Diltiazem, Docetaxel, Doxorubicin, Erythromycin,
Contraindications: Women who are or may become
pregnant; male partners of pregnant women,
autoimmune hepatitis, hemoglobinopathies; creatinine
clearance <50 mL/minute.
Dose:
Chronic HCV infection, in combination with peg-interferon
alfa-2a, by mouth, ADULT, genotype 1, 4, HIV-free: <75
kg, 1000 mg daily, divided into 2 doses x 48 weeks, ≥75
kg, 1200 mg daily, divided into 2 doses x 48 weeks;
genotype 2/3, HIV-free: 800 mg daily divided into 2
doses x 24 weeks; HIV-HCV co-infection: 800 mg daily,
divided into 2 doses plus peg-interferon alfa-2a 180 mcg
SC every week x 24 weeks; CHILD 5-17 years old, 15
mg/kg divided into 2 doses with weekly SC peg-
interferon alfa-2a.
Dose Adjustment:
Renal impairment:
CrCl ≥50 mL/min: dose adjustment not necessary.

277

CrCl <50 mL/min: use is contraindicated.
Hepatic impairment:
Avoid use in decompensated hepatic disease;
contraindicated in HCV-HIV co-infected patients with
cirrhosis and baseline Child-Pugh score ≥6.
Precautions:
HCV treatment regimens (Do not use ribavirin alone for
treatment of chronic HCV infection);
Fetal/neonatal morbidity and mortality (Teratogenic and/or
embroyocidal. Exercise extreme care to avoid pregnancy
in female patients and in female partners of male
patients);
Hematologic effects (Hemolytic anemia reported in patients
receiving oral ribavirin in conjunction with interferon alfa;
anemia usually occurs 1-2 weeks after initiation of
therapy);
Cardiovascular effects (Fatal and nonfatal MI reported in
patients with anemia due to oral ribavirin.);
J
Hepatic failure (Patients with chronic HCV infection and
cirrhosis may be at risk of hepatic decompensation and
death during interferon alfa therapy);
Pancreatitis (Temporarily interrupt oral ribavirin in patients
with manifestations of pancreatitis.);
Dental and periodontal disorders;
Pregnancy (Take extreme care to avoid pregnancy).
Adverse Drug Reactions:
Common: Fatigue, headache, hemolysis, myalgia, nausea,
rigors, fever, insomnia, depression, decreased Hgb,
hyperbilirubinemia, arthralgia, alopecia, irritability,
musculoskeletal pain, rash, anorexia, dizziness, pruritus,
flu-like syndrome, dyspnea, nasal congestion, dyspepsia,
impaired concentration, thrombocytopenia, sinusitis,
vomiting, emotional liability, and decreased WBC.
Less Common: Hemolytic anemia, weakness, chest pain,
taste perversion, and nervousness.
Rare: Dehydration, hearing impairment, hearing loss, retinal
detachment, pure red cell aplasia, serious skin
reactions, liver and renal graft rejection, homicidal
ideation, and growth inhibition in pediatric patients.
Drug Interactions:
Monitor closely with:
Increases toxicity of the following drugs:
Lamivudine, Tobramycin (Inhalation)
Avoid concomitant use with:
Increases toxicity of Abacavir
Decreases effects of Zidovudine
Administration: Take tablet with food. Do not crush or break
tablet.
Pregnancy Category: X
ATC Code: J05AP01
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ANTI-INFECTIVES FOR SYSTEMIC USE
Rx SOFOSBUVIR
Oral: 400 mg tablet
Sofosbuvir inhibits HCV NS5B RNA-dependent RNA
polymerase, essential for viral replication, and acts as a
chain terminator.
Indications: Treatment of hepatitis C genotypes 1, 2, 3, 4, 5,
and 6 in combination with other direct acting antivirals.
Contraindications: Hypersensitivity to sofosbuvir or any
component of the formulation; males whose female
partners may become pregnant.
Dose:
Hepatitis C genotype 1, by mouth, ADULT, treatment-naïve
or peginterferon + ribavirin treatment-experienced
without cirrhosis: 400 mg once daily in combination with
simeprevir or daclatasvir for 12 weeks; patients with
decompensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
liver transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin or simeprevir
with or without ribavirin for 12 weeks.
Hepatitis C genotype 2, by mouth, ADULT, treatment-naïve
or peginterferon + ribavirin treatment-experienced
patients: 400 mg once daily in combination with
daclatasvir for 12 weeks (without cirrhosis) or 16-24
weeks (with compensated cirrhosis); patients with
decompensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
liver transplant recipients with or without cirrhosis,
including decompensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
renal transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks.
Hepatitis C genotype 3, by mouth, ADULT, treatment-naïve
or peginterferon + ribavirin treatment-experienced
without cirrhosis: 400 mg once daily in combination with
daclatasvir for 12 weeks; treatment-naïve patients with
compensated cirrhosis: 400 mg once daily in
combination with daclatasvir with or without ribavirin for
24 weeks; patients with decompensated cirrhosis: 400
mg once daily in combination with daclatasvir and
ribavirin for 12 weeks; liver transplant recipients with or
without cirrhosis, including decompensated cirrhosis:
400 mg once daily, in combination with daclatasvir and
for 12 weeks; renal transplant recipients without
cirrhosis or with compensated cirrhosis: 400 mg once
daily in combination with daclatasvir and ribavirin for 12
weeks.
Hepatitis C genotype 4, by mouth, ADULT, patients with
decompensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
liver transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily, in
combination with daclatasvir and ribavirin or simeprevir
with or without ribavirin for 12 weeks.
Hepatitis C genotype 5 and 6, by mouth, ADULT, liver
transplant recipients without cirrhosis or with
compensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks;
renal transplant recipients without cirrhosis or with
ANTI-INFECTIVES FOR SYSTEMIC USE

compensated cirrhosis: 400 mg once daily in
combination with daclatasvir and ribavirin for 12 weeks.
Dose Adjustment:
Renal impairment:
No dosage adjustments provided in the manufacturer’s
labeling.
Hepatic impairment:
No dosage adjustment necessary.
Precautions:
Hepatitis B virus reactivation has been reported in HBsAg
positive patients and in patients with serologic evidence
of resolved HBV infection.
Adverse Drug Reactions:
Common: Fatigue, headache, insomnia, chills, irritability,
pruritus, skin rash, nausea, decreased appetite,
diarrhea, anemia, neutropenia, asthenia, myalgia, flu-
Hepatitis C genotype 1, by mouth, ADULT, treatment-naïve
patients without cirrhosis or with compensated cirrhosis
or peginterferon/ribavirin treatment-experienced
patients without cirrhosis: one tablet once daily for 12
weeks; peginterferon/ribavirin treatment-experienced
patients with compensated cirrhosis: one tablet once
daily with concomitant ribavirin for 12weeks; NS3
protease inhibitor + peginterferon/ribavirin treatment-
experienced patients: without cirrhosis, one tablet once
daily for 12 weeks, with compensated cirrhosis, one
tablet once daily with concomitant ribavirin for 12 weeks;
non-NS5A inhibitor, sofosbuvir containing regimen-
experienced patients without cirrhosis: one tablet once
daily with concomitant ribavirin for 12 weeks;
decompensated cirrhosis: one tablet once daily with
concomitant ribavirin for 12 weeks, 24 weeks if ribavirin-
ineligible; decompensated cirrhosis in patients with
sofosbuvir or NS5A-based treatment failure: one tablet
once daily with concomitant ribavirin for 24 weeks; liver
transplant recipients with or without cirrhosis: one tablet

J
like symptoms, and fever. once daily with concomitant ribavirin for 12 weeks;
Less Common: Thrombocytopenia kidney transplant recipients without cirrhosis or with
Rare: Angioedema, bradycardia, pancytopenia, reactivation compensated cirrhosis: one tablet once daily for 12
of HBV, severe depression, and suicidal ideation. weeks.
Hepatitis C genotype 4, by mouth, ADULT, treatment-naïve
Drug Interactions: patients without cirrhosis or with compensated cirrhosis
Monitor closely with: and peginterferon/ribavirin treatment-experienced
Increases the level or effect of Tenofovir: patients without cirrhosis: one tablet once daily for 12
Sofosbuvir weeks; peginterferon/ribavirin treatment-experienced
patients with compensated cirrhosis: one tablet once
Increases toxicity of Warfarin daily with concomitant ribavirin for 12weeks;
decompensated cirrhosis: one tablet once daily with
Avoid concomitant use with: concomitant ribavirin for 12 weeks, 24 weeks if ribavirin-
Decreases the level or effect of Sofosbuvir: ineligible; decompensated cirrhosis in patients with
Carbamazepine, Oxacarbazepine, Phenobarbital, sofosbuvir or NS5A-based treatment failure: one tablet
Phenytoin, Rifabutin, Rifampin. once daily with concomitant ribavirin for 24 weeks; liver
transplant recipients with or without cirrhosis: one tablet
Increases toxicity of Amiodarone once daily with concomitant ribavirin for 12 weeks;
kidney transplant recipients without cirrhosis or with
Increases the level or effect of Sofosbuvir: compensated cirrhosis: one tablet once daily for 12
Daclatasvir weeks.
Hepatitis C genotype 5 or 6, by mouth, ADULT, treatment-
Administration: Administer with or without food. naïve and peginterferon/ribavirin treatment-experienced
patients without cirrhosis or with compensated cirrhosis:
Pregnancy Category: B one tablet once daily for 12 weeks; decompensated
cirrhosis: one tablet once daily with concomitant ribavirin
ATC Code: J05AP08 for 12 weeks, 24 weeks if ribavirin-ineligible;
decompensated cirrhosis in patients with sofosbuvir or
NS5A-based treatment failure: one tablet once daily with
concomitant ribavirin for 24 weeks; liver transplant
Rx SOFOSBUVIR + LEDIPASVIR recipients with or without cirrhosis: one tablet once daily
with concomitant ribavirin for 12 weeks.
Oral: 400 mg sofosbuvir + 90 mg ledipasvir tablet
Dose Adjustment:
Ledipasvir inhibits the HCV NS5A protein necessary for viral Renal impairment:
replication; sofosbuvir inhibits NS5B RNA-dependent No dosage adjustments provided in the manufacturer’s
RNA polymerase essential for viral replication, and acts labeling.
as a chain terminator.
Hepatic impairment:
Indications: For the treatment of hepatitis C genotypes 1, 4, No dosage adjustment necessary.
5, and 6.
Precautions:
Contraindications: Hypersensitivity to any component of the Hepatitis B virus reactivation has been reported in HBsAg
formulation. positive patients and in patients with serologic evidence
of resolved HBV infection.
Dose:

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 ANTI-INFECTIVES FOR SYSTEMIC USE

Adverse Drug Reactions:

Common: Headache, fatigue, and weakness. Decreases levels/effects of Sofosbuvri/Velpatasvir:
Less Common: Irritability, insomnia, dizziness, depression, Aspirin, Antacids
nausea, diarrhea, hyperbilirubinemia, myalgia, increased
creatine phosphokinase, cough, and dyspnea. Avoid concomitant use with:
Rare: Angioedema, reactivation of HBV, and skin rash. Increases toxicity of Amiodarone

Drug Interactions: Decreases leves/effects of Sofosbuvir/Velpatasvir:

Monitor closely with: Carbamazepine, Colchicine, Dexamethasone,
Increased toxicity due to Sofosbuvir/Ledipasvir: Doxorubicin, Efavirenz, Lansoprazole, Nevirapine,
Amiodarone, Warfarin Omeprazole, Oxcarbazepine, Phenobarbital, Phenytoin,
Avoid concomitant use with: Rifabutin, Rifampin, Vinblastine.
Increases the level/ effect of Colchicine
Administration: Administer with or without food.
Decreases levels of Sofosbuvir/Ledipasvir:
Carbamazepine, Oxcarbamazepine, Phenobarbital, Pregnancy Category: B
Phenytoin, Rifabutin, And Rifampin
ATC Code: J05AP55
Administration: Administer with or without food.
J

Pregnancy Category: B
IMMUNE SERA AND
ATC Code: J05AP51 IMMUNOGLOBULINS

IMMUNE SERA
Rx SOFOSBUVIR + VELPATASVIR
Rx ANTI-RABIES SERUM (EQUINE)
Oral: 400 mg sofosbuvir + 100 mg velpatasvir tablet

Velpatasvir inhibits the HCV NS5A protein necessary for viral Inj.: 200 IU/mL, 5 mL vial (IM)
replication while sofosbuvir inhibits NS5B RNA- 400 IU/mL, 5 mL vial (IM)
dependent RNA polymerase and acts as a chain
terminator. Indications: For the seroprophylaxis of rabies in individuals
who are suspected to have been exposed to the rabies
Indications: Treatment of chronic hepatitis C genotypes 1, virus, when rabies immunoglobulin (human) is
2, 3, 4, 5, and 6. unavailable or unaffordable.

Contraindications: Hypersensitivity to sofosbuvir, NOTE: The lethal risk associated with rabies overcomes any
velpatasvir, or any component of the formulation. potential.

Dose: Dose:
Chronic hepatitis C genotypes 1, 2, 3, 4, 5, and 6, by mouth, Prophylaxis of rabies from suspected individuals, by
ADULT, 400/100 mg tablet once daily. filtration, ADULT and CHILD, 40 IU/kg of body weight in
and around the cleansed wound; if infiltration of whole
Dose Adjustment: volume is not possible, give the remainder by IM injection
Renal and Hepatic impairment: slowly (wounds in certain anatomical sites, such as
No dosage adjustment required. fingertips, should be infiltrated with care to prevent a
local increase in pressure in the tissue).
Precautions:
May cause hepatitis B reactivation. NOTE: When the volume required to infiltrate the wound(s)
exceeds the recommended dose, some clinicians
Adverse Drug Reactions: recommend diluting the calculated dose in saline to yield
Common: Headache, and fatigue. a two- to threefold increase in solution volume to ensure
Less Common: Irritability, insomnia, depression, skin rash, that all wound areas receive adequate infiltration.
nausea, weakness
Rare: Reactivation of hepatitis B virus and angioedema. Precautions:
Do NOT administer intravenously; ensure that the needle
Drug Interactions: has not penetrated a blood vessel; do not give repeated
Monitor closely with: doses once rabies vaccine is given as this may reduce
Increases level/effect of the following drugs: the immunologic response to the vaccine; despite the
Alprazolam, Atorvastatin, Clonidine, Colchicine, high degree of purification of the serum, it is
Diazepam, Digoxin, Doxorubicin, Enalapril, Ergotamine, recommended to perform a skin test before
Everolimus, Fentanyl, Imatinib, Irinotecan, Methotrexate, administering rabies antiserum; if the recommended
Midazolam, Mitoxantrone, Nitrofurantoin, Rosuvastatin, dosage is not strictly observed (i.e. overdosage), there is
Simvastatin, Tacrolimus, Valsartan, Warfarin.

280
ANTI-INFECTIVES FOR SYSTEMIC USE
a risk of immunosuppressive interference with rabies
vaccine
In patients with a history of bleeding disorders, including
thrombocytopenia, and patients on anticoagulant
therapy.
NOTE: Immunoglobulins may interfere with the immune
response to live virus vaccines.
Adverse Drug Reactions:
Common: Acute febrile reaction, injection site swelling and
pain, serum sickness-like reactions.
Rare: Anaphylaxis.
Drug Interactions:
Reduces therapeutic effect of Anti-rabies Serum:
Corticosteroids, Vaccines (Live, attenuated, virus)
Administration:
Administer as soon as possible, at the same time as the
rabies vaccine, or up to 7 days after vaccine injection;
the remaining serum should be administered via the IM
route (into the gluteal region) in a single injection.
NOTE: Vaccines should be stored within the safe
temperature range of 2-8°C. Freezing is the most
common cause of vaccine damage; do not use a
defrosted vaccine unless freezing is the recommended
storage condition.
Pregnancy Category: C
ATC Code: J06AA06
ANTI-TETANUS SERUM
Rx
(EQUINE)
Inj.: 4,000 IU/mL, 2.5 mL vial (IM)
1,500 IU/0.7 mL solution for injection, vial/ampule
(IM)
1,500 IU/mL, 1 mL and 1.5 mL vial/ampule (IM)
Indications: Prophylaxis against tetanus in non-immune
individuals after serious injury or bite when tetanus
immunoglobulin (human) is unavailable or unaffordable;
treatment of tetanus when tetanus immunoglobulin is
unavailable or unaffordable.
Contraindications: Known Hypersensitivity to tetanus
antitoxin or any other component within the serum, and
any product prepared from horse serum.
Dose:
Post-exposure prophylaxis against tetanus, by IM injection,
3,000-5,000 IU.
Treatment of tetanus infection, by IM injection, ADULT and
CHILD, 50,000-100,000 IU single dose; NEONATE, 500
UNITS/KG OR 5,000-10,000 IU in tetanus neonatorum.
NOTE: The above doses could be given ½ IV and the rest IM
after appropriate testing for sensitivity and
desensitization, if necessary.
Precautions:
WARNING: Increased risk of fatal prophylaxis in
hypertensive individuals.
Informed consent and skin test are required (a negative skin
or eye test is not an absolute indication of the absence
of sensitivity), a syringe with 0.3 mL of 1:1000 aqueous
solution of epinephrine should be always at hand.
NOTE: Immunoglobulins may interfere with the immune
response of live virus vaccines which should normally be
given either at least 3 weeks before or at 3 months after
administration of an immunoglobulin.
Adverse Drug Reactions:
Common: Acute febrile reaction, injection site swelling and
pain, serum sickness-like reactions.
Rare: Anaphylaxis.
Drug Interactions:
J
Avoid concomitant use with:
Reduces therapeutic effect of Anti-Tetanus Serum:
Vaccines (Live, attenuated, virus)
Administration:
The serum should be administered via the IM route. If a
large volume is required, it is recommended to
administer the serum in divided doses at different sites.
NOTE: Vaccines should be stored within the safe
temperature range of 2-8°C. Freezing is the most
common cause of vaccine damage; do not use a
defrosted vaccine unless freezing is the recommended
storage condition.
Pregnancy Category: C
ATC Code: J06AA02
Rx COBRA ANTIVENIN
Inj.: 800 MU/4.8 mL, 1 mL ampule (IV infusion)
800 IU/mL, 5 ml ampule (IV infusion)
Indications: Management of patients with Naja spp.
Envenomations (i.e., N. philippinensis, N. samarensis
and N. sumatrana), signs of neurotoxicity or swelling
involving more than half the bitten extremity.
Contraindications: Allergy to horse-based products, or
antivenin by history or because of an appropriate
sensitivity test; hypersensitivity to any component of the
formulation, including papaya or papain; cross
allergenicity with dust mite and latex allergens.
Dose:
Naja spp. envenomations, by IM injection, ADULT and
CHILD, usual dose is 0.5 mL, severe cases: initial dose of
5-10 vials IV and repeated every 1-2 hours until local
manifestations, coagulation tests, and systemic signs
are observed to be normal. The antivenin can be diluted
in 500 mL isotonic fluid to run for 1-2 hours, or given
undiluted IV over 10-15 minutes.
281

NOTE: Begin infusion slowly, watching carefully for adverse
effects. Stop the infusion temporarily if these occur. If
there is no adverse reaction, increase the rate, aiming to
give the entire infusion over about 15-20 minutes.
Precautions:
WARNING: Antivenins should never be administered
prophylactically to asymptomatic patients. Pain and
fang marks are not intrinsically signs of envenomation.
Patients sensitive to antivenin or horse serum may develop
anaphylaxis. Prior to IV or IM antivenin administration,
proper skin test should be performed and interpreted
(therapy may be modified if indicated); in life threatening
situations, pre-treat with antihistamine
(diphenhydramine, 50-100 mg IV), followed by slow IV
infusion of very dilute antivenin. At the first sign of
hypersensitivity reaction, stop infusion and administer
subcutaneously 0.5-1.0 mL epinephrine (1:1000), pre-
existing renal, hepatic, cardiac, or respiratory treatment
J
with anticoagulant or antiplatelet drugs (increased risk
of serious outcomes, including death from snakebite),
the elderly (may require more vigorous treatment),
children (should not be given weight-adjusted doses, the
amount required depends on the amount of venom to be
neutralized).
STORAGE: Cold-chain management in hospitals.
Adverse Drug Reactions:
Common: Anaphylaxis or anaphylactoid reactions, chest
discomfort, chills, dizziness, dyspnea, edema of the face,
tongue, and throat, fever, flushing, headache,
hypotension, pruritus, rash, serum sickness, tachypnea,
urticaria.
Less Common: Abdominal pain, angioedema, arthralgia,
bradycardia, bronchospasm, collapse, myalgia, nausea,
neurological impairment, pain at the infusion site,
sweating, tachycardia, vertigo, vomiting, wheezing.
Rare: Cardiac arrest
Administration:
The treatment should begin as soon as possible and
preferably within 4-6 hours of envenomation; monitor for
1 hour following the infusion.
Pregnancy Category: C
ATC Code: J06AA03
Rx DIPHTHERIA ANTITOXIN
Inj.: 10,000 IU and 20,000 IU, 5 mL and 10 mL (IV)
Indications: Treatment of probable or confirmed diphtheria,
recommended in exceptional circumstances for post-
exposure prophylaxis in individuals with known or
suspected exposure to toxigenic Corynbacteria.
Contraindications: Hypersensitivity to immune globulin or
any component of the formulation.
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ANTI-INFECTIVES FOR SYSTEMIC USE
Dose:
Pharyngeal or laryngeal disease, by IV or IM injection, ADULT
and CHILD, 20,000-40,000 units for 448 hours duration.
Nasopharyngeal disease, by IV or IM injection, ADULT and
CHILD, 40,000-60,000 units for 448 hours duration.
Precautions:
Regardless of allergic history or history of prior
administration of preparations containing equine serum,
sensitivity testing must be performed in all individuals
prior to administration of diphtheria antitoxin; Patients
should be carefully monitored for evidence of
hypotension and bronchoconstriction during sensitivity
testing and desensitization to diphtheria antitoxin and
during administration of the antitoxin.
Adverse Drug Reactions:
Common: Anaphylaxis or anaphylactoid reactions, chest
discomfort, chills, dizziness, dyspnea, edema of the face,
tongue, and throat, fever, flushing, headache,
hypotension, pruritus, rash, serum sickness, tachypnea,
urticaria.
Less Common: Abdominal pain, angioedema, arthralgia,
bradycardia, bronchospasm, collapse, myalgia, nausea,
neurological impairment, pain at the infusion site,
sweating, tachycardia, vertigo, vomiting, wheezing.
Rare: Cardiac arrest
Administration: A test dose of diluted diphtheria antitoxin
should be given intradermally to exclude hypersensitivity.
STORAGE: It should be stored at 2-8°C and not be allowed
to freeze.
Pregnancy Category: C
ATC Code: J06AA01
IMMUNOGLOBULINS
IMMUNOGLOBULINS, NORMAL HUMAN
IMMUNOGLOBULIN NORMAL,
Rx
HUMAN IM (IGIM)
Inj.: 160 mg/mL, 2 mL, 5 mL, and 10 mL vial (IM)
Indications: Provide passive immunity in susceptible
individuals under the following circumstances:
Hepatitis A: Within 14 days of exposure and prior to
manifestation of disease;
Measles: For use within 6 days of exposure in an
unvaccinated person, who has not previously had
measles.
Varicella: When varicella zoster immune globulin is not
available.
Rubella: Post-exposure prophylaxis (within 72 hours)
Contraindications: IgA deficiency; severe thrombocytopenia
or coagulation disorders where IM injections are
contraindicated.
Dose:
ANTI-INFECTIVES FOR SYSTEMIC USE

Hepatitis A, by IM injection, ADULT and CHILD, Pre-exposure IMMUNOGLOBULIN NORMAL,

prophylaxis upon travel into endemic areas (hepatitis A Rx
HUMAN IV (IGIV)
vaccine preferred):
0.02mL/kg for anticipated risk of exposure <3 months,
Inj.: 50 mg/mL, 10 mL, 20 mL, 50 mL, 100 mL, and 200
0.06mL/kg for anticipated risk of exposure ≥3 months,
mL vial (IV)
repeat approximate dose every 5 months if exposure
1 g/bottle freeze-dried powder + 33 mL and 50 mL
continues;
reconstitution fluid (IV)
Post-exposure prophylaxis: 0.02mL/kg/dose given
2.5 g/bottle freeze-dried powder + 100 mL
within 14 days of exposure. IG is not needed of at least
reconstitution fluid (IV)
1 dose of hepatitis A, vaccine was given at ≥1 month
5 g/bottle freeze-dried powder + 100 mL diluent vial
before exposure.
(IV)
Measles, by IM injection, ADULT and CHILD, Prophylaxis,
10 g/bottle freeze-dried powder + 260 mL diluent vial
immunocompetent: 0.25mL/kg (maximum dose: 15mL)
(IV)
given within 6 days of exposure followed by live
attenuated measles vaccine in 5-6 months when
Indications: Treatment of primary immunodeficiency
indicated;
syndromes, chronic inflammatory demyelinating
Prophylaxis, immunocompromised: 0.5mL/kg
polyneuropathy (CIDP) and immune (idiopathic)
(maximum dose: 15mL) immediately following exposure.
thrombocytopenic purpura (ITP) and Kawasaki disease.
Rubella, by IM injection, ADULT and CHILD, Prophylaxis
Prevention of bacterial infection in B-cell chronic
during pregnancy: 0.55mL/kg/dose within 72 hours of
lymphocytic leukemia (CLL).

J
exposure.
Varicella, by IM injection, ADULT and CHILD, Prophylaxis:
Contraindications: Hypersensitivity to immune globulin or
0.6-1.2mL/kg (varicella zoster immune globulin
any component of the formulation; selective IgA
preferred) within 72 hours of exposure.
deficiency; hyperprolinemia.
IgG deficiency, by IM injection, ADULT and CHILD,
0.66mL/kg/dose every 3-4 weeks. A double dose may be
Dose:
given at onset of therapy; some patients may require
Prevention of HIV infection, by IV infusion, CHILD, 400
more frequent injections.
mg/kg every 2-4 weeks.
Primary immunodeficiency disorder, by IV infusion, ADULT
Precautions:
and CHILD, 200-800mg/kg per month.
Hypersensitivity and anaphylactic reactions can occur;
B-cell chronic lymphocytic leukemia (CLL), by IV infusion,
immediate treatment (including epinephrine 1:1000)
ADULT and CHILD, 400mg/kg/dose every 3-4 weeks.
should be available;
Immune (idiopathic) thrombocytopenic purpura (ITP), acute,
Product of human plasma; may potentially contain
by IV infusion, ADULT and CHILD, 400mg/kg/day for 2-5
infectious agents which could transmit disease;
days;
Screening of donors, as well as testing and/or inactivation
Chronic, by IV infusion, ADULT and CHILD, 400mg/kg as
or removal of certain viruses, reduces the risk; Skin
needed to maintain platelet count ≥30,000/mm3 or to
testing should not be performed as local irritation can
control significant bleeding; may increase dose if needed
occur and be misinterpreted as a positive reaction.
(range: 800-1000mg/kg).
Chronic inflammatory demyelinating polyneuropathy (CIDP),
Adverse Drug Reactions:
by IV infusion, ADULT and CHILD, Loading dose:
Flushing, angioedema, chills, lethargy, fever, urticaria,
2000mg/kg divided over 2-4 consecutive days;
erythema, nausea, vomiting, tenderness, muscle
Maintenance 1000mg/kg/day for 1 day every 3 weeks
stiffness at IM site, myalgia, hypersensitivity reactions.
or 500mg/kg/day for 2 consecutive days every 3 weeks.
Kawasaki disease, by IV infusion, ADULT and CHILD, initiate
Drug Interactions:
IVIG therapy within 10 days of disease onset; must be
Avoid concomitant use with:
used in combination with aspirin, 80-100mg/kg/day in 4
Reduces therapeutic effects of the following drugs:
divided doses for 14 days; when fever subsides, dose
Live vaccines (except: influenza virus vaccine
aspirin at 3-5mg/kg once daily for ≥6-8 weeks.
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
Hematopoietic stem cell transplantation with
zoster vaccine
hypogammaglobulinemia, by IV infusion, CHILD,
400mg/kg per month; increase dose or frequency to
Administration:
maintain IgG levels >400mg/dL; ADULT,
NOT for IV administration.
500mg/kg/week.
Administer IM in the anterolateral aspects of the upper thigh
or deltoid muscle of the upper arm. Avoid gluteal region
Precautions:
due to risk of injury to sciatic nerve; use upper outer
quadrant only. Divide doses >10mL. WARNING: Acute renal dysfunction (increased serum
creatinine, oliguria, acute renal failure, osmotic
Pregnancy Category: C nephrosis) can rarely occur usually within 7 days of
use (more likely with products stabilized with
ATC Code: J06BA01 sucrose). Use with caution in the elderly, patients
with renal disease, diabetes mellitus, volume
depletion, sepsis, paraproteinemia, and nephrotoxic
medications due to risk of renal dysfunction.

283

In patients at risk of renal dysfunction, the rate of infusion
and concentration of solution should be minimized.
Discontinue of renal function deteriorates;
High dose regimens (1000mg/kg for 1-2 days) are not
recommended for individuals with fluid overload or
where fluid volume may be of concern;
Hypersensitivity and anaphylactic reactions can occur,
immediate treatment (including epinephrine 1:1000)
should be available;
Product of human plasma; may potentially contain
infectious agents which could transmit disease.
Adverse Drug Reactions:
Chest tightness, edema, flushing of the face, hypertension,
hypotension, palpitation, tachycardia, anxiety, aseptic
meningitis syndrome, chills, dizziness, drowsiness,
fatigue, fever, headache, irritability, lethargy,
lightheadedness, malaise, migraine, pain, bruising,
petechiae, pruritus, purpura, rash, urticaria, abdominal
cramps, abdominal pain, diarrhea, discomfort,
J
dyspepsia, nausea, sore throat, vomiting, anemia,
autoimmune hemolytic anemia, hemolysis (mild),
hemorrhage, thrombocytopenia, bilirubin increased, pain
or irritation at the infusion site, autoimmune pure red cell
aplasia.
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine
Administration:
IV infusion over 2-24 hours; for initial treatment, a lower
concentration and/or a slower rate of infusion should be
used. Administer in separate infusion line from other
medications; if using primary line, flush with saline prior
administration. Refrigerated product should be warmed
to room temperature prior to infusion. Some products
require filtration; refer to individual product labeling.
Antecubital veins should be used, especially with
concentrations ≥10% to prevent injection site
discomfort. Decrease dose, rate and/or concentration of
infusion in patients who may be at risk of renal failure.
Decreasing the rate or stopping the infusion may help
relieve some adverse effects (flushing, changes in pulse
rate, changes in blood pressure). Epinephrine should be
available during administration.
Pregnancy Category: C
ATC Code: J06BA02
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ANTI-INFECTIVES FOR SYSTEMIC USE
SPECIFIC IMMUNOGLOBULINS
HEPATITIS B
Rx
IMMUNOGLOBULIN (HUMAN)
Inj.: 0.5 mL, 1 mL, and 2 mL vial (IM)
Indications: Passive prophylactic immunity to hepatitis B
following: Acute exposure to blood containing hepatitis B
surface antigen (HBsAg); perinatal exposure of infants
born to HBsAg-positive mothers; sexual exposure to
HBsAg-positive persons; household exposure to persons
with acute HBV infection. Prevention of hepatitis B virus
recurrence after liver transplantation in HBsAg-positive
transplant patients.
Contraindications: Hypersensitivity to hepatitis B immune
globulin or any component of the formulation; severe
allergy to gamma globulin or anti-immunoglobulin
therapies.
Dose:
Post-exposure prophylaxis, by IM injection, ADULT and
CHILD ≥12 months, 0.06mL/kg as soon as possible after
exposure (i.e. within 24 hours of needlestick, ocular, or
mucosal exposure or within 14 days of sexual exposure);
usual dose: 3-5mL; repeat at 28-30 days after exposure
in non-responders to hepatitis B vaccine or in patients
who refuse vaccination.
Prevention of hepatitis B virus recurrence after liver
transplantation, by IV infusion, ADULT, 20,000 int.
units/dose according to the following schedule:
Anhepatic phase (Initial dose): One dose given with the
liver transplant;
Week 1 post-op: One dose daily for 7 days (days 1-7);
Week 2 post-op: One dose every 2 weeks starting day 14;
Month 4 onwards: One dose monthly starting on month
4.
Dose Adjustment:
Prevention of hepatitis B virus recurrence after liver
transplantation: Adjust dose to reach anti-HBs levels of
500 IU/L within the first week after transplantation. In
patients with surgical bleeding, abdominal fluid drainage
>500mL or those undergoing plasmapheresis,
administer 10,000 IU/dose every 6 hours until target
anti-HBs levels are reached.
Precautions:
Hypersensitivity and anaphylactic reactions can occur;
immediate treatment (including epinephrine 1:1000)
should be available;
Use with caution in patients with previous systemic
hypersensitivity to human immunoglobulins;
Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be
contraindicated;
Use with caution in patients with IgA deficiency;
Product of human plasma; may potentially contain
infectious agents which could transmit disease.
Adverse Drug Reactions:
Tremor and hypotension
ANTI-INFECTIVES FOR SYSTEMIC USE
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine
Administration:
For IM: Post-exposure: Only in anterolateral aspect of upper
thigh and deltoid muscle of upper arm to prevent injury
from injection, care should be taken when giving to
patients with thrombocytopenia or bleeding disorders.
For IV: Administer at 2mL/minute. Decrease infusion to ≤1
mL/minute for patient discomfort or infusion-related
adverse events. Actual volume of infusion is dependent
upon potency labeled on each individual vial.
Pregnancy Category: C
ATC Code: J06BB04
RABIES IMMUNOGLOBULIN
Rx
(HUMAN)
Inj.: 150 IU/mL, 2 mL and 5 mL vial (IM)
150 IU/mL, 2 mL, 5 mL, and 10 mL ampule (IM)
Indications: Part of post-exposure prophylaxis of persons
with rabies exposure who lack a history of pre-exposure
or post-exposure prophylaxis with rabies vaccine or a
recently documented neutralizing antibody response to
previous rabies vaccination.
Dose:
Post-exposure prophylaxis, by IM injection, ADULT and
CHILD, local would infiltration: 20 units/kg in a single
dose, RIG should always be administered as part of
rabies vaccine regimen. If anatomically feasible, the full
rabies immune globulin dose should be infiltrated
around and into the wound/s; remaining volume should
be administered IM at a site distant from the vaccine
administration site.
Precautions:
Hypersensitivity and anaphylactic reactions can occur;
immediate treatment (including epinephrine 1:1000)
should be available;
Use with caution in patients with isolated IgA deficiency or a
history of systemic hypersensitivity to human
immunoglobulins;
Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be
contraindicated;
Product of human plasma; may potentially contain
infectious agents which could transmit disease.
Adverse Drug Reactions:
Fever, headache, malaise, angioedema, rash, urticaria,
soreness at injection site, tenderness, stiffness,
nephrotic syndrome, anaphylaxis.
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine
Administration:
Do not administer IV.
Post-exposure would infiltration: If anatomically feasible,
the full rabies immune globulin dose should be infiltrated
around the wound; remaining volume should be
administered IM in the deltoid muscle of the upper arm
or lateral thigh muscle. The gluteal area should be
avoided to reduce the risk of sciatic nerve damage. Do
not administer rabies vaccine in the same syringe or at
the same administration site as rabies immunoglobulin.
If rabies vaccine was initiated without RIG, RIG may be
administered through the seventh day after the
administration of the first dose of the vaccine.
Administration of RIG is not recommended after the
seventh day post vaccine since an antibody response to
the vaccine is expected during this time period.
J
Pregnancy Category: C
ATC Code: J06BB05
TETANUS IMMUNOGLOBULIN
Rx
(HUMAN)
Inj.: 1,000 IU/mL, 1.5 mL vial (IM)
1,500 IU/mL, 1 mL ampule (IM)
250 IU/mL, 1 mL, 2 mL, and 4 mL ampule (IM)
250 IU/mL, 1 mL pre-filled syringe (IM)
250 units/mL, 1 mL and 2 mL vial (IM)
Indications: Prophylaxis against tetanus following injury in
patients where immunization is not known or certain.
Passive immunization for TIG is recommended for the
following:
Persons with a wound that is not clean or minor and in
whom contraindications to a tetanus-toxoid containing
vaccine exist and they have not completed a primary
series of tetanus toxoid immunization;
Persons who are wounded in bombings or similar mass
casualty events who have penetrating injuries or
nonintact skin exposure and who cannot confirm receipt
of a tetanus booster within the previous 5 years. In case
of shortage, use should be reserved for persons ≥60
years of age.
Dose:
Prophylaxis of tetanus, by IM injection, CHILD <7 years, 4
units/kg; some recommend 250 units to small children;
CHILD ≥7 years and ADULT, 250 units.
Treatment of tetanus, by IM injection, CHILD and ADULT,
500-6000 units; infiltration of part of the dose around
the wound is recommended.
285
 ANTI-INFECTIVES FOR SYSTEMIC USE

Tetanus Prophylaxis in Wound Management mothers do not have evidence of immunity to varicella;
Number of Clean, minor All other hospitalized premature infants born at <28 weeks of
Prior wounds wounds gestation or who weigh 1,000 g at birth, regardless of
Tetanus their mothers' evidence of immunity to varicella. In
Toxoid Td TIG Td TIG pregnant women, for the prevention or reduction in
Doses severity of maternal infection within 4 days of exposure
Unknown or to the varicella zoster virus.
Yes No Yes Yes
<3
≥3 No No No No Contraindications: Severe reaction associated with past
human immune globulin administration; IgA deficiency.
Precautions:
Hypersensitivity and anaphylactic reactions can occur; Dose:
immediate treatment (including epinephrine 1:1000) Prevention or reduction of maternal infection, by IM/IV
should be available; injection, ADULT, 125 int. units/10kg Administer within
Use with caution in patients with isolated IgA deficiency or a 96 hours of exposure.
history of systemic hypersensitivity to human
immunoglobulins; Dose Adjustment:
Use with caution in patients with thrombocytopenia or No dosage adjustments necessary.
coagulation disorders, IM injections may be
contraindicated; Precautions:
J

Product of human plasma; may potentially contain
infectious agents which could transmit disease.
Adverse Drug Reactions:
Temperature increased, angioneurotic edema, pain at
injection site, soreness, tenderness, nephritic syndrome,
anaphylactic shock
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine
Administration:
Do not administer IV.
Administer in the anterolateral aspects of the upper thigh or
the deltoid muscle of the upper arm. Avoid gluteal region
due to risk of injury to sciatic nerve; if gluteal region is
used, administer only in the upper outer quadrant. If
tetanus vaccine and TIG are administered
simultaneously, separate sites should be used for each
injection. When used for the treatment of tetanus,
infiltration of part of the dose around the wound is
recommended.
Pregnancy Category: C
ATC Code: J06BB02
VARICELLA ZOSTER
Rx
IMMUNOGLOBULIN (VZIG)
Inj.: 125 units/1.25 mL vial (IM)
An immune globulin specific for varicella zoster virus.
Hypersensitivity and anaphylactic reactions can occur;
immediate treatment (including epinephrine 1:1000)
should be available;
Use with caution in patients with isolated IgA deficiency or a
history of systemic hypersensitivity to human
immunoglobulins;
Use with caution in patients with thrombocytopenia or
coagulation disorders, IM injections may be
contraindicated;
Product of human plasma, may potentially contain
infectious agents which could transmit disease.
Adverse Drug Reactions:
Common: Headache, injection site pain.
Less Common: Dizziness, fever, pain, chills, fatigue,
flushing, insomnia, rash, dermatitis, erythematous rash,
nausea, dysgeusia, injection site bruising, itching,
tenderness, neck pain, myalgia.
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effects of the following drugs:
Live vaccines (except: influenza virus vaccine
(live/attenuated); rotavirus vaccine; yellow fever vaccine;
zoster vaccine
Administration: Bring to room temperature prior to use.
Should be given as soon as possible following exposure;
efficacy has not been established for use >96 hours
following exposure.
For IM injection, administer into deltoid muscle or
anterolateral aspect of upper thing; avoid gluteal region.
For IV administration, inject over 3-5 minutes.
Pregnancy Category: A
ATC Code: J06BB03

Indications: Post exposure prophylaxis in the following :

immunocompromised patients without evidence of
immunity; newborn infants whose mothers have signs
and symptoms of varicella around the time of delivery
(i.e., 5 days before to 2 days after).; hospitalized
premature infants born at ≥28 weeks of gestation whose

286
ANTI-INFECTIVES FOR SYSTEMIC USE
VACCINES
BACTERIAL VACCINES
Rx BCG VACCINE
Inj.: Freeze-dried power, 100 micrograms/0.1 mL, 1 mL,
1.5 mL and 2 mL vial (ID)
500 microgram/mL vial + 1 mL diluent in ampule (ID),
20 doses
A vaccine prepared from bacillus Calmette-Guerin, an
attenuated strain of Mycobacterium bovis, which
reduces the incidence of meningeal and military TB in
early childhood.
Indication: Active immunization against tuberculosis
Contraindications: Known hypersensitivity to the vaccine or
any of its components; previous TB infection, or
tuberculin reactions >5 mm; HIV infection; significant
fever (give at least 1 month after fever subsides);
patients receiving immunosuppressive therapy; primary
and secondary immune deficiency states; generalized
septic skin conditions; burns; pregnancy.
Dose:
Immunization against tuberculosis, by ID injection, ADULT
and CHILD >12 months 0.1 mL; INFANT up to 12 months,
0.05 mL.
NOTE: Tuberculin test must be done before vaccination
(except in infants <6 months); give vaccine if induration
is <5 mm 48-72 hours after dose of 10 tuberculin units.
Vaccine is preferably given at birth, or any time after
birth; may be given at the same time as other live
vaccines, if not given simultaneously, should be given 4
weeks apart; when given to infants, no need to delay
primary immunizations.
Precautions:
Eczema and scabies;
Patients at high risk for HIV infection.
Pregnancy (first trimester: theoretical risk of congenital
malformations; but the need for vaccination may,
sometimes, outweigh the possible risk to fetus).
Adverse Drug Reactions:
Common: Enlargement of regional lymph nodes, ulcer at
injection site (2–6 weeks after vaccination)
Less Common: Fainting, fever, injection site reactions (pain,
redness, itching, small hard lump that may persist for
some weeks)
Rare: Abscess, allergic reactions including anaphylaxis,
disseminated infection, keloid formation, lymphadenitis,
osteitis
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Other vaccines and immunoglobulins [administer at
least 4 weeks apart]
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
Anti-infectives
Immunosuppressive Agents e.g. Corticosteroids
Antineoplastic (decreases antibody response)
TEST INTERACTION. May suppress response to tuberculin
test if given within 4–6 weeks of vaccination.
Administration: Give by ID injection. Stretch skin between
thumb and finger above the insertion of the deltoid
muscle onto the humerus.
Store at 2-8°C. Freezing is the most common cause of
vaccine damage. Do NOT use a defrosted vaccine unless
freezing is the recommended storage condition.
Pregnancy Category: C
ATC Code: J07AN01
J
Rx DIPHTHERIA-TETANUS TOXOIDS (DT)
Inj.: 30 IU diphtheria toxoid + 40 IU tetanus toxoid per 0.5
mL ampule (IM)
A combination vaccine that promotes active immunity to
diphtheria and tetanus by inducing production of specific
antibodies.
Indication: For primary and booster immunization against
diphtheria and tetanus in infants and children 6 weeks
up to 7 years of age.
NOTE: For less than 10 years old
Contraindication: Hypersensitivity to diphtheria, tetanus
toxoid, or any component of the formulation
Dose:
Primary immunization, by IM injection, CHILD 6 weeks to ≤6
years, 0.5-mL administered as follows:
First 3 doses at 2, 4, and 6 months of age; may be given
as early as 6 weeks of age and repeated every 4–8
weeks;
Fourth dose at ~15 to 18 months of age, but at least 6
months after third dose; may be given as early as 12
months of age, but at least 6 months after third dose and
the fourth dose;
Fifth dose at 4–6 years of age, prior to starting school or
kindergarten; if the fourth dose is given at ≥4 years of
age, fifth dose may be omitted [NOTE: For use when
pertussis-containing vaccine is contraindicated].
Booster immunization, by IM injection, CHILD, refer to
Diphtheria and Tetanus Toxoids and Acellular Pertussis
Vaccine monograph for additional information.
Precautions:
Anaphylactoid or hypersensitivity reactions;
Arthus-type hypersensitivity; syncope (has been reported
with use);
Acute illness;
Bleeding disorders, including thrombocytopenia;
Guillain-Barré syndrome;
287
 ANTI-INFECTIVES FOR SYSTEMIC USE

Altered immunocompetence (may have a reduced response same bleeding risks and treated as those with clotting
to vaccination); factor disorders.
Children (pediatric dosage form (DT) should only be used in
patients 6 weeks to ≤6 years of age; Pregnancy Category: C
Administer Td for children ≥7 years of age; apnea has
occurred following administration in premature infants). ATC Code: J07AM51
Pregnancy (reproduction studies have not been conducted);
Lactation (not known if excreted into breast milk;
inactivated vaccines do not affect the safety of
breast­feeding for the mother or the infant). Rx DIPHTHERIA-TETANUS TOXOID (Td)

Adverse Drug Reactions: Inj.: ≥ 2 IU diphtheria toxoid + ≥ 40 IU tetanus toxoid per

Common: Headache, tiredness, chills, fever, rash, lymph
node swelling, nausea, vomiting, diarrhea, injection site
reactions (pain, erythema, swelling), body ache, muscle
weakness, sore or swollen joints
Less Common: Allergic reactions, anaphylactic reactions,
arthralgia, dizziness, fatigue, injection site reactions
(cellulitis, induration, nodules, warmth),
lymphadenopathy, musculoskeletal stiffness, myalgia,
J
0.5 mL ampule (IM) (For 7 yrs. old and above)
≥ 2 IU diphtheria toxoid + ≥ 40 IU tetanus toxoid per
0.5 mL (IM), multidose vial (10 doses per vial)
A combination vaccine that promotes active immunity to
diphtheria and tetanus by inducing production of specific
antibodies.

pain, pain in extremities, paresthesia, peripheral edema, Indication: Tetanus and diphtheria toxoids adsorbed for
seizure, syncope, weakness adult use

Drug Interactions: NOTE: For 10 years old and above.

Avoid concomitant use with:
Reduces therapeutic effect of Diphtheria-Tetanus Toxoids: Contraindications: Hypersensitivity to diphtheria, tetanus
Belimumab toxoid, or any component of the formulation
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3 Dose:
months after fingolimod discontinuation] Primary immunization, by IM injection, ADULT (NOT
Immunosuppressants [Cytarabine, Liposomal] previously immunized), 2 primary doses of 0.5 mL each,
[administer at least 2 weeks apart; if vaccinated during given at an interval of 8 weeks, then a third (reinforcing)
immunosuppressant therapy, revaccinate at least 3 dose of 0.5 mL 6–8 months later.
months after immunosuppressant discontinuation] Booster immunization, by IM injection, ADULT (with
Meningococcal Polysaccharide (Groups A / C / Y and complete primary immunization series), 0.5 mL every 10
W­135) Tetanus Toxoid Conjugate Vaccine [administer years; CHILD 11–12 years, 0.5 mL as a single dose when
the meningococcal polysaccharide (groups A / C / Y and at least 5 years have elapsed since last dose of toxoid-
W135) tetanus toxoid conjugate vaccine either together containing vaccine; subsequent routine doses are not
with or at least one month before a tetanus toxoids- recommended more often than every 10 years [NOTE: If
containing vaccine] Tdap is given as part of catch­up dosing at 7–10 years of
age, the 11–12 year booster is not needed; regular Td
Administration: For IM administration only. Administer into booster immunizations should begin 10 years after the
the anterolateral aspect of the thigh or the deltoid last dose of the primary series].
muscle. Do NOT inject in the gluteal area. Do NOT inject Tetanus prophylaxis in wound management should be
by IV or SC. based on if the status of the wound (clean or
contaminated) and the immunization status of the
Shake suspension well before use. Do NOT mix with patient. Wound management includes proper use of
other vaccines or injections. Use different needles and tetanus toxoid and/or tetanus immune globulin (TIG),
syringes for each injection. wound cleaning, and (if required) surgical debridement
and the proper use of antibiotics.
Administer while patient is seated or lying down to
prevent syncope related injuries. History of Clean, Minor
All Other Wounds
Tetanus Wounds
NOTE: For patients at risk of hemorrhage following IM Immuniza Tetanu
injection, administer by IM only if, in the opinion of the Tetanus
tion TIG s TIG
physician familiar with the patient's bleeding risk, the Doses Toxoid
Toxoid
vaccine can be administered by this route with
Uncertain
reasonable safety. Use a fine needle (23 gauge or
or <3 Yes No Yes Yes
smaller) and apply firm pressure to the site (without
doses
rubbing) for at least 2 minutes.
No
If the patient receives anti-hemophilia or other similar Yes if No
therapy, intramuscular vaccination can be scheduled 3 or more ≥10 Yes if
No No
shortly after such therapy is administered. Patients on doses years ≥5
anticoagulant therapy should be considered to have the since years
last dose

288
ANTI-INFECTIVES FOR SYSTEMIC USE
Administration: For IM administration only into the deltoid
muscle. Do NOT administer by IV or SC administration.
Shake suspension well before use. Do NOT mix with
other vaccines or injections. Use different needles and
syringes for each injection.
Administer while patient is seated or lying down to
prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
See Diphtheria-Tetanus Toxoids (DT) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07AM51
DIPHTHERIA-TETANUS
Rx TOXOIDS AND PERTUSSIS
VACCINE (DTP)
Inj.: 0.5 mL ampule (IM)
0.5 mL pre-filled syringe (IM)
0.5 mL, 5 mL, 7.5 mL, and 10 mL vial (IM)
A three-component preparation of diphtheria, tetanus and
pertussis (whole-cell) vaccines whose rates of local and
systemic reactions are higher than acellular pertussis
vaccine.
Indications: Active immunization against diphtheria,
tetanus, and pertussis
Contraindications: Hypersensitivity to the any component of
the formulation; severe acute neurological illness within
7 days of pertussis vaccination; thrombocytopenia or any
coagulation disorders
Dose:
Primary immunization, by IM injection, ADULT, 0.5 mL;
CHILD 1–6 years of age, two 0.5 mL doses separated by
an interval of 2 months, administer a third dose after 6–
12 months; INFANT ≥6 weeks, three 0.5 mL doses with
an interval of at least 4 weeks between each dose.
Precautions:
Whole cell pertussis component is associated with more
frequent minor adverse effects than acellular pertussis
component.
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Arthus-type hypersensitivity; syncope (has been reported
with use);
Acute illness;
Bleeding disorders, including Guillain-Barré syndrome;
Neurologic disorders;
Thrombocytopenia;
Immunodeficiency.
Elderly (frequency of adverse effects increases with age and
number of injections);
Children with proven, or suspected, underlying active or
progressive neurologic disorders;
Pregnancy (adult vaccine may be used if necessary).
Adverse Drug Reactions:
Common: Crying, drowsiness, irritability, limb swelling,
restlessness
Less Common: Fever, lethargy, malaise, myalgia, transient
J
injection site reactions (pain, redness, itching, burning,
small hard lump that persists for some weeks)
Rare: Allergic reactions including anaphylaxis, collapse,
encephalopathy, headache, hypotonic-hyporesponsive
episodes, seizure, urticaria, peripheral neuropathy,
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Other vaccines and immunoglobulins [administer at
least 4 weeks apart]
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
Anti-infectives (may interfere with the development of a
protective immune response)
Immunosuppressive Agents e.g. Corticosteroids
Antineoplastic (decreases antibody response)
Administration: For IM administration only into the
anterolateral aspect of the thigh or the deltoid muscle.
Do NOT administer by IV or SC.
Shake suspension well before use. Store at 2–8°C.
Freezing is the most common cause of vaccine damage.
Do NOT use a defrosted vaccine unless freezing is the
recommended storage condition.
Administer vaccines while patient is seated or lying down
to prevent syncope related injuries.
NOT recommended for adolescents and adults.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety.
If the patient receives anti-hemophilia or other similar
therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
289

Administer to travelers regardless of the limitations if
time is short.
Pregnancy Category: B / C (product specific)
ATC Code: J07AJ51
DIPHTHERIA-TETANUS
Rx TOXOIDS AND ACELLULAR
PERTUSSIS VACCINE (DTaP)
Inj.: 0.5 mL pre-filled syringe (IM)
0.5 mL vial (IM)
A three-component preparation of diphtheria and tetanus
toxoids, and acellular pertussis vaccine that promotes
active immunity to diphtheria, tetanus, and pertussis by
inducing production of specific antibodies.
J
Indications: Active immunization against diphtheria,
tetanus, and pertussis
Contraindications: Hypersensitivity to diphtheria, tetanus
toxoids, pertussis, or any component of the formulation;
progressive neurologic disorder, including infantile
spasms, uncontrolled epilepsy or progressive epilepsy;
encephalopathy occurring within 7 days of
administration and not attributable to another cause
Dose:
NOTE: Whenever possible, use the same product for all
doses. Interruption of recommended schedule does not
require starting the series over. A delay between doses
should not interfere with final immunity.
Primary immunization, by IM injection, CHILD and INFANT 6
weeks to <7 years, five 0.5 mL doses administered as
follows:
Three doses at 2, 4, and 5 months of age; may be given
as early as 6 weeks of age and repeated every 4–8
weeks;
Fourth doses at ~15 to 20 months of age but at least 6
months after third dose; may be given as early as 12
months of age;
Fifth doses at 4–6 years of age, prior to starting school
or kindergarten; if fourth dose is given at ≥4 years of age,
the fifth dose may be omitted.
Booster immunization, by IM injection, ADULT ≥19 years,
0.5 mL as a single dose 5 years after last dose of tetanus
toxoid, diphtheria toxoid, and/or pertussis-containing
vaccine [NOTE: Administer a single dose to replace a
single dose of the 10 year Td booster in patients who
have not previously received Tdap or for whom vaccine
status is not known];
CHILD ≥10 years and ADOLESCENT ≤18 years, 0.5 mL as
a single dose 5 years after last dose of tetanus toxoid,
diphtheria toxoid, and/or pertussis-containing vaccine
[NOTE: Administer as a single booster dose at 11 or 12
years of age in adolescents who have completed a
childhood DTaP vaccination series, followed by booster
doses of Td every 10 years. Adolescents who have not
received Tdap at age 11 or 12 should receive a single
dose of Tdap in place of a single Td booster dose].
290
ANTI-INFECTIVES FOR SYSTEMIC USE
For Wound Management, see Diphtheria-Tetanus Toxoid
(Td) under Vaccines – Bacterial Vaccines in Chapter 7:
Anti-infectives for Systemic Use for other information.
Adverse Drug Reactions:
Common: Apathy, drowsiness, irritability, lethargy,
headache, fatigue, chills, skin rash, increased arm
circumference, GI disease, adenopathy, injection site
reactions (erythema, pain, edema, tenderness, swelling),
crying (prolonged or persistent), fever, fussiness,
myalgia, arthralgia
Less Common: Anaphylaxis, angioedema, apnea, back pain,
brain disease, bronchitis, cellulitis, cough, cyanosis,
diabetes mellitus, diarrhea, encephalitis, erythema,
facial paralysis, fatigue, Guillain-Barré syndrome,
hypersensitivity reaction, headache, hypoesthesia,
hypotonia, hypotonic or hyporesponsive episode, IgA
vasculitis, immune thrombocytopenia, infantile spasm,
injection site reaction (bruising, induration, mass,
nodule, pruritus, rash, sterile abscess, warmth),
intussusception, lymphadenitis, lymphadenopathy,
myalgia, myocarditis, myositis, nausea, nerve
compression, otalgia, paresthesia, peripheral edema
(extensive), pruritus, respiratory tract infection,
screaming, seizure, sudden infant death syndrome,
syncope, thrombocytopenia, urticaria
Administration: For IM administration only into the
anterolateral aspect of the thigh or the deltoid muscle.
Do NOT administer by IV or SC.
Shake suspension well before use. Store at 2–8°C.
Freezing is the most common cause of vaccine damage.
Do NOT use a defrosted vaccine unless freezing is the
recommended storage condition.
Administer vaccines while patient is seated or lying down
to prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety.
If the patient receives antihemophilia or other similar
therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
Administer to travelers regardless of the limitations if
time is short.
See Diphtheria-Tetanus Toxoids (DT) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07AJ52
ANTI-INFECTIVES FOR SYSTEMIC USE
HEMOPHILUS INFUENZAE
Rx TYPE B CONJUGATED
VACCINE (Hib)
Inj.: 10 micrograms/0.5 mL, 1 dose vial + 0.5 mL diluent
with tetanus protein (IM)
10 micrograms/0.5 mL vial + 0.9% sodium chloride
with diphtheria CRM 197 protein (IM)
0.5 mL vial with meningococcal protein (IM)
An inactivated bacterial vaccine that stimulates the
production of anticapsular antibodies and provides
active immunity to Haemophilus influenzae type b.
Indications: Active immunization for the prevention of
invasive disease caused by Haemophilus influenzae type
b (Hib)
Contraindications: Hypersensitivity to Haemophilus b
polysaccharide or any component of the formulation
Dose:
Immunization, by IM injection, ADULT, 0.5 mL [NOTE: For
adult recipients of successful hematopoietic stem cell
transplant, revaccinate with a 3-dose regimen beginning
6–12 months after transplant, regardless of vaccination
history; administer ≥4 weeks apart].
Primary immunization, by IM injection, CHILD, 0.5 mL per
dose; number of doses for completion of Hib series
depends on products, including some combination
formulations, see specific product monographs for
specific dosing information.
Booster immunization, by IM injection, CHILD ≥12 months,
0.5 mL as a single dose.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
Bleeding disorders (bleeding or hematoma may occur from
IM administration);
Guillain-Barré syndrome;
Immunodeficiency;
Children (apnea has occurred following vaccination in
premature infants);
Pregnancy (animal reproduction studies have not been
conducted).
Adverse Drug Reactions:
Common: Crying (unusual, high-pitched, prolonged),
drowsiness, fussiness, irritability, lethargy, pain,
restlessness, seizure, skin rash, urticaria, anorexia,
diarrhea, vomiting, thrombocytopenia, erythema,
induration, pain, soreness, swelling, weakness, otitis
media, tracheitis, upper respiratory tract infection, fever
Less Common: Abscess at injection site (sterile),
anaphylaxis, anaphylactoid reaction, apnea,
angioedema, febrile seizures, Guillain-Barré syndrome,
hypersensitivity reaction, hypotonic / hyporesponsive
episode, lymphadenopathy, malaise, mass, peripheral
edema, pneumonia, pruritus, swelling of the injected
limb (extensive), syncope, vasodepressor syncope
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Hib Vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
TEST INTERACTION. May interfere with urine antigen
detection test; antigenuria may occur up to 2 weeks
following immunization.
Administration: For IM administration into the anterolateral
thigh or deltoid muscle. Do NOT administer into buttocks
due to potential risk of injury to sciatic nerve. Do NOT
inject by IV, ID, or SC.
J
Shake well prior to use. Do NOT mix with other vaccines
or injections. Use different needles and syringes for each
injection.
Administer while seated or lying down to prevent syncope
related injuries.
Pregnancy Category: C
ATC Code: J07AG01; J07AG53
MENINGOCOCCAL
Rx (Neisseria meningitidis)
POLYSACCHARIDE VACCINE
Inj.: 50 micrograms/0.5 mL dose (Group A + C) lyophilized
powder, single dose + 0.5 mL diluent syringe (IM, SC)
50 micrograms/0.5 mL dose (Group A + C) lyophilized
powder, multi-dose (10 doses) + 5 mL diluent vial (IM,
SC)
50 micrograms/0.5 mL dose (Serogroup A +
Serogroup B + Serogroup W135 + Serogroup Y)
lyophilized powder, multi-dose (10 doses) + diluent
vial (IM, SC)
An inactivated bacterial vaccine that induces the formation
of bactericidal antibodies to meningococcal antigens.
The presence of these antibodies is strongly correlated
with immunity to meningococcal disease caused by
Neisseria meningitidis.
Indication: Active immunization of patients 2 years and
older to prevent invasive meningococcal disease caused
by Neisseria meningitidis
Contraindication: Hypersensitivity to any component of the
formulation
Dose:
Immunization, by SC injection, ADULT, ADOLESCENT, and
CHILD ≥2 years, 0.5 mL per dose.
291

Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
Meningococcal infections (not to be used to treat
meningococcal infections);
Immunodeficiency;
Elderly (no specific data available; recommended only when
traveling to highly endemic areas);
Pregnancy (animal reproduction studies have not been
conducted);
Lactation (not known if excreted in breastmilk).
Adverse Drug Reactions:
Common: Headache, fatigue, malaise, drowsiness,
irritability, chills, fever, rash, diarrhea, anorexia,
vomiting, injection site reactions (pain, redness,
induration, swelling), arthralgia
J
Less Common: Dizziness, Guillain-Barré syndrome,
hypersensitivity (angioedema, dyspnea, pruritus, rash,
urticaria), myalgia, nausea, paresthesia, vasovagal
syncope, weakness
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Meningococcal Vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Administration: Administer by SC injection into the deltoid
region. Do NOT administer by ID, IM, or IV.
Administer while seated or lying down to prevent syncope
related injuries.
Reconstitute using provided diluent. Shake well. Store at
2–8oC. Do NOT freeze. Use single-dose vial immediately
after reconstitution. Use multidose vial within 35 days of
reconstitution. Do NOT mix with other vaccines or
injections. Use different needles and syringes for each
injection.
Pregnancy Category: C
ATC Code: J07AH02
PNEUMOCOCCAL
Rx
CONJUGATE VACCINE
Inj.: 13 – valent, 0.5 mL single dose vial and 0.5 mL pre-
filled syringe, suspension for IM injection
An inactivated bacterial vaccine that promotes active
immunization against invasive disease caused by S.
pneumoniae.
292
ANTI-INFECTIVES FOR SYSTEMIC USE
Indications: Immunization of infants and children against
Streptococcus pneumoniae infection and invasive
diseases caused by serotypes included in the vaccine
Contraindication: Hypersensitivity to any component of the
vaccine
Dose:
Primary immunization, by IM injection, CHILD ≥12 months
to <6 years (previously unvaccinated), two 0.5 mL doses,
administered at least 2 months apart;
CHILD 7–11 months (previously unvaccinated), three 0.5
mL doses, administer first 2 doses at least 1 month
apart, administer the third dose after 1 year of age,
separated from the second dose by at least 2 months;
INFANT 6 weeks to 6 months,
three-dose primary series, three 0.5 mL doses, followed
by a booster dose (for a total of 4 doses); may administer
first dose as early as 6 weeks of age, but is typically given
at 2 months of age; administer second and third doses
at 4 and 6 months of age; administer booster dose at 12
to 15 months of age; allow a minimum interval of 1
month between each of the first 3 doses, and 6 months
between third dose and booster dose;
two-dose primary series, two 0.5 mL doses, followed by
a booster dose (for a total of 3 doses); may administer
first dose as early as 6 weeks of age, but is typically given
at 2 months of age; administer second dose at 4 months
of age; administer booster dose at 11–12 months of age;
allow a minimum interval of 2 months between the first
2 doses, and 6 months between second dose and
booster dose.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Apnea;
Syncope (has been reported with use);
AcUte illness;
Bleeding disorders;
Pneumococcal infections (not to be used to treat
pneumococcal infections);
Immunodeficiency;
Pregnancy (animal reproduction studies have not been
conducted).
Adverse Drug Reactions:
Common: Irritability, drowsiness, fever, loss of appetite,
injection site reactions (pain, redness, swelling,
induration)
Less Common: Abnormal crying, allergic reactions (allergic
dermatitis, atopic dermatitis, eczema), apnea
(premature infants), diarrhea, injection site reactions
(hematoma, hemorrhage, nodule), rash, seizure (febrile
and nonfebrile), urticaria, vomiting
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Pneumococcal Vaccine:
Belimumab
Fingolimod [administer at least 2 weeksapart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
ANTI-INFECTIVES FOR SYSTEMIC USE
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Administration: Administer by IM injection only, preferably
into the anterolateral aspect of the thigh in infants and
into the deltoid in children. Do NOT inject by IV or ID.
Avoid SC route.
Shake well prior to use.
Pregnancy Category: C
ATC Code: J07AL02
PNEUMOCOCCAL
Rx CONJUGATE VACCINE
(13-VALENT)
Inj.: 0.5 mL single dose vial and 0.5 mL, pre-filled syringe,
suspension for IM injection
An inactivated bacterial vaccine that promotes
immunization against invasive disease caused by S.
pneumoniae capsular serotypes 1, 3, 4, 5, 6A, 6B, 7F,
9V, 14, 18C, 19A, 19F, and 23F, all which are individually
conjugated to CRM197 protein.
Indication: Immunization against Streptococcus
pneumoniae infection caused by serotypes included in
the vaccine
Contraindication: Severe allergic reaction (e.g., anaphylaxis)
to pneumococcal vaccine, any component of the
formulation, or any diphtheria toxoid-containing vaccine
Dose:
Immunization, by IM injection, ADULT, 0.5 mL as a single
dose.
Primary immunization, by IM injection, CHILD and INFANT 6
weeks to 15 months, four 0.5 mL doses; administer first
dose at 8 weeks of age, may be given as early as 6 weeks
of age; administer 3 remaining doses at 4, 6, and 12–15
months of age; recommended dosing interval is 4–8
weeks with minimum interval of 1 month in children <1
year of age; minimum interval between third and fourth
doses is 8 weeks.
Catch-up immunization (unvaccinated with PCV13), by IM
injection, ADOLESCENT and CHILD 6–17 years, 0.5 mL
as a single dose; CHILD 24–71 months (healthy), 0.5 mL
as a single dose; CHILD 24–71 months (with underlying
medical condition), two 0.5 mL doses separated by 8
weeks; CHILD 12–23 months, two 0.5 mL doses
separated by at least 8 weeks; INFANT 7–11 months,
three 0.5 mL doses, administer first 2 doses at least 4
weeks apart, followed by a third dose at 12 months of
age and at least 8 weeks after the second dose.
Dose Adjustment:
Geriatric:
All patients ≥65 years should receive both pneumococcal
conjugate vaccine (PCV 13) and pneumococcal
polysaccharide vaccine (PPSV23).
Pneumococcal vaccine-naïve, by IM injection, 0.5 mL
PCV13 as a single dose, followed by PPSV23 6 to 12
months later (minimum interval of 8 weeks).
Received previous pneumococcal polysaccharide
vaccine (PPSV23), by IM injection,
Received at age <65 years, 0.5 mL PCV13 as a single
dose ≥1 year after the last dose of PPSV23, followed by
PPSV23 at least 6 to 12 months after the PCV13 dose
and at least 5 years after the last dose of PPSV23.
Received at age ≥65 years, 0.5 mL PCV13 as a single
dose ≥1 year after the last dose of PPSV23; no additional
doses of PPSV23 are needed for routine vaccination.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Fever;
Syncope (has been reported with use);
J
Acute illness;
Asplenia;
Bleeding disorders;
Chronic illness;
HIV;
Pneumococcal infections (not to be used to treat
pneumococcal infections);
Sickle cell disease;
Immunodeficiency.
Elderly (antibody responses are lower in older adults >65
years);
Children (antibody responses are lower in preterm infants
<37 weeks gestational age);
Lactation (not known if excreted into breastmilk).
Adverse Drug Reactions:
Common: Chills, drowsiness, fatigue, fever, headache,
insomnia, irritability, rash, hives, decreased appetite,
diarrhea, vomiting, limitation of arm motion, injection
site reactions (erythema, pain, swelling, tenderness),
arthralgia, myalgia
Less Common: Abnormal crying, erythema multiforme,
febrile seizures, hypersensitivity reaction
(bronchospasm, dyspnea, facial edema), seizure,
urticaria, urticaria­like rash
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Influenza Virus Vaccine
(Inactivated) [administer at least 1 month apart]
Avoid concomitant use with:
Reduces therapeutic effect of PCV13 vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Administration: Administer by IM injection into he deltoid
muscle for toddlers, young children, and adults or lateral
midthigh in infants. Do NOT inject by IV or SC. Avoid ID
route.
293

Shake well prior to use. Do NOT use if a homogenous
white suspension does not form. Do NOT mix with other
vaccines or injections. Use different needles and
syringes for each injection.
Administer while seated or lying down to prevent syncope
related injuries.
NOTE: Concurrent administration of PCV13 and PPV23 has
not been studied and is not recommended.
For patients at risk of hemorrhage following IM injection,
administer by IM only if, in the opinion of the physician
familiar with the patient's bleeding risk, the vaccine can
be administered by this route with reasonable safety.
Use a fine needle (23 gauge or smaller) and apply firm
pressure to the site (without rubbing) for at least 2
minutes.
If the patient receives anti-hemophilia or other similar
therapy, IM vaccination can be scheduled shortly after
J
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
Pregnancy Category: B
ATC Code: J07AL02
PNEUMOCOCCAL
Rx
POLYVALENT VACCINE
Inj.: 25 micrograms/0.5 mL (polysaccharide from each
capsular type) solution for injection, 0.5 mL pre-filled
syringe (IM, SC)
25 micrograms/0.5 mL solution for injection, 2.5 mL
vial (IM, SC) (multidose)
An inactivated bacterial vaccine that promotes active
immunization against invasive disease caused by S.
pneumoniae.
Indications: Immunization of infants and children against
Streptococcus pneumoniae infection and invasive
diseases caused by serotypes included in the vaccine
Contraindication: Hypersensitivity to any component of the
vaccine
Dose:
Primary immunization, by IM injection, CHILD ≥12 months
to <6 years (previously unvaccinated), two 0.5 mL doses,
administered at least 2 months apart;
CHILD 7–11 months (previously unvaccinated), three 0.5
mL doses, administer first 2 doses at least 1 month
apart, administer the third dose after 1 year of age,
separated from the second dose by at least 2 months;
INFANT 6 weeks to 6 months,
three-dose primary series, three 0.5 mL doses, followed
by a booster dose (for a total of 4 doses); may administer
first dose as early as 6 weeks of age, but is typically given
at 2 months of age; administer second and third doses
at 4 and 6 months of age; administer booster dose at 12
to 15 months of age; allow a minimum interval of 1
month between each of the first 3 doses, and 6 months
between third dose and booster dose;
294
ANTI-INFECTIVES FOR SYSTEMIC USE
two-dose primary series, two 0.5 mL doses, followed by
a booster dose (for a total of 3 doses); may administer
first dose as early as 6 weeks of age, but is typically given
at 2 months of age; administer second dose at 4 months
of age; administer booster dose at 11–12 months of age;
allow a minimum interval of 2 months between the first
2 doses, and 6 months between second dose and
booster dose.
Administration: Administer by IM injection only, preferably
into the anterolateral aspect of the thigh in infants and
into the deltoid in children. Do NOT inject by IV or ID.
Avoid SC route.
Shake well prior to use.
See Pneumococcal Conjugated Vaccine under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07AL01
POLYSACCHARIDE POLYVALENT
Rx PNEUMOCOCCAL VACCINE
SOLUTION
Inj.: 25 micrograms/0.5 mL solution, 2.5 mL multi-dose
vial (IM, SC)
An inactivated bacterial vaccine that promotes active
immunization against invasive disease caused by S.
pneumoniae.
Indication: Active immunization for the prevention of
pneumococcal disease
Contraindication: Hypersensitivity to any component of the
vaccine
Dose:
Immunization, by IM or SC injection, ADULT, 0.5 mL.
Precautions:
Acute illness;
Severely compromised cardiovascular or pulmonary
function;
Chronic cerebrospinal fluid leakage (may not be effective
due to congenital lesions, skull fractures, or
neurosurgical procedures);
Immunodeficiency.
Children (not approved for use in children <2 years).
Pregnancy (animal reproduction studies have not been
conducted);
Lactation (not known if excreted into breastmilk).
Adverse Drug Reactions:
Common: Injection site reactions (erythema, pain, soreness,
tenderness, swelling, induration), headache, asthenia or
fatigue, myalgia, chills, fever, dyspepsia, nausea, neck
pain, upper respiratory infection
Less Common: Pruritus, diarrhea, back pain, pharyngitis,
cellulitis, malaise, decreased limb mobility, peripheral
ANTI-INFECTIVES FOR SYSTEMIC USE
edema, rash, vomiting, lymphadenitis,
lymphadenopathy, hemolytic anemia, thrombocytopenia,
leukocytosis, serum sickness, anaphylactoid reactions,
angioneurotic edema, arthralgia, arthritis, paresthesia,
radiculoneuropathy, Guillain-Barré syndrome, febrile
convulsion, urticaria, erythema multiforme, increased
serum C-reactive protein
Rare: Ecchymosis
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Pneumococcal Vaccine:
Other Vaccines [administer at least 4 weeks apart]
Administration: Administer by IM or SC injection only into the
deltoid muscle or lateral midthigh. Do NOT inject by IV or
ID.
Shake well prior to use.
Pregnancy Category: C
ATC Code: J07AL01
Rx TETANUS TOXOID
Inj.: 0.5 mL ampule (IM)
10 mL vial (IM)
A sterile solution of tetanus toxoid in isotonic sodium
chloride solution, which is used as a booster injection
against tetanus.
Indications: Active immunization against tetanus when
combination antigen preparations are not indicated;
tetanus prophylaxis in wound management
Contraindication: Hypersensitivity to tetanus toxoid or any
component of the formulation
Dose:
Primary immunization, by IM injection, ADULT and CHILD ≥7
years, 0.5 mL, administer a second dose 4–8 weeks
after the first dose and a third dose at 6–12 months after
the second dose; administer a routine booster dose
every 10 years.
For Wound Management, see Diphtheria-Tetanus Toxoid
(Td) under Vaccines – Bacterial Vaccines in Chapter 7:
Antiinfectives for Systemic Use for other information.
Adverse Drug Reactions:
Common: Hypotension, brachial neuritis, fever, pain,
malaise, nausea, injection site reactions (edema,
induration, rash, redness, urticaria, warmth), arthralgia,
Guillain-Barré syndrome, Arthrus-type hypersensitivity
reaction, anaphylactic reaction
Administration: For IM administration only into the
anterolateral aspect of the thigh or the deltoid muscle.
Do NOT inject in the gluteal area.
Shake suspension well before use. Do NOT administer if
product does not form a suspension.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
See Diphtheria-Tetanus Toxoids (DT) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information.
J
Pregnancy Category: C
ATC Code: J07AM01
Rx TYPHOID VACCINE
Oral: live attenuated S. typhi (not less than 109) viable
strain, enteric-coated tablet (encapsulated)
Inj.: 25 micrograms Vi-capsular polysaccharide S. typhi in
0.5 mL pre-filled syringe (IM)
A bacterial vaccine containing virulent strains of Salmonella
typhi that confer immunity by the provocation of a local
immune response in the intestinal tract induced by oral
ingestion of a live strain with subsequent aborted
infection.
Indication: Active immunization against typhoid fever
caused by Salmonella typhi
Contraindications: Hypersensitivity to any component of the
vaccine; acute febrile illness; congenital or acquired
immunodeficient state
Dose:
Primary immunization, by mouth, ADULT and CHILD ≥6
years, 1 capsule on alternate days for 4 doses,
completed at least 1 week prior to expected exposure;
by IM injection, ADULT and CHILD ≥2 years, 0.5 mL at
least 2 weeks prior to expected exposure.
Reimmunization, by mouth, ADULT and CHILD ≥6 years,
repeat full course of primary immunization every 5 years;
by IM injection, ADULT and CHILD ≥2 years, 0.5 mL every
2 years.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1: 1,000 should be
available during vaccine use; syncope; acute illness;
bleeding disorders, including thrombocytopenia; typhoid
fever.
Pregnancy (animal reproduction studies have not been
conducted);
Lactation (not known if excreted into breastmilk).
295
 ANTI-INFECTIVES FOR SYSTEMIC USE

Prednisolone (Systemic); Prednisone; Triamcinolone

Adverse Drug Reactions:
Common:
[Inj.]: Malaise, headache, generalized ache, pruritus,
nausea, vomiting, injection site reactions (tenderness,
pain, induration, erythema, swelling), muscle
tenderness, myalgia, fever
[Oral]: Headache, skin rash, abdominal pain, nausea,
diarrhea, vomiting
Less Common:
[Inj.]: Abdominal pain, anaphylaxis, angioedema,
arthralgia, asthma, diarrhea, dizziness, flu­like
symptoms, Guillain-Barré syndrome, hypotension,
inflammation at injection site (angioedema, urticaria),
intestinal perforation (jejunum), hypersensitivity
reaction, loss of consciousness, lymphadenopathy,
malaise, neck pain, serum sickness, skin rash, syncope
(with and without convulsions), tremor, urticaria,
vasodilation, weakness
J
(Systemic) [separate administration by at least 3
months]; Leflunomide [separate administration by at
least 3 months]
Mercaptopurine [avoid doses >1.5 mg/kg daily]
Methotrexate [avoid doses >0.4 mg/kg weekly]
Proguanil [separate administration by at least 10 days]
Administration: For oral administration, swallow capsules
whole soon after placing into mouth with a cold or
lukewarm beverage (≤37˚C/98.6˚F). Do NOT chew or
open capsule.
To be taken 1 hour prior to a meal. Avoid alcohol 1 hour
before or 2 hours after administration to prevent
disruption of the enteric coating.
For IM administration, administer as a single 0.5 mL (25
micrograms) injection into the deltoid muscle. Younger
children may also receive the dose in the anterolateral

[Oral]: Anaphylaxis, demyelinating disease, myalgia, thigh. Do NOT inject into the gluteal muscle. Do NOT
pain, rheumatoid arthritis, sepsis, urticaria, weakness administer by IV.

Drug Interactions: Administer while patient is seated or lying down to

Avoid concomitant use with: prevent syncope related injuries.
Increases risk of adverse or toxic effects of Typhoid Vaccine:
Azathioprine, Belimumab, Corticosteroids (Systemic), NOTE: For patients at risk of hemorrhage following IM
Dimethyl Fumarate (vaccinal infection), Fingolimod injection, administer by IM only if, in the opinion of the
(vaccinal infection) physician familiar with the patient's bleeding risk, the
Immunosuppressants, Leflunomide, Mercaptopurine, vaccine can be administered by this route with
Methotrexate reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
Reduces diagnostic effect of Tuberculin Test [separate rubbing) for at least 2 minutes.
administration by at least 4–6 weeks]
If the patient receives anti-hemophilia or other similar
Reduces therapeutic effect of Typhoid Vaccine: therapy, intramuscular vaccination can be scheduled
Antibiotics [except Acetic Acid (Otic); Acetic Acid (Topical); shortly after such therapy is administered. Patients on
Aluminum Acetate; Azithromycin (Ophthalmic); anticoagulant therapy should be considered to have the
Aztreonam (Oral Inhalation); Bacitracin (Ophthalmic); same bleeding risks and treated as those with clotting
Bacitracin; Benzoin; Capreomycin; Ciprofloxacin factor disorders.
(Ophthalmic); Clindamycin (Topical); Dapsone (Topical);
Erythromycin; Fidaxomicin; Framycetin; Fusidic Acid; Pregnancy Category: C
Gatifloxacin; Gentamicin, Ophthalmic and Topical;
Gentian Violet; Hexachlorophene; Mafenide; ATC Code: J07AP01 (oral)
Metronidazole (Topical); Neomycin; Oxychlorosene; J07AP02 (parenteral)
Polymyxin B; Povidone-Iodine; Rifaximin; Silver Nitrate;
Silver Sulfadiazine; Sulfacetamide (Ophthalmic);
Sulfacetamide (Topical); Tobramycin (Ophthalmic) [live
attenuated Ty21a strain only; [postpone vaccination until
at least 3 days after cessation of antibacterial agents]
Azathioprine [avoid doses >3 mg/kg daily]
Corticosteroids, Systemic [avoid doses greater than an
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Dimethyl Fumarate
Fingolimod
Immune Globulins [consult full interaction monograph
for dose interval recommendations]
Immunosuppressants [except Azathioprine;
Beclomethasone (Oral Inhalation); Betamethasone
(Systemic); Budesonide (Systemic); Budesonide,
(Systemic and Oral Inhalation); Corticotropin; Cortisone;
Cytarabine (Liposomal); Deflazacort; Dexamethasone
(Systemic); Fludrocortisone; Fluticasone (Oral
Inhalation); Hydrocortisone (Systemic); Leflunomide;
Mercaptopurine; Methotrexate; Methylprednisolone;

296
ANTI-INFECTIVES FOR SYSTEMIC USE
VIRAL VACCINES
HEPATITIS A VACCINE
Rx
(INACTIVATED)
Inj.: Viral antigen not less than 720 EU in 0.5 mL
monodose vial (IM) (junior)
Viral antigen not less than 1440 EU in 1 mL
monodose vial (IM) (adult)
80 units/0.5 mL (GBM strain) pre-filled syringe single
dose (IM) (pediatric)
160 units/0.5 mL (GBM strain) pre-filled syringe
single dose (IM) (adult)
An inactivated viral vaccine that induces active immunity
against hepatitis A virus infection.
Indication: For active immunization of persons 12 months
and older against diseases caused by hepatitis A virus
(HAV)
Contraindication: Immediate and/or severe allergic or
hypersensitivity reaction to hepatitis A containing
vaccines or any component of the formulation, including
neomycin
Dose:
Primary immunization, by IM injection, ADULT, 1 mL (50
units) with a booster dose of 1 mL (50 units) to be given
6–18 months after first dose; CHILD ≥12 months, 1 mL
(50 units) at 12–23 months with a booster dose of 1 mL
(50 units) to be given 6–18 months after first dose
[NOTE: When used for primary immunization, administer at
least 2 weeks prior to expected exposure; when used
prior to an international adoption, begin series when
adoption is planned, ideally ≥2 weeks prior to expected
arrival of adoptee].
Dose Adjustment:
Hepatic Impairment:
May require dose adjustment. Patients with chronic liver
disease have lower antibody response.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
Bleeding disorders, including thrombocytopenia;
Hepatic impairment;
Immunodeficiency;
Pregnancy (animal reproduction studies have not been
conducted);
Lactation (not known if excreted into breastmilk).
Adverse Drug Reactions:
Common: Drowsiness, headache, irritability, chills, fatigue,
insomnia, malaise, skin rash, menstrual disease,
decreased appetite, abdominal pain, anorexia,
constipation, diarrhea, gastroenteritis, nausea, vomiting,
injection site reactions (erythema, soreness, warmth,
pain, swelling, tenderness, bruising, induration),
weakness, arm pain, back pain, myalgia, stiffness,
conjunctivitis, otitis media, asthma, cough, nasal
congestion, nasopharyngitis, pharyngitis, rhinitis,
rhinorrhea, upper respiratory tract infection, fever,
excessive crying
Less Common: Anaphylaxis, angioedema, arthralgia, ataxia
(cerebellar), bronchoconstriction, croup, bronchiolitis,
dehydration, dermatitis, dizziness, dysgeusia, dyspnea,
encephalitis, erythema multiforme, eye irritation, flu­like
symptoms, hepatitis, hyperhidrosis, otitis, Guillain-Barré
syndrome, hypersensitivity reaction, hypertonia,
hypoesthesia, increased creatine kinase, increased
serum transaminases (transient), injection site reactions
(hematoma, nodule, rash), insomnia, jaundice,
lymphadenopathy, multiple sclerosis, myelitis,
neuropathy, paresthesia, photophobia, pneumonia,
pruritus, respiratory congestion, seizure, serum
sickness-like reaction, syncope, thrombocytopenia,
urticaria, vasculitis, vertigo, viral exanthem, wheezing
Drug Interactions:
Avoid concomitant use with:
J
Reduces therapeutic effect of HAV vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Administration: For IM administration into the deltoid
muscle for older children and adults or into the
anterolateral aspect of the thigh in infants and young
children. Do NOT administer to the gluteal region. Do
NOT administer by IV, ID, or SC.
Shake well prior to use. Discard if suspension is
discolored, does not appear homogenous after shaking,
or if there are cracks in the vial or syringe. Do NOT dilute.
Administer while patient is seated or lying down to
prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
Pregnancy Category: C
ATC Code: J07BC02
297
 ANTI-INFECTIVES FOR SYSTEMIC USE

HEPATITIS B VACCINE apnea, arthritis, Bell's palsy, bronchospasm,

Rx constipation, eczema, conjunctivitis, encephalitis,
(RECOMBINANT DNA)
erythema nodosum, erythema multiforme, febrile
seizures, Guillain-Barré syndrome, herpes zoster,
Inj.: 10 micrograms/0.5 mL monodose vial (IM) (pediatric)
hypersensitivity reaction, hypoesthesia, increased
10 micrograms/0.5 mL, 5 mL (10 dose) vial (IM)
erythrocyte sedimentation rate, keratitis, lichen planus,
20 micrograms/mL monodose vial (IM) (adult) (for
limb pain, lupus-like syndrome, meningitis, migraine,
more than 10 years old)
multiple sclerosis, myasthenia, myelitis, neuritis,
20 micrograms/mL, 10 mL VIAL (10 doses/vial) adult
neuropathy, optic neuritis, palpitations, paralysis,
paresis, periarteritis nodosa, peripheral neuropathy,
N.B.: Formulations of diferent manufaturers are of equal or
petechia, purpura, radiculopathy, seizure, serum
similar immunogenicity. Follow strictly the
sickness-like reaction, Stevens-Johnson syndrome,
recommended dose of each manufacturer.
syncope, systemic lupus erythematosus, tachycardia,
thrombocytopenia, tinnitus, transverse myelitis, uveitis,
A noninfectious subunit viral vaccine, which confers active
vasculitis, visual disturbance
immunity via formation of anti-hepatitis B antibodies.
The vaccine is derived from hepatitis B surface antigen
Drug Interactions:
(HBsAg) produced through recombinant DNA techniques
Avoid concomitant use with:
from yeast cells.
Reduces therapeutic effect of HBV vaccine:
Belimumab
J

Indication: Active immunization against infection caused by

Fingolimod [administer at least 2 weeks apart; if
all known subtypes of hepatitis B virus (HBV)
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Contraindications: Severe allergic or hypersensitivity
Immunosuppressants [Cytarabine, Liposomal]
reaction to yeast, hepatitis B vaccine, or any component
[administer at least 2 weeks apart; if vaccinated during
of the formulation
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Dose:
Primary immunization, by IM injection, ADULT, three 1 mL
Administration: For IM administration into the deltoid
doses at 0, 1, and 6 months; ADOLESCENT, CHILD, and
muscle for adults or into the anterolateral aspect of the
INFANT, three 0.5 mL doses at 0, 1, and 6 months.
thigh in infants and young children. Do NOT administer
to the gluteal region. Do NOT administer by IV, ID, or SC.
Dose Adjustment:
Renal Impairment:
Shake well prior to withdrawal and use. Do NOT mix with
For adult pre-dialysis and dialysis patients ≥20 years,
other vaccines or injections. Use different needles and
administer 40 micrograms per dose at 0, 1, and 6
syringes for each injection.
months.
Administer while patient is seated or lying down to
prevent syncope related injuries.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
NOTE: For patients at risk of hemorrhage following IM
treatment, including epinephrine 1:1000 should be
injection, administer by IM only if, in the opinion of the
available during vaccine use);
physician familiar with the patient's bleeding risk, the
Syncope (has been reported with use);
vaccine can be administered by this route with
Acute illness;
reasonable safety. Use a fine needle (23 gauge or
Bleeding disorders, including thrombocytopenia;
smaller) and apply firm pressure to the site (without
Multiple sclerosis;
rubbing) for at least 2 minutes.
Immunodeficiency;
Severely compromised cardiopulmonary status;
If the patient receives anti-hemophilia or other similar
Pregnancy (animal reproduction studies have not been
therapy, intramuscular vaccination can be scheduled
conducted);
shortly after such therapy is administered. Patients on
Lactation (not known if excreted into breastmilk).
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
Adverse Drug Reactions:
factor disorders.
Common: Flushing, hypotension, body pain, chills,
dizziness, drowsiness, fatigue, headache, insomnia,
Pregnancy Category: C
irritability, malaise, paresthesia, tingling sensation,
vertigo, diaphoresis, pruritus, skin rash, urticaria,
ATC Code: J07BC01
abdominal pain, anorexia, decreased appetite, diarrhea,
dyspepsia, nausea, stomach cramps, vomiting, dysuria,
lymphadenopathy, angioedema, influenza, injection site
reactions (bruising, erythema, induration, nodule,
itching, soreness, pain, swelling, tenderness, warmth),
arthralgia, back pain, myalgia, neck pain, neck stiffness,
shoulder pain, weakness, otalgia, cough, pharyngitis,
rhinitis, upper respiratory tract infection, fever
Less Common: Acute exacerbations of multiple sclerosis,
agitation, alopecia, anaphylactoid reaction, anaphylaxis,

298
ANTI-INFECTIVES FOR SYSTEMIC USE
HUMAN PAPILLOMAVIRUS
Rx QUADRIVALENT (TYPE 6, 11, 16, 18)
VACCINE (RECOMBINANT)
Inj.: 0.5 mL suspension, glass pre-filled syringe (IM)
0.5 mL glass vial
An inactivated viral vaccine containing inactive human
papillomavirus (HPV) proteins HPV 6 L1, HPV 11 L1, HPV
16 L1, and HPV 18 L1, which produce neutralizing
antibodies to prevent cervical cancer, cervical
adenocarcinoma, cervical, vaginal and vulvar neoplasia,
and genital warts caused by HPV.
Indications: For the prevention of cervical, vulvar, vaginal,
and anal cancer caused by HPV types 16 and 18;
prevention of genital warts (condyloma acuminatum)
caused by HPV types 6 and 11; prevention of
precancerous or dysplastic lesions caused by HPV types
6, 11, 16, and 18, including cervical intraepithelial
neoplasia (CIN) grade 2/3 and cervical adenocarcinoma
in situ, CIN grade 1, vulvar intraepithelial neoplasia grade
2 and 3, vaginal intraepithelial neoplasia grade 2 and 3,
and anal intraepithelial neoplasia grades 1, 2, and 3;
Contraindications: Hypersensitivity, including severe allergic
reactions to yeast (a vaccine component), or a previous
dose of the vaccine
Dose:
Immunization, by IM injection, ADULT ≤26 years,
ADOLESCENT, and CHILD ≥9 years two 0.5 mL doses at
0 and 6 months.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
Bleeding disorders, including thrombocytopenia;
Human papillomavirus (HPV) infection (not for the treatment
of the active disease);
Immunodeficiency;
Severely compromised cardiopulmonary status;
Pregnancy (teratogenic effects not observed in animal
reproduction studies);
Lactation (not known if excreted into breastmilk).
Adverse Drug Reactions:
Common: Headache, fever, dizziness, malaise, insomnia,
nausea, diarrhea, vomiting, toothache, injection site
reactions (pain, erythema, swelling, bruising, pruritus,
hematoma), arthralgia, myalgia, pharyngolaryngeal pain,
cough, nasal congestion
Less Common: Alopecia areata, acute disseminated
encephalomyelitis, appendicitis, anaphylactic or
anaphylactoid reaction, arrhythmia, arthritis, asthma,
autoimmune hemolytic anemia and other autoimmune
diseases, bronchospasm, cellulitis, cerebrovascular
accident, chills, DVT, fatigue, gastroenteritis, Guillain-
Barré syndrome, hypersensitivity reaction, ITP, injection
site joint movement impairment, JIA, lymphadenopathy,
hyper- or hypothyroidism, motor neuron disease,
pancreatitis, paralysis, pelvic inflammatory disease,
pulmonary embolus, RA, acute renal failure, seizure,
sepsis, syncope, transverse myelitis, urticaria, weakness
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of HPV vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
Administration: For IM administration into the deltoid
muscle or higher anterolateral thigh area.
Shake well prior to use. Do NOT mix with other vaccines
or injections. Use different needles and syringes for each
J
injection.
Administer while patient is seated or lying down to
prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
Pregnancy Category: B
ATC Code: J07BM01
HUMAN PAPILLOMAVIRUS
Rx VACCINE (TYPE 16 AND 18)
(RECOMBINANT, AS04 ADJUVANT)
Inj.: 0.5 mL suspension in a pre-filled syringe (type 1 glass)
with a plunger stopper (rubber butyl) with sterile
needle
0.5 mL in 3 mL monodose type 1 glass vial
1 mL in 3 mL glass vial
An inactivated viral vaccine containing human
papillomavirus (HPV) proteins HPV 16 L1, and HPV 18
L1, which produce neutralizing antibodies to prevent
cervical cancer, cervical adenocarcinoma, and cervical
neoplasia cause by HPV.
Indications: Prevention of oncogenic HPV types 16 and 18,
including Cervical cancer, cervical intraepithelial
neoplasia (CIN) grade 2 or higher and adenocarcinoma
in situ, and CIN grade 1, in females 9–25 years of age
299

Contraindication: Severe hypersensitivity (e.g. anaphylaxis)
to papillomavirus recombinant vaccine or any
component of the formulation
Dose:
Immunization, by IM injection, ADULT ≤25 years,
ADOLESCENT, and CHILD ≥9 years (FEMALE), two 0.5
mL doses at 0 and 6 months.
Adverse Drug Reactions:
Common: Fatigue, urticaria, injection site reactions (pain,
redness, swelling, pruritus), myalgia, arthralgia,
nasopharyngitis, pharyngolaryngeal pain, upper
respiratory tract infection, influenza, pharyngitis,
chlamydia infection, vaginal infection
Less Common: Allergic reactions, anaphylactic or
anaphylactoid reactions, angioedema, erythema
multiforme, syncope, vasovagal response,
lymphadenopathy
J
Administration: For IM administration into the deltoid
muscle. Do NOT inject by IV, SC, or ID.
Shake well prior to use. Do NOT use if discolored,
contains particulate matter, or if syringe is cracked. Do
NOT mix with other vaccines or injections. Use different
needles and syringes for each injection.
Administer while patient is seated or lying down to
prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
See Human Papillomavirus Quadrivalent (Type 6, 11, 16,
18) Vaccine (Recombinant) under Vaccines – Viral
Vaccines in Chapter 7: Antiinfectives for Systemic Use for
other information.
Pregnancy Category: B
ATC Code: J07BM02
300
ANTI-INFECTIVES FOR SYSTEMIC USE
Rx INFLUENZA POLYVALENT VACCINE
Inj.: 0.5 mL vial + pre-filled syringe diluent (IM)
0.5 mL suspension in a pre-filled syringe or ampule
(IM) (adult)
15 micrograms/0.5 mL, 5 mL multidose glass vial
N.B.: Strains as recommended by WHO
A sterile, aqueous suspension of inactivated influenza virus,
which promotes immunity to seasonal influenza virus by
inducing specific antibody production.
Indication: Active immunization against influenza caused by
influenza virus
NOTE: The Advisory Council on Immunization Practices
(ACIP) recommends routine annual vaccination for all
persons ≥6 months of age who do not otherwise have
contraindications to the vaccine.
Contraindication: Severe allergic reactions (e.g.,
anaphylaxis) to previous doses of influenza vaccine,
chicken or egg protein, hydrocortisone, or any
component of the formulation
Dose:
Immunization, by IM injection, ADULT, ADOLESCENT, and
CHILD ≥9 years, 0.5 mL/dose as a single dose per
season; CHILD 6 months to 8 years, one or two 0.5 mL
doses per season [NOTE: For infants and children 6
months to <9 years, the 2 doses need not have been
received during the same season or consecutive
seasons].
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Oculorespiratory syndrome;
Syncope (has been reported with use);
Acute illness;
Bleeding disorders, including thrombocytopenia;
Febrile seizures;
Guillain-Barré Syndrome;
HIV infection;
Neurologic disorders;
Immunodeficiency;
Elderly (antibody responses may be lower and decline
faster);
Pregnancy (has not shown to cause fetal harm when given
to pregnant women).
Adverse Drug Reactions:
Common: Chest tightness, hypertension, chills, drowsiness,
fatigue, headache, irritability, malaise, migraine,
shivering, diaphoresis, ecchymoses, abdominal pain,
anorexia, diarrhea, gastroenteritis, nausea, sore throat,
vomiting, varicella infection, injection site reactions
(bruising, erythema, hematoma, induration,
inflammation, itching, pain, rash, soreness, swelling,
tenderness), arthralgia, back pain, myalgia, bronchitis,
cough, dyspnea, nasal congestion, nasopharyngitis,
oropharyngeal pain, pharyngitis, pharyngolaryngeal pain,
ANTI-INFECTIVES FOR SYSTEMIC USE

rhinitis, rhinorrhea, upper respiratory tract infection, same bleeding risks and treated as those with clotting
wheezing, fever factor disorders.
Less Common: Abnormal gait, anaphylactic shock,
anaphylaxis, angioedema, arthritis, asthma, Bell's palsy, Pregnancy Category: C
brachial plexopathy, brain disease, bronchospasm,
cellulitis, chest pain, confusion, constriction of the ATC Code: J07BB01 (inactivated)
pharynx, cranial nerve palsy, dizziness, dysphagia, eye J07BB03 (live attenuated)
pain, facial paralysis, febrile seizures, flu-like symptoms,
flushing, Guillain-Barré syndrome, hot flash, Henoch-
Schönlein purpura (immunoglobulin A vasculitis), INFLUENZA POLYVALENT VACCINE
hypoesthesia, pallor, hypersensitivity reaction, Rx
(SPLIT VIRION, INACTIVATED)
hypokinesia, insomnia, laryngitis, limb pain,
lymphadenopathy, maculopapular rash, microscopic
Inj.: 7.5 micrograms/0.25 mL suspension, 0.25 mL single
polyangiitis, myasthenia, myelitis, neuralgia, neuritis,
dose pre-filled syringe
ocular hyperemia, optic neuritis, paralysis, paresthesia,
pharyngeal edema, photophobia, presyncope, pruritus,
A sterile, aqueous suspension of inactivated influenza virus,
optic neuropathy, seizure, serum sickness, skin rash,
which promotes immunity to seasonal influenza virus by
Stevens-Johnson syndrome, swelling of injected limb (>1
inducing specific antibody production.
week), syncope, thrombocytopenia, transverse myelitis,
tremor, urticaria, vasculitis, vasodilatation, vesicobullous
Indication: Active immunization against influenza caused by

J
rash, voice disorder, weakness
influenza virus
Drug Interactions:
NOTE: NOT recommended for use in children <3 years.
Monitor closely with:
Reduces therapeutic effect of Influenza Vaccine:
Contraindications: Severe allergic reactions (e.g.,
Pneumococcal Conjugate Vaccine (13-valent)
anaphylaxis) to previous doses of influenza vaccine,
Venetoclax
chicken or egg protein, hydrocortisone, or any
component of the formulation; active illness with high or
Reduces therapeutic effect of Pneumococcal Conjugate
moderate temperature; acute illness
Vaccine (13-valent)
Dose:
Avoid concomitant use with:
Immunization, by IM or SC injection, ADULT and CHILD 9 to
Reduces therapeutic effect of Influenza Vaccine:
17 years, one 0.5 mL dose; CHILD <9 years, two 0.5 mL
Belimumab
doses administered at least 4 weeks apart.
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
Adverse Drug Reactions:
months after fingolimod discontinuation]
Common: Headache, myalgia, malaise, injection site
Immunosuppressants [Cytarabine, Liposomal]
reactions (pain, swelling, redness, induration), fever,
[administer at least 2 weeks apart; if vaccinated during
shivering
immunosuppressant therapy, revaccinate at least 3
Less Common: Dizziness, diarrhea, nausea, fatigue,
months after immunosuppressant discontinuation]
injection site reactions (bruising, itching, warmth), hot
flush, lymphadenopathy, moaning, restlessness,
Administration: For IM administration into the deltoid
thrombocytopenia (transient), upper abdominal pain,
muscle for adults and older children, or into the
arthralgia
anterolateral aspect of the thigh for infants and young
Rare: Paresthesia, sleepiness, hyperhidrosis, flu-like
children. Children ≥1 year with adequate deltoid muscle
symptoms, asthenia, injection site discomfort
mass may be vaccinated in the deltoid. Do NOT inject
into the gluteal region or areas where there may be a
Administration: For IM or SC administration.
major nerve trunk.
See Influenza Polyvalent Vaccine under Vaccines – Viral
Shake well prior to use. Visually inspect for particulate
Vaccines in Chapter 7: Antiinfectives for Systemic Use for
matter and discoloration prior to administration.
other information.
NOTE: For patients at risk of hemorrhage following IM
Pregnancy Category: C
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
ATC Code: J07BB02
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.

If the patient receives anti-hemophilia or other similar

therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the

301

MEASLES VACCINE
Rx
(LIVE ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
Multi-dose vial + 5 mL diluent (SC)
A live, attenuated, single-antigen vaccine propagated on
human diploid cells.
Indication: Active immunization against measles
Contraindications: Hypersensitivity to any component of the
formulation; severe immunodeficiency; febrile states;
acute infectious diseases; leukemia; severe anemia;
other severe blood disorders; severe renal impairment;
decompensated heart diseases; pregnancy
Dose:
Immunization, by SC injection, ADULT and CHILD, single 0.5
J
mL dose.
Administration: For deep SC injection into the anterolateral
aspect of the upper thigh in toddlers and deltoid muscle
in older children.
Reconstitute only with the supplied diluent using a sterile
syringe and needle. Use reconstituted vaccine
immediately. If not used immediately, store in the dark at
2–8oC for no longer than 6 hours. Discard all opened
containers after 6 hours.
See Measles, Mumps, and Rubella (MMR) Vaccine (Live
Attenuated) under Vaccines – Viral Vaccines in Chapter
7: Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07BD01
MEASLES, MUMPS, AND
Rx RUBELLA (MMR) VACCINE
(LIVE ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
Multi-dose vial + 5 mL diluent (SC)
A bacterially sterile, freeze-dried preparation of live,
attenuated strains of measles, mumps, and rubella virus
that offers active immunity to disease caused by the
measles, mumps, and rubella viruses.
Indications: Active immunization for simultaneous
vaccination against measles, mumps, and rubella in
patients ≥12 months of age
Contraindications: Hypersensitivity to measles, mumps,
and/or rubella vaccine or any component of the
formulation (including neomycin); current febrile
respiratory illness or other febrile infection; primary and
acquired immunodeficiency states; patients on
immunosuppressive therapy; blood dyscrasias,
leukemia, lymphomas, or other malignant neoplasms
affecting the bone marrow or lymphatic systems; family
302
ANTI-INFECTIVES FOR SYSTEMIC USE
history of congenital or hereditary immunodeficiency;
pregnancy
Dose:
NOTE: The minimum interval between 2 doses is 28 days.
Immunization, by SC injection, ADULT, one or two 0.5 mL
doses administered at least 28 days apart; CHILD ≥12
months, two 0.5 mL doses, first dose is recommended at
12–15 months of age; second dose is recommended at
4–6 years of age, prior to entering kindergarten or first
grade; second dose may be administered at any time
provided 28 days have elapsed.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
CNS disorders;
Measles, Mumps and Rubella exposure;
Thrombocytopenia;
Tuberculosis;
Immunodeficiency;
Elderly (antibody responses may be lower and decline
faster);
Children (safety and efficacy of measles vaccine have not
been established in children <6 months of age; safety
and efficacy of mumps and rubella vaccines have not
been established in children <12 months of age);
Pregnancy (animal reproduction studies have not been
conducted; not known if can cause fetal harm; avoid
pregnancy for 28 days after vaccination).
Adverse Drug Reactions:
Common: Syncope, vasculitis, acute disseminated
encephalomyelitis, ataxia, dizziness, brain disease,
encephalitis, Guillain-Barré syndrome, headache,
irritability, malaise, measles inclusion body encephalitis,
paresthesia, polyneuropathy, retrobulbar neuritis,
seizure, subacute sclerosing panencephalitis, transverse
myelitis, erythema multiforme, morbilliform rash,
pruritus, rash, Stevens-Johnson syndrome, urticaria,
diabetes mellitus, nausea, diarrhea, pancreatitis,
parotitis, sore throat, vomiting, epididymitis,
leukocytosis, orchitis, purpura, anaphylactoid reaction,
thrombocytopenia, anaphylaxis, angioedema, injection
site reactions (burning, induration, redness, stinging,
swelling, tenderness, vesiculation, wheal, flare),
arthropathy, myalgia, conjunctivitis, oculomotor nerve
paralysis, optic neuritis, optic papillitis, retinitis, nerve
deafness, otitis media, bronchospasm, cough,
pneumonia, pneumonitis, rhinitis, atypical measles,
febrile seizures, fever, panniculitis, lymphadenopathy
Less Common: Aseptic meningitis
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of MMR Vaccine:
Azathioprine
Belimumab
Corticosteroids (Systemic)
Dimethyl Fumarate (vaccinal infection)
Fingolimod (vaccinal infection)
Immunosuppressants
ANTI-INFECTIVES FOR SYSTEMIC USE
Leflunomide
Mercaptopurine
Methotrexate
Reduces diagnostic effect of Tuberculin Test [separate
administration by at least 4–6 weeks]
Reduces therapeutic effect of MMR Vaccine:
Azathioprine [avoid doses >3 mg/kg daily]
Corticosteroids (Systemic) [avoid doses greater than an
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Dimethyl Fumarate
Fingolimod
Immune Globulins [consult full interaction monograph
for dose interval recommendations]
Immunosuppressants [except Azathioprine;
Beclomethasone (Oral Inhalation); Betamethasone
(Systemic); Budesonide (Systemic); Budesonide
(Systemic and Oral Inhalation); Corticotropin; Cortisone;
Cytarabine (Liposomal); Deflazacort; Dexamethasone
(Systemic); Fludrocortisone; Fluticasone (Oral
Inhalation); Hydrocortisone (Systemic); Leflunomide;
Mercaptopurine; Methotrexate; Methylprednisolone;
Prednisolone (Systemic); Prednisone; Triamcinolone,
(Systemic) [separate administration by at least 3
months]
Leflunomide [separate administration by at least 3
months]
Mercaptopurine [avoid doses >1.5 mg/kg daily]
Methotrexate [avoid doses >0.4 mg/kg weekly]
TEST INTERACTION. Temporarily suppresses tuberculin skin
test reactivity.
Administration: For SC administration into the outer aspect
of the upper arm in patients ≥12 months. Do NOT inject
by IV.
Reconstitute vaccine using the provided diluent. Gently
agitate to mix thoroughly. Discard if powder does not
dissolve. Use immediately after reconstitution. Do NOT
mix with other vaccines or injections. Use different
needles and syringes for each injection.
Administer while patient is seated or lying down to
prevent syncope related injuries.
Store the powder at 2–8°C prior to reconstitution.
Protect from light. Store diluent in refrigerator or at room
temperature. Do NOT freeze diluent. Store the lyophilized
vaccine between ­50 to 8˚C to maintain potency. May be
stored under refrigeration for up to 8 hours. Discard
unused portions after 8 hours.
Pregnancy Category: C
ATC Code: J07BD52
MEASLES AND RUBELLA (MR) VACCINE
Rx
(LIVE ATTENUATED)
Inj: multidose (10 doses/vial) + 5 mL diluent (SC), with
vaccine vial monitor (VVM)
The vaccine is prepared from the live, attenuated strains of
Edmonston-Zagreb measles virus and Wistar RA 27/3
rubella virus. Both measles and rubella viruses are
propagated on human diploid cells.
Indications: Immunization against measles and rubella.
Contraindications: Patients receiving corticosteroids,
immunosuppressive drugs or undergoing radiotherapy,
febrile states, pregnancy, acute infectious diseases,
leukemia, severe anemia, severe blood diseases, severe
renal impairment, decompensated heart diseases,
patients receiving gammaglobulin or blood transfusion,
or known allergies to vaccine components, and
J
anaphylactic reactions to neomycin.
Dose:
Immunization against measles and rubella, by
subcutaneous injection, ADULT and CHILD, 0.5 mL.
Dose Adjustment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
May cause mild pain and tenderness at the injection site.
Adverse Drug Reactions:
Common: Fever, arthralgia, arthritis, lymphadenopathy,
myalgia, paresthesia.
Less Common: Rash.
Rare: Encephalitis, thrombocytopenia, anaphylactic
reactions, urticarial, pruritus, and allergic rash.
Drug Interactions:
Immunoglobulins- risk of inactivation.
Administration: The vaccine should be administered by
deep subcutaneous injection into the anterolateral
aspect of upper thigh in toddlers and upper arm in older
children.
Pregnancy Category: X
ATC Code: J07BD53
MUMPS VACCINE
Rx
(LIVE ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
A preparation of live, attenuated organisms of the Jeryl Lynn
(B level) strain of mumps virus that stimulates active
immunity to mumps infection.
Indication: Active immunization against mumps
NOTE: NOT for children <12 months old.
303

Contraindications: Hypersensitivity to any component of the
formulation (including neomycin); immunocompromised
patients; thrombocytopenia; neurodevelopment
disorders (i.e., autism); tuberculosis
Dose:
Primary immunization, by SC injection, CHILD and INFANT
12 months to 12 years, 2 doses, administer first dose at
12–15 months of age and the second dose at 4–6 years
of age; the second dose may be given earlier provided at
least 28 days have elapsed since the first dose.
Administration: For SC administration into the upper-outer
triceps area or into the anterolateral thigh.
Administer while patient is seated or lying down to
prevent syncope related injuries.
See Measles, Mumps, and Rubella (MMR) Vaccine (Live
Attenuated) under Vaccines – Viral Vaccines in Chapter
J
7: Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07BE01
ORAL POLIO VACCINE, BIVALENT (LIVE
Rx
ATTENUATED) (TYPE 1 and 3)
Oral: 2 mg vial (20 doses)
Consists of bivalent, live attenuated poliomyelitis virus
vaccine of the Sabin strains Type 1 and Type 3
Indication: is indicated for active immunization in all age
groups against infection caused by poliomyelitis viruses
of Type 1 and 3.
Contraindications: is contraindicated in those with known
hypersensitivity to neomycin or polymyxin or any other
component of the vaccine. in subjects having shown
signs of hypersensitivity after previous administration of
oral poliomyelitis vaccines
Dose:
Primary vaccination or booster doses should be given
following official recommendations.
Dose Adjustment:
Renal and Hepatic Impairment:
no information
Precautions:
Hypersensitivity reactions
Pregnancy
Gastrointestinal infections (e.g., diarrhea and vomiting)
fecal excretion of the vaccine viruses may persist for
several weeks and may be transmitted to the contacts of
the vaccinees; contacts of vaccinees should be warned
about need for strict personal hygiene.
Adverse Drug Reactions:
Fever, vomiting, diarrhea
Rare: Vaccine-associated paralysis,
304
ANTI-INFECTIVES FOR SYSTEMIC USE
Drug Interactions:
Can be administered at the same time as the Haemophilus
influenzae type b vaccine, hepatitis B vaccine, diphtheria,
pertussis and/or tetanus vaccine, measles, rubella
and/or mumps vaccine, yellow fever vaccine, or BCG
vaccine if this fits into the vaccination schedule
Immunosuppressive treatment may reduce the immune
response, may favor the multiplication of the vaccine
viruses, and may increase the length of excretion of the
vaccine viruses in the stools
Administration: For oral use only, do NOT inject.
The vaccine dose is two drops (0.1 mL measured using a
multi-dose container)
The vaccinating dose can be administered directly in the
mouth or on a sugar lump.
If a dropper is used, care must be taken not to contaminate
the dropper with the saliva.
Should be administered to breastfed infants, preferably two
hours before or after breastfeeding, to avoid contact with
the antibodies present in the breast milk.
Store in the freezer (-20 °C). Do not use after the expiration
date printed on the syringe.
After thawing, the product can be stored for 6 months in the
refrigerator (2 °C to 8 °C).
Pregnancy Category: C
ATC Code: J07BF02
POLIOMYELITIS VACCINE
Rx
(TYPE 1, 2, 3) (INACTIVATED)
Inj.: 0.5 mL per dose suspension for injection, single dose
/multi-dose vial (IM, SC)
An inactivated viral vaccine that induces active immunity
against poliovirus types 1, 2, and 3 infection.
Indication: Active immunization against poliomyelitis
caused by poliovirus type 1, 2, and 3.
Contraindication: Hypersensitivity to any component of the
vaccine
Dose:
Immunization, by IM or SC injection, ADULT (previously
unvaccinated), three 0.5 mL doses, administer 2 doses
at 1–2 month intervals and the third dose 6–12 months
later; ADULT (incompletely vaccinated), for adults with
<3 doses of OPV and/or IPV, administer at least one 0.5
mL dose; ADULT (completely vaccinated by at increased
risk of exposure), one 0.5 mL dose.
Primary immunization, by IM or SC injection, CHILD and
INFANT 6 weeks to 47 months, three 0.5 mL doses at 2,
4, and 6–18 months of age.
Booster immunization, by IM or SC injection, CHILD 4 to 6
years, 0.5 mL as a single dose at least 6 months after
last dose; administer final booster dose at ≥4 years of
age, regardless of number of previous doses.
ANTI-INFECTIVES FOR SYSTEMIC USE
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use); syncope (has been
reported with use); acute illness; immunodeficiency.
Elderly (boosters may be necessary since antibody titers
may diminish with age).
Pregnancy (animal reproduction studies have not been
conducted).
Adverse Drug Reactions:
Common: Irritability, tiredness, fever, anorexia, vomiting,
injection site reactions (tenderness, swelling, erythema),
persistent crying
Less Common: Agitation, anaphylactic shock, allergic
reaction, anaphylaxis, hypersensitivity reactions,
arthralgia, febrile seizures, lymphadenopathy, headache,
myalgia, paresthesia, rash, seizures, somnolence,
urticaria
Rare: Guillain-Barré syndrome
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Influenza Vaccine:
Belimumab
Fingolimod [administer at least 2 weeks apart; if
vaccinated during fingolimod therapy, revaccinate 2–3
months after fingolimod discontinuation]
Immunosuppressants [Cytarabine, Liposomal]
[administer at least 2 weeks apart; if vaccinated during
immunosuppressant therapy, revaccinate at least 3
months after immunosuppressant discontinuation]
TEST INTERACTION. May temporarily suppress tuberculin
skin test sensitivity (4–6 weeks).
Administration: For IM or SC administration into the
midlateral aspect of the thigh in infants and small
children or in the deltoid area in adults or older children.
Administer while patient is seated or lying down to
prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety. Use a fine needle (23 gauge or
smaller) and apply firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other similar
therapy, intramuscular vaccination can be scheduled
shortly after such therapy is administered. Patients on
anticoagulant therapy should be considered to have the
same bleeding risks and treated as those with clotting
factor disorders.
Pregnancy Category: C
ATC Code: J07BF03
RABIES VACCINE – CHICK
Rx EMBRYO CELL
(PURIFIED, INACTIVATED)
Inj.: 2.5 IU/mL lyophilized powder, 1 dose vial + 1 mL
diluent (ID, IM)
Purified vaccine containing inactivated rabies virus
cultivated in chick embryo cells.
Indications: Active immunization against rabies; pre-
exposure and post-exposure prevention
NOTE: WHO recommends pre-exposure immunization of
individuals at high risk of contracting rabies, including
people living or traveling to enzootic areas and those at
risk due to occupational exposure, such as health and
laboratory workers, animal handlers, veterinary
surgeons, etc.
J
Contraindications: Hypersensitivity to the vaccine or any of
its components; fever; acute illness
Dose:
Pre-exposure vaccination, by IM injection, ADULT and
CHILD, three 0.5 mL doses on days 0, 7, and 28, followed
by one 0.5 mL booster dose after 1 year and every 5 year
hence after; may administer third dose as early as day
21 if time is limited;
by ID injection, ADULT and CHILD, three 0.1 mL doses on
days 0, 7, 28, followed by one 0.5 mL booster dose after
1 year and every 5 year hence after; may administer third
dose as early as day 21 if time is limited.
Pre-exposure vaccination, by IM injection, ADULT and CHILD
(fully immunized within the last 5 years, with a cell
culture rabies vaccine), two 0.5 mL doses on days 0 and
3; ADULT and CHILD (non-immunized, immunized more
than 5 years ago, or incomplete vaccination), five 0.5 mL
doses on days 0, 3, 7, 14, and 28 with 20 IU/kg of body
weight human rabies immunoglobulins (RIG) or 40 IU/kg
of body weight equine RIG, administered at the same
time as the first injection for severe injuries [NOTE:
Administer vaccine contralaterally to the RIG
administration sites];
by ID injection, ADULT and CHILD (fully immunized within
the last 5 years, with a cell culture rabies vaccine), two
0.1 mL doses on days 0 and 3; ADULT and CHILD (non-
immunized, immunized more than 5 years ago, or
incomplete vaccination), one 0.1 mL dose at 2 sites on
days 0, 3, 7, 14, and 28 with 20 IU/kg of body weight
human rabies immunoglobulins (RIG) or 40 IU/kg of body
weight equine RIG, administered at the same time as the
first injection for severe injuries [NOTE: Administer
vaccine contralaterally to the RIG administration sites].
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Immunodeficiency;
Elderly (boosters may be necessary since antibody titers
may diminish with age).
Pregnancy (requires dose adjustment).
305

SKILLED TASKS. May cause post-vaccination dizziness.
Avoid performing tasks, which require mental alertness,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Injection site reactions (pain, erythema, edema,
pruritus, induration), fever, shivering, malaise, asthenia,
headache, dizziness, arthralgia, myalgia, nausea,
abdominal pain
Rare: Anaphylactoid reaction, urticaria, rash
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Rabies Vaccine:
Immunoglobulins
Avoid concomitant use with:
Reduces therapeutic effect of Rabies Vaccine:
Corticosteroids (may cause failure of vaccination)
Other Immunosuppressants (may cause failure of
J
vaccination)
Administration: For IM administration into the deltoid region
in adults and children or the anterolateral thigh for
children <2 years of age. Do NOT inject into the gluteal
area because weaker levels of neutralizing antibodies
have been observed when this area is used.
May also administer by ID injection as an alternative into
the upper or forearm. ID route must be administered only
by medical staff trained in this technique to ensure
vaccine is delivered by ID and NOT by SC. Use sterile
syringe with fixed needle (insulin type). Do NOT inject by
IV or SC.
Thoroughly clean bite wound prior to administration.
Immediately flush out and wash with soap or detergent
to eliminate rabies virus at the infection site. Thoroughly
remove all traces of soap then apply 70% alcohol
solution, tincture or solution of iodine, or 0.1%
quaternary ammonium solution.
Reconstitute using the solvent provided. Shake gently to
obtain a homogenous suspension, appearing as a limpid
liquid. Immediately administer vaccine. Reconstituted
vaccine may be used for up to 8 hours provided it is
maintained at 2–8oC. Discard unused portions after 8
hours.
Pregnancy Category: C
ATC Code: J07BG01
RABIES VACCINE – VERO CELL
Rx
(PURIFIED)
Inj.: 2.5 IU/0.5 mL lyophilized powder, vial + diluent (ID,
IM)
2.5 IU/mL suspension, 1 mL vial (IM)
Purified vaccine containing inactivated rabies virus
cultivated in vero cells.
Indications: Active immunization against rabies; pre-
exposure and post-exposure prevention
306
ANTI-INFECTIVES FOR SYSTEMIC USE
NOTE: WHO recommends pre-exposure immunization of
individuals at high risk of contracting rabies, including
people living or traveling to enzootic areas and those at
risk due to occupational exposure, such as health and
laboratory workers, animal handlers, veterinary
surgeons, etc.
Contraindication: Hypersensitivity to the vaccine or any of its
components; fever; acute illness
Dose:
Pre-exposure vaccination, by IM injection, ADULT and
CHILD, three 0.5 mL doses on days 0, 7, and 28, followed
by one 0.5 mL booster dose after 1 year and every 5 year
hence after; may administer third dose as early as day
21 if time is limited;
by ID injection, ADULT and CHILD, three 0.1 mL doses on
days 0, 7, 28, followed by one 0.5 mL booster dose after
1 year and every 5 year hence after; may administer third
dose as early as day 21 if time is limited.
Pre-exposure vaccination, by IM injection, ADULT and CHILD
(fully immunized within the last 5 years, with a cell
culture rabies vaccine), two 0.5 mL doses on days 0 and
3; ADULT and CHILD (non-immunized, immunized more
than 5 years ago, or incomplete vaccination), five 0.5 mL
doses on days 0, 3, 7, 14, and 28 with 20 IU/kg of body
weight human rabies immunoglobulins (RIG) or 40 IU/kg
of body weight equine RIG, administered at the same
time as the first injection for severe injuries [NOTE:
Administer vaccine contralaterally to the RIG
administration sites];
by ID injection, ADULT and CHILD (fully immunized within
the last 5 years, with a cell culture rabies vaccine), two
0.1 mL doses on days 0 and 3; ADULT and CHILD (non-
immunized, immunized more than 5 years ago, or
incomplete vaccination), one 0.1 mL dose at 2 sites on
days 0, 3, 7, 14, and 28 with 20 IU/kg of body weight
human rabies immunoglobulins (RIG) or 40 IU/kg of body
weight equine RIG, administered at the same time as the
first injection for severe injuries [NOTE: Administer
vaccine contralaterally to the RIG administration sites].
Administration: For IM administration into the deltoid region
in adults and children or the anterolateral thigh for
children <2 years of age. Do NOT inject into the gluteal
area because weaker levels of neutralizing antibodies
have been observed when this area is used.
May also administer by ID injection as an alternative into
the upper or forearm. ID route must be administered only
by medical staff trained in this technique to ensure
vaccine is delivered by ID and NOT by SC. Use sterile
syringe with fixed needle (insulin type). Do NOT inject by
IV or SC.
Thoroughly clean bite wound prior to administration.
Immediately flush out and wash with soap or detergent
to eliminate rabies virus at the infection site. Thoroughly
remove all traces of soap then apply 70% alcohol
solution, tincture or solution of iodine, or 0.1%
quaternary ammonium solution.
Reconstitute using the solvent provided. Shak gently to
obtain a homogenous suspension, appearing as a limpid
liquid. Immediately administer vaccine. Reconstituted
vaccine may be used for up to 8 hours provided it is
ANTI-INFECTIVES FOR SYSTEMIC USE
maintained at 2–8oC. Discard unused portions after 8
hours.
See Rabies Vaccine – Chick Embryo Cell (Purified,
Inactivated) under Vaccines – Viral Vaccines in Chapter
7: Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07BG01
RUBELLA VACCINE
Rx
(LIVE ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
Multi-dose vial + 5 mL diluent (SC)
A preparation of live, attenuated rubella virus that
stimulates active immunity to rubella infection.
Indication: Active immunization against rubella (German
measles)
Contraindication: Hypersensitivity to any component of the
formulation
Dose:
Primary immunization, by SC injection, ADULT and
ADOLESCENT ≥13 years, one or two 0.5 mL doses
administered at least 28 days apart; CHILD, two 0.5 mL
doses; administer first dose at 12–15 months of age and
the second dose at 4–6 years of age; second dose may
be given earlier provided at least 28 days have elapsed
since the first dose and both doses are given at or after
12 months of age.
Administration: For SC administration into the upper-outer
triceps area or into the anterolateral thigh. Do NOT inject
by IV.
Reconstitute using the provided diluent and agitate the
vial. Do NOT use if the lyophilized vaccine does not
dissolve completely.
Visually inspect for particulate matter and discoloration
prior to administration. Use only sterile syringes and
needles that are free of preservatives, antiseptics, and
detergents.
Administer while patient is seated or lying down to
prevent syncope related injuries.
See Measles, Mumps, and Rubella (MMR) Vaccine (Live
Attenuated) under Vaccines – Viral Vaccines in Chapter
7: Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07BJ01
VARICELLA VACCINE
Rx
(LIVE ATTENUATED)
Inj.: Freeze-dried powder, not less than 2,000 PFU (OKA
strain varicella zoster virus) monodose vial + diluent
(0.5 mL water for injection) ampule (SC only)
A live attenuated viral vaccine that offers active immunity to
disease caused by the varicella-zoster virus by inducing
cell-mediated and humoral immune responses.
Indication: For the prevention of varicella in persons 12
months and older
Contraindications: Severe allergic or anaphylactic reaction
to the vaccine, neomycin, gelatin, or any component of
the formulation; leukemia; lymphoma; other malignant
neoplasms affecting the bone marrow or lymphatic
systems; HIV infection; patients on immunosuppressive
J
therapy; immunosuppressed or immunodeficient
individuals; active, untreated tuberculosis; primary and
acquired immunodeficiency states; current febrile
illness; pregnancy
Dose:
Immunization, by SC injection, ADULT, two 0.5 mL doses
separated by ≥4 weeks; CHILD ≥12 months, two 0.5 mL
doses separated by ≥3 months.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
HIV infection;
Immunodeficiency;
Pregnancy (avoid pregnancy for 3 months after vaccination).
Adverse Drug Reactions:
Common: Injection site reactions (rash), fever, chills,
disturbed sleep, fatigue, headache, irritability, malaise,
nervousness, contact dermatitis, diaper rash, varicella-
like rash, dermatitis, eczema, milliaria, pruritus, urticaria,
abdominal pain, xeroderma, constipation, decreased
appetite, diarrhea, nausea, period of tooth development,
vomiting, herpes labialis, lymphadenopathy,
hypersensitivity reaction, arthralgia, myalgia, neck
stiffness, otitis, cough, respiratory tract disease
Less Common: Anaphylactic shock, anaphylaxis,
angioedema, aseptic meningitis, ataxia, aplastic anemia,
Bell's palsy, cellulitis, cerebellar ataxia (acute),
cerebrovascular accident, dizziness, encephalitis,
erythema multiforme, facial edema, febrile seizures,
hemiparesis (acute), Guillain-Barré syndrome, hepatitis,
herpes zoster, IgA vasculitis, impetigo, paresthesia,
necrotizing retinitis, pharyngitis, pneumonia,
pneumonitis, peripheral edema, seizure (nonfebrile),
Stevens-Johnson syndrome, thrombocytopenia
(including immune thrombocytopenia), transverse
myelitis, secondary skin infection, varicella
(disseminated or vaccine strain)
Drug Interactions:
Avoid concomitant use with:
307

Increases risk of adverse or toxic effects of Varicella
Vaccine:
5-ASA Derivatives (Reye's Syndrome), Azathioprine,
Belimumab
Corticosteroids (Systemic)
Dimethyl Fumarate (vaccinal infection)
Fingolimod (vaccinal infection), Immunosuppressants,
Leflunomide
Mercaptopurine, Methotrexate
Salicylates e.g. Aspirin (Reye's Syndrome)
Smallpox Vaccine, Live (skin lesions)
Reduces diagnostic effect of Tuberculin Test [separate
administration by at least 4–6 weeks]
Reduces therapeutic effect of Varicella Vaccine:
Acyclovir-Valacyclovir [avoid concomitant use within 14
days of vaccination]
Azathioprine [avoid doses >3 mg/kg daily]
Corticosteroids, Systemic [avoid doses greater than an
J
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Dimethyl Fumarate
Famciclovir [avoid concomitant use within 14 days of
vaccination]
Fingolimod
Immune Globulins [consult full interaction monograph
for dose interval recommendations]
Immunosuppressants [except Azathioprine;
Beclomethasone (Oral Inhalation); Betamethasone
(Systemic); Budesonide (Systemic); Budesonide
(Systemic and Oral Inhalation); Corticotropin; Cortisone;
Cytarabine (Liposomal); Deflazacort; Dexamethasone
(Systemic); Fludrocortisone; Fluticasone (Oral
Inhalation); Hydrocortisone (Systemic); Leflunomide;
Mercaptopurine; Methotrexate; Methylprednisolone;
Prednisolone (Systemic); Prednisone; Triamcinolone
(Systemic) [separate administration by at least 3
months]
Leflunomide [separate administration by at least 3
months]
Mercaptopurine [avoid doses >1.5 mg/kg daily]
Methotrexate [avoid doses >0.4 mg/kg weekly]
Administration: For SC administration only into the outer
aspect of upper arm or the anterolateral thigh. Do NOT
administer by IV or IM.
Administer while patient is seated or lying down to
prevent syncope related injuries.
Store the powder at ­50 to -15˚C prior to reconstitution.
Reconstituted vaccine may be stored under refrigeration
at 2–8°C for up to 72 hours. Protect from light. Store
diluent at 20–25°C or in refrigerator. Do NOT freeze
diluent.
Use the total volume of the provided diluent to
reconstitute vaccine. Gently agitate to mix thoroughly.
Administer within 30 minutes of preparation. Discard
reconstituted vaccine if unused within 30 minutes.
Do NOT mix with other vaccines or injections. Use
different needles and syringes for each injection.
Pregnancy Category: C
308
ANTI-INFECTIVES FOR SYSTEMIC USE
ATC Code: J07BK01
Rx YELLOW FEVER VACCINE
Inj.: 1,000 DL 50 mouse min (attenuated) vial + 0.5 mL
solvent syringe (IM, SC)
NOTE: For Bureau of Quarantine use only.
A live vaccine that offers active immunization against yellow
fever infection at an effective immune response rate of
nearly 100% of patients.
Indication: Active immunization against yellow fever virus,
primarily among persons traveling to or living in areas
where yellow fever infection exists and laboratory
workers who may be exposed to the virus
Contraindications: Acute hypersensitivity to egg or chick
embryo protein, or any component of the formulation,
including gelatin; infants <6 months; acute or febrile
disease; immunosuppressed patients (e.g., HIV infection,
leukemia, lymphoma, thymic disease, generalized
malignancy, or immunosuppression due to drugs or
radiation) ; breastfeeding women
Dose:
Immunization, by SC injection, ADULT, ADOLESCENT, CHILD,
and INFANT ≥9 months, one 0.5 mL dose ≥10 days
before travel.
Precautions:
Anaphylactoid or hypersensitivity reactions (immediate
treatment, including epinephrine 1:1000 should be
available during vaccine use);
Syncope (has been reported with use);
Acute illness;
Immunodeficiency;
Elderly (increased incidence of serious adverse events in
patients ≥60 years of age);
Children (risk of encephalitis if used in infants <9 months of
age);
Pregnancy (avoid use during pregnancy; animal
reproduction studies have not been conducted);
Lactation (excreted into breastmilk).
Adverse Drug Reactions:
Common: Chills, fever, focal neurological defects,
headache, malaise, seizure, rash, urticaria, injection site
reactions (edema, erythema, hypersensitivity, mass,
pain, pruritus, rash, warmth), weakness, myalgia,
Guillain-Barré syndrome, hypersensitivity (immediate)
Rare: Vaccine-associated neurotropic disease, viscerotropic
disease
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Varicella
Vaccine:
Azathioprine
Belimumab
Corticosteroids (Systemic)
Dimethyl Fumarate (vaccinal infection)
Fingolimod (vaccinal infection)
Immunosuppressants
ANTI-INFECTIVES FOR SYSTEMIC USE
Leflunomide
Mercaptopurine
Methotrexate
Reduces diagnostic effect of Tuberculin Test [separate
administration by at least 4–6 weeks]
Reduces therapeutic effect of Varicella Vaccine:
Azathioprine [avoid doses >3 mg/kg daily]
Corticosteroids, Systemic [avoid doses greater than an
equivalent of 2 mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Dimethyl Fumarate, Fingolimod, Immunosuppressants
[except Azathioprine; Beclomethasone (Oral Inhalation);
Betamethasone (Systemic); Budesonide (Systemic);
Budesonide (Systemic and Oral Inhalation);
Corticotropin; Cortisone; Cytarabine (Liposomal);
Deflazacort; Dexamethasone (Systemic);
Fludrocortisone; Fluticasone (Oral Inhalation);
Hydrocortisone (Systemic); Leflunomide;
Mercaptopurine; Methotrexate; Methylprednisolone;
Prednisolonen (Systemic); Prednisone; Triamcinolone
(Systemic) [separate administration by at least 3
months]
Leflunomide [separate administration by at least 3
months]
Mercaptopurine [avoid doses >1.5 mg/kg daily]
Methotrexate [avoid doses >0.4 mg/kg weekly]
Administration: For SC administration only. Do NOT
administer by IV or IM. If inadvertently administered by
IM, the dose does not need repeated.
Administer while patient is seated or lying down to
prevent syncope related injuries.
Store at 2–8°C. Reconstitute using only provided
diluent. Inject diluent slowly into vial and allow to stand
for 1–2 minutes. Gently swirl until a uniform suspension
forms before withdrawing dose. Avoid vigorous shaking
to prevent foaming of suspension. Administer within 60
minutes of preparation. Keep suspension refrigerated
until used. Discard reconstituted vaccine if unused
within 60 minutes.
Do NOT mix with other vaccines or injections. Use
different needles and syringes for each injection.
Pregnancy Category: C
ATC Code: J07BL01
BACTERIAL AND VIRAL VACCINES,
COMBINED
DTaP + HEMOPHILUS
Rx
INFLUENZA TYPE B (Hib)
Inj.: 0.5 mL pre-filled syringe (IM)
A combination product containing adsorbed diphtheria,
tetanus, acellular pertussis, and Haemophilus
influenzae type b vaccines.
Indications: Active immunization against diphtheria,
tetanus, pertussis, and invasive disease caused by
Haemophilus influenzae type b (Hib)
Contraindications: Hypersensitivity to any component of the
formulation; progressive neurologic disorder, including
infantile spasms, uncontrolled epilepsy or progressive
epilepsy; encephalopathy occurring within 7 days of
administration and not attributable to another cause
See individual monographs for Diphtheria-Tetanus Toxoids
and Acellular Pertussis Vaccine (DTaP) and Hemophilus
Influenzae Type B Conjugate Vaccine (Hib) under
Vaccines – Bacterial Vaccines in Chapter 7:
Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07AG52; J07AJ52
J
DTP + HEMOPHILUS
Rx
INFLUENZA TYPE B (Hib)
Inj.: 0.5 mL DTP diluent in pre-filled syringe + freeze-dried
10 micrograms Hib vial (IM, SC)
A combination product containing adsorbed diphtheria,
tetanus, whole cell pertussis, and Haemophilus
influenzae type b vaccines.
Indication: Active immunization against diphtheria, tetanus,
pertussis, and invasive disease caused by Haemophilus
influenzae type b (Hib)
Contraindications: Hypersensitivity to the any component of
the formulation; severe acute neurological illness within
7 days of pertussis vaccination; thrombocytopenia or any
coagulation disorders
See individual monographs for Diphtheria-Tetanus Toxoids
and Pertussis Vaccine (DTP) and Hemophilus Influenzae
Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines in Chapter 7: Antiinfectives for
Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07AG52; J07AJ51
DTP + HEPATITIS B VACCINE
Rx
(RECOMBINANT)
Inj.: 0.5 mL vial (IM, SC)
A combination vaccine that promotes active immunity to
diphtheria, tetanus, pertussis, and hepatitis B by
inducing production of specific antibodies and antitoxins.
Indication: Active immunization against diphtheria, tetanus,
pertussis, and hepatitis B
Contraindications: Hypersensitivity to diphtheria and
tetanus toxoids, pertussis, hepatitis B, poliovirus
309

vaccine, or any component of the vaccine;
encephalopathy (within 7 days of a previous pertussis
vaccine not attributable to another identifiable cause);
progressive neurologic disorders (including infantile
spasms, uncontrolled epilepsy, or progressive
encephalopathy)
Dose:
Primary immunization, by IM injection, CHILD <7 years and
INFANT ≥6 weeks, three 0.5 mL doses administered at
2, 4, and 6 months of age in 6–8 week intervals.
Administration: For IM administration into the anterolateral
aspect of the thigh or the deltoid muscle. Do NOT
administer by IV or SC.
Shake suspension well before use. Store at 2–8°C.
Discard if frozen. Do NOT use a defrosted vaccine. May
be stored at room temperature for up to 24 hours.
J
Do NOT mix with other vaccines or injections. Use
different needles and syringes for each injection.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety.
If the patient receives anti-hemophilia or other similar
therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
See individual monographs for Diphtheria-Tetanus Toxoids
and Pertussis Vaccine (DTP) under Vaccines – Bacterial
Vaccines and Hepatitis B Vaccine (Recombinant DNA)
under Vaccines – Viral Vaccines in Chapter 7:
Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07CA05
DTP + INACTIVATED POLIO
Rx
VACCINE (IPV)
Inj.: 0.5 mL monodose vial (IM, SC)
0.5 mL pre-filled syringe (IM, SC)
A combination vaccine that promotes active immunity to
diphtheria, tetanus, pertussis, and poliovirus (types 1, 2
and 3) by inducing production of specific antibodies and
antitoxins.
Indications: Active immunization against diphtheria,
tetanus, pertussis, and poliovirus
Contraindications: Hypersensitivity to any component of the
vaccine; severe acute neurological illness within 7 days
of pertussis vaccination; thrombocytopenia or any
coagulation disorders
Dose:
310
ANTI-INFECTIVES FOR SYSTEMIC USE
Immunization, by IM injection, CHILD 4–6 years, 0.5 mL as
a single dose.
Administration: For IM administration only into the deltoid
muscle. Do NOT administer by ID, IV, or SC.
Shake suspension well before use. Do NOT use unless a
homogenous, turbid, white suspension forms. Discard if
the suspension is discolored, or if there are cracks in the
vial or syringe.
Store at 2–8°C. Do NOT freeze. Discard if frozen.
NOTE: For patients at risk of hemorrhage following IM
injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety.
If the patient receives anti-hemophilia or other similar
therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding
risks and treated as those with clotting factor disorders.
See individual monographs for Diphtheria-Tetanus Toxoids
and Pertussis Vaccine (DTP) under Vaccines – Bacterial
Vaccines and Poliomyelitis Vaccine (Type 1, 2, 3)
(Inactivated) under Vaccines – Viral Vaccines in Chapter
7: Antiinfectives for Systemic Use for other information.
Pregnancy Category: C
ATC Code: J07CA02
Rx DTP + IPV + Hib
Inj.: 0.5 mL pre-filled syringe (IM, SC)
A combination vaccine that promotes active immunity to
diphtheria, tetanus, pertussis, poliovirus (types 1, 2 and
3) and Haemophilus influenzae type b (Hib) by inducing
production of specific antibodies and antitoxins.
Indications: Active immunization against diphtheria,
tetanus, pertussis, poliovirus (type 1, 2, 3), and invasive
disease caused by Haemophilus influenzae type b
Contraindications: Hypersensitivity to any component of the
vaccine; severe acute neurological illness within 7 days
of pertussis vaccination; thrombocytopenia or any
coagulation disorders
Dose:
Immunization, by IM injection, CHILD and INFANT 6 weeks
to <5 years, four 0.5 mL doses at 2, 4, 6, and 15–18
months of age; first dose may be administered as early
as 6 weeks of age.
Administration: For IM administration only into the
anterolateral aspect of the thigh in children <1 year of
age or into the deltoid muscle of older children. Do NOT
administer to the gluteal area or areas near a major
nerve trunk. Do NOT administer by IV or SC.
ANTI-INFECTIVES FOR SYSTEMIC USE

Combine DTP and IPV, and gently shake suspension well Pregnancy Category: C
before use. Withdraw liquid contents and inject into vial
containing Hib power. Gently swirl until a cloudy ATC Code: J07CA11
suspension result.

Store at 2–8°C. Do NOT freeze. Discard if frozen.

Do NOT mix with other vaccines or injections. Use

different needles and syringes for each injection.

NOTE: For patients at risk of hemorrhage following IM

injection, administer by IM only if, in the opinion of the
physician familiar with the patient's bleeding risk, the
vaccine can be administered by this route with
reasonable safety.

If the patient receives anti-hemophilia or other similar

therapy, IM vaccination can be scheduled shortly after
such therapy is administered. Patients on anticoagulant
therapy should be considered to have the same bleeding

J
risks and treated as those with clotting factor disorders.
See individual monographs for Diphtheria-Tetanus Toxoids
and Pertussis Vaccine (DTP) and Hemophilus influenzae
Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines and Poliomyelitis Vaccine (Type 1, 2,
3) (Inactivated) under Vaccines – Viral Vaccines in
Chapter 7: Antiinfectives for Systemic Use for other
information.

Pregnancy Category: C

ATC Code: J07CA06

DIPHTHERIA, TETANUS,
PERTUSSIS, HEPATITIS B
(RECOMBINANT), AND
Rx
HEMOPHILUS INFLUENZA
TYPE B (Hib) COMBINED
VACCINE

Inj.: 0.5 mL vial suspension for injection (IM)

A combination vaccine that promotes active immunity to

diphtheria, tetanus, pertussis, hepatitis B and
Haemophilus influenzae type b (Hib) by inducing
production of specific antibodies and antitoxins.

Indications: Active immunization against diphtheria,

tetanus, pertussis, hepatitis B, and invasive disease
caused by Haemophilus influenzae type b

Contraindications: Hypersensitivity to any component of the

vaccine; severe acute neurological illness within 7 days
of pertussis vaccination; thrombocytopenia or any
coagulation disorders

See individual monographs for Diphtheria-Tetanus Toxoids

and Pertussis Vaccine (DTP) and Hemophilus influenzae
Type B Conjugate Vaccine (Hib) under Vaccines –
Bacterial Vaccines and Hepatitis B Vaccine
(Recombinant DNA) under Vaccines – Viral Vaccines in
Chapter 7: Antiinfectives for Systemic Use for other
information.

311
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Renal impairment (e.g. hemorrhagic cystitis, pyelitis,

ANTINEOPLASTIC AND ureteritis, and hematuria; urotoxicity appears to be
IMMUNOMODULATING AGENTS dependent on dose and treatment duration; may occur
with short-term use; discontinue use when severe
hemorrhagic cystitis occurs; use with caution in patients
ANTINEOPLASTIC AGENTS with active UTI)
Elderly (watch out for signs of infections such as fever and
elevated WBC)
For antineoplastic agents, these should be administered Pregnancy (may cause fetal harm; adverse renal effects,
under the supervision of an experienced hematologist- e.g. unilateral agenesis; women of childbearing potential
oncologist in the use of cancer chemotherapeutic should avoid pregnancy for up to 1 year after completion
agents. Administer in a facility sufficient to appropriately of treatment; males with female partners who are or may
diagnose and manage complications. The dosing become pregnant should use condoms during and for at
regimen will depend on the protocol being used by the least 4 months after treatment);
institution. Lactation (excreted in breastmilk; leukopenia and
thrombocytopenia have been reported in nursing infant).
For a comprehensive information on adverse events and
dose modifications, please refer to
https://ctep.cancer.gov/protocoldevelopment/electroni
c_applications/doc/CTCAE_v5_Quick_Reference_5x7.p Rx CHLORAMBUCIL
df
Oral: 2 mg tablet
ALKYLATING AGENTS
L

A nitrogen mustard analogue that interferes with DNA

NITROGEN MUSTARD ANALOGUES replication and RNA transcription through alkylation and
crosslinking of DNAstrands producing cytotoxic effects.
General Information
Indications: Chronic lymphocytic leukemia (CLL); Hodgkin
lymphoma; non-Hodgkin’s lymphoma (NHL)
Nitrogen mustard analogues are characterized by the
presence of the bischloroethyl group. They exhibit
Contraindications: Prior (demonstrated) resistance to
anticancer activity by initially producing an aziridinium
chlorambucil
ring through intramolecular displacement of the chloride
by the amine nitrogen. The reactive aziridinium ring act
Dose:
as a DNA alklylating agent.
Chronic lymphocytic leukemia, by mouth, ADULT, 0.1 mg/kg
daily for 3–6 weeks; or 0.4 mg/kg pulsed doses
Precautions:
administered intermittently, biweekly, or monthly, then
Allergic reactions and hypersensitivity
increased by 0.1 mg/kg per dose until response or
Bone marrow suppression and immunosuppression (e.g.
toxicity is observed.
leukopenia, neutropenia, thrombocytopenia, and
Hodgkin lymphoma, by mouth, ADULT, 0.2 mg/kg daily for
anemia; may lead to serious, fatal infections, or may
3–6 weeks.
activate latent infections; may require dose reduction or
Non-Hodgkin’s lymphoma, by mouth, ADULT, 0.1-0.2 mg/kg
discontinuation of treatment)
daily for 3–6 weeks.
Wound healing impairment
Cardiotoxicity (e.g. arrhythmias, congestive heart failure,
NOTE: For adults with bone marrow lymphocytic infiltration
heart block, hemorrhagic myocarditis,
involvement or when the bone marrow is hypoplastic, the
hemopericardium, pericarditis, pericardial effusion, and
maximum dose is 0.1 mg/kg daily.
tachyarrhythmias usually with high doses associated
with transplant conditioning regimens)
Reduce initial dose if administered within 4 weeks
Fertility effects (e.g. sterility in males and females;
after full course of radiation/ myelosuppressive therapy.
amenorrhea in females; probably mutagenic and
teratogenic)
Dose Adjustment:
Gastrointestinal adverse effects (e.g. nausea and vomiting)
Geriatric:
Hyponatremia (e.g. syndrome resembling SIADH)
Initiate at the lower end of dosing range. Toxicity to
Pulmonary toxicities (e.g. pneumonitis, pulmonary fibrosis,
immunosuppressants is increased in the elderly.
pulmonary veno-occlusive disease, and ARDS)
Secondary malignancies (e.g. bladder cancer,
Renal Impairment:
myelodysplasia, acute leukemias, lymphomas, thyroid
For patients with CrCl 10–50 mL/minute, administer 75%
cancer, and sarcomas)
of dose.
Seizures (use with caution in patients with a history of
For patients with CrCl <10 mL/minute and patients
seizure disorder or head trauma);
undergoing peritoneal dialysis, administer 50% of dose.
Skin reactions (e.g, erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis).
Hepatic Impairment:
Hepatic impairment (e.g. hepatic sinusoidal obstruction
Chlorambucil is primarily metabolized in the liver. Consider
syndrome (SOS))
dose reduction.

312
ANTINEOPLASTIC AND IMMODULATING AGENTS
Precautions:
WARNING: Chlorambucil is a carcinogen in humans
and can severely suppress bone marrow function.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Please see other precautions under General
Adverse Drug Reactions:
Common: Drug fever, fever, angioneurotic edema, rash,
urticaria, amenorrhea, infertility, skin hypersensitivity,
azoospermia, neutropenia, bone marrow failure
(irreversible), bone marrow suppression, cystitis,
leukemia (secondary), leukopenia, lymphophenia,
pancytopenia, anemia, thrombocytopenia,
hepatotoxicity, jaundice, peripheral neuropathy,
interstitial pneumonia, pulmonary fibrosis, allergic
reactions, malignancies (secondary)
Less Common: Diarrhea, nausea, oral ulceration, vomiting
Rare: Agitation, ataxia, confusion, focal / generalized
seizure, hallucinations, erythema multiforme, Stevens-
Johnson syndrome, toxic epidermal necrolysis, SIADH,
flaccid paralysis, muscular twitching, myoclonia, tremor
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Chlorambucil:
Denosumab (serious infections), Trastuzumab
(neutropenic effect)
Increases risk of adverse or toxic effects of Leflunomide
(hematologic toxicity, including pancytopenia,
agranulocytosis, and/or thrombocytopenia)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Chlorambucil:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Tofacitinib [except antirheumatic doses of Methotrexate,
nonbiologic DMARD] (immunosuppressive effect)
Increases risk of adverse or toxic effects of Chlorambucil:
Dipyrone (agranulocytosis), Pimecrolimus,
Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Natalizumab (concurrent
infection), Vaccines (Live)
Reduces therapeutic effect of Chlorambucil:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (Inactivated) [complete all
age-appropriate vaccinations at least 2 weeks prior to
starting Chlorambucil; if vaccinated during Chlorambucil
therapy, revaccinate at least 3 months after
discontinuation], Vaccines (Live) [do not administer
vaccines for at least 3 months after Chlorambucil
therapy]
Administration: May be administered as a single daily dose,
preferably on an empty stomach.
See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
and Immunomodulating Agents for other information.
Pregnancy Category: D
ATC Code: L01AA02
Rx CYCLOPHOSPHAMIDE
Inj.: 200 mg, 500 mg, and 1 g powder, vial (IV)
A precursor nitrogen mustard analogue that acts as an
antineoplastic agent preventing cell division by
crosslinking of DNA strands and decreasing DNA
synthesis. As a prodrug, it must be metabolized in the
liver to form the active aldophosphamide. It is a cell cycle
L
phase nonspecific agent that possesses potent
immunosuppressive activity.
Indication: Malignant diseases, including lymphomas,
leukemia, neuroblastoma, adenocarcinoma, carcinoma
of the breast and mycosis fungoides, management for
lupus in patients irresponsive to traditional therapy or
with kidney damage
Contraindications: Urinary outflow obstruction
Dose:
Malignancy, by IV injection, ADULT, 40–50 mg/kg (400-
1800 mg/m2) in divided doses over 2–5 days, may be
repeated at intervals of 2-4 weeks; or 10–15 mg/kg
every 7–10 days; or 3–5 mg/kg twice weekly; or 60-120
mg/m2/day (1-2.5 mg/kg/day continuous daily therapy;
500-1500 mg/m2 IV at intervals of 2-3 weeks in
combination with other neoplastic agents
Lupus nephritis, by IV infusion, ADULT, 50–150 mg daily as
a single dose.
Malignant Diseases, CHILD, IV (intermittent therapy): 40-50
mg/kg (400-1800 mg/m²) divided over 2-5 days; may be
repeated at intervals of 2-4 weeks
IV (continuous daily therapy): 60-120 mg/m²/day (1-2.5
mg/kg/day)
PO (intermittent therapy): 400-1000 mg/m² divided over
4-5 days
PO (continuous daily therapy): 50-100 mg/m²/day
Juvenile Idiopathic Arthritis/Vasculitis, CHILD, 10 mg/kg
IV every 2 weeks
Nephrotic Syndrome, CHILD, 2-3 mg/kg/day for up to 12
weeks when corticosteroids are unsuccessful
Systemic Lupus Erythematosus, CHILD, 500-750 mg/m²
IV monthly; not to exceed 1 g/m²
Dose Adjustment:
Geriatric:
Titrate dose carefully, initiating therapy at the lowest end of
the dosage range. Adjust dose for renal function. Safety
and efficacy have not been studied.
Renal Impairment:
313
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Use with caution. Elevated levels of metabolites may occur.
Reduce dose if serum creatinine concentration >120
micromoles/liter.
CrCl <10 mL/min, give 75% of normal dose
Cyclophosphamide and its metabolites are dialyzable.
Differences in amount dialyzed may occur due to dialysis
system used. Maintain a consistent interval between
administration and dialysis.
Hepatic Impairment:
Use with caution. Dose adjustment may be needed.
Give 75% of normal dose if transaminase levels are >3
times upper limit of normal or bilirubin is 3.1-5 mg/dl
Obesity:
Maximum dose should not exceed 0.1 mg/kg daily.
Precautions:
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
L
Increases risk of adverse or toxic effects of
Cyclophosphamide:
Allopurinol (bone marrow suppression), Azathioprine
(hepatotoxic effect), Denosumab (serious infections),
Filgrastim (pulmonary toxicity), Pentostatin (cardiotoxic
effect), Protease Inhibitors (neutropenia, infection,
mucositis), Thiazide Diuretics (granulocytopenia)
Increases risk of adverse or toxic effects of the following
drugs:
Amiodarone (pulmonary toxicity)
Antineoplastic Agents, Anthracycline,
Sargramostim (pulmonary toxicity)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Cyclophosphamide:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Tofacitinib [except antirheumatic doses of Methotrexate
or nonbiologic DMARD] (immunosuppressive effect)

Adverse Drug Reactions:

Common: Alopecia, amenorrhea, azoospermia, gonadal
Increases metabolism of Cyclophosphamide:
suppression, oligospermia, oogenesis impaired, sterility,
CYP2B6 Inducers
abdominal pain, anorexia, diarrhea, mucositis, nausea,
vomiting, stomatitis, hemorrhagic cystitis, anemia,
Increases risk of adverse or toxic effects of
leukopenia, myelosuppression, neutropenia,
Cyclophosphamide:
neutropenic fever, thrombocytopenia, infection
Belimumab, Dipyrone (agranulocytosis, pancytopenia),
Less Common: Acute respiratory distress syndrome,
Etanercept (solid cancer development), Pimecrolimus
anaphylactic reactions, anaphylaxis, arrhythmias,
Tacrolimus, Topical
bladder or urinary fibrosis, blurred vision, cardiac
tamponade, cardiotoxicity, confusion, dizziness,
Increases risk of adverse or toxic effects of the following
dyspnea, decreased ejection fraction, erythema
drugs:
multiforme, gastrointestinal hemorrhage, hearing
Clozapine (agranulocytosis), Leflunomide (hematologic
disorders, heart block, heart failure, hematuria,
toxicity), Natalizumab (concurrent infection), Vaccines
hemopericardium, hemorrhagic colitis, hemorrhagic
(Live)
myocarditis, hemorrhagic ureteritis, hepatic sinusoidal
obstruction syndrome, hepatitis, hepatotoxicity,
Increases serum concentration of Succinylcholine
hypersensitivity reactions, hyperuricemia, hypokalemia,
hyponatremia, interstitial pneumonitis, interstitial
Reduces therapeutic effect of the following drugs:
pulmonary fibrosis, jaundice, latent infection
BCG (Intravesical), Vaccines (Inactivated) [complete all
reactivation, malaise, acute mesenteric ischemia,
age-appropriate vaccinations at least 2 weeks prior to
methemoglobinemia, multiorgan failure, myocardial
starting Cyclophosphamide; if vaccinated during
necrosis, neurotoxicity, neutrophilic eccrine hidradenitis,
Cyclophosphamide therapy, revaccinate at least 3
ovarian fibrosis, pancreatitis, pericarditis, pigmentation
months after discontinuation], Vaccines (Live) [do not
changes (skin, fingernails), pneumonia, pulmonary
administer vaccines for at least 3 months after
hypertension, pulmonary infiltrates, pulmonary veno--
Cyclophosphamide therapy]
occlusive disease, pyelonephritis, radiation recall, rash,
renal tubular necrosis, reversible posterior
Reduces therapeutic effect of Cyclophosphamide:
leukoencephalopathy syndrome, rhabdomyolysis,
Echinacea
secondary malignancy, septic shock, sepsis, SIADH,
Stevens-Johnson syndrome, testicular atrophy,
Administration: If reconstituted in normal saline (NS),
thrombocytopenia, thrombotic disorders, toxic epidermal
administer by direct IV injection, IVPB, or continuous IV
necrolysis, toxic megacolon, tumor lysis syndrome,
infusion.
weakness, wound healing impaired
Increase normal fluid intake during and for 1–2 days
after treatment to minimize bladder toxicity. Most adult
Drug Interactions:
patients will require at least 2 L of fluid intake per day.
Monitor closely with:
High-dose regimens should be accompanied by vigorous
Decreases metabolism of Cyclophosphamide:
hydration.
CYP2B6 Inhibitors
Infusion rate may vary based on protocol (refer to specific
Enhances therapeutic effect of Cyclophosphamide:
protocol for infusion rate). Administer by direct IV
Cyclosporine (immunosuppressive effect)
injection (if reconstituted in NS), IVPB, or continuous IV
Trastuzumab (neutropenic effect)
infusion.

314
ANTINEOPLASTIC AND IMMODULATING AGENTS
NOTE: Cyclophosphamide is associated with a moderate to
high emetic potential depending on dose, regimen, or
administration route. Antiemetics are recommended to
prevent nausea and vomiting.
To minimize bladder toxicity, increase normal fluid intake
during and for 1-2 days after cyclophosphamide dose.
Most adult patients will require a fluid intake of at least
2 L daily. High-dose regimens should be accompanied by
vigorous hydration with mesna therapy.
See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
and Immunomodulating Agents for other information.
Pregnancy Category: D
ATC Code: L01AA01
Rx IFOSFAMIDE
Inj.: 1 g and 2 g powder, vial (IV infusion)
A nitrogen mustard analogue structurally related to
cyclophosphamide and is inhibitory to protein synthesis and
DNA synthesis by causing crosslinking of DNA strands
and by binding with nucleic acids and other intracellular
structures.
Indication: Treatment of germ cell testicular cancer (third-
line), lymphoma, sarcoma, solid tumors
Contraindications: Urinary outflow obstruction; severe renal
and hepatic impairment
Dose:
Testicular cancer, by IV infusion, ADULT,
combination chemotherapy with mesna: 1,200 mg/m2
daily for 5 days over at least 30 minutes, repeat every 3
weeks or after hematologic recovery;
VIP regimen (etoposide, mesna, cisplatin) or VeIP
regimen (vinblastine, mesna, cisplatin): 1,200 mg/m2
daily for 5 days every 3 weeks for 4 cycles.
Lymphoma, sarcoma, solid tumors, by IV infusion, ADULT,
Regimen 1: 8–12 g/m2 divided over 3–5 days, repeat
course every 2–4 weeks;
Regimen 2: 6 g/m2 divided over 5 days, repeat course
every 3 weeks;
Regimen 3: 5–6 g/m2 (maximum, 10 g), give as a single
24-hour infusion, repeat course every 3 to 4 weeks;
CHILD, 1,200 to 1,800 mg/m2/day for 3 to 5 days every 21
to 28 days.
Dose Adjustment:
Renal Impairment:
Consider dose reduction. Ifosfamide and metabolites are
excreted renally and may accumulate in patients with
renal dysfunction.
For patients with CrCl <10 mL/min, Ifosfamide is
not recommended.
Ifosfamide and metabolites are dialyzable.
Hepatic Impairment:
Extensively hepatically metabolized to both active and
inactive metabolites. Use with caution.
For patients with bilirubin >3 mg/dL, administer 25% of
dose.
Obesity:
Utilize patient’s actual body weight (full weight) for
calculation of body surface area-based or weight-based
dosing, particularly when the intent of therapy is curative.
If a dose reduction is utilized due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, once cause of toxicity is resolved.
Precautions:
HIGH-ALERT MEDICATION
The Institute for Safe Medication Practices (ISMP)
includes this drug in the list of drug classes with a
heightened risk of causing significant patient harm
when used in error.
WARNING: Nephrotoxicity can be severe and may
result in renal failure.
L
Myelosuppression is increased with single high doses
and decreased renal function. Severe
myelosuppression may occur when administered
in combination with other chemotherapy agents or
radiation therapy. Antimicrobial prophylaxis may
be necessary in some neutropenic patients.
CNS toxicities can be severe and may result in
encephalopathy and death.
Hemorrhagic cystitis can be severe and can be
reduced by the prophylactic use of mesna.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Adverse Drug Reactions:
Common: CNS toxicity, encephalopathy, fever, alopecia,
metabolic acidosis, nausea, vomiting, anorexia, anemia,
thrombocytopenia, phlebitis, leukopenia, neutropenic
fever, liver dysfunction, renal impairment, hematuria,
infection, somnolence, depression, hallucinations
Less Common: Abdominal pain, acute renal failure, acute
respiratory distress syndrome, acute tubular necrosis,
agranulocytosis, allergic reaction, alveolitis (allergic),
amenorrhea, aminoaciduria, amnesia, anaphylactic
reaction, angina, angioedema, anuria, arrhythmia,
arthralgia, atrial ectopy, atrial fibrillation, atrial flutter,
asterixis, azoospermia, bladder irritation, bleeding,
blurred vision, bone marrow failure, bradyphrenia,
bronchospasm, bradycardia, bundle branch block,
capillary leak syndrome, cardiac arrest, cardiogenic
shock, cardiotoxicity, catatonia, cardiomyopathy, cecitis,
chest pain, chills, cholestasis, chronic renal failure,
coagulopathy, conjunctivitis, constipation, cough, colitis,
cylindruria, cytolytic hepatitis, delirium, delusion,
dermatitis, disseminated intravascular coagulation, DVT,
dysarthria, diarrhea, dysesthesia, dyspnea, dysuria,
echolalia, edema, decreased ejection fraction,
enterocolitis, enuresis, enzymuria, erythema, decreased
315

estrogen, extrapyramidal disorder, facial swelling,
Fanconi syndrome, fatigue, fecal incontinence, flushing,
GI hemorrhage, gait disturbance, glycosuria,
granulocytopenia, growth retardation (children), hearing
loss, heart failure, hemolytic uremic syndrome,
hemorrhagic cystitis, hepatic failure, hemolytic anemia,
hepatic sinusoidal obstruction syndrome (SOS), hepatitis
fulminant, hepatitis (viral), hepatorenal syndrome,
herpes zoster, hyperhidrosis, hypoxia, hypertension,
hypotension, hyperpigmentation, hypersensitivity
reactions, hypesthesia, ileus, hypocalcemia,
hypokalemia, hyponatremia, hypophosphatemia,
infertility, infusion site reactions, immunosuppression,
interstitial lung disease, interstitial pneumonitis,
jaundice, increased LDH, leukoencephalopathy, limb
pain, logorrhea, lymphopenia, malaise, mania, mental
status change, MI, mucosal inflammation or ulceration,
methemoglobinemia, multiorgan failure, muscle
twitching, mutism, myalgia, myocardial hemorrhage,
myocarditis, neuralgia, nail disorder, nephrogenic
diabetes insipidus, neutropenia, oligospermia,
osteomalacia, oliguria, ovarian failure, ovulation
disorder, pain, palmar-plantar erythrodysesthesia
L
syndrome, pancreatitis, pancytopenia, paranoia, panic
attack, paresthesia, pericardial effusion, pericarditis,
peripheral neuropathy, petechiae, phosphaturia,
physical deterioration, pleural effusion, Pneumocystis
jiroveci pneumonia, pneumonia, pneumonitis,
pollakiuria, polydipsia, polyneuropathy, polyuria, portal
vein thrombosis, premature atrial contractions,
progressive multifocal leukoencephalopathy, premature
menopause, proteinuria, pruritus, pulmonary edema,
pulmonary embolism, pulmonary fibrosis, pulmonary
hypertension, abnormal QRS complex, radiation recall
dermatitis, rash, renal parenchymal damage, renal
tubular acidosis, respiratory failure, rickets, reversible
posterior leukoencephalopathy syndrome (RPLS),
seizures, rhabdomyolysis, salivation, secondary
malignancy, sepsis, septic shock, SIADH, skin necrosis,
impaired spermatogenesis, status epilepticus, Stevens-
Johnson syndrome, toxic epidermal necrolysis,
stomatitis, abnormal ST-segment, supraventricular
extrasystoles, sterility, tachycardia, tinnitus,
tubulointerstitial nephritis, tumor lysis syndrome, T-wave
inversion, uremia, urticaria, vasculitis, ventricular
extrasystoles, ventricular failure, ventricular fibrillation,
ventricular tachycardia, vertigo, visual impairment,
wound healing impairment
Severe (Potentially Fatal): Severe myelosuppression,
hemorrhagic cystitis, nephrotoxicity, cardiotoxicity, coma
Drug Interactions:
NOTE: Ifosfamide is a substrate of CYP2B6 (major),
CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor),
CYP3A4 (minor).
Monitor closely with:
Decreases metabolism of Ifosfamide:
CYP2B6 Inhibitors
Enhances therapeutic effect of Ifosfamide:
Trastuzumab (neutropenic effect)
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
316
ANTINEOPLASTIC AND IMMODULATING AGENTS
Increases risk of adverse or toxic effects of Ifosfamide:
Allopurinol (bone marrow suppression), Busulfan
(hemorrhagic cystitis), Cisplatin, Denosumab (serious
infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases serum concentration of Ifosfamide:
Dabrafenib
Enhances therapeutic effect of Ifosfamide:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases metabolism of Ifosfamide:
CYP2B6 Inducers
Increases risk of adverse or toxic effects of Ifosfamide:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Vaccines (Live)
Reduces therapeutic effect of Ifosfamide:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG, Vaccines (Inactivated) [complete all age-
appropriate vaccinations at least 2 weeks prior to
starting Ifosfamide; if vaccinated during Ifosfamide
therapy, revaccinate at least 3 months after
discontinuation], Vaccines (Live) [do not administer
vaccines for at least 3 months after Ifosfamide therapy]
Administration: Administer IV infusion over at least 30
minutes (infusion times may vary by protocol; refer to
specific protocol for infusion duration) with adequate
hydration of at least 2 L of oral or IV fluid daily.
NOTE: Administer with mesna and hydration of at least 2 L
of oral or IV fluid per day to prevent bladder toxicity.
Associated with a moderate emetic potential.
Antiemetics are recommended to prevent nausea and
vomiting.
See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
and Immunomodulating Agents for other information.
Pregnancy Category: D
ATC Code: L01AA06
ANTINEOPLASTIC AND IMMODULATING AGENTS
Rx MELPHALAN
Oral: 2 mg tablet
A derivative of mechlorethamine, melphalan is an alkylating
agent that acts on both resting and rapidly dividing tumor
cells. It inhibits DNA and RNA syntheses and crosslinks
DNA strands.
Indications: Treatment of multiple myeloma, polycythemia
vera, and nonresectable epithelial ovarian carcinoma
Contraindications: Resistance to prior melphalan therapy;
severe bone marrow suppression; pregnancy
Dose:
Multiple myeloma, remission induction treatment, by
mouth, ADULT, used in combination with other
chemotherapeutic agents (VMP regimen) 9mg/m2 on
days 1 to 4 of a 28-day cycle
Palliative treatment, by mouth, ADULT, initially 6 mg once
daily for 2–3 weeks, followed by up to 4 weeks rest, then
2 mg daily as maintenance dose as hematologic recovery
begins; or
10 mg daily for 7–10 days, then 2 mg daily as
maintenance dose after WBC >4,000 cells/mm3 and
platelets >100,000 cells/mm3 for approximately 4–8
weeks, titrate maintenance dose to hematologic
response; or 0.15 mg/kg daily for 7 days, with 2–6
weeks of rest, followed by <0.05 mg/kg daily as
maintenance dose as hematologic recovery begins; or
0.25 mg/kg daily for 4 days (0.2 mg/kg daily for 5 days),
repeat at 4– to 6–week intervals as ANC and platelet
counts return to normal;
Usually combined with corticosteroids and rest period of
up to 6 weeks to allow hematologic recovery, then repeat
the course or start maintenance treatment with 1–3 mg
or up to 50 micrograms/kg daily, adjust therapy to
produce moderate leucopenia (WBC count of 3,000 to
3,500 cells/mm3).
Ovarian carcinoma, by mouth, ADULT, 0.2 mg/kg daily for 5
days, repeat every 4–5 weeks.
Polycythemia vera, by mouth, ADULT, 6–10 mg daily for 5–
7 days; 2–4 mg daily for remission induction;
maintenance dose, 2–6 mg weekly.
Dose Adjustment:
Geriatric:
Toxicity may be increased with the elderly. Initiate therapy
at the lower end of the dosing range.
Renal Impairment:
In moderate-to-severe renal impairment, consider dose
reduction.
In patients with multiple myeloma or ovarian
adenocarcinoma, reduce dose by 50% for usual dose.
Closely monitor patients with azotemia.
Hepatic Impairment:
Melphalan is hepatically metabolized, however, dose
adjustment does not appear to be necessary.
Precautions:
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Adverse Drug Reactions:
Common: Nausea, vomiting, diarrhea, oral ulceration,
myelosuppression, anemia, thrombocytopenia,
leukopenia, secondary malignancy (dose and duration
dependent)
Less Common: Agranulocytosis, allergic reactions, alopecia,
amenorrhea, bleeding (high doses), bone marrow failure
(irreversible), cardiac arrest, cardiotoxicity (high doses),
encephalopathy, hemolytic anemia, hemorrhagic cystitis,
hepatitis, interstitial pneumonitis, infection, jaundice,
mucositis (high doses), ovarian suppression, paralytic
ileus (high doses), pruritus, pulmonary fibrosis, radiation
myelopathy, rash (maculopapular), renal toxicity (high
doses), seizure (high doses), sepsis, SIADH, skin
hypersensitivity, sterility, stomatitis, testicular
suppression, tingling sensation, vasculitis, warmth
sensation
Rare: Anaphylaxis
L
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Melphalan:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Melphalan:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of the following
drugs:
Carmustine (lung toxicity), Cyclosporine, Systemic
(nephrotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Melphalan:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Melphalan:
Dipyrone (agranulocytosis, pancytopenia), Nalidixic Acid
(necrotic enterocolitis in pediatric patients),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Vaccines (Live)
Reduces therapeutic effect of Melphalan:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (Inactivated) [complete all
age-appropriate vaccinations at least 2 weeks prior to
starting Melphalan; if vaccinated during Melphalan
therapy, revaccinate at least 3 months after
317

discontinuation], Vaccines (Live) [do not administer
vaccines for at least 3 months after Melphalan therapy]
TEST INTERACTION. Produces a false-positive result with Coomb’s
test.
Administration: Administer on an empty stomach. Food
reduces oral absorption. Avoid excessive alcohol intake.
See General Information on Nitrogen Mustard Analogues
under Antineoplastic Agents in Chapter 8: Antineoplastic
and Immunomodulating Agents for other information.
Pregnancy Category: D
ATC Code: L01AA03
OTHER ALKYLATING AGENTS
Rx DACARBAZINE
L
Inj.: 100 mg and 200 mg powder, vial (IV, IV infusion)
A non-cell cycle specific antineoplastic that functions as an
alkylating agent after it has been activated in the liver.
Indications: Treatment of metastatic melanoma; Hodgkin
lymphoma
Dose:
Metastatic melanoma, by IV injection, ADULT, 250 mg/m2
per dose days 1–5, every 3 weeks; or 2–4.5 mg/kg per
day for 10 days, repeat at 4-week intervals; by IV
infusion, ADULT, 850 mg/m2 once every 3 weeks.
Hodgkin’s lymphoma, by IV injection, ABVD regimen, ADULT,
375 mg/m2 per dose on day 1 to be repeated every 15
days; CHILD, 150 mg/m2 for 5 days, repeat at 4-week
intervals.
Dose Adjustment:
Renal Impairment:
Use with caution and monitor for toxicity. Consider dose
reduction as follows:
CrCl 46-60 mL/min Administer 80% of dose
CrCl 31-45 mL/min Administer 75% of dose
CrCl <30mL/min Administer 70% of dose
Hepatic Impairment:
May cause hepatotoxicity. Use with caution and monitor
closely for signs of toxicity. Consider dose reduction.
Precautions:
WARNING: Carcinogenic and/or teratogenic in
animals. Adverse effects have been observed in
animal studies.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Anaphylaxis; bone marrow suppression (leukopenia and
thrombocytopenia may be severe; may result in
treatment delays or discontinuation)
318
ANTINEOPLASTIC AND IMMODULATING AGENTS
Extravasation (may result in tissue damage and severe
pain)
Gastrointestinal toxicity; hepatic effects (e.g. hepatotoxicity
with hepatocellular necrosis and hepatic vein
thrombosis)
Renal and hepatic impairment (half-life is increased)
Adverse Drug Reactions:
Common: Alopecia, nausea, vomiting, anorexia,
myelosuppression, thrombocytopenia, pain on infusion,
leukopenia
Less Common: Anaphylactic reactions, anemia, diarrhea,
eosinophilia, erythema, facial flushing, facial
paresthesia, flulike syndrome, hepatic necrosis, hepatic
vein occlusion, photosensitivity, rash, paresthesia, taste
alteration, urticaria
Drug Interactions:
Monitor closely with:
Decreases metabolism of Dacarbazine:
CYP1A2 Inhibitors, CYP2E1 Inhibitors
Enhances therapeutic effect of Dacarbazine:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Dacarbazine:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia), MAO
Inhibitors [except Linezolid, Tidezolid] (orthostatic
hypotension)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases metabolism of Dacarbazine:
CYP1A2 Inhibitors, CYP2E1 Inhibitors
Enhances therapeutic effect of Dacarbazine:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases metabolism of Dacarbazine:
CYP1A2 Inducers
Increases risk of adverse or toxic effects of Dacarbazine:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Natalizumab (concurrent
infection), Vaccines (Live)
Increases serum concentration of Dacarbazine:
Vemurafenib
Reduces therapeutic effect of Dacarbazine:
Echinacea
ANTINEOPLASTIC AND IMMODULATING AGENTS
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (Inactivated) [complete all
age-appropriate vaccinations at least 2 weeks prior to
starting Dacarbazine; if vaccinated during Dacarbazine
therapy, revaccinate at least 3 months after
discontinuation], Vaccines (Live) [do not administer
vaccines for at least 3 months after Dacarbazine
therapy]
Administration: Administer by slow IV infusion over 30 to 60
minutes. Rapid infusion may cause severe venous
irritation.
NOTE: Associated with a moderate emetic potential.
Antiemetics are recommended to prevent nausea and
vomiting.
Pregnancy Category: C
ATC Code: L01AX04
ANTIMETABOLITES
FOLIC ACID ANALOGUES
Rx METHOTREXATE
Oral: 2.5 mg tablet (as base, sodium salt or disodium salt)
Inj.: 5 mg/mL, 3 mL vial (IM, IV) (as sodium salt)
25 mg/mL, 2 mL ampule/vial (IM, IV, Intrathecal) (as
base)
25 mg/mL, 2 mL and 20 mL vial (IM, IV, Intrathecal)
(as sodium salt, preservative-free)
100 mg/mL, 10 mL vial (as base)
100 mg/mL, 10 mL vial (IM, IV, intrathecal) (as
sodium salt, preservative-free)
An antimetabolite antineoplastic that acts as an antagonist
of folic acid. Methotrexate competitively inhibits the
enzyme dihydrofolatereductase and prevents the
formation of tetrahydrofolate, subsequently inhibiting
the formation of DNA and RNA. It is most active against
cells in the S phase of the cell cycle.
Indications: Therapy of acute lymphoblastic leukemia (ALL);
prophylaxis and treatment of ALL meningeal leukemia;
treatment of trophoblastic neoplasms (gestational
choriocarcinoma, chorioadenoma destruens and
hydatidiform mole); breast cancer; head and neck cancer
(epidermoid); cutaneous T-cell lymphoma (advanced
mycosis fungoides); lung cancer (squamous cell and
small cell); advanced non-Hodgkin’s lymphomas (NHL);
osteosarcoma
Contraindications: Breastfeeding
Dose:
Acute Lymphoblastic Leukemia, maintenance phase of
treatment, typically in combination with mercaptopurine,
by mouth, ADULT 20 mg/m2 weekly.
Meningeal leukemia, prophylaxis and treatment, by
intrathecal injection, ADULT, 12 mg every 2–7 days,
continue for 1 dose beyond CSF cell count normalization
(maximum, 15 mg/dose); CHILD ≥3 years, 12 mg/dose;
CHILD 2 years old, 10 mg/dose; CHILD 1 year old, 8
mg/dose; CHILD <1 year, 6 mg/dose.
Meningeal leukemia, early intensification, CALGB 8811
regimen, by intrathecal injection, ADULT, 15 mg day 1 of
early intensification phase, repeat in 4 weeks; by IV
infusion, CHILD, 1,000 mg/m2 over 24 hours in week 1
and 20 mg/m2intramuscularly on day 1 of week 2,
repeat very 2 weeks for 12 courses (use 50% dose
reduction if on same day as intrathecal methotrexate); or
5,000 mg/m2 over 24 hours days on 8, 22, 36, and 50
of consolidation phase with leucovorin rescue
Meningeal leukemia, CNS prophylaxis or interim
maintenance phase, CALGB 8811 regimen, by
intrathecal injection, ADULT, 15 mg on day 1, 8, 15, 22,
and 29; then by mouth, 20 mg/m2 day 36, 43, 50, 57,
and 64
Meningeal leukemia, CNS prophylaxis, by intrathecal
injection, ADULT, 12 mg on day 2 of each cycle, duration
depends on risk
Meningeal leukemia, interim maintenance, by mouth,
CHILD, 15 mg/m2 on day 0, 7, 14, 21, 28, and 35; by IV
injection, CHILD, 100 mg/m2 on day 0, 10, 20, 30, and
L
40, escalate by 50 mg/m2 each dose
Meningeal leukemia, maintenance, CALGB 8811 regimen,
by mouth, ADULT, 20 mg/m2 days 1, 8, 15, and 22 every
4 weeks for 24 months from diagnosis; CHILD, 20 mg/m2
days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77.
Meningeal leukemia, maintenance, in combination with
prednisone, vincristine, and mercaptopurine, by IV
injection, ADULT, 10 mg/m2 daily for 5 days every month
for 2 years; by IM injection, CHILD, 20 mg/m2 weekly on
day 1 of weeks 25–130
Meningeal leukemia, dose-intensive regimen, in
combination with cytarabine, alternates with Hyper-
CVAD, by IV injection, ADULT, 200 mg/m2 over 2 hours,
followed by 800 mg/m2 over 24 hours beginning on day
1, followed by leucovorin rescue of even numbered
cycles
Breast cancer, in combination with cyclophosphamide and
fluorouracil, by IV injection, ADULT, 40 mg/m2 on days 1
and 8 every 4 weeks for 6–12 cycles; ADULT>60 years,
30 mg/m2 on days 1 and 8 every 4 weeks for up to 12
cycles
Choriocarcinoma, chorioadenoma, gestational
trophoblastic diseases, by mouth or IM injection, ADULT,
15–30 mg daily for a 5-day course, may repeat for 3–5
courses; by IV infusion, ADULT, 100 mg/m2 over 30
minutes followed by 200 mg/m2 IV over 12 hours, with
leucovorin 24 hours after the start of methotrexate,
administer second course if hCG levels plateau for 3
consecutive weeks
Head and neck cancer, advanced, by IV injection, ADULT, 40
mg/m2 once weekly until disease progression or
unacceptable toxicity.
Non-Hodgkin’s lymphoma, CODOX­M/IVAC regimen, cycles
1 and 3 of CODOX­M, alternating with IVAC, by IV
injection, ADULT >65 years, 100 mg/m2 over 1 hour on
day 10, followed by 900 mg/m2 over 23 hours with
leucovorin rescue; ADULT ≤65 years, 300 mg/m2 over 1
hour on day 10, followed by 2700 mg/m2 over 23 hours
with leucovorin rescue.
Non-Hodgkin’s lymphoma, hyper-CVAD alternating with
high-dose methotrexate or cytarabine regimen, by IV
injection, ADULT, 1000 mg/m2 over 24 hours on day 1
during even courses (days 2, 4, 6, and 8) of 21-day
319

treatment cycles; by IV bolus, ADULT, 200 mg/m2 on day
1 followed by IV infusion of 800 mg/m2 over 24 hours
during even courses (days 2, 4, 6, and 8) of 21-day
treatment cycles, with leucovorin rescue.
T-cell lymphoma, early stages, by mouth or IM injection,
ADULT, 5–50 mg once weekly or 15 to 37.5 mg twice
weekly; by mouth, 25 mg once weekly, may increase to
50 mg once weekly; by IV injection, CHILD, 15 mg/m2 on
day 0, 7, 14, 21, 28, and 35; for low-dose therapy, 40
mg/m2 on day 2; for high-dose therapy, 500 mg/m2 over
30 minutes followed by 4,500 mg/m2 over 23.5 hours
on day 22 with leucovorin rescue.
Osteosarcoma, MAP regimen, by IV injection, ADULT ≤30
years, 12 g/m2 over 4 hours, followed by leucovorin
rescue for 4 doses during induction (before surgery) at
weeks 3, 4, 8, and 9, and for 8 doses during
maintenance (after surgery) at weeks 15, 16, 20, 21, 25,
26, 30, and 31, in combination with doxorubicin and
cisplatin (maximum dose, 20 g); CHILD, 12 mg/m2 of
methotrexate at weeks 0, 1, 5, 6, 13, 14, 18, 19, 23, 24,
37, 38 followed by leucovorin 15 mg PO every six hours
for 10 doses. Surgery follows with doxorubicin and
cisplatin.
L
Dose Adjustment:
Geriatric:
Reduce recommended doses when initiating therapy due to
possible decreased metabolism, reduced renal function,
and presence of interacting diseases and drugs, as well
as decreased
CSF volume and turnover. Use caution and monitor closely
due to increased risk of toxicity.
Renal Impairment:
For patients with CrCl 46–60 mL/minute, administer 65%
of the dose.
For patients with CrCl 31–45 mL/minute and patients on
intermittent hemodialysis or continuous renal
replacement therapy (CRRT), administer 50% of the
dose.
For patients with CrCl <30 mL/minute, avoid use.
Renal Impairment in Children:
For patients with CrCl 10–50 mL/minute/1.73 m2 and
patients on continuous renal replacement therapy
(CRRT), administer 50% of the dose.
For patients with CrCl <10 mL/minute/1.73 m2 andpatients
on intermittent hemodialysis or continuous ambulatory
peritoneal dialysis (CAPD), administer 30% of the dose.
Hepatic Impairment:
Use with caution in patients with impaired hepatic function
or preexisting hepatic damage.
For patients with bilirubin 3.1–5 mg/dL or transaminases
>3 times ULN, administer 75% of the dose.
For patients with bilirubin >5 mg/dL, avoid use.
Precautions:
WARNING: Methotrexate should be used only by
health care providers whose knowledge and
experience include the use of antimetabolite
therapy and only in life-threatening neoplastic
diseases due to the possibility of serious toxic,
potentially fatal reactions. Serious and fatal
toxicities have occurred at all dose levels.
320
ANTINEOPLASTIC AND IMMODULATING AGENTS
Errors have occurred (some resulting in death) when
methotrexate was administered as a “daily” dose
instead of a “weekly” dose intended for some
indications.
Do NOT use methotrexate formulations and/or
diluents containing preservatives for intrathecal or
high-dose methotrexate therapy.
Methotrexate-induced lung disease, including acute
or chronic interstitial pneumonitis, is a potentially
dangerous lesion, which may occur acutely at any
time during therapy and may require interruption
of treatment and careful investigation.
Potentially fatal opportunistic infections, specially
Pneumocystis carinii and Pneumocystis jirovecii
pneumonia, may occur.
Concurrent administration with NSAIDs may cause
severe bone marrow suppression, aplastic
anemia, and GI toxicity; do not administer NSAIDS
prior to or during high-dose methotrexate therapy.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Chronic leukoencephalopathy; chemical arachnoiditis; Bone
marrow suppression (e.g. anemia, leukopenia, or
thrombocytopenia)
CNS effects (e.g. seizures, dizziness, fatigue)
Dermatologic toxicity (e.g. TEN, Stevens-Johnson syndrome,
exfoliative dermatitis, skin necrosis, and erythema
multiforme)
Gastrointestinal toxicity (e.g. hemorrhagic enteritis or death
from intestinal perforation); peptic ulcer disease and
ulcerative colitis (diarrhea and stomatitis may occur);
hepatotoxicity (e.g. acute and potentially fatal chronic
hepatotoxicity, fibrosis, cirrhosis)
Renal impairment (may cause acute renal failure with high
doses; monitor renal function and methotrexate levels
closely)
Pneumonitis; Malignant lymphomas; Tumor lysis syndrome;
Fertility effects (e.g. oligospermia, menstrual
dysfunction)
Radiotherapy (concomitant use with radiotherapy may
increase the risk of soft tissue necrosis and
osteonecrosis)
Elderly (increased risk for toxicity)
Pregnancy (may cause fetal death and/or congenital
anomalies; low birth weight and developmental delay);
lactation (low amounts of methotrexate are excreted into
breastmilk)
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
NOTE: Adverse reactions vary by route and dosage.
Common: Arterial thrombosis, cerebral thrombosis, chest
pain, deep vein thrombosis, hypotension, pericardial
effusion, pericarditis, pulmonary embolism, retinal
ANTINEOPLASTIC AND IMMODULATING AGENTS

thrombosis, thrombophlebitis, vasculitis, chills, Avoid concomitant use with:

dizziness, headache, abnormal cranial sensation, brain Enhances therapeutic effect of Methotrexate:
disease, chemical arachnoiditis, cognitive dysfunction, Roflumilast (immunosuppressive effect)
drowsiness, fatigue, leukoencephalopathy, malaise,
mood changes, neurological signs and symptoms (high Increases risk of adverse or toxic effects of Methotrexate:
doses), severe neurotoxicity, alopecia, speech Acitretin (hepatotoxic effect), Cyclosporine, Systemic
disturbance, skin photosensitivity, skin rash, acne (nausea, vomiting, oral ulcers, hepatotoxicity and/or
vulgaris, dermal ulcer, diaphoresis, skin abnormalities nephrotoxicity), Dipyrone (agranulocytosis,
related to radiation recall, ecchymoses, erythematous pancytopenia), Foscarnet (nephrotoxic effect),
rash, erythema multiforme, furunculosis, Pimecrolimus, Sulfonamide derivatives, Tacrolimus
hyperpigmentation, hypopigmentation, exfoliative (Topical), Trimethoprim
dermatitis, skin necrosis, Stevens-Johnson syndrome,
toxic epidermal necrolysis, urticaria, telangiectasia, Increases risk of adverse or toxic effects of the following
decreased libido, diabetes mellitus, gynecomastia, drugs:
menstrual disease, diarrhea, nausea, vomiting, Clozapine (agranulocytosis), Cyclosporine, Systemic
stomatitis, abdominal distress, anorexia, aphthous (nephrotoxicity), Dipyrone (agranulocytosis,
stomatitis, enteritis, GI hemorrhage, gingivitis, pancytopenia), Natalizumab (concurrent infection),
hematemesis, intestinal perforation, melena, azotemia, Vaccines (Live)
cystitis, defective oogenesis, defective spermatogenesis,
impotence, dysuria, infertility, oligospermia, pancreatitis, Increases serum concentration of Methotrexate:
proteinuria, severe renal disease, vaginal discharge, Cyclosporine (Systemic), Dexketoprofen [avoid
hematuria, leukopenia (WBC <3000/mm3), concomitant administration with 15 mg methotrexate
agranulocytosis, anemia, bone marrow depression weekly or more], Loop Diuretics e.g. Furosemide,

L
(nadir, 7–10 days), aplastic anemia, decreased NSAIDS, Probenecid, Salicylates e.g. Aspirin
hematocrit, eosinophilia, hypogammaglobulinemia,
gastric ulcer, lymphoma, lymphoproliferative disorder, Increases serum concentration of the following drugs:
lymphadenopathy, neutropenia, non-Hodgkin’s Cyclosporine (Systemic), Loop Diuretics e.g., Furosemide
lymphoma, tumor lysis syndrome, cirrhosis (chronic use),
hepatic failure, hepatic fibrosis (chronic use), Reduces therapeutic effect of the following drugs:
hepatotoxicity, hepatitis (acute), cryptococcosis, BCG (Intravesical), Loop Diuretics e.g. Furosemide,
anaphylactoid reaction, cytomegalovirus disease, herpes Vaccines (Inactivated) [complete all age-appropriate
simplex infection, herpes zoster, histoplasmosis, vaccinations at least 2 weeks prior to starting
infection, Pneumocystis jiroveci pneumonia, vaccinia Methotrexate; if vaccinated during Methotrexate
(disseminated), arthralgia, myalgia, myelopathy therapy, revaccinate at least 3 months after
(subacute), osteonecrosis (with radiotherapy), discontinuation], Vaccines (Live) [do not use
osteoporosis, stress fracture, blurred vision, concomitantly with high-dose Methotrexate (≥0.4 mg/kg
conjunctivitis, eye pain, visual disturbance, tinnitus, per week)]
renal failure, chronic obstructive pulmonary disease,
cough, epistaxis, pharyngitis, pneumonia, pulmonary Reduces therapeutic effect of Methotrexate:
alveolitis, pulmonary disease, pulmonary fibrosis, Echinacea
respiratory failure, upper respiratory tract infection,
fever, nodule, tissue necrosis Reduces absorption of Methotrexate:
Milk-rich Foods
Drug Interactions:
Monitor closely with: Administration:
Enhances therapeutic effect of Methotrexate: For oral administration, administer without regard to
Trastuzumab (neutropenic effect) food. This is the preferred route for low doses.

Enhances therapeutic effect of Tofacitinib For IV administration, administer as slow IV push at a

(immunosuppressive effect) rate of 10 mg/minute, as bolus injection, or as 24-hour
continuous infusion. The route and rate of administration
Increases risk of adverse or toxic effects of Methotrexate: depends on indication and/or protocol.
Systemic (hepatotoxicity), Denosumab (serious
infections), Leflunomide (pancytopenia and/or For intrathecal administration, do NOT prepare during
hepatotoxicity), Sulfasalazine (hepatotoxicity) the preparation of any other agents. After preparation,
store in an isolated location or container clearly marked
Increases risk of adverse or toxic effects of Tegafur with a label "intrathecal" use only. Administer only with
other medications intended for administration into the
Reduces absorption of Methotrexate: central nervous system.
Bile Acid Sequestrants
NOTE: Optimal intrathecal chemotherapy dosing should be
Reduces diagnostic effect of Coccidioides immitis Skin Test based on age rather than on body surface area (BSA) as
CSF volume correlates with age and not to BSA.

321

Doses ≥250 mg/m2 (≥12 g/m2in children) are
associated with moderate emetic potential. Antiemetics
may be recommended to prevent nausea and vomiting.
Doses >500 mg/m2 require leucovorin calcium rescue.
Doses between 100–500 mg/m2 may require leucovorin
calcium rescue.
Monitoring High Dose Methotrexate Treatment
Plasma MTX levels should also be monitored closely to
detect any delay in MTX clearance. Depending on the
treatment protocol, plasma MTX assays may be
appropriate at 24, 48, and 72 hours after the start of
MTX infusion. Other protocols may require serum MTX
measurements at 36 hours (i.e. 12 hours after the end
of a 24-hour infusion) or at 42 hours from the start.
Importantly, leucovorin or folinic acid doses are adjusted
based on plasma MTX drug levels, and other supportive-
care measures such as hydration and alkalinization can
be fine-tuned to ensure adequate urine output.
Pregnancy Category: X
L
ATC Code: L01BA01; L04AX03
PURINE ANALOGUES
Rx MERCAPTOPURINE
Oral: 50 mg tablet
A purine antagonist that acts as a false metabolite in DNA
and RNA syntheses, thereby inhibiting these processes.
It is most active against cells in the S phase of the cell
cycle.
Indication: First-line maintenance therapy in conjunction
with methotrexate for the maintenance of drug-induced
remission in adults and pediatric patients with acute
lymphocytic leukemia (ALL)
Contraindications: Patients whose disease showed prior
resistance to mercaptopurine
Dose:
Acute lymphocytic leukemia, maintenance, by mouth,
ADULT and CHILD, 50 – 75 mg/m2 once daily in
conjunction with methotrexate (evening schedule
recommended), continue based on blood counts.
Depending upon the protocol used based on risk
stratification in acute lymphoblastic leukemia, dose in
maintenance phase for children varies between 50–75
mg/m2 orally.
Dose Adjustment:
Geriatric:
Initiate treatment at the low end of dosing range due to
renal decline with age.
Renal Impairment:
322
ANTINEOPLASTIC AND IMMODULATING AGENTS
Administer at the low end of the dosing range or increase
dosing interval to every 36–48 hours to avoid
accumulation.
Renal Impairment in Children:
For CrCl ≤50 mL/minute/1.73 m2, pediatric patients
receiving hemodialysis, continuous ambulatory
peritoneal dialysis (CAPD), or continuous renal
replacement therapy (CRRT), administer every 48 hours.
Some renal adverse effects may be minimized with
hydration and prophylactic anti-hyperuricemic therapy.
Hepatic impairment:
Administer at the low end of the dosing range with close
monitoring for toxicity.
NUDT15 Genetic Variation:
For patients homozygous for either TPMT or NUDT15
enzyme defect (or heterozygous for both), dose reduction
of ≥50% may be required.
TPMT Deficiency:
For patients with homozygous TPMT deficiency, i.e. little or
no TPMT activity, reduce initial dose of mercaptopurine
to 10%, with further adjustments based on the
occurrence of myelotoxicity.
For patients with heterozygous TPMT deficiency, i.e. low or
intermediate TPMT activity, usual dose may be tolerated
but reduce dose as necessary.
Concomitant use of Allopurinol:
Administer 25–33% of the usual dose to avoid severe
myelotoxicity.
Precautions:
WARNING: Discontinued temporarily at the first sign
of an unexpected abnormally large or rapid
decrease in any of the formed elements of the
blood that is not attributable to disease or another
drug. Decrease dose or discontinue use according
to severity and rapidity of hematologic effects.
Discontinue permanently if deterioration of liver
function tests, jaundice, hepatomegaly, anorexia
with tenderness in the right hypochondrion, or
other evidence of toxic hepatitis or biliary stasis
occurs, until the exact etiology is determined.
Avoid using the terms “6-mercaptopurine” or “6-
MP” as use of these terms has been associated
with six-fold overdoses.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Hematologic effects (e.g. anemia, leukemia,
thrombocytopenia, or any combination of; consider bone
marrow examination to distinguish between leukemia
progression, resistance to therapy, or marrow hypoplasia
induced by mercaptopurine).
Hepatic effects (hepatotoxicity manifested by rapid-onset
jaundice, cholestasis, ascites, hepatic encephalopathy,
elevated hepatic enzyme concentrations, possibly fatal
ANTINEOPLASTIC AND IMMODULATING AGENTS
hepatic necrosis, severe fibrosis, anorexia, diarrhea;
monitor hepatic function weekly with initiation, then
monthly, or more frequently as needed).
Immunosuppression (lethargy and confusion following
infection; common signs of infection, e.g. fever and
leukocytosis may not occur).
Malignancies and lymphoproliferative disorders
(hepatosplenic T-cell lymphoma has been reported).
Elderly (increased risk of toxicity).
Adverse Drug Reactions:
Common: Anorexia, bone marrow depression (onset: 7-10
days; nadir: 14 days; recovery: 21 days), diarrhea,
hyperbilirubinemia, hyperpigmentation, hyperuricemia,
malaise, nausea (minimal), oral lesion, pancreatitis, skin
rash, urticaria, vomiting
Frequency Not Defined: Alopecia, anemia, ascites,
cholestasis, granulocytopenia, hemorrhage, hepatic
encephalopathy, hepatic fibrosis, hepatic injury, drug
fever, hepatomegaly, hepatosplenic T-cell lymphomas,
hepatotoxicity, hepatic necrosis, immunosuppression,
intrahepatic cholestasis, infection, jaundice, leukopenia,
lymphocytopenia, metastases, mucostasis, renal toxicity,
neutropenia, oligospermia, pulmonary fibrosis, sprue-
like symptoms, stomach pain, thrombocytopenia, toxic
hepatitis, ulcerative bowel lesion, uricosuria
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Mercaptopurine:
Sulfamethoxazole (myelosuppressive effect),
Trastuzumab (neutropenic effect), Trimethoprim
(myelosuppressive effect)
Increases risk of adverse or toxic effects of Mercaptopurine:
5-ASA Derivatives, e.g. Mesalamine, Olsalazine,
Sulfasalazine (hematologic toxicity), Denosumab
(serious infections), Doxorubicin (hepatotoxicity)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of Vitamin K Antagonists, e.g.
Warfarin (anticoagulant effect)
Avoid concomitant use with:
Enhances therapeutic effect of Mercaptopurine:
Azathioprine (profound myelosuppression), Roflumilast
(immunosuppressive effect), Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Mercaptopurine:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Mercaptopurine by
inhibiting its metabolism:
Allopurinol, Febuxostat
Reduces therapeutic effect of Mercaptopurine:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: Administer preferably on an empty stomach,
1 hour before or 2 hours after meals.
Pregnancy Category: D
ATC Code: L01BB02
PYRIMIDINE ANALOGUES
Rx CAPECITABINE
Oral: 150 mg and 500 mg tablet
Metabolized in the liver to form a fluorinated pyrimidine
antimetabolite that inhibits the enzyme thymidylate
synthetase, subsequently preventing DNA and RNA
L
syntheses.
Indications: Palliative treatment of metastatic breast cancer
in patients resistant to paclitaxel and not candidates for
further anthracycline therapy; (in combination with
docetaxel) treatment of metastatic breast cancer in
patients that failed to respond to or have relapsed
following anthracycline chemotherapy; adjuvant therapy
for patients with stage III (Dukes’ C) colon cancer after
complete resection of the primary tumor; first-line
treatment of metastatic colorectal cancer
Contraindications: Severe renal impairment (CrCl <30
mL/minute)
Dose:
Breast cancer, metastatic, by mouth, ADULT, alone or in
combination with docetaxel, 1,250 mg/m2 twice daily for
2 weeks, every 21 days
Colorectal cancer, metastatic, by mouth, ADULT, 1,250
mg/m2 twice daily for 2 weeks, every 21 days.
Dukes’ C colon cancer, adjuvant therapy, by mouth, ADULT,
1,250 mg/m2 twice daily for 2 weeks, every 21 days, for
a total duration of 24 weeks (8 cycles of 2 weeks drug
administration and 1-week rest period).
Dose Adjustment:
Renal Impairment:
For CrCl 30–50 mL/minute, administer 75% of dose.
For CrCl <30 mL/minute, use is contraindicated.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
323

North American descent:
Initiate at 1,000 mg/m2 twice daily for 2 weeks, every 21
days. Increased incidence of capecitabine toxicities,
particularly hand-and-foot syndrome.
Dihydropyrimidine Dehydrodeganase (DPD) Mutations:
May require therapy interruption or permanent
discontinuation. Partial, total, or near total absence of
DPD are at an increased risk for acute early-onset toxicity
(potentially severe, life-threatening, or fatal), which may
include mucositis or stomatitis, diarrhea, neutropenia,
and neurotoxicity.
Toxicity:
Monitor closely for toxicity and adjust dose as needed.
Doses reduced should not be increased later on.
For combination therapy, monitor and adjust doses for
docetaxel as well.
If treatment delay is required for either capecitabine or
docetaxel, withhold both agents until appropriate.
Precautions:
L
WARNING: May increase the anticoagulant effects of
warfarin. Bleeding events, including death, have
occurred with concomitant use. An increased risk of
coagulopathy is correlated with a cancer diagnosis
and age >60 years. Monitor PT and INR frequently
and adjust anticoagulant dose accordingly.
In patients with colorectal cancer, treatment with
capecitabine immediately following 6 weeks of
fluorouracil/leucovorin (FU/LV) therapy has been
associated with an increased incidence of grade ≥3
toxicity, when compared to patients receiving the
reverse sequence, capecitabine (two 3­week
courses) followed by FU/LV.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (use with caution, dose reduction
may be required; not recommended in patients with
baseline platelets <100,000/mm3 and/or neutrophils
<1,500/mm3)
Cardiotoxicity (e.g. myocardial infarction, ischemia, angina,
dysrhythmias, cardiac arrest, cardiac failure, sudden
death, cardiomyopathy, ECG changes)
Dermatologic toxicity (e.g. SJS, TEN); (permanently
discontinue use if severe dermatologic or
mucocutaneous reaction occurs).
Gastrointestinal toxicity (NEC, severe prolonged diarrhea,
dehydration); (antidiarrheal therapy, e.g. loperamide is
recommended; adequately hydrate prior to initiation of
treatment)
Hand-and-foot syndrome (numbness, dysesthesia or
paresthesia, tingling, painless or painful swelling,
erythema, desquamation, blistering, and severe pain
may occur).
Hepatotoxicity (grade 3 and 4 hyperbilirubinemia,
transaminase, alkaline phosphatase elevations may
occur; use with caution in mild-to-moderate hepatic
impairment due to liver metastases).
Renal toxicity (dehydration may occur and result in possibly
fatal acute renal failure; use with caution in mild-to-
moderate renal impairment).
324
ANTINEOPLASTIC AND IMMODULATING AGENTS
Elderly (increased risk for adverse events; may experience
a greater incidence of grade 3 or 4 adverse events, e.g.,
diarrhea, hand-and-foot syndrome, nausea, vomiting; at
higher risk for dehydration).
Adverse Drug Reactions:
Common: Abdominal distention, abdominal pain, abnormal
gait, abnormal hepatic function tests, alopecia, anemia,
angina pectoris, anorexia, ataxia, arthralgia, atrial
fibrillation, back pain, bradycardia, brain disease,
cardiac arrest, cardiac arrhythmia, cardiomyopathy,
cardiac failure, chest mass, chest pain, collapse,
conjunctivitis, constipation, cough, decreased appetite,
dehydration, depression, dermal ulcer, dermatitis,
diarrhea, dizziness, drug-induced hypersensitivity,
dysarthria, dysgeusia, ECG changes, dyspepsia,
dysphagia, dysphasia, eye irritation, dyspnea, edema,
epistaxis, equilibrium disturbance, erythema,
extrasystoles, fatigue, fever, flu-like symptoms, GI
hemorrhage, GI motility disorder, GI inflammation,
headache, granulocytopenia, hemoptysis, hemorrhage,
hot flash, hoarseness, hyperbilirubinemia, immune
thrombocytopenia, hypokalemia, hypomagnesemia,
increased thirst, insomnia, intestinal obstruction,
irritability, keratoconjunctivitis, ischemic heart disease,
laryngitis, lethargy, lymphedema, limb pain,
lymphocytopenia, mood changes, myalgia, myasthenia,
myocardial infarction, nail disease, nausea, necrotizing
enterocolitis, neutropenia, palmar-plantar
erythrodysesthesia, paresthesia, oral discomfort,
pericardial effusion, peripheral sensory neuropathy,
pharyngeal disease, pain, pruritus, rectal pain, sedation,
skin discoloration, skin rash, stomatitis,
thrombocytopenia, toxic dilation of intestine, tremor,
sore throat, upper abdominal pain, venous thrombosis,
ventricular premature contractions, vertigo, viral
infection, visual disturbance, vomiting, weakness, weight
gain
Less Common: Acute renal failure, arthritis, ascites,
asthma, blood coagulation disorder, bronchitis, bone
marrow depression, bronchopneumonia, bronchospasm,
cerebrovascular accident, flu-like symptoms, cachexia,
cholestatic hepatitis, confusion, cutaneous lupus
erythematosus, diaphoresis, ecchymoses, esophagitis,
fibrosis, fungal infection, gastric ulcer, gastroenteritis, GI
perforation, hepatic failure, hepatic fibrosis,
hypertension, hypotension, hepatitis, hypersensitivity,
jaundice, keratitis, lacrimal stenosis,
leukoencephalopathy, loss of consciousness,
leukopenia, nocturia, ostealgia, pancytopenia, phlebitis
(venous), photophobia, myocarditis, pneumonia,
pulmonary embolism, radiation recall phenomenon,
renal insufficiency, respiratory distress, sepsis, SJS, TEN,
syncope, tachycardia
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Capecitabine:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Capecitabine:
Denosumab (serious infections), Leucovorin Calcium-
Levo-leucovorin
Reduces diagnostic effect of Coccidioides immitis Skin Test
ANTINEOPLASTIC AND IMMODULATING AGENTS
Avoid concomitant use with:
Decreases metabolism of Capecitabine:
CYP2C9 Substrates
Enhances therapeutic effect of Capecitabine:
Roflumilast (immunosuppressive effect), Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Capecitabine:
Dipyrone (agranulocytosispancytopenia), Pimecrolimus,
Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Capecitabine:
Gimeracil [active metabolite, fluoruracil]
Increases serum concentration of the following drugs:
Diclofenac (Systemic), Fosphenytoin, Phenytoin, Vitamin
K antagonists, e.g. Warfarin
Reduces therapeutic effect of Capecitabine:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: Swallow tablets whole. Do NOT cut or crush
tablets. Administer with water, within 30 minutes after a
meal. Usually given in 2 divided doses, 12 hours apart.
Pregnancy Category: D
ATC Code: L01BC06
Rx CYTARABINE
Inj.: 20 mg/mL solution, 5 mL ampule (IM, SC, intrathecal)
100 mg/mL solution for injection, 1 mL, 5 mL, and 10
mL ampule/vial
A pyrimidine analogue that inhibits the enzyme DNA
polymerase resulting in decreased DNA synthesis and
repair. It is specific for cells in the S phase of the cell
cycle.
Indications: Remission induction in acute myeloid leukemia
(AML); treatment of acute lymphocytic leukemia (ALL);
treatment of chronic myeloid leukemia (CML);
prophylaxis and treatment of meningeal leukemia
Dose:
Acute myeloid leukemia, remission induction, by continuous
IV infusion, 100 mg/m2 daily for 7 days; or
200 mg/m2 daily (as 100 mg/m2 over 12 hours every 12
hours) for 7 days.
Acute myeloid leukemia, remission induction, by continuous
IV infusion, ADULT, 7 + 3 regimens, may administer a
second induction course if needed; or
100 mg/m2 daily for 7 days, in combination with
daunorubicin, doxorubicin, idarubicin, or mitoxantrone;
ADULT<60 years, 200 mg/m2 daily for 7 days, in
combination with daunorubicin.
CHILD, standard AML induction therapy in children
comprises 3 days of anthracycline (e.g. daunorubicin,
idarubicin or mitoxantrone) and 7-10 days of cytarabine
(100 – 200 mg/m2). CNS prophylaxis, by intrathecal
injection, doses are age-adjusted: age 1 – 1.9 yrs 30 mg,
age 2 to 2.9 yrs 50 mg, more than 3 yrs 70 mg.
Acute myeloid leukemia, consolidation, by IV infusion,
ADULT, HiDAc regimen, standard dose of 3 g/m2 over 2
hours every 12 hours on days 1, 3, and 5 of a 21 to 28
day regimen for 4 cycles
Meningeal leukemia, by intrathecal injection, 30 mg/m2
every 4 days, range of 5–75 mg/m2 once daily for 4 days
or once every 4 days until CNS findings normalize,
followed by 1 additional treatment.
Consolidation chemotherapy for AML in remission (High
Dose Cytarabine), 1 - 3 g/m2 12 hourly in 500 mL sodium
chloride 0.9 % intravenous infusion over 4 hours
(frequency and number of doses will depend upon the
protocol in use)
L
*This course should be given once blood counts have
recovered to: Neutrophils >1x109/L and Platelets
>100x109/L.
Dose Adjustment:
Renal Impairment:
May be at a higher risk of CNS toxicities, especially if on
high-dose cytarabine (1–3 g/m2).
For CrCl 46–60 mL/minute, administer 60% of dose.
For CrCl 31–45 mL/minute, administer 50% of dose.
For CrCl <30 mL/minute, use alternative drug.
Hepatic Impairment:
May be at a higher risk of CNS toxicities.
For transaminases or if bilirubin >2 mg/dL, administer 50%
of dose. May increase subsequent doses in the absence
of toxicities.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician. Induction treatment
should be in a facility with sufficient laboratory and
supportive resources that can handle its potential
toxicities
325

High-dose regimens (1–3 g/m2) have been
associated with GI, CNS, pulmonary, ocular
toxicities, and cardiomyopathy. GI toxicities may
present as nausea, vomiting, diarrhea, abdominal
pain, oral ulcerations and hepatic dysfunction.
CNS toxicity may present as acute cerebellar
toxicity with or without cerebral impairment,
personality changes, seizure and/or coma. High
doses (>18 g/m2 per cycle) and age >50 years also
increase the risk for cerebellar toxicity. Ocular
toxicities may present as reversible corneal toxicity
or hemorrhagic conjunctivitis.
May cause myelosuppression, characterized by
leukopenia, thrombocytopenia and anemia.
Cytarabine (conventional) is not the same with
cytarabine (liposomal).
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
L
Bone marrow suppression (monitor blood counts frequently;
monitor bone marrow frequently once blasts are no
longer apparent in peripheral blood; monitor for signs of
infection, neutropenia fever, or bleeding); pancreatitis;
tumor lysis syndrome (may occur, with subsequent
hyperuricemia).
Cytarabine syndrome (fever, myalgia, bone pain, occasional
chest pain, maculopapular rash, conjunctivitis, and
malaise may occur); hypersensitivity (rarely causes
anaphylaxis resulting in acute cardiopulmonary arrest).
Sudden respiratory distress syndrome (severe dyspnea,
refractory hypoxia, diffuse pulmonary infiltrates, possibly
fatal respiratory failure, progressing to pulmonary
edema and cardiomegaly, have been reported in high-
dose cytarabine).
Adverse Drug Reactions:
Common: Anal inflammation, anal ulceration, anemia,
anorexia, bleeding, hepatic dysfunction, fever, diarrhea,
megaloblastosis, nausea, leukopenia, mucositis,
myelosuppression, neutropenia (onset: 1–7 days; nadir
[biphasic]: 7–9 days and at 15–24 days; recovery
[biphasic]: 9–12 days and at 24–34 days), decreased
reticulocytes, thrombocytopenia (onset: 5 days; nadir:
12–15 days; recovery 15–25 days), thrombophlebitis,
rash, vomiting
Less Common: Abdominal pain, acute respiratory distress
syndrome, allergic edema, alopecia, anaphylaxis,
angina, aseptic meningitis, bowel necrosis,
cardiopulmonary arrest (acute), cerebral dysfunction,
chest pain, conjunctivitis, cytarabine syndrome (bone
pain, dizziness, dyspnea, esophageal ulceration,
esophagitis, fever, headache, hepatic sinusoidal
obstruction syndrome, hyperuricemia, injection site
cellulitis, injection site pain or inflammation (SC
injection), interstitial pneumonitis, jaundice, rash,
malaise, myalgia, neural toxicity, neuritis, pancreatitis,
exanthematous pustulosis, paralysis (intrathecal and IV
combination therapy), pericarditis, renal dysfunction,
pruritus, sepsis, rhabdomyolysis, skin freckling, skin
ulceration, sore throat, toxic megacolon, urinary
326
ANTINEOPLASTIC AND IMMODULATING AGENTS
retention, urticaria, reversible posterior
leukoencephalopathy syndrome (RPLS)
Associated with high-dose cytarabine: Alopecia (complete),
cardiomegaly, cerebellar toxicity, coma, cardiomyopathy
(combination with cyclophosphamide), corneal toxicity,
GI ulcer, desquamation, hemorrhagic conjunctivitis,
hyperbilirubinemia, liver abscess, liver damage,
necrotizing colitis, neurotoxicity (up to 55% in renal
impairment), pancreatitis, peripheral neuropathy (motor
and sensory), peritonitis, personality change,
pneumatosis cystoides intestinalis, pulmonary edema,
rash (severe), sepsis, somnolence, syndrome of sudden
respiratory distress
Associated with intrathecal administration: Accessory nerve
paralysis, aphonia, blindness (with concurrent systemic
chemotherapy and cranial irradiation), cough, diplopia,
dysphagia, fever, hoarseness, nausea, necrotizing
leukoencephalopathy (concurrent cranial irradiation,
intrathecal methotrexate, and intrathecal
hydrocortisone), neurotoxicity, paraplegia, vomiting
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Cytarabine:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Cytarabine:
Denosumab (serious infections), Cyclophosphamide
(fatal cardiomyopathy)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Cytarabine:
Tofacitinib (immunosuppressive effect)
Increases risk of adverse or toxic effects of Cytarabine:
Dipyrone (agranulocytosis, pancytopenia), Tacrolimus
(Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Reduces therapeutic effect of Cytarabine:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Flucytosine, Vaccines (live virus
vaccines may progress to infection)
Administration:
For continuous IV infusion, reconstitute standard dose
with bacteriostatic water for injection, then further dilute
in 0.9% NaCl or D5W. This is the preferred route for AML
therapy (100–200 mg/m2 daily).
For intrathecal injection, administer doses immediately
after preparation due to absence of preservatives.
Reconstitute with preservative free sodium chloride
0.9%. May be further diluted to preferred final volume
ANTINEOPLASTIC AND IMMODULATING AGENTS
with Elliott's B solution, sodium chloride 0.9% or lactated
Ringer’s.
Do NOT prepare intrathecal medications during the
preparation of other agents.
NOTE: Optimal intrathecal chemotherapy dosing should be
based on age rather than on BSA as CSF volume
correlates with age.
Doses >1,000 mg/m2 (>200 mg/m2 in children) are
associated with a moderate emetic potential. Doses at
3,000 mg/m2 have a high emetic potential in children.
Antiemetics are recommended to prevent nausea and
vomiting.
Pregnancy Category: D
ATC Code: L01BC01
Rx FLUOROURACIL
Inj.: 50 mg/mL, 10 mL ampule / vial (IV, IV infusion)
A pyrimidine analogue antimetabolite that intercalates with
RNA and inhibits thymidylate synthetase, subsequently
interfering with DNA synthesis and results to tumor cell
cytotoxicity.
Indications: Treatment of breast cancer, colon cancer, rectal
cancer, pancreatic cancer, and stomach (gastric) cancer
Contraindications: Poor nutritional states; depressed bone
marrow function; potentially serious infections
Dose:
ADULTS, for various cancer protocols:
• 500 mg/m2 on Days 1-5, OR
• 450-600 mg/m2 weekly, OR
• 400 mg/m2 IV bolus on Day 1, then 1200 mg/m2/day x
2 days continuous infusion every 2 weeks
Dose Adjustment:
Renal Impairment:
Use with extreme caution.
For patients with CrCl <50 mL/minute or on continuous
renal replacement therapy (CRRT), dose adjustment is
not necessary.
For patients undergoing hemodialysis, administer 50% of
standard dose following hemodialysis.
Hepatic Impairment:
Use with extreme caution.
Administer <50% of dose, then increase if toxicity does not
occur.
For patients with bilirubin >5 mg/dL, avoid use.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Dihydropyrimidine Dehydrodeganase (DPD) Mutations:
Genetic absence of DPD has been associated with
prolonged clearance and increased toxicity, e.g.
diarrhea, neutropenia, neurotoxicity.
Precautions:
WARNING: Discontinue treatment for stomatitis or
esophagopharyngitis, rapidly falling WBC count,
leukopenia (WBC <3,500/mm3), intractable
vomiting, diarrhea, frequent bowel movements, GI
ulcer or bleeding, watery stools, thrombocytopenia
(platelets <100,000/mm3), hemorrhage, or MI.
To be administered only by or under the supervision of
an experienced cancer chemotherapy physician who
is well versed in the use of potent antimetabolites.
Hospitalize patients during the initial course of
therapy due to the possibility of severe toxic
reactions.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
L
Hand-and-foot syndrome (tingling sensation, pain,
symmetrical swelling, erythema, tenderness,
desquamation may occur).
Adverse Drug Reactions: Agranulocytosis, acute cerebellar
syndrome, alopecia, anaphylaxis, anemia,angina,
anorexia, arrhythmia, bleeding, confusion, dermatitis,
diarrhea, disorientation, epistaxis, esophagopharyngitis,
euphoria, dry skin, fissuring, generalized allergic
reactions, headache, heart failure, lacrimal duct
stenosis, lacrimation, MI, leukopenia (nadir: days 9–14;
recovery by day 30), mesenteric ischemia (acute),
myocardial ischemia, nail changes (nail loss), palmar-
plantar erythrodysesthesia syndrome, nausea,
nystagmus, pancytopenia, photophobia,
photosensitivity, sloughing, pruritic maculopapular rash,
stomatitis, Stevens-Johnson syndrome, stroke,
thrombocytopenia, thrombophlebitis, toxic epidermal
necrolysis, ulceration, vasospasm, vein pigmentation,
visual changes, ventricular ectopy, vomiting
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Fluorouracil:
Leucovorin Calcium-Levo-leucovorin,
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Fluorouracil:
Denosumab (serious infections), Leucovorin Calcium-
Levo-leucovorin
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Fluorouracil:
Roflumilast, Tofacitinib (immunosuppressive effect)
Increases risk of adverse or toxic effects of Fluorouracil:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
327

Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of the following drugs:
CYP2C9 Substrates, Diclofenac (Systemic),
Fosphenytoin, Phenytoin, Vitamin K Antagonists, e.g.,
Warfarin
Reduces therapeutic effect of Fluorouracil:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: May be administered by IV push, IV bolus, or
continuous IV infusion.
Avoid extravasation. Consider increasing dietary intake
of thiamine in patients taking this drug.
Pregnancy Category: D
L
ATC Code: L01BC02
Rx GEMCITABINE
Inj.: 200 mg and 1 g (as hydrochloride), vial (IV infusion)
A pyrimidine antimetabolite that inhibits DNA polymerase
and ribonucleotide reductase subsequently inhibiting
DNA synthesis.
Indications: First-line treatment of metastatic breast cancer,
in combination with paclitaxel after failure of adjunct
chemotherapy with an anthracycline (unless
contraindicated); first-line treatment of inoperable,
locally advanced or metastatic (stage IIIA, IIIB, or IV) Non-
small cell lung cancer (NSCLC), in combination with
cisplatin; treatment of advanced ovarian cancer, in
combination with carboplatin that has relapsed at least
6 months following completion of platinum based
chemotherapy; first-line treatment of locally advanced or
metastatic pancreatic adenocarcinoma (nonresectable
stage II, III, or stage IV)
Dose:
Breast cancer, metastatic, by IV infusion, ADULT, in
combination with paclitaxel, 1,250 mg/m2 over 30
minutes on days 1 and 8, repeat cycle every 21 days.
NSCLC, locally advanced or metastatic, by IV infusion,
ADULT, in combination with cisplatin, 1,000 mg/m2 over
30 minutes days 1, 8, and 15, repeat cycle every 28
days; or
in combination with cisplatin, 1,250 mg/m2 over 30
minutes on days 1 and 8, repeat cycle every 21 days.
Ovarian cancer, advanced, by IV infusion, ADULT, in
combination with carboplatin, 1,000 mg/m2 over 30
minutes days 1 and 8, repeat cycle every 21 days.
Pancreatic cancer, locally advanced or metastatic, by IV
infusion, ADULT, 1,000 mg/m2 over 30 minutes once
weekly for 7 weeks followed by 1-week rest, then once
weekly for 3 weeks out of every 4 weeks.
328
ANTINEOPLASTIC AND IMMODULATING AGENTS
NOTE: NOT indicated for use with concurrent radiation
therapy.
Dose Adjustment:
Renal Impairment:
Use with caution in patients with pre-existing renal
dysfunction. Discontinue if severe renal toxicity or
hemolytic uremic syndrome (HUS) occur during
treatment.
For mild-to-severe renal impairment, dose adjustment is not
necessary.
For patients with ESRD on hemodialysis, initiate
hemodialysis 6–12 hours after gemcitabine infusion.
Hepatic Impairment:
Use with caution. Discontinue if severe hepatotoxicity
occurs during treatment.
For elevated transaminases with normal bilirubin, dose
adjustment is not necessary.
For serum bilirubin >1.6 mg/dL, initiate at 800 mg/m2, may
escalate dose if tolerated.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: Has radio-sensitizing activity when used
concomitantly with radiation therapy or ≤7 days apart
and may cause radiation recall when administered
>7 days apart. Radiation toxicity, including tissue
injury, severe mucositis, esophagitis, or pneumonitis,
has been reported.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. neutropenia,
thrombocytopenia, anemia); capillary leak syndrome
(discontinue if capillary leak syndrome occurs).
Hemolytic uremic syndrome (may lead to renal failure and
dialysis, including fatalities; elevation of bilirubin or LDH,
reticulocytosis, severe thrombocytopenia, and/or renal
failure; discontinue if HUS or severe renal impairment
occurs).
Hepatotoxicity (may lead to liver failure and death; use in
patients with hepatic impairment or hepatic metastases
may worsen hepatic impairment; monitor hepatic
function at baseline and periodically during treatment).
Posterior reversible encephalopathy syndrome (blindness,
confusion, headache, hypertension, lethargy, seizure,
and other visual and neurologic disturbances may occur;
discontinue if posterior reversible encephalopathy
diagnosis confirmed).
Pulmonary toxicity (ARDS, interstitial pneumonitis,
pulmonary edema, pulmonary fibrosis; may lead to
possibly fatal respiratory failure despite discontinuation;
discontinue if unexplained dyspnea or other evidence of
pulmonary toxicity occurs).
Infusion duration >60 minutes and administration
frequency more than once weekly have been shown to
increase toxicity.
ANTINEOPLASTIC AND IMMODULATING AGENTS

Adverse Drug Reactions: Pregnancy Category: D

Common: Alopecia, anemia, bronchospasm, diarrhea,
drowsiness, dyspnea, edema, fever, flu-like symptoms, ATC Code: L01BC05
hematuria, hemorrhage, vomiting, paresthesia, skin
rash, peripheral edema, proteinuria, stomatitis,
thrombocytopenia
Less Common: ARDS, anaphylactoid reaction, anorexia, Rx TEGAFUR + URACIL
arthralgia, bullous skin disease, capillary leak syndrome,
cardiac arrhythmia, cardiac failure, cellulitis, Oral: 100 mg + 224 mg capsule
cerebrovascular accident, desquamation, digital
vasculitis, constipation, gangrene of skin or other tissue, Tegafur is a prodrug of fluorouracil. Uracil is an inhibitor of
hemolytic uremic syndrome, hepatic veno-occlusive thee nzyme dihydropyrimidine dehydrogenase, which is
disease, hepatic failure, hypertension, hypocalcemia, MI, responsible for the degradation of fluorouracil.
hypotension, interstitial pneumonitis, neuropathy,
petechiae, pruritus, pulmonary edema, pulmonary Indications: First-line treatment for metastatic colorectal
fibrosis, radiation recall phenomenon, renal failure, cancer, in combination with leucovorin calcium;
respiratory failure, reversible posterior treatment of head and neck, gastric, colorectal,
leukoencephalopathy syndrome, sepsis, hepatocellular, hepatobiliary, lung, pancreatic, breast,
supraventricular cardiac arrhythmia, thrombotic bladder, and uterine or cervical cancers
thrombocytopenic purpura
Rare: Hepatotoxicity Contraindications: Women who are or may become
pregnant; breastfeeding; infants, children, or
Drug Interactions:

L
adolescents; severe hepatic impairment; evidence of
Monitor closely with: bone marrow suppression from prior radiation therapy or
Enhances therapeutic effect of Gemcitabine: prior chemotherapy; known deficiency of hepatic
Trastuzumab (neutropenic effect) CYP2A6; known or suspected dihydropyrimidine
dehydrogenase (DPD) deficiency; concurrent or recent
Enhances therapeutic effect of Warfarin (anticoagulant treatment with DPD inhibitors; concurrent use, or within
effect) 7 days of tegafur + gimeracil + oteracil

Increases risk of adverse or toxic effects of Gemcitabine: Dose:

Denosumab (serious infections) Colorectal cancer, metastatic, by mouth, ADULT, in
combination with oral leucovorin calcium 300 mg/m2
Reduces diagnostic effect of Coccidioides immitis Skin Test tegafur + 672 mg/m2 uracil daily in 3 divided doses, or
every 8 hours on days 1 through 28 every 35 days, begin
Avoid concomitant use with: subsequent cycles after a 7-day break.
Enhances therapeutic effect of Gemcitabine: Head and neck, gastric, colorectal, hepatocellular,
Roflumilast (immunosuppressive effect) hepatobiliary, pancreatic, lung, breast, and bladder
cancer, by mouth, ADULT, 300–600 mg tegafur
Enhances therapeutic effect of Tofacitinib component daily in 2–3 divided doses.
(immunosuppressive effect) Uterine or cervical cancers, by mouth, ADULT, 600 mg
tegafur component daily in 2–3 divided doses.
Increases risk of adverse or toxic effects of Gemcitabine:
Dipyrone (agranulocytosis, pancytopenia), Dose based on BSA, number of tegafur + uracil (UFT)
Pimecrolimus, Tacrolimus (Topical) capsules required:

Increases risk of adverse or toxic effects of the following

UFT Daily Schedule
drugs:
BSA capsules
Bleomycin (pulmonary toxicity), Clozapine Morning Noon Evening
daily
(agranulocytosis), Leflunomide (hematologic toxicity
such as pancytopenia, agranulocytosis, and/or <1.17 3 1 1 1
thrombocytopenia), Natalizumab (concurrent infection) 1.17–
4 2 1 1
1.49
Reduces therapeutic effect of Gemcitabine:
1.5–1.83 5 2 2 1
Echinacea
>1.83 6 2 2 2
Reduces therapeutic effect of the following drugs: Dose Adjustment:
BCG (Intravesical), Vaccines (live virus vaccines may Obesity:
progress to infection) Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Administration: Administer IV infusion over 30 minutes. therapy is curative.
Infusion duration >60 minutes and frequency more than If dose reduction is done due to toxicity, consider
once weekly have been shown to increase toxicity. resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Avoid extravasation.

329

Dihydropyrimidine dehydrodeganase (DPD) mutations:
Genetic DPD deficiency of has been associated with
prolonged clearance and increased and potentially fatal
toxicity, e.g., diarrhea, neutropenia, neurotoxicity.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. anemia, leukopenia,
neutropenia, thrombocytopenia; may require dosage
modification; monitor blood counts as necessary)
Cardiovascular effects (e.g. myocardial infarction, ischemia,
angina; use with caution in patients with history of
significant cardiac disease)
Gastrointestinal toxicity (e.g. milddiarrhea, nausea,
vomiting, anorexia, stomatitis, and abdominal pain;
withhold treatment for grade 2 or higher diarrhea)
Hepatotoxicity (e.g. fatal fulminant hepatitis, hepatic
cirrhosis; long-term administration may lead to cirrhosis
without remarkable increase in transaminases;
discontinue if prolonged prothrombin time or decreased
L
albumin occurs).
Fertility effects (both men and women of childbearing
potential should use effective contraception during and
for 3 months following cessation of treatment; may
cause irreversible infertility).
Pregnancy (may cause fetal harm)
Adverse Drug Reactions:
Common: Abdominal pain, ageusia, alopecia, anemia,
anorexia, arthralgia, back pain, blood coagulation
disorder, cachexia, candidiasis, chills, confusion,
conjunctivitis, constipation, cough, deep vein
thrombophlebitis, dehydration, depression, diaphoresis,
diarrhea (may be dose limiting), dizziness, drowsiness,
dysgeusia, dyspepsia, dyspnea, eructation, exfoliative
dermatitis, febrile neutropenia, fever, flatulence,
headache, insomnia, intestinal obstruction, lacrimation,
leukopenia, malaise, mucositis, myalgia, nail disease,
nausea and vomiting, neutropenia (may be dose
limiting), pain, paresthesia, pharyngitis, pruritus, skin
discoloration, skin photosensitivity, skin rash, peripheral
edema, stomatitis, thrombocytopenia, weakness, weight
loss, xeroderma, xerostomia
Less Common: Abnormal gait, acute myelocytic leukemia
(including promyelocytic), acute pancreatitis, acute renal
failure, agranulocytosis, altered sense of smell, amnesia,
angina pectoris, anosmia, cardiac arrest, cardiac
arrhythmia, ascites, cardiac failure, dermatological
reaction (including blistering, dermatitis), chest pain,
duodenal ulcer, disseminated intravascular coagulation,
enteritis, enterocolitis, fatigue, extrapyramidal reaction,
fulminant hepatitis, gastric ulcer, gastritis, hematuria,
hemolytic anemia, hepatic cirrhosis, hepatic failure,
hepatic fibrosis, hepatitis, hypoesthesia, ileitis, impaired
consciousness, increased susceptibility to infection,
intestinal perforation, ischemic colitis, jaundice,
impotence, leukoencephalopathy, lupus erythematous-
like rash (discoid), movement disorder, myelodysplastic
syndrome, MI, multi-organ failure, nephrotic syndrome,
palmar-plantar erythrodysesthesia, pneumonia,
pancytopenia, paralysis (extremities), paralytic ileus,
pulmonary embolism, renal insufficiency, sepsis, shock,
330
ANTINEOPLASTIC AND IMMODULATING AGENTS
speech disturbance, SJS, urinary incontinence, urinary
retention, urticaria
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Tegafur + Uracil:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Tegafur + Uracil:
Denosumab (serious infections), Leucovorin Calcium-
Levo-leucovorin, Methotrexate
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases serum concentration of Tegafur + Uracil:
Moderate and Strong [active metabolites of tegafur]
(inhibits conversion of tegafur to 5-fluorouracil)
Enhances therapeutic effect of Tegafur + Uracil:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Tegafur + Uracil:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Tegafur + Uracil:
Gimeracil [active metabolites of tegafur, specifically
fluorouracil]
Increases serum concentration of the following drugs:
Diclofenac (Systemic), Fosphenytoin, Phenytoin, Vitamin
K Antagonists, e.g., Warfarin
Reduces therapeutic effect of Tegafur + Uracil:
Allopurinol, Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: To be taken at least 1 hour before or 1 hour
after meals.
NOTE: Do not make up doses that are withheld during the
28 days of consecutive treatment. If tegafur and uracil
treatment is withheld, leucovorin calcium should also be
withheld. Do NOT reduce leucovorin calcium dose if
tegafur and uracil dose is reduced.
Pregnancy Category: X
ATC Code: L01BC53
ANTINEOPLASTIC AND IMMODULATING AGENTS

PLANT ALKALOIDS AND

Should be administered under the supervision of an
OTHER NATURAL PRODUCTS experienced cancer chemotherapy physician,
experienced in vinblastine administration.
VINCA ALKALOIDS

WARNING: Hazardous agent. Use appropriate

Rx VINBLASTINE precautions for handling and disposal.

Inj.: 10 mg powder for reconstitution (as sulfate), vial (IV)

Bone marrow suppression (e.g. leukopenia,
1 mg/mL (as sulfate), 10 mL vial (IV)
granulocytopenia, thrombocytopenia, anemia may
occur; monitor for infections if WBC <2,000/mm3;
It inhibits microtubule formation and arrests division,
leukopenia may be more pronounced in cachectic
specifically for cells in the M and S phases of the cell
patients, patients with skin ulcerations)
cycle.
Ischemic heart disease
Pulmonary toxicity (e.g. acute shortness of breath, severe
Indications: Treatment of Hodgkin’s lymphoma; lymphocytic
bronchospasm).
lymphoma; histiocytic lymphoma; mycosis fungoides;
Gastrointestinal toxicity (stomatitis may occur; may be
testicular cancer; Kaposi’s sarcoma; Langerhans Cell
disabling but is usually reversible)
Histiocytosis (LCH)
Hepatic impairment (use with caution; toxicity may be
increased).
Contraindications: Significant granulocytopenia, unless as a
Neurotoxicity (e.g. seizures, severe permanent CNS
result of a condition being treated; bacterial infection

L
damage; seizures, CNS damage has occurred with
higher then recommended doses and/or when
Dose:
administered more frequently than recommended).
NOTE: Determine dose frequency and duration based on
indication, concomitant combination chemotherapy and
Adverse Drug Reactions:
hematologic response.
Common: Alopecia, bone pain, constipation, hypertension,
jaw pain, leukopenia or granulocytopenia (nadir, 5–10
Hodgkin’s lymphoma, lymphocytic lymphoma, histiocytic
days; recovery, 7–14 days; dose-limiting toxicity),
lymphoma, mycosis fungoides, testicular cancer,
malaise, myelosuppression, tumor pain
Kaposi’s sarcoma, or Langerhans Histiocytosis (LCH), by
Less Common: Abdominal pain, anemia, angina, anorexia,
IV infusion, ADULT, 3.7 mg/m2, adjust dose every 7 days
aspermia, auditory damage, bronchospasm, cellulitis
based on WBC response up to 5.5 mg/m2 for the second
(with extravasation), cerebrovascular accident, coronary
dose, 7.4 mg/m2 for the third dose; 9.25 mg/m2 for the
ischemia, deafness, deep tendon reflex loss, depression,
fourth dose, and 11.1 mg/m2 for the fifth dose; do not
dermatitis, diarrhea, dizziness, dyspnea, ECG
administer more frequently than every 7 days; usual
abnormalities, GI bleeding, headache, hemolytic uremic
dose range, 5.5–7.4 mg/m2 every 7 days (maximum
syndrome, hemorrhagic enterocolitis, ileus, irritation,
dose, 18.5 mg/m2), goal of dose adjustment is to reduce
limb ischemia, metallic taste, MI, myalgia, myocardial
WBC count to ~3,000/mm3.
ischemia, nausea (mild), neurotoxicity (>24 hours),
Hodgkin’s lymphoma, by IV infusion, CHILD, initially 6
nystagmus, paresthesia, peripheral neuritis, paralytic
mg/m2, do not administer more frequently than every 7
ileus, pharyngitis, phlebitis (with extravasation),
days.
photosensitivity (rare), radiation recall, rash, Raynaud's
Langerhans Histiocytosis or (LCH), by IV infusion, CHILD,
phenomenon, rectal bleeding, seizure, skin blistering,
initially 6.5 mg/m2, do not administer more frequently
stomatitis, SIADH, thrombocytopenia (recovery within a
than every 7 days.
few days), thrombotic thrombocytopenic purpura, toxic
Testicular cancer, by IV infusion, CHILD, initially 3 mg/m2,
megacolon, urinary retention, vertigo, vestibular
do not administer more frequently than every 7 days.
damage, vomiting (mild), weakness
Dose Adjustment:
Hepatic Impairment:
Drug Interactions:
For serum bilirubin >3 mg/dL, administer 50% of dose.
Monitor closely with:
Enhances therapeutic effect of Vinblastine:
Obesity:
Trastuzumab (neutropenic effect)
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
Increases risk of adverse or toxic effects of Vinblastine:
therapy is curative.
Denosumab (serious infections)
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
Increases risk of adverse or toxic effects of the following
cycles, especially if cause of toxicity is resolved.
drugs:
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
Precautions:
hypotension), Mitomycin (Systemic) (pulmonary toxicity)
WARNING: For IV use only. Fatal if given by other
routes. Reduces diagnostic effect of Coccidioides immitis Skin Test

Avoid concomitant use with:

331

Decreases serum concentration of Vinblastine:
Dabrafenib, Mitotane, Sofosbuvir
Decreases serum concentration of the following drugs:
Afatinib, Dabigatran Etexilate, Doxorubicin
(Conventional), Ledipasvir, Linagliptin
Enhances therapeutic effect of Vinblastine:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Vinblastine:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Posaconazole, Tacrolimus (Topical),
Voriconazole
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
L
Increases serum concentration of Vinblastine:
Fusidic Acid (Systemic), Lopinavir, Macrolide Antibiotics,
e.g. Erythromycin, Clarithromycin [except Azithromycin,
systemic, Fidaxomicin], Mifepristone, Posaconazole,
Ritonavir, Tolterodine
Reduces therapeutic effect of Vinblastine:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: For IV use only. A short IV infusion in a 25–
50 mL mini-bag is preferred. If not possible, administer
undiluted as a 1-minute infusion into a free flowing IV line
to prevent venous irritation or extravasation.
Local injection of hyaluronidase and the application of
moderate heat to the area of leakage help disperse the
drug and are thought to minimize discomfort and the
possibility of cellulitis.
NOTE: Extravasation may cause significant irritation. If
extravasation occurs, discontinue immediately and
initiate appropriate extravasation management,
including local injection of hyaluronidase and moderate
heat application to the affected area. Use a separate
vein to administer any remaining portion of the dose.
Prolonged administration times (≥30 to 60 minutes)
and/or increased administration volumes may increase
the risk of vein irritation and extravasation.
Pregnancy Category: D
ATC Code: L01CA01
332
ANTINEOPLASTIC AND IMMODULATING AGENTS
Rx VINCRISTINE
Inj.: 1 mg/mL (as sulfate), 1 mL and 2 mL vial (IV)
It inhibits microtubule formation and arrests division,
specifically for cells in the M and S phases of the cell
cycle.
Indications: Treatment of acute lymphocytic leukemia (ALL),
acute myeloid leukemia (AML), chronic myelogenous
leukemia (CML), Hodgkin’s lymphoma, non-Hodgkin’s
lymphomas, Wilms' tumor, neuroblastoma, small cell
lung cancer, and rhabdomyosarcoma
Contraindication: Demyelinating form of Charcot-Marie-
Tooth syndrome
Dose:
NOTE: Dosing and frequency may vary by protocol and/or
treatment phase. Cap doses at a maximum of 2
mg/dose.
Cancer chemotherapy, by IV infusion, ADULT, 1.4 mg/m2 per
dose, frequency may vary based on protocol; CHILD ≤10
kg, 0.05 mg/kg per dose once weekly; CHILD >10 kg, 1.5
– 2.0 mg/m2 per dose, frequency may vary based on
protocol. Maximum allowable dose is 2 mg.
Dose Adjustment:
Hepatic Impairment:
For serum bilirubin >3 mg/dL, administer 50% of dose.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: For IV use only. Fatal if given by other
routes.
Should be administered under the supervision of
an experienced cancer chemotherapy physician,
experienced in vinblastine administration.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Gastrointestinal effects (e.g. constipation, paralytic ileus,
intestinal necrosis and/or perforation; responds to high
enemas and laxatives).
Hepatic impairment (e.g. hepatic sinusoidal obstruction
syndrome, characterized by bilirubin >1.4 mg/dL,
unexpected weight gain, ascites, hepatomegaly, or
unexplained right upper quadrant pain).
Neurotoxicity (alterations in mental status such as
depression, confusion, or insomnia may occur; use with
caution in patients with pre-existing neuromuscular
disease and/or with concomitant neurotoxic agents).
Pulmonary toxicity (e.g. acute shortness of breath, severe
bronchospasm, or progressive dyspnea; use caution in
ANTINEOPLASTIC AND IMMODULATING AGENTS
patients with preexisting pulmonary disease;
permanently discontinue if pulmonary dysfunction
occurs)
Uric acid nephropathy
Elderly (may cause or exacerbate syndrome of
inappropriate antidiuretic hormone secretion or
hyponatremia; monitor sodium closely); children
(increased risk of developing hepatic impairment in
children <3 years of age).
Adverse Drug Reactions:
Common and Less Common: Abdominal cramps, abdominal
pain, acute uric acid nephropathy, alopecia, anemia
(mild), anorexia, ataxia, back pain, bladder atony, bone
pain, bronchospasm, coma, cortical blindness
(transient), cranial nerve dysfunction (e.g., extraocular
muscle impairment, auditory damage, laryngeal muscle
impairment, paresis, vestibular damage, vocal cord
paralysis), constipation, deafness, deep tendon reflex
loss, paralysis, diarrhea, difficulty walking, dizziness,
dyspnea, dysuria, edema, fever, foot drop, gait changes,
headache, hemolytic uremic syndrome, hepatic
sinusoidal obstruction syndrome, intestinal necrosis,
hypertension or hypotension, hyperuricemia, intestinal
perforation, jaw pain, leukopenia (mild), limb pain, MI,
motor difficulties, muscle wasting, myalgia, myocardial
ischemia, nausea, neuropathic pain, neurotoxicity (dose-
related), nystagmus, optic atrophy with blindness, oral
ulcers, paralysis, paralytic ileus, paresthesia, parotid
pain, peripheral neuropathy, pharyngeal pain, polyuria,
rash, seizure, sensorimotor dysfunction, sensory loss,
thrombocytopenia (mild), thrombotic thrombocytopenic
purpura, phlebitis, vertigo, tissue irritation or necrosis (if
infiltrated), urinary retention, vomiting, weight loss
Rare: Allergic reactions, anaphylaxis, hypersensitivity,
SIADH
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Vincristine:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Vincristine:
Denosumab (serious infections), Teniposide (neurotoxic
effect)
Increases risk of adverse or toxic effects of the following
drugs:
MAO Inhibitors [except Linezolid, Tedizolid] (orthostatic
hypotension),
Mitomycin, Systemic (pulmonary toxicity)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases serum concentration of Vincristine:
Dabrafenib, Mitotane
Enhances therapeutic effect of Vincristine:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases serum concentration of Vincristine:
Fusidic Acid (Systemic), Itraconazole, Lopinavir,
Macrolide Antibiotics, e.g. Erythromycin, Clarithromycin
[except Azithromycin, systemic], Mifepristone,
Posaconazole, Ritonavir
Increases risk of adverse or toxic effects of Vincristine:
Itraconazole, Pimecrolimus, Posaconazole, Tacrolimus
(Topical), Voriconazole
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
Natalizumab (concurrent infection)
Reduces therapeutic effect of Vincristine:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: For IV use only. A short 5– to 10– minute IV
infusion in a 25–50 mL mini-bag is preferred. If not
L
possible, administer as a slow 1-minute IV push.
Administer concomitantly with prophylactic bowel
management regimen to minimize GI adverse effects.
NOTE: Extravasation may cause significant irritation. If
extravasation occurs, discontinue immediately and
initiate appropriate extravasation management,
including local injection of hyaluronidase and moderate
heat application to the affected area. Use a separate
vein to administer any remaining portion of the dose.
Pregnancy Category: D
ATC Code: L01CA02
PODOPHYLLOTOXIN DERIVATIVES
Rx ETOPOSIDE
Inj.: 100 mg vial (IV)
20 mg/mL powder, 10 mL vial (IV)
20 mg/mL, 5 mL ampule / vial (IV)
A topoisomerase II inhibitor that arrests cells in the late S or
early G2 phase of cell division.
Indications: Treatment of small cell lung cancer (SCLC; first-
and second-line) ; treatment of non-small cell lung
cancer (NSCLC); treatment of non-Hodgkin’s lymphomas
(first-line) ; treatment of testicular cancer (first-line);
Hemophagocytic Lymphohistiocytosis (HLH); Childhood
solid malignancies (e.g. Retinoblastoma,
Neuroblastoma)
Contraindications: Hypersensitivity to etoposide or any
component of the formulation; severe leukopenia or
thrombocytopenia; severe hepaticimpairment; severe
renal impairment
333

Dose:
Non-Hodgkin’s lymphoma (in combination with other
agents), NSCLC (alone or in combination), SCLC (first-line
in combination; second-line alone or in combination),
testicular cancer (in combination), by IV infusion, ADULT,
50–100 mg/m2 daily for 5 days, administer doses >200
mg in 2 divided doses.
Hemophagocytic Lymphohistiocytosis, Acute myeloid
leukemia, CHILD under 3 yrs, 3.3 mg/kg/day IV infusion
for 4 days; CHILD above 3 yrs, 100 mg/m2/d IV infusion
for 4 days.
Dose Adjustment:
Renal Impairment:
For CrCl >50 mL/minute, dose adjustment is not required.
For CrCl 15–50 mL/minute, administer 75% of dose.
For CrCl <15 mL/minute, consider further dose reductions.
No data available.
Infants, children, and adolescents:
GFR >50 ml/min/1.73 m2: no dosage adjustment
GFR 10-50 ml/min/ 1.73 m2: administer 75% of dose
GFR < 10 ml/min/1.73 m2: administer 50% of dose
L
Hepatic Impairment:
For mild-to-moderate impairment, no recommended dose
adjustment.
For severe impairment, use is contraindicated.
Infants, children, and adolescents:
Bilirubin 1.5-3 mg/dL or AST > 3 times ULN: administer 50%
of dose
Bilirubin > 3mg/dL: administer 25% of dose or consider
avoiding dose
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based dosing. Use adjusted body weight 25% (ABW25)
for weight-based (mg/kg) dosing for hematopoietic stem
cell transplant conditioning regimens in adults.
ABW25:
Adjusted wt (kg) = Ideal body weight (kg) + 0.25 [actual
wt (kg) –ideal body weight (kg)]
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Toxicity:
If hypersensitivity reaction occurs, interrupt infusion.
For severe non-hematologic adverse reactions, reduce dose
or discontinue treatment.
If WBC 2,000–3,000/mm3 or platelets 75,000–
100,000/mm3, reduce dose by 50%.
If ANC <500/mm3 or platelets <50,000/mm3, withhold
treatment until recovery.
Precautions:
WARNING: Should be administered under the
supervision of a qualified healthcare provider,
experienced in the use of cancer
chemotherapeutic agents.
Severe myelosuppression, with resulting infection
or bleeding, may occur.
334
ANTINEOPLASTIC AND IMMODULATING AGENTS
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Hypersensitivity reaction (anaphylactic-like reactions
manifested by chills, fever, tachycardia, bronchospasm,
dyspnea, and hypotension may occur; facial or tongue
swelling, coughing, chest tightness, cyanosis,
laryngospasm, diaphoresis, hypertension, back pain,
loss of consciousness, and flushing); hypotension (may
occur due to rapid administration).
Secondary malignancies (secondary acute leukemias); low
serum albumin (at an increased risk for toxicities).
Elderly (may be more likely to develop severe
myelosuppression and/or GI effects); children (at an
increased risk of anaphylactic-like reactions when used
at concentrations higher than recommended).
Adverse Drug Reactions:
Common: Abdominal pain, alopecia, anaphylactic-like
reaction, anorexia, diarrhea, hepatic toxicity, anemia,
hypotension (infusion-related), nausea, vomiting,
leukopenia (nadir, 7–14 days; recovery, by day 20),
peripheral neuropathy, stomatitis, thrombocytopenia
(nadir, 9–16 days; recovery, by day 20)
Less Common: Amenorrhea, back pain, blindness
(transient; cortical), constipation, cyanosis, cough,
diaphoresis, dysphagia, erythema, esophagitis,
extravasation (induration; necrosis), facial swelling,
fatigue, fever, hyperpigmentation, hypersensitivity,
hypersensitivity-associated apnea, interstitial
pneumonitis, laryngospasm, maculopapular rash,
metabolic acidosis, MI, malaise, mucositis, myocardial
ischemia, optic neuritis, ovarian failure, perivasculitis,
pruritus, pulmonary fibrosis, radiation-recall dermatitis,
rash, reversible posterior leukoencephalopathy
syndrome (RPLS), seizure, Stevens-Johnson syndrome,
tongue swelling, somnolence, toxic epidermal necrolysis,
toxic megacolon, urticaria, vasospasm, weakness
Associated with higher doses: Alopecia, ethanol
intoxication, hepatitis, hypotension (infusion-related),
metabolic acidosis, nausea and vomiting (severe),
secondary malignancy, mucositis, skin lesions
(resembling Stevens-Johnson syndrome)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Etoposide:
Trastuzumab (neutropenic effect)
Enhances therapeutic effect of Vitamin K Antagonists [e.g.
Warfarin (anticoagulant effect)]
Increases risk of adverse or toxic effects of Etoposide:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases metabolism of Etoposide:
Cyclosporine (Systemic), CYP3A4 Inhibitors
Decreases serum concentration of Etoposide:
Dabrafenib, Mitotane,
Enhances therapeutic effect of Etoposide:
ANTINEOPLASTIC AND IMMODULATING AGENTS
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Etoposide:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Etoposide:
Fusidic Acid (Systemic), Mifepristone
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: For IV infusion, administer diluted over 30–
60 minutes to prevent occurrence of hypotension.
Do NOT administer by IV push, by IM or SC.
Avoid extravasation.
NOTE: Extravasation may cause significant irritation. Tissue
irritation and inflammation have occurred following
extravasation.
Concentrations >0.4 mg/mL may form precipitate within
a few minutes. For large doses, where dilution to ≤0.4
mg/mL is not feasible, consider slow infusion of the
undiluted drug through a running normal saline, dextrose
or saline and dextrose infusion, or use etoposide
phosphate. An inline filter may be used to address the
risk for precipitation. Etoposide solutions of 0.1–0.4
mg/mL may be filtered through a 0.22 micron filter.
Pregnancy Category: D
ATC Code: L01CB01
TAXANES
Rx DOCETAXEL
Inj.: 10 mg/mL solution for infusion, 2 mL and 8 mL vial
(IV)
20 mg/0.5 mL (anhydrous), 0.5 mL vial (IV infusion)
20 mg/mL concentrate for solution (as trihydrate), 1
mL (IV infusion)
40 mg/mL (anhydrous), 2 mL vial (IV infusion)
80 mg/4 mL concentrate for solution (as trihydrate),
4 mL (IV infusion)
A taxane derivative that inhibits DNA, RNA, and protein
synthesis by preventing the depolymerization of
microtubules during cell division, specifically during the
M phase.
Indications: Treatment of locally advanced or metastatic
breast cancer (adjuvant treatment of operable node-
positive); treatment of advanced gastric
adenocarcinoma; treatment of recurrent and/or
metastatic squamous cell head and neck cancer;
treatment of locally advanced or metastatic NSCLC;
treatment of metastatic ovarian cancer following failure
of first-lineor subsequent chemotherapy; treatment of
hormone refractory, metastatic prostate cancer
Contraindications: Hypersensitivity to other medications
containing polysorbate 80; neutrophil count
<1,500/mm3, severe hepatic impairment; pregnancy;
breastfeeding
Dose:
Breast cancer, locally advanced or metastatic, by IV
infusion, ADULT, as combination therapy, 75 mg/m2
every 3 weeks;
as a single agent, 100 mg/m2 every 3 weeks.
Breast cancer, operable, node-positive, adjuvant treatment,
by IV infusion, ADULT, in combination with doxorubicin
and cyclophosphamide, 75 mg/m2 every 3 weeks for 6
L
courses.
Gastric adenocarcinoma, by IV infusion, ADULT, in
combination with cisplatin and fluorouracil, 75 mg/m2
every 3 weeks.
Locally advanced or metastatic NSCLC, metastatic ovarian
cancer, recurrent and/or metastatic head and neck
cancer, by IV infusion, ADULT, as combination therapy,
75 mg/m2 every 3 weeks; as a single agent, 100 mg/m2
every 3 weeks.
Metastatic prostate cancer, hormone-refractory, by IV
infusion, ADULT, in combination with prednisone or
prednisolone, 75 mg/m2 every 3 weeks.
Dose Adjustment:
Hepatic Impairment:
If total bilirubin is greater than the ULN, or if AST and/or ALT
>1.5 times ULN concomitant with alkaline phosphatase
>2.5 times ULN, use is not recommended.
Specific for gastric or head and neck cancer:
AST/ALT >2.5 to ≤5 times ULN and alkaline phosphatase
≤2.5 times ULN, administer 80% of dose.
AST/ALT >1.5 to ≤5 times ULN and alkaline phosphatase
>2.5 to ≤5 times ULN, administer 80% of dose.
AST/ALT >5 times ULN and /or alkaline phosphatase >5
times ULN, discontinue use.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: Patients with abnormal liver function, those
receiving higher doses, and patients with NSCLC and
a history of prior treatment with platinum derivatives
who receive single-agent docetaxel at a dose of 100
mg/m2 are at higher risk for treatment-related
mortality.
335

Avoid use in patients with bilirubin exceeding upper limit
of normal (ULN) or AST and/or ALT >1.5 times ULN in
conjunction with alkaline phosphatase >2.5 times
ULN. Patients with isolated transaminase elevations
>1.5 times ULN at an increased risk of neutropenic
fever, although no increased incidence of toxic death.
Do NOT give to patients with neutrophil counts of
<1,500 cells/mm3. Perform frequent blood cell
counts to monitor occurrence of neutropenia.
Do NOT administer to patients with a history of severe
hypersensitivity to docetaxel or polysorbate 80.
Severe hypersensitivity reactions, characterized by
generalized rash or erythema, hypotension,
bronchospasms, or anaphylaxis may occur and may
be fatal.
Severe fluid retention, characterized by pleural effusion,
ascites, peripheral edema, dyspnea at rest, cardiac
tamponade, generalized edema, and weight gain,
L
has been reported.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bone marrow suppression (neutropenia may occur;
neutropenia is the dose limiting toxicity; platelets should
be >100,000/mm3 prior to treatment; patients with
increased liver function tests may experience more
episodes of neutropenia with more frequent severe
infections);
Cutaneous reactions (e.g. erythema with edema and
desquamation)
Fluid retention (may begin as lower extremity peripheral
edema and become generalized; weight gain may be
around 2 kg; administer corticosteroid, starting 1 day
prior to administration, to reduce the incidence and
severity of fluid retention).
Hepatic impairment (increased risk of grade 4 neutropenia,
infections, stomatitis, severe thrombocytopenia, skin
toxicity, or toxic death).
Hypersensitivity reactions (severe reactions occur; minor
reactions include flushing or localized skin reactions;
discontinue for severe reactions; administer
corticosteroid, starting 1 day prior to administration, to
prevent or reduce the severity ofhypersensitivity
reactions)
Neurosensory symptoms (e.g. paresthesia, dysesthesia,
neuropathic pain; reversal of symptoms may be delayed
after discontinuation).
Ocular adverse effects (cystoid macular edema may occur;
promptly administer a comprehensive ophthalmic exam
if vision impairment occurs; majority experience tearing
which subsided after therapy completion)
Secondary malignancies (treatment-related AML or
myelodysplasia)
Weakness (fatigue or weakness may occur; weakness may
be severe, lasting for a few days up to several weeks).
Adverse Drug Reactions:
Common: Alopecia, anemia (dose-dependent), arthralgia,
CNS toxicity (including neuropathy), decreased left
336
ANTINEOPLASTIC AND IMMODULATING AGENTS
ventricular ejection fraction, dermatological reaction,
diarrhea, dysgeusia, epiphora (associated with
canalicular stenosis), febrile neutropenia (dose-
dependent), fever, fluid retention (dose-dependent),
hypotension, infection (dose-dependent), infusion site
reactions (including hyperpigmentation, inflammation,
redness, dryness, phlebitis, extravasation, swelling of the
vein), leukopenia, myalgia, nail disease, nausea,
neuromuscular reaction, neutropenia (dose-dependent),
peripheral motor neuropathy (mainly distal extremity
weakness), pulmonary reaction, stomatitis,
thrombocytopenia (dose-dependent), vomiting,
weakness
Less Common: Abdominal pain, acute myelocytic leukemia,
acute respiratory distress, anorexia, anaphylactic shock,
ascites, atrial fibrillation, atrial flutter, AV block,
bronchospasm, cardiac arrhythmia, cardiac failure,
cardiac tamponade, bradycardia, chest pain, chest
tightness, colitis, confusion, conjunctivitis, constipation,
cystoid macular edema, deepvein thrombosis,
dehydration, disease of the lacrimal apparatus (duct
obstruction), disseminated intravascular coagulation,
drug fever, duodenal ulcer, ECG abnormality, dyspnea,
erythema multiforme, esophagitis, gastrointestinal
hemorrhage, GI obstruction, GI perforation, hearing loss,
hemorrhagic diathesis, hepatitis, hypertension,
hyponatremia, intestinalobstruction, interstitial
pulmonary disease, ischemic colitis, ischemic heart
disease, loss of consciousness (transient), lymphedema
(peripheral), multiorgan failure, lacrimation,
myelodysplastic syndrome, pain, myocardial infarction,
neutropenic enterocolitis, ototoxicity, palmar-plantar
erythrodysesthesia, pericardial effusion, pleural
effusion, pneumonia, pneumonitis, pulmonary
edema,pulmonary embolism, pulmonary fibrosis,
pruritus, radiation pneumonitis, radiation recall
phenomenon, renal failure, renal insufficiency,
respiratory failure, skin changes (scleroderma-like),
seizure, sepsis, sinus tachycardia, SJS, subacute
cutaneous lupus erythematosus, syncope, tachycardia,
thrombophlebitis, TEN, unstable angina pectoris, visual
disturbance (transient)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Docetaxel:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Docetaxel:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases metabolism of Docetaxel:
Antifungal Agents, Azole Derivatives, Systemic [except
Fluconazole]
Decreases serum concentration of Docetaxel:
Dabrafenib, Mitotane
Enhances therapeutic effect of Docetaxel:
Platinum Derivatives [e.g., Cisplatin, Carboplatin,
Oxaliplatin (myelosuppressive effect)], Roflumilast
(immunosuppressive effect)
ANTINEOPLASTIC AND IMMODULATING AGENTS
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Antineoplastic Agents [Anthracycline, Systemic (e.g.,
Doxorubicin, Epirubicin, Idarubicin)], Clozapine
(agranulocytosis), Dipyrone (agranulocytosis,
pancytopenia), Leflunomide (hematologic toxicity such
as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases risk of adverse or toxic effects of Docetaxel:
Pimecrolimus, Tacrolimus (Topical)
Increases serum concentration of Docetaxel:
Dronedarone, Fusidic Acid (Systemic), Mifepristone,
Reduces therapeutic effect of Docetaxel:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: Dilute with NS or D5W to a final
concentration of 0.3-0.74 mg/mL, and prepare in a glass
bottle, polypropylene, or polyolefin plastic bag to prevent
leaching of plasticizers. Non-PVC tubing must be used.
Preparation instructions may vary by manufacturer, refer to
specific prescribing information.
NOTE: Extravasation may cause significant irritation. Ensure
proper needle or catheter placement prior to and during
infusion. If extravasation occurs, discontinue
immediately and initiate appropriate extravasation
management, including local injection of hyaluronidase
and moderate heat application to the affected area. Use
a separate vein to administer any remaining portion of
the dose.
Some preparations contain alcohol, which may affect the
CNS and cause symptoms of alcohol intoxication.
Pre-medicate with corticosteroids for 3 days, beginning 1
day prior to docetaxel administration, to reduce the
severity of hypersensitivity reactions and fluid retention.
Patients being treated for prostate cancer with
concurrent prednisone should be premedicated with oral
dexamethasone at 12 hours, 3 hours, and 1 hour prior
to docetaxel administration.
Pregnancy Category: D
ATC Code: L01CD02
Rx PACLITAXEL
Inj.: 6 mg/mL, 5 mL, 16.7 mL, 17 mL, 25 mL, and 43.4
mL vial (IV, IV infusion)
A taxane derivative that stabilizes microtubule formation
which interferes with the late G2 phase of cell division.
Indications: Adjuvant treatment of node-positive breast
cancer; treatment of metastatic breast cancer after
failure of combination chemotherapy or relapse within 6
months of adjuvant chemotherapy (prior therapy should
have included an anthracycline); second-line treatment
of AIDS-related Kaposi’s sarcoma (KS); first-line
treatment of non-small cell lung cancer (in combination
with cisplatin) in patients who are notcandidates for
potentially curative surgery and/or radiation therapy;
subsequent therapy for treatment of advanced ovarian
cancer; first-linetherapy of ovarian cancer (in
combination with cisplatin)
L
Contraindications: Hypersensitivity to paclitaxel, polyoxyl 35
or polyoxyethylated castor oil, or any component of the
formulation; treatment of solid tumors in patients with
baseline neutrophil counts <1,500/mm3; treatment of
Kaposi’s sarcoma inpatients with baseline neutrophil
counts <1,000/mm3
Dose:
Breast cancer, adjuvant treatment, by IV infusion, ADULT,
175 mg/m2 over 3 hours every 3 weeks for 4 cycles,
following an anthracycline-containing regimen.
Breast cancer, metastatic or relapsed, by IV infusion,
ADULT, 175 mg/m2 over 3 hours every 3 weeks; 80
mg/m2/IV Day 1 weekly.
Non-small cell lung cancer, by IV infusion, ADULT, in
combination with cisplatin, 135 mg/m2 over 24 hours
every 3 weeks.
Ovarian cancer, advanced, previously treated, by IV infusion,
ADULT, 135 or 175 mg/m2 over 3 hours every 3 weeks.
Ovarian cancer, advanced, previously untreated, by IV
infusion, ADULT, in combination with cisplatin, 175
mg/m2 over 3 hours every 3 weeks; or 135 mg/m2 over
24 hours administered every 3 weeks.
Kaposi’s sarcoma, AIDS related, by IV infusion, ADULT, 135
mg/m2 over 3 hours every 3 weeks or 100 mg/m2 over
3 hours every 2 weeks (due to dose-related toxicity; use
100 mg/m2 dose only for patients with lower
performance status).
Dose Adjustment:
Hepatic Impairment:
NOTE: Recommendations are for the first course of therapy
where the usual dose is 135 mg/m2 (over 24 hours) or
175 mg/m2 (over 3 hours).
Dosing in subsequent courses should be based upon
individual tolerance.
24-hour infusion:
If transaminases <2 times upper limit of normal (ULN) and
bilirubin level ≤1.5 mg/dL, administer 135 mg/m2.
If transaminases 2 to <10 times ULN and bilirubin level ≤1.5
mg/dL, administer 100 mg/m2.
If transaminases <10 times ULN and bilirubin level 1.6 to
7.5 mg/dL, administer 50 mg/m2.
337

If transaminases ≥10 times ULN or bilirubin level >7.5
mg/dL, avoid use.
3-hour infusion:
If transaminases <10 times ULN and bilirubin level ≤1.25
times ULN, administer 175 mg/m2.
If transaminases <10 times ULN and bilirubin level 1.26 to
2 times ULN, administer 135 mg/m2.
If transaminases <10 times ULN and bilirubin level 2.01 to
5 times ULN, administer 90 mg/m2.
If transaminases ≥10 times ULN or bilirubin level >5 times
ULN, avoid use.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Immunosuppression (in advanced HIV) or Toxicity:
NOTE: Reduce the dexamethasone premedication dose to 10 mg and
L
initiate G-CSF treatment as clinically indicated.
For severe peripheral neuropathy or severe neutropenia
(neutrophil <500/mm3for ≥7 days), reduce dose by 20%.
For neutrophil <1000 cells/mm3 or platelet
<100,000/mm3, do not administer paclitaxel.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician, experienced in the use of
cancerchemotherapeutic agents. Administer in a
facility sufficient to appropriately diagnose and
manage complications.
Severe bone marrow suppression, primarily
neutropenia, with resulting infection or bleeding,
may occur. Do NOT administer if baseline
neutrophil count is <1,500/mm3 for solid tumors
or <1,000/mm3 for AIDS-related Kaposi’s
sarcoma.
Anaphylaxis and severe hypersensitivity reactions
have occurred in 2–4% of patients in clinical
studies. Some reactions have been fatal. If severe
hypersensitivity occurs, STOP INFUSION AND DO
NOT RECHALLENGE.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bone marrow suppression (usually in the form of
neutropenia; dose-dependent; dose-limiting toxicity)
Cardiovascular effects (e.g. infusion-related hypotension,
bradycardia, and/or hypertension; rare but severe
conduction abnormalities).
Injection-site reactions (e.g. skin discoloration, tenderness,
erythema, or swelling; more severe reactions, e.g.
phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis,
induration; skin reactions may occur despite
administering through a different IV site);
Hypersensitivity reactions (e.g. flushing, skin reactions,
dyspnea, hypotension, or tachycardia);
338
ANTINEOPLASTIC AND IMMODULATING AGENTS
Peripheral neuropathy (commonly occurs; patients with
preexisting neuropathies may be at a higher risk).
Elderly (at an increased risk of toxicity, including severe
neutropenia, neuropathy, and cardiovascular events).
Adverse Drug Reactions:
Common: Abdominal pain (with intraperitoneal paclitaxel),
increased alkaline phosphatase, alopecia, anemia,
arthralgia or myalgia, bleeding, bradycardia, diarrhea,
dyspnea, abnormal ECG, edema, febrile neutropenia,
flushing, hypersensitivity reaction, hypertension,
hypotension, infection, injection site reaction (erythema,
tenderness, skin discoloration, swelling), leukopenia,
mucositis, nail changes, nausea, vomiting, neutropenia,
peripheral neuropathy, rhythm abnormalities, rash,
stomatitis (at doses >390 mg/m2), syncope,
thrombocytopenia, tachycardia, weakness, venous
thrombosis
Less Common: Anaphylaxis, arrhythmia, ataxia, atrial
fibrillation, AV block, back pain, cardiac conduction
abnormalities, cellulitis, CHF, chills, conjunctivitis,
enterocolitis, extravasation recall, dehydration, hepatic
encephalopathy, hepaticnecrosis, induration, intestinal
obstruction, intestinal perforation, interstitial
pneumonia, increased lacrimation, maculopapular rash,
ischemic colitis, malaise, MI, myocardial ischemia,
necrotic changes and ulceration following extravasation,
neuroencephalopathy, neutropenic enterocolitis,
neutropenic typhlitis, ototoxicity (tinnitus; hearing loss),
pancreatitis, paralytic ileus, phlebitis, pneumonitis,
pruritus, pulmonary embolism, pulmonary fibrosis,
radiation recall, radiation pneumonitis, renal
insufficiency, seizure, skin edema (diffuse), skin
exfoliation, scleroderma exacerbation, skin fibrosis, skin
necrosis, skin sclerosis,skin thickening, SJS, TEN
ventricular tachycardia (asymptomatic), supraventricular
tachycardia, visual disturbances (scintillating scotomata)
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Paclitaxel:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of Vinorelbine
(neurotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases metabolism of Doxorubicin (Conventional)
Decreases serum concentration of Paclitaxel:
Dabrafenib, Mitotane
Decreases serum concentration of Aripiprazole
Enhances therapeutic effect of Paclitaxel:
Platinum Derivatives [e.g., Cisplatin, Carboplatin,
Oxaliplatin (myelosuppressive effect)], Roflumilast
(immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
ANTINEOPLASTIC AND IMMODULATING AGENTS
Increases risk of adverse or toxic effects of Paclitaxel:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Sorafenib, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Antineoplastic Agents [Anthracycline, Systemic (e.g.,
Doxorubicin, Epirubicin, Idarubicin)], Clozapine
(agranulocytosis), Leflunomide (hematologic toxicity
such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Paclitaxel:
Atazanavir, Fusidic Acid (Systemic), Mifepristone
Reduces therapeutic effect of Paclitaxel:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: Administer by IV infusion over 3 or 24 hours,
depending on indication or protocol, through a
0.22micronin-linefilter and polyethylene-lined (non-PVC)
administration set.
Pre-medicate with corticosteroids, diphenhydramine,
and H2 antagonists prior to infusion.
NOTE: Pre-medication with dexamethasone (20 mg orally or
IV at 12 and 6 hours before the dose; reduce to 10 mg
with advanced HIV disease), diphenhydramine (50 mg IV
30 to 60 minutes prior to the dose), and cimetidine 300
mg, famotidine 20 mg, or ranitidine 50 mg (IV 30 to 60
minutes prior to the dose) is recommended.
Irritant with vesicant-like properties. Avoid extravasation.
Ensure proper needle or catheter position prior to
administration.
Pregnancy Category: D
ATC Code: L01CD01
CYTOTOXIC ANTIBIOTICS
AND RELATED SUBSTANCES
ACTINOMYCINES
Rx DACTINOMYCIN (ACTINOMYCIN D)
Inj.: 500 micrograms powder, vial (IV)
An actinomycine derivative that binds to guanine portions of
the DNA to intercalate between base pairs and inhibit
DNA, RNA, and protein synthesis.
Indications: Treatment of Wilms' tumor, childhood
rhabdomyosarcoma, metastatic testicular tumors (non-
seminomatous), Ewing's sarcoma, and gestational
trophoblastic neoplasm; regional perfusion (palliative or
adjunctive) of locally recurrent orlocoregional solid
tumors (sarcomas, carcinomas, and adenocarcinomas)
Contraindications: Patients with concurrent or recent
chickenpox or herpes zoster
Dose:
NOTE: Dose intensity per 2-week cycle should not exceed 15
micrograms/kg daily for 5 days or 400–600
micrograms/m2 daily for 5 days.
Calculate dose for obese or edematous adult patients
based on BSA to relate dosage to lean body mass.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Testicular cancer, metastatic, by slow IV push, ADULT, in
combination with cyclophosphamide, bleomycin,
cisplatin, and vinblastine, 1,000 micrograms/m2 on day
1.
Gestational trophoblastic neoplasm, by slow IV push,
L
ADULT, 12 microgams/kg daily for 5 days;
in combination with etoposide, methotrexate, leucovorin,
vincristine, cyclophosphamide, and cisplatin, 500
micrograms/dose on days 1 and 2.
Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma, by
slow IV push, ADULT and CHILD>6 months, in various
combination regimens and schedules, 15
micrograms/kg daily for 5 days.
Regional perfusion, by IV injection, ADULT,
lower extremity or pelvis, 50 micrograms/kg;
upper extremity, 35 micrograms/kg;
[NOTE: Doses and techniques may vary by institution.
Obese patients and patients with prior chemotherapy or
radiation therapy may require lower doses. Regional
perfusion therapy may result in local limb edema, soft
tissue damage, and possible venous thrombosis.
Dactinomycin leakage into systemic circulation may
result in hematologic toxicity, infection, impaired wound
healing, and mucositis.]
Dose Adjustment:
Renal Impairment
Based onthe amount of urinary excretion, dose adjustment
may not be necessary.
Hepatic Impairment:
For mild impairment, no dose adjustments provided.
For moderate-to-severe impairment, consider dose
reduction.
For patients with hyperbilirubinemia, reduce doses by 33–
50%.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Radiation Therapy Recipients:
339

Use with caution in patients who have received radiation
therapy. Reduce doses in patients receiving concomitant
radiation therapy. Avoid dactinomycin use within
2months of radiation treatment for right-sided Wilms'
tumor.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician, experienced in the use of
cancer chemotherapeutic agents. Administer in a
facility sufficient to appropriately diagnose and
manage complications.
WARNING: Highly toxic. Use caution in handling
andadministration of both powder and solution.
Review special handling procedures and follow
diligently to minimize toxic effects of dactinomycin,
e.g., mutagenicity, teratogenicity, carcinogenicity,
corrosivity.
Secondary malignancies (second primary tumors may
L
occur; long-term observation of cancer survivors is
recommended due to increased risk following radiation
and chemotherapy treatment).
Toxic effects (e.g. severe myelosuppression, diarrhea or,
stomatitis; discontinue treatment if toxic effects occur)
Hepatotoxicity (e.g. hepatic sinusoidal obstruction
syndrome / SOS, characterized by bilirubin >1.4 mg/dL,
unexpected weight gain, ascites, hepatomegaly, and
unexplained right upper quadrant pain)
Concurrent radiation therapy (potentiates the effects of
radiation therapy; may result in increased toxicity, e.g.,
GI toxicity, myelosuppression, severe oropharyngeal
mucositis; may reactivate erythema from prior radiation
therapy; may increase the risk of hepatotoxicity)
Extravasation (extravasation during IV use causes severe
damage to soft tissues; has rarely led to contracture of
the arms).
Elderly (may be associated with an increased risk of
myelosuppression)
Children (avoid use in infants <6 months of age due to a
more frequent occurrence of toxic effects; risk of fatal
hepatic sinusoidal obstruction syndrome (SOS) is
increased in children <4 years).
Pregnancy (avoid exposure during pregnancy).
Adverse Drug Reactions: Abdominal pain, acne, alopecia
(reversible), anaphylactoid reaction, agranulocytosis,
anemia, anorexia, aplastic anemia, ascites, bilirubin
increased, cheilitis, diarrhea, dysphagia, edema,
epidermolysis, erythema, erythema multiforme,
esophagitis, fatigue, febrile neutropenia, fever, GI
ulceration, growth retardation, hepatic failure, hepatitis,
hepatic sinusoidal obstruction syndrome (SOS),
hepatomegaly, hepatopathy thrombocytopenia
syndrome, hepatotoxicity, abnormal liver function test,
hyperuricemia, hypocalcemia, increased pigmentation,
infection, lethargy, leukopenia, myalgia,
myelosuppression, pain, malaise, mucositis, nausea,
neutropenia, or erythema of previously irradiated skin;
skin eruptions, pancytopenia, pharyngitis, proctitis,
pneumonitis, abnormal renal function, sepsis (including
neutropenic sepsis), sloughing, Stevens-Johnson
syndrome, reticulocytopenia, stomatitis,
340
ANTINEOPLASTIC AND IMMODULATING AGENTS
thrombocytopenia, thrombocytopenia (immune-
mediated), tissue necrosis, toxic epidermal necrolysis,
ulceration (following extravasation), vomiting
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Dactinomycin:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Dactinomycin:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Dactinomycin:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Dactinomycin:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Reduces therapeutic effect of Dactinomycin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: For IV administration only. Do NOT
administer by IM or SC.
Administer by slow IV push or by IV infusion over 10–
15minutes. Do NOT filter with cellulose ester membrane
filters.
Avoid inhalation of vapors or contact with skin, mucous
membrane, or eyes.
NOTE: Avoid extravasation. Vesicant and extremely
corrosive to soft tissue. Ensure proper needle or catheter
position prior to and during administration.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Pregnancy Category: D
ATC Code: L01DA01
ANTINEOPLASTIC AND IMMODULATING AGENTS
ANTHRACYCLINES AND
RELATED SUBSTANCES
Rx DOXORUBICIN
Inj.: 10 mg and 50 mg powder (as hydrochloride), vial (IV)
2 mg/mL (as hydrochloride), 5 mL and 25 mL vial (IV)
An anthracycline that inhibits DNA and RNA synthesis by
intercalating with DNA and by inhibiting DNA repair
through topoisomerase II inhibition.
Indications: Adjuvant therapy in women with evidence of
axillary lymph node involvement following resection of
primary breast cancer; treatment of acute lymphoblastic
leukemia, acute myeloid leukemia,Wilms’ tumor,
neuroblastoma, soft tissue and bone sarcomas, breast
cancer, ovarian cancer, thyroid carcinoma, transitional
cell bladder carcinoma, gastric carcinoma, Hodgkin’s
lymphoma, non-Hodgkin’s lymphoma, and bronchogenic
carcinoma in which thesmall cell histologic type is the
most responsive compared with other cell types
Contraindications: Hypersensitivity to doxorubicin, other
anthracyclines, e.g., daunorubicin, epirubicin, idarubicin,
anthracenediones, e.g., mitoxantrone, or any component
of the formulation; severe myocardial insufficiency;
recent MI (within 4–6 weeks); severe arrhythmia;
previous therapy with high cumulative doses of
doxorubicin, daunorubicin, idarubicin, or other
anthracyclines, e.g., epirubicin, and anthracenediones,
e.g., mitoxantrone; severe persistent drug-induced
myelosuppression or baseline neutrophil count
<1500/mm3; severe hepatic impairment, i.e., Child-Pugh
class C or bilirubin >5 mg/dL; G6PD deficiency
Dose:
Breast cancer, by IV push, ADULT, in combination with
cyclophosphamide, 50-60 mg/m2 on day 1 of a 14 or 21-
day cycle for 4-6 cycles.
Metastatic solid tumors, leukemia, or lymphoma, by IV push,
ADULT, as single-agent, 60–75 mg/m2 every 21 days;
in combination therapy, 40–75 mg/m2 every 21 to 28
days.
Acute lymphoblastic leukemia, acute myeloid leukemia,
Wilms’ tumor. Ewing’s sarcoma, osteosarcoma, and soft
tissue sarcoma, CHILD: Always consult institutional
protocols. Maximum cumulative dose in children in 450
mg/m2. Lifetime cumulative dose above 550 mg/m2 are
associated with an increased risk of cardiotoxicity.
Dose Adjustment:
Hepatic Impairment:
Reduce doses in patients with impaired hepatic function.
For transaminases 2–3 times Upper Limit of Normal (ULN),
administer 75% of dose.
For transaminases >3 times ULN or serum bilirubin 1.2 to 3
mg/dL, administer 50% of dose.
For serum bilirubin 3.1–5 mg/dL, administer 25% of dose.
In severe hepatic impairment, i.e., Child-Pugh class C or
bilirubin >5 mg/dL, use is contraindicated.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Inadequate Marrow Reserve:
Consider lower doses due to advanced age, prior treatment,
or neoplastic marrow infiltration. Cumulative doses
above 550 mg/m2 are associated with an increased risk
of cardiomyopathy. Discontinue in patients who develop
signs or symptoms of cardiomyopathy.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician, experienced in the use of
cancerchemotherapeutic agents. Administer in a
facility sufficient to appropriately diagnose and
manage complications.
L
The risk for myocardial toxicity increases with
cumulative exposure and with concomitant
cardiotoxic therapy. The incidence of irreversible
myocardial toxicity increases as the total
cumulative (lifetime) doses approach 300–500
mg/m2 (with an every-3-week regimen). Assess left
ventricular ejection fraction (LVEF) with either an
echocardiogram or MUGA scan before, during, and
after therapy. Increase frequency of assessments
as the cumulative dose exceeds 300 mg/m2.
Secondary acute myelogenous leukemia (AML) and
myelodysplastic syndrome (MDS) have been
reported following treatment.
May cause severe myelosuppression, which may
result in serious infection, septic shock,
transfusion requirements, hospitalization, and
death. May cause hemolytic anemia with G6PD
deficiency.
WARNING: Hazardous agent. Use appropriate precautions for
handling and disposal.
Bone marrow suppression (e.g. leukopenia, neutropenia,
anemia, thrombocytopenia; monitor blood counts at
baseline and regularly during therapy).
Cardiotoxicity (delayed cardiotoxicity, sub-acute effects,
e.g., pericarditis or myocarditis, early toxicity, e.g.,
tachyarrhythmias, sinus tachycardia, premature
ventricular contractions, ventricular tachycardia, or
bradycardia, and ECG changes; dose-limiting, delayed
toxicity may occur late in treatment or months to years
after therapy; total cumulative dose should be taken into
account before treating with other anthracyclinesor
anthracenediones, cardiotoxic agents, or irradiation of
chest; irreversible cardiotoxicity may occur at any dose
level).
Fertility impairment (e.g. damage to spermatozoa and
testicular tissue, oligospermia, azoospermia, or loss of
fertility may occur in men; infertility, amenorrhea,
premature menopause may occur in women of
reproductive potential).
341

Secondary malignancy (may occur within 1-3 years of
treatment)
Tumor lysis syndrome (tumor lysis syndrome or
hyperuricemia; urinary alkalinization and anti-
hyperuricemic prophylaxis may be required; monitor
electrolytes, renal function, and hydration status).
Concurrent radiation therapy (radiation recall may occur;
may increase radiation-induced toxicity to the
myocardium, mucosa, skin, and liver).
Extravasation (extravasation during IV use causes severe
local tissue damage leading to tissue injury, blistering,
ulceration, and necrosis may occur, requiring wide
excision of the affected area and skin grafting).
Children (at an increased risk for developing delayed
cardiotoxicity;may contribute to prepubertal growth
failure in children; may also contribute to gonadal
impairment, usually temporary; radiation recall
pneumonitis has been reported in children receiving
concomitant dactinomycin and doxorubicin).
Adverse Drug Reactions:
Common: Abdominal pain, acute cardiotoxicity (AV block,
bradycardia, bundle branch block, ECG abnormalities,
L
extrasystoles (atrial orventricular), sinus tachycardia, ST-
T wave changes, SVT, VT, tachyarrhythmia), alopecia,
amenorrhea, anemia, anorexia, colon necrosis,
dehydration, delayed cardiotoxicity (decreased LVEF,
CHF, myocarditis, pericarditis), diarrhea, fluid
discoloration (saliva, sweat, tears, urine), GI ulceration,
hyperuricemia, infertility (may be temporary), itching,
leukopenia or neutropenia, malaise, mucositis, nausea,
photosensitivity, radiation recall, rash, skin “flare” at
injection site, thrombocytopenia, urticaria, vomiting,
weakness
Less Common: Anaphylaxis, azoospermia, bilirubin
increased, chills, coma (in combination with cisplatin or
vincristine), conjunctivitis, fever, gonadal impairment
(children), growth failure (prepubertal), hepatitis,
hyperpigmentation (nail, skin, oral mucosa), keratitis,
lacrimation, myelodysplastic syndrome, neutropenic
fever, infection, neutropenic typhlitis, oligospermia,
onycholysis, phlebosclerosis, radiation recall
pneumonitis (children), secondary acute myelogenous
leukemia, seizure (in combination with cisplatin or
vincristine), sepsis, shock, systemic hypersensitivity
(including urticaria, pruritus, angioedema, dysphagia,
and dyspnea), SJS, TEN, urticaria
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Doxorubicin:
Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections)
Increases risk of adverse or toxic effects of Mercaptopurine
(hepatotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases metabolism of Doxorubicin:
Taxane Derivatives [e.g., Paclitaxel (except Docetaxel)]
Decreases serum concentration of Doxorubicin:
Dabrafenib, Mitotane, P-glycoprotein / ABCB1 Inducers,
342
ANTINEOPLASTIC AND IMMODULATING AGENTS
Enhances therapeutic effect of Doxorubicin:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Doxorubicin:
Dipyrone (agranulocytosis, pancytopenia),
Pimecrolimus, Tacrolimus (Topical), Trastuzumab
(cardiotoxic effects)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Taxane Derivatives (e.g. Paclitaxel, Docetaxel),
Zidovudine
Increases serum concentration of Doxorubicin:
Abiraterone Acetate, Cyclosporine, CYP2D6 Inhibitors
(Moderate), CYP2D6 Inhibitors (Strong), Fusidic Acid
(Systemic), Mifepristone, P-glycoprotein / ABCB1
Inhibitors,
Reduces therapeutic effect of Doxorubicin:
Dexrazoxane, Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Stavudine, Vaccines (immune
response; live virus vaccines may progress to infection),
Zidovudine
Administration: For IV administration only. Administer IV
push over at least 3–10 minutes or by continuous IV
infusion via a central venous line. Rate of administration
varies by protocol, refer to individual protocol for details.
Do NOT administer by IM or SC.
Protect from light until completionof infusion. Avoid
contact with alkaline solutions.
Monitor for local erythematous streaking along vein
and/or facial flushing, which indicates rapid infusion
rate. Decrease rate if this occurs.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Pregnancy Category: D
ATC Code: L01DB01
ANTINEOPLASTIC AND IMMODULATING AGENTS
Rx EPIRUBICIN
Inj.: 10 mg and 50 mg powder (as hydrochloride), vial (IV)
Inhibits DNA and RNA synthesis by intercalating between
DNA base pairs and disrupting topoisomerase II repair. It
also inhibits DNA helicase.
Indications: Adjuvant therapy component for primary breast
cancer in patients with evidence of axillary node
involvement following tumor resection
Contraindications: Hypersensitivity to epirubicin, other
anthracyclines, anthracenediones, or any component of
the formulation; cardiomyopathy and/or heart failure;
recent myocardial infarction, severe arrhythmias;
previous treatment with anthracyclines
Dose:
Breast cancer, adjuvant treatment, by slow IV push, ADULT,
100–120 mg/m2 per 3– or 4–week treatment cycle as
follows:
in combination with cyclophosphamide and fluorouracil
(CEF-120 regimen), 60 mg/m2 on days 1 and 8 every 28
days for 6 cycles; or
in combination with cyclophosphamide and fluorouracil
(FEC-100 regimen), 100 mg/m2 on day 1 every 21 days
for 6 cycles.
Dose Adjustment:
Geriatric:
Plasma clearance in elderly female patients was reduced by
35%. Monitor toxicity and adjusting subsequent dosage
in elderly patients with great care, particularly females
>70 years of age.
Renal Impairment:
In severe renal impairment (serum creatinine >5 mg/dL),
lower doses.
Hepatic Impairment:
Reduce doses in with impaired hepatic function.
In bilirubin 1.2–3 mg/dL or AST 2–4 times the upper limit
of normal, administer 50% of recommended starting
dose.
In bilirubin >3 mg/dL or AST >4 times the upper limit of
normal, administer 25% of recommended starting dose.
In severe impairment, use is not recommended.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Toxicity:
In heavily-treated patients and patients with preexisting
bone marrow depression or neoplastic bone marrow
infiltration, consider lower starting doses of 75–90
mg/m2.
Delay day 1 dose of subsequent cycles until platelets are
≥100,000/mm3, ANC ≥1500/mm3, and nonhematologic
toxicities have recovered to ≤grade 1.
Reduce day 1 dose in subsequent cycles to 75% of
previous day 1 dose if patient experiences nadir platelet
counts <50,000/mm3, ANC <250/mm3, neutropenic
fever, or grade 3/4 nonhematologic toxicity during the
previous cycle.
For CEF-120 regimen, reduce day 8 dose to 75% of day 1
dose if platelet counts are 75,000 to 100,000/mm3 and
ANC is 1000 to1499/mm3; omit day 8 dose if platelets
are <75,000/mm3, ANC <1000/mm3, or grade 3/4
nonhematologic toxicity.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to
appropriately diagnose and manage complications.
Severe myelosuppression may occur.
Secondary acute myeloid leukemia (AML) has been
reported.
Cardiac toxicity, including fatal CHF, may occur either
during therapy or months to years after termination
L
of therapy. In the adjuvant treatment of breast
cancer, the maximum cumulative dose is 720
mg/m2. The risk of developing CHF increases rapidly
with increasing total cumulative doses >900 mg/m2.
Children may be at increased risk for developing
acute and delayed cardiotoxicity.
Patients receiving 120 mg/m2 per cycle as part of
combination therapy (CEF-120 regimen) should also
receive prophylactic antibiotic therapy with
sulfamethoxazole/trimethoprim or a fluoroquinolone.
Lower starting doses may be necessary for heavily
pretreated patients, patients with preexisting
myelosuppression, or with bone marrow involvement.
Maximum lifetime dose is 900 mg/m2.
Prophylactic antibiotics should be administered with
the CDF-120 regimen.
May have radiosensitizing activity. Radiation recall
(inflammatory) has been reported. Use with caution
in radiation recipients.
Patients should recover from acute toxicities
(stomatitis, myelosuppression, infections) prior to
initiating treatment. Assess baseline labs (blood
counts, bilirubin, ALT, AST, serum creatinine) and
cardiac function (LVEF).
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. leukopenia,
thrombocytopenia, anemia; myelosuppression may
result in severe neutropenia and severe infection,
needing supportive care)
Thromboembolic events (e.g. thrombophlebitis,
thromboembolic phenomena, including pulmonary
embolism).
Hepatic impairment (evaluate hepatic function at baseline
and during treatment; predominantly hepatically
eliminated; impaired function may lead to increased
exposure and toxicity); renal impairment (evaluate renal
function at baseline and during treatment).
Myocardial toxicity (e.g. tachyarrhythmias, sinus
tachycardia, premature ventricular contractions,
343
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ventricular tachycardia, bradycardia, ECG changes; Reduces therapeutic effect of Epirubicin:

cardiotoxicity is dose-limiting; risk increases with
cumulative dose, but irreversible cardiotoxicity may
occur at any level; regularly monitor LVEF and
discontinue at first sign of impairment).
Secondary malignancy (latency period for secondary
leukemias may be as short as 1–3 years);
Tumor lysis syndrome (monitor serum uric acid, potassium,
calcium, phosphate, and serum creatinine after initial
administration; hydration and anti-hyperuricemic
prophylaxis may minimize potential TLS complications).
Adverse Drug Reactions:
Common: Alopecia, amenorrhea, anemia, anorexia,
conjunctivitis, diarrhea, fever, HF, hot flashes, infection,
injection site reactions, leukopenia, lethargy, mucositis,
nausea, decreased LVEF, vomiting, neutropenia,
neutropenic fever, rash, skin changes, thrombocytopenia
Less Common: Abdominal pain, acute lymphoid leukemia,
acute myelogenous leukemia, AV block, anaphylaxis,
arterial embolism, ascites, arrhythmia, bradycardia,
bundle-branch block, cardiomyopathy, chills,
dehydration, dyspnea, ECG abnormalities, erythema,
L
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration:
For IV administration, infuse over 15–20 minutes or slow
IV push. If lower doses due to dose reduction are
administered, reduce infusion time proportionally. Do
NOT infuse over <3 minutes.
Infuse into a free-flowing IV solution (NS or D5W). Avoid
the use of veins over joints or inextremities with
compromised venous or lymphatic drainage.
Do NOT administer by IM or SC route.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.

esophagitis, flushing, GI burning sensation, GI erosions

or ulcerations, GI pain, GI bleeding, hepatomegaly, Injection into a small vein or repeated administration in
hyperpigmentation (oral mucosa, nails, skin), the same vein may result in venous sclerosis.
hypersensitivity, hyperuricemia, myelodysplastic
syndrome, myocarditis, neutropenic typhlitis, phlebitis, Associated with a high emetic potential. Antiemetics are
pneumonia, premature menopause, premature recommended to prevent nausea and vomiting.
ventricular contractions, pulmonary edema, pulmonary
embolism, photosensitivity, radiation recall, sepsis, Pregnancy Category: D
shock, sinus tachycardia, stomatitis, ST wave changes,
tachyarrhythmias, thromboembolism, thrombophlebitis, ATC Code: L01DB03
toxic megacolon, urticaria, urine discoloration (red),
ventricular tachycardia

Drug Interactions: Rx IDARUBICIN

Monitor closely with:
Increases risk of adverse or toxic effects of Epirubicin:
Inj.: 5 mg powder (as hydrochloride), vial (IV)
Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections)
Inhibits DNA and RNA synthesis by intercalating between
DNA base pairs and disrupting topoisomerase II repair.
Reduces diagnostic effect of Coccidioides immitis Skin Test
Indications: Treatment of acute myeloid leukemia (AML) in
Avoid concomitant use with:
combination with other approved chemotherapy agents
Enhances therapeutic effect of Epirubicin:
Roflumilast (immunosuppressive effect)
Contraindications: Hypersensitivity to idarubicin, other
anthracyclines, anthracenediones, or any component of
Enhances therapeutic effect of the following drugs:
the formulation; bilirubin >5 mg/dL
Tofacitinib (immunosuppressive effect)
Increases risk of adverse or toxic effects of Epirubicin:
Dose:
Dipyrone (agranulocytosis; pancytopenia),
AML, induction, by slow IV injection, ADULT, 12 mg/m2 IV
Pimecrolimus, Tacrolimus (Topical), Taxane Derivatives
everyday over 10-15 minutes for 3 days with
(e.g. Paclitaxel, Docetaxel), Trastuzumab (cardiotoxic
concomitant cytarabine; CHILD, 12 mg/m2 for 3 days in
effects)
combination with cytarabine and etoposide.
AML, consoldation, ADULT, 10-12mg/m2/day IV for 2 days.
Increases risk of adverse or toxic effects of the following
AML Protocol (including Down Syndrome), CHILD, 5 to 8
drugs:
mg/m2 four-hour IV infusion (depending upon phase of
Clozapine (agranulocytosis), Leflunomide (hematologic
treatment).
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Dose Adjustment:
Renal Impairment:
Increases serum concentration of Epirubicin:
Reduce doses.
Cimetidine
ADULT
In CrCl 10–50 mL/minute, administer 75% of dose.

344
ANTINEOPLASTIC AND IMMODULATING AGENTS
In CrCl <10 mL/minute, administer 50% of dose.
INFANT, CHILD, and ADOLESCENT
In GFR ≤50 mL/minute/1.73 m2, and in patients
receiving intermittent hemodialysis, peritoneal dialysis,
or continuous renal replacement therapy, administer
75% of dose.
Hepatic Impairment:
Reduce doses in impaired hepatic function.
In bilirubin 2.6–5 mg/dL, administer 50% of dose.
In bilirubin >5 mg/dL, avoid use.
Impaired Bone Marrow Function:
Lower doses of 60–75 mg/m2 are recommended.
Toxicity:
If patients experience severe mucositis during the first
induction cycle, delay administration of the second cycle
until mucositis has resolved. Consider reducing the dose
by 25%.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to
appropriately diagnose and manage complications.
Severe myelosuppression may occur.
Systemic infections should be controlled prior to
initiation of treatment.
May cause myocardial toxicity. May lead to heart
failure. Cardiotoxicity is more common in patients
who have previously received anthracyclines (e.g.
doxorubicin, epirubicin) or have preexisting cardiac
disease.
Patients >60 years who were undergoing induction
therapy experienced heart failure, serious
arrhythmias, chest pain, MI, and asymptomatic
declines in LVEF more frequently than younger
patients.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. neutropenia,
thrombocytopenia; risk of infection and bleeding;
monitor blood counts frequently).
Hyperuricemia (rapid lysis of leukemic cells may lead to
hyperuricemia; ensure adequate hydration; consider use
of anti-hyperuricemic prophylaxis).
Myocardial toxicity (e.g. potentially fatal heart failure,
cardiomyopathies, or acute arrhythmias, which may be
life-threatening; risk of myocardial toxicity increased in
patients with concomitant or prior mediastinal or
pericardial irradiation, anemia, bone marrow depression,
infections, leukemic pericarditis, or myocarditis).
Adverse Drug Reactions:
Common: Alopecia, CHF (dose-related), diarrhea,
discoloration of urine (darker yellow), headache,
myelosuppression, nausea, peripheral neuropathy,
radiation recall, seizure, skin rash, stomatitis, transient
ECG abnormalities (SVT, ST wave changes, atrial or
ventricular extrasystoles), GI hemorrhage, urticaria,
vomiting
Less Common: Cardiomyopathy, hyperuricemia,
myocarditis, neutropenic typhlitis
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Idarubicin:
Bevacizumab (cardiotoxic effect), Cyclophosphamide
(cardiotoxic effect), Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Idarubicin:
Roflumilast (immunosuppressive effect)
L
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Idarubicin:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical), Taxane Derivatives
(e.g. Paclitaxel, Docetaxel), Trastuzumab (cardiotoxic
effects)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Reduces therapeutic effect of Idarubicin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: For IV administration only. Administer
through a slow injection over 10–15 minutes into a
rapidly flowing IV solution of NS or D5W. Refer to
individual protocols for infusion rate details.
NOT for IM or SC administration.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Pregnancy Category: D
ATC Code: L01DB06
345

Rx MITOXANTRONE
Inj.: 2 mg/mL solution, 5 mL and 10 mL
A cell-cycle nonspecific agent that intercalates into DNA and
inhibits DNA topoisomerase II to inhibit DNA and RNA
synthesis.
Indications: Initial treatment of acute myelogenous
leukemias; treatment of advanced hormone-refractory
prostate cancer; treatment of metastatic breast cancer,
relapsed leukemia, lymphoma, and hepatocellular
carcinoma
Contraindications: Prior substantial anthracycline exposure
and abnormal cardiac function prior to initiation of
mitoxantrone therapy; presence of
severemyelosuppression due to prior chemoand/or
radiotherapy; severe hepatic impairment; intrathecal
administration
L
Dose:
Acute leukemia, relapsed, induction, by slow IV infusion,
ADULT, 12 mg/m2 once daily for 5 consecutive days, may
repeat once if needed.
Acute myeloid leukemia (AML), induction, by slow IV
infusion, ADULT, 12mg/m2/day IV on days 1-3 with
cytarabine 100mg/m2/day IV continuous infusion on
days 1-7. May be given with etoposide. Second induction
with same doses of mitoxantrone for 2 days and
cytarabine for 5 days may be given if incomplete
antileukemic response and no severe nonhematologic
toxicity in first induction. AML, consolidation, ADULT, in
combination with cytarabine, 12 mg/m2 once daily for 2
days, repeat in 4 weeks; CHILD, 10 mg/m2 in
combination with high dose cytarabine
Breast cancer, metastatic or lymphoma, initial, by slow IV
infusion, ADULT, 14 mg/m2 every 21 days, reduce to ≤12
mg/m2 for myelosuppression due to previous treatment
or for poor general health; reduce to 10–12mg/m2 when
used in combination with other agents.
Hepatocellular cancer, initial, by slow IV infusion, ADULT, 14
mg/m2 every 21 days; reduce initial dose to ≤12 mg/m2
for myelosuppression due to previous treatment or for
poor general health.
Prostate cancer, advanced, hormone-refractory, by IV
infusion, ADULT, in combination with corticosteroids,
12–14mg/m2 every 3 weeks.
Dose Adjustment:
Hepatic Impairment:
In mild-to-moderate impairment, consider dose
adjustments and monitor closely.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
346
ANTINEOPLASTIC AND IMMODULATING AGENTS
Toxicity:
AML:
In severe or life-threatening nonhematologic toxicity,
withhold treatment until toxicity resolves.
Hepatocellular cancer, lymphoma, or breast cancer
(metastatic):
In WBC nadir >1,500/mm3 or platelet nadir >50,000/mm3,
and recovery ≤21 days, repeat previous dose or increase
dose by 2mg/m2 if myelosuppression is inadequate.
In WBC nadir >1,500/mm3 or platelet nadir >50,000/mm3,
and recovery >21 days, withhold treatment until recovery
then resume at previous dose.
In WBC nadir <1,500/mm3 or platelet nadir <50,000/mm3,
withhold treatment until recovery then decrease
previous dose by 2 mg/m2.
In WBC nadir <1,000/mm3 or platelet nadir <25,000/mm3,
withhold treatment until recovery then decrease
previous dose by 4 mg/m2.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician. Administer in a facility
sufficient to appropriately diagnose and manage
complications.
Administer only if baseline neutrophil count
<1,500 cells/mm3 (except in AML). Monitor blood
counts and monitor for infection due to
neutropenia.
Use increases the risk of developing secondary
acute myeloid leukemia (AML).
Congestive heart failure, potentially fatal, may
occur during therapy or months to years after
termination of therapy. Cardiotoxicity risk
increases with cumulative dose. Assess all
patients for cardiac signs and symptoms by
history, physical examination, and ECG. Evaluate
all patients for baseline quantitative evaluation of
left ventricular ejection fraction.
Patients >60 years who were undergoing induction
therapy experienced heart failure, serious
arrhythmias, chest pain, MI, and asymptomatic
declines in LVEF more frequently than younger
patients.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (use is not recommended in
patients with pre-existing myelosuppression from prior
chemotherapy unless expected benefit outweighs risk)
Hyperuricemia (caused by rapid lysis of tumor cells)
Secondary malignancy (e.g. excessive bruising, bleeding,
recurrent infections, which may be symptoms of
secondary malignancy; acute promyelocytic leukemia;
risk for secondary leukemia is increased in patients who
are heavily pretreated, with higher doses, and with
combination chemotherapy).
ANTINEOPLASTIC AND IMMODULATING AGENTS
Elderly (decreased clearance; use with caution).
Adverse Drug Reactions:
Common: Abdominal pain, abnormal urine, alkaline
phosphatase increased, alopecia, amenorrhea, anemia
or decreased hemoglobin, anorexia, anxiety, aphthosis,
arrhythmia, arthralgia, back pain, bleeding, blurred
vision, cardiac function changes, chills, conjunctivitis,
CHF, constipation, cough, increasedcreatinine,
cutaneous mycosis, depression, diaphoresis, diarrhea,
dyspepsia, dyspnea, ECG changes, edema, fatigue,
fever, fungal infection, granulocytopenia, headache,
hematuria, hemorrhage, hyperglycemia, hypertension,
pain, LVEF decreased, hypocalcemia, hypokalemia,
hyponatremia, impotence, infection, ischemia, jaundice,
leukopenia, lymhopenia, menorrhagia, menstrual
disorder, mucositis, myalgia, nail bed changes, nausea,
neutropenia, neutropenic petechiae or bruising,
pharyngitis, pneumonia, proteinuria, renal failure,
rhinitis, secondary acute leukemias (including AML and
APL), fever, seizure, sepsis, sinusitis, skin infection,
sterility, stomatitis, systemic infection,
thrombocytopenia, upper respiratory tract infection,
urinary tract infection, vomiting, weakness, weight gain
or loss
Less Common: Allergic reaction, anaphylactoid reactions,
anaphylaxis, chest pain, dehydration, extravasation at
injection site (erythema, pain, burning, skin
discoloration, swelling, or tissue necrosis), interstitial
pneumonitis, hypotension, hyperuricemia, phlebitis at
the infusion site, rash, sclera discoloration (blue),
tachycardia, urine discoloration (blue-green), urticaria
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Mitoxantrone:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Mitoxantrone:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Mitoxantrone:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Mitoxantrone:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection)
Increases serum concentration of Mitoxantrone:
Cyclosporine (Systemic)
Reduces therapeutic effect of Mitoxantrone:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: For IV administration only. Dilute in at least
50mL of NS or D5W. Administer via a free-flowing IV, as
a short IV infusion over 5–15 minutes or continuous IV
infusion over 24 hours. Do NOT infuse over <3 to 5
minutes. Must be diluted prior to use.
Do NOT administer by SC, IM, or intraarterial injection. Do
NOT administer intrathecally to prevent serious
permanent neurologic damage.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
May cause urine, saliva, tears, and sweat to turn blue-
L
green for 24 hours post-infusion; whites of eyes may
have blue-green tinge.
Pregnancy Category: D
ATC Code: L01DB07
OTHER CYTOTOXIC ANTIBIOTICS
Rx BLEOMYCIN
Inj.: 15 IU powder (as sulfate), ampule / vial (IM, IV)
Inhibits synthesis of DNA by binding to DNA leading to single
and double-strand breaks. It also inhibits RNA and
protein synthesis.
Indications: Treatment of squamous cell carcinomas of the
head and neck; Hodgkin’s Lymphoma; extracranial germ
cell tumors; sclerosing agent for malignant pleural
effusion; treatment of testicular cancer
Dose:
NOTE: Doses below expressed as USP units; 1 USP unit = 1 mg (by
potency) = 1,000 international units.
Squamous cell carcinomas, by IM or IV injection, 10-15 x
103 IU/m2 body surface area (BSA), once or twice a week,
at intervals of 3-4 weeks up to a lifetime cumulative dose
of 360 x 103 IU; by IV infusion, 10-15 x 103 IU/m2/day
for 6-24 hours on 4 to 7 consecutive days, at intervals of
3-4 week.
Lymphoma, test dose, by IM, IV, or SC injection, 1–2 units
before the first 1–2 doses; monitor vital signs every 15
minutes; wait a minimum of 1 hour before administering
remainder of dose; if no acute reaction occurs, follow
regular dosing schedule [NOTE: Test doses may not be
predictive of a reaction and/or may produce false-negative
results].
347

Malignant pleural infusion, by intrapleural route, 60 units as
a single instillation, mixed in 50–100 mL of NS.
Extracranial germ cell tumors (yolk sac tumor,
choriocarcinoma, embryonal carcinoma), CHILD, 15
units/m2 on day 1 in combination with cisplatin and
etoposide.
Hodgkin’s Lymphoma, CHILD, 10 units/m2 in combination
with various chemotherapy regimen.
Dose Adjustment:
Renal Impairment:
In CrCl 40–50mL/minute, administer 70% of dose.
In CrCl 30–40mL/minute, administer 60% of dose.
In CrCl 20–30mL/minute, administer 55% of dose.
In CrCl 10–20mL/minute, administer 45% ofdose.
In CrCl 5–10mL/minute, administer 40% of dose.
Obesity:
Consider use of fixed doses, independent of body weight or
BSA, due to toxicity concerns.
Toxicity:
If pulmonary changes occur, discontinue until determined
not to be drug-related.
L
If the pulmonary diffusion capacity for carbon monoxide
(DLCO) is <30–35% of baseline, discontinue treatment.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to
appropriately diagnose and manage complications.
Occurrence of pulmonary fibrosis is the most severe
toxicity. It commonly presents as pneumonitis,
occasionally progressing to pulmonary fibrosis. Risk
is higher in elderly patients, glomerular filtration rate
<80 mL/minute advanced disease, or patients
receiving >400 units total lifetime dose or >300 units
cumulative dose. Risk is also increased in surgery
patients receiving O2.
A severe idiosyncratic reaction consisting of
hypotension, mental confusion, fever, chills, and
wheezing has been reported.
WARNING: Hazardous agent; use appropriate precautions for
handling and disposal.
Hepatotoxicity; Renal toxicity
Pulmonary toxicity (e.g. bronchiolitis obliterans and
organizing pneumonia, eosinophilic hypersensitivity, and
interstitial pneumonitis, progressing to pulmonary
fibrosis)
Idiosyncratic reaction (since reactions usually occur after
first or second dose, careful monitoring is essential after
these doses)
Elderly (at greater risk of pulmonary toxicity); children (has
been associated with a higher incidence of pulmonary
toxicity).
Adverse Drug Reactions:
Common: Acute febrile reactions, acute or chronic
interstitial pneumonitis, alopecia, anaphylactoid-like
348
ANTINEOPLASTIC AND IMMODULATING AGENTS
reactions (hypotension, confusion, fever, chills, and
wheezing), cough, bilateral pulmonary infiltrates,
anorexia, dyspnea, erythema, diffuse scleroderma,
hypoxia (potentially fatal), pain at the tumor site,
hyperpigmentation, idiosyncratic reactions,
hyperkeratosis, induration, mucositis, nailbed changes,
onycholysis, rash, peeling of the skin (hands and feet),
phlebitis, pruritus, skin thickening, pulmonary fibrosis,
rales, stomatitis, striae, tachypnea, vesiculation, weight
loss
Less Common: Angioedema, cerebrovascular accident,
cerebral arteritis, chest pain, coronary artery disease,
flagellate hyperpigmentation, MI, hepatotoxicity,
malaise, myocardial ischemia, nausea, pericarditis,
Raynaud’s phenomenon, renal toxicity, scleroderma-like
skin changes, SJS, TEN, thrombotic microangiopathy,
vomiting
Rare: Myelosuppression
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Bleomycin:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Bleomycin:
Denosumab (serious infections), Filgrastim (pulmonary
toxicity)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Bleomycin:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Bleomycin:
Gemcitabine (pulmonary toxicity), Pimecrolimus,
Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
Natalizumab (concurrent infection)
Reduces therapeutic effect of Bleomycin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: For IV injections, administer slowly over 10
minutes.
For IM or SC administration, may cause pain at injection
site.
Pregnancy Category: D
ATC Code: L01DC01
ANTINEOPLASTIC AND IMMODULATING AGENTS
OTHER ANTINEOPLASTIC AGENTS
PLATINUM COMPOUNDS
Rx CARBOPLATIN
Inj.: 150 mg and 450 mg powder, vial (IV)
10 mg/mL, 15 mL and 45 mL vial (IV)
A platinum compound alkylating agent, which covalently
binds to DNA, interfering with DNA function by producing
interstrand DNA crosslinks.
Indications: Initial treatment of advanced ovarian cancer in
combination with other established chemotherapy
agents; palliative treatment of recurrent ovarian cancer
after prior chemotherapy. Childhood solid malignancy:
neuroblastoma, retinoblastoma; relapsed Non-Hodgkin’s
lymphoma (NHL); recurrent soft tissue sarcomas
Contraindications: History of severe allergic reaction to
carboplatin, cisplatin, other platinum-containing
formulations, mannitol, or any component of the
formulation; severe bone marrow depression; significant
bleeding
Dose:
NOTE: Doses for adults are commonly calculated by the
target AUC using the Calvert formula, where
Total dose (mg) = Target AUC x (GFR + 25)
If estimating glomerular filtration rate (GFR) instead of a
measured GFR, consider capping estimated GFR at a
maximum of 125 mL/minute to avoid potential toxicity.
Ovarian cancer, advanced, by IV infusion, ADULT, as a single
agent, 360 mg/m2 every 4 weeks; in combination with
cyclophosphamide 300 mg/m2 every 4 weeks; as a
single agent in previously-treated patients, target AUC 4–
6.
Neuroblastoma, induction and post induction, CHILD, 500
mg/m2/d for 2 days on 1 cycle.
Retinoblastoma, CHILD < 36 months, 18.6 mg/kg/dose
(single dose each cycle); CHILD > 36 months, 560
mg/m2/dose (single dose each cycle).
Recurrent soft tissue sarcoma, CHILD, 150 mg/m2/d as 3h
IV infusion for 2 days.
Dose Adjustment:
Geriatric:
Calculate dose based on Calvert formula:
Total dose (mg) = Target AUC x (GFR + 25)
Obesity:
Consider dosing based on GFR. GFR should not exceed 125
mL/minute.
Use actual body weight (full weight) for calculation of BSA-
based dosing for hematopoietic stem cell transplant
conditioning regimens in adults.
Renal Impairment:
Dose determination with Calvert formula uses GFR and,
therefore, inherently adjusts for renal dysfunction.
For baseline CrCl 41–59 mL/minute, initiate at 250 mg/m2
and adjust subsequent doses based on bone marrow
toxicity.
For baseline CrCl 16–40 mL/minute, initiate at 200 mg/m2
and adjust subsequent doses based on bone marrow
toxicity.
In hemodialysis, administer on a non-dialysis day,
hemodialysis should occur between 12–24 hours after
administration. Calculate dose as follows:
Carboplatin dose (mg) = Target AUC x 25
Bone Marrow Suppression:
Reduce dose. Delay cycles until WBC and platelet counts
have recovered.
Toxicity:
If platelets <50,000 cells/mm3 or ANC <500 cells/mm3,
administer 75% of dose.
L
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer chemotherapy
physician. Administer in a facility sufficient to
appropriately diagnose and manage complications.
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (increased risk with prior
myelosuppressive therapy, renal dysfunction);
neurotoxicity
Hypersensitivity or anaphylactoid reactions (risk increased
in patients previously exposed to platinum therapy;
consider skin testing or desensitization protocols).
Liver function abnormalities (may be caused by high doses
of >4 times the recommended dose)
Ototoxicity (may occur when given together with
aminoglycosides; long-term audiology monitoring is
recommended)
Renal toxicity (limited unless given together with
aminoglycosides)
Vision loss (reported with higher than recommended doses;
usually reversible weeks after discontinuation)
Elderly (increased incidence of peripheral neuropathy and
severe thrombocytopenia; increased incidence of
neurotoxicity; considered inappropriate for elderly use)
Children (children <6 months are at an increased risk of
ototoxicity)
Adverse Drug Reactions:
Common: Abdominal pain, alopecia, anemia, pain, bleeding
complications, constipation, decreased creatinine
clearance, bone marrow depression (dose related; dose
limiting), dysgeusia, hemorrhage, hypersensitivity,
hypocalcemia, hypokalemia, hypomagnesemia,
hyponatremia, diarrhea, infection, leukopenia,
mucositis, nausea, neurotoxicity, neutropenia,
ototoxicity, peripheral neuropathy, stomatitis,
thrombocytopenia, visual disturbance, vomiting,
weakness
349

Less Common: Anaphylaxis, bronchospasm, cardiac failure,
cerebrovascular accident, dehydration, anorexia,
embolism, febrile neutropenia, erythema, hemolytic
anemia (acute), HUS, hypertension, hypotension,
injection site reaction (pain, redness, swelling), limb
ischemia (acute), malaise, metastases, pruritus, skin
rash, tissue necrosis (associated with extravasation),
urticaria, vision loss
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Carboplatin:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Carboplatin:
Denosumab (serious infections), Aminoglycosides [e.g.
Streptomycin, Amikacin (ototoxic effect)]
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Carboplatin:
Roflumilast (immunosuppressive effect)
L
Enhances therapeutic effect of the following drugs:
Taxane Derivatives [e.g. Paclitaxel, Docetaxel
(myelosuppressive effect)], Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Carboplatin:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Sorafenib, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Topotecan
Reduces therapeutic effect of Carboplatin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: For IV administration. Infuse over 15–60
minutes. Some protocols may require infusions up to 24
hours.
Do NOT use needles or IV administration sets that
contain aluminum during preparation or administration.
Aluminumcan react with carboplatin resulting in
precipitate formation and loss of potency.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
When administered as sequential infusions, with taxane
derivaties, administer taxane derivatives before
350
ANTINEOPLASTIC AND IMMODULATING AGENTS
platinum derivatives to limit myelosuppression and to
enhance efficacy.
Pregnancy Category: D
ATC Code: L01XA02
Rx CISPLATIN
Inj.: 1 mg/mL, 10 mLand 50 mL vial (IV)
A platinum compound that inhibits DNA synthesis by the
formation of DNA crosslinks.
Indications: Treatment of advanced bladder cancer
(transitional cell) in patients who are no longer
candidates for local therapy including surgery and/or
radiation therapy; treatment of metastatic ovarian
cancer in patients who have previously received
appropriate surgery and/or radiation therapy; for
refractory tumors in patients who have not previously
received cisplatin; treatment of metastatic testicular
cancer in patients who have previously received
appropriate surgery and/or radiation therapy; Childhood
solid malignancies: Hodgkin’s Lymphoma (HD); Brain
tumors; neuroblastoma; malignant bone tumors;
hepatoblastoma; germ cell tumor (GCT).
Contraindications: Preexisting renal impairment;
myelosuppression; hearing impairment
Dose:
Bladder cancer, advanced, by slow IV infusion, ADULT, 50–
70 mg/m2 every 3–4 weeks; or 50 mg/m2 every 4 weeks
in heavily pretreated patients.
Ovarian cancer, metastatic, by slow IV infusion, ADULT, 100
mg/m2 every 4 weeks.
Germ Cell Tumors, CHILD, 20 mg/m2 IV as a single dose
once daily for 5 days with bleomycin and etoposide (PEB
regimen); repeat every 3 weeks; Refer to institutional
protocols for other dosing regimen for CNS tumors,
neuroblastoma, hepatoblastoma.
Hodgkin’s Lymphoma, CHILD, 90 mg/m2 as IV infusion for
6h (single dose per cycle)
Germinoma, CHILD, 20 mg/m2/d for 5 days
Neuroblastoma, induction, CHILD, 40 mg/m2/d for 5 days
on 2 cycles; post induction, 40 mg/m2/d for 5 days on 1
cycle
Osteosarcoma, CHILD, 60 mg/m2/d for 2 days
Hepatoblastoma, low risk (PRETEXT I, II), CHILD < 10 kg, 3.3
mg/kg/d; CHILD > 10 kg, 100 mg/m2/d;
Hepatoblastoma, high risk (PRETEXT III, IV), CHILD, 80
mg/m2/d for Day 1 then 70 mg/m2/d on succeeding
days
Dose Adjustment:
Renal Impairment:
If serum creatinine is >1.5 mg/dL and/or BUN is >25
mg/dL, do not repeat course.
ANTINEOPLASTIC AND IMMODULATING AGENTS
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician, experienced in the use of
cancerchemotherapeutic agents.Administer in a
facility sufficient to appropriately diagnose and
manage complications.
Doses >100 mg/m2/cycle (once every 3–4 weeks)
are rare. Verify with prescriber prior to
administration. At the approved dose, cisplatin
should not be administered more frequently than
once every 3–4 weeks.
Exercise caution to avoid inadvertent overdose due
to potential sound-alike/look-alike confusion
between cisplatin and carboplatin or prescribing
practices that fail to differentiate daily doses from
the total dose per cycle.
Associated with severe cumulative renal toxicity, as
well as dose-related myelosuppression, nausea,
and vomiting.
Anaphylactic-like reactions have occurred. Facial
edema, bronchoconstriction, tachycardia, and
hypotension may occur within minutes of
administration. Epinephrine, corticosteroids, and
antihistamines have been effectively employed to
alleviate symptoms.
Significant ototoxicity. Manifests as tinnitus or loss of
high frequency hearing, and occasionally
deafness. May be more pronounced in children.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Gastrointestinal events (e.g. nausea, vomiting, diarrhea;
dose-related); hyperuricemia (more pronounced with
doses >50 mg/m2; consider anti-hyperuricemic therapy).
Neurotoxicity (severe, possibly irreversible neuropathies
e.g. stocking-glove paresthesias, areflexia, loss of
proprioception or vibratory sensation, seizures, loss of
motor function, loss of taste, leukoencephalopathy,
posterior reversible leukoencephalopathy syndrome)
Ototoxicity (cumulative; may be severe; audiometric testing
should be performed at baseline, prior to each dose, and
several years after discontinuing therapy)
Renal toxicity (monitor serum creatinine, BUN, creatinine
clearance, and serum electrolytes closely)
Secondary malignancies
Elderly (may be more susceptible to nephrotoxicity and
peripheral neuropathy; considered potentially
inappropriate for elderly)
Adverse Drug Reactions:
Common: Anemia, local irritation, leukopenia (dose related),
nausea, nephrotoxicity (acute renal failure and chronic
renal insufficiency), neurotoxicity, peripheral neuropathy
(dose and duration dependent), ototoxicity,
thrombocytopenia, vomiting
Less Common: Alopecia (mild), anaphylaxis, aortic
thrombosis, autonomic neuropathy, bradycardia,
bronchoconstriction, cardiac arrhythmia, cardiac failure,
ageusia, cerebrovascular accident, cerebral arteritis,
dehydration, diarrhea, extravasation, heart block,
hemolytic anemia (acute), hypercholesterolemia,
hemolytic-uremic syndrome, hyperuricemia,
hypomagnesemia, hypocalcemia, hypokalemia,
hyponatremia, skin rash, hiccups, hypophosphatemia,
hypotension, increased serum amylase, ischemic heart
disease, leukoencephalopathy, Lhermitte's sign,
myocardial infarction, neutropenic enterocolitis, optic
neuritis, pancreatitis, papilledema, SIADH, peripheral
L
ischemia (acute), phlebitis, reversible posterior
leukoencephalopathy syndrome, vision loss, seizure,
tachycardia, tetany, thrombotic thrombocytopenic
purpura, vision color changes
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Cisplatin:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Cisplatin:
Denosumab (serious infections), Loop Diuretics [e.g.
Furosemide (nephrotoxiceffect)]
Increases risk of adverse or toxic effects of the following
drugs:
Aminoglycosides [e.g., Streptomycin
(nephrotoxiceffect)], Vinorelbine (granulocytopenia)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of Cisplatin:
Alpha-Lipoic Acid
Avoid concomitant use with:
Enhances therapeutic effect of Cisplatin:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Taxane Derivatives [e.g. Paclitaxel, Docetaxel
(myelosuppressive effect)], Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Cisplatin:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Topotecan
351

Reduces therapeutic effect of Cisplatin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: For IV administration, infuse over 6–8
hours. Do NOTadminister as a rapid IV injection.
Hydrate with 1–2 L of fluid prior to administration.
Adequate post hydration and urinary output (>100
mL/hour) should be maintained for 24 hours after
administration. Monitor serum electrolytes, particularly
magnesium and potassium, and replace as needed
during and after therapy.
Do NOT use needles or IV administration sets that
contain aluminum during preparation or administration.
Aluminumcan react with carboplatin resulting in
precipitate formation and loss of potency.
NOTE: Avoid extravasation. Ensure proper needle or
L
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Pregnancy Category: D
ATC Code: L01XA01
Rx OXALIPLATIN
Inj.: 50 mg powder, vial (IV infusion)
5 mg/mL concentrate solution, 10 mL and 20 mLvial
(IV infusion)
A platinum derivative that acts as an alkylating agent. It
forms DNA cross links to inhibit DNA replication.
Indications: Adjuvant treatment of stage III colon cancer
after complete resectionof primary tumor; treatment of
advanced colorectal cancer
Contraindications: Pregnancy; breastfeeding; severe renal
impairment
Dose:
Advanced colorectal cancer, by IV infusion, ADULT, in
combination with fluorouracil and leucovorin, 85 mg/m2
every 2 weeks until disease progression or
unacceptable toxicity; in combination with Capecitabine,
130 mg/m2 every 3 weeks.
Stage III colon cancer, adjuvant, by IV infusion, ADULT, in
combination with fluorouracil and leucovorin, 85 mg/m2
every 2 weeks for 6 months (12 cycles); in combination
with Capecitabine, 130 mg/m2 every 3 weeks.
Dose Adjustment:
Renal Impairment:
In CrCl <30 mL/minute, reduce dose to 65 mg/m2.
352
ANTINEOPLASTIC AND IMMODULATING AGENTS
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Toxicity:
Neurosensory events:
For persistent grade 2 neurosensory events lasting >7 days,
consider withholding oxaliplatin despite dose reduction:
In stage III colon cancer, reduce dose to 75 mg/m2.
In advanced colorectal cancer, reduce dose to 65
mg/m2.
For persistent grade 3 neurosensory events lasting >7 days:
In stage III colon cancer, discontinue use.
In advanced colorectal cancer, reduce dose to 65
mg/m2; if not resolved prior to the next cycle, discontinue
use.
For persistent grade 4 neurosensory events:
In advanced colorectal cancer, discontinue use.
Gastrointestinal toxicity (grade 3/4):
In stage III colon cancer, delay next dose until recovery
from toxicity, then reduce dose to 75 mg/m2.
In advanced colorectal cancer, delay next dose until
recovery from toxicity, then reduce dose to 65 mg/m2.
Hematologic toxicity (grade 3/4 neutropenia, grade 3/4
thrombocytopenia, or febrile neutropenia,):
In stage III colon cancer, delay next dose until neutrophils
recover to ≥1,500/mm3 and platelets to ≥75,000/mm3,
then reduce dose to 75 mg/m2.
In advanced colorectal cancer, delay next dose until
neutrophils recover to ≥1,500/mm3 and platelets to
≥75,000/mm3, then reduce dose to 65 mg/m2.
Precautions:
WARNING: Anaphylactic-like reactions have been
reported and may occur within minutes of
administration. Epinephrine, corticosteroids, and
antihistamines have been employed to alleviate
symptoms of anaphylaxis.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Hypersensitivity or anaphylactoid reactions (e.g. pruritus,
bronchospasm, erythema, hypotension, rash, urticaria,
flushing, diaphoresis, diarrhea, chest pain, shortness of
breath, disorientation, or syncope may occur; grade 3 or
4 hypersensitivity)
Neuropathy (e.g. acute, reversible, peripheral sensory
neuropathy which may interfere with daily activities (e.g.,
writing, buttoning, swallowing; cold-triggered neuropathy
commonly recurs with subsequent doses and may last
up to 7 days after administration).
Hepatotoxicity (e.g. hepatitis and hepatic failure); Renal
impairment
ANTINEOPLASTIC AND IMMODULATING AGENTS
Pulmonary fibrosis (withhold treatment for unexplained
pulmonary symptoms until interstitial lung disease or
pulmonary fibrosis are excluded)
Reversible posterior leukoencephalopathy syndrome (e.g.
headache, mental status changes, seizure, blurred
vision, blindness, other vision changes)
Elderly (more sensitive to adverse events, particularly
diarrhea, dehydration, hypokalemia, leukopenia, fatigue,
and syncope)
Adverse Drug Reactions:
Common :Abdominal pain, abnormal lacrimation, alopecia,
anemia, anorexia, arthralgia, back pain, constipation,
cough, dehydration, diarrhea, dizziness, dysgeusia,
dyspepsia, dysphagia, dyspnea, dysuria, edema,
epistaxis, fatigue, fever, flatulence, flushing, chest pain,
GERD, headache, hiccups, hypersensitivity reaction,
hypokalemia, injection site reaction (redness, swelling,
pain), insomnia, leukopenia, mucositis, neutropenia,
nausea, palmar-plantar erythrodysesthesia, peripheral
edema, peripheral neuropathy (dose limiting),
pharyngitis, pain, pharyngolaryngeal dysesthesia,
rhinitis, rigors, skin rash, stomatitis, thrombocytopenia,
thromboembolism, upper respiratory tract infection,
vomiting
Less Common: Abnormal gait, acute renal failure,
anaphylaxis,anaphylactic shock, anaphylactoid reaction,
angioedema, aphonia, blepharoptosis, cerebral
hemorrhage, colitis, cranialnerve palsy, decreased deep
tendon reflex, deafness, decreased visual acuity,
diplopia, dysarthria, eosinophilic
pneumonitis,fasciculations, febrile neutropenia,
hematuria, hemolysis, hemolytic anemia
(immunoallergic), ataxia, hemolytic-
uremicsyndrome,hemorrhage, hepatic failure, hepatic
sinusoidal obstruction syndrome, hepatitis,
hepatotoxicity, hypomagnesemia, hypoxia, hypertension,
idiopathic noncirrhotic portal hypertension (nodular
regenerative hyperplasia)I , infusion related reaction
(extravasation), interstitial pulmonary disease, intestinal
obstruction, laryngospasm, Lhermittes' sign, interstitial
nephritis (acute), metabolic acidosis, myoclonus,
neutropenic enterocolitis, neutropenic infection (sepsis),
optic neuritis, pancreatitis, muscle spasm, purpura,
rectal hemorrhage, renal tubular necrosis, reversible
posterior leukoencephalopathy syndrome, seizure,
rhabdomyolysis, sepsis, temporary vision loss,
thrombocytopenia (immunoallergic), trigeminal
neuralgia, visual field loss, voice disorder
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Oxaliplatin:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Oxaliplatin:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Oxaliplatin:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Taxane Derivatives [e.g. Paclitaxel, Docetaxel
(myelosuppressive effect)], Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Oxaliplatin:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity such as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Topotecan
Reduces therapeutic effect of Oxaliplatin:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration: Administer as IV infusion over 2 hours.
L
Longer infusion time (6 hours) may mitigate acute
toxicities (e.g., pharyngolaryngeal dysesthesia). Extend
infusion time to 6 hours for acute toxicities.
Do NOT use needles or IV administration sets that
contain aluminum during preparation or administration.
Aluminum can react with carboplatin resulting in
precipitate formation and loss of potency.
Avoid mucositis prophylaxis with ice chips to prevent
exacerbation of acute neurological symptoms associated
with exposure to coldtemperatures, or consumption of
cold food or beverages during or within hours of
administration.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, discontinue infusion immediately
and apply ice to the affected area.
Associated with a high emetic potential. Antiemetics are
recommended to prevent nausea and vomiting.
Do NOT prepare using a chloride-containing solution
such as NaCl. Flush infusion line with D5W prior to, and
following, administration of concomitant medications via
same IV line.
When used in combination with a fluoropyrimidine (e.g.,
fluorouracil), infuse oxaliplatin first.
Pregnancy Category: D
ATC Code: L01XA03
353

MONOCLONAL ANTIBODIES
Rx RITUXIMAB
Inj.: 10 mg/mL, 10 mL and 50 mL vial (IV)
A monoclonal antibody directed against the CD20 antigen
on B lymphocytes. It binds to the antigen to initiate killing
of B-cells, delaying the progression of structural damage.
Indications: Treatment of CD20-positive non-Hodgkin’s
lymphomas (NHL); treatment of CD20-positive chronic
lymphocytic leukemia (CLL); treatment of
granulomatosis with polyangiitis (GPA; Wegener’s
granulomatosis); treatment of microscopic polyangiitis
(MPA)
Contraindications: Type 1 hypersensitivity or anaphylactic
reaction to murine proteins, Chinese Hamster Ovary
(CHO) cell proteins, or any component of the formulation;
current or a history of progressive multifocal
L
leukoencephalopathy (PML)
Dose:
CLL, by slow IV infusion, ADULT, in combination with
fludarabine and cyclophosphamide, 375 mg/m2 the day
prior to fludarabine / cyclophosphamide in cycle 1, then
500mg/m2 on day 1 (every 28 days) of cycles 2–6.
Fludarabine dose: 25 mg/m2 IV per day for 3 days,
Cyclophosphamide dose: 250 mg/IV per day for 3 days.
Granulomatosis with polyangiitis, by slow IV infusion,
ADULT, in combination with methylprednisolone IV for 1–
3 days followed by daily prednisone, 375 mg/m2 once
weekly for 4 doses.
Non-Hodgkin’s lymphoma (NHL), low-grade or follicular
CD20-positive, B-cell, previously untreated, by slow IV
infusion, ADULT, 375 mg/m2 once weekly for 4 or 8
doses. May give IV formulation at first cycle, followed by
subcutaneous formulation injected at a fixed dose of
1400mg per cycle for up to 8 cycles. As maintenance for
previously untreated follicular lymphoma who have
responded to induction treatment, 1400mg
subcutaneously once every 2 months (starting 2 months
after the last dose of induction therapy) until disease
progression or a maximum period of 2 years.
NHL, low-grade or follicular CD20-positive, B-cell, relapsed/
refractory, by slow IV infusion, ADULT, 375 mg/m2 once
weekly for 4 or 8 doses. May give IV formulation at first
cycle, followed by subcutaneous formulation injected at
a fixed dose of 1400 mg per cycle for up to 8 cycles. As
maintenance for relapsed/ refractory follicular
lymphoma who have responded to induction treatment,
1400 mg subcutaneously once every 3 months (starting
3 months after the last dose of induction therapy) until
disease progression or a maximum period of 2 years.
NHL, diffuse large B-cell, in combination with CHOP therapy.
Rituximab given by slow IV infusion, 375 mg/m2,
followed by rituximab subcutaneous formulation injected
at a fixed dose of 1400 mg per cycle in total of 8 cycles.
NHL, CD20-positive, B-cell, non-progressing, low-grade,
after 6–8 cycles of first line CVP, by slow IV infusion,
ADULT, 375 mg/m2, once weekly for 4 doses every 6
months for a maximum of 16 doses.
354
ANTINEOPLASTIC AND IMMODULATING AGENTS
NHL, by slow IV infusion, ADULT, in combination with
ibritumomab, 250 mg/m2 IV day 1, repeat in 7–9 days
with ibritumomab.
NHL, CD20-positive, mature B-cell lymphoma, Diffuse Large
B-Cell Lymphoma, CHILDREN and ADOLESCENTS, 375
mg/m2 prior to consolidation therapy (frequency and
number of doses depend upon treatment protocol).
Microscopic polyangiitis (MPA), by slow IV infusion, ADULT,
in combination with methylprednisolone IV for 1–3 days
followed by daily prednisone, 375 mg/m2 once weekly
for 4 doses.
Pemphigus vulgaris, moderate-to-severe, Initial: 1000 mg IV
once then repeat dose in 2 weeks used in combination
with tapering course of glucocorticoids; Maintenance:
500 mg at month 12 and every 6 months thereafter or
based on clinical evaluation; Treatment relapse: 1000
mg IV and consider resuming or increasing glucocorticoid
dose based on clinical evaluation.
Rheumatoid Arthritis, rituximab only, 1000 mg IV infusion
(not to exceed 1000 mg/dose), repeat after 2 weeks (2
infusions separated by 2 weeks is 1 course). Repeat
course every 24 weeks or based on clinical evaluation
(but no sooner than 16 weeks); use in combination with
methotrexate.
Precautions:
WARNING: Can result in serious, including fatal,
infusion reactions. Deaths within 24 hours of
infusion have been reported. Carefully monitor
patients during infusions. Discontinue when severe
reactions occur and administer medical treatment
for grade 3 or 4 infusion reactions.
Severe, sometimes fatal, mucocutaneous reactions
(e.g., paraneoplastic pemphigus, Stevens-Johnson
syndrome, lichenoid dermatitis, toxic epidermal
necrolysis, vesiculobullous dermatitis) have been
reported.
Hepatitis B virus (HBV) reactivation can occur, in
some cases resulting in fulminant hepatitis,
hepatic failure, and death. Screen all patients for
HBV infection by measuring HBsAg and anti-HBc
before treatment initiation. Monitor patients during
and after treatment. Discontinue in the event of
HBV reactivation.
JC virus infection resulting in progressive multifocal
leukoencephalopathy (PML) and death can occur.
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bowel obstruction or perforation (e.g. abdominal pain,
bowel obstruction, perforation; complaints of abdominal
pain or repeated vomiting should be evaluated,
especially if early in the treatment course)
Cardiovascular disease (use with caution; discontinue if
serious cardiac arrhythmia occurs); respiratory disease
(use with caution in patients)
Hepatitis B virus reactivation (monitor patients for clinical
and laboratory signs of hepatitis or HBV during and
several months after treatment; reactivation may occur
even in those with previously resolved HBV infection, and
ANTINEOPLASTIC AND IMMODULATING AGENTS

up to 24 months after therapy discontinuation; use with fulminant hepatitis, gastrointestinal perforation,
caution in those with evidence of prior HBV infection) hemolytic anemia, hepatic failure, hepatitis, hepatitis B
Infections (serious and potentially fatal bacterial, fungal, reactivation, hypogammaglobulinemia (prolonged), optic
and either new or reactivated viral infections may occur neuritis, interstitial pneumonitis, hyperviscosity
during treatment and after; monitor immunoglobulin syndrome (Waldenström’s macroglobulinemia), hypoxia,
levels as necessary; discontinue in patients who develop laryngeal edema, lichenoid dermatitis, lupus-like
other serious infections and initiate appropriate anti- syndrome, marrow hypoplasia, mucositis,
infectivetreatment; use is not recommended in active mucocutaneous reaction, pleuritis, neutropenia,
infection) pancytopenia (prolonged), pure red cell aplasia,
Infusion reactions (e.g. hypotension, angioedema, paraneoplastic pemphigus, renal toxicity, pneumonia,
bronchospasm, hypoxia, urticaria, pulmonary infiltrates, pneumonitis, polyarticular arthritis, polymyositis,
ARDS, myocardial infarction, ventricular fibrillation, posterior reversible encephalopathy syndrome (PRES),
cardiogenic shock, or anaphylaxis; closely monitor progressive multifocal leukoencephalopathy (PML),
patients with history of prior cardiopulmonary reactions, serum sickness, Stevens-Johnson syndrome, toxic
with preexisting cardiac or pulmonary conditions, or with epidermal necrolysis, reversible posterior
high numbers of circulating malignant cells, i.e., leukoencephalopathy syndrome (RPLS),
>25,000/mm3; perform cardiacmonitoring during and supraventriculararrhythmia, systemic vasculitis,
after the infusion in patients who develop clinically tuberculosis reactivation, tumor lysis syndrome, uveitis,
significant arrhythmias or who have a history of ventricular fibrillation, vasculitis withrash, ventricular
arrhythmia or angina; mild-to-moderate infusion-related tachycardia, vesiculobullous dermatitis, viral reactivation
reactions, e.g., chills, fever, or rigors, occur frequently (JC virus, cytomegalovirus, herpes simplex virus,
and are typically managed through slowing or parvovirus B19, varicella zoster virus, West Nile virus, and
interrupting the infusion; due to the potential for hepatitis C), wheezing

hypotension, consider withholding antihypertensives 12
hours prior to treatment)
Mucocutaneous reactions (discontinue in severe
mucocutaneous skin reactions); progressive multifocal
leukoencephalopathy (e.g. confusion or disorientation,
motor weakness or hemiparesis, altered vision or
speech, and poor motor coordination; promptly evaluate
patients with neurological changes; discontinue in
patients who develop PML; consider reduction or
discontinuation of concurrent chemotherapy
orimmunosuppressants)
Renal toxicity (may be fatal; discontinue with increasing
serum creatinine or oliguria);
Tumor lysis syndrome (may lead to acute renal failure
requiring dialysis, may be fatal; hyperkalemia,
hypocalcemia, hyperuricemia, and/or
hyperphosphatemia may occur; correct electrolyte
abnormalities; monitor renal function and hydration
status).
Elderly (use with caution; at higher risk of cardiac and
pulmonary adverse events).
Adverse Drug Reactions:
Common: Abdominal pain, anemia, angioedema, anxiety,
arthralgia, bronchospasm, back pain, chills, cough,
cytopenias (may be prolonged), diarrhea, dizziness,
dyspepsia, dyspnea, dyspnea, epistaxis, fatigue,
flushing, headache, positive human antichimeric
antibody (HACA), fever, hyperglycemia, hypertension,
hypotension, infection, infusion-related reactions
(decreases with subsequent infusions), night sweats,
insomnia, increased LDH, leukopenia, lymphopenia,
migraine, muscle spasm, myalgia, nausea, neuropathy,
neutropenia, neutropenic fever, paresthesia, peripheral
edema, pruritus, rash, rhinitis, sinusitis, throat irritation,
pain, thrombocytopenia, upper respiratory tract
infection, urticaria, vomiting, weakness, weight gain
Less Common: Acute renal failure, anaphylactoid reaction
or anaphylaxis, angina, aplastic anemia, arrhythmia,
bowel obstruction or perforation, ARDS, bronchiolitis
obliterans, cardiac failure, MI, cardiogenic shock,
disease progression (Kaposi’s sarcoma),
encephalomyelitis, fatal infusion-related reactions,
L
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Rituximab:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Rituximab:
Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Enhances therapeutic effect of Rituximab:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Certolizumab Pegol
(immunosuppressive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Abatacept, Balimumab, Clozapine (agranulocytosis),
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
Natalizumab (concurrent infection), Tofacitinib
Increases risk of adverse or toxic effects of Rituximab:
Antihypertensives (hypotensive effect), Dipyrone
(agranulocytosis; pancytopenia), Pimecrolimus,
Tacrolimus (Topical)
Reduces therapeutic effect of Rituximab:
Echinacea
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response; live
virus vaccines may progress to infection)
Administration:
Refer to institutional guideline on administration, if available.
For IV infusion only.
For initial IV infusion, start at a rate of 50 mg/hour. If
there is no reaction, increase the rate by 50 mg/hour

355

increments every 30 minutes, to a maximum rate of 400
mg/hour.
For subsequent IV infusions,
Standard infusion rate:
If patient tolerated initial infusion, start at 100 mg/hour.
If there is no reaction, increase the rate by 100 mg/hour
increments every 30 minutes, to a maximum rate of 400
mg/hour.
Accelerated infusion rate (90 minutes):
For patients with previously untreated follicular NHL and
diffuse large B-cell NHL who are receiving a
corticosteroid concurrently, with a circulating lymphocyte
count <5000/mm3, or have no significant cardiovascular
disease, after tolerance has been established (no grade
3 or 4 infusion-related event) at the recommended
infusion rate in cycle 1, a rapid infusion rate may be used
beginning with cycle 2. Administer dose over 90 minutes,
with 20% of the dose administered over the first 30
minutes and the remaining 80% is given over 60
minutes, after the daily corticosteroid, acetaminophen,
and diphenhydramine. If the 90-minute infusion in cycle
L
2 is tolerated, the same rate may be used for the
remainder of the treatment regimen (through cycles 6 or
8).
Do NOT administer by IV push or bolus. If a reaction
occurs, slow or stop the infusion. Once reaction abates,
restart infusion at 50% of the previous rate. Discontinue
infusion in the event of serious or life-threatening cardiac
arrhythmias.
NOTE: Pretreatment with acetaminophen and an
antihistamine is recommended.
Anti-hyperuricemic therapy and aggressive hydration are
recommended for patients with a high tumor burden or
lymphocytes >25,000/mm3.
In patients with CLL, Pneumocystis jirovecii pneumonia
(PCP) and antiherpetic viral prophylaxis is recommended
during treatment (and for up to 12 months following
treatment).
In granulomatosis with polyangiitis (GPA) and
microscopic polyangiitis (MPA), PCP prophylaxis is
recommended during and for 6 months after treatment.
Pregnancy Category: C
ATC Code: L01XC02
Rx TRASTUZUMAB
Inj.: 150 mg lyophilized powder (IV infusion)
600 mg/5 mL (120 mg/mL) solution for injection, 5
mL vial (SC)
A monoclonal antibody which binds to the extracellular
domain of the human epidermal growth factor receptor
2 protein (HER-2). It mediates antibody-dependent
cellular cytotoxicity by inhibiting proliferation of cells
which over express HER-2 protein.
356
ANTINEOPLASTIC AND IMMODULATING AGENTS
Indications: Treatment of HER-2 overexpressing node
positive or node negative (estrogen receptor or
progesterone receptor negative or with 1 high risk
feature) in early stage breast cancer, alone or in
combination
Contraindication: Hypersensitivity to trastuzumab, Chinese
hamster ovary (CHO) cell proteins, or any component of
the formulation
Dose:
HER2+ early stage breast cancer, adjunct treatment, by IV
infusion, ADULT,
in combination with paclitaxel or docetaxel, initially 4
mg/kg as loading dose, infused over 90 minutes,
followed by 2 mg/kg maintenance dose, infused over 30
minutes weekly for total of 12 weeks, followed 1 week
later, after completion of concurrent chemotherapy, by 6
mg/kg infused over 30–90 minutes every 3 weeks for
total therapy duration of 52 weeks;
in combination with docetaxel and carboplatin, initially 4
mg/kg as loading dose, infused over 90 minutes,
followed by 2 mg/kg maintenance dose, infused over 30
minutes weekly for total of 18 weeks, followed 1 week
later, after completion of concurrent chemotherapy, by 6
mg/kg infused over 30–90 minutes every 3 weeks for
total therapy duration of 52 weeks;
following completion of multi-modality anthracycline-
based chemotherapy, initially 8 mg/kg, as loading dose,
infused over 90 minutes, followed by 6 mg/kg
maintenance dose, infused over 30–90 minutes every 3
weeks for total therapy duration of 52 weeks.
Dose Adjustment:
Cardiotoxicity:
For LVEF ≥16% decrease from baseline or LVEF below
normal limits and ≥10% decrease from baseline,
withhold treatment for at least 4 weeks and repeat LVEF
every 4 weeks. Resume treatment if LVEF returns to
normal limits within 4–8 weeks and remains at ≤15%
decrease from baseline value. Discontinue permanently
for persistent (>8 weeks) LVEF decline or for >3 incidents
of treatment interruptions for cardiomyopathy.
Infusion-related events:
If mild-moderate infusion reactions occur, decrease
infusion rate.
If dyspnea or clinically significant hypotension occurs,
interrupt infusion.
If severe or life-threatening infusion reactions occur,
discontinue.
Precautions:
WARNING: Associated with symptomatic and
asymptomatic reductions in left ventricular
ejection fraction (LVEF) and heart failure. Incidence
and severity were highest in concurrent use with
anthracycline-containing chemotherapy regimens.
Evaluate left ventricular function in all patients
prior to and during treatment.
Infusion reactions, including fatalities, have been
associated with use. Discontinue for anaphylaxis or
angioedema. Interrupt infusion for dyspnea or
significant hypotension.
ANTINEOPLASTIC AND IMMODULATING AGENTS

(membranous, focal and fibrillary), coma,

May cause serious pulmonary toxicity, including glomerulopathy, hematemesis, hemorrhage,
dyspnea, hypoxia, interstitial pneumonitis, hemorrhagic cystitis, hepatic failure, hepatic injury,
pulmonary infiltrates, pleural effusion, hepatitis, herpes zoster, hiccups, hypoprothrombinemia,
noncardiogenic pulmonary edema, pulmonary hydrocephalus, hydronephrosis, hypercalcemia,
insufficiency, acute respiratory distress syndrome hypervolemia, hypotension, hypothyroidism, hypoxia,
[ARDS], and/or pulmonary fibrosis. Discontinue for intestinal obstruction, interstitial pneumonitis, jaundice,
ARDS or interstitial pneumonitis. laryngeal edema, laryngitis, lethargy, leukemia (acute),
limb pain, lymphangitis, madarosis, mania, mastalgia,
Conventional trastuzumab and ado-trastuzumab meningitis, musculoskeletal pain, myopathy,
emtansine are different products and are NOT neutropenia, neutropenic sepsis, nephrotic syndrome,
interchangeable. oligohydramnios, onychoclasis, osteonecrosis,
pancreatitis, paresis, oxygen desaturation,
pancytopenia, paroxysmal nocturnal dyspnea,
WARNING: Hazardous agent. Use appropriate pathological fracture, pericardial effusion, pericarditis,
precautions for handling and disposal. pleural effusion, pneumonitis, shock, pulmonary edema
(noncardiogenic), pulmonary fibrosis, pulmonary
hypertension, pneumothorax, renal failure, pulmonary
Cardiomyopathy (e.g. arrhythmias, hypertension, mural infiltrates, pyelonephritis, radiation injury, respiratory
thrombus formation, stroke, cardiac death may occur; distress, respiratory failure, seizure, sepsis, syncope,
observe extreme caution in patients with pre-existing stomatitis, thrombosis (including mural), urticaria,
cardiac disease or dysfunction; monitor cardiac function vertigo, thyroiditis (autoimmune), ventricular
closely; consider discontinuation in clinically significant dysfunction, wheezing

reduction in LVEF during therapy; withhold treatment for
≥16% decrease from pretreatment levels or LVEF below
normal limits and ≥10% decrease from baseline)
Infusion reactions (e.g. fever, chills, nausea, vomiting, pain,
headache, dizziness, dyspnea, hypotension, rash,
weakness)
Renal toxicity (e.g. nephrotic syndrome with evidence of
glomerulopathy; complications may include volume
overload and HD)
Pulmonary toxicity (use caution; pulmonary events may
occur during or within 24 hours of administration)
Pregnancy (can result in oligohydramnios and
oligohydramnios sequence manifesting as pulmonary
hypoplasia, skeletal abnormalities, and neonatal death)
Adverse Drug Reactions:
Common: Abdominal pain, accidental injury, acne vulgaris,
anemia, anorexia, arthralgia, back pain, arrhythmia,
cardiac failure, chills, constipation, decreased left
ventricular ejection fraction, depression, diarrhea,
dizziness, dyspepsia, cough, dyspnea, edema, epistaxis,
fever, flu-like symptoms, headache, herpes simplex
infection, hypersensitivity reaction, hypertension,
infection, influenza, infusion related reaction (chills,
fever), insomnia, leukopenia, muscle spasm, myalgia,
nasopharyngitis, nausea, neuropathy, ostealgia, nail
disease, pain, palpitations, paresthesia, peripheral
edema, pharyngitis, peripheral neuritis,
pharyngolaryngeal pain, pruritus, skin rash, rhinitis,
sinusitis, tachycardia, upper respiratory tract infection,
urinary tract infection, vomiting, weakness
Less Common: Abnormality in thinking, amblyopia, adult
respiratory distress syndrome, apnea, anaphylactic
shock, anaphylactoid reaction, anaphylaxis,
angioedema, ascites, asthma, ataxia, blood coagulation
disorder, bradycardia, bronchitis, bronchospasm,
cardiogenic shock, cardiomyopathy, cellulitis, cerebral
edema, cerebrovascular accident, cerebrovascular
disease, cardiac arrest, chest discomfort, colitis,
confusion, cystitis, deafness, dermal ulcer, dermatitis,
dysuria, erysipelas, esophageal ulcer, febrile
neutropenia, focal segmental glomerulosclerosis,
gastritis, gastroenteritis, glomerulonephritis
L
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Immunosuppressants
(neutropenic effect)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Anthracycline {Systemic (cardiotoxic effect) [avoid
anthracycline therapy for up to 7 months after
discontinuation of trastuzumab]}, Belimumab
Administration: For IV infusion. Infuse loading doses over 90
minutes and maintenance doses over 30 minutes, if
tolerated.
Do NOT administer by IV push or by rapid bolus. Do NOT
extend treatment beyond 1 year.
Do NOT administer with D5W. Do NOT mix with any other
medications.
Observe patients closely during the infusion for fever,
chills, or other infusion-related symptoms.
NOTE: Pretreatment with acetaminophen and an
antihistamine is recommended for managing infusion-
related events.
MISSED DOSE.
If a dose is missed by ≤1 week, administer usual
maintenance dose as soon as possible. Do NOT wait until
next planned cycle. Administer subsequent maintenance
doses 7 or 21 days later based on patient’s maintenance
dose or schedule.
If a dose is missed by >1 week, administer a reloading
dose or 4 mg/kg if on a weekly schedule, or 8 mg/kg if
on an every-3-week schedule, followed by the usual
maintenance dose administered 7 or 21 days later
based on patient’s maintenance dose or schedule.
Pregnancy Category: D

357

ATC Code: L01XC03
PROTEIN KINASE INHIBITORS
Rx IMATINIB
Oral: 100 mg and 400 mg tablet (as mesilate)
A protein kinase inhibitor that inhibits BCR-ABL kinase, as
well as the c-KIT kinase 234 and the platelet-derived
growth factor receptor (PDGFR) kinase.
Indications: Treatment of newly diagnosed, relapsed, or
refractory Philadelphia chromosome–positive (Ph+)
acute lymphoblasticleukemia (ALL) in adults; treatment
of newly diagnosed Ph+ ALL in children; treatment of
aggressive systemic mastocytosis without D816V c-Kit
mutation (or c-Kit mutational status unknown) in adults;
treatment of Ph+ chronic myeloid leukemia (CML) in
chronic phase (newly diagnosed) in adults andchildren;
L
treatment of Ph+ CML in blast crisis, accelerated phase,
or chronic phase after failure of interferon-alfa therapy;
treatment with unresectable, recurrent, and/or
metastatic dermatofibrosarcoma protuberans (DFSP) in
adults; treatment of Kit (CD117)-positive unresectable
and/or metastatic malignant gastrointestinal stromal
tumors (GIST); adjuvant treatment of Kit (CD117)–
positive GIST following complete gross resection;
treatment of hypereosinophilic syndrome (HES) and/or
chroniceosinophilic leukemia (CEL) in adult patients who
have the FIP1L1–platelet-derived growth factor (PDGF)
receptor alpha fusion kinase (mutational analysis or
fluorescent in situ hybridization [FISH] demonstration of
CHIC2 allele deletion) and for patients with HES and/or
CEL who are FIP1L1-PDGF receptor alpha fusion kinase
negative or unknown; treatment of myelodysplastic
syndrome/myeloproliferative diseases (MDS/MPD)
associated with PDGF receptor gene rearrangements in
adults
Dose:
For patients with CML, during treatment with TKI,
quantitative reverse-transcriptase polymerase chain
reaction (qRT-PCR) for BCR-ABL monitoring should be
done every 3 months until a major molecular response
(MMR) is achieved, then every 3-6 months. Karyotyping
(Chromosomal Band Analysis, CBA of marrow cells) may
also be used at 3, 6, and 12 months until a complete
cytogenetic response (CCyR) is achieved, then every 12
months. Once CCyR is achieved, peripheral blood FISH
for BCR-ABL may be used.
Ph+ CML, chronic phase, by mouth, ADULT, 400 mg once
daily, if BCR-ABL by qRT-PCR is >10% or CBA shows >
35% Ph+ cells at 3 months, evaluate compliance to
therapy and drug interactions, consider mutational
analysis; switch to 2nd line TKI and evaluate for allo-
HSCT.
Ph+ CML, accelerated phase or blast crisis, by mouth,
ADULT 800 mg daily (400 mg twice daily), must be
evaluated for allo-HSCT at diagnosis; for blast phase,
consider lineage-directed chemotherapy + TKI; if BCR-
ABL by qRT-PCR is >10% or CBA shows > 35% Ph+ cells
at 3 months, evaluate compliance to therapy and drug
358
ANTINEOPLASTIC AND IMMODULATING AGENTS
interactions, consider mutational analysis; switch to 2nd
line TKI and evaluate for allo-HSCT
Ph+ CML, chronic phase, newly diagnosed, by mouth,
ADOLESCENT and CHILD ≥1 year, starting dose is:
Chronic Phase: 260 - 300 mg/m2 (maximum absolute dose
400 mg)
Accelerated Phase: 400 mg/m2 (maximum absolute dose
600 mg)
Blastic Crisis: 500 mg/m2 (maximum absolute dose 800
mg)
Ph+ ALL, newly diagnosed or relapsed or refractory, by
mouth, ADULT, 600-800 mg once daily, alone or in
combination with steroids ± chemotherapy
Ph+ ALL, newly diagnosed, induction, by mouth, ADULT, 600
mg once daily;
ADOLESCENT and CHILD ≥1 year, in combination with
chemotherapy, 340 mg/m2 daily (maximum, 600 mg
daily).
GIST, adjuvant treatment following complete resection, by
mouth, ADULT, 400 mg once daily for 3 years.
GIST, unresectable and/or metastatic malignant, by mouth,
ADULT, 400 mg once daily; may be increased up to 800
mg daily (400 mg twice daily), if tolerated, for disease
progression.
Aggressive systemic mastocytosis with eosinophilia, by
mouth, ADULT, initially 100 mg once daily, titrate up to a
maximum of 400 mg once daily, if tolerated for
insufficient response to lower dose.
ASM without D816V c-Kit mutation or c-Kit mutation status
unknown, by mouth, ADULT, 400 mg once daily.
DFSP, by mouth, ADULT, 400 mg twice daily.
HES and/or CEL, by mouth, ADULT, 400 mg once daily.
HES/CEL with FIP1L1-PDGFRα fusion kinase, by mouth,
ADULT, initially 100 mg once daily, titrate up to a
maximum of 400 mg once daily, if tolerated, for
insufficient response to lower dose.
MDS/MPD, by mouth, ADULT, 400 mg once daily.
Dose Adjustment:
Renal Impairment:
In CrCl 40–59 mL/minute, maximum dose is 600 mg.
In CrCl 20–39 mL/minute, decrease starting dose by 50%.
Increase doses as tolerated. The maximum dose is 400
mg.
In CrCl <20 mL/minute, 100 mg daily has been tolerated.
Hepatic Impairment:
In mild-to-moderate impairment, an initial dose of 400 mg
once daily is the minimum effective dose.
In severe impairment, initiate at 200 mg once daily, may
increase up to 300 mg once daily in the absence of
severe toxicity. Decrease dose with unacceptable
toxicity.
During therapy:
If elevations of bilirubin >3 times ULN or transaminases
>5 times ULN occur, withhold treatment until bilirubin
<1.5 times ULN and transaminases <2.5 times ULN.
Resume treatment at a reduced doseas follows:
CURRENT REDUCED
DOSE DOSE
300 mg
400 mg daily
daily
ADULT
400 mg
600 mg daily
daily
ANTINEOPLASTIC AND IMMODULATING AGENTS
800 mg daily
600 mg
daily
260
CHILD ≥1 year 340 mg/m2
mg/m2
ADOLESCENT daily
daily
NOTE: Consider the initial severity of hepatotoxicity
when deciding to resume treatment.
Hematologic Toxicity:
In chronic phase CML, initiate at 400 mg daily in adults or
340 mg/m2 daily in children. In accelerated phase or
blast crisisCML or Ph+ ALL, adjust dose as follows;
ADULT (ANC <500/mm3 and/or platelets <10,000/mm3,
unrelated to leukemia), if initial dose is 600 mg daily,
reduce dose to 400 mg daily; if cytopenia persists for an
additional 2 weeks, further reduce dose to 300 mg daily;
if cytopenia persists for 4 weeks, withhold treatment
until ANC ≥1,000/mm3 and platelets ≥20,000/mm3,
then resume treatment at 300 mg daily.
In ASM, MDS/MPD, and HES/CEL, initiate at 400mg daily.
In GIST, initiate at 400 mg daily or 400–600 mg daily. If ANC
<1,000/mm3 and/orplatelets <50,000/mm3, withhold
until ANC ≥1,500/mm3 and platelets ≥75,000/mm3.
Resume treatment at original starting dose. For recurrent
neutropenia and/or thrombocytopenia, withhold until
recovery, and reinstitute treatment at a reduced dose as
follows:
INITIAL REDUCED
DOSE DOSE
400 mg 300 mg
daily daily
ADULT
600 mg 400 mg
daily daily
CHILD ≥1 year 340 mg/m2 260 mg/m2
ADOLESCENT daily daily
Precautions:
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. anemia, neutropenia,
thrombocytopenia; usually occurs within first several
months of treatment; monitor blood counts weekly for
the first month, biweekly for the second month, and
asclinically necessary thereafter)
Cardiovascular effects (e.g. severe heart failure and left
ventricular dysfunction; usually occurs in patients with
comorbidities and/or risk factors; also reported in
hypereosinophilic syndrome and cardiac involvement)
Dermatologic reactions (e.g. severe bullous dermatologic
reactions, erythema multiforme, SJS and DRESS; if
symptoms of DRESS occur, interrupt therapy and
consider permanently discontinuing)
CNS effects (e.g. dizziness, blurred vision, somnolence)
Fluid retention or edema (occasionally serious and may lead
to significant complications, including pleural effusion,
pericardial effusion, pulmonary edema, and ascites; use
withcaution in patients where fluid accumulation may be
poorly tolerated, such as in cardiovascular disease and
pulmonary disease)
Gastric surgery (imatinib exposure may be reduced in
patients who have had gastric surgery, e.g. bypass,
major gastrectomy, or resection; monitor imatinib trough
concentrations); GI toxicity (e.g GI irritation, GI
perforation)
Hemorrhage (e.g. severe hemorrhage, grades 3 and 4,
including GI hemorrhage and tumor hemorrhage;
incidence is higher in patients with GIST; gastric antral
vascular ectasia; monitor for GI symptoms with
treatment initiation)
Hepatotoxicity (fatal hepatic failure and severe hepatic
injury requiring liver transplantation; use with caution in
patients with hepatic impairment; monitor liver function
prior to initiation and monthly or as needed thereafter);
renal impairment (use with caution)
Thyroid disease (e.g. hypothyroidism; monitor thyroid
function; consider doubling levothyroxine doses upon
initiation of imatinib)
Tumor lysis syndrome (increased risk in high tumor burden
or high proliferation rate; monitor closely).
Children (e.g. growth retardation in prepubertal children;
growth velocity restored during puberty)
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
L
Common: Abdominal distention, abdominal pain, alopecia,
anemia, anorexia, anxiety, arthralgia, back pain, blurred
vision, cardiac failure, cerebral hemorrhage, chest pain,
chills, conjunctival hemorrhage, conjunctivitis,
constipation, cough, decreased appetite, depression,
dermatitis, diaphoresis, diarrhea, dizziness, dyspepsia,
dyspnea, edema, dry eyes, eosinophilia, epistaxis,
erythema, eyelid edema, facial edema, fatigue, febrile
neutropenia, fever, flatulence, flu-like symptoms, fluid
retention, flushing, gastritis, gastroenteritis, GERD, GI
hemorrhage, headache, hemorrhage, hyperglycemia,
hyperkalemia, hypertension, hypocalcemia,
hypoesthesia, hypokalemia, hypophosphatemia,
hypotension, hypoxia, hypoproteinemia, increased
lacrimation, infection, influenza, insomnia, joint swelling,
leukopenia, limb pain, lymphocytopenia,
musculoskeletal pain, muscle cramps, myalgia, nail
disease, nasopharyngitis, nausea, neutropenia,
oropharyngeal pain, night sweats, ostealgia, palpitations,
pancytopenia, pain, paresthesia, periorbital edema,
peripheral neuropathy, pharyngitis, pharyngolaryngeal
pain, pleural effusion, pneumonia, pneumonitis, pruritus,
purpura, rhinitis, rigors, sinusitis, skin photosensitivity,
stomatitis, taste disorder, skin rash, thrombocytopenia,
upper respiratory tract infection, vomiting, weakness,
weight gain, weight loss, xeroderma, xerostomia
Less Common: Actinic keratosis, acute generalized
exanthematous pustulosis, anaphylactic shock,
anginapectoris, angioedema, aplastic anemia, arthritis,
ascites, atrial fibrillation, avascular necrosis of bones,
blepharitis, bullous rash, cardiac arrest, cardiac
arrhythmia, cardiac tamponade, cataract, cellulitis,
cerebral edema, cardiogenic shock, cheilitis,
coldextremities, colitis, confusion, decreased libido,
decreased linear skeletal growth rate (children), DRESS
syndrome, dehydration, diverticulitis, dysphagia,
drowsiness, dyschromia, embolism, eructation,
erythema multiforme, esophagitis, exfoliative dermatitis,
folliculitis, fungal infection, gastric ulcer, GI obstruction,
GI perforation, glaucoma, gout, gynecomastia, hearing
loss, hematemesis, hematoma, hematuria, hepatic
failure, hepatic necrosis, hepatitis, hepatotoxicity,
hemolytic anemia, herpes simplex infection, herpes
359
 ANTINEOPLASTIC AND IMMODULATING AGENTS

zoster, hypercalcemia, hypersensitivity angiitis, Increases serum concentration of the following drugs:
hypermenorrhea, hyperuricemia, IgA vasculitis, Avanafil, Budesonide (Systemic, Oral Inhalation, Topical),
hypomagnesemia, hyponatremia, inflammatory Cilostazol, Colchicine, Dapoxetine, Domperidone,
boweldisease, hypothyroidism, increased intracranial Doxorubicin (Conventional), Eletriptan, Eplerenone,
pressure, interstitial pneumonitis, interstitial pulmonary Everolimus, Fentanyl, Ibrutinib, Ivabradine, Ivacaftor,
disease, intestinal obstruction, jaundice, left ventricular Olaparib, Pazopanib, Pimozide, Ranolazine, Simeprevir,
dysfunction, lichen planus, lower respiratory tract Tolvaptan, Topotecan, Ulipristal, Zopiclone
infection, lymphadenopathy, macular edema, melena,
memory impairment, menstrual disease, MI, migraine, Reduces therapeutic effect of Imatinib:
myopathy, onychoclasis, optic neuritis, oral mucosa Echinacea (immunosuppressive effects)
ulcer, osteonecrosis (hip), palmar-plantar
erythrodysesthesia, pleuritic chest pain, ovarian Reduces therapeutic effect of the following drugs:
cyst(hemorrhagic), papilledema, pericarditis, BCG, (Intravesical), Fludarabine (myelosuppressive
pancreatitis, petechia, psoriasis, pulmonary fibrosis, effect), Vaccines (live virus vaccines may progress to
pulmonary hemorrhage, polyuria,pulmonary infection)
hypertension, Raynaud's phenomenon, renal failure,
respiratoryfailure, restless leg syndrome, retinal Administration: Administered with a meal and a large glass
hemorrhage, rhabdomyolysis, ruptured corpus luteal of water to minimize irritation.
cyst, sciatica, scrotal edema, seizure, sepsis, sexual
disorder, subconjunctival hemorrhage, subdural Do NOT crush or chew tablets due to bitter taste. Tablets
hematoma, Stevens-Johnson syndrome, tumor lysis may be dispersed in water or apple juice (~50 mL for 100
syndrome, Sweet’s syndrome, syncope, tachycardia, mg tablet and ~200 mL for 400 mg tablet). Stir until
telangiectasia (gastric antral), thrombocythemia, dissolved and administer immediately.
L

thrombosis, tinnitus, TEN, tremor, tumor hemorrhage

(GIST), urinary tract infection, urticaria, vertigo, vesicular In adults, doses ≤600 mg may be given once daily. 800
eruption, vitreous hemorrhage mg dose should be administered in 2 divided doses.
Dosing in children may be once or twice daily for CML and
Drug Interactions: once daily for Ph+ALL.
Monitor closely with: For daily dosing ≥800 mg, use 400 mg tablets to reduce
Decreases metabolism of the following drugs: iron exposure.
Simvastatin
Avoid grapefruit juice.
Enhances therapeutic effect of Imatinib:
Trastuzumab (neutropenic effect) NOTE: Associated with moderate emetic potential.
Antiemetics may be recommended to prevent nausea
Reduces diagnostic effect of Coccidioides immitis Skin Test and vomiting.

Increases risk of adverse or toxic effects of Imatinib: Pregnancy Category: D

Denosumab (serious infections), Lansoprazole
(dermatologic adverse effect), Paracetamol (hepatotoxic ATC Code: L01XE01
effect), Propacetamol (hepatotoxic effect)

Avoid concomitant use with: OTHER ANTINEOPLASTIC AGENTS

Deceases metabolism of the following drugs
Warfarin
Decreases serum concentration of Imatinib:
Dabrafenib, Dexamethasone (Systemic), Ibuprofen,
Mitotane, Rifamycin Derivatives, e.g. Rifampicin,
Rifabutin, Rifaximin
Enhances therapeutic effect of Imatinib:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Tofacitinib (immunosuppressive effect), Warfarin
(anticoagulant effect)
Increases risk of adverse or toxic effects of Imatinib:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus
Rx ASPARAGINASE
Inj.: 10,000 IU lyophilized powder, vial (IV)
An enzyme that hydrolyzes L-asparagine in leukemic cells to
ammonia and L-aspartic acid, leading to depletion of
asparagine. Asparagine depletion in leukemic cells leads
to inhibition of protein synthesis and apoptosis.
Indication: Treatment of acute lymphoblastic leukemia (ALL)
Contraindications: Hepatic insufficiency; pancreatitis;
pregnancy; breastfeeding; recent yellow fever
vaccination; concurrent administration with phenytoin;
hypersensitivity to asparaginase

Increases risk of adverse or toxic effects of the following Dose:

drugs: NOTE: Dose, frequency, number of doses, and start date
Clozapine (agranulocytosis), Leflunomide (hematologic may vary by protocol and treatment phase.
toxicity), Natalizumab, Oxycodone

360
ANTINEOPLASTIC AND IMMODULATING AGENTS

ALL, daily administration, by IV infusion, 200–1,000
units/kg daily for 28 consecutive days; continue
induction therapy for an additional 14 days if not
inremission or begin maintenance therapy if in
remission;
ALL, intermittent administration, by IV infusion, 400
units/kg on Monday and Wednesday and 600 units/kg
on Friday; repeat for 4 weeks; continue induction therapy
for an additional 2 weeks if not in remission or begin
maintenance therapy if in remission.
ALL, induction phase, CHILDREN AND ADOLESCENTS,
6,000 units/m2 3x weekly for 9 doses.
Precautions:
WARNING: Should be administered under the
supervision of an experienced cancer
chemotherapy physician. Administer in a facility
sufficient to appropriately diagnose and manage
complications.
Allergic reactions may occur during therapy,
particularly in patients with known hypersensitivity
and/or development of a pancreatic pseudocyst; avoid
alcohol use).
Tumor lysis syndrome (monitor, consider anti-hyperuricemic
therapy, hydration and urinary alkalization).
Elderly (increased risk of thrombosis); children (at an
increased risk of allergic reactions).
Adverse Drug Reactions:
Common and Less Common: Abdominal pain, acute
pancreatitis (may be fatal), allergic reactions (including
anaphylactic shock, anaphylaxis, bronchospasm,
edema, hypotension, laryngeal edema, skin rash,
urticaria), antithrombin III deficiency, amenorrhea,
azoospermia, blood coagulation disorder (change in
hemostatic function), bone marrow depression, CNS
disease (including delusion, disorientation, mild
depression, personality disorder, Parkinsonian-like
syndrome, seizure), cerebral hemorrhage,
cerebrovascular accident (hemorrhagic stroke and
thrombotic stroke), cerebrovascular hemorrhage,
cholestatic injury, decreased clotting factors (factors VII,
VIII, IX, and X), fever, decreased glucose tolerance,
diarrhea (infrequent), hepatic injury, hepatoxicity (rarely

L
to other forms of L-asparaginase. fatal), hyperammonemia (with clinical signs of metabolic
encephalopathy, e.g., impaired consciousness with
Adverse effects on liver function may be observed, coma, confusion, stupor), hyperbilirubinemia, decreased
including exacerbation of preexisting liver plasminogen, hypercholesterolemia, hyperglycemia,
impairment. hypertriglyceridemia, hypoalbuminemia,
hypocholesterolemia, hypofibrinogenemia,
hyperuricemia jaundice, liver steatosis, nausea
WARNING: Hazardous agent. Use appropriate (frequent; rarely severe), prolonged partial
precautions for handling and disposal. thromboplastin time, or prothrombin time, renal failure,
respiratory distress (with retrosternal pressure),
septicemia, thrombosis (including cerebral thrombosis),
Allergic reactions (immediate treatment for hypersensitivity
vomiting (frequent; rarely severe), weight loss
reactions should be available during administration; may
Rare: Intestinal perforation
exhibit cross-sensitivity between E. coli asparaginase,
asparaginase (Erwinia), or pegaspargase).
Drug Interactions:
Coagulopathy (increased prothrombin time, partial
Monitor closely with:
thromboplastin time, hypofibrinogenemia,
Increases serum concentration of Dexamethasone
cerebrovascular thrombosis, and hemorrhage may
(Systemic)
occur; monitor coagulation parameters at baseline and
periodically during and after therapy); thrombotic events
Administration:
(serious thrombosis, including sagittal sinus thrombosis
L-asparaginase can be administered intravenously (IV),
may occur)
subcutaneously (SC) or intramuscularly (IM). Refer to
Hepatotoxicity (monitor liver function tests at least weekly
institutional guidelines for administration, if available.
during therapy)
Hyperammonemia (may induce excessive ammonia
For IV administration, infuse over at least 30 minutes
production; monitor for signs of metabolic
through the side arm of a NS or D5W infusion.
encephalopathy, e.g., confusion, stupor, coma);
hyperglycemia (may cause hyperglycemia or glucose
For IM route, L-asparaginase can be (1) dissolved with
intolerance, which may be irreversible, and diabetic
Lidocaine (Refer to institutional guideline for more
ketoacidosis; monitor blood glucose as clinically
information); OR (2) reconstituted (10,000 IU vial) with
necessary)
1-2 mL sterile water; limit volume of single injection site
Neurotoxicity (posterior reversible encephalopathy
to 2 mL; if volume of dose exceeds 2 mL, use multiple
syndromehas been observed and may manifest as
injection sites.
altered mental status, hypertension, seizures,
headache, or visual disturbances).
Observe patients for 1 hour after administration. Have
Pancreatitis (may cause serious and possibly fulminant or
epinephrine, diphenhydramine, and hydrocortisone at
fatal pancreatitis (signs/symptoms: vomiting, severe
the bedside. A physician should be readily accessible.
abdominal pain); promptly evaluate patients with
abdominal pain; may consider continuing therapy for
May administer corticosteroids 1–2 days prior to initiating
asymptomatic chemical pancreatitis (amylase or lipase
reinduction therapy to prevent hypersensitivity reaction.
>3 times ULN) or only radiologic abnormalities; monitor
closely for rising amylase and/or lipase levels;
Pregnancy Category:X
discontinue permanently for clinical pancreatitis with
amylase/lipase elevation >3 times ULN for >3 days

361

ATC Code: L01XX02
Rx HYDROXYUREA
Oral: 500 mg capsule
Inhibitor of ribonucleotide reductase, which causes
inhibition of DNA synthesis.
Indications: Treatment of acute blastic and chronic phases
of chronic myelogenous leukemia (CML); management of
myeloproliferative neoplasms (e.g. essential
thrombocythemia, polycythemia vera, primary
myelofibrosis, hypereosinophilia, β-thalassemia);
cytoreduction in hyperleukocytosis secondary to acute
leukemia; treatment of sickle cell and thalassemic crisis
Contraindications: Marked bone marrow depression (i.e.,
leukopenia with <2,500 WBC/mm3 or thrombocytopenia
<100,000/mm3); severe anemia
L
Dose:
NOTE: All doses should be based on patient’s actual or ideal
weight, whichever is less.
CML, as initial therapy and for control of hyperleukocytosis
in AML - 20-30 mg/kg/day; depending on the height of
the WBC count, up to 6 g/day; may require higher doses
at extremely high total WBC count. Reduce dose to 1 to
2g/day when total WBC count reaches 20 x 109/L; in
CML, continue therapy until tyrosine kinase inhibitor
(TKI) therapy is started; blood cell counts must be
monitored closely if used together with TKIs; in AML,
discontinue once definitive chemotherapy is started;
hold therapy for leukopenia or thrombocytopenia,
recheck after 3 days and resume if WBC and platelet
counts normalize.
Head and neck carcinoma, by mouth, ADULT, 80 mg/kg
single dose every third day; begin administration at least
7 days prior to radiation therapy and continue during and
after radiation; administer radiation therapy at maximum
dose.
Solid tumors, intermittent therapy, by mouth, ADULT, 80
mg/kg single dose every third day;
Solid tumors, continuous therapy, by mouth, ADULT, 20–30
mg/kg daily single dose; CHILDREN/ADOLESCENTS, 20–
30 mg/kg orally.
Polycythemia vera, essential thrombocythemia, primary
myelofibrosis (cellular phase), by mouth, ADULT, 15
mg/kg once daily. Titrate to control platelets & maintain
WBC count.
β-thalassemia intermedia, CHILD, starting dose of 10 mg/kg
/day with dose escalation of 3-5 mg/kg/day every 8
weeks to maximal tolerated dose. Not to exceed 20
mg/kg/day.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Bone marrow suppression (e.g. leukopenia,
thrombocytopenia, or anemia; monitor blood status
before and periodically during treatment; determine
362
ANTINEOPLASTIC AND IMMODULATING AGENTS
hemoglobin, total leukocyte count, platelet count at least
once a week; address severe anemia with whole blood
replacement prior to treatment; during treatment,
address anemia with whole blood replacement without
interrupting hydroxyurea therapy; megaloblastic
erythropoiesis is self-limiting and may occur without
anemia; may delay plasma iron clearance and reduce
iron utilization of RBC).
Dermatologic toxicity (e.g. vasculitic ulcerations, gangrene;
discontinue treatment if cutaneous vasculitic toxicity
occurs in myeloproliferative disorders); mucositis (may
occur in combination therapy); post-radiation erythema.
Gastric distress (e.g. nausea, vomiting, anorexia; may be
controlled by temporary interruption); hepatotoxicity
(fatal hepatotoxicity has occurred in concomitant use of
antiretroviral agents, particularly didanosine with or
without stavudine); pancreatitis (fatal pancreatitis has
occurred in concomitant use of antiretroviral agents,
particularly didanosine with or without stavudine); renal
dysfunction (use with caution).
Elderly (more sensitive to adverse effects).
Adverse Drug Reactions:
NOTE: Combining hydroxyurea with radiation therapy with
may increase the incidence and severity of its side
effects.
Common: Bone marrow depression (leukopenia, anemia,
thrombocytopenia), drowsiness (large doses), renal
tubular function impairment (temporary)
Less Common: Abnormal bromsulphalein (BSP) retention,
chills, dermatological reactions (maculopapular rash,
facial erythema), fever, GI symptoms (stomatitis,
anorexia, nausea, vomiting, diarrhea, constipation),
malaise
Rare: Alopecia, dysuria, neurological disturbances
(headache, dizziness, disorientation, convulsion,
hallucination)
Drug Interactions:
Pancreatitis, hepatotoxicity, and peripheral neuropathy
have occurred when hydroxyurea was administered
concomitantly with antiretroviral drugs, including
didanosine and stavudine
Concomitant use with a live virus vaccine may potentiate the
replication of the vaccine virus and/or may increase the
adverse reactions of the vaccine virus and result in
severe infections
Interference with uric acid, urea, or lactic acid assays may
falsely elevate results in patients treated with
hydroxyurea
Administration: Taken orally.
Capsule contents may be emptied into a glass of water
and taken immediately. Some inert material used as a
vehicle in the capsule may not dissolve and may float on
the surface.
Pregnancy Category: D
ATC Code: L01XX05
ANTINEOPLASTIC AND IMMODULATING AGENTS
Rx IRINOTECAN
Inj.: 40 mg/2 mL concentrate (as hydrochloride), vial (IV
infusion)
100 mg/5 mL concentrate (as hydrochloride), vial (IV
infusion)
Irinotecan and its active metabolite bind reversibly to
topoisomerase I-DNA complex, preventing relegation of
the cleaved DNA strand. This results in the accumulation
of cleavable complexes and double-strand DNA breaks,
causing cell death consistent with S-phase cell cycle
specificity, leading to termination of cellular replication.
Indication: Treatment of metastatic carcinoma of the colon
or rectum
Dose:
NOTE: Consider reducing the starting dose by 1 dose level
for prior pelvic or abdominal radiotherapy, performance
status of 2, or known homozygosity for UGT1A1*28
allele. Subsequent dose adjustments should be based
on individual tolerance.
Colorectal cancer, metastatic, weekly-regimen, by IV
infusion, ADULT, 125 mg/m2 over 90 minutes on days 1,
8, 15, and 22 of a 6-week treatment cycle, may adjust
upward to 150mg/m2 if tolerated; adjusted dose level 1,
100 mg/m2; adjusted dose level 2, 75 mg/m2; further
adjust to 50 mg/m2 in decrements of 25 to 50 mg/m2, if
needed.
Colorectal cancer, metastatic, single-agent therapy or once-
every-3-week regimen, by IV infusion, ADULT, 350 mg/m2
over 90 minutes, once every 3 weeks; adjusted dose
level 1, 300 mg/m2; adjusted dose level 2, 250 mg/m2;
further adjust to 200 mg/m2 in decrements of 25 to 50
mg/m2, if needed.
Colorectal cancer, metastatic, six-week (42-day) cycle,
regimen 1, by IV infusion, ADULT, in combination with
bolus fluorouracil and leucovorin (administer leucovorin
immediately following irinotecan and fluorouracil
immediately following leucovorin), 125 mg/m2 over 90
minutes on days 1, 8, 15, and 22; adjusted dose level 1,
100 mg/m2; adjusted dose level 2, 75 mg/m2; further
adjust if needed in decrements of ~20%.
regimen 2, by IV infusion, ADULT, in combination with
fluorouracil bolus or infusion and leucovorin infusion
(administer leucovorin immediately following irinotecan
and fluorouracil immediately following leucovorin), 180
mg/m2 over 90 minutes on days 1, 15, and 29; adjusted
dose level 1:150 mg/m2; adjusted dose level 2:120
mg/m2; further adjust if needed in decrements of ~20%.
Dose Adjustment:
Geriatric:
For every 3-week dosing colorectal cancer schedule, initiate
at 300 mg/m2 per dose for patients ≥70 years.
Hepatic Impairment:
In bilirubin >ULN to ≤2 mg/dL, consider reducing initial dose
bone dose level. In bilirubin >2 mg/dL, use is not
recommended.
Obesity:
Use actual body weight (full weight) for calculation of BSA-
based or weight-based dosing, especially if the intent of
therapy is curative.
If dose reduction is done due to toxicity, consider
resumption of full weight-based dosing with subsequent
cycles, especially if cause of toxicity is resolved.
Precautions:
WARNING: Early and late forms of diarrhea may occur.
Early diarrhea may be accompanied by cholinergic
symptoms that may be prevented or ameliorated
by atropine. Late diarrhea can be life-threatening
and should be treated promptly with loperamide.
Monitor patients with diarrhea and give fluid and
electrolytes as needed. Institute antibiotic therapy
if patients develop ileus, fever, or severe
neutropenia. Interrupt irinotecan and reduce
subsequent doses if severe diarrhea occurs.
Severe myelosuppression may occur.
WARNING: Hazardous agent. Use appropriate
L
precautions for handling and disposal.
Bone marrow suppression (severe neutropenia, followed by
death due to sepsis has been reported; withhold therapy
temporarily if neutropenic fever occurs or if the absolute
neutrophil count is <1,000/mm3); thromboembolism
(thromboembolic events have been reported).
Hypersensitivity reactions (severe hypersensitivity reactions
(including anaphylaxis) have occurred; discontinue
therapy if hypersensitivity occurs).
Pulmonary toxicity (fatal cases of interstitial pulmonary
disease-like events have been reported; monitor for
respiratory symptoms before and during treatment;
promptly evaluate progressive changes in baseline
pulmonary symptoms or any new-onset pulmonary
symptoms).
Renal toxicity (renal impairment and acute renal failure
have been reported; use with caution; use has not been
studied; not recommended in patients undergoing
dialysis).
Adverse Drug Reactions:
Common: Abdominal fullness, abdominal pain, alkaline
phosphatase increased, alopecia, anemia, anorexia,
ascites, back pain, cholinergic toxicity (including rhinitis,
increased salivation, miosis, lacrimation, diaphoresis,
flushing, intestinal hyperperistalsis), chills, confusion,
constipation, cramps, dehydration, diaphoresis, diarrhea
(early and late), dizziness, dyspepsia, dyspnea, cough,
edema, fever, flatulence, headache, hemorrhage,
hypotension, infection, insomnia, jaundice, leukopenia,
mucositis, neutropenia, neutropenic fever, neutropenic
infection, pain, nausea, pneumonia, rash, rhinitis,
somnolence, stomatitis, thrombocytopenia,
thromboembolic events, vasodilation, vomiting,
weakness, weight loss
Less Common: Anaphylactoid reaction, anaphylaxis, angina,
arterial thrombosis, bradycardia, cardiac arrest,
bleeding, cerebrovascular accident, circulatory failure,
colitis, deep thrombophlebitis, dysarthria, dysrhythmia,
embolus, GI bleeding, GI obstruction, hepatomegaly,
hiccups, ileus, hyperglycemia, hypersensitivity,
hyponatremia, interstitial pulmonary disease (IPD),
363

intestinal perforation, ischemic colitis, lymphocytopenia,
megacolon, MI, muscle cramps, myocardial ischemia,
neutropenic typhlitis, pancreatitis, paresthesia,
peripheral vascular disorder, pulmonary toxicity
(dyspnea, fever, reticulonodular infiltrates on chest x-
ray), pulmonary embolus, renal failure (acute), renal
impairment, syncope, thrombosis, typhlitis, ulcerative
colitis, thrombocytopenia (immune mediated),
thrombophlebitis, ulceration, vertigo
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Irinotecan:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Irinotecan:
Bevacizumab, Denosumab (serious infections)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Avoid concomitant use with:
Decreases serum concentration of Irinotecan:
Dabrafenib
L
Enhances therapeutic effect of Irinotecan:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Irinotecan:
Dipyrone (agranulocytosis; pancytopenia),
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity), Natalizumab (concurrent infection)
Increases serum concentration of Irinotecan:
Fusidic Acid (Systemic), Gemfibrozil, Grapefruit Juice,
Mifepristone, UGT1A1 Inhibitors
Reduces therapeutic effect of Irinotecan:
Conivaptan, Echinacea (immunosuppressive effects)
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (live virus vaccines may
progress to infection)
Administration: Administer by IV infusion, usually over 90
minutes.
NOTE: Avoid extravasation. Ensure proper needle or
catheter position prior to and during administration. If
extravasation occurs, flush the external site with sterile
water and apply ice to the affected area.
Associated with moderate emetic potential. Antiemetics
are recommended to prevent nausea and vomiting.
Premedication with dexamethasone and a 5-HT3 blocker
is recommended 30 minutes prior to administration.
Prochlorperazine may be considered for subsequent use,
if needed.
364
ANTINEOPLASTIC AND IMMODULATING AGENTS
Consider premedication of atropine 0.25–1 mg IV or SC
for cholinergic symptoms or early-onset diarrhea.
The recommended regimen to manage late diarrhea is
loperamide 4 mg orally at onset, followed by 2 mg every
2 hours (or 4 mg every 4 hours at night) until 12 hours
have passed without a bowel movement. If diarrhea
recurs, repeat administration. Do NOT use loperamide
for more than 48 consecutive hours.
Pregnancy Category: D
ATC Code: L01XX19
ADJUNCTS TO ANTINEOPLASTIC
CHEMOTHERAPY
CALCIUM FOLINATE (LEUCOVORIN
Rx
CALCIUM, FOLINIC ACID)
Inj.: 10 mg/mL, 5 mL ampule/vial (IM, IV)
50 mg vial (IM, IV)
A reduced form of folic acid that supplies the necessary co-
factor blocked by methotrexate. It actively competes with
methotrexate for transport sites, displaces methotrexate
from intracellular binding sites, and restores active folate
stores required for DNA/RNA synthesis. Leucovorin
stabilizes the binding of 5-dUMP and thymidylate
synthetase, enhancing the activity of fluorouracil.
Indications: Rescue agent after high-dose methotrexate
treatment; to diminish toxicity and counteract the effects
of impaired methotrexate elimination and of inadvertent
overdosage of folic acid antagonists; treatment of
megaloblastic anemias due to folic acid deficiency when
oral therapy is not feasible; palliative treatment of
advanced colorectal cancer
Contraindication: Pernicious anemia and other
megaloblastic anemias secondary to vitamin B12-
deficiency
Dose:
Colorectal cancer, by IV injection, ADULT, in combination
with fluorouracil, 200 mg/m2 daily over at least 3
minutes for 5 days every 4 weeks for 2 cycles, then every
4–5 weeks or 20 mg/m2 daily for 5 days every 4 weeks
for 2 cycles, then every 4–5 weeks.
Folate-deficient megaloblastic anemia, by IM or IV injection,
ADULT, ≤1 mg once daily.
High-dosemethotrexate-rescue, initial, by IM or IV injection,
ADULT, 15 mg (~10 mg/m2); start 24 hours after
beginning methotrexate infusion; continue every 6 hours
for 10 doses, until methotrexate level is <0.05
micromolar; adjust dose as follows:
normal methotrexate elimination (serum methotrexate
level ~10 micromolar at 24 hours after administration, 1
micromolar at 48 hours, and <0.2 micromolar at 72
hours),15 mg every 6 hours for 60 hours (10 doses)
beginning 24 hours after the start of methotrexate
infusion;
delayed late methotrexate elimination (serum
methotrexate level remaining >0.2 micromolar at 72
ANTINEOPLASTIC AND IMMODULATING AGENTS
hours and >0.05 micromolar at 96 hours after
administration), continue leucovorin calcium 15 mg
every 6 hours until methotrexate level is <0.05
micromolar;
delayed early methotrexate elimination and/or acute
renal injury (serum methotrexate level ≥50 micromolar
at 24 hours, or ≥5 micromolar at 48 hours, or a doubling
of serum creatinine level at 24 hours after methotrexate
administration), 150 mg every 3 hours until
methotrexate level is <1 micromolar, then 15 mg every 3
hours until methotrexate level is <0.05 micromolar.
CHILD, starting dose is 10 mg/m2 every 6 hours to start 24-
36 hours after start of methotrexate infusion, continue
until serum levels drop below 0.1 micromolar.
Leucovorin dose should be increased dramatically at
100 mg/m2 every 3 hours when serum methotrexate
levels are elevated above 5 micromolar at 42 hours after
the start of methotrexate infusion.
Methotrexate overdose, inadvertent, begin as soon as
possible after overdose, by IM, or IV injection, ADULT, 10
mg/m2 every 6 hours until methotrexate level is < 0.01
micromolar; if serum creatinine is increased more than
50% above baseline 24 hours after methotrexate
administration, if 24-hour methotrexate level is >5
micromolar, or if 48-hour methotrexate level is >0.9
micromolar, increase leucovorin dose to 100 mg/m2 IV
every 3 hours until the methotrexate level is <0.01
micromolar. [NOTE: Monitor methotrexate serum
concentrations to determine dose and duration of
leucovorin therapy. Do NOT wait for the results of a
methotrexate level before initiating leucovorin. Adjust
leucovorin dose once methotrexate level is known. Dose
may need to be increased or administration prolonged in
situations where methotrexate excretion may be
delayed, e.g., ascites, pleural effusion, renal
insufficiency, inadequate hydration.]
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Renal impairment (excreted renally; risk for toxicities may
be increased).
Seizures (seizures or syncope have been rarely reported;
reported in patients with cancer receiving leucovorin,
usually in association with fluoropyrimidine
administration, and most commonly in patients with CNS
metastases or other predisposing factors).
Adverse Drug Reactions: Allergic reactions, anaphylactoid
reactions, erythema, pruritus, rash, thrombocytosis,
urticaria, wheezing
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Fluorouracil (Systemic) (anticancer effects), Tegafur
(anticancer effects)
Increases risk of adverse or toxic effects of the following
drugs:
Capecitabine, Fluorouracil (Systemic and Topical),
Tegafur
Avoid concomitant use with:
Reduces therapeutic effect of the following drugs:
Raltitrexed, Trimethoprim
Administration: Administer by IV or IM routeas a rescue after
folate antagonists. Administer by IM injection, IV push, or
by IV infusion or 15 minutes to 2 hours.
Do NOT administer intrathecally.
Do NOT administer IV solutions at a rate >160
mg/minute due to calcium content.
NOTE: Do NOT administered concurrently with
methotrexate. It is commonly initiated 24 hours after the
start of methotrexate. Toxicity to normal tissues may be
irreversible if leucovorin is not initiated by ~40 hours
after the start of methotrexate.
Fluorouracil is usually given after, or at the midpoint, of
leucovorin infusion by IV bolus injection or short IV
infusion over 10–120 minutes. Other administration
schedules have been used; refer to individual protocols.
L
Pregnancy Category: C
ATC Code: Not available
MESNA (SODIUM-2-
Rx
MERCAPTOETHANE SULPHONATE)
Inj.: 100 mg/mL, 4 mL ampule (IV)
Mesna provides a free thiol group which binds to and
inactivates acrolein, the urotoxic metabolite of
ifosfamide and cyclophosphamide.
Indication: Preventive agent for
cyclophosphamide/ifosfamide-induced hemorrhagic
cystitis
Contraindication: NOT indicated to reduce the risk of
hematuria due to other conditions such as
thrombocytopenia
Dose:
Prevention of cyclophosphamide and ifosfamide-induced
hemorrhagic cystitis, standard dose ifosfamide, by IV
bolus, ADULT, 20% of ifosfamide dose given for 3 doses
at hour 0, at hour 4, and at hour 8 after ifosfamide (total
daily mesna dose is 60% of the ifosfamide dose); CHILD,
intravenous injection for 15-30 minutes at 20% of the
simultaneously administered
cyclophosphamide/ifosfamide on a weight for weight
basis (w/w). The same dose is repeated after 4 and 8
hours. The total dose of mesna is 60% (w/w) of
cyclophosphamide/ifosfamide dose. This is repeated on
each occasion that the cytotoxic agents are used.
NOTE: Repeat mesna dosing schedule each day ifosfamide
is received. Adjust mesna dose based on ifosfamide
dose to maintain the mesna-to-ifosfamide ratio.
365

Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Anaphylaxis or hypersensitivity reactions (watch out for
fever, hypotension, tachycardia, acute renal impairment,
hypoxia, respiratory distress, urticaria, angioedema,
signs of disseminated intravascular coagulation,
hematologic abnormalities, nausea, vomiting, arthralgia;
monitor for signs or symptoms of reactions; may require
discontinuation).
Dermatologic toxicity (e.g. rash, pruritus, urticaria,
erythema, burning sensation, angioedema, periorbital
edema, flushing, and stomatitis; reactions consistent
with SJS or TEN have been reported).
Hematuria (monitor urine for hematuria; severe hematuria
despite utilization of mesna may require ifosfamide dose
reduction or discontinuation; examine morning urine
specimen for hematuria prior to ifosfamide or
cyclophosphamide treatment).
Ifosfamide or cyclophosphamide toxicities (intended for the
prevention of hemorrhagic cystitis and will not prevent or
L
alleviate other toxicities associated with ifosfamide or
cyclophosphamide).
Adverse Drug Reactions:
Common: Anorexia, arthralgia, conjunctivitis, back pain,
constipation, cough, diarrhea, dizziness, fever,
flatulence, flu-like syndrome, flushing, headache,
hyperesthesia, rash, injection site reactions, nausea,
pharyngitis, rhinitis, rigors, somnolence, vomiting
Less Common: Allergic reaction, anaphylactic reaction,
hypersensitivity, hypertension, injection site erythema,
hypotension, injection site pain, limb pain, malaise,
myalgia, platelets decreased, ST-segment increased,
tachycardia, tachypnea
Drug Interactions: No information found
TEST INTERACTIONS.
May produce false-positive results for urinary ketones
with nitroprusside-based urine tests, including dipstick
tests
May produce falsely low creatinine kinase levels by
interfering with enzymatic creatinine kinase activity
tests, which use thiol compounds
May produce false-positive results for ascorbic acid with
Tillman’s reagent-based urine screening tests for
ascorbic acid
Administration: Administer as an IV bolus. Refer to specific
protocol for administration rate or details.
Maintain adequate hydration and urinary output during
ifosfamide treatment.
Pregnancy Category: B
ATC Code: Not available
366
ANTINEOPLASTIC AND IMMODULATING AGENTS
ENDOCRINE THERAPY
HORMONES AND RELATED AGENTS
PROGESTOGENS
Rx MEGESTROL
Oral: 40 mg and 160 mg tablet (as acetate)
A progestogen structurally related to progesterone with anti-
estrogenic properties that disrupt estrogen receptor
cycle. It is an antineoplastic progestin thought to act
through an anti-leutenizing effect mediated via the
pituitary.
Indications: Breast cancer; endometrial cancer
Dose:
Breast cancer, advanced, by mouth, ADULT, 160 mg per day
in divided doses of 40 mg given 4 times daily for at least
2 months.
Endometrial cancer, advanced, by mouth, ADULT, 40 to 320
mg daily in divided doses for at least 2 months.
Dose Adjustment:
Geriatric:
Use with caution. Avoid use in elderly.
Renal Impairment:
Use with caution. Urinary excretion is substantial.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Adrenal suppression (may suppress hypothalamic-pituitary-
adrenal axis with chronic use); Cushing syndrome
(associated with long-term use).
AIDS-related cachexia; diabetes (new-onset diabetes
mellitus or exacerbation of pre-existing diabetes;
associated with long-term use); thromboembolism (use
with caution).
Elderly (increased risk of thrombosis and possibly death);
children (safety and efficacy have not been established).
Females (may cause vaginal bleeding or discharge).
Pregnancy (may cause fetal harm); lactation (excreted in
breastmilk; discontinue breastfeeding while receiving
megestrol).
Adverse Drug Reactions:
Common: Hypertension, cardiomyopathy, chest pain,
edema, palpitations, headache, pain, insomnia,
abnormality in thinking, confusion, convulsions,
peripheral edema, depression, hypoesthesia,
neuropathy, paresthesia, skin rash, alopecia,
dermatological disease, diaphoresis, pruritus,
vesicobullous dermatitis, decreased libido, albuminuria,
gynecomastia, increased lactate dehydrogenase,
diarrhea, flatulence, vomiting, hyperglycemia, nausea,
dyspepsia, abdominal pain, constipation, oral moniliasis,
sialorrhea, xerostomia, impotence, urinary incontinence,
urinary tract infection, breakthrough bleeding, urinary
ANTINEOPLASTIC AND IMMODULATING AGENTS

frequency, sarcoma, hepatomegaly, candidiasis, herpes Dose:

virus infection, weakness, leukopenia, amblyopia, Prostate cancer, advanced, by SC implant, ADULT (male), for
dyspnea, pharyngitis, cough, pulmonary disorder, 28-day implants, 3.6 mg every 28 days; for 12-week
pneumonia, fever implants, 10.8 mg every 12 weeks.
Less Common: Cardiac failure, lethargy, malaise, mood Prostate cancer, stage B2 to C, by SC implant, ADULT (male),
changes, adrenocortical insufficiency, amenorrhea, in combination with an antiandrogen and radiotherapy,
Cushing’s syndrome, carpal tunnel syndrome, diabetes for combination 28-day or 12-week implants, 3.6 mg,
mellitus, hot flash, HPA-axis suppression, hypercalcemia, then 10.8 mg after 28 days (initiate therapy 8 weeks
weight gain, tumor flare, hyperventilation, prior to radiotherapy); for 28-day implant (alternate
thromboembolic phenomena dosing), 3.6 mg repeated every 28 days for 4 doses
(initiate therapy 8 weeks prior to radiotherapy).
Drug Interactions: Breast cancer, advanced, by SC implant, ADULT (female),
Monitor closely with: 3.6 mg every 28 days.
Enhances therapeutic effect of C1 Inhibitors Endometriosis, by SC implant, ADULT (female), 3.6 mg every
28 days for 6 months.
Reduces therapeutic effect of the following drugs: Endometrial thinning, by SC implant, ADULT (female), 3.6
Antidiabetic Agents, Choline C11 mg every 28 days for 1 or 2 doses.

Avoid concomitant use with: Precautions:

Increases serum concentration of Dofetilide WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Reduces diagnostic effect of Indium111 Capromab
Pendetide

Reduces therapeutic effect of Megestrol:
Ulipristal [avoid progestins within 5 days of stopping
ulipristal]
Reduces therapeutic effect of the following drugs:
Anticoagulants, Ulipristal [avoid progestins within 5 days
of stopping ulipristal]
Administration: To be taken with food. Swallow tablet whole.
Do NOT crush, break, or chew.
Pregnancy Category: D
ATC Code: L02AB01
GONADOTROPIN-RELEASING HORMONE
ANALOGUES
Rx GOSERELIN
Inj.: 3.6 mg depot solution (as acetate), pre-filled syringe
(SC)
10.8 mg depot solution (as acetate), pre-filled syringe
(SC)
A synthetic analogue of gonadotropin-releasing hormone,
which causes an initial increase in luteinizing hormone
(LH) and follicle stimulating hormone (FSH). Chronic
administration of goserelin results in a sustained
suppression of pituitary gonadotropins, causing serum
testosterone to fall to levels comparable to surgical
castration.
Indications: Management of prostate cancer; breast cancer
(advanced); endometriosis; endometrial thinning
L
Cervical resistance (may be increased; use with caution)
Decreased bone density (may be irreversible);
Hypercalcemia
Hyperglycemia (may manifest as diabetes or worsening of
preexisting diabetes);
Hypersensitivity
Injection site injury (may manifest as pain, hematoma,
hemorrhage, or hemorrhagic shock)
Pituitary apoplexy (may present as sudden headache,
vomiting, visual or mental status changes, or
cardiovascular collapse; immediate medical attention
required)
Tumor flare (may result in worsening of disease signs and
symptoms during first few weeks of treatment; spinal
cord compression and urinary tract obstruction have
been reported).
Cardiovascular disease (increased risk for myocardial
infarction (MI), sudden cardiac death, and stroke have
been reported; may cause prolongation of QT / QTc
interval; correct electrolytes prior to initiation).
Obesity (may result in decreased AUC when using 3-month
implant); underweight.
Women of childbearing potential (may result in effects on
reproductive function due to anti-gonadotropic
properties).
Adverse Drug Reactions:
Common: Vasodilatation, peripheral edema, headache,
emotional lability, depression, pain, dyspareunia,
insomnia, diaphoresis, acne vulgaris, seborrhea, hot
flash, decreased or increased libido, abdominal pain,
vaginitis, breast atrophy or hypertrophy, sexual disorder,
decrease in erectile frequency, pelvic symptoms,
genitourinary signs and symptoms, tumor flare, infection,
decreased bone mineral density, weakness, edema,
hypertension, cardiac failure, cardiac arrhythmia,
cerebrovascular accident, peripheral vascular disease,
varicose veins, chest pain, myocardial infarction,
palpitations, tachycardia, lethargy, migraine, malaise,
dizziness, chills, anxiety, nervousness, voice disorder,
abnormality in thinking, drowsiness, paresthesia, skin
rash, hair disease, pruritus, alopecia, skin discoloration,
xeroderma, gynecomastia, gout, hyperglycemia, weight
gain, anorexia, gastric ulcer, constipation, diarrhea,

367
 ANTINEOPLASTIC AND IMMODULATING AGENTS

vomiting, increased appetite, dyspepsia, flatulence,

xerostomia, pelvic pain, mastalgia, uterine hemorrhage, Rx LEUPRORELINE (LEUPRORELIN)
vulvovaginitis, breast swelling, urinary tract obstruction,
urinary tract infection, urinary frequency, vaginal Inj.: 1.88 mg powder (as acetate), single-dose vial with
hemorrhage, anemia, bruise, hemorrhage, syringe (IM, SC)
hypersensitivity reaction, sepsis, application site 3.75 mg powder (as acetate), single-dose vial with
reaction, myalgia, leg cramps, hypertonia, arthralgia, syringe (IM, SC)
arthropathy, amblyopia, dry eye syndrome, renal 11.25 mg powder (as acetate), depot solution, vial +
insufficiency, upper respiratory tract infection, chronic syringe (IM, SC)
obstructive pulmonary disease, flu-like symptoms, 3.75 mg/2 mL (as acetate), vial with syringe (IM, SC)
pharyngitis, sinusitis, bronchitis, cough, epistaxis,
rhinitis, fever An analogue of gonadorelin with similar properties, is used
Less Common: Anaphylaxis, bone fracture, convulsions, for the suppression ofgonadal sex hormone production
deep vein thrombosis, diabetes mellitus, hypercalcemia, in the treatment of malignant neoplasms of the prostate.
hypotension, injection site reaction, osteoporosis,
ovarian cyst, ovarian hyperstimulation syndrome, Indications: Endometriosis; prostate cancer; uterine
pituitary apoplexy, hyperlipidemia, pituitary neoplasm, leiomyomata (fibroids)
pulmonary embolism, psychotic reaction, transient
ischemic attacks Contraindications: Women who are or may become
pregnant, breast‐feeding, undiagnosed abnormal
Drug Interactions: vaginal bleeding
Monitor closely with: Dose:
Reduces therapeutic effect of the following drugs:
L

Prostate cancer, advanced, by IM or SC depot injection,

Antidiabetic Agents, Choline C11 ADULT, administer 3.75 mg once a month or 11.25 mg
every 3 months.
Avoid concomitant use with: Endometriosis; uterine leiomyomata (fibroids), by IM or SC
Enhances QTc-prolonging effect of Goserelin: depot injection, ADULT, administer 3.75 mg once a
Ivabradine, Mefepristone, QTc-prolonging Agents month or 11.25 mg every 3 months, for up to 6 months.
(Highest and Moderate Risk)
Dose Adjustment:
Reduces diagnostic effect of Indium111 Capromab Renal and Hepatic Impairment:
Pendetide Use with caution. No studies have been conducted.

Reduces therapeutic effect of the following drugs: Precautions:

Corifollitropin Alfa
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Administration: Administer by SC injection.
Cardiovascular diseases (may increase risk for
Insert needle at a 30- to 45-degree angle into the
cardiovascular disease; sudden cardiac death and
anterior abdominal wall below the navel line. Use caution
stroke have been reported among men; may prolong the
while injecting into the anterior abdominal wall due to the
QT / QTc interval)
proximity of underlying inferior epigastric artery and its
Decreased bone density (use with caution in patients with
branches.
additional risk factors for bone loss);
Endometriosis (may exacerbate endometriosis or uterine
Goserelin is an implant. Do NOT attempt to eliminate air
leiomyomata)
bubbles prior to injection to prevent displacing the
Hyperglycemia (diabetes and/or worsening of glycemic
implant.
control have been reported in men).
Pituitary apoplexy (may present as sudden headache,
Do NOT attempt to aspirate prior to injection. If a large
vomiting, visual or mental status changes, and
vessel is penetrated, blood will be visualized in the
infrequently cardiovascular collapse; immediate medical
syringe chamber. If this occurs, withdraw needle and
attention required);
inject elsewhere with a new syringe.
Prostate cancer (may increase risk for cardiovascular
disease, diabetes, insulin resistance, obesity, alterations
Do NOT penetrate muscle or peritoneum. Implant may be
in lipids, and fractures).
detected by ultrasound if removal is required. Monitor for
Psychiatric illness (use with caution; alteration in mood,
signs or symptoms of abdominal hemorrhage. Use extra
memory impairment, and depression have been
care when administering to patents with a low BMI
associated with use)
and/or to patients receiving full dose anticoagulation.
Seizures
Spinal cord compression (monitor closely for weakness and
Pregnancy Category: X (endometriosis, endometrial
paresthesia in first few weeks of therapy)
thinning); D (advanced breast cancer)
Tumor flare
Urinary tract obstruction (monitor closely for urinary tract
ATC Code: L02AE03
obstruction and hematuria in first few weeks of therapy).

368
ANTINEOPLASTIC AND IMMODULATING AGENTS
Adverse Drug Reactions:
Common: Edema, headache, pain, depression, insomnia,
fatigue, dizziness, allergic skin reaction, hot flash, weight
changes, hyperlipidemia, decreased libido, nausea and
vomiting, gastrointestinal disease, change in bowel
habits, vaginitis, testicular atrophy, genitourinary
complaint, burning sensation at injection site, weakness,
arthropathy, flu-like symptoms, respiratory tract disease
Less Common: Angina pectoris, atrial fibrillation,
bradycardia, cardiac arrhythmia, cardiac failure, deep
thrombophlebitis, hypertension or hypotension,
palpitations, vasodilation, syncope, tachycardia,
nervousness, paresthesia, anxiety, agitation, confusion,
delusions, dementia, emotional lability, mood changes,
neuropathy, paralysis, seizure, ostealgia, headache,
pain, acne vulgaris, alopecia, diaphoresis, cellulitis, hair
disease, pruritus, seborrhea, skin rash, dehydration,
gynecomastia, hyperglycemia, menstrual disorder,
hyperphosphatemia,, peptic ulcer, hirsutism, anorexia,
GI hemorrhage, dysphagia, eructation, intestinal
obstruction, constipation, gastroenteritis, gastric ulcer,
diarrhea, mastalgia, impotence, balanitis, breast
hypertrophy, lactation, penile disease, testicular disease,
urinary incontinence, urinary tract infection, nocturia,
testicular pain, dysuria, bladder spasm, erectile
dysfunction, hematuria, urinary retention, urinary
urgency, bruise, eosinophilia, myalgia, leukopenia,
ecchymoses, lymphadenopathy, neoplasm, anemia,
hepatomegaly, hypersensitivity reaction, pathological
fracture, infection, neuromuscular disease, arthralgia,
altered urine specific gravity, fever, polyuria,
emphysema, epistaxis, hemoptysis, increased bronchial
secretions, pleural effusion, pulmonary edema, dyspnea,
cough, weight gain, vaginal discharge, vaginal
hemorrhage, vaginitis, injection site reaction
Rare: Abnormal gait, abscess at injection site, alopecia,
anaphylaxis, anaphylactoid reaction, arthralgia, asthma,
body odor, bone fracture (spine), bradycardia,
cerebrovascular accident, cervix disease, constipation,
convulsions, coronary artery disease, cough, decreased
appetite, decreased visual acuity, decreased white blood
cell count, depression, diabetes mellitus, dizziness,
drowsiness, dysmenorrhea, dyspepsia, dysphagia,
epistaxis, excessive crying, feminization, fever,
fibromyalgia syndrome, flu‐like symptoms, gingivitis,
goiter, growth suppression, gynecomastia, hemoptysis,
hepatic injury, hepatotoxicity, hirsutism, hepatic
insufficiency, hyperhidrosis, hyperkinesia, limb pain,
hypersensitivity reaction, hypertension, hyperuricemia,
hypokalemia, increased appetite, induration at injection
site, infection, interstitial pulmonary disease,
lacrimation, leucocytosis, musculoskeletal pain,
leukoderma, myalgia, myocardial infarction, myopathy,
nausea, nervousness, obesity, pallor, osteopenia,
paralysis, penile swelling, peripheral edema, peripheral
neuropathy, personality disorder, pharyngitis, pituitary
apoplexy, precocious puberty, prolonged QT interval,
prostate pain, pulmonary embolism, pulmonary
infiltrates, purpura, retroperitoneal fibrosis, rhinitis,
seizure, sinusitis, skin photosensitivity, skin striae,
suicidal ideation, syncope, tenosynovitis,
thrombocytopenia, transient ischemic attacks, urinary
incontinence, vomiting, weakness
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents, Choline C11
Avoid concomitant use with:
Enhances QTc-prolonging effect of Leuproreline:
Hydroxychloroquine, Promazine, QTc-prolonging Agents
(Highest and Moderate Risk)
Administration:
For IM administration, administer as a single injection to
the gluteal area, anterior thigh, or deltoid. Rotate
injection site periodically.
For SC administration, rotate injection site. Choose site
with adequate SC tissue but without excessive pigment,
nodules, lesions, or hair (e.g., upper or mid‐abdomen,
upper buttocks). Avoid areas with brawny or fibrous
tissues or areas that may be compressed or rubbed (e.g.,
belt or waistband). Administer within 30 minutes of
preparation.
L
Pregnancy Category: X
ATC Code: L02AE02
HORMONE ANTAGONISTS AND RELATED AGENTS
ANTI-ESTROGENS
Rx TAMOXIFEN
Oral: 10 mg and 20 mg tablet (as citrate)
A triphenylethylene-derivative, non-steroidal estrogen
agonist antagonist. It competitively binds to estrogen
receptors on tumors and other tissue targets, producing
a nuclear complex that decreases DNA synthesis and
inhibits estrogen effects.
Indications: Adjunct in the treatment of breast cancer after
primary treatment with surgery and radiation; reduce risk
of invasive breast cancer in women with ductal
carcinoma in situ (DCIS) after surgery and radiation and
in women at high risk
Contraindications: Concurrent warfarin therapy; history of
deep vein thrombosis or pulmonary embolism
Dose:
Breast cancer, treatment adjunct, by mouth, ADULT
(premenopausal women), 20 mg once daily for 5 years.
Breast cancer, treatment adjunct, by mouth, ADULT
(postmenopausal women), 20 mg once daily for 2-3
years, followed by an aromatase inhibitor to complete 5
years;
for extended therapy, 20 mg once daily for 4.5 to 6 years,
followed by aromatase inhibitor for 5 years.
Breast cancer, early (ER-positive), by mouth, ADULT, 20 mg
once daily for 10 years.
369

Breast cancer, metastatic, by mouth, ADULT (male and
female), 20–40 mg daily; doses >20 mg should be given
in 2 divided doses.
Breast cancer, ductal carcinoma in situ (DCIS), by mouth,
ADULT (female), 20 mg once daily for 5 years.
Endometrial carcinoma, recurrent, metastatic, or high-risk,
by mouth, ADULT, 20 mg once daily for 5 years.
Dose Adjustment:
Hepatic Impairment:
Use with caution. No studies have been conducted.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Use for breast cancer risk reduction is associated
with an increased incidence of uterine or
endometrial cancers (some fatal). Monitor and
promptly evaluate abnormal vaginal bleeding.
L
Bone marrow suppression (e.g. thrombocytopenia and/or
leukopenia)
Gynecological effects (e.g. endometrial hyperplasia, polyps,
endometriosis, uterine fibroids, ovarian cysts;
amenorrhea, and menstrual irregularities have been
reported)
Hepatotoxicity
Ocular effects (e.g. decreased visual acuity, retinal vein
thrombosis, retinopathy, corneal changes, color
perception changes and increased incidence of
cataracts)
Thromboembolic events (increased risk)
Bone mineral density (may be associated with an increased
risk of fractures)
Hyperlipidemia
Metastatic breast cancer (local disease flare and increased
bone and tumor pain may occur; may be associated with
(good) tumor response; discontinue if severe).
Children (safety and efficacy have not been established for
treatment longer than 1 year).
Pregnancy (vaginal bleeding, birth defects, and fetal loss
have been reported); lactation (not known if excreted in
breast milk; may inhibit lactation).
Adverse Drug Reactions:
Common: Vasodilation, flushing, hypertension, peripheral
edema, chest pain, venous thrombotic events,
cardiovascular ischemia, angina, deep venous
thrombus, MI, mood changes, edema, depression,
insomnia, dizziness, headache, anxiety, fatigue, skin
changes, rash, alopecia, hot flashes, fluid retention,
altered menses, pain, amenorrhea, oligomenorrhea,
breast pain, breast neoplasm, hypercholesterolemia,
weight loss, weight gain, menstrual disorder, nausea,
vomiting, abdominal pain, constipation, diarrhea,
dyspepsia, abdominal cramps, anorexia, vaginal
discharge, urinary tract infection, leukorrhea, vaginal
bleeding, vaginal hemorrhage, vaginitis, vulvovaginitis,
ovarian cyst, thrombocytopenia, anemia, weakness,
arthritis, arthralgia, back pain, bone pain, osteoporosis,
arthrosis, joint disorder, flu-like syndrome, fracture,
myalgia, paresthesia, muskoskeletal pain, cataract, cyst,
pharyngitis, cough, dyspnea, bronchitis, sinusitis,
370
ANTINEOPLASTIC AND IMMODULATING AGENTS
lymphedema, infection or sepsis, diaphoresis, neoplasm,
allergic reaction
Less Common: Cholestasis, corneal changes,
endometriosis, endometrial cancer, endometrial
hyperplasia, endometrial polyps, fatty liver, hepatic
necrosis, hepatitis, hypercalcemia, lightheadedness,
phlebitis, pruritus vulvae, pulmonary embolism, retinal
vein thrombosis, retinopathy, second primary tumours,
stroke, superficial phlebitis, taste disturbances, tumour
pain, local disease flare, uterine fibroids, vaginal
dryness, angioedema, bullous pemphigoid, erythema
multiforme, hypersensitivity reactions, impotence
(males), interstitial pneumonitis, loss of libido (males),
pancreatitis, SJS, visual color perception changes
Drug Interactions:
Monitor closely with:
Enhances QTc-prolonging effect of Tamoxifen:
QTc-prolonging Agents (Moderate Risk)
Avoid concomitant use with:
Decreases metabolism of Tamoxifen:
Grapefruit Juice
Decreases serum concentration of Tamoxifen:
Dabrafenib, Mitotane
Decreases serum concentration of Anastrozole
Enhances QTc-prolonging effect of Tamoxifen:
QTc-prolonging Agents (Highest Risk)
Increases metabolism of Tamoxifen:
Rifamycin Derivatives e.g. Rifampicin
Increases serum concentration of Tamoxifen:
Abiraterone, Conivaptan, Fusidic Acid (Systemic),
Idelalisib, Mifepristone
Increases serum concentration of the following drugs:
Amodiaquine, Colchicine (may increase distribution of
colchicine into certain tissues, e.g., brain), Dabigatran
Etexilate, Doxorubicin (Conventional), Pazopanib,
Silodosin, Topotecan, Vincristine (Liposomal), Vitamin K
Antagonists, e.g., Warfarin
Reduces therapeutic effect of Tamoxifen:
SSRIs e.g. Fluoxetine
Administration: May be taken with or without meals.
Pregnancy Category: D
ATC Code: L02BA01
ANTINEOPLASTIC AND IMMODULATING AGENTS
ANTI-ANDROGENS
Rx BICALUTAMIDE
Oral: 50 mg and 150 mg tablet / FC tablet
A non-steroidal anti-androgen that acts as an androgen
receptor inhibitor. It competes with dihydrotestosterone
and testosterone to prevent stimulation of cell growth in
prostate cancer.
Indication: Metastatic prostate cancer
Contraindications: Women
Dose:
Prostate cancer, metastatic, by mouth, ADULT, in
combination with an LNRH analogue, 50 mg once daily.
Dose Adjustment:
Hepatic Impairment:
Use with caution in moderate-to-severe hepatic impairment.
Clearance may be delayed in severe impairment.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Cardiovascular disease (may increase the risk of
cardiovascular disease; may cause QT/QTc prolongation;
correct electrolytes prior to initiation; consider periodic
electrolyte and ECG monitoring)
Decreased bone mineral density (associated with prolonged
use; increased risk of osteoporosis and fracture)
Diabetes (loss of glycemic control and decrease in glucose
tolerance has been reported).
Gynecomastia
Anemia (may occur with testosterone suppression; monitor
CBC periodically)
Hepatotoxicity
Hypersensitivity (e.g. angioneuretic edema and urticaria);
interstitial lung disease; fertility (may lead to
spermatogenesis inhibition; may impair male fertility)
Pregnancy (may affect fetal development).
Anti-androgen withdrawal symptom (discontinue use
immediately if disease worsens).
Children (safety and efficacy have not been established).
Adverse Drug Reactions:
Common: Peripheral edema, pain, hot flash, gynecomastia,
constipation, nausea, diarrhea, abdominal pain,
mastalgia, pelvic pain, hematuria, nocturia, anemia,
infection, back pain, weakness, dyspnea, chest pain,
hypertension, angina pectoris, cardiac arrest, cardiac
failure, coronary artery disease, edema, myocardial
infarction, syncope, dizziness, paresthesia, headache,
insomnia, myasthenia gravis, anxiety, chills, confusion,
drowsiness, hypertonia, nervousness, neuropathy,
depression, skin rash, diaphoresis, alopecia, pruritus,
xeroderma, weight loss, hyperglycemia, weight gain,
decreased libido, dehydration, gout,
hypercholesterolemia, dyspepsia, anorexia, flatulence,
vomiting, dysphagia, hernia, melena, periodontal
abscess, xerostomia, urinary tract infection, impotence,
difficulty in micturition, urinary retention, dysuria, urinary
urgency, urinary incontinence, gastrointestinal
carcinoma, rectal hemorrhage, skin carcinoma, herpes
zoster, sepsis, ostealgia, arthritis, leg cramps, myalgia,
neck pain, pathological fracture, cataract, polyuria,
hydronephrosis, increased blood urea nitrogen and
serum creatinine, cough, pharyngitis, flu-like symptoms,
bronchitis, asthma, epistaxis, sinusitis, pneumonia,
rhinitis, cyst, fever
Less Common: Decreased glucose tolerance, hepatic
failure, hepatitis, hepatotoxicity, hypersensitivity,
interstitial pneumonitis, interstitial pulmonary disease,
pulmonary fibrosis
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Choline C11
Increases risk of adverse or toxic effects of the following
drugs:
Aminolevulinic Acid (photosensitizing effect), Porfimer
(photosensitizing effect), Verteporfin (photosensitizing
L
effect)
Avoid concomitant use with:
Increases serum concentration of the following drugs:
Astemizole, Cisapride, Pimozide, Terfenadine
Reduces diagnostic effect of Indium111 Capromab
Pendetide
Administration: May be taken with or without food. Doses
should be taken at the same time each day, either in the
morning or in the evening.
Treatment for metastatic cancer should be started
concomitantly with an LHRH analogue.
Pregnancy Category: X
ATC Code: L02BB03
Rx CYPROTERONE
Oral: 50 mg tablet (as acetate)
A progestogen with antiandrogenic, anti-gonadotropic, and
progestin-like activity. It blocks the binding of
dihydrotestosterone (DHT) to prostatic cancer cells and
exerts negative feedback to hypothalamic-pituitary axis
by inhibiting luteinizing hormone (LH) secretion leading
to decreased testosterone production.
Indication: Palliative treatment of advanced prostate cancer
Contraindications: Liver disease or hepatic dysfunction;
Dubin-Johnson syndrome; Rotor syndrome; previous or
existing liver tumors (not due to metastases from
prostate cancer); presence or history of meningioma;
wasting diseases; severe chronic depression; existing
thromboembolic processes; use in women
371
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose: malaise, meningioma (chronic use), personality disorder,

Prostate cancer, advanced, palliative treatment, by mouth, psychotic depression, pyrexia, restlessness, vascular
ADULT, 200–300 mg daily in 2–3 divided doses headache, vasovagal reactions, dry skin (sebum
(maximum dose, 300 mg daily); following orchiectomy, reduction), eczema, erythema nodosum, exfoliative
reduce dose to 100–200 mg daily. dermatitis, hirsutism, skin discoloration,
maculopapuplar rash, patchy loss of body hair,
Dose Adjustment: photosensitivity, pruritus, rash scleroderma, urticarial,
Renal Impairment: adrenal suppression (dose-related), fatigue, benign
Use with caution. No studies have been conducted, nodular breast hyperplasia, diabetes mellitus,
however, 33% is excreted renally. galactorrhea, gynecomastia, hypercalcemia,
hypernatremia, impotence, inhibition of
Precautions: spermatogenesis, decreased libido, negative nitrogen
WARNING: Hazardous agent. Use appropriate balance, hot flashes, constipation, diarrhea, dyspepsia,
precautions for handling and disposal. glossitis, nausea, pancreatitis, vomiting, weight gain or
loss, bladder carcinoma, crystalluria, urinary frequency,
Cardiovascular disease (use with caution in conditions that enlarged uterine fibroids, uterine hemorrhage, anemia,
may be aggravated by fluid retention, or cardiovascular increased fibrinogen, haemolytic anemia, hemorrhage,
disease) hypochromic anemia, leukopenia, leucocytosis,
Respiratory effects (shortness of breath was observed in normocytic anemia, anorexia, decreased PT,
doses 300 mg daily; use with caution in pulmonary thrombocytopenia, ascites, cholestatic jaundice,
dysfunction). cirrhosis, hepatic carcinoma, hepatic coma, hepatic
CNS depression (lassitude, weakness, and fatigue may dysfunction (dose-related), hepatitis, hepatic failure,
hepatic necrosis, hepatomegaly, hepatoma, injection
L

occur during the first few weeks of treatment);

Depression (associated with an increased incidence of site reaction, myasthenia, abnormal gait, renal failure,
depression, particularly early in the initial 6–8 weeks of weakness, abnormal accommodation, abnormal vision,
therapy). blindness, optic neuritis, optic atrophy, retinal vascular
Diabetes (use with caution; may cause alterations in disorder, retinal vein thrombosis, hematuria,
glucose metabolism; may require adjustments in osteoporosis, asthma, cough, dyspnea, hyperventilation,
diabetes medications); gynecomastia (hyperplasia of the pulmonary oil microembolism, pulmonary embolism,
breast has been reported); thromboembolism (may pulmonary fibrosis, allergic reaction, diaphoresis
increase risk).
Hepatotoxicity (usually develops after a few weeks to Drug Interactions:
several months of treatment initiation; monitor hepatic Monitor closely with:
function; discontinue in hepatic injury); lipid effects (may Enhances absorption of Aripiprazole
increase HDL-cholesterol and triglycerides; may
decrease LDL-cholesterol). Enhances therapeutic effect of C1 Inhibitors (thrombogenic
Fertility (in males, reduced sperm count and volume of effect)
ejaculate, and production of abnormal spermatozoa has
been reported; reversible upon discontinuation Reduces therapeutic effect of the following drugs:
oftherapy); carcinogenesis (benign and malignant Antidiabetic Agents, Choline C11
hepatic tumors have been observed; rule out presence
of tumor in severe upper abdominal discomfort, hepatic Avoid concomitant use with:
enlargement, or intra-abdominal hemorrhage). Decreases serum concentration of Cyproterone:
Adrenocortical function suppression (reported with use; Dabrafenib, Mitotane
monitor adrenal function periodically during therapy);
antiandrogen withdrawal syndrome (may promote Increases risk of adverse or toxic effects of Cyproterone:
prostate cancer growth; discontinue therapy Stiripentol
immediately with increasing prostate specific antigen
(PSA) levels; monitor for 6–8 weeks for withdrawal Increases serum concentration of Cyproterone:
response prior to initiating alternative treatment); Conivaptan, Fusidic Acid (Systemic), Idelalisib,
orchiectomy (may lower 5-year survival rate). Mifepristone
Anemia (hypochromic anemia has been observed; monitor
CBC regularly); meningioma formation (reported with Increases serum concentration of the following drugs:
chronic therapy (years) at doses >25 mg daily). Amodiaquine, HMG-CoA Reductase Inhibitors e.g.,
Pregnancy (effect on fertilization or embryo formation is Simvastatin
unknown).
Reduces diagnostic effect of Indium111 Capromab
SKILLED TASKS. May impair ability to perform tasks, which Pendetide
require mental alertness, like driving or operating
machinery. Reduces therapeutic effect of Cyproterone:
Ethyl Alcohol (interferes with antiandrogenic effect of
Adverse Drug Reactions:Edema, heart failure, hypotension, cyproterone), GnRH Agonist (lowers 5-year survival rate),
phlebitis, shock, stroke, syncope, tachycardia, Ulipristal
thrombosis (DVT), embolus, MI, superficial venous
thrombosis, aphasia, chills, coma, depression, dizziness, Reduces therapeutic effect of the following drugs:
encephalopathy, headache, hemiplegia, lassitude, Anticoagulants, Ulipristal

372
ANTINEOPLASTIC AND IMMODULATING AGENTS

Administration: To be taken after meals, with liquids.
Administer tablets at the same time each day. Tablets
may be divided into equal halves.
Pregnancy Category: D
jaundice, macrocytic anemia, MI, malignant neoplasm of
breast (male), skin methemoglobinemia, oligospermia,
pulmonary embolism, photosensitivity, thrombophlebitis,
sulf-hemoglobinemia, urine discoloration (amber, yellow-
green)

ATC Code: Not available Drug Interactions:

Monitor closely with:
Increases risk of adverse or toxic effects
(methemoglobinemia) of Flutamide:
Rx FLUTAMIDE Dapsone (Topical), Nitric Oxide, Prilocaine, Sodium
Nitrite
Oral: 250 mg tablet
Reduces therapeutic effect of Choline C11
A nonsteroidal antiandrogen that inhibits androgen uptake
and/or inhibits binding of androgen in target tissues. Avoid concomitant use with:
Indication: Prostate cancer Decreases serum concentration of Flutamide:
Dabrafenib, Mitotane
Contraindications: Severe hepatic impairment
Enhances therapeutic effect of Warfarin
Dose:
Prostate cancer, metastatic, by mouth, ADULT, 250 mg Increases serum concentration of Flutamide:
Conivaptan, Fusidic Acid (Systemic), Idelalisib,

given 3 times daily (every 8 hours), preferably at least 3
days before gonadorelin analogue treatment.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Hospitalization and death (rare) due to liver failure
have been reported. Use is not recommended in
patients with ALT values greater than 2 times ULN.
Gynecomastia (may occur when administered in
combination with medical castration)
Hepatic impairment (e.g. elevated serum transaminase
levels, jaundice, hepatic encephalopathy, and acute
hepatic failure; hepatotoxicity is reversible; monitor
serum transaminase levels periodically).
Cardiovascular disease (may increase risk of cardiovascular
disease)
Hemoglobin M disease (increased risk of toxicities
associated with aniline exposure).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
and smoking (increased risk of toxicities associated with
aniline exposure)
Women (should not be used in women, particularly for non-
serious or nonlife-threatening conditions).
Pregnancy (may cause fetal harm); lactation (no information
available; use is not recommended).
Adverse Drug Reactions:
Common: Edema, hypertension, anxiety, confusion,
depression, dizziness, drowsiness, headache, insomnia,
nervousness, skin rash, ecchymoses, pruritus,hot flash,
decreased libido, increased lactate dehydrogenase,
gynecomastia, diarrhea, vomiting, nausea, proctitis,
anorexia, tumor flare, constipation, dyspepsia, increased
appetite, impotence, cystitis, breast tenderness, gastric
distress, hematuria, rectal hemorrhage, anemia,
anemia, leukopenia, thrombocytopenia, herpes zoster,
weakness
Less Common: Cholestatic jaundice, hemolytic anemia,
hepatic encephalopathy, hepatic failure, hepatic
necrosis, hepatitis, hypersensitivity pneumonitis,
L
Mifepristone, Stiripentol, Tizanidine [if concomitant use
cannot be avoided, initiate tizanidine at 2 mg and
increase in 24 mg increments based on patient
response], Vemurafenib
Reduces diagnostic effect of Indium111 Capromab
Pendetide
Administration: May be administered with or without food.
Pregnancy Category: D
ATC Code: L02BB01
AROMATASE INHIBITORS
Rx LETROZOLE
Oral: 2.5 mg tablet / FC tablet
A nonsteroidal competitive inhibitor of the aromatase
enzyme which catalyzes the conversion of androgens to
estrogens. Inhibition of the enzyme leads to significant
reduction in plasma estrogen.
Indication: Adjuvant treatment of postmenopausal,
hormone-receptor positive early stage breast cancer
Contraindications: Women of child-bearing potential
Dose:
NOTE: American Society of Clinical Oncology (ASCO)
guidelines for Adjuvant Endocrine Therapy of Hormone
Receptor‐Positive Breast Cancer recommend a
maximum duration of 5 years of aromatase inhibitor
therapy for postmenopausal women. Aromatase
inhibitors may be combined with tamoxifen for up to 10
years of endocrine therapy.

373

Breast cancer, advanced (first-line or second-line
treatment), by mouth, ADULT, 2.5 mg once daily;
continue until tumor progression.
Breast cancer, early, adjuvant treatment, by mouth, ADULT,
2.5 mg once daily for a planned duration of 5 years;
discontinue if relapse occurs.
Breast cancer, early, extended adjuvant treatment, by
mouth, ADULT, 2.5 mg once daily for a planned duration
of 5 years after 5 years of tamoxifen; discontinue if
relapse occurs.
Dose Adjustment:
Renal Impairment:
Use with caution. Dose adjustments have not been studied
for patients with CrCl <10 mL/minute.
Hepatic Impairment:
Use with caution. Dose adjustment is recommended in
patients with cirrhosis or severe hepatic dysfunction.
For patients with severe impairment (Child-Pugh class C)
and cirrhosis, administer 2.5 mg every other day. Effect
has not been determined in non-cirrhotic patients with
elevated bilirubin.
L
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
CNS depression (may cause dizziness, fatigue, and
somnolence)
Decreased bone mineral density (may cause decrease in
bone mineral density)
Increased cholesterol (may increase total serum
cholesterol; monitor cholesterol panel).
SKILLED TASKS. May impair ability to perform tasks, which require
mental alertness, like driving or operating machinery.
Adverse Drug Reactions:
Common: Edema, chest pain, hypertension, chest wall pain,
thromboembolism, angina pectoris, myocardial
infarction, transient ischemic attacks, headache,
dizziness, fatigue, insomnia, pain, cerebrovascular
accident, anxiety, depression, drowsiness, diaphoresis,
night sweats, skin rash, alopecia, pruritus,
hypercholesterolemia, weight gain or loss, hot flash,
hypercalcemia, nausea, constipation, diarrhea, vomiting,
abdominal pain, anorexia, dyspepsia, mastalgia, urinary
tract infection, vaginal dryness, vaginal hemorrhage,
vaginal irritation, metastases, infection, viral infection,
influenza, weakness, decreased bone mineral density,
arthralgia, arthritis, ostealgia, back pain, osteoporosis,
bone fracture, limb pain, myalgia, cataract, renal
disease, dyspnea, cough, pleural effusion
Less Common: Anaphylaxis, angioedema, arterial
thrombosis, cardiac failure, carpal tunnel syndrome,
endometrial carcinoma, endometrial hyperplasia,
erythema multiforme, hepatitis, leukopenia, memory
impairment, stomatitis, tachycardia, tenosynovitis
(trigger finger), thrombocytopenia, TEN
Drug Interactions:
Avoid concomitant use with:
Decreases serum concentration of the following drugs:
Artesunate, Tegafur
374
ANTINEOPLASTIC AND IMMODULATING AGENTS
Increases serum concentration of the following drugs:
Artesunate, CYP2A6 Substrates
Administration: May be taken with or without food.
Pregnancy Category: X
ATC Code: L02BG04
IMMUNOSTIMULANTS
COLONY STIMULATING FACTORS
Rx FILGRASTIM (G-CSF)
Inj.: 150 micrograms/0.6 mL vial (IV, SC)
300 micrograms/0.5 mL solution, pre-filled syringe
(IV, SC)
300 micrograms/mL vial (IV, SC)
300 micrograms/1.2 mL vial (IV, SC)
A granulocyte colony stimulating factor (G-CSF) produced by
recombinant DNA technology. It stimulates the
production, maturation, and activation of neutrophils.
Indications: To decrease the incidence of infection
(neutropenic fever) in patients with non-myeloid
malignancies receiving myelosuppressive chemotherapy
associated with a significant incidence of severe
neutropenia with fever; to reduce the time to neutrophil
recovery and the duration of fever following induction or
consolidation chemotherapy in adults with acute myeloid
leukemia (AML); to reduce the duration of neutropenia
and neutropenia-related events in patients with non-
myeloid malignancies receiving myeloablative
chemotherapy followed by marrow transplantation; to
increase survival in patients acutely exposed to
myelosuppressive doses of radiation; for mobilization of
peripheral blood progenitor cells (PBPCs) for collection
by leukapheresis in autologous or allogeneic
hematopoietic cell transplantation; long-term
administration to reduce the incidence and duration of
neutropenic complications in symptomatic patients with
congenital, cyclic, or idiopathic neutropenia.
Contraindication: History of serious allergic reactions to
human granulocyte colony-stimulating factors, such as
filgrastim or pegfilgrastim, or any component of the
formulation
Dose:
Myelosuppressive chemotherapy recipient with non-myeloid
malignancies, by SC injection or IV infusion, ADULT/
CHILD/ ADOLESCENT, 5 micrograms/kg per day, may
increase by 5 micrograms/kg for each chemotherapy
cycle according to the duration and severity of the
neutropenia; continue for up to 14 days until the
absolute neutrophil count (ANC) reaches 10,000/mm3;
discontinue if the ANC surpasses 10,000/mm3 after the
expected chemotherapy-induced neutrophil nadir.
AML following induction or consolidation chemotherapy, by
SC injection or IV infusion, ADULT/ CHILD/ ADOLESCENT,
ANTINEOPLASTIC AND IMMODULATING AGENTS
5 micrograms/kg per day, may increase by 5
micrograms/kg (for each chemotherapy cycle) according
to the duration and severity of the neutropenia; continue
for up to 14 days until the absolute neutrophil count
(ANC) reaches 10,000/mm3; discontinue if the ANC
surpasses 10,000/mm3 after the expected
chemotherapy-induced neutrophil nadir.
Bone marrow transplantation, by IV infusion, ADULT, 10
micrograms/kg per day, ≥24 hours after chemotherapy
and ≥24 hours after bone marrow infusion; adjust the
dose according to the duration and severity of
neutropenia;
If ANC >1,000/mm3 for 3 consecutive days, reduce dose
to 5 micrograms/kg per day;
If ANC remains >1,000/mm3 for 3 more consecutive
days, discontinue;
If ANC decreases to <1,000/mm3, resume at 5
micrograms/kg per day;
If ANC decreases to <1,000/mm3 during the 5
micrograms/kg per day dose, increase dose to 10
micrograms/kg per day and follow the above steps.
Hematopoietic radiation injury syndrome, by SC injection,
ADULT, 10 micrograms/kg once daily; begin as soon as
possible after suspected or confirmed radiation doses
>2 gray (Gy) and continue until ANC remains
>1,000/mm3 for 3 consecutive CBCs or ANC exceeds
10,000/mm3 after the radiation-induced nadir. [NOTE:
Initiate within 24 hours of exposure of a dose ≥2 Gy
and/or significant decrease in absolute lymphocyte
count, or for anticipated neutropenia <500/mm3 for ≥7
days.]
Peripheral blood progenitor cell collection and therapy, by
SC injection, ADULT, 10 micrograms/kg daily, usually for
6–7 days with apheresis occurring on days 5, 6, and 7;
begin at least 4 days before the first apheresis and
continue until the last apheresis; discontinue for WBC
>100,000/mm3.
Severe chronic neutropenia, congenital, by SC injection,
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older,
initially 6 micrograms/kg per day in 2 divided doses;
adjust dose based on ANC and clinical response; mean
dose is 6 micrograms/kg daily;
Severe chronic neutropenia, idiopathic, by SC injection,
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older,
initially 5 micrograms/kg once daily; adjust dose based
on ANC and clinical response; mean dose is 1.2
micrograms/kg daily;
Severe chronic neutropenia, cyclic, by SC injection,
ADULT/ADOLESCENT/ CHILD/INFANT 7 months & older,
initially 5 micrograms/kg once daily; adjust the dose
based on ANC and clinical response; mean dose is 2.1
micrograms/kg daily.
Primary prophylaxis for children with high likelihood of
febrile neutropenia (e.g., children receiving dose-intense
chemotherapy for Ewing’s sarcoma/Primitive
neuroectodermal tumors, rhabdomyosarcoma), 5-10
mcg/kg 48-72 hours after completion of chemotherapy.
Dose Adjustment:
Renal Impairment:
If patient develops glomerulonephritis, consider dose
reduction or treatment interruption.
Precautions:
Allergic reactions (serious allergic reactions, including
anaphylaxis may occur; may be managed
symptomatically with antihistamines, steroids,
bronchodilators, or epinephrine; reactions may recur
within days after initial allergy management has been
stopped; permanently discontinue in serious allergic
reactions).
Alveolar hemorrhage (pulmonary infiltrates, hemoptysis
may occur; resolved upon discontinuation)
Respiratory distress syndrome
Capillary leak syndrome (hypoalbuminemia, hypotension,
edema, or hemoconcentration may occur; may vary in
frequency and severity; may be life-threatening if
treatment is delayed)
Cutaneous vasculitis (generally occurs in patients with
severe chronic neutropenia on chronic therapy; withhold
treatment if cutaneous vasculitis occurs)
Hematologic effects (excessive leukocytosis or
thrombocytopenia may occur; discontinue when
absolute neutrophil count (ANC) exceeds 10,000/mm3
after the ANC nadir has occurred; monitor CBC twice
weekly during therapy; monitor platelet counts)
Severe chronic neutropenia (myelodysplastic syndrome
(MDS) and acute myeloid leukemia (AML) have been
reported)
L
Sickle cell disorders (may precipitate severe sickle cell
crises, some fatal; discontinue in patients undergoing
sickle cell crisis)
Nephrotoxicity (glomerulonephritis, resulting in azotemia,
hematuria, or proteinuria may occur; if
glomerulonephritis is suspected, evaluate for cause).
Splenic rupture (if upper abdominal pain, left upper
quadrant pain, or shoulder tip pain occurs, withhold
treatment and evaluate for enlarged spleen or splenic
rupture).
Adverse Drug Reactions:
Common: Alopecia, anemia, antibody development,
arthralgia, back pain, cardiac arrhythmia, chest pain,
dizziness, dyspnea, epistaxis, erythema, cough, fatigue,
fever, headache, hypertension, hypoesthesia, increased
lactate dehydrogenase and uric acid (mild-to-moderate;
reversible), leukocytosis, limb pain, maculopapular rash,
musculoskeletal pain, MI, muscle spam, nausea,
ostealgia (dose and cycle related), pain, petechia,
splenomegaly, skin rash, thrombocytopenia, transfusion
reaction, upper respiratory tract infection, urinary tract
infection, vomiting
Less Common: Anaphylaxis, capillary leak syndrome,
cerebral hemorrhage, constipation, decreased bone
mineral density, decreased hemoglobin, diarrhea,
ethema nodosum, exacerbation of psoriasis, facial
edema, hematuria, hemoptysis, hepatomegaly,
hypersensitivity reaction, renal insufficiency,
hypersensitivity angiitis, injection site reaction,
hypotension, malaise, mouth pain, oropharyngeal pain,
osteoporosis, peripheral edema, proteinuria, pulmonary
hemorrhage, pulmonary infiltrates, severe sickle cell
crisis, respiratory distress syndrome, splenic rupture,
Sweet’s syndrome, tachycardia, weakness, urticaria,
wheezing
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Bleomycin (pulmonary toxicity), Cyclophosphamide
375

Avoid concomitant use with:
Increases risk of adverse or toxic effects of Topotecan
Drugs that may potentiate the release of neutrophils‚ such
as lithium‚ should be used with caution
DRUG-DIAGNOSTIC TEST INTERACTION. May interfere with bone
imaging studies, increased hematopoietic activity of the bone
marrow may appear as transient positive bone imaging changes.
Administration:
For IV administration, administer as a short infusion over
15–30 minutes for chemotherapy-induced neutropenia,
by continuous infusion for chemotherapy-induced
neutropenia, or as an infusion of no longer than 24 hours
for bone marrow transplantation.
For SC administration, administer into the outer upper
arm, abdomen (except within 2 inches of navel), front
middle thigh, or the upper outer buttocks area. Rotate
the injection site. Do NOT inject into areas that are
tender, red, bruised, hardened, or scarred, or sites with
stretch marks.
L
Do NOT administer earlier than 24 hours after or in the
24 hours prior to cytotoxic chemotherapy.
Should NOT be routinely used in the treatment of
established neutropenic fever.
Vials may be diluted in D5W to >15 mcg/mL for infusion. DO
NOT dilute with saline at any time, because the product
may precipitate.
For 5-15 mcg/mL dilution: Add human albumin to a final
concentration of 2 mg/mL to protect from adsorption to
plastic materials
Pregnancy Category: C
ATC Code: L03AA02
INTERFERONS
Rx INTERFERON ALFA-2b (HUMAN)
Inj.: 3 million IU and 5 million IU per mL vial + diluent (IM,
SC)
Binds to a cell wall receptor to initiate intracellular activity
resulting in induction of gene transcription, cellular
growth inhibition, alteration of the state of cellular
differentiation, interference with oncogene expression,
alteration of cell surface antigen expression, increase in
phagocytic activity of macrophages, and augmentation
of cytotoxicity of lymphocytes for target cells.
Indications: Treatment of AIDS-related Kaposi’s sarcoma in
18 years and older; treatment of chronic hepatitis B in
patients 1 year and older with compensated liver
disease; treatment of chronic hepatitis C in patients 18
years and older with compensated liver disease who
have a history of blood or blood-product exposure and/or
are hepatitis C virus (HCV) antibody-positive; treatment
of chronic hepatitis C in patients 3 years and older with
compensated liver disease previously untreated with
376
ANTINEOPLASTIC AND IMMODULATING AGENTS
alpha interferon therapy and in patients 18 years and
older who have relapsed following alpha interferon
therapy; initial treatment of clinically aggressive follicular
non-Hodgkin lymphoma in patients 18 years and older;
treatment of hairy cell leukemia in patients 18 years and
older; adjuvant to surgical treatment of malignant
melanoma in patients 18 years and older who are free of
disease but at high risk for systemic recurrence, within
56 days of surgery
Contraindications: Decompensated liver disease;
autoimmune hepatitis; combination therapy with
interferon alfa-2b and ribavirin in women who are
pregnant, in males with pregnant partners, in patients
with hemoglobinopathies, or in creatinine clearance <50
mL/minute
Dose:
Hairy cell leukemia, by IM or SC injection, ADULT, 2 million
units/m2 3 times weekly for up to 6 months, may
continue treatment with sustained treatment response;
discontinue for disease progression or failure to respond
after 6 months.
Lymphoma, follicular, by SC injection, ADULT, 5 million units
3 times weekly for up to 18 months.
Malignant melanoma, maintenance, by SC injection,
ADULT,10 million units/m2 3 times weekly for 48 weeks.
AIDS-related Kaposi’s sarcoma, by IM or SC injection,
ADULT, 30 million units/m2 3 times weekly until disease
progression or until maximal response has been
achieved after 16 weeks.
Chronic hepatitis B, by IM or SC injection, ADULT, 5 million
units daily or 10 million units 3 times weekly for 16
weeks; CHILD 1–17 years, 3 million units/m2 3 times
weekly for 1 week, followed by 6 million units/m2 3 times
weekly (maximum, 10 million units per dose; total
duration of therapy, 16–24 weeks).
Chronic hepatitis C, by IM or SC injection, ADULT, 3 million
units 3 times weekly; in normalization of ALT at 16
weeks, continue treatment if tolerated for 18–24
months; consider discontinuation if normalization does
not occur at 16 weeks; CHILD 1–17 years, with ribavirin,
3–5 million units/m2 3 times weekly for 48 weeks
regardless of HCV genotype (maximum, 3 million units
per dose).
Dose Adjustment:
Renal Impairment:
In impaired renal function and CrCl ≥50 mL/minute, use
combination therapy with ribavirin (hepatitis C) with
caution.
If a patient with lymphoma (follicular) develops a serum
creatinine >2 mg/dL, permanently discontinue.
Hepatic Impairment:
If patient develops severe (grade 3) hepatic injury or hepatic
decompensation (Child-Pugh class B and C),
permanently discontinue.
If a patient with lymphoma (follicular) develops an AST >5
times ULN, permanently discontinue.
If ALT/AST increases to >5 to 10 times ULN during induction
and maintenance of malignant melanoma, temporarily
withhold. Resume with a 50% dose reduction when
adverse reaction abates. If ALT/AST increases to >10
times ULN, permanently discontinue.
ANTINEOPLASTIC AND IMMODULATING AGENTS
Toxicity:
Hematologic toxicity:
If ANC <500/mm3 or platelets <25,000/mm3,
discontinue treatment.
Neuropsychiatric disorders during treatment:
In clinical depression or other psychiatric problem, monitor
closely during and for 6 months after treatment.
In severe depression or other psychiatric disorder,
discontinue treatment.
In persistent or worsening psychiatric symptoms, suicidal
ideation, or aggression towards others, discontinue
treatment and follow with appropriate psychiatric
intervention.
In follicular lymphoma:
In neutrophils >1,000/mm3 to <1,500/mm3, reduce dose
by 50%, may re-escalate to starting dose when
neutrophils return to >1,500/mm3.
In severe toxicity where neutrophils <1,000/mm3 or
platelets <50,000/mm3, temporarily withhold treatment.
In AST >5 times ULN or serum creatinine >2 mg/dL,
permanently discontinue.
In hairy cell leukemia:
In platelet count <50,000/mm3, administer by SC injection
ONLY.
In severe toxicity, reduce dose by 50%; or temporarily
withhold and resume with 50% dose reduction.
Permanently discontinue if persistent or recurrent severe
toxicity is noted.
Chronic hepatitis B:
In WBC <1,500/mm3, granulocytes <750/mm3, or platelet
count <50,000/mm3, other laboratory abnormality, or
severe adverse reaction, reduce dose by 50%, may re-
escalate to starting dose upon resolution of hematologic
toxicity. Discontinue for persistent intolerance.
In WBC <1,000/mm3, granulocytes <500/mm3, or platelet
count <25,000/mm3, permanently discontinue.
Chronic hepatitis C:
In severe toxicity, reduce dose by 50% or temporarily
withhold until toxicity subsides. Permanently discontinue
for persistent toxicities after dosage reduction.
AIDS-related Kaposi sarcoma:
In severe toxicity, reduce dose by 50% or temporarily
withhold, may resume at reduced dose with toxicity
resolution. Permanently discontinue for persistent or
recurrent toxicities.
Malignant melanoma:
In severe toxicity including neutrophils >250/mm3 to
<500/mm3 or ALT/AST >5 to 10 times ULN, temporarily
withhold and resume with a 50% dose reduction when
adverse reaction abates.
In neutrophils <250/mm3, ALT/AST >10 times ULN, or
severe and persistent adverse reactions, permanently
discontinue.
Precautions:
WARNING: May cause or aggravate severe
neuropsychiatric adverse events. Monitor closely with
periodic clinical evaluations. Discontinue treatment
for severe persistent or worsening symptoms.
May cause or aggravate fatal or life-threatening
autoimmune disorders, ischemic disorders, or
infectious disorders. Monitor closely with periodic
clinical and laboratory evaluations. Discontinue for
severe persistent or worsening symptoms. Some
cases may resolve with discontinuation.
Autoimmune disease (e.g. thrombocytopenia, vasculitis,
Raynaud’s disease, rheumatoid arthritis, lupus
erythematosus, and rhabdomyolysis; worsening of
psoriasis and sarcoidosis have been reported)
Hypersensitivity (acute hypersensitivity reactionshave been
rarely reported; transient rashes have occurred in some
patients following injection but have not necessitated
treatment interruption)
Flu-like symptoms (fever and flu-like symptoms commonly
occur)
Bone marrow suppression (potentially severe cytopenia,
aplastic anemia, or hemolytic anemia may occur;
hemolytic anemia has been observed)
Coagulation disorders (use with caution; monitor closely)
Hypertriglyceridemia.
Cardiovascular disease (e.g. hypotension, arrhythmia,
L
tachycardia, cardiomyopathy and/or MI;monitor
baseline and periodic ECGs; supraventricular
arrhythmias occur rarely and are associated with
preexisting cardiac disease or prior therapy with
cardiotoxic agents).
Cerebrovascular events (hemorrhagic and ischemic
cerebrovascular events have been observed);
neuropsychiatric disorders (depression psychosis,
mania, suicidal ideation, suicide attempts, completed
suicides, homicidal ideation may occur; if psychiatric
symptoms persist or worsen, or suicidal or homicidal
ideation or aggressive behavior towards others is
identified, discontinue treatment and follow the patient
closely; careful neuropsychiatric monitoring is
recommended during and for 6 months after treatment
in patients who develop psychiatric disorders).
Dental and periodontal disorders (dry mouth leading to
teeth and mucous membrane damage may occur;
damage may occur in chronic therapy);
Ocular effects (e.g. decreased or loss of vision, macular
edema, retinal hemorrhages, cotton wool spots, optic
neuritis, papilledema, serious retinal detachment, and
retinal artery or vein thrombosis; monitor closely;
perform a complete eye exam promptly if ocular
symptoms develop).
Diabetes (discontinue if diabetes cannot be effectively
managed with medication; use with caution in patients
with a history of diabetes mellitus, particularly if prone to
DKA).
Hepatic effect (hepatotoxicity, some fatal, transient
increase in ALT (≥2 times baseline), jaundice, hepatic
encephalopathy, or hepatic failure may occur; worsening
and potentially fatal liver disease has been reported;
patients with cirrhosis are at increased risk of hepatic
decompensation).
Pulmonary effects (dyspnea, pulmonary infiltrates,
pulmonary hypertension, interstitial pneumonitis,
pneumonia, bronchiolitis obliterans, and sarcoidosis
may be induced or aggravated by treatment, sometimes
resulting in respiratory failure or fatality; monitor closely
and consider discontinuing treatment with evidence of
impaired pulmonary function).
377

Thyroid disorders (hyperthyroidism or hypothyroidism may
occur; discontinue interferon use in patients who
develop thyroid abnormalities during treatment and in
patients with thyroid disease who subsequently cannot
maintain normal ranges with thyroid medication).
Elderly (higher doses may result in increased CNS toxicity,
e.g., obtundation, coma)
Children (suicidal ideation or attempts may occur more
frequently).
Adverse Drug Reactions:
Common: Abdominal pain, agitation, amenorrhea, alopecia,
amnesia, anemia, anorexia, anxiety, arthralgia, back
pain, bronchitis, candidiasis, chest pain, chills,
confusion, constipation, cough, depression, dermatitis,
diaphoresis, diarrhea, dizziness, drowsiness, dysgeusia,
dyspepsia, decreased libido, dyspnea, edema, epistaxis,
fatigue, fever (children), gingivitis, headache, herpes
virus infection, hypertension, flu-like symptoms,
hypoesthesia, infection, injection site reaction, insomnia,
lack of concentration, irritability, loose stools, malaise,
leukopenia, myalgia, nasal congestion, nausea,
neutropenia, pain, paresthesia, pharyngitis, polyuria,
L
pruritus, purpura, right upper quadrant pain, rigors,
sinusitis, skeletal pain, skin rash, thrombocytopenia,
vertigo, weight loss, urinary tract infection, vomiting,
weakness, xeroderma, xerostomia
Less Common: Abnormal hepatic function tests, abscess,
aggressive behavior, alcohol intolerance, amyotrophy,
anaphylaxis, angina pectoris, angioedema, aphasia,
aphthous stomatitis, arteritis, arthritis, ascites, asthma,
ataxia, atrial fibrillation, auditory impairment, Bell’s
palsy, blurred vision, bradycardia, biliary colic,
bronchoconstriction, bronchospasm, bronchiolitis
obliterans, cardiac arrhythmia, cardiac failure,
cardiomegaly, cardiomyopathy, carpal tunnel syndrome,
cerebrovascular accident, colitis, coma, conjunctivitis,
coronary artery disease, cyanosis, cystitis, dehydration,
diabetes mellitus, dysphasia, dysuria, eczema,
epidermal cyst, erythema, erythema multiforme,
erythematous rash, esophagitis, exacerbation of
psoriasis, exacerbation of sarcoidosis, cellulitis,
extrapyramidal reaction, extrasystoles, flushing,
folliculitis, fungal infection, gastritis, goiter, GI
hemorrhage, granulocytopenia, hallucination, hearing
loss, heart valve disease, hematuria, hemolytic anemia,
hepatic encephalopathy, hemoptysis, hepatitis,
hepatotoxicity, hirsutism, hypercalcemia, hyperglycemia,
hypersensitivity reaction (acute), hyperbilirubinemia, hot
flash, hypertriglyceridemia, hepatic failure, homicidal
ideation, hyperthyroidism, hypochromic anemia,
hyporeflexia, hypotension, hypothermia, immune
thrombocytopenia, hypoventilation, impotence,
interstitial pneumonitis, jaundice, leg cramps,
leukorrhea, hypothyroidism, lichenoid dermatitis, lipoma,
lymphadenitis, lymphadenopathy, macular edema,
lymphocytosis, lymphocytopenia, optic neuritis,
maculopapular rash, mania, mastitis, menorrhagia,
migraine, mucositis, myocardial infarction, myositis,
nephrotic syndrome, nervousness, neuralgia,
neuropathy, nocturia, nystagmus, palpitations,
pancreatitis, pelvic pain, pancytopenia, papilledema,
paranoia, periarteritis nodosa, peripheral ischemia,
peripheral neuropathy, photophobia, pituitary
insufficiency, pneumonia, pneumothorax, pleural
effusion, proteinuria, psoriasis, psychoneurosis,
378
ANTINEOPLASTIC AND IMMODULATING AGENTS
psychosis, pulmonary embolism, pulmonary fibrosis,
pulmonary hypertension, pulmonary infiltrates,
Raynaud's phenomenon, rectal hemorrhage, reduced
ejection fraction, renal failure, renal insufficiency, pure
red cell aplasia, respiratory insufficiency, retinal cotton-
wool spot, retinal detachment (serous), retinal
thrombosis, retinal vein occlusion, rheumatoid arthritis,
rhabdomyolysis, sarcoidosis, seizure, sexual disorder,
skin photosensitivity, spondylitis, sepsis, Stevens-
Johnson syndrome, stomatitis, suicidal ideation,
syncope, systemic lupus erythematosus, thrombotic
thrombocytopenic purpura, tachycardia, tendonitis,
thrombosis, tissue necrosis at injection site, toxic
epidermal necrolysis, upper respiratory tract infection,
tremor, urinary incontinence, urticaria, uterine
hemorrhage, vasculitis, Vogt-Koyanagi-Harada
syndrome, wheezing
Rare: Aplastic anemia
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Ribavirin (hemolytic anemia), Zidovudine
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Interferon Alfa-
2b:
Dipyrone (agranulocytosis; pancytopenia)
Increases risk of adverse or toxic effects of the following
drugs:
Aldesleukin (myocardial and renal toxicity), Clozapine
(agranulocytosis), Telbivudine (peripheral neuropathy)
Increases serum concentration of Tizanidine
Reduces therapeutic effect of BCG (Intravesical)
Administration: For parenteral administration. Allow to
reach room temperature prior to injection.
For IM administration, administer dose in the evening to
enhance tolerability. Rotate injection sites. Preferred
sites for injection are anterior thigh, deltoid, and
superolateral buttock. In hairy cell leukemia treatment, if
platelets are <50,000/mm3, administer by SC injection
ONLY.
For SC administration, rotate injection site. Preferred
sites for injection are abdomen (except around the
navel), anterior thigh, and outer upper arm. Administer
dose in the evening if possible to enhance tolerability.
Patient should be well hydrated.
NOTE: Associated with moderate emetic potential.
Antiemetics may be recommended to prevent nausea
and vomiting.
Consider premedication with acetaminophen prior to
administration to reduce the incidence of some adverse
reactions. Not all dosage forms and strengths are
appropriate for all indications.
ANTINEOPLASTIC AND IMMODULATING AGENTS
Due to differences in dosage, patients should not change
brands of interferons without the concurrence of their
health care provider.
Pregnancy Category: C; X (in combination with ribavirin)
ATC Code: L03AB05
Rx PEGINTERFERON ALFA-2a
Inj.: 135 micrograms/0.5 mL pre-filled syringe (SC)
An alpha interferon subtype, which binds to a cell wall
receptor to initiate intracellular activity resulting in
induction of gene transcription, cellular growth inhibition,
alteration of the state of cellular differentiation,
interference with oncogene expression, alteration of cell
surface antigen expression, increase in phagocytic
activity of macrophages, and augmentation of
cytotoxicity of lymphocytes for target cells.
Indications: Management of HBeAg positive and negative in
adults, chronic hepatitis B virus (HBV) infection who have
compensated liver disease and evidence of viral
replication and liver inflammation; Management of
chronic hepatitis C (CHC) with compensated liver disease
in adults; Treatment of pediatric patients ≥5 years with
CHC and compensated liver disease; management of
chronic hepatitis C in compensated liver disease, in
patients with contraindications, or in significant
intolerance to other HCV antiviral drugs
NOTE: NOT for the treatment of chronic HCV who previously
failed therapy with an interferon alfa.
NOT for treatment of CHC who have had solid organ
transplantation.
Contraindications: Autoimmune hepatitis; hepatic
decompensation in cirrhotic patients (Child-Pugh score
>6, class B and C) before treatment; hepatic
decompensation with Child-Pugh score ≥6 in cirrhotic
CHC coinfected with HIV before treatment; neonates and
infants (due to benzyl alcohol component); pregnancy;
men whose female partners are pregnant
Dose:
Chronic hepatitis C, mono-infection or co-infection with HIV,
by SC injection, ADULT, as monotherapy or in
combination with ribavirin, 180 micrograms once weekly
for 48 weeks;
Duration of combination therapy for mono-infection
based on genotype:
Genotype Duration of therapy
Genotypes Refer to the individual HCV
1, 2 antiviral agents
24 weeks (peginterferon +
Genotype 3 ribavirin without other HCV
antiviral drugs)
48 weeks (peginterferon +
Genotype 4 ribavirin without other HCV
antiviral drugs)
Genotypes
No dosing recommendations
5, 6
48 weeks, regardless of HCV
Co-infection
genotype (without other HCV
with HIV
antiviral drugs)
NOTE: Discontinue in patients with HCV (genotype 1) after 12
weeks if HCV RNA does not decrease by at least 2 log
(compared to pretreatment) or if detectable HCV RNA is
present at 24 weeks.
When used in combination with other antiviral drugs, refer to
individual agents for duration of therapy.
Chronic hepatitis C, by SC injection, ADOLESCENT and
CHILD ≥5 years, with ribavirin, 180 micrograms/1.73 m2
x body surface area (BSA) once weekly (maximum dose,
180 micrograms);
Duration of therapy based on genotype:
Genotype Duration of therapy
Genotypes 1, 4, 5, 6 48 weeks
Genotype 2, 3 24 weeks
NOTE: Children who reach their 18th birthday during treatment
should remain on the pediatric regimen until completion of
therapy.
L
Chronic hepatitis B, by SC injection, 180 micrograms once
weekly for 48 weeks.
Dose Adjustment:
Renal Impairment:
For patients with CrCl <30 mL/minute, 135 micrograms
once weekly and monitor for toxicity.
For patients with end-stage renal disease (ESRD) requiring
hemodialysis, 135 mcg once weekly and monitor for
toxicity. If severe adverse reactions or laboratory
abnormalities occur, reduce dose to 90 micrograms
once weekly until adverse reactions resolve. If
intolerance persists after dose adjustment, discontinue.
Hepatic Impairment:
For HCV or HBV in adult patients with ALT progressively
rising above baseline, decrease dose to 135 micrograms
once weekly or temporarily discontinue. Monitor
transaminases more frequently. If ALT continues to rise
despite dose reduction or ALT increase is accompanied
by increased bilirubin or hepatic decompensation,
discontinue therapy immediately. Resume therapy after
ALT flare subsides.
For HCV in children with ALT ≥5 but <10 x ULN, decrease
interferon dose to 135 micrograms per 1.73 m2 x BSA
once weekly. Monitor weekly. Further modify dose if
needed until ALT stabilizes or decreases. For persistent
ALT ≥10 x ULN, discontinue treatment.
Toxicity:
For HCV in adolescents and children ≥5 years with
moderate-to severe adverse reactions, initially decrease
to 135 micrograms/1.73 m2 x BSA once weekly. Further
reduce dose to 90 micrograms/1.73 m2 x BSA once
weekly; or 45 micrograms/1.73 m2 x BSA once weekly if
reaction persists or recurs.
Based on hematologic parameters:
If ANC 750–999/mm3, week 1 to 2, 135 micrograms per
1.73 m2 x BSA once weekly; weeks 3 to 48, no
modification.
If ANC 500–749/mm3, week 1 to 2, delay or hold dose until
ANC >750/mm3 then resume dose with 135
micrograms/1.73 m2 x BSA once weekly. Assess WBC
379

weekly for 3 weeks to verify ANC>750/mm3; weeks 3 to
48, 135 micrograms per 1.73 m2 x BSA once weekly.
If ANC 250 to 499/mm , week 1 to 2, delay or hold dose
3 and after therapy until growth catch-up has occurred)
until ANC >750/mm3 then resume dose with 90
micrograms/1.73 m2 x BSA once weekly; weeks 3 to 48,
delay or hold dose until ANC >750/mm3 then resume
dose with 135 micrograms/1.73 m2 x BSA once weekly.
If ANC <250/mm3 or in febrile neutropenia, discontinue
treatment.
If platelet count <50,000/mm3, 90 micrograms/1.73 m2 x
BSA once weekly.
For HCV / HBV in adults with moderate-to-severe adverse
reactions, decrease to 135 micrograms weekly for initial
dose reduction. Further dose reductions to 90
micrograms weekly may be necessary in some cases if
reaction persists or recurs.
Based on hematologic parameters:
If ANC <750/mm3, 135 micrograms once weekly.
If ANC <500/mm3, suspend therapy until ANC
>1,000/mm3, then restart at 90 micrograms once
weekly.
L
If platelet count <50,000/mm3, 90 micrograms once
weekly.
If platelet count <25,000/mm3, discontinue therapy.
Precautions:
WARNING: Peginterferon alfa-2a may cause or
aggravate fatal or life-threatening neuropsychiatric,
autoimmune, ischemic, and infectious disorders.
Withdraw therapy in patients with persistently severe
or worsening signs or symptoms of these conditions.
Use with caution in the elderly. Certain adverse effects
(e.g., neuropsychiatric, cardiac, flu-like reactions)
may be more severe.
Autoimmune disease (e.g. thyroiditis, thrombotic
thrombocytopenic purpura, idiopathic thrombocytopenic
purpura, rheumatoid arthritis, interstitial nephritis,
systemic lupus erythematosus, myositis, hepatitis, and
psoriasis)
Hypersensitivity reactions
Bone marrow suppression (e.g. severe cytopenias and
aplastic anemia)
Infectious disorders (interferon therapy is commonly
associated with flu-like symptoms, including fever)
Cardiovascular disease (hypertension, chest pain, MI, and
supraventricular arrhythmias)
Pulmonary effects (may cause or aggravate dyspnea,
pulmonary infiltrates, pneumonia, bronchiolitis
obliterans, interstitial pneumonitis, pulmonary
hypertension, and sarcoidosis, which may result in
potentially fatal respiratory failure)
CNS depression
Ischemic disorders (reported in patients without risk factors
for stroke)
Neuropsychiatric disorders (e.g. depression, suicidal
ideation, suicide attempt, homicidal ideation, drug
overdose, and relapse of drug addiction)
Dermatologic effects (e.g. serious cutaneous reactions,
including vesiculobullous eruptions, SJS, and exfoliative
dermatitis)
Diabetes (may require adjustments in antidiabetic
medications)
380
ANTINEOPLASTIC AND IMMODULATING AGENTS
Growth impairment (height and weight may be decreased in
pediatric use; closely monitor growth in children during
Thyroid disorders
Gastrointestinal effects (e.g. GI hemorrhage, ulcerative and
hemorrhagic/ischemic colitis; may be severe and/or life-
threatening; Pancreatitis
Hepatic effects (monitor hepatic function closely during
use); Hepatitis B (transient and potentially severe
increases in serum ALT may occur during or after
treatment)
Renal impairment
Ophthalmic effects (e.g. decreased or loss of vision and
retinopathy, including macular edema, optic neuritis,
papilledema, retinal hemorrhages, serous retinal
detachment, cotton wool spots, and retinal artery or vein
thrombosis; prior to use, all patients should have a visual
exam)
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Abdominal pain, alopecia, anemia, anorexia,
anxiety, arthralgia, back pain, bacterial infection, blurred
vision, cough, depression, dermatitis, diaphoresis,
dizziness, dyspnea, diarrhea, eczema, fatigue, growth
suppression (children), headache, hepatic
decompensation, hyperthyroidism, hypothyroidism,
injection site reaction, fever, insomnia, irritability,
lymphocytopenia, lack of concentration, memory
impairment, mood changes, myalgia, nervousness,
neutropenia, nausea, pain, pruritus, rigors,
thrombocytopenia, vomiting, weakness, weight loss,
xeroderma, skin rash, xerostomia
Less Common: Aggressive behavior, anaphylaxis, angina
pectoris, angioedema, aplastic anemia, auditory
impairment, autoimmune disorders, bipolar mood
disorder, bronchiolitis obliterans, bronchoconstriction,
cerebral hemorrhage, chest pain, cholangitis, colitis,
coma, corneal ulcer, cardiac arrhythmia, dehydration,
dyspepsia, diabetes mellitus, erythema multiforme
major, endocarditis, dyspnea on exertion, exfoliative
dermatitis, GI hemorrhage, hallucination, hearing loss,
decreased hematocrit and hemoglobin, hepatic
insufficiency, exacerbation of hepatitis B, graft rejection
(hepatic, renal), hyperglycemia, hypersensitivity reaction,
hyperpigmentation, hypertension, hypoglycemia,
influenza, interstitial pneumonitis, liver steatosis,
macular edema, mania, myocardial infarction, myositis,
optic neuritis, pancreatitis, papilledema, peptic ulcer,
peripheral neuropathy, pneumonia, psychiatric
disturbance, psychosis, pulmonary embolism, pulmonary
infiltrates, pure red cell aplasia, retinal thrombosis (in
artery or vein), retinal cotton-wool spot, retinal
detachment, retinal hemorrhage, retinopathy,
rheumatoid arthritis, sarcoidosis, seizures, SJS,
substance overdose, SLE, supraventricular arrhythmia,
thrombotic thrombocytopenic purpura, suicidal ideation,
suicide, urticaria, vesiculobullous reaction, vision loss
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Ribavirin
(hemolytic anemia), Zidovudine
ANTINEOPLASTIC AND IMMODULATING AGENTS
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Aldesleukin (myocardial and renal toxicity), Clozapine
(agranulocytosis), Dipyrone (agranulocytosis;
pancytopenia), Telbivudine (peripheral neuropathy)
Increases serum concentration of Tizanidine
Reduces therapeutic effect of this drug:
BCG (Intravesical)
Administration: For SC administration, administer in the
abdomen or thigh. Rotate injection site. Administer on
the same day and at approximately the same time each
week.
NOTE: Due to differences in dosage, do NOT change brands
of interferons without the concurrence of healthcare
provider.
Pregnancy Category: C; X (combined with ribavirin)
ATC Code: L03AB11
IMMUNOSUPPRESSANTS
SELECTIVE IMMUNOSUPPRESSANTS
ANTILYMPHOCYTE
Rx IMMUNOGLOBULIN (ALG)
(EQUINE)
Inj.: 100 mg/5 mL vial (IV)
Polyclonal antibodies which is active against all lymphocyte
subsets. It is produced by the purification of sera from
immunized animals.
Indications: Adjunct to existing immunosuppressant
regimens to treat acute rejection episodes in organ or
tissue transplantation; prophylaxis in combination with
several immunosuppressant agents; severe aplastic
anemia
Dose:
Prophylaxis of renal graft rejection, by IV infusion, 15 mg/kg
daily for 14 days, then every other day for 14 days, to a
total of 21 doses in 28 days; give first dose within 24
hours before or after the transplant.
Treatment of renal graft rejection, by IV infusion, ADULT,
10–15 mg/kg daily for 14 days; may administer
additional alternate-day therapy, up to a total of 21
doses; CHILD, 5–25 mg/kg daily.
Aplastic anemia, by IV infusion, 10–20 mg/kg daily for 8–
14 days; may administer additional alternate-day
therapy, up to a total of 21 doses. (May refer to your
institutional guideline.)
Precautions:
Hemodialysis (clotting of arteriovenous fistulas may occur);
Hematologic effect (e.g. leukopenia or thrombocytopenia;
fulminant hemolysis rarely reported).
Infection (various infections, including CMV, or reactivation
of infection may occur)
Infusion site reactions (e.g. pain, swelling, or redness)
Malignancies (e.g. secondary malignancies, including
lymphoma and post-transplant lymphoproliferative
disease (PTLD))
Serum sickness (anaphylaxis may occur, some fatal;
respiratory distress may indicate an anaphylactoid
reaction)
Renal failure
Adverse Drug Reactions:
Common and Less Common: Arthralgia, abnormal
involuntary movements, abnormal renal and/or liver
function tests, acute renal failure, chills, bradycardia,
burning sensation in the soles or palms, chest and/or
back pain, CHF, dizziness, dyspnea, edema, fever, GI
disturbances, headache, hepatosplenomegaly,
hypertension, hypotension, iliac vein obstruction,infusion
site reactions, laryngospasm, leukopenia, malaise,
lymphadenopathy, myalgia, myocarditis, night sweats,
pain, paresthesia, proteinuria, pruritus, rash, renal artery
or deep-vein thrombosis, rigidity, seizures, soreness of
L
the mouth or throat, stomatitis, TEN, tachycardia,
thrombocytopenia, tremor, urticaria, weakness, wound
dehiscence
Rare: Fulminant hemolysis
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
devices:
Intrauterine Contraceptive Devices (infection)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Vaccines, Live (infection)
Reduces therapeutic effect of the following drugs:
Vaccines, Live (diminished immune response)
Administration: Dilute in an appropriate infusion solution
(i.e., sodium chloride 0.9% or glucose 5% plus sodium
chloride at either 0.225% or 0.45%). The final
concentration should not exceed 4 mg/mL
Administer the appropriately diluted infusion over at
least 4 hours, via an inline filter (0.2–1 micrometer), into
a vein with rapid blood flow to prevent thrombophlebitis.
NOTE: Premedication with antihistamines and/or
corticosteroids may prevent or reduce the intensity of
adverse effects.
A skin sensitivity test is recommended before the first
infusion.
Pregnancy Category: C
ATC Code: L04AA03
381
 ANTINEOPLASTIC AND IMMODULATING AGENTS

ANTITHYMOCYTE Drug Interactions:

Rx IMMUNOGLOBULIN (ATG) Monitor closely with:
Enhances therapeutic effect of Antithymocyte
(RABBIT) Immunoglobulin:
Trastuzumab (neutropenic effect)
Inj: 25 mg/5 mL vial (IV)
Increases risk of adverse or toxic effects of Antithymocyte
Polyclonal antibody which appears to cause Immunoglobulin:
immunosuppression by acting on T-cell surface antigens Denosumab (serious infection)
and depleting CD4 lymphocytes.
Reduces diagnostic effect of Coccidioides immitis Skin Test
Indications: Management of acute rejection of renal
transplant; used in conjunction with concomitant Avoid concomitant use with:
immunosuppression; severe aplastic anemia Enhances therapeutic effect of Antithymocyte
Immunoglobulin:
Contraindications: Acute or chronic infection Roflumilast (immunosuppressive effect)
Dose: Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy for the
Increases risk of adverse or toxic effects of Antithymocyte
treatment of renal transplant patients. Medical
Immunoglobulin:
surveillance is required during infusion.
Pimecrolimus
L

Tacrolimus, Topical
Acute renal transplant rejection, by IV infusion, 1.5 mg/kg
daily for 7–14 days. Increases risk of adverse or toxic effects of the following
Aplastic anemia, 3.5 mg/kg/day for 5 days; may administer drugs:
additional therapy Leflunomide (hematologic toxicity, i.e., pancytopenia,
agranulocytosis, thrombocytopenia); Natalizumab
Double check with FDA if approved indication (concurrent infection); Vaccines, Live (infection)

Dose Adjustment: Reduces therapeutic effect of the following drugs:

Obesity: BCG, Intravesical; Vaccines (diminished immune
Use actual body weight (full weight) for calculation of weight- response)
based dosing (mg/kg) for hematopoietic stemcell
transplant conditioning regimens. Administration: Infuse the first dose over at least 6 hours
through a high-flow vein. Administer subsequent doses
Toxicity: over at least 4 hours through an in-line 0.22–micron
If WBC count is 2,000–3,000 cells/mm3 or platelet count is filter.
50,000–75,000 cells/mm3, reduce dose by 50%. NOTE: Premedication with acetaminophen, antihistamines,
If WBC count is <2,000 cells/mm3 or platelet count is
and/or corticosteroids may reduce infusion-related
<50,000 cells/mm3, consider discontinuing treatment.
reactions.
Precautions:
Anaphylaxis Pregnancy Category: C
Cytokine release syndrome [CRS] (ranging from a mild, self-
limiting “flu-like reaction” to severe, life-threatening ATC Code: L04AA04
reactions with symptoms of hypotension, acute
respiratory distress syndrome, pulmonary edema,
myocardial infarction, and tachycardia) Rx EVEROLIMUS
Infection; Malignancy (lymphoma, post-transplant
lymphoproliferative disease [PTLD] or other
malignancies) Oral: 250 micrograms and 500 micrograms tablet
Hematologic toxicity (reversible neutropenia and
thrombocytopenia) Macrolide immunosuppressant and a mechanistic target ofr
apamycin (mTOR) inhibitor which has antiproliferative
Adverse Drug Reactions: and antiangiogenic properties.
Common: Abdominal pain, chills, antirabbit antibody
development, diarrhea, fever, cytomegalovirus infection, Indications: Prophylaxis of organ rejection in liver
dizziness, dyspnea, gastritis, GI moniliasis, headache, transplantation; prophylaxis of organ rejection in renal
herpes simplex infection, hyperkalemia, hypertension, transplant patients at low to moderate immunologic risk
malaise, nausea, leukopenia, oral moniliasis, pain,
peripheral edema, sepsis, systemic infection, Contraindications: Hypersensitivity to everolimus
tachycardia, thrombocytopenia, UTI, weakness
Less Common: Anaphylaxis, cytokine release syndrome,
PTLD, neutropenia, serum sickness

382
ANTINEOPLASTIC AND IMMODULATING AGENTS
Dose:
Breast cancer, advanced, hormone receptor-positive, HER2-
negative, by mouth, in combination with exemestane, 10
mg once daily, continue until no longer clinically
beneficial or until unacceptable toxicity.
Advanced pancreatic neuroendocrine tumors (PNET), renal
angiomyolipoma, or renal cell cancer (RCC), by mouth,
10 mg once daily, continue until no longer clinically
beneficial or until unacceptable toxicity.
Liver transplantation, rejection prophylaxis, by mouth, in
combination with reduced doses of tacrolimus and
corticosteroids, initially 1 mg twice daily beginning at
least 30 days post-transplant; adjust maintenance dose
if needed at a 4 to 5-day interval based on serum
concentrations, tolerability, and response; goal serum
concentration is between 3 and 8 nanograms/mL; if
trough is <3 nanograms/mL, double total daily dose; if
trough >8 nanograms/mL on 2 consecutive measures,
decrease dose by 0.25 mg twice daily.
Renal transplantation, rejection prophylaxis, by mouth, in
combination with induction of basiliximab, and
concurrently with corticosteroids and reduced doses of
cyclosporine, initially 0.75 mg twice daily; adjust
maintenance dose if needed at a 4 to 5-day interval
based on serum concentrations, tolerability, and
response; goal serum concentration is between 3 and 8
nanograms/mL; if trough is <3 nanograms/mL, double
total daily dose; if trough >8 nanograms/mL on 2
consecutive measures, decrease dose by 0.25 mg twice
daily.
Subependymal giant cell astrocytoma (SEGA), by mouth,
ADULT and CHILD ≥1 year, initially 4.5 mg/m2 once daily;
round to nearest tablet size; if trough <5 nanograms/mL,
increase dose by 2.5 mg daily; if trough >15
nanograms/mL, reduce dose by 2.5 mg daily; if dose
reduction necessary inpatients receiving the lowest
strength available, administer every other day;
Dose Adjustment:
Concomitant CYP3A4 Inducer or Inhibitor and/or P-
glycoprotein Inhibitor use:
For patients receiving concomitant strong CYP3A4 and/or p-
glycoprotein inducers (e.g., carbamazepine,
phenobarbital, phenytoin, rifabutin, rifampin,
rifapentine), double everolimus dose using increments of
≤5 mg with careful monitoring up to a maximum
dailydose of 20 mg. If inducer is discontinued, allow 3–5
days prior to reducing the everolimus dose to
recommended starting dose.
For patients receiving concomitant moderate CYP3A4
and/or p-glycoprotein inhibitors (e.g., amprenavir,
aprepitant, diltiazem, erythromycin, fluconazole,
fosamprenavir, verapamil), reduce everolimus dose to
2.5 mg once daily; increase from 2.5–5 mg once daily
based on patient tolerance; further reductions may be
necessary for adverse reactions; if dose reduction is
required for patients receiving the lowest available
strength, consider alternate-day dosing. If inhibitor is
discontinued, allow 2–3 days prior to reducing the
everolimus dose to recommended starting dose.
Renal transplantation:
Adjust dose based on everolimus serum concentrations.
Hepatic Impairment:
Mild impairment (Child-Pugh class A):
Breast cancer, PNET, RCC, renal angiomyolipoma, 7.5 mg
once daily; may further reduce to 5 mg once daily if not
tolerated.
Liver or renal transplantation, reduce initial dose by ~33%;
individualize subsequent dosing based on therapeutic
drug monitoring; target trough concentration is 3–8
nanograms/mL.
SEGA, 75% of usual dose based on calculated BSA, rounded
to the nearest strength; target trough concentration is 5–
15 nanograms/mL; may increase dose within the target
range to achieve higher concentrations as tolerated
Moderate impairment (Child-Pugh class B):
Breast cancer, PNET, RCC, renal angiomyolipoma, 5 mg
once daily; may further reduce to 2.5 mg once daily if not
tolerated.
Liver or renal transplantation, reduce initial dose by ~50%;
individualize subsequent dosing based on therapeutic
drug monitoring; target trough concentration is 3–8
nanograms/mL.
SEGA, 50% of usual dose based on calculated BSA, rounded
to the nearest strength; target trough concentration is 5–
15 nanograms/mL; may increase dose within the target
L
range if tolerated.
Severe impairment (Child-Pugh class C):
Breast cancer, PNET, RCC, renal angiomyolipoma,
maximum dose is 2.5 mg once daily.
Liver or renal transplantation, reduce initial dose by ~50%;
individualize subsequent dosing based on therapeutic
drug monitoring; target trough concentration is 3–8
nanograms/mL.
Precautions:
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
laboratory and supportive medical resources must be
readily available.
NOT recommended for use in heart transplant; has
immunosuppressant properties which may result in
infection.
Use may result in the development of malignancy,
including lymphoma and skin cancer.
An increased risk of renal arterial and venous
thrombosis has been reported with use in renal
transplantation, which may result in graft loss.
Angioedema
Edema (generalized edema, including peripheral edema
and lymphedema, and local fluid accumulation, e.g.,
pericardial effusion, pleural effusion, or ascites)
Bone marrow suppression; Malignancy
Fertility effects (e.g. menstrual irregularities, secondary
amenorrhea, and increases in luteinizing hormone and
follicle-stimulating hormone in females may occur;
azoospermia and oligospermia in males; may cause
infertility).
Hepatic artery thrombosis; Hepatic impairment
Hereditary galactose intolerance (may result in diarrhea and
malabsorption);
Metabolic effects (e.g. hyperglycemia, hyperlipidemia, and
hypertriglyceridemia; increased risk for new-onset
diabetes)
383

Infections (sepsis, respiratory failure, hepatic failure, or
fatality may occur; polyomavirus infection in transplant
patients may be serious and/or fatal; reactivation of
hepatitis B)
Mucositis or stomatitis
Nephrotoxicity (e.g. elevations in serum creatinine, renal
failure, and proteinuria; an increased incidence of rash,
infection and dose interruptions have been reported in
patients with CrCl ≤60 mL/minute)
Pulmonary toxicity (e.g. noninfectious pneumonitis,
interstitial lung disease (ILD), and/or noninfectious
fibrosis, some fatal)
Wound healing complication (may delay wound healing and
increase the occurrence of wound-related
complications)
Adverse Drug Reactions:
Common: Abdominal distention, abdominal pain, abnormal
hepatic function tests, acidosis, acneiform eruption,
acne vulgaris, agitation, alopecia, amenorrhea, anemia,
angina pectoris, angioedema, anorexia, anxiety,
arthralgia, ascites, atelectasis, atrial fibrillation, back
pain, bacteremia, behavioral problems, BK virus
L
infection, bladder spasm, blurred vision, bronchitis,
candidiasis, cardiac failure, cataract, cellulitis, chest
discomfort, chest pain, chills, conjunctivitis,
constipation, cough, cushingoid appearance,
cyanocobalamin deficiency, cystitis, decreased appetite,
deep vein thrombosis, dehydration, depression, diabetes
mellitus (new onset), diaphoresis, diarrhea, dizziness,
drowsiness, dyspepsia, dysgeusia, dysphagia,
dysmenorrhea, dyspnea, dysuria, edema, eyelid edema,
epigastric distress, epistaxis, erectile dysfunction,
erythema, fatigue, fever, flatulence, fluid retention,
folliculitis, gastroenteritis, GERD, gingival hyperplasia,
gout, hallucination, headache, hematemesis, hematuria,
herpes virus infection, hemiparesis, hemorrhage,
hemorrhoids, hepatitis (non-infectious), hepatitis C,
hirsutism, hydronephrosis, hypercalcemia,
hypercholesterolemia, hyperparathyroidism,
hyperglycemia, hyperkalemia, hypermenorrhea,
hypersensitivity, hypertension, hypertensive crisis,
hypertrichosis, hypertriglyceridemia, hyperuricemia,
hypocalcemia, hypoesthesia, hypoglycemia,
hypokalemia, hypomagnesemia, hyponatremia,
hypophosphatemia, hypotension, incisional pain,
infection, influenza, irregular menses, insomnia,
interstitial nephritis, iron deficiency, intestinal
obstruction, jaw pain, joint swelling, lethargy,
leukocytosis, leukopenia, lower respiratory tract
infection, lymphadenopathy, limb pain,
lymphocytopenia, lymphorrhea, malaise, menstrual
disease ,migraine, mucositis, muscle spasm,
musculoskeletal pain, myalgia, myasthenia, nail disease,
nasal congestion, nasopharyngitis, nausea, neoplasm,
neuralgia, neutropenia, night sweats, onychomycosis,
oral candidiasis, onychoclasis, oral herpes, oral mucosa
ulcer, oropharyngeal pain, otitis media,osteomyelitis,
osteonecrosis, osteoporosis, ovarian cyst, palmar-
plantar erythrodysesthesia, pain, palpitations,
pancytopenia, paresthesia, perinephric abscess,
perinephric hematoma, peripheral edema, peritoneal
effusion, pharyngolaryngeal pain, peritonitis, pleural
effusion, pneumonia, pneumonitis, pollakiuria, polyuria,
postoperative wound complication (incisional hernia,
lymphocele, seroma, wound dehiscence, wound healing
384
ANTINEOPLASTIC AND IMMODULATING AGENTS
impairment), pyuria, procedural pain, prolonged PTT,
proteinuria, pulmonary edema, pulmonary embolism,
renal artery thrombosis, pruritus, pyelonephritis, renal
failure, renal insufficiency, renal tubular necrosis,
respiratory tract infection, rhinitis, rhinorrhea, scrotal
edema, sepsis, sinus congestion, sinusitis, skin lesion,
spondylitis, stomatitis, streptococcal pharyngitis,
syncope, tachycardia, thrombocytopenia, tinea pedis,
tremor, thrombocythemia, upper respiratory tract
infection, urethritis, urinary retention, urinary tract
infection, urinary urgency, uterine hemorrhage, vaginal
hemorrhage, venous thromboembolism, viral infection,
vomiting, weakness, weight loss, wheezing, wound
infection, xeroderma, xerostomia
Less Common: Ageusia, arterial thrombosis, aspergillosis,
azoospermia, cardiac arrest, cholecystitis, cholelithiasis,
complex regional pain syndrome, contact dermatitis,
eczema, excoriation, gastritis, infertility (male), hemolytic
uremic syndrome, hypersensitivity angiitis, pancreatitis,
nephrotoxicity, noninfectious pneumonitis, oligospermia,
pericardial effusion, pharyngitis, pityriasis rosea,
Pneumocystis jiroveci, polyoma pneumonia, HBV
reactivation, progressive multifocal
leukoencephalopathy, respiratory distress, seizure,
thrombosis of vascular graft (kidney), thrombotic
thrombocytopenic purpura
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Everolimus:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Everolimus:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors, e.g., Captopril, Enalapril (angioedema)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of the following drugs:
Antidiabetic Agents e.g. Gliclazide
Avoid concomitant use with:
Decreases serum concentration of Everolimus:
Dabrafenib, Efavirenz
Enhances therapeutic effect of Everolimus:
Roflumilast (immunosuppressive effect), Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Everolimus:
Cyclosporine, Systemic (nephrotoxicity), Dipyrone
(agranulocytosis, pancytopenia); Pimecrolimus;
Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Leflunomide (hematologic
toxicity), Natalizumab, (concurrent infection), Vaccines
(Live) (infection)
ANTINEOPLASTIC AND IMMODULATING AGENTS
Increases serum concentration of Everolimus:
Conivaptan, Cyclosporine (Systemic), Fusidic Acid
(Systemic), Idelalisib, Mifepristone, P-glycoprotein /
ABCB1 Inhibitors
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines
FOOD INTERACTION. Grapefruit Juice may increase the
serum concentration of Everolimus.
Administration: May be taken with or without food. Take
consistently with regard to food to reduce variability.
Swallow whole with a glass of water. Do NOT break,
chew, or crush. Do NOT administer crushed or broken
tablets. Avoid contact with or exposure to crushed or
broken tablets.
NOTE: Limit exposure to sunlight and ultraviolet light by
wearing protective clothing and using effective
sunscreen to minimize the risk for skin cancer.
For breast cancer, pancreatic neuroendocrine tumors,
renal cell cancer, renal angiolipoma, or SEGA, administer
at the same time each day.
For liver transplantation, administer consistently ~12
hours apart, at the same time as tacrolimus.
For renal transplantation, administer consistently ~12
hours apart, at the same time as cyclosporine.
Pregnancy Category: C
ATC Code: L04AA18
Rx MYCOPHENOLATE MOFETIL
Oral: 500 mg tablet
It provides a cytostatic effect on T and B lymphocytes. It
inhibits inosine monophosphate dehydrogenase
(IMPDH), which inhibits denovo guanosine nucleotide
synthesis, thus limiting T and B lymphocyte proliferation.
Indication: Prophylaxis of organ rejection
Contraindication: Hypersensitivity to mycophelate mofetil
Dose:
NOTE: Identify dosing with caution due to possibility of
increased hepatic, renal, or cardiac dysfunction.
Renal transplant, by mouth, ADULT, CHILD, and INFANT ≥3
months or BSA >1.5 m2, 1 g twice daily; doses>2 g daily
are not recommended; 1 g twice daily.
Cardiac transplant or hepatic transplant, by mouth, ADULT,
1.5 g twice daily.
Dose Adjustment:
Renal Impairment:
In renal transplant patients with GFR <25 mL/minute per
1.73 m2 outside the immediate post-transplant period,
>1 g twice daily.
Precautions:
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
laboratory and supportive medical resources must
be readily available.
Do NOT use mycophenolate mofetil and
mycophenolic acid dosage forms interchangeably
due to differences in absorption.
May lead to an increased susceptibility to
bacterial, viral, fungal, and protozoal infections,
including opportunistic infections.
May lead to an increased risk of development of
L
lymphoma and other malignancies, i.e., skin.
Associated with an increased risk of congenital
malformations and first trimester pregnancy loss
when used by pregnant women. Females of
reproductive potential must be counseled about
pregnancy prevention and planning.
Gastrointestinal disorders (e.g. gastric or duodenal ulcers,
GI bleeding and/or perforation)
Hypoxanthine-guaninephosphoribosyl transferase
deficiency
Lymphoproliferative disorders; Neutropenia; Pure red cell
aplasia [PRCA]
Infections; New or reactivated viral infections (e.g.
polyomavirus associated nephropathy (PVAN), JC virus-
associated progressive multifocal leukoencephalopathy
(PML), cytomegalovirus (CMV) infections, and
reactivation of hepatitis B (HBV) or hepatitis C (HCV))
Renal impairment (increased toxicity).
Pregnancy (consider alternative agents for women planning
pregnancy; external ear abnormalities, cleft lip and
palate, anomalies of the distal limbs, heart, esophagus,
kidney, and nervous system have been reported;
spontaneous abortions have been noted; discontinue at
least 6 weeks prior to trying to conceive).
Elderly (at an increased risk of certain infections, GI
hemorrhage, and pulmonary edema).
Adverse Drug Reactions:
Common: Abdominal pain, abscess, acidosis, acne,
agitation, albuminuria, increased, alkalosis, alopecia,
amblyopia, anemia, angina, anorexia, anxiety, apnea,
arrhythmia, arterial thrombosis, arthralgia, ascites,
asthma, atelectasis, atrial fibrillation, atrial flutter, back
pain, bradycardia, bronchitis, bruising, Candida
infection, cardiac arrest, cardiac failure, cataract,
cellulitis, chest pain, chills with fever, cholangitis,
cholestatic jaundice, CMV tissue invasive disease, CMV
viremia or syndrome, coagulation disorder, confusion,
conjunctivitis, constipation, cough, cyst, Cushing's
syndrome, dehydration, delirium, depression, diabetes
385

mellitus, diaphroresis, diarrhea, dizziness, dyspepsia,
dysphagia, dyspnea, dysuria, ear disorder, edema,
emotional lability, enlarged abdomen, epistaxis,
esophagitis, extrasystole, eye hemorrhage, facial edema,
fever, flatulence, gout, flu-like syndrome, fungal
dermatitis, gastritis, gum hyperplasia, gastroenteritis, GI
hemorrhage, GI moniliasis, hyper-hypophosphatemia,
increased gamma glutasyl transferase, gingivitis,
hallucinations, headache, hematuria, hemoptysis,
hemorrhage, hernia, herpes simplex infection, herpes
zoster cutaneous disease, hiccup, hirsutism,
hydronephrosis, hypercalcemia, hypocalcemia,
hypercholesterolemia, hyper/hypovolemia, ileus,
hyperglycemia, hyperkalemia, hyperlipemia,
hypertension, hypertonia, hyperuricemia,
hyperventilation, hypochloremia, hypoesthesia,
hypoglycemia, hypokalemia, hypomagnesemia,
hyponatremia, hypoproteinemia, hypotension,
hypothyroidism, hypoxia, infection, impotence, infection,
insomnia, joint disorder, lacrimation disorder, leg
cramps, leukocytosis, leukopenia, liver damage, lung
disorder, malaise, melena, mouth ulceration, myalgia,
myasthenia, nausea, neck pain, neoplasm, nervousness,
L
neuropathy, neutropenia, oral moniliasis, orthostatic
hypotension, osteoporosis, pain, pallor, palpitation,
pancytopenia, parathyroid disorder, paresthesia, pelvic
pain, pericardial effusion, peripheral edema, peripheral
vascular disorder, peritonitis, petechia, pharyngitis,
pleural effusion, pneumonia, pneumothorax,
polycythemia, prostatic disorder, prothrombin time
increased, pruritus, psychosis, pulmonary edema,
pulmonary hypertension, pyelonephritis, rash, renal
failure, respiratory acidosis, respiratory moniliasis,
respiratory tract infection, rhinitis, scrotal edema,
seizure, sepsis, sinusitis, skin carcinoma, skin
hypertrophy, skin ulcer, somnolence, sputum increased,
stomach disorder, stomach ulcer, stomatitis,
supraventricular extrasystoles, supraventricular
tachycardia, tachycardia, thirst, syncope, thinking
abnormal, thrombocytopenia, increased thromboplastin
time, thrombosis, tinnitus, tremor, urinary tract disorder,
vasodilation, vasospasm, increased venous pressure,
ventricular extrasystole, ventricular tachycardia, vertigo,
vesiculobullous rash, vision abnormal, voice alteration,
vomiting, weakness, weight gain/loss, xerostomia
Less Common: Atypical mycobacterial infection, BK virus-
associated nephropathy, bronchiectasis, colitis, GI
perforation, infectious endocarditis, interstitial lung
disorder, intestinal villous atrophy, lymphoproliferative
disease, lymphoma, malignancy, meningitis, progressive
multifocal leukoencephalopathy, pancreatitis,
pulmonary fibrosis (fatal), pure red cell aplasia,
tuberculosis
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Mycophenolate:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Mycophenolate:
Denosumab (serious infection)
Reduces diagnostic effect of Coccidioides immitis Skin Test
386
ANTINEOPLASTIC AND IMMODULATING AGENTS
Avoid concomitant use with:
Decreases serum concentration of Mycophenolate:
Bile Acid Sequestrants, e.g. Ursodeoxycholic Acid,
Cholestyramine Resin, Cyclosporine, Magnesium Salts,
Rifamycin Derivatives, e.g., Rifampicin, Rifaximin,
Sevelamer
Decreases serum concentration of the following drugs:
Contraceptives, Estrogens and Progestins
Enhances therapeutic effect of Mycophenolate:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Mycophenolate:
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity), Natalizumab
(concurrent infection), Live Vaccines (infection)
Increases serum concentration of Mycophenolate:
Probenecid
Reduces absorption of Mycophenolate:
Antacids [except Sodium Bicarbonate]
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines (immune response)
Administration: To be taken on an empty stomach, 1 hour
before or 2 hours after meals, to avoid variability in
mycophenolate absorption.
May be administered with food in stable renal transplant
patients when necessary.
MISSED DOSE: Administer as soon as remembered. If it is
close to the next scheduled dose, skip the missed dose
and resume at next regularly scheduled time. Do NOT
double a dose to make up for a missed dose.
Females of reproductive potential should have a
negative pregnancy test with a sensitivity of ≥25 mIU/mL
immediately before therapy and the test should be
repeated 8–10 days later. Pregnancy tests should be
repeated during routine follow-up visits. They are also
required to have contraceptive counseling and use
acceptable birth control unless heterosexual intercourse
is completely avoided. Intrauterine device, tubal
sterilization, or vasectomy of the female patient's partner
are acceptable contraceptive methods that can be used
alone. Hormonal contraceptives require the use of an
additional barrier method because mycophenolate
affects the effectiveness of hormonal contraceptive
agents.
NOTE: Limit exposure to sunlight and ultraviolet light by
wearing protective clothing and using effective
sunscreen to minimize the risk for lymphoproliferative
disorders.
Pregnancy Category: D
ANTINEOPLASTIC AND IMMODULATING AGENTS
ATC Code: Not available
MYCOPHENOLIC ACID
Rx
(AS MYCOPHENOLATE SODIUM)
Oral: 360 mg tablet
Mycophenolic acid has a cytostatic effect on T and B
lymphocytes. It inhibits inosine monophosphate
dehydrogenase (IMPDH), which inhibits de novo
guanosine nucleotide synthesis, thus limiting T and B
lymphocyte proliferation.
Indication: Prophylaxis of organ rejection
Contraindication: Hypersensitivity to mycophenolic acid
Dose:
Renal transplant, by mouth, ADULT, 720 mg twice daily
(total daily dose, 1440 mg); CHILD ≥5 years, usual dose,
400 mg/m2 per dose twice daily (maximum dose, 720
mg twice daily);
Dose Adjustment:
Weight-based:
For BSA >1.58 m2, 720 mg twice daily (maximum, 1,440 mg
daily).
For BSA 1.19–1.58m2, 540 mg twice daily (maximum,
1,080 mg daily).
For BSA <1.19 m2, use is not recommended
Administration: To be taken on an empty stomach, 1 hour
before or 2 hours after meals, to avoid variability in
mycophenolate absorption.
May be administered with food in stable renal transplant
patients when necessary.
MISSED DOSE: Administer as soon as remembered. If it is
close to the next scheduled dose, skip the missed dose
and resume at next regularly scheduled time. Do NOT
double a dose to make up for a missed dose.
Females of reproductive potential should have a
negative pregnancy test with a sensitivity of ≥25 mIU/mL
immediately before therapy and the test should be
repeated 8–10 days later. Pregnancy tests should be
repeated during routine follow-up visits. They are also
required to have contraceptive counseling and use
acceptable birth control unless heterosexual intercourse
is completely avoided. Intrauterine device, tubal
sterilization, or vasectomy of the female patient's partner
are acceptable contraceptive methods that can be used
alone. Hormonal contraceptives require the use of an
additional barrier method because mycophenolate
affects the effectiveness of hormonal contraceptive
agents.
NOTE: Limit exposure to sunlight and ultraviolet light by
wearing protective clothing and using effective
sunscreen to minimize the risk for lymphoproliferative
disorders.
See Mycophenolate Mofetil under Immunosuppressants –
Selective Immunosuppressants in Chapter 8:
Antineoplastic and Immunomodulating Agents for other
information.
Pregnancy Category: D
ATC Code: L04AA06
Rx SIROLIMUS
Oral: 0.5 mg and 1 mg tablet
Inhibits the regulatory kinase, mTOR (mechanistic target of
rapamycin). This inhibition suppresses cytokine
mediated T-cell proliferation and the proliferation of
lymphangioleiomyomatosis cells, thus preventing acute
rejection of allografts and prolongs graft survival.
Indications: Management of lymphangioleiomyomatosis;
prophylaxis of organ rejection in renal transplants
L
Dose:
Low-to-moderate immunologic risk renal transplant, by
mouth, ADULT and CHILD ≥13 years or<40 kg, in
combination with cyclosporine and corticosteroids,
initially, 3 mg/m2 on day 1 as loading dose, followed by 1
mg/m2 once daily as maintenance;
ADULT and CHILD ≥13 years or ≥40 kg, 6 mg on day 1 as
loading dose, followed by 2 mg once daily as
maintenance
[NOTE: May be withdrawn after 2–4 months, in conjunction with
an increase in sirolimus dosage].
High immunologic risk renal transplant patients, by mouth,
ADULT, in combination with cyclosporine and
corticosteroids for the first year, 15 mg on day 1 as
loading dose, followed by 5 mg daily as maintenance;
obtain trough concentration between days 5–7 and
adjust accordingly; continue concurrent cyclosporine +
sirolimus + corticosteroid therapy for 1 year following
transplantation; further adjustment of the regimen must
be based on clinical status [NOTE: Adjustment of
immunosuppressive therapy beyond 12 months should
be considered based on clinical judgment].
Lymphangioleiomyomatosis, by mouth, ADULT, initially 2 mg
once daily; obtain trough concentration in 10–20 days
and adjust dose to maintain a target concentration of 5–
15 nanograms/mL.
Note: Maximum dose for all approved indications (Adults,
Geriatric, Adolescents) is 40 mg/day.
Dose Adjustment:
Hepatic Impairment:
For mild-to-moderate impairment (Child-Pugh classes A and
B), reduce maintenance dose by ~33%.
For severe impairment (Child-Pugh class C), reduce
maintenance dose by ~50%.
Precautions:
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
laboratory and supportive medical resources must be
readily available.
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 ANTINEOPLASTIC AND IMMODULATING AGENTS

segmental glomerulosclerosis, gingival hyperplasia,

Therapeutic drug monitoring is recommended,
headache, hemolytic-uremic syndrome, hepatic
however, variations in methods to determine
necrosis, herpes simplex infection, hepatotoxicity,
sirolimus whole blood concentrations, as well as
hyperglycemia, herpes zoster, hypercholesterolemia,
interlaboratory variations, may result in improper
incisional hernia, hypermenorrhea, hypersensitivity
dosage adjustments, which may lead to
angiitis, hypertension, hypertriglyceridemia,
subtherapeutic or toxic levels. Determine the assay
hypophosphatemia, hypervolemia, increased
method used to assure consistency, and be aware of
susceptibility to infection, hypokalemia, interstitial
alterations to assay method or reference range and
pulmonary disease (dose-related), joint disorders,
that values from different assays may not be
leukopenia, lymphedema, lymphocele, lympho
interchangeable.
proliferative disorder, pain, menstrual disease, myalgia,
May cause increased susceptibility to infection and the mycobacterium infection, nasopharyngitis, nausea,
development of lymphoma and other malignancies. nephrotic syndrome, neutropenia, osteonecrosis,
ovarian cyst, pancreatitis, pancytopenia, pericardial
NOT recommended for use in liver transplantation. effusion, pleural effusion, pneumonia due to
Associated with an increased risk of hepatic artery Pneumocystis jiroveci (P. carinii), peripheral edema,
thrombosis (HAT), graft failure, and increased pneumonia, progressive multifocal
mortality with evidence of infection. leukoencephalopathy, proteinuria, pseudomembranous
colitis, pulmonary alveolitis, pulmonary hemorrhage,
NOT recommended for use in lung transplantation. pulmonary embolism, pyelonephritis, renal disease,
Bronchial anastomotic dehiscence cases have been sepsis, skin carcinoma, reversible posterior
reported, mostly fatal. leukoencephalopathy syndrome, skin rash, stomatitis,
tachycardia, thrombocytopenia, thrombotic
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thrombocytopenic purpura, upper respiratory tract

Anaphylactic or hypersensitivity reactions (e.g. anaphylactic infection, tuberculosis, urinary tract infection, weight
or anaphylactoid reactions, angioedema, exfoliative loss, wound dehiscence, wound healing impairment
dermatitis, and hypersensitivity vasculitis); angioedema
Infections (opportunistic infections including activation of Drug Interactions:
latent viral infections, fatal infections, and sepsis may Monitor closely with:
occur; progressive multifocal leukoencephalopathy Enhances therapeutic effect of Sirolimus:
(PML), an opportunistic CNS infection caused by Trastuzumab (neutropenic effect)
reactivation of the JC virus, has been reported)
Interstitial lung disease (e.g. pneumonitis, bronchiolitis Increases risk of adverse or toxic effects of Sirolimus:
obliterans organizing pneumonia [BOOP], pulmonary Denosumab (serious infections)
fibrosis; may be fatal; may be associated with pulmonary
hypertension). Increases risk of adverse or toxic effects of ACE Inhibitors,
Hemolytic uremic syndrome (HUS); Thrombotic e.g., Captopril, Enalapril
thrombocytopenic purpura, or thrombotic
microangiopathy; Reduces diagnostic effect of Coccidioides immitis Skin Test
Hyperlipidemia
Lymphocele or fluid accumulation (e.g. peripheral edema, Reduces therapeutic effect of the following drugs:
lymphedema, ascites, and pleural and pericardial Antidiabetic Agents, Sipuleucel-T
effusions)
Malignancy (increased risk of other malignancies such as Avoid concomitant use with:
skin cancer) Decreases serum concentration of Sirolimus:
Proteinuria (may increase urinary protein excretion; new Dabrafenib, Efavirenz, Enzalutamide, Fosphenytoin,
onset nephrotic syndrome has been reported) Mitotane, Phenytoin, Rifampin
Renal effects (may increase serum creatinine and decrease
GFR; may delay recovery of renal function in patients Decreases serum concentration of Tacrolimus (Systemic)
with delayed allograft function)
Wound dehiscence or healing (may cause wound Enhances therapeutic effect of Sirolimus:
dehiscence and impaired healing) Roflumilast (immunosuppressive effect)
Children (safety and efficacy of de novo use of sirolimus
without cyclosporine have not been established; safety Enhances therapeutic effect of Tofacitinib
and efficacy have not been established in <13 years or (immunosuppressive effect)
in renal transplant patients <18 years).
Increases risk of adverse or toxic effects of Sirolimus:
Adverse Drug Reactions: Pimecrolimus, Tacrolimus
Common and Less Common: Abdominal pain, abnormal
hepatic function tests, acne vulgaris, amenorrhea, Increases risk of adverse or toxic effects of the following
anemia, anaphylactoid reaction, anaphylaxis, drugs:
angioedema, arthralgia, ascites, azoospermia, cardiac Clozapine (agranulocytosis), Cyclosporine (Systemic)
tamponade, chest pain, constipation, cytomegalovirus, (calcineurin inhibitor-induced hemolytic uremic
deep vein thrombosis, dehiscence (fascial), diabetes syndrome, thrombotic thrombocytopenic purpura, or
mellitus, diarrhea, dizziness, edema, epistaxis, Epstein- thrombotic microangiopathy), Dipyrone
Barr infection, exfoliative dermatitis, fluid retention, focal (agranulocytosis; pancytopenia), Leflunomide

388
ANTINEOPLASTIC AND IMMODULATING AGENTS

(hematologic toxicity such as pancytopenia, Precautions:

agranulocytosis, and/or thrombocytopenia),
WARNING: Should only be used by physicians
Natalizumab (concurrent infection), Tacrolimus
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
Increases serum concentration of Sirolimus:
laboratory and supportive medical resources must
Boceprevir, Conivaptan, Crizotinib, Cyclosporine
be readily available.
(Systemic), Dasabuvir, Fluconazole, Fusidic Acid
(Systemic), Itraconazole, Ketoconazole (Systemic), Re-exposure to basiliximab with a subsequent
Macrolide Antibiotics [except Azithromycin, Fidaxomicin, course of therapy should only be done with
Spiramycin], Mifepristone, Ritonavir, Telaprevir; extreme caution.
Vaccines, Live (infection), Voriconazole

Reduces therapeutic effect of the following drugs: Anaphylactoid/hypersensitivity reactions

BCG (Intravesical), Vaccines (immune response) Diabetes (new-onset diabetes)
Human antimurine antibodies [HAMA] (lymphoproliferative
FOOD INTERACTION. Grapefruit Juice may decrease the clearance of disorders (may increase incidence)); opportunistic
Sirolimus. infections (may increase incidence))

Administration: Administer consistently with regards to Adverse Drug Reactions:

meals. Ingestion with high-fat meals decreases peak Common: Abdominal pain, abnormal heart sounds,
concentrations but increases AUC by 23–35%. abnormal vision, accidental trauma, acidosis, acne,
agitation, albuminuria, anemia, angina, anxiety,
Administer initial dose as soon as possible after arrhythmia (tachycardia), arthralgia, arthropathy, atrial

L
transplant. To be taken 4 hours after oral cyclosporine. fibrillation, back pain, bladder disorder, bronchitis,
bronchospasm, cataract, chest pain, conjunctivitis,
Do NOT crush, split, or chew the tablet. constipation, cough, cramps, cyst, cytomegalovirus
(CMV) infection, dehydration, depression, diabetes
NOTE: Limit exposure to sunlight and ultraviolet light by mellitus, diarrhea, fever, dizziness, dyspepsia, dyspnea,
wearing protective clothing and using effective dysuria, fluid overload, enlarged abdomen, esophagitis,
sunscreen to minimize the risk for malignancy. fatigue, flatulence, fracture, gastroenteritis, generalized
edema, genital edema (male), GI hemorrhage, gingival
Pregnancy Category: C hyperplasia, increased glucocorticoids, headache, heart
failure, hematoma, hematuria, hernia, herpes infection
ATC Code: L04AA10 (simplex and zoster), hypercholesterolemia, hyper-
/hypocalcemia, hyper-/hypokalemia, hyperglycemia,
insomnia, hyperlipemia, hypertension, hypertrichosis,
INTERLEUKIN INHIBITORS hyperuricemia, impotence, hypoesthesia, hypoglycemia,
hypomagnesemia, hyponatremia, leg pain, hypotension,
infection, upper respiratory infection, leukopenia,
Rx BASILIXIMAB moniliasis, malaise, melena, myalgia, nausea,
neuropathy, oliguria, pain, paresthesia, peripheral
edema, pharyngitis, pneumonia, polycythemia, pruritus,
Inj.: 20 mg vial (IV infusion)
pulmonary edema, purpura, rash, renal tubular necrosis,
rhinitis, rigors, sepsis, sinusitis, skin disorder, skin
Chimeric (murine/human) immunosuppressant monoclonal
ulceration, tremor, stomatitis, thrombocytopenia,
antibody, which blocks the alpha-chain of the interleukin-
thrombosis, ureteral disorder, urinary frequency, urinary
2 (IL-2) receptor complex. This receptor is expressed on
retention, urinary tract infection, viral infection, vomiting,
activated T-lymphocytes and is a critical pathway for
weakness, weight gain, wound complications
activating cell-mediated allograft rejection.
Less Common: Anaphylaxis, capillary leak syndrome,
cytokine release syndrome, diabetes (new onset),
Indication: Prophylaxis of acute organ rejection in renal
lymphoproliferative disease, hypersensitivity reaction
transplantation
Drug Interactions:
Dose:
Monitor closely with:
Acute renal transplant rejection prophylaxis, by IV infusion,
Enhances therapeutic effect of Basiliximab:
ADULT and CHILD≥35 kg, with cyclosporine and
Trastuzumab (neutropenic effect)
corticosteroids, 20 mg within 2 hours prior to transplant
surgery, followed by a second 20 mg dose 4 days after
Increases risk of adverse or toxic effects of
transplantation; withhold second dose if complications
Basiliximab:
occur;
Denosumab (serious infections)
CHILD<35 kg, with cyclosporine and corticosteroids, 10
mg within 2 hours prior to transplant surgery, followed by
Reduces diagnostic effect of Coccidioides immitis Skin Test
a second 10 mg dose 4 days after transplantation; the
second dose should be withheld if complications occur
Avoid concomitant use with:
(including severe hypersensitivity reactions or graft loss).
Enhances therapeutic effect of Basiliximab:
Roflumilast (immunosuppressive effect)

389

Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Basiliximab:
Pimecrolimus, Tacrolimus (Topical),
Increases risk of adverse or toxic effects of the following
drugs:
Belimumab, Leflunomide (hematologic toxicity, such as
pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Live Vaccines (infection)
Reduces therapeutic effect of the following drugs:
BCG (Intravesical), Vaccines
Administration: For IV administration only. Administer by IV
bolus infusion or IV infusion over 20–30 minutes.
Administer only after assurance that patient will receive
renal graft and immunosuppression.
L
NOTE: Bolus dosing is associated with nausea, vomiting,
and local pain at the injection site.
Pregnancy Category: B
ATC Code: L04AC02
CALCINEURIN INHIBITORS
Rx CYCLOSPORINE (CICLOSPORIN)
Oral: 25 mg, 50 mg, and 100 mg capsule
100 mg/mL solution, 50 mL
Opthalmic emulsion: 0.05%, 0.4 mL bottle
Inhibits the production and release of interleukin II and
inhibits interleukin II-induced activation of resting T-
lymphocytes.
Indications: Prophylaxis of organ rejection in kidney, liver,
and heart transplants; prophylaxis of graft rejection
following bone marrow transplantation; treatment of
chronic organ rejection; treatment of severe, active
rheumatoid arthritis (RA) not responsive to methotrexate
alone; treatment of severe, recalcitrant plaque psoriasis
in non-immunocompromised adults unresponsive to or
unable to tolerate other systemic therapy; induction and
maintenance of remission in steroid
dependent/resistant nephrotic syndrome due to
glomerular disease (e.g. minimal change nephropathy,
membranous glomerulonephritis, focal and segmental
glomerulosclerosis); maintenance of steroid induced
remission in nephrotic syndrome allowing for steroid
dose reduction or withdrawal; for the treatment of severe
aplastic anemia, in combination with Horse ATG; for
steroid-refractory chronic immune thrombocytopenia
Contraindications: Rheumatoid arthritis and psoriasis
patients with abnormal renal function, uncontrolled
hypertension, or malignancies; concomitant treatment
with PUVA or UVB therapy, methotrexate and other
390
ANTINEOPLASTIC AND IMMODULATING AGENTS
immunosuppressive agents, coal tar, or radiation
therapy in patients with psoriasis; rheumatoid arthritis
and psoriasis patients with primary or secondary
immunodeficiency excluding autoimmune disease,
uncontrolled infection, or malignancy (excluding non-
melanoma skin cancer)
Dose:
Psoriasis, by mouth, ADULT, initially 2.5 mg/kg daily, divided
twice daily; increase by 0.5 mg/kg daily if insufficient
response is seen after 4 weeks of treatment; additional
dose increases may be made every 2 weeks if needed
(maximum dose, 4 mg/kg daily) [NOTE: Discontinue if no
benefit is seen by 6 weeks of therapy at the maximum
dose. Once adequately controlled, decrease dose to the
lowest effective dose; doses lower than 2.5 mg/kg daily
may be effective; treatment > 1 year is not
recommended].
Rheumatoid arthritis, by mouth, ADULT, initially 2.5 mg/kg
daily, divided twice daily; may increase dose by 0.5–0.75
mg/kg daily if insufficient response is seen after 8 weeks
of treatment;additional dose increases may be made
again at 12 weeks (maximum dose, 4 mg/kg daily)
[NOTE: Discontinue if no benefit is seen by 16 weeks of
therapy].
Solid organ transplant, newly transplanted patients, by
mouth, ADULT, administer initial dose 4–12 hours prior
to transplant or postoperatively,
Organ Dose Frequency
9 ± 3 mg/kg
Kidney
daily
Liver
8 ± 4 mg/kg 2 divided
daily doses
7 ± 3 mg/kg
Heart
daily
Blood and marrow transplantation, by mouth, ADULT,
initially 12.5–15 mg/kg daily in 2 divided doses
beginning 1 day prior to transplant, then ~12.5 mg/kg
daily in 2 divided doses every 12 hours for at least 3–6
months as maintenance; gradually decrease dose to
zero by 1 year following transplant. [NOTE: Patients who
develop GVHD after discontinuation of cyclosporine may
be reinitiated on therapy with a loading dose of 10–12.5
mg/kg followed by the previously established
maintenance dose. Patients with mild, chronic GVHD
should be treated with lowest effective dose].
Nephrotic syndrome, by mouth, ADULT, initially 3.5 mg/kg
daily in 2 divided doses every 12 hours; titrate for
induction of remission and renal function; individualize
maintenance dose based on proteinuria, serum
creatinine, and tolerability and maintained at lowest
effective dose (maximum dose: 5 mg/kg daily);
CHILD,initially 4.2 mg/kg daily in 2 divided doses every
12 hours; titrate for induction of remission and renal
function; individualize maintenance dose based on
proteinuria, serum creatinine, and tolerability and
maintained at lowest effective dose (maximum dose: 6
mg/kg daily) [NOTE: Discontinue if no improvement is
observed after 3 months.].
Severe aplastic anemia, non-HSCT eligible, by mouth,
ADULT and CHILD, 10 to 12 mg/kg per day for at least 4
to 6 months. Dosage adjustments may be required to
maintain trough blood levels of 200 to 400
nanograms/mL. In responding children, cyclosporine is
continued for a minimum of 12 months, followed by slow
tapering of the drug (0.25-0.5 mg/kg/month).
ANTINEOPLASTIC AND IMMODULATING AGENTS

Dose Adjustment: Neurotoxicity (e.g. seizures and encephalopathy)

Renal Impairment: Thrombotic microangiopathy (syndromes of
Serum Dose microangiopathic hemolytic anemia and
Condition
Creatinine Levels Adjustment thrombocytopenia have occurred and may result in graft
Serum creatinine failure in transplant patients)
Severe
≥25% above
psoriasis Decrease dose Adverse Drug Reactions:
pretreatment
and by 25–50%; Common: Abdominal distress, diarrhea, dyspepsia, edema,
levels, consistent
abnormal discontinue if female genital tract disease, gingival hyperplasia,
for 2 weeks
renal not reversed headache, hirsutism, hypertension, hypertrichosis,
Serum creatinine
function after 2 dose increased susceptibility to infection, leg cramps, nausea,
≥50% above
during adjustments paresthesia, renal insufficiency, tremor, upper
pretreatment
treatment respiratory tract infection, urinary tract infection, viral
levels
Serum creatinine infection
Reduce dose; Less Common: Anaphylaxis, CNS toxicity, cholestasis,
≥30% above
Rheumatoid discontinue if exacerbation of psoriasis, fatigue, gout, hemolytic uremic
pretreatment
arthritis and not reversed syndrome, hepatitis, hyperbilirubinemia, hyperkalemia,
levels, consistent
abnormal within 30 days hypertrichosis, hypomagnesemia, impaired
for 2 weeks
renal consciousness, increased susceptibility to infection,
Reduce dose
function Serum creatinine hepatic insufficiency, jaundice, malignant lymphoma,
by 50%;
during ≥50% above migraine, myalgia, myopathy/rhabdomyolysis, myositis,
discontinue if
treatment pretreatment papilledema, progressive multifocal
not reversed
levels leukoencephalopathy, pseudotumor cerebri, pulmonary

L
within 30 days
edema (noncardiogenic), renal disease (polyoma virus-
Nephrotic Initiate at 2.5
associated), reversible posterior leukoencephalopathy
syndrome mg/kg daily
syndrome, rhabdomyolysis, thrombotic microangiopathy
Serum creatinine
>30% above Drug Interactions:
Decrease dose
pretreatment Monitor closely with:
by 25–50%
levels, consistent Enhances absorption of Cyclosporine:
for 2 weeks Metoclopramide

Hepatic Impairment: Enhances therapeutic effect of Cyclosporine:

May require dose reduction. Undergoes extensive hepatic Cyclophosphamide (immunosuppressive effect),
metabolism. Trastuzumab (neutropenic effect)

Hypertension: Enhances therapeutic effect of the following drugs:

If sustained hypertension develops during therapy but there
is no history of hypertension, decrease dose by 25–50%
and discontinue if hypertension persists. Increase
frequency of blood pressure monitoring after each dose
adjustment.
Precautions:
WARNING: Should only be used by physicians
experienced in immunosuppressive therapy and
management of transplant patients. Adequate
laboratory and supportive medical resources must
be readily available.
Some brands are not bioequivalent and cannot be
used interchangeably.
Neuromuscular-Blocking Agents e.g., Succinylcholine
Increases risk of adverse or toxic effects of Cyclosporine:
Aminoglycosides e.g., Streptomycin, Gentamicin
(nephrotoxic effect), Amphotericin B (nephrotoxic effect),
Angiotensin II Receptor Blockers, e.g. Losartan,
Candesartan (hyperkalemic effect), Denosumab (serious
infections); Melphalan (nephrotoxic effect); Sulfonamide
Derivatives, e.g. Sulfamethoxazole (nephrotoxic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Imipinem (neurotoxic effect), Loop Diuretics, e.g.,
Furosemide
Minoxidil (severe hypertrichosis)

May cause hypertension. Reduces diagnostic effect of Coccidioides immitis Skin Test

Increased risk of lymphomas and other Reduces therapeutic effect of Glyburide

malignancies, some fatal, particularly skin
cancers.
Renal impairment, including structural kidney
damage has occurred (dose-related).
Avoid concomitant use with:
Decreases excretion of Cholic Acid
Decreases metabolism of Etoposide

Hyperkalemia; Hyperuricemia Decreases serum concentration of Cyclosporine:

Gingival hyperplasia; Rheumatoid arthritis Barbiturates, e.g., Phenobarbital, Bosentan,
Hepatotoxicity; Nephrotoxicity Carbamazepine, CYP3A4 Inducers, Dabrafenib,
Infections; Malignancy (e.g. skin cancer) Efavirenz, Enzalutamide, Fibric Acid Derivatives (e.g.,

391
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Gemifibrozil), Fosphenytoin, Mitotane, Orlistat, TEST INTERACTION. Cross-reacts with radioimmunoassay

Phenytoin, Rifamycin Derivatives (e.g., Rifampicin), and fluorescence polarization immunoassay.
Somatostatin Analogs
Administration: Administer consistently with relation to time
Decreases serum concentration of Mycophenolate of day and meals.

Enhances therapeutic effect of Cyclosporine: For oral solutions, do NOT administer liquid from plastic
Echinacea, Roflumilast or styrofoam cup. May dilute with milk, chocolate milk, or
orange juice. Avoid changing diluents frequently.
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect) Mix thoroughly and drink at once. Use syringe provided
to measure dose. Mix in a glass container and rinse
Increases risk of adverse or toxic effects of Cyclosporine: container with more diluent to ensure total dose is taken.
Androgens, e.g. Testosterone (hepatotoxic effect) Do NOT rinse syringe before or after use to prevent dose
Eplerenone (hyperkalemic effect), Foscarnet variation.
(nephrotoxic effect), Methotrexate (nephrotoxicity),
NSAIDs (nephrotoxicity), Pimecrolimus, Potassium- NOTE: Limit exposure to sunlight and ultraviolet light by
Sparing Diuretics, e.g., Spironolactone wearing protective clothing and using effective
(hyperkalemic effect), Sirolimus (calcineurin inhibitor- sunscreen to minimize the risk for malignancy or skin
induced hemolytic uremic syndrome / thrombotic cancer.
thrombocytopenic purpura / thrombotic
microangiopathy), Tacrolimus (nephrotoxicity), Pregnancy Category: C
Temsirolimus (calcineurin inhibitor-induced hemolytic
L

uremic syndrome / thrombotic thrombocytopenic ATC Code: L04AD01

purpura / thrombotic microangiopathy)

Increases risk of adverse or toxic effects of the following

drugs: Rx TACROLIMUS
Caspofungin, Fibric Acid Derivatives, e.g., Gemfibrozil
(nephrotoxic effect), Leflunomide (hematologic toxicity Oral: 1 mg and 5 mg capsule
such as pancytopenia, agranulocytosis, and/or 1 mg and 5 mg slow-release capsules
thrombocytopenia), Methotrexate (nausea, vomiting,
oral ulcers, hepatotoxicity and/or nephrotoxicity), Suppresses cellular immunity, thus inhibiting T-lymphocyte
Natalizumab (concurrent infection), Tacrolimus activation, by binding to an intracellular protein, FKBP-12
(nephrotoxic effect), Vaccines, Live (infection) and complexes with calcineurin dependent proteins to
inhibit calcineurin phosphatase activity.
Increases serum concentration of Cyclosporine:
Amiodarone, Androgens e.g. Testosterone, Azole Indications: Prevention of organ rejection in heart, kidney,
Derivatives, Systemic, e.g., Ketoconazole, or liver transplant; treatment of refractory rejection in
Itraconazole [except Fluconazole] Non-dihydropyridine kidney or liver transplant; treatment of active rheumatoid
Calcium Channel Blockers (e.g., Verapamil, Diltiazem), arthritis in adult patients nonresponsive to DMARD
carvedilol, chloramphenicol, Crizotinib, CYP3A4 therapy or when DMARD therapy is inappropriate; for the
Inhibitors, Dasabuvir, Ezetimibe, Fusidic Acid (Systemic), prevention of GVHD in Allogeneic-HSCT, in combination
Methotrexate, Mifepristone, NSAIDs, Pravastatin, with MTX.
Protease Inhibitors (e.g. Lopinavir), Ritonavir, Simeprevir,
Tacrolimus, Telaprevir Dose:
Liver transplant, by mouth, ADULT, initially 0.1–0.15 mg/kg
Increases serum concentration of the following drugs: daily in 2 divided doses, given every 12 hours; titrate to
Afatinib, Aliskiren, Ambrisentan, Atorvastatin, target trough concentrations;
Boceprevir, Bosentan, Non-dihydropyridine Calcium CHILD, initially 0.15–0.20 mg/kg daily in 2 divided
Channel Blockers (e.g., Verapamil, Diltiazem), doses, given every 12 hours; titrate to target trough
Caspofungin, Colchicine (enhanced distribution), concentrations [NOTE: Initiate therapy in pediatric
Dabigatran Etexilate, Doxorubicin (Conventional), patients at the HIGH end of the recommended adult
Etoposide Phosphate, Everolimus, Fluvastatin, dosing ranges].
Lercanidipine, Methotrexate, Mitoxantrone, NSAIDs, Heart transplant, by mouth, ADULT, in combination with
Pazopanib, Pitavastatin, Pravastatin, Protease Inhibitors azathioprine or mycophenolate mofetil, initially 0.075
e.g. Lopinavir, Rosuvastatin, Silodosin, Simeprevir, mg/kg daily in 2 divided doses, given every 12 hours;
Simvastatin, Tacrolimus, Topotecan, Vincristine titrate to target trough concentrations.
(Liposomal) Kidney transplant, by mouth, ADULT, in combination with
azathioprine, initially 0.2 mg/kg daily; in combination
Reduces therapeutic effect of the following drugs: with mycophenolate mofetil, initially 0.1 mg/kg daily;
BCG, Intravesical, Vaccines (immune response) titrate to target trough concentrations; administer in 2
divided doses, given every 12 hours [NOTE: Administer
FOOD INTERACTION. Grapefruit Juice may increase the initial postoperative dose no sooner than 6 hours after
serum concentration of Cyclosporine by decreasing its liver or heart transplant and within 24 hours of kidney
metabolism.

392
ANTINEOPLASTIC AND IMMODULATING AGENTS
transplant or until renal function has recovered; titrate to
target trough concentrations.].
Rheumatoid arthritis, by mouth, ADULT, 3 mg once daily.
Blood and marrow transplantation, by mouth, ADULT, 0.15
mg/kg daily in 2 divided doses beginning 2 days prior to
transplant, dose adjusted to maintain trough level
between 10-20 ng/mL, up to 3 months, thereafter,
adjust dose to keep trough level around 10 ng/ml.
Dose Adjustment:
Renal Impairment:
Use lowest recommended dose. Additional dose reductions
may be necessary.
In patients who have undergone kidney transplant, and with
postoperative oliguria, initiate therapy no sooner than 6
hours and within 24 hours post-transplant, or until renal
function displays evidence of recovery.
Hepatic Impairment:
Use lowest recommended dose. Additional dose reductions
may be necessary.
Precautions:
WARNING: Should be administered under the
supervision of a physician experienced in
immunosuppressive therapy and organ
transplantation in a facility appropriate for
monitoring and managing therapy.
May contain lactose. NOT recommended for
patients who may be lactose intolerant.
May be associated with the development of
lymphoma and other malignancies.
Increased risk of infection, such as bacterial, viral,
fungal, and protozoal infections, including
opportunistic infections.
Cardiovascular effects (e.g. myocardial hypertrophy,
prolongation of the QT/QTc and torsade de pointes);
hypertension
Diabetes mellitus, post-transplant (new-onset diabetes and
insulin-dependent post-transplant diabetes mellitus may
occur); hyperkalemia (mild-to-severe); gastrointestinal
perforation
Infections (may result in serious and fatal outcomes; latent
viral infections may be activated); malignancy (e.g.
lymphoma, skin malignancies, post-transplant
lymphoproliferative disorder; pure red cell aplasia /
PRCA
Nephrotoxicity
Neurotoxicity (including tremor, headache, coma, delirium,
seizures, posterior reversible encephalopathy
syndrome).
Adverse Drug Reactions:
Common: Abdominal pain, abnormal dreams, abnormal
hepatic function tests, abnormality in thinking, abscess,
acidosis, acne vulgaris, acute renal failure, agitation,
albuminuria, alkalosis, allergic rhinitis, alopecia,
amblyopia, amnesia, anasarca, anemia, angina pectoris,
anorexia, anuria, anxiety, aphasia, aphthous stomatitis,
arthralgia, arthropathy, ascites, asthma, ataxia,
atelectasis, atrial fibrillation, atrial flutter, back pain,
bacterial infection, bladder spasm, blood coagulation
disorder, blurred vision, bradycardia, brain disease,
bronchitis, bruise, cardiac arrest, cardiac arrhythmia,
cardiorespiratory arrest, cardiac failure, carpal tunnel
syndrome, cellulitis, cerebral infarction, cerebral
ischemia, chest pain, chills, cholangitis, colitis,
cholestatic jaundice, condyloma acuminatum,
confusion, conjunctivitis, constipation, convulsions,
cough, Cushing's syndrome, cystitis, cytomegalovirus
disease, decreased prothrombin time, dehydration, deep
vein thrombophlebitis, deep vein thrombosis, delayed
gastric emptying, depression, dermal ulcer, dermatitis,
dermatological reaction, diabetes mellitus (post-
transplant), diaphoresis, diarrhea, dizziness, drowsiness,
duodenitis, dyspepsia, dysphagia, dyspnea, dysuria,
edema, emotional lability, emphysema, enlargement of
abdomen, falling, Epstein-Barr virus infection,
esophagitis, excessive crying, fever, exfoliative
dermatitis, fatigue, flaccid paralysis, flatulence, flu-like
symptoms, flushing, gastric ulcer, gastritis,
gastroenteritis, GERD, GI hemorrhage, GI perforation,
graft complications, hallucination, gout, headache,
hematuria, hemolytic/hypochromic anemia,
hemorrhage, hemorrhagic stroke, hepatic injury, hearing
loss, hepatitis, hernia, herpes simplex infection,
hirsutism, hiccups, hydronephrosis, hyper-/hypokalemia,
L
hypersensitivity reaction, hyperphosphatemia,
hypercalcemia, hypoglycemia/ hyperglycemia,
hypertension, hypertonia, hypertrophic cardiomyopathy,
hypervolemia, hypocalcemia, hyponatremia, increased
appetite, hypoesthesia, hypomagnesemia,
hypophosphatemia, hypotension, hypotrichosis,
infection, leg cramps, insomnia, intestinal obstruction,
ischemic heart disease, jaundice, Kaposi’s sarcoma,
mood elevation, leukocytosis, leukopenia, localized
phlebitis, malignant neoplasm of bladder, malignant
neoplasm of thyroid (papillary), mental status changes,
muscle weakness of the extremities, myalgia,
myasthenia, MI, muscle spasm, myoclonus, nausea,
nervousness, neuropathy, neurotoxicity, nightmares,
nocturia, neutropenia, oliguria, orthostatic hypotension,
oral candidiasis, osteopenia, osteoporosis, otalgia, otitis
externa, otitis media, pancreatic disease (pseudocyst),
pancreatitis, paresis, paresthesia, pericardial effusion,
pancytopenia, peripheral edema, peripheral neuropathy,
peritonitis, pharyngitis, phlebitis, pleural effusion,
peripheral vascular disease, pneumonia, pneumothorax,
polycythemia, polyoma virus infection, postoperative
pain, postoperative wound complication, proteinuria,
pruritus, skin rash, psychosis, pulmonary disease,
pulmonary edema, pulmonary infiltrates, rectal disease,
renal disease (BK nephropathy), renal function
abnormality, renal tubular necrosis, respiratory
depression, respiratory failure, respiratory tract infection,
rhinitis, seizure, sepsis, tachycardia, serious infection,
sinusitis, skin discoloration, skin neoplasm, skin
photosensitivity, stomach cramps, stomatitis, syncope,
thrombocytopenia, thrombosis, tinea versicolor, tinnitus,
toxic nephrosis, tremor, urinary frequency, urinary
incontinence, urinary retention, urinary tract infection,
urinary urgency, vasodilatation, ventricular premature
contractions, vaginitis, vertigo, visual disturbance, voice
disorder, vomiting, weakness, weight changes, wound
healing impairment, writing difficulty
Less Common: Adult respiratory distress syndrome,
agranulocytosis, anaphylactoid reaction, basal cell
carcinoma, anaphylaxis, angioedema, biliary tract
disease (stenosis), cerebrovascular accident, coma,
deafness, delirium, disseminated intravascular
393

coagulation, dysarthria, blindness, graft versus host
disease, hemiparesis, hemolytic-uremic syndrome,
hepatic cirrhosis, hepatic failure, hemorrhagic cystitis,
hepatic necrosis, hepatic veno-occlusive disease,
hepatosplenic T-cell lymphomas, hepatotoxicity,
hyperpigmentation, interstitial pulmonary disease,
leukemia, liver steatosis, lymphoproliferative disorder
(post-transplant or related to EBV), malignant lymphoma,
malignant melanoma, multiorgan failure,
leukoencephalopathy, mutism, prolonged partial
thromboplastin time, osteomyelitis, optic atrophy,
photophobia, polyarthritis, progressive multifocal
leukoencephalopathy, prolonged QT interval, pulmonary
hypertension, pure red cell aplasia, quadriplegia,
rhabdomyolysis, status epilepticus, septicemia,
reversible posterior leukoencephalopathy syndrome,
squamous cell carcinoma, Stevens-Johnson syndrome,
SVT, supraventricular extrasystole, thrombocytopenic
purpura, thrombotic thrombocytopenic purpura,
torsades de pointes, toxic epidermal necrolysis, urticaria,
venous thrombosis, ventricular fibrillation
Drug Interactions:
L
Monitor closely with:
Enhances therapeutic effect of Tacrolimus:
Trastuzumab (neutropenic effect)
Enhances therapeutic effect of the following drugs:
Moderate Risk QTc-Prolonging Agents, Indeterminate
Risk and Risk Modifying
Increases risk of adverse or toxic effects of Tacrolimus:
Denosumab (serious infections), Levofloxacin, Systemic
(QTc-prolonging effect), NSAIDs (nephrotoxic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Fenofibrate and its Derivatives (nephrotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of Antidiabetic Agents
Avoid concomitant use with:
Decreases serum concentration of Tacrolimus:
Dabrafenib, Efavirenz, Enzalutamide, Mitotane,
Rifamycin Derivatives (e.g., Rifampicin), Sirolimus,
Temsirolimus
Enhances absorption of Tacrolimus:
Ethyl Alcohol
Enhances therapeutic effect of Tacrolimus:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Dronedarone (QTc-prolonging effect). Highest Risk QTc-
Prolonging Agents, (Indeterminate Risk and Risk
Modifying), Tofacitinib (immunosuppressive effect)
Increases risk of adverse or toxic effects of Tacrolimus:
Cyclosporine, Systemic (nephrotoxic effect),
Eplerenone (hyperkalemic effect), Foscarnet
(nephrotoxic effect), Mifepristone (QTc-prolonging
effect), Pimecrolimus, Potassium-Sparing Diuretics, e.g.,
394
ANTINEOPLASTIC AND IMMODULATING AGENTS
Spironolactone (hyperkalemic effect), Sirolimus,
Tacrolimus (Topical), Temsirolimus
Increases risk of adverse or toxic effects of the following
drugs:
Clozapine (agranulocytosis), Cyclosporine, Systemic
(nephrotoxic effect), Dipyrone (agranulocytosis;
pancytopenia), Leflunomide (hematologic toxicity such
as pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Sirolimus, Temsirolimus
Vaccines, Live virus (infection)
Increases serum concentration of Tacrolimus:
Antidepressants, Serotonin Reuptake Inhibitor /
Antagonist, Boceprevir, Chloramphenicol, Conivaptan,
Crizotinib, Cyclosporine (Systemic), CYP3A4 Inhibitors,
Dasabuvir, Fluconazole, Fusidic Acid, (Systemic),
Grapefruit Juice, Itraconazole, Ketoconazole (Systemic),
Posaconazole, Protease Inhibitors, e.g., Lopinavir, Proton
Pump Inhibitors, e.g., Omeprazole, Ritonavir,
Voriconazole
Increases serum concentration of the following drugs:
Afatinib, Bosutinib, Colchicine (enhanced distribution),
Dabigatran Etexilate, Doxorubicin (Conventional),
Everolimus, Pazopanib, Silodosin, Topotecan, Vincristine
(Liposomal)
Reduces therapeutic effect of the following drugs:
BCG, Intravesical, Vaccines (immune response)
FOOD INTERACTION. Grapefruit juice may increase serum
level and/or toxicity of tacrolimus.
Administration: May be administered with or without food. If
GI intolerance occurs and food becomes necessary,
administer consistently with regard to timing and
composition of meals. Food decreases rate and extent of
absorption. High-fat meals have the most pronounced
effect.
NOTE: If dosed once daily, administer in the morning. If twice
daily, administer 12 hours apart. If the morning and
evening doses differ, administer the larger dose in the
morning. If dosed 3 times daily, administer 8 hours apart.
For combination therapy with everolimus in liver
transplant, administer both doses at the same time.
Immediate release and extended release capsules are
NOT interchangeable or substitutable. Serious adverse
events, including organ rejection, may occur.
Limit exposure to sunlight and ultraviolet light by wearing
protective clothing and using effective sunscreen to
minimize the risk for malignancy.
Pregnancy Category: C
ATC Code: L04AD02
ANTINEOPLASTIC AND IMMODULATING AGENTS
OTHER IMMUNOSUPPRESSANTS
Rx AZATHIOPRINE
Oral: 50 mg tablet
An imidazolyl derivative of mercaptopurine, which
incorporates its metabolites into replicating DNA,
stopping replication. It also blocks the pathway for purine
synthesis.
Indications: Adjunctive therapy in prevention of rejection of
kidney transplants; treatment of active rheumatoid
arthritis (RA); second line therapy for steroid-refractory
chronic idiopathic thrombocytopenic purpura (ITP).
Contraindication: Pregnancy
Dose:
Renal transplantation, by mouth, ADULT, initially 3–5 mg/kg
daily, usually as a single daily dose, then 1–3 mg/kg daily
as maintenance [NOTE: Treatment usually started the day of
transplant; has been initiated, rarely, 1–3 days prior to
transplant].
Rheumatoid arthritis, by mouth, ADULT, initially 1 mg/kg
daily (50–100 mg) given once daily or divided twice daily
for 6–8 weeks; may increase by 0.5 mg/kg every 4
weeks until response or up to 2.5 mg/kg daily; an
adequate trial should be a minimum of 12 weeks; reduce
dose by 0.5 mg/kg (~25 mg daily) every 4 weeks until
lowest effective dose is reached to determine
maintenance dose; may be discontinued abruptly but
monitor for delayed toxicities.
Steroid-refractory chronic idiopathic thrombocytopenic
purpura, by mouth, the starting dosage is 1-
3mg/kg/body weight/day and should be adjusted
according to the clinical response and haematological
tolerance. The maintenance dosage required may range
from less than 1 mg/kg body weight/day to 3
mg/kg/body weight/day depending on the clinical
condition being treated and the individual patient
response including haematological tolerance.
Dose Adjustment:
Geriatric:
Start with lowest recommended adult dose. Adjust dose to
creatinine clearance.
Renal Impairment:
For CrCl 10–50mL/minute and patients undergoing CRRT,
administer 75% of normal dose.
For CrCl <10 mL/minute and patients undergoing
hemodialysis, administer 50% of normal dose.
Oliguric patients, particularly those with tubular necrosis in
the immediate post-transplant period may have delayed
clearance, administer lower doses.
Precautions:
WARNING: Should be prescribed by physicians
familiar with the risks, including hematologic
toxicities and mutagenic potential. Adequate
laboratory and supportive medical resources must
be readily available.
Patients with thiopurine methyltransferase (TPMT)
activity are at risk for developing severe, life-
threatening myelotoxicity. Conduct TPMT testing in
abnormally low CBC unresponsive to dose
reduction. Consider discontinuation in abnormal
blood counts unresponsive to dose reduction.
Increases risk of developing malignancy.
Lymphoma (post-transplant) and hepatosplenic T-
cell lymphoma (in inflammatory bowel disease)
have been reported.
Gastrointestinal toxicity (e.g. severe nausea, vomiting,
diarrhea, rash, fever, malaise, myalgia, hypotension, and
liver enzyme abnormalities)
L
Hematologic toxicity (dose-related hematologic toxicities,
i.e., leukopenia, thrombocytopenia, and anemias,
including macrocytic anemia or pancytopenia)
Hepatotoxicity; Infections
Malignancy (HSTCL, a rare white blood cell cancer that is
usually fatal, may occur)
Elderly (increased toxicity)
Adverse Drug Reactions:
Common and Less Common: Abdominal pain, acute
myelocytic leukemia, alopecia, arthralgia, bone marrow
depression, anemia, diarrhea, fever, hemorrhage,
hepatic veno-occlusive disease, hepatosplenic T-cell
lymphomas, hepatotoxicity, hypersensitivity,
hypotension, increased susceptibility to infection,
interstitial pneumonitis (reversible), JC virus infection,
leukopenia, macrocytic anemia, malaise, malignant
lymphoma, malignant neoplasm of skin, myalgia, nausea
and vomiting, negative nitrogen balance, neoplasia,
pancreatitis, progressive multifocal
leukoencephalopathy, skin rash, steatorrhea, Sweet's
syndrome (acute febrile neutrophilic dermatosis),
pancytopenia, thrombocytopenia
Drug Interactions:
Monitor closely with:
Decreases metabolism of Azathioprine:
5-ASA Derivatives, e.g., Mesalazine, Sulfasalazine
Enhances therapeutic effect of Azathioprine:
ACE Inhibitors, e.g., Captopril, Enalapril
(myelosuppressive effect), Sulfamethoxazole
(myelosuppressive effect), Trastuzumab (neutropenic
effect), Trimethoprim (myelosuppressive effect)
Increases risk of adverse or toxic effects of Azathioprine:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of
Cyclophosphamide (hepatotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
395
 ANTINEOPLASTIC AND IMMODULATING AGENTS

Reduces therapeutic effect of Vitamin K Antagonists, e.g.,

Warfarin (anticoagulant effect)

Avoid concomitant use with:

Enhances immunosuppressive effect of Azathioprine:
Roflumilast

Enhances therapeutic effect of the following drugs:

Mercaptopurine (myelosuppressive effect)
Tofacitinib (immunosuppressive effect)

Increases risk of adverse or toxic effects of Azathioprine:

Pimecrolimus, Tacrolimus (Topical)

Increases risk of adverse or toxic effects of the following

drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia),
Natalizumab (concurrent infection), Live Vaccines
(infection)

Increases serum concentration of Azathioprine:

Allopurinol, Febuxostat, Ribavirin
L

Reduces therapeutic effect of the following drugs:

BCG (Intravesical), Vaccines (immune response)

Administration: Administering after meals or in divided

doses may decrease adverse GI events.
NOTE: When used concomitantly with allopurinol, reduce azathioprine
dose to one-third or one-fourth the usual dose. Patients with low
or absent TPMT activity may require further dose reductions or
discontinuation.

Limit exposure to sunlight and ultraviolet light by wearing

protective clothing and using effective sunscreen to minimize the
risk for malignancy.

Pregnancy Category: D

ATC Code: L04AX01

396
MUSCULO-SKELETAL SYSTEM

Neonates (regular use of high doses could impair platelet

MUSCULO-SKELETAL SYSTEM function and produce hypoprothrombinemia if neonatal
vitamin K stores are low; possible risk of Reye
syndrome).
Pregnancy (avoid analgesic doses, if possible, in the last few
ANTIINFLAMMATORY AND weeks).
ANTIRHEUMATIC PRODUCTS
Adverse Drug Reactions:
Common: Abdominal pain, asymptomatic blood loss, back
NON-SELECTIVE COX INHIBITORS pain, bleeding time increased, diarrhea, dyspepsia,
dyspnea, epistaxis, fatigue, GI irritation, headache,
malaise, melena, nausea, vomiting
Rx ASPIRIN Less Common: Anorexia, asthenia, confusion, dizziness,
fever, flushing, gastritis, hemorrhage rectum,
hemorrhoids, thirst, hypoglycemia (children),
Oral: 80 mg, 100 mg, 300 mg and 325 mg tablet
hypotension, myalgia, palpitations, syncope,
tachycardia, tinnitus, vertigo
An irreversible, cyclooxygenase (COX) inhibitor, which
Rare: Arrhythmia, convulsions, deafness, edema, GI ulcer
prevents platelet aggregation, and is useful in the long-
and perforation, intracranial hemorrhage,
term management of MI and the prevention of further
hypersensitivity reactions, including Stevens-Johnson
attacks.
syndrome; interstitial nephritis, iron-deficiency anemia,
myocarditis, paresthesia, renal insufficiency, seizures,
Indications: Pain and inflammation associated with
thrombocytopenia, toxic epidermal necrolysis
musculoskeletal and join disorders; juvenile rheumatoid
arthritis
Drug Interactions:

M
Monitor closely with:
Contraindications: Children and adolescents <16 years (risk
Enhances therapeutic effect of Aspirin:
of Reye syndrome); active peptic ulceration or bleeding
Valproic Acid (blood coagulation; platelet function)
GI ulcers; hemophilia and other bleeding disorders;
aspirin-sensitive asthma; thrombocytopenia; ulcerative
Enhances therapeutic effect of the following drugs:
colitis; lactating mothers; acute hemorrhagic stroke or
Oral Hypoglycemics, Phenytoin, Valproic Acid
intracerebral bleeding
Increases risk of adverse or toxic effects of Aspirin:
Dose:
Corticosteroids (GI bleeding and ulceration)
Pain and inflammation associated with musculoskeletal
and join disorders, by mouth, ADULT, initially 2.4–3.6 g
Increases risk of adverse or toxic effects of the following
daily in divided doses; usual maintenance dose, 3.6–5.4
drugs:
g daily.
Anticoagulant Therapy, e.g., Heparin, Warfarin
Juvenile rheumatoid arthritis, by mouth, CHILD, 80 to 100
(bleeding), Valproic Acid
mg/kg daily in 5 or 6 divided doses, up to 130 mg/kg
daily in acute exacerbations if necessary.
Avoid concomitant use with:
Increases excretion of Aspirin:
Dose Adjustment:
Antacids, e.g., Aluminum and Magnesium Hydroxide
Renal Impairment:
For mild-to-moderate renal impairment, dose adjustments
Increases risk of adverse or toxic effects of the following
are not necessary.
drugs:
For severe impairment, the drug is not recommended.
ACE Inhibitors, e.g., Enalapril (renal impairment when
aspirin is given in doses of >300 mg daily), NSAIDs, e.g.,
Hepatic Impairment:
Ibuprofen, Naproxen (gastric ulceration)
Avoid use in severe liver disease.
Reduces therapeutic effect of Aspirin:
Precautions:
NSAIDs, e.g., Ibuprofen, Naproxen (anti-platelet activity;
Increased risk of gastritis and GI bleeding;
cardioprotective effect)
Asthma;
Urticaria;
Reduces therapeutic effect of the following drugs:
Allergic disease;
ACE Inhibitors, e.g., Enalapril (hyponatremic and
Uncontrolled hypertension;
hypotensive effect), Diuretics, e.g., Spironolactone
Renal impairment (avoid use; due to sodium and water
(inhibition of renal prostaglandins)
retention – deterioration in renal function may increase
risk of GI bleeding);
Administration: Take tablets from packaging immediately
Hepatic impairment (avoid in severe impairment – there is
before use. Should be taken with food or immediately
increased risk of GI bleeding);
after meals.
G6PD-deficiency;
Dehydration;
Pregnancy Category: C; D in 3rd trimester
Gout;
Elderly;
ATC Code: Not Available

397

Rx DICLOFENAC
Oral: 25 mg and 50 mg tablet or capsule (as sodium or
potassium salt)
50 mg enteric-coated or MR tablet (as sodium salt)
100 mg MR tablet or capsule (as sodium or
potassium salt)
Inj.: 25 mg/mL (as sodium salt), 3 mL ampule (IM, IV)
A reversible cyclooxygenase­1 and 2 (COX­1 and -2) inhibitor
that acts by decreasing the formation of prostaglandin
precursors. It exhibits antipyretic, analgesic, and anti-
inflammatory properties.
Indications: Relief of signs and symptoms of rheumatoid
arthritis and osteoarthritis; ankylosing spondylitis
Contraindications: Treatment of perioperative pain in the
setting of coronary artery bypass graft (CABG) surgery
[Inj.]: Moderate to severe renal impairment in the
perioperative period and who are at risk for volume
depletion
Dose:
M
Rheumatoid arthritis, by mouth, ADULT, immediate-release
tablet, 150-200 mg daily in 3-4 divided doses;
delayed-release tablet, 150-200 mg daily in 3-4 divided
doses;
extended-release tablet, 100 mg daily, may increase
dose to 200 mg daily in 2 divided doses.
Osteoarthritis, by mouth, ADULT, immediate-release tablet,
150-200 mg daily in 3-4 divided doses;
delayed-release tablet, 150-200 mg daily in 2-4 divided
doses;
extended-release tablet, 100 mg daily, may increase
dose to 200 mg daily in 2 divided doses;
immediate-release capsule, 35 mg 3 times daily.
Ankylosing spondylitis, by mouth, ADULT, delayed-release
tablet, 100-125 mg daily in 4-5 divided doses.
Dose Adjustment:
Geriatric:
Initiate therapy using the lowest recommended dose and
frequency.
Renal Impairment:
In patients with advanced renal disease or significant renal
impairment, use is not recommended.
Hepatic Impairment:
May require dose adjustment. Drug undergoes extensive
hepatic metabolism.
In moderate to severe impairment, use of injectables is not
recommended (has not been studied).
Precautions:
WARNING: May cause an increased risk of serious
cardiovascular thrombotic events, MI, and stroke,
which can be fatal. Risk may increase with duration
of use.
398
MUSCULO-SKELETAL SYSTEM
Increased risk of serious GI adverse reactions,
including bleeding, inflammation, ulceration, and
perforation of the stomach or intestines, which can
be fatal. May occur at any time during use and
without warning symptoms.
Do NOT interchange products. Different formulations
of oral diclofenac are not bioequivalent, even if the
milligram strength is the same.
Anaphylactoid reactions;
Skin reactions;
Asthma;
CNS effects e.g. drowsiness, dizziness, blurred vision, and
other neurologic effects;
Genitourinary effects e.g. cystitis, or hematuria;
Hematologic effects e.g. anemia and prolonged bleeding
time;
Dehydration;
Hepatic effects;
Renal effects;
Renal disease;
Diabetes;
Elderly;
Lactation (breast-feeding is not recommended; use with
caution in breast­feeding women).
SKILLED TASKS. May cause drowsiness or blurred vision.
Avoid performing tasks, which require mental alertness,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Edema, MI, cerebrovascular accident,
hypertension, significant cardiovascular event,
headache, dizziness, procedural pain, falling, pruritus,
skin rash, exfoliative dermatitis, Stevens-Johnson
syndrome, toxic epidermal necrolysis, constipation,
abdominal pain or discomfort, fluid retention, diarrhea,
dyspepsia, esophageal perforation, flatulence, UTI, GI or
duodenal ulcer, heartburn, intestinal perforation,
nausea, vomiting, bruise, anemia, hemorrhage,
prolonged bleeding time, anaphylactoid reaction,
infusion site reaction, tinnitus, influenza, osteoarthritis,
arthralgia, back pain, limb pain, renal insufficiency, renal
function abnormality, wound healing impairment, GI
inflammation, upper respiratory tract infection,
nasopharyngitis, sinusitis, cough, bronchitis
Less Common: Abnormal dreams, agranulocytosis,
alopecia, anaphylactoid reaction, anaphylaxis,
angioedema, anxiety, aplastic anemia, aseptic
meningitis, auditory impairment, azotemia, asthma,
blurred vision, cardiac arrhythmia, cardiac failure,
cerebrovascular accident, change in appetite, chest
pain, coma, confusion, colitis, congestive heart failure,
conjunctivitis, convulsions, cystitis, depression,
diaphoresis, diplopia, disorientation, drowsiness,
dyspnea, dysuria, ecchymoses, eosinophilia, eructation,
erythema multiforme, esophageal ulcer, exfoliative
dermatitis, fever, esophagitis, fluid retention, fulminant
hepatitis, gastritis, gastrointestinal hemorrhage,
glossitis, hallucination, hematemesis, hematuria,
hearing loss, hemolytic anemia, hepatic failure, hepatic
necrosis, hepatotoxicity, peptic ulcer, hepatitis,
hypertension, hypotension, skin photosensitivity,
infection, insomnia, interstitial nephritis, intestinal
perforation, jaundice, sepsis, leukopenia,
MUSCULO-SKELETAL SYSTEM
lymphadenopathy, malaise, melena, memory
impairment, meningitis, nervousness, oliguria,
palpitations, pancreatitis, pancytopenia, paresthesia,
pneumonia, polyuria, proteinuria, psychotic reaction,
purpura, rectal hemorrhage, renal failure, renal papillary
necrosis, respiratory depression, seizure, stomatitis,
syncope, taste disorder, tachycardia, thrombocytopenia,
toxic epidermal necrolysis, tremor, urticaria, vasculitis,
vertigo, weakness, weight changes, xerostomia
Drug Interactions:
Monitor closely with:
Decreases excretion of Aminoglycosides
Enhances therapeutic effect of the following drugs:
ACE Inhibitors (antihypertensive effect), Agents with
Antiplatelet Properties, Anticoagulants
Increases risk of adverse or toxic effects of Diclofenac:
ACE Inhibitors (significantly decreased renal function),
Angiotensin II Receptor Blockers (significantly decreased
glomerular filtration and renal function), (antiplatelet
effect), Dasatinib, Thrombolytic Agents (anticoagulant
effect), Glucosamine Multivitamins / Fluoride with ADE,
Multivitamins / Minerals with ADEK, Folate, Iron,
Multivitamins / Minerals with AE, no Iron, Omega-3 Fatty
Acids, Pentoxifylline, Prostacyclin Analogues, Serotonin /
Norepinephrine Reuptake Inhibitors, Tipranavir, Vitamin
E, Antidepressants, Tricyclic or Tertiary Amine
(antiplatelet effect), Ibrutinib, Limaprost (antiplatelet
effect), Pentosan Polysulfate Sodium, Treprostinil
(bleeding)
Increases risk of adverse or toxic effects of the following
drugs:
5-ASA Derivatives, Aliskiren, Tacrolimus Systemic
(nephrotoxic effect), Bisphosphonate Derivatives (GI
ulceration; nephrotoxicity), Collagenase Systemic
(injection site bruising and/or bleeding), Deferasirox (GI
ulceration, irritation, or bleeding), Deoxycholic Acid
(bleeding or bruising in the treatment area),
Desmopressin, Drospirenone (hyperkalemic effect),
Eplerenone, Potassium-sparing Diuretics (hyperkalemic
effect), Haloperidol (drowsiness; confusion),
Ibritumomab (impaired platelet function; increased risk
of bleeding), Obinutuzumab (serious bleeding-related
events), Porfimer, Verteporfin (photosensitizing effect),
Quinolone Antibiotics e.g. Ciprofloxacin (neuroexcitatory
and/or seizure-potentiating effect), Salicylates
(bleeding), Tositumomab, Iodine I131 Tositumomab
Reduces therapeutic effect of the following drugs:
Aliskiren, Angiotensin II Receptor Blockers, Beta Blockers
[except Levobunolol, Metipranolol], Eplerenone,
Hydralazine, Potassium-sparing Diuretics
(antihypertensive effect), Prostaglandins Ophthalmic,
Thiazide Diuretics
Avoid concomitant use with:
Decreases serum concentration of Diclofenac:
Salicylates
Enhances therapeutic effect of the following drugs:
Dabigatran Etexilate, Rivaroxaban, Urokinase, Vitamin K
Antagonists (anticoagulant effect)
Increases risk of adverse or toxic effects of Diclofenac:
Dexketoprofen, Floctafenine, Ketorolac, Morniflumate,
NSAIDs, Selective Serotonin Reuptake Inhibitors
(antiplatelet effect), Sodium Phosphates (nephrotoxic
effect, specifically acute phosphate nephropathy),
Talniflumate
Increases risk of adverse or toxic effects of the following
drugs:
Apixaban (bleeding), Corticosteroids Systemic
(nephrotoxicity; hypertension), COX-2 Inhibitors,
Cyclosporine Systemic (nephrotoxic effect), Herbs with
Anticoagulant / Antiplatelet Properties, Salicylates
[Choline Magnesium Trisalicylate] (bleeding),
Omacetaxine (bleeding-related events), Tenofovir
(tenofovir-associated nephrotoxicity)
Increases serum concentration of Diclofenac:
Corticosteroids Systemic, Voriconazole
Increases serum concentration of the following drugs:
Corticosteroids Systemic, Lithium, Methotrexate,
Pemetrexed, Tizanidine [if concomitant use cannot be
avoided, initiate tizanidine at 2 mg and increase in 2–4
mg increments based on patient response]
M
Reduces absorption of Diclofenac:
Bile Acid Sequestrants e.g. Cholestyramine
Reduces therapeutic effect of the following drugs:
Loop Diuretics (diuretic effect), Salicylates [Choline
Magnesium Trisalicylate] (cardioprotective effect),
Selective Serotonin Reuptake Inhibitors
Administration: May be taken with food or milk to decrease
GI distress.
Do NOT crush modified-release tablets.
For IV route, administer as an IV bolus over 15 seconds.
Injection dosage form is not indicated for long-term use.
NOTE: Some products may contain phenylalanine.
Pregnancy Category: C; D (≥30 weeks gestation)
ATC Code: M01AB05
OTC IBUPROFEN
Oral: 200 mg and 400 mg tablet
100 mg/5 mL syrup/suspension, 60 mL
200 mg/5 mL suspension, 60 mL
A propionic acid-derived, nonselective, nonsteroidal anti-
inflammatory medicine, which is useful for the
management of pain due to inflammation.
Indications: Acute pain and inflammation in rheumatic
diseases and other musculoskeletal disorders
Contraindications: Active or history of peptic ulceration
399
 MUSCULO-SKELETAL SYSTEM

Dose: Aspirin (antiplatelet activity; cardioprotective effect),

Inflammatory musculoskeletal disorders, by mouth, ADULT, Diuretics, e.g., Loop Diuretics, Thiazide Diuretics (diuretic
1.2–1.8 g daily in 3–4 divided doses, increased if effect)
necessary (maximum dose, 2.4 g daily; 3.2 g daily in
inflammatory disease); maintenance dose of 0.6–1.2 g Avoid concomitant use with:
daily may be sufficient. Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
Dose Adjustment:
Renal and Hepatic Impairment: Increases risk of adverse or toxic effects of Ibuprofen:
Keep dose as low as possible. Alendronate (gastric ulceration), Drugs Affecting Clotting
Process, e.g., Ketorolac (bleeding, including GI bleeding),
Precautions: Vitamin K Antagonists, e.g., Warfarin (serious bleeding)
WARNING: Associated with an increased risk of
adverse cardiovascular thrombotic events, Increases risk of adverse or toxic effects of the following
including fatal MI and stroke. drugs:
May increase risk of GI irritation, inflammation, Drugs which are Renally Excreted, e.g., Calcineurin
ulceration, bleeding, and perforation. Inhibitors, Drugs which Increase Potassium
Concentration, e.g., Amiloride, Triamterene
(hyperkalemia)
Renal impairment;
Hepatic impairment; Reduces therapeutic effect of the following drugs:
Cardiac disease; Antihypertensives, e.g., Beta Blockers, ARBs
Coagulation defects; (hypotensive effect)
Allergic disorders.
Elderly; Administration: Should be taken with food.
Pregnancy (avoid use unless the potential benefit outweighs
M

risk; third trimester); Pregnancy Category: C, prior to 30 weeks gestation; D, ≥30

Lactation. weeks gestation
Adverse Drug Reactions: ATC Code: M01AE01
Common: Diarrhea, dizziness, dyspepsia, headache, GI
ulceration or bleeding, hemorrhage, hypertension,
nausea, raised liver enzymes, salt and fluid retention,
vomiting OTC NAPROXEN
Less Common: Bronchospasm, confusion, heart failure,
esophageal ulceration, hyperkalemia, rash, renal
Oral: 275 mg (as sodium salt) (250 mg base) and 550 mg
impairment
(as sodium salt) (500 mg base) tablet
Rare: Acute renal failure, aseptic meningitis, blood
dyscrasias, blurred vision, colitis, cystitis, fluid retention,
A naphthyl-propionic acid-derived, nonsteroidal anti-
hepatitis, stroke, anaphylactic and anaphylactoid
inflammatory medicine, that inhibits prostaglandin
reactions, interstitial nephritis, MI, nephrotic syndrome,
synthesis. It is pharmacologically related to ibuprofen but
photosensitivity reaction, Stevens-Johnson syndrome,
has a longer half-life.
tinnitus, toxic epidermal necrolysis, vertigo
Indications: Rheumatoid arthritis; osteoarthritis; ankylosing
Drug Interactions:
spondylitis; juvenile idiopathic arthritis; for the relief of
Monitor closely with:
signs and symptoms of tendonitis and bursitis; acute
Increases risk of adverse or toxic effects of Ibuprofen:
gout; management of pain due to inflammation (e.g.,
Angiotensin II Receptor Blockers (significantly decreased
period pain, migraine); management of primary
renal function), Corticosteroids Oral, e.g., Hydrocortisone
dysmenorrhea; inflammatory joint pain
(gastric ulceration), Digoxin (reduced renal function),
Other NSAIDs
Contraindications: Treatment of perioperative pain in the
setting of Coronary Artery Bypass Graft (CABG) surgery;
Increases risk of adverse or toxic effects of the following
active peptic ulcers; active GI inflammatory disease
drugs:
ACE Inhibitors (renal impairment; hyperkalemia),
Dose:
Atenolol, Ciprofloxacin, Levofloxacin (convulsions),
Acute gout, by mouth, ADULT, initially 750 mg, followed by
Digoxin (exacerbation of heart failure), Diuretics e.g.,
250 mg every 8 hours until the attack subsides.
Loop Diuretics, Thiazide Diuretics (nephrotoxicity)
Acute musculoskeletal disorders, by mouth, ADULT, initially
500 mg, then 250 mg 2-3 times daily.
Increases serum concentration of Digoxin
Ankylosing spondylitis, osteoarthritis, rheumatoid arthritis,
by mouth, ADULT, 500 mg to 1 g daily in 2 divided doses;
Reduces therapeutic effect of the following drugs:
may increase to 1.5 g daily of naproxen base if tolerating
ACE Inhibitors, Angiotensin II Receptor Blockers
well and clinically indicated (for a limited period, <6
(antihypertensive effect)
months).
Dysmenorrhea, by mouth, ADULT, initially 500 mg, followed
by 250 mg every 6-8 hours as required.

400
MUSCULO-SKELETAL SYSTEM
Inflammatory joint pain, by mouth, ADULT, 500 mg twice
daily.
Juvenile idiopathic arthritis, by mouth, CHILD >2 years, 10
mg/kg daily in 2 divided doses (up to 15 mg/kg daily has
been tolerated).
Pain (mild to moderate), acute tendonitis, bursitis, by
mouth, ADULT, initially 500 mg, followed by 500 mg
every 12 hours or 250 mg every 6-8 hours (maximum
daily dose; Day 1: 1.25 g naproxen base; subsequent
daily doses should not exceed 1 g naproxen base).
NOTE: For relief of acute pain, naproxen sodium may be
preferred due to more rapid absorption and onset.
Dose Adjustment:
Renal Impairment:
In mild impairment, reduce dose due to nephrotoxicity.
In moderate to severe impairment, avoid use.
Hepatic Impairment:
In severe impairment, avoid use due to hepatotoxicity.
Precautions:
WARNING: NSAIDs are associated with an increased
risk of adverse cardiovascular thrombotic events,
including fatal MI and stroke.
NSAIDs may increase risk of GI irritation,
inflammation, ulceration, bleeding, and
perforation.
Anaphylactoid reactions may occur (do not use in patients
who experience bronchospasm, asthma, rhinitis, or
urticaria with aspirin or NSAID therapy);
Cardiovascular events (use the lowest effective dose for the
shortest duration of time, consistent with individual
patient goals);
CNS effects e.g. drowsiness, dizziness, blurred vision and
other neurologic effects;
In patients with history of GI diseases, or concurrent therapy
with aspirin, anticoagulants and/or corticosteroids,
smoking, use of alcohol, the elderly or debilitated
patients;
Hematologic effects e.g. prolonging bleeding time;
Hyperkalemia (use of NSAID may increase the risk of
hyperkalemia, particularly in the elderly, diabetics, or
renal disease);
Skin reactions (discontinue use at first sign of skin rash or
hypersensitivity);
Aseptic meningitis;
Hepatic and renal impairment;
Hypertension;
Asthma
Elderly;
Chronic use of NSAIDs in women of reproductive age may
be associated with infertility, which is reversible upon
discontinuation;
Breastfeeding.
SKILLED TASKS. May impair ability to perform skilled tasks,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Abdominal pain, bleeding time increased,
constipation, diaphoresis, diarrhea, dizziness,
drowsiness, dyspepsia, dyspnea, edema, flatulence, fluid
retention, gross bleeding or perforation; headache,
heartburn, hemolysis, indigestion, lightheadedness,
nausea, palpitation, pruritus, pseudoporphyria, rash,
skin eruption, stomatitis, tinnitus, ulcers, vertigo, visual
disturbance, vomiting
Rare: Allergic pneumonitis, aplastic anemia, aseptic
meningitis, cognitive dysfunction, erythema multiforme,
hemolytic anemia, hepatic impairment, non-peptic GI
ulceration, Stevens-Johnson syndrome, toxic epidermal
necrolysis, ulcerative stomatitis, vasculitis
Drug Interactions:
Monitor closely with:
Decreases excretion of Aminoglycosides
Increases risk of adverse or toxic effects of Naproxen:
ACE Inhibitors (renal impairment), Angiotensin II
Receptor Blockers (decreased renal function),
Corticosteroids Oral (gastric ulceration), Other NSAIDs
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors (hyperkalemia), Diuretics, e.g., Loop
Diuretics, Thiazide Diuretics (nephrotoxicity), Quinolone
Antibiotics (neuroexcitatory and/or seizure-potentiating
M
effect)
Reduces therapeutic effect of the following drugs:
ACE Inhibitors, Angiotensin II Receptor Blockers
(antihypertensive effect), Diuretics, e.g., Loop Diuretics,
Thiazide Diuretics (renal function; diuretic effect)
Avoid concomitant use with:
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin
Increases risk of adverse or toxic effects of Naproxen:
Alendronate (gastric ulceration)
Increases risk of adverse or toxic effects of the following
drugs:
Drugs affecting clotting process, e.g., Ketorolac
(bleeding, including GI bleeding), Drugs which are renally
excreted e.g., Calcineurin Inhibitors, Drugs which
increase Potassium Concentration, e.g., Amiloride,
Triamterene (hyperkalemia), Vitamin K Antagonists e.g.,
Warfarin (serious bleeding)
Increases serum concentration of Digoxin
Reduces therapeutic effect of the following drugs:
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
(reduced antihypertensive effect)
Administration: Administer with food, milk, or antacids to
decrease GI adverse effects (drug may cause GI upset,
bleeding, ulceration, and perforation).
Pregnancy Category: C
ATC Code: M01AE02
401

Rx KETOPROFEN
Oral: 100 mg tablet
Inj.: 50 mg/mL, 2 mL ampule (IM)
A reversible cyclooxygenase­1 and 2 (COX­1 and 2) inhibitor,
which decreases formation of prostaglandin precursors.
It has antipyretic, analgesic, and anti-inflammatory
properties.
Indications: Osteoarthritis; rheumatoid arthritis
Contraindications: Perioperative pain in the setting of
coronary artery bypass graft (CABG) surgery
Dose:
Osteoarthritis or Rheumatoid Arthritis, by mouth, ADULT, 50
mg 4 times daily or 75 mg 3 times daily (maximum, 300
mg daily).
Dose Adjustment:
Geriatric:
Initial dose should be decreased in patients >75 years. Use
with caution when changing dosage.
M
Renal Impairment:
In patients with advanced renal disease, use is not
recommended.
In patients with mild impairment, maximum dose is 150 mg
daily.
In patients with severe impairment (GFR <25 mL/minute
per 1.73 m2), maximum dose is 100 mg daily.
NOTE: Some products are contraindicated with severe
impairment (refer to local product labeling).
Hepatic Impairment:
In patients with hepatic impairment (serum albumin <3.5
g/dL), maximum initial dose is 100 mg daily).
NOTE: Some products are contraindicated with severe
impairment (refer to local product labeling).
Precautions:
WARNING: May cause an increased risk of serious
cardiovascular thrombotic events, myocardial
infarction (MI), and stroke, which can be fatal.
Causes an increased risk of serious GI adverse
reactions, including bleeding, ulceration, and
perforation of the stomach or intestines, which can
be fatal. These reactions can occur at any time
during use and without warning symptoms.
Anaphylactoid reactions may occur (do not use in patients
who experience bronchospasm, asthma, rhinitis, or
urticaria with aspirin or NSAID therapy);
Cardiovascular events (use the lowest effective dose for the
shortest duration of time, consistent with individual
patient goals);
CNS effects (may cause drowsiness, dizziness, blurred
vision and other neurologic effects which may impair
physical or mental ability);
402
MUSCULO-SKELETAL SYSTEM
In patients with history of GI diseases (bleeding or ulcers),
or concurrent therapy with aspirin, anticoagulants
and/or corticosteroids, smoking, use of alcohol, the
elderly or debilitated patients;
Hematologic effects (platelet adhesion and aggregation
may be decreased; thus prolonging bleeding time);
Hyperkalemia;
Ophthalmic events (blurred or diminished vision has been
reported);
Skin reactions (may cause serious skin reactions;
discontinue use at first sign of skin rash or
hypersensitivity);
Aseptic meningitis;
Hepatic and renal impairment;
Hypertension;
Asthma;
Surgical or dental procedures (withhold use for at least 4–6
half-lives prior to surgical or dental procedures);
Elderly
Pregnancy;
Chronic use of NSAIDs in women of reproductive age may
be associated with infertility, which is reversible upon
discontinuation);
Breastfeeding (small amounts are excreted into breast
milk).
SKILLED TASKS. May impair ability to perform skilled tasks,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Peripheral edema, headache, depression,
dizziness, dreams, insomnia, malaise, nervousness,
somnolence, rash, dyspepsia, abdominal pain,
constipation, diarrhea, flatulence, nausea,
gastrointestinal bleeding, peptic ulcer, anorexia,
stomatitis, vomiting, urinary tract irritation, abnormal
liver function test, visual disturbances, tinnitus renal
dysfunction
Less Common: Agranulocytosis, allergic reaction, allergic
rhinitis, alopecia, anaphylaxis, anemia, angioedema,
arrhythmia, aseptic meningitis, blurred vision, bone
marrow suppression, bronchospasm, buccal necrosis,
bullous rash, chills, cholestatic hepatitis, confusion, CHF,
conjunctivitis, cystitis, diabetes mellitus (aggravated),
drowsiness, dysphoria, dyspnea, eczema, edema,
epistaxis, erythema multiforme, exfoliative dermatitis,
facial edema, fecal occult blood, fluid retention, gastritis,
gastrointestinal perforation, GI ulceration, gynecomastia,
hallucinations, hearing decreased, hematemesis,
hematuria, hemolytic anemia, hemoptysis, hepatic
dysfunction, hepatitis, hepatotoxicity (idiosyncratic).
Peripheral edema, headache, depression, dizziness,
dreams, insomnia, malaise, nervousness, somnolence,
rash, dyspepsia, abdominal pain, constipation, diarrhea,
flatulence, nausea, GI bleeding, peptic ulcer, anorexia,
stomatitis, vomiting, urinary tract irritation, abnormal
liver function test, visual disturbances, tinnitus renal
dysfunction, hot flashes, hypertension, hyponatremia,
impotence, infection, interstitial nephritis, intestinal
ulceration, jaundice, laryngeal edema, leukopenia, libido
disturbance, melena, microvesicular steatosis, migraine,
myocardial infarction, nephrotic syndrome, onycholysis,
palpitation, pancreatitis, peptic ulcer, peripheral
neuropathy, peripheral vascular disease,
photosensitivity, polydipsia, polyuria, pruritus, purpura,
purpuric rash, renal failure, renal papillary necrosis,
MUSCULO-SKELETAL SYSTEM
retinal hemorrhage, septicemia, shock, Stevens-Johnson
syndrome, tachycardia, thrombocytopenia, toxic
amblyopia, toxic epidermal necrolysis, tubulopathy,
ulcerative colitis, urticaria, vasodilation, xerostomia
Drug Interactions:
Monitor closely with:
Decreases excretion of the following drugs:
Aminoglycosides, Pralatrexate
Enhances therapeutic effect of Ketoprofen:
Tricyclic Antidepressants e.g., Antidepressants, Tertiary
Amine, Dasatinib, Glucosamine, Iodine I131
Tositumomab, Multivitamins / Fluoride with ADE,
Multivitamins / Minerals with ADEK, Folate, Iron,
Multivitamins / Minerals with AE, no Iron, Omega-3 Fatty
Acids, Other Agents with Antiplatelet Properties e.g.,
Aspirin, Pentoxifylline, Prostacyclin Analogues, Serotonin
/ Norepinephrine Reuptake Inhibitors e.g. Duloxetine,
Tipranavir, Vitamin E (anticoagulant effect)
Enhances therapeutic effect of the following drugs:
Anticoagulants, Thrombolytic Agents (anticoagulant
effect)
Increases risk of adverse or toxic effects of Ketoprofen:
ACE Inhibitors e.g. Enalapril (decreased renal function),
Angiotensin II Receptor Blockers e.g., Losartan
(significantly decreased glomerular filtration and renal
function), Corticosteroids Systemic, Ibrutinib, Limaprost,
Nonsteroidal Anti-Inflammatory Agents, Pentosan
Polysulfate Sodium, Treprostinil (bleeding),
Tositumomab (bleeding-related adverse events)
Increases risk of adverse or toxic effects of the following
drugs:
5-ASA Derivatives, Aliskiren, Tacrolimus, Systemic
(nephrotoxic effect), Bisphosphonate Derivatives (GI
ulceration; nephrotoxicity), Collagenase Systemic
(injection site bruising and/or bleeding), Deferasirox (GI
ulceration, irritation, or bleeding), Deoxycholic Acid
(bleeding or bruising in the treatment area),
Desmopressin, Drospirenone (hyperkalemic effect),
Eplerenone, Potassium-sparing Diuretics (hyperkalemic
effect), Haloperidol (drowsiness; confusion),
Ibritumomab (impaired platelet function; bleeding),
Obinutuzumab (serious bleeding-related events),
Porfimer, Verteporfin (photosensitizing effect),
Quinolone Antibiotics e.g. Levofloxacin (neuroexcitatory
and/or seizure-potentiating effect), Salicylates
(bleeding),
Reduces therapeutic effect (antihypertensive effect) of the
following drugs:
ACE Inhibitors e.g. Enalapril, Aliskiren, Angiotensin II
Receptor Blockers, Beta Blockers [except Levobunolol,
Metipranolol], Hydralazine, Potassium-sparing Diuretics
e.g. Eplerenone, Prostaglandins Ophthalmic, Thiazide
Diuretics e.g., Hydrochlorothiazide
Avoid concomitant use with:
Decreases serum concentration of Ketoprofen:
Salicylates
Enhances therapeutic effect of Ketoprofen:
Selective Serotonin Reuptake Inhibitors (antiplatelet
effect)
Enhances therapeutic effect of the following drugs:
Cyclosporine Systemic (nephrotoxic effect), Dabigatran
Etexilate, Rivaroxaban, Urokinase, Vitamin K Antagonists
e.g., Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Ketoprofen:
Dexketoprofen, Diclofenac Systemic, loctafenine,
Ketorolac, Morniflumate, Sodium Phosphates
(nephrotoxic effect; acute phosphate nephropathy),
Talniflumate, Tenofovir (Tenofovir-associated
nephrotoxicity)
Increases risk of adverse or toxic effects of the following
drugs:
Apixaban, Salicylates [except Choline Magnesium
Trisalicylate] (bleeding), COX-2 Inhibitors e.g. Celecoxib,
Omacetaxine (bleeding-related events),
Increases serum concentration of the following drugs:
Dabigatran Etexilate, Lithium, Methotrexate,
Pemetrexed, Tizanidine [if concomitant use cannot be
avoided, initiate Tizanidine at 2 mg and increase in 2–4
M
mg increments based on patient response]
Reduces absorption of Ketoprofen:
Bile Acid Sequestrants e.g. Cholestryamine
Reduces therapeutic effect of the following drugs:
Loop Diuretics (diuretic effect), Salicylates [except
Choline Magnesium Trisalicylate] (cardioprotective
effect), Selective Serotonin Reuptake Inhibitors e.g.,
Fluoxetine
TEST INTERACTIONS: Interfere with tests used to detect
albumin, bile salts, 17­ketosteroids or
17­hydroxycorticosteroids in urine and tests that rely
upon acid precipitation as an end-point or on color
reactions for carbonyl groups.
Administration: May be taken with food to reduce GI upset.
Administer with food or milk to minimize gastrointestinal
effects.
Pregnancy Category: C
ATC Code: M01AE03
Rx MEFENAMIC ACID
Oral: 250 mg and 500 mg tablet or capsule
A fenamate-derived (anthranilic acid), nonsteroidal anti-
inflammatory medicine, which possesses greater anti-
inflammatory and analgesic properties than ibuprofen or
aspirin.
Indications: Symptomatic relief of acute pain and
inflammation; symptomatic relief of dysmenorrhea;
menorrhagia due to dysfunctional causes or the
presence of an IUD when organic pelvic pathology has
been excluded; premenstrual syndrome
403
 MUSCULO-SKELETAL SYSTEM

Contraindications: Patients with inflammatory bowel
disease, GI ulcers and history of GI bleeding or
perforation, related to NSAID therapy; active or history of
recurrent peptic ulcer or hemorrhage; severe heart
failure, hepatic failure, and renal failure; pain treatment
after coronary artery bypass surgery; during the last
trimester of pregnancy
Dose:
Dysmenorrhea, by mouth, ADULT, 500 mg 3 times daily, to
be administered on the onset of menstrual pain and
continue while symptoms persist according to the clinical
judgment of the physician.
Menorrhagia, by mouth, ADULT, 500 mg 3 times daily,
starting with the onset of bleeding and associated
symptoms and continued according to the clinical
judgment of the physician.
Premenstrual syndrome, by mouth, ADULT, 500 mg 3 times
daily, starting with the onset of symptoms and continued
until the anticipated cessation of symptoms according to
the judgment of the physician.
Dose Adjustment:
Renal and Hepatic Impairment:
Use drug with caution for mild to moderate impairment.
M
Less Common: Bronchospasm, confusion, esophageal
ulceration, heart failure, hyperkalemia, rash, renal
impairment
Rare: Similar to Ibuprofen; see under Ibuprofen
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Mefenamic Acid:
Angiotensin II Receptor Blockers e.g., Losartan
(significant decrease in renal function), Corticosteroids
Oral (gastric ulceration), Diuretics e.g., Loop Diuretics,
Thiazide Diuretics (reduced renal function;
nephrotoxicity), Other NSAIDs
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors e.g. Enalapril (renal impairment;
hyperkalemia)
Reduces therapeutic effect of the following drugs:
ACE Inhibitors e.g. Enalapril, Angiotensin II Receptor
Blockers e.g., Losartan (antihypertensive effect),
Diuretics e.g., Loop Diuretics, Thiazide Diuretics (diuretic
effect)

Avoid concomitant use with:

Precautions: Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
WARNING: NSAIDs are associated with an increased Warfarin (anticoagulant effect)
risk of adverse cardiovascular thrombotic events,
including fatal MI and stroke. Increases risk of adverse or toxic effects of Mefenamic Acid:
NSAIDs may increase risk of GI irritation, Alendronate (gastric ulceration)
inflammation, ulceration, bleeding, and
perforation. Increases risk of adverse or toxic effects of the following
drugs:
Drugs affecting clotting process e.g., Ketorolac
Undesirable effects may be minimized by using the lowest
(bleeding), Drugs which are renally excreted e.g.,
effective dose for the shortest duration necessary to
Calcineurin Inhibitors, Drugs which increase Potassium
control symptoms; Concentration e.g., Amiloride, Triamterene
Anemia, agranulocytosis, and Coombs’-positive (hemolytic (hyperkalemia), Vitamin K Antagonists e.g., Warfarin
anemia is seen with prolonged use; should not be given
(serious bleeding)
for longer than 7 days);
Use with caution among patients with history of GI diseases
Reduces therapeutic effect of the following drugs:
or bleeding;
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
Hepatic and renal disease, hypoprothrombinemia, or
(reduced antihypertensive effect)
vitamin K deficiency;
Use with caution in patients with hypertension, CHF and Administration: Should be taken with food or immediately
cardiovascular disease; after meals.
May adversely affect BP control;
Anaphylactoid reactions may be seen; Pregnancy Category: C; D (prolonged use or near term)
Caution is required for patients suffering, or with a previous
history of, bronchial asthma (may precipitate ATC Code: M01AG01
bronchospasm);
Patient’s response to NSAIDs is variable, switch to another
preparation if the response is inadequate;
Monitor stool for blood and kidney function if NSAIDs are to
be used chronically (patients on prolonged therapy
should be kept under surveillance with particular
attention to liver dysfunction, rash, blood dyscrasias or
development of diarrhea);
Elderly;
Pregnancy (avoid during last trimester).

Adverse Drug Reactions:

Common: Diarrhea, dizziness, dyspepsia, GI ulceration or
bleeding, headache, hemorrhage, hypertension, nausea,
raised liver enzymes, salt and fluid retention, vomiting

404
MUSCULO-SKELETAL SYSTEM
SELECTIVE COX 2 INHIBITOR
Rx CELECOXIB
Oral: 100 mg, 200 mg, and 400 mg capsule
A diaryl-substituted, pyrazole-derived, selective COX-2
inhibitor, which is associated with less GI side effects
and susceptibility to bruising and bleeding than
nonselective NSAIDs.
Indications: Relief of the signs and symptoms of
osteoarthritis, ankylosing spondylitis, and rheumatoid
arthritis; and short-term (≤7 days) management of
moderate to severe acute injury (post-operative,
musculoskeletal or soft tissue), or following dental
extraction
Contraindications: Active GI disease or bleeding; heart
failure, angina, peripheral arterial disease or
cerebrovascular disease; perioperative setting of
Coronary Artery Bypass Graft (CABG) surgery; third
trimester of pregnancy; breastfeeding; severe liver
impairment or active liver disease; severe renal
impairment; inflammatory bowel disease; known
hyperkalemia
Dose:
NOTE: Risk of cardiovascular adverse events is dose-
related; do not use >200 mg daily long-term; use lowest
effective dose for the shortest duration of time,
consistent with patient treatment goals.
Acute dental pain, by mouth, ADULT, 400 mg, followed by
an additional 200 mg if needed on Day 1; maintenance
dose, 200 mg twice daily, as needed, not to exceed 7
days.
Ankylosing spondylitis, by mouth, ADULT, up to 200 mg
daily, in 1 or 2 divided doses twice daily.
Osteoarthritis, by mouth, ADULT, 200 mg daily as a single
dose or in 2 divided doses.
Pain, acute (post-operative, musculoskeletal or soft tissue),
by mouth, ADULT, 400 mg as a single dose on the 1st
day, then 200 mg once or twice daily if needed
(maximum, 7 days treatment).
Rheumatoid arthritis, by mouth, ADULT, 100 mg twice daily;
may be increased to 200 mg twice daily (short-term use
only).
Dose Adjustment:
Geriatric:
Initiate at the lowest recommended dose of the medicine in
patients weighing <50 kg (AUC may be increased by
50%).
Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction by
50% is warranted.
Precautions:
WARNING: Associated with an increased risk of serious
(and potentially fatal) adverse cardiovascular events,
including MI, stroke, ischemic heart disease,
cerebrovascular disease, and congestive heart
failure. This risk may increase with duration of use.
Patients with cardiovascular disease or risk factors
for cardiovascular disease may be at greater risk.
NSAIDs cause an increased risk of serious GI adverse
events, including bleeding, ulceration, and
perforation of the stomach or intestines, which can
be fatal. These events can occur at any time during
their use and without warning symptoms.
Pre-existing renal impairment increases the risk of
NSAID-induced impairment.
Hypertension, Congestive heart failure or cardiovascular
disease;
GI diseases or bleeding (use with caution);
Vitamin K deficiency, or hypoprothrombinemia,
Anaphylactoid reactions;
Asthma, especially with rhinitis or nasal polyps;
Persistent urinary symptoms, hematuria, or cystitis;
Renal impairment;
M
Elderly;
Pregnancy;
Women (reconsider use if planning for pregnancy).
Adverse Drug Reactions:
Common: Abdominal pain, back pain, cough, diarrhea,
dizziness, dyspepsia, fever, flatulence, headache,
insomnia, nasopharyngitis, nausea, peripheral edema,
pharyngitis, rash, rhinitis, sinusitis, upper respiratory
tract infection, vomiting
Less Common: Alopecia, anemia, angina, anorexia, anxiety,
arthrosis, bradycardia, bronchospasm, cellulitis, chest
pain, constipation, cystitis, depression, dermatitis,
dryness of skin, dysphagia, dyspnea, facial edema,
fatigue, gastroesophageal reflux, GI ulcer,
hypercholesterolemia, hypertension, hypokalemia, MI,
migraine, myalgia, nervousness, pain palpitations,
paresthesia, photosensitivity, pruritus, sinus
tachycardia, somnolence, tinnitus, urinary frequency,
urticaria, ventricular hypertrophy, vertigo, xerostomia
Rare: Acute renal failure, agranulocytosis, anaphylactoid
reactions, angioedema, aplastic anemia,
cerebrovascular accidents, CHF, cholelithiasis, colitis,
DVT, erythema multiforme, esophageal perforation,
exfoliative dermatitis, gangrene, GI bleeding, hepatic
failure and necrosis, hepatitis, hypoglycemia,
hyponatremia, intestinal obstruction and perforation,
intracranial hemorrhage, jaundice, leukopenia,
pancreatitis, pancytopenia, pulmonary embolism, renal
papillary necrosis, sepsis, Stevens-Johnson syndrome,
suicide, syncope, taste disturbance, thrombocytopenia,
thrombophlebitis, toxic epidermal necrolysis, vasculitis,
ventricular fibrillation
Drug Interactions:
Monitor closely with:
Decreases excretion of the following drugs:
Aminoglycosides e.g. Streptomycin
405

Enhances therapeutic effect of the following drugs:
Anticoagulants, Antidepressants, Benzodiazepines e.g.
Midazolam
Increases risk of adverse or toxic effects of Celecoxib:
Angiotensin II Receptor Blockers e.g. Losartan
(significant decrease in renal function)
Increases risk of adverse or toxic effects of the following
drugs:
ACE Inhibitors e.g. Enalapril (significant decrease in renal
function), Agents with Antiplatelet Properties e.g.,
NSAIDs, SSRIs (bleeding), Anticoagulants (serious
bleeding), Haloperidol, Quinolone Antibiotics e.g.
Levofloxacin (neuroexcitatory and/or seizure-
potentiating effect)
Reduces therapeutic effect of the following drugs:
ACE Inhibitors e.g. Enalapril, Angiotensin II Receptor
Blockers (antihypertensive effect), Diuretics e.g.,
Potassium-sparing Diuretics, Thiazide Diuretics, Beta
Blockers (antihypertensive effect)
Avoid concomitant use with:
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
M
Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Celecoxib:
Aspirin (increased rate of GI ulceration or other
complications), Other NSAIDs
Increases risk of adverse or toxic effects of Vitamin K
Antagonists, e.g., Warfarin (serious bleeding)
Reduces therapeutic effect of the following drugs:
Loop Diuretics e.g. Furosemide (antagonism of
prostaglandin-mediated effect)
Administration: May be administered without regard to
meals.
Pregnancy Category: C; D in the 3rd trimester or near
delivery.
ATC Code: M01AH01
MUSCLE RELAXANTS
PERIPHERALLY-ACTING AGENTS
Rx ATRACURIUM
Inj.: 10 mg/mL (as besilate), 2.5 mL and 5 mL ampule (IV)
A non-depolarizing, neuromuscular-blocking agent that
restricts neural transmission at the myoneural junction
by binding with cholinergic receptor sites.
Indications: As an adjunct to general anesthesia; to
facilitate endotracheal intubation; to provide skeletal
muscle relaxation during surgery or mechanical
ventilation
406
MUSCULO-SKELETAL SYSTEM
Contraindications: Hypersensitivity to atracurium besylate
or any component of the formulation; known
hypersensitivity to benzyl alcohol (multiple-dose vials)
Dose:
NOTE: Dose to effect. Doses will vary due to interpatient
variability.
Adjunct to surgical anesthesia, by IV bolus, ADULT, 0.4–0.5
mg/kg, then 0.08–0.1 mg/kg after 20–45 minutes to
maintain neuromuscular block; repeat dose at 15– to
25–minute intervals as needed; CHILD >2 years and
ADOLESCENT, 0.4–0.5 mg/kg, then 0.08–0.1 mg/kg
after 20–45 minutes; repeat dose at 15– to 25–minute
intervals as needed; CHILD 1 month – 2 years, initially
0.3–0.4 mg/kg followed by maintenance doses as
needed;
If to be administered after succinylcholine for intubation
(balanced anesthesia), initiate at 0.3–0.4 mg/kg;
Pretreatment or priming, administer 10% of intubating
dose given 2–4 minutes before the larger second dose.
[NOTE: Maintenance doses may be required with slightly
greater frequency in infants and children compared to
adults. Initial dose may be reduced to 0.3–0.4 mg/kg in
patients with significant cardiovascular disease or
history of elevated risk of histamine release. Priming may
be uncomfortable for the patient, may increase the risk
of aspiration and difficulty swallowing. Intubating
conditions after priming may not be as good as that seen
with succinylcholine].
Maintenance infusion for continued surgical relaxation
during extended surgical procedures, by continuous IV
infusion, ADULT and CHILD, at initial signs of recovery
from bolus dose, initiate at a rate of 9 to 10
micrograms/kg per minute (0.54–0.6 mg/kg per hour) ;
block is usually maintained by a rate of 5–9
micrograms/kg per minute (0.3–0.54 mg/kg per hour);
if under balanced anesthesia, administer 2–15
micrograms/kg per minute (0.12–0.9 mg/kg per hour).
Dose Adjustment:
Obesity:
Morbidly-obese patients should be dosed using ideal body
weight or an adjusted body weight. Time to recovery of
twitch response may be prolonged.
Precautions:
Anaphylaxis;
Bradycardia;
Cross-sensitivity;
Burn injury (resistance may occur if burns ≥20% of total
body surface area).
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia,
demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma may occur);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
metabolic acidosis, metabolic alkalosis, respiratory
acidosis, Lambert-Eaton syndrome and myasthenia
gravis may occur);
Elderly (use with caution; effects and duration are more
variable; consider dose reduction);
Immobilized patients (resistance may occur);
Children.
MUSCULO-SKELETAL SYSTEM
Some dosage forms may contain benzyl alcohol (amounts
≥99 mg/kg per day of benzyl alcohol have been
associated with a potentially fatal toxicity called “gasping
syndrome” in neonates; see manufacturer’s labeling for
contents prior to administration in neonates).
Pregnancy (use with caution);
Lactation (not known if excreted in breast milk).
Adverse Drug Reactions:
Common: Flushing
Less Common: Bronchial secretions, erythema, hives,
itching, wheezing, allergic reaction, bradycardia,
bronchospasm, dyspnea, hypotension, injection site
reaction, seizure, acute quadriplegic myopathy
syndrome (prolonged use), laryngospasm, myositis
ossificans (prolonged use), tachycardia, urticaria
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Atracurium:
Aminoglycosides e.g. Streptomyicn (respiratory
depressant effect), Calcium Channel Blockers e.g.
Amlodipine, Capreomycin (neuromuscular-blocking
effect), Clindamycin Topical, Cyclosporine Systemic,
Inhalational Anesthetics, Lincosamide, Lithium, Loop
Diuretics, Magnesium Salts, Minocycline, Procainamide,
Quinidine, Spironolactone, Tetracycline Derivatives,
Vancomycin
Increases risk of adverse or toxic effects of Atracurium:
Ketorolac (apnea)
Increases risk of adverse or toxic effects of Cardiac
Glycosides (arrhythmogenic effect)
Reduces therapeutic effect of Atracurium:
Acetylcholinesterase Inhibitors e.g., Neostigmine,
Fosphenytoin-Phenytoin, Loop Diuretics
Avoid concomitant use with:
Enhances therapeutic effect of Atracurium:
Colistimethate, Polymyxin B, Quinine
Increases risk of adverse or toxic effects of the following
drugs:
Corticosteroids, Systemic (increased muscle weakness;
polyneuropathies; myopathies)
Administration: May be given undiluted as a bolus IV
injection or via continuous IV infusion.
Do NOT administer by IM as this may cause excessive
tissue irritation.
Use infusion solutions within 24 hours of preparation.
Pregnancy Category: C
ATC Code: M03AC04
Rx PANCURONIUM
Inj.: 2 mg/mL (as bromide), 2 mL ampule (IM, IV)
A non-depolarizing, neuromuscular-blocking agent, that
induces muscle relaxation by restricting neural
transmission at the myoneural junction after binding to
cholinergic receptor sites.
Indications: Facilitation of endotracheal intubation and
relaxation of skeletal muscles during surgery; facilitation
of mechanical ventilation in ICU patients
Contraindication: Hypersensitivity to pancuronium,
bromide, or any component of the formulation
Dose:
NOTE: Dose to effect. Doses will vary due to interpatient
variability.
Intubation, by IV injection, ADULT and CHILD, initially 0.06–
0.1 mg/kg or 0.05 mg/kg after initial dose (maintenance
dose, 0.01 mg/kg administered 60 to 100 minutes after
initial dose, then 0.01 mg/kg every 25 – 60 minutes);
M
Pretreatment or priming, 10% of intubating dose given
3–5 minutes before intubating dose.
ICU paralysis (e.g., facilitate mechanical ventilation) in
select adequately sedated patients, by IV bolus, ADULT
and CHILD, 0.06–0.1 mg/kg followed by either:
By continuous infusion, 1–2 micrograms/kg per minute
(0.06–0.12 mg/kg per hour), or;
By continuous infusion, 0.8–1.7 micrograms/kg per
minute (0.048–0.102 mg/kg per hour); or
By intermittent bolus, 0.1–0.2 mg/kg every 1–3 hours.
Dose Adjustment:
Renal Impairment:
For patients with CrCl of 10–50 mL/minute or patients on
CRRT, administer 50% of normal dose.
Avoid use in patients with CrCl <10 mL/minute, or patients
on hemodialysis or peritoneal dialysis.
Hepatic Impairment:
Large doses may be required and problems may arise in
antagonism.
Obesity:
Use ideal body weight for obese patients.
Precautions:
WARNING: Should be administered by adequately
trained individuals familiar with its use.
Cross-sensitivity (use extreme caution in patients with
previous anaphylactic reactions);
Burn injury (resistance may occur if burns ≥20% of total
body surface area);
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia,
demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma may occur);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
metabolic acidosis, metabolic alkalosis, respiratory
407

acidosis, Lambert-Eaton syndrome and myasthenia
gravis may occur).
Hepatic and renal impairment (use with caution);
Elderly;
Immobilized patients (resistance may occur).
Some dosage forms may contain benzyl alcohol (amounts
≥99 mg/kg per day of benzyl alcohol have been
associated with a potentially fatal toxicity called “gasping
syndrome” in neonates; see manufacturer’s labeling for
contents prior to administration in neonates);
Pregnancy (may be used short-term in cesarean section;
reduced doses recommended in patients also receiving
magnesium sulfate due to enhanced effects).
Adverse Drug Reactions:
Common and Less Common: Elevated blood pressure and
cardiac output, tachycardia, edema, skin flushing,
circulatory collapse, rash, itching, erythema, burning
sensation along the vein, excessive salivation, profound
muscle weakness, wheezing, bronchospasm,
hypersensitivity reaction, acute quadriplegic myopathy
syndrome (prolonged use), anaphylactoid reactions,
anaphylaxis, myositis ossificans (prolonged use)
Drug Interactions:
M
Monitor closely with:
Enhances therapeutic effect of Pancuronium:
Aminoglycosides (respiratory depressant effect),
Calcium Channel Blockers e.g., Amlodipine, Capreomycin
(neuromuscular-blocking effect), Clindamycin (Topical),
Cyclosporine (Systemic), Inhalational Anesthetics,
Lincosamide, Lithium, Loop Diuretics e.g., Furosemide,
Magnesium Salts, Minocycline, Procainamide, Quinidine,
Spironolactone, Tetracycline Derivatives, Vancomycin
Increases risk of adverse or toxic effects of Pancuronium:
Ketorolac (apnea)
Increases risk of adverse or toxic effects of the following
drugs:
Cardiac Glycosides e.g., Digoxin (arrhythmogenic effect)
Reduces therapeutic effect of Pancuronium:
Acetylcholinesterase Inhibitors e.g., Neostigmine,
Fosphenytoin-Phenytoin, Loop Diuretics
Avoid concomitant use with:
Enhances therapeutic effect of Pancuronium:
Colistimethate, Polymyxin B, Quinine
Increases risk of adverse or toxic effects of Pancuronium:
Theophylline Derivatives e.g., Aminophylline
Increases risk of adverse or toxic effects of the following
drugs:
Corticosteroids (Systemic) (increased muscle weakness;
polyneuropathies; myopathies)
Reduces therapeutic effect of Pancuronium:
Theophylline Derivatives e.g., Aminophylline
Administration: May be administered undiluted by rapid IV
injection.
Pregnancy Category: C
408
MUSCULO-SKELETAL SYSTEM
ATC Code: M03AC01
Rx ROCURONIUM
Inj.: 10 mg/mL (as bromide), 5 mL ampule / vial (IV)
A non-depolarizing, neuromuscular-blocking agent with a
rapid to intermediate onset depending on the dose and
intermediate duration. It acts by competing for
cholinergic receptors at the motor end-plate.
Indications: Adjunct to general anesthesia to facilitate both
rapid sequence and routine tracheal intubation; to
provide skeletal muscle relaxation during surgery or
mechanical ventilation
Contraindication: Known hypersensitivity to rocuronium or
other neuromuscular blocking agents
Dose:
NOTE: Individualize doses and use a peripheral nerve
stimulator to monitor drug effect, need for additional
doses, adequacy of spontaneous recovery or
antagonism, and to decrease the complications of over
dosage if additional doses are administered.
Tracheal intubation, by IV injection, ADULT, initially 0.6
mg/kg (expected to provide 31 (15–85) minutes of
clinical relaxation under opioid, nitrous oxide, or oxygen
anesthesia) [NOTE: Maximum blockade is achieved in
most patients in less than 3 minutes. Under halothane,
isoflurane, and enflurane anesthesia, some extension of
the period of clinical relaxation should be expected].
Rapid sequence intubation, by IV injection, ADULT, 0.6–1.2
mg/kg (will provide excellent or good intubating
conditions in most patients in less than 2 minutes).
Endotracheal intubation, mechanical ventilation in intensive
care, or muscle relaxant in general anesthesia, by IV
injection, ADULT, initially 600 micrograms/kg, may
reduce to 75–100 micrograms/kg for prolonged
inhalational anesthesia; maintenance, 150
micrograms/kg; ADULT ≥65 years, maintenance, 75–
100 micrograms/kg.
Rapid sequence intubation, by IV injection, ADULT, 1 mg/kg.
Dose Adjustment:
Geriatric:
Use with caution. Patients ≥65 years exhibited a slightly
prolonged median clinical duration.
Renal Impairment and biliary tract disease:
Maintenance dose: 75–100 micrograms/kg per hour by
injection or 300–400 micrograms/kg per hour by
infusion.
Hepatic Impairment:
Use with caution. Median clinical duration may be slightly
prolonged.
Maintenance dose: 75–100 micrograms/kg per hour by
injection or 300–400 micrograms/kg per hour by
infusion.
Obesity:
Reduce dose based on the patient’s ideal body weight.
MUSCULO-SKELETAL SYSTEM
Patients with Prolonged Circulation Time:
Do not increase initial dosage to reduce onset time. When
feasible, allow more time for the drug to achieve onset of
effect.
Precautions:
WARNING: This drug should only be administered by
experienced clinicians or trained individuals
supervised by an experienced clinician familiar
with the use, actions, characteristics, and
complications of neuromuscular blocking agents.
Should not be administered unless facilities for
intubation, mechanical ventilation, oxygen therapy,
and an antagonist are immediately available
Drugs or conditions causing potentiation of neuromuscular
block (administer rocuronium prior to potent inhalation
anesthesia to minimize potentiation);
Anaphylaxis (may be life-threatening and fatal);
Cross-reactivity between neuromuscular blocking agents,
both depolarizing and nondepolarizing, has been
reported;
Residual paralysis (extubate patient only after sufficient
recovery from neuromuscular block);
Malignant hyperthermia (use with caution);
Prolonged circulation time;
QT interval prolongation;
Pulmonary vascular resistance (use with caution);
Extravasation (may be associated with signs and symptoms
of local irritation);
Cardiovascular disease;
Respiratory disease;
Myasthenia gravis or myasthenic syndrome, e.g. Lambert-
Eaton;
Biliary tract disease;
Neuromuscular disease;
Previous poliomyelitis;
Burn injury;
Severe electrolyte disturbances;
Renal and hepatic impairment.
Elderly;
Children;
Obesity;
Pregnancy (use with caution)
Adverse Drug Reactions:
Common: Transient hypotension and hypertension,
anaphylaxis, residual paralysis, myopathy, increased
pulmonary vascular resistance; anaphylaxis (potentially
fatal)
Less Common: Arrhythmia, abnormal electrocardiogram,
tachycardia, nausea, vomiting, asthma, hiccup, rash,
injection site edema, pruritus
Drug Interactions:
Enhances therapeutic effect of Rocuronium:
Antibiotics, Beta Blockers e.g., Propranolol, Calcium
Channel Blockers e.g., Amlodipine, Corticosteroids,
Diuretics, Inhalation Anesthetics, Lithium (increased
duration), Local Anesthetics (increased duration),
Magnesium, Phenytoin [acute administration],
Procainamide (increased duration), Quinine
Increases risk of adverse or toxic effects of Rocuronium:
Antibiotics (prolongation of neuromuscular block)
Increases risk of adverse or toxic effects of Rocuronium:
Quinidine (recurrent paralysis)
Reduces therapeutic effect of the following drugs:
Anticonvulsants, Calcium Chloride, Carbamazepine,
Phenytoin [chronic administration], Potassium Chloride,
Protease Inhibitors e.g., Ritonavir
Administration: For IV administration only.
Inspect visually for particulate matter and clarity prior to
administration whenever solution and container permit.
Do NOT use solution if particulate matter is present.
Pregnancy Category: C
ATC Code: M03AC09
SUXAMETHONIUM
Rx
(SUCCINYLCHOLINE)
Inj.: 20 mg/mL (as chloride), 10 mL vial (IV)
M
A short-acting muscle relaxant that acts like acetylcholine. It
produces depolarization of the motor end-plate at the
myoneural junction which causes sustained flaccid
skeletal muscle paralysis.
Indications: To facilitate both rapid sequence and routine
endotracheal intubation; to relax skeletal muscles during
surgery
Contraindications: Personal or familial history of malignant
hyperthermia; myopathies associated with elevated
serum creatine phosphokinase (CPK) values; acute
phase of injury following major burns, multiple trauma,
extensive denervation of skeletal muscle, or upper motor
neuron injury
Dose:
NOTE: Dose to effect. Doses will vary due to interpatient
variability.
Initial dose of succinylcholine must be increased when
nondepolarizing agent pretreatment is used.
Intubation, by IV injection, ADULT, 0.6 mg/kg (range, 0.3–
1.1 mg/kg); OLDER CHILD and ADOLESCENT, initially 1
mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
10 minutes as needed); YOUNGER CHILD, initially 2
mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
10 minutes as needed).
Rapid sequence intubation, by IV injection, ADULT, 1–1.5
mg/kg; OLDER CHILD and ADOLESCENT, initially 1
mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
10 minutes as needed); YOUNGER CHILD, initially 2
mg/kg per dose (maintenance, 0.3–0.6 mg/kg every 5–
10 minutes as needed).
Muscle relaxant in general anesthesia, by IV injection,
ADULT, 0.3–1.1 mg/kg as single dose, supplementary
doses of 50–100% the initial dose may be given at 5- to
10-minute intervals; CHILD 1-12 years, 1 mg/kg; CHILD
<1 year, 2 mg/kg;
409

for prolonged procedures, ADULT, 0.1 – 0.2% at 2.54
mg/minute, adjusted as necessary.
Dose Adjustment:
Obesity:
Use ideal body weight for obese patients.
Precautions:
WARNING: Acute rhabdomyolysis with hyperkalemia,
ventricular arrhythmias and cardiac arrest have
been reported (rarely) in children with undiagnosed
skeletal muscle myopathy. Prolonged resuscitation
may be required. Use in children should be
reserved for emergency intubation or where
immediate airway control is necessary.
Patients with reduced plasma cholinesterase activity due to
genetic abnormalities of plasma cholinesterase or when
associated with other conditions, e.g., pregnancy, severe
liver disease, renal disease (consider dose reduction);
Bradycardia;
Intraocular pressure, IOP (use caution with narrow-angle
glaucoma or penetrating eye injuries);
Malignant hyperthermia (risk may be increased with
concomitant administration of volatile anesthetics);
M
Vagal tone;
Burn injury;
Conditions which may antagonize neuromuscular blockade
(e.g., alkalosis, hypercalcemia, demyelinating lesions,
peripheral neuropathies, denervation, infection, muscle
trauma, and diabetes mellitus);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, severe hyponatremia,
severe hypocalcemia, severe hypokalemia,
hypermagnesemia, neuromuscular diseases, acidosis,
acute intermittent porphyria, Lambert-Eaton syndrome,
myasthenia gravis, renal failure, and hepatic failure);
Hyperkalemia;
Plasma pseudocholinesterase disorders;
Elderly;
Pregnancy (use with caution);
Lactation (use with caution).
Adverse Drug Reactions:
Common and Less Common: Arrhythmias, bradycardia,
cardiac arrest, hypertension or hypotension, tachycardia,
rash, hyperkalemia, excessive salivation, jaw rigidity,
muscle fasciculation, postoperative muscle pain,
rhabdomyolysis (with possible myoglobinuric acute renal
failure), increased intraocular pressure, acute renal
failure (secondary to rhabdomyolysis), apnea, respiratory
depression (prolonged), anaphylaxis, malignant
hyperthermia, acute quadriplegic myopathy syndrome
(prolonged use), myositis ossificans (prolonged use)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Suxamethonium:
Aminoglycosides (respiratory depressant effect),
Bambuterol, Capreomycin, Clindamycin Topical,
Cyclosporine Systemic, Lincosamide, Lithium, Loop
Diuretics, Magnesium Salts, Minocycline, Procainamide,
Quinidine, Tetracycline Derivatives, Vancomycin
Increases risk of adverse or toxic effects of the following
drugs:
410
MUSCULO-SKELETAL SYSTEM
Analgesics Opioid (bradycardic effect), Cardiac
Glycosides e.g., Digoxin (arrhythmogenic effect)
Reduces therapeutic effect of Suxamethonium:
Loop Diuretics e.g., Furosemide
Avoid concomitant use with:
Enhances therapeutic effect of Suxamethonium:
Colistimethate, Phenelzine (neuromuscular-blocking
effect), Polymyxin B, Quinine
Increases risk of adverse or toxic effects of Suxamethonium:
Acetylcholinesterase Inhibitors e.g., Neostigmine
(prolonged neuromuscular blockade)
Increases serum concentration of Suxamethonium:
Acetylcholinesterase Inhibitors e.g., Neostigmine,
Cyclophosphamide, Echothiophate Iodide
Administration: May be given by rapid IV injection without
further dilution.
Pregnancy Category: C
ATC Code: M03AB01
Rx VECURONIUM
Inj.: freeze-dried powder (as bromide), 4 mg/mL ampule +
1 mL solvent (IV)
A non-depolarizing, neuromuscular-blocking agent that
prevents acetylcholine from binding to receptors on the
motor end-plate thereby inhibiting depolarization. It has
a shorter duration of action than pancuronium.
Indications: To facilitate endotracheal intubation; to relax
skeletal muscles during surgery; to facilitate mechanical
ventilation in ICU patients
Contraindication: Hypersensitivity to vecuronium or any
component of the formulation
Dose:
NOTE: Dose to effect. Doses will vary due to interpatient
variability.
Tracheal intubation, by IV injection, ADULT and CHILD,
initially 0.08–0.1 mg/kg; pretreatment or priming, 10%
of intubating dose given 3–5 minutes before intubating
dose. [NOTE: If intubation is performed using
succinylcholine, reduce initial vecuronium dose to 0.04–
0.06 mg/kg with inhalation anesthesia and 0.05–0.06
mg/kg with balanced anesthesia. Children 1­10 years
may require slightly higher initial doses and more
frequent supplementation].
Maintenance for continued surgical relaxation (only after
return of neuromuscular function), by intermittent IV
injection, ADULT, 0.01–0.015 mg/kg;
by continuous IV infusion, ADULT, 0.8–1.2
micrograms/kg per minute (0.048–0.072 mg/kg per
hour).
[NOTE: Use lower end of the dosing range when
anesthesia is maintained with an inhaled anesthetic
MUSCULO-SKELETAL SYSTEM

agent, with the redosing interval guided by monitoring Some dosage forms may contain benzyl alcohol (see
with a peripheral nerve stimulator]. manufacturer’s labeling for contents prior to
ICU paralysis in selected adequately sedated patients, by IV administration in neonates);
administration, ADULT, initially 0.08–0.1 mg/kg by IV Elderly;
bolus, then by continuous IV infusion of 0.8–1.7 Immobilized patients (resistance may occur);
micrograms/kg per minute (0.048–0.102 mg/kg per Children;
hour) ; monitor depth of blockade every 1–2 hours Pregnancy;
initially until stable dose, then every 8–12 hours (usual Lactation.
maintenance infusion dose range, 0.8–1.2
micrograms/kg per minute (0.048–0.072 mg/kg per Adverse Drug Reactions:
hour); Less Common: Bradycardia, circulatory collapse, edema,
by intermittent IV bolus, 0.1–0.2 mg/kg per dose; may flushing; hypersensitivity reaction, itching, rash, acute
be repeated when neuromuscular function returns. quadriplegic myopathy syndrome (prolonged use),
[NOTE: Adjust rate of administration in increments of 0.3 myositis ossificans (prolonged use)
micrograms/kg per minute (or 0.018 mg/kg/hour) or by
50% reductions of previous dose according to peripheral Drug Interactions:
nerve stimulation response or desired clinical response. Monitor closely with:
Discontinue infusion if neuromuscular function does not Enhances therapeutic effect of Vecuronium:
return. When possible, minimize depth and duration of Aminoglycosides (respiratory depressant effect),
paralysis. It is recommended to stop the infusion daily for Calcium Channel Blockers, Capreomycin
some time until forced to restart based on patient (neuromuscular-blocking effect), Clindamycin (Topical),
condition to reduce post-paralytic complications]. Cyclosporine (Systemic), Dantrolene (neuromuscular-
blocking effect), Inhalational Anesthetics, Lincosamide,
Dose Adjustment: Lithium, Loop Diuretics, Magnesium Salts, Minocycline,
Geriatric: Piperacillin (neuromuscular-blocking effect),

M
Select doses with caution. Start at low end of dosage range Procainamide, Quinidine, Spironolactone, Tetracycline
and titrate slowly to evaluate response. Derivatives, Vancomycin

Pediatric: Increases risk of adverse or toxic effects of Vecuronium:

May require slightly higher initial doses and slightly more Ketorolac (apnea)
frequent supplementation
Increases risk of adverse or toxic effects of the following
Renal Impairment: drugs:
In patients who are anephric, clinical duration is prolonged. Cardiac Glycosides e.g., Digoxin (arrhythmogenic effect)

Hepatic Impairment: Reduces therapeutic effect of Vecuronium:

Dose reduction may be required. Acetylcholinesterase Inhibitors e.g., Neostigmine,
Fosphenytoin-Phenytoin, Loop Diuretics
Obesity:
For obese adult patients of ≥130% of IBW, use ideal body Avoid concomitant use with:
weight (IBW). Onset time may be slightly delayed using Enhances therapeutic effect of Vecuronium:
IBW. Colistimethate, Polymyxin B, Quinine

Precautions: Increases risk of adverse or toxic effects of the following

WARNING: Should be administered by adequately drugs:
trained individuals familiar with its actions, Corticosteroids (Systemic) (increased muscle weakness;
characteristics, and hazards polyneuropathies; myopathies)

Administration: Concentration of 1 mg/mL may be

Cross-sensitivity (use extreme caution in patients with administered by rapid IV injection.
previous anaphylactic reactions);
Prolonged paralysis; May be used for IV infusion in fluid-restricted patients.
Burn injury (resistance may occur if burns ≥20% of total
body surface area); Pregnancy Category: C
Conditions which may antagonize neuromuscular blockade
(e.g., respiratory alkalosis, hypercalcemia, ATC Code: M03AC03
demyelinating lesions, peripheral neuropathies,
denervation, and muscle trauma);
Conditions which may potentiate neuromuscular blockade
(e.g., electrolyte abnormalities, neuromuscular diseases,
metabolic acidosis, metabolic alkalosis, respiratory
acidosis, Lambert-Eaton syndrome and myasthenia
gravis);
Hepatic and renal impairment;
Respiratory disease;

411

CENTRALLY ACTING AGENTS
Rx BACLOFEN
Oral: 10 mg tablet
A GABA analog that acts as a muscle relaxant and anti-
spastic by inhibiting both monosynaptic and polysynaptic
reflexes at the spinal level by hyperpolarizing afferent
terminals.
Indication: For the alleviation of signs and symptoms of
spasticity resulting from multiple sclerosis
Dose:
NOTE: The determination of optimal dosage requires
individual titration. Start therapy at a low dosage and
increase gradually until optimum effect is achieved
(usually between 40-80 mg daily).
Suggested dosage titration schedule:
5 mg 3 times a day for 3 days
10 mg 3 times a day for 3 days
15 mg 3 times a day for 3 days
M
20 mg 3 times a day for 3 days
Additional increases may be necessary. Maximum dose, 80
mg daily.
Dose Adjustment:
Renal Impairment:
Use with caution. Baclofen is primarily excreted unchanged
through the kidneys. Dose reduction may be necessary.
Precautions:
WARNING: Slowly reduce dose when discontinued.
Hallucinations and seizures have occurred on
abrupt withdrawal of baclofen.
Stroke;
Children;
Pregnancy (use with caution);
Lactation.
Adverse Drug Reactions:
Common: Transient drowsiness, dizziness, weakness,
fatigue, confusion, headache, insomnia, hypotension,
nausea, constipation, urinary frequency, rash, pruritus,
ankle edema, excessive perspiration, weight gain, nasal
congestion
Rare: Euphoria, excitement, depression, hallucinations,
paresthesia, muscle pain, tinnitus, slurred speech,
coordination disorder, tremor, rigidity, dystonia, ataxia,
blurred vision, nystagmus, strabismus, miosis, mydriasis,
diplopia, dysarthria, epileptic seizure, dyspnea,
palpitation, chest pain, syncope, dry mouth, anorexia,
taste disorder, abdominal pain, vomiting, diarrhea,
positive test for occult blood in stool, enuresis, urinary
retention, dysuria, impotence, inability to ejaculate,
nocturia, hematuria
Drug Interactions: No information found.
412
MUSCULO-SKELETAL SYSTEM
Administration: The lowest dose compatible with an optimal
response is recommended. If benefits are not evident
after a reasonable trial period, patients should be slowly
withdrawn from the drug.
Pregnancy Category: C
ATC Code: M03BX01
Rx DIAZEPAM
Oral: 5 mg tablet
Inj.: 5 mg/mL, 2 mL ampule (IM, IV)
A benzodiazepine that binds to stereospecific
benzodiazepine receptors on the postsynaptic GABA
neuron which results to enhanced inhibitory effect of
GABA on neuronal excitability. This results to increased
neuronal membrane permeability to chloride ions.
Indications: Skeletal muscle relaxant; preoperative or
preprocedural sedation and amnesia
Contraindications: Respiratory depression; marked
neuromuscular respiratory weakness, including unstable
myasthenia gravis; acute pulmonary insufficiency; sleep
apnea syndrome; phobic or obsessional states;
hyperkinesis; severe hepatic impairment
Dose:
NOTE: See Precautions prior to administration.
Oral absorption is more reliable than IM.
Muscle spasm, by IM or IV injection, ADULT, initially 5–10
mg, then 5–10 mg after 3–4 hours, if necessary [NOTE:
Larger doses may be required if associated with tetanus].
Muscle spasm associated with tetanus, by IM or IV injection,
CHILD ≥5 years, 5–10 mg per dose every 3 – 4 hours as
needed; CHILD <5 years and INFANT >30 days, 1–2 mg
per dose every 3–4 hours as needed.
Skeletal muscle relaxant (adjunct therapy), by mouth,
ADULT, 2–10 mg 3–4 times daily; CHILD, 0.12–0.8
mg/kg per day in divided doses every 6–8 hours;
by IM or IV injection, CHILD, 0.04–0.3 mg/kg per dose
every 2–4 hours to a maximum of 0.6 mg/kg within an
8–hour period if needed.
Dose Adjustment:
Geriatric:
Reduce dose.
Renal Impairment:
Reduce dose if used for prolonged periods.
Hepatic Impairment:
Reduce maintenance dose.
Precautions:
WARNING: Overdose may produce coma and
respiratory depression.
When given intravenously, agents for correcting
hypotension and facilities for supporting ventilation (e.g.,
MUSCULO-SKELETAL SYSTEM

AMBU bag, oxygen) in cases of respiratory depression

should be available. In such cases, the patient should be Rx EPERISONE HYDROCHLORIDE
referred to the nearest hospital immediately;
Hepatic impairment and renal impairment (avoid prolonged Oral: 50 mg tablet
use and abrupt withdrawal);
Respiratory disease; A centrally acting skeletal muscle relaxant used to improve
Muscle weakness may worsen; myotonic symptoms.
History of alcohol or drug abuse, marked personality
disorder (use only if the indication is clear, such as Indications: Used in the improvement of myotonic
seizure control) symptoms in cervical syndrome periarthritis of the
Porphyria; shoulder lumbago
Pregnancy (high doses during late pregnancy or labor may
cause neonatal hypothermia, hypotonia, and respiratory Contraindications: Children; pregnancy; kidney dysfunction;
depression) neonates
Breastfeeding (monitor infant for drowsiness).
Dose:
Adverse Drug Reactions: Muscle spasms, by mouth, ADULT, 50 mg every 8 hours.
Common: Coma or sensorial depression, hypotension,
respiratory depression Dose Adjustment:
Rare: Allergic reactions including anaphylaxis, jaundice, Geriatric:
transient elevated liver function tests Administer half the dose.

Drug Interactions: Precautions:

Monitor closely with: Hepatic Impairment;
Enhances therapeutic effect of Diazepam: Children (use is not recommended).

M
Amlodipine (hypotensive effect)
SKILLED TASKS. May impair ability to perform certain tasks,
Enhances therapeutic effect of the following drugs: e.g., operating machinery or driving.
CNS Depressants, e.g., Alcohol, Sedatives, Tranquilizers
(CNS depression; sedative effect), Enalapril, Adverse Drug Reactions:
Furosemide, Hydrochlorothiazide, Methyldopa, Nitrates, Common and Less Common: Weakness, dizziness,
e.g., Isosorbide Dinitrate (hypotensive effect), insomnia, drowsiness, numbness or trembling in the
extremities, hepatic and renal dysfunction,
Increases risk of adverse or toxic effects of Diazepam: hematological changes, skin rashes, itching, GI
Azole Derivatives, e.g., Fluconazole disturbances, urinary disorders
Rare: Shock
Increases risk of adverse or toxic effects of the following
drugs: Drug Interactions:
Chlorphenamine, Chlorpromazine (sedative effect), Avoid concomitant use with:
Seizure-inducing Drugs (lowers seizure threshold) Enhances therapeutic effect of Eperisone:
Tolperisone HCl
Reduces therapeutic effect of Diazepam:
Theophylline (sedative effects) Administration: Should be taken with food. Take after
meals.
Avoid concomitant use with:
Reduces therapeutic effect of Diazepam: Pregnancy Category: Varied classification, A / B / C
Rifampicin
ATC Code: M03BX09
Administration: For IV administration, give at a rate not
faster than 2 mg/minute.
DIRECTLY ACTING AGENTS
Avoid extravasation, intra-arterial and IM injection.

NOTE: Avoid dilution and infusion of injection, as diazepam Rx DANTROLENE

has a low solubility and adsorbs to PVC-giving sets.

Pregnancy Category: D Oral: 25 mg and 50 mg capsule (as sodium salt)

Inj.: 20 mg (as sodium salt) with 3 g mannitol/vial (for
ATC Code: Not Available reconstitution with 60 mL sterile water for injection)
(IV)

A skeletal muscle relaxant that acts directly on skeletal

muscles by interfering with release of calcium ions from
the sarcoplasmic reticulum. This prevents or reduces the
increase in myoplasmic calcium ion concentration.

413

Indications: Treatment of spasticity associated with upper
motor neuron disorders (e.g., spinal cord injury, stroke,
cerebral palsy, or multiple sclerosis)
NOTE: Dantrolene prophylaxis is not recommended for most
MH-susceptible patients, provided non-triggering
anesthetics are used and an adequate supply of
dantrolene is available.
Contraindications: Active liver disease; should not be used
when spasticity is used to maintain posture/balance
during locomotion or to obtain or maintain increased
function
Dose:
NOTE: Individualize dose and titrate to maximum effect. Use
the lowest dose compatible with optimal response. Some
patients may not respond until a higher daily dosage is
achieved. Each dose level should be maintained for 7
days to determine patient response. If no further benefit
observed with the higher dose level, then decrease
dosage to previous dose level.
Spasticity, by mouth, ADULT, initially 25 mg once daily for 7
days; increase to 25 mg 3 times daily for 7 days, increase
M
to 50 mg 3 times daily for 7 days, and then increase to
100 mg 3 times daily; some patients may require 100
mg 4 times daily (maximum dose, 400 mg daily); CHILD,
initially 0.5 mg/kg per dose once daily for 7 days;
increase to 0.5 mg/kg per dose 3 times daily for 7 days,
increase to 1 mg/kg per dose 3 times daily for 7 days,
and then increase to 2 mg/kg per dose 3 times daily;
some patients may require 2 mg/kg per dose 4 times
daily (maximum dose, 400 mg daily).
Precautions:
WARNING: Potential for hepatotoxicity. Do NOT use in
conditions other than those recommended.
Prescribe the lowest possible effective dose for the
individual patient. If no observable benefit is
derived from dantrolene after a total of 45 days,
discontinue therapy.
Use dantrolene only in conjunction with
appropriate monitoring of hepatic function,
including frequent determination of AST or ALT.
Greater risk of hepatic injury in women, patients
>35 years, and patients taking other
medication(s).
CNS effects (lightheadedness, dizziness, somnolence, and
vertigo may occur and may persist for 48 hours post-
dose);
Muscle weakness (e.g., loss of grip strength, weakness in
the legs, dyspnea, respiratory muscle weakness,
dysphagia, and decreased inspiratory capacity has
occurred with IV dantrolene; monitor patients for the
adequacy of ventilation and for difficulty swallowing or
choking);
Dysphagia (use caution at meal time on day of
administration);
Photosensitivity (oral therapy may cause photosensitivity;
discontinue if skin erythema occurs)
Cardiovascular and respiratory disease (use oral therapy
with caution).
Hepatotoxicity;
414
MUSCULO-SKELETAL SYSTEM
Hepatic disease (use oral therapy with caution)
Pregnancy (closely monitor mother and newborn);
Lactation (low amounts are excreted into breast milk; use
with caution).
SKILLED TASKS. May impair ability to perform certain tasks,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Tachycardia, drowsiness, dizziness, headache,
myasthenia, dysphagia, nausea, vomiting, cardiac
failure, phlebitis, variable blood pressure, chills, choking
sensation, confusion, depression, insomnia, malaise,
nervousness, seizure, speech disturbance, diaphoresis,
eczematous rash, fatigue, hair disease (abnormal
growth), pruritus, urticaria, abdominal cramps, anorexia,
constipation, diarrhea, dysgeusia, gastric irritation,
gastrointestinal hemorrhage, sialorrhea, crystalluria,
difficulty in micturition, erectile dysfunction, hematuria,
nocturia, urinary incontinence, urinary retention, urinary
frequency, anemia, aplastic anemia, leukopenia,
thrombocytopenia, lymphocytic lymphoma, local tissue
necrosis, back pain, myalgia, diplopia, epiphora, visual
disturbance, pleural effusion (with pericarditis),
respiratory depression, Acneiform eruption, Flushing,
atrioventricular block, voice disorder, feeling abnormal,
erythema, injection site reaction, hepatitis, limb pain,
blurred vision, dyspnea
Less Common: Fever, hepatic disease, Hepatotoxicity
Decrease in forced vital capacity, dyspnea, respiratory
muscle failure
Rare: Pulmonary edema
Drug Interactions:
Monitor closely with:
Enhances CNS depressant effect of Dantrolene:
Doxylamine, Dronabinol, Hydroxyzine, Magnesium
Sulfate, Minocycline, Nabilone, Other CNS Depressants
[except Nasal Levocabastine]
Enhances therapeutic effect of the following drugs:
Alcohol, Mirtazapine (CNS depressant effect),
Metyrosine, Pramipexole, Ropinrole, Rotigotine (sedative
effect), Vecuronium (neuromuscular-blocking effect)
Increases risk of adverse or toxic effects of Dantrolene:
Dexketoprofen, Lacidipine
Increases risk of adverse or toxic effects of the following
drugs:
Rufinamide (sleepiness; dizziness), SSRI (psychomotor
impairment)
Avoid concomitant use with:
Decreases serum concentration of Dantrolene:
Dabrafenib, Mitotane
Enhances therapeutic effect of Dantrolene:
Droperidol, Perampanel, Sodium Oxybate (CNS
depressant effect), Methotrimeprazine (potentiates CNS
depressant effect) [if concomitant use cannot be
avoided, reduce dantrolene dose by 50%], Tapentadol [if
concomitant use cannot be avoided, start tapentadol at
1/3 to ½ of the normal dose]
Enhances therapeutic effect of the following drugs:
MUSCULO-SKELETAL SYSTEM
Azelastine (Nasal), Buprenorphine [if concomitant use
cannot be avoided, initiate buprenorphine patches at 5
micrograms/hour], Hydrocodone [if concomitant use
cannot be avoided, start with a 20–30% lower
hydrocodone dose], Orphenadrine, Paraldehyde,
Suvorexant, Thalidomide, Zolpidem CNS depressant
effect),
Increases risk of adverse or toxic effects of the following
drugs:
Calcium Channel Blockers, Non-Dihydropyridine e.g.
(hyperkalemic and negative inotropic effects)
Administration: For IV preparation, reconstitute with 60 mL
sterile water for injection.
Therapeutic or emergency dose can be administered
with rapid continuous IV push. Follow-up doses should be
administered over at least 1 minute (Ryanodex) or 1 hour
(Dantrium, Revonto).
EXTRAVASATION MANAGEMENT: Ensure proper needle or
catheter placement prior to and during infusion to avoid
extravasation. If extravasation occurs, stop infusion
immediately and disconnect (leave cannula or needle in
place), then gently aspirate extravasated solution (do
NOT flush the line). Remove needle or cannula and
elevate extremity.
Pregnancy Category: C
ATC Code: M03CA01
ANTIGOUT PREPARATIONS
Rx ALLOPURINOL
Oral: 100 mg and 300 mg tablet
A xanthine oxidase inhibitor that prevents the conversion of
hypoxanthine to xanthine and eventually to uric acid. It
acts on purine catabolism, reducing the production of
uric acid without disrupting the biosynthesis of vital
purines.
Indications: For chronic gout; management of recurrent
calcium oxalate calculi (with uric acid excretion >800 mg
daily in men and >750 mg daily in women); management
of primary or secondary gout (acute attack, tophi, joint
destruction, uric acid lithiasis, and/or nephropathy);
management of hyperuricemia associated with cancer
treatment for leukemia, lymphoma, or solid tumor
malignancies
Contraindication: Severe hypersensitivity reaction to
allopurinol or any component of the formulation
Dose:
NOTE: Oral doses >300 mg should be given in divided
doses.
Chronic gout, by mouth, ADULT, initially 100 mg once daily,
increase at weekly intervals in increments of 100
mg/day as needed to achieve desired serum uric acid
level; usual dosage range, 200 to 300 mg daily in mild
gout; 400–600 mg daily in moderate to severe
tophaceous gout (maximum daily dose, 800 mg).
Management of hyperuricemia associated with
chemotherapy and/or radiation therapy, by mouth,
ADULT, 600–800 mg daily in divided doses; CHILD 6–10
years, 300 mg daily; CHILD <6 years, 150 mg daily.
Recurrent calcium oxalate stones, by mouth, ADULT, 200–
300 mg daily in single or divided doses; may adjust dose
as needed to control hyperuricosuria.
Dose Adjustment:
Renal Impairment:
Lower doses are required in renal impairment due to
potential for accumulation of allopurinol and
metabolites.
For patients with CrCl 10–20 mL/minute, administer 200
mg daily.
For patients with CrCl 3–10 mL/minute, administer ≤100
mg daily.
For patients with CrCl <3 mL/minute, administer ≤100
mg/dose at extended intervals.
M
When used in the management of hyperuricemia associated
with chemotherapy, administer 50% of the dose.
When used for gout, initiate therapy at 50–100 mg daily,
and gradually increase to a maintenance dose to achieve
a serum uric acid level of ≤6 mg/dL. Closely monitor
serum uric acid levels and for hypersensitivity.
In patients with stage 4 CKD or worse, initiate therapy at 50
mg daily, increasing the dose every 2–5 weeks to
achieve desired uric acid levels of ≤6 mg/dL. Doses
>300 mg daily are permitted so long as they are
accompanied by appropriate patient education and
monitoring for toxicity. Some patients may require
therapy targeted at a serum uric acid level <5 mg/dL to
control symptoms.
In patients undergoing hemodialysis, initiate therapy at 100
mg alternate days given post-dialysis, increase
cautiously to 300 mg based on response. If dialysis is
daily, an additional 50% of the dose may be required
post-dialysis.
Precautions:
Allergic reaction (discontinue at first sign of rash);
Bone marrow suppression (use with caution);
Hepatotoxicity (ruse with caution in patients with preexisting
hepatic impairment);
Renal impairment (use with caution; adjust doses as
recommended);
Full effect on serum uric acid levels in chronic gout may take
several weeks to become evident; gradual titration is
recommended.
Elderly (adjust dose based on renal function);
Lactation (use with caution).
Adverse Drug Reactions:
Common: Skin rash, gout (acute), diarrhea, nausea.
Less Common: Abdominal pain, ageusia, agranulocytosis,
alopecia, angioedema, aplastic anemia, arthralgia,
bronchospasm, cataract, cholestatic jaundice,
drowsiness, dysgeusia, dyspepsia, ecchymoses,
eczematoid dermatitis, eosinophilia, epistaxis,
exfoliative dermatitis, fever, gastritis, gynecomastia,
415

headache, hepatic necrosis, hepatitis, hepatomegaly,
hepatotoxicity (idiosyncratic), hypersensitivity reaction,
hyperbilirubinemia, leukocytosis, leukopenia, lichen
planus, macular retinitis, myopathy, necrotizing angiitis,
nephritis, neuritis, neuropathy, onycholysis, pancreatitis,
paresthesia, pruritus, purpura, renal failure, skin
granuloma (annulare), Stevens-Johnson syndrome,
thrombocytopenia, toxic epidermal necrolysis, toxic
pustuloderma, uremia, vasculitis, vesicobullous
dermatitis, vomiting
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Allopurinol:
Thiazide Diuretics e.g. Hydrochlorothiazie (allergic or
hypersensitivity reactions)
Increases risk of adverse or toxic effects of the following
drugs:
Amoxicillin, Ampicillin (allergic or hypersensitivity
reactions), Bendamustine (severe skin reactions),
Cyclophosphamide (bone marrow suppression), Loop
Diuretics
Avoid concomitant use with:
M
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Allopurinol:
ACE Inhibitors (allergic or hypersensitivity reactions)
Increases risk of adverse or toxic effects of Pegloticase
(blunts increases in serum urate)
Increases serum concentration of the following drugs:
Azathioprine [active metabolite/s, specifically
mercaptopurine] [if concomitant use cannot be avoided,
reduce azathioprine dose 1/3 to ¼ of usual dose],
Didanosine, Mercaptopurine [active thioguanine
nucleotides] [if concomitant use cannot be avoided,
reduce mercaptopurine dose to 1/3 to ¼ of usual dose]
Reduces absorption of Allopurinol:
Antacids [except Sodium Bicarbonate]
Reduces therapeutic effect of Tegafur
Administration: Administer after meals with plenty of fluid.
Administer fluids to yield neutral or slightly alkaline urine
and an output of ~2 L in adults.
Pregnancy Category: C
ATC Code: M04AA01
416
MUSCULO-SKELETAL SYSTEM
Rx COLCHICINE
Oral: 500 micrograms tablet
Colchicine disrupts cytoskeletal functions by inhibiting β-
tubulin polymerization. It also prevents the activation,
degranulation, and migration of neutrophils associated
with mediating some gout symptoms.
Indications: Management of acute gout; treatment of
familial Mediterranean fever in adults and children 4
years and older; prophylaxis and treatment of acute gout
flares
Contraindications: Concomitant use of a P-glycoprotein (P-
gp) or strong CYP3A4 inhibitor in presence of renal or
hepatic impairment
Dose:
Familial Mediterranean fever, by mouth, ADULT, 1.2–2.4 mg
daily in 1–2 divided doses, increase or decrease dose in
0.3 mg daily increments based on efficacy or adverse
effects; CHILD >10 years and ADOLESCENT, initially 1.5
mg daily in 1–2 divided doses; CHILD 5–10 years,
initially 1 mg daily in 1–2 divided doses; CHILD <5 years,
initially 0.5 mg once daily.
NOTE: Titrate dosage in increments of 0.25 mg (maximum
daily dose, 2 mg).
Gout, flare treatment, by mouth, ADULT, initially 1 mg at first
sign of flare, followed by 0.5 mg every 2 to 6 hours
(maximum cumulative dose, 2.5 mg in the first 24 hours
and 6 mg over 4 days); following acute treatment course,
wait 3 days before administering additional colchicine.
Gout, prophylaxis, by mouth, ADULT, 0.5 mg once weekly or
up to 0.5 mg 2–3 times daily.
Dose Adjustment:
Geriatric:
Use with caution. Reduce prophylactic daily dose by 50% in
individuals >70 years.
Renal Impairment:
Dose adjustment may be required. Consult product labeling.
Familial Mediterranean fever:
In patients with CrCl of 30–80 mL/minute, monitor closely
for adverse effects. Dose reduction may be necessary.
In patients with CrCl <30 mL/minute, initiate therapy at 0.3
mg daily. Use caution if dose is titrated. Monitor for
adverse effects.
In patients undergoing dialysis, administer 0.3 mg as a
single dose. Use caution if dose is titrated. Dosing can be
increased with close monitoring. Monitor for adverse
effects. Colchicine is not removed by dialysis.
Gout prophylaxis:
In patients with CrCl of 30–80 mL/minute, dose adjustment
is not required. Monitor closely for adverse effects.
In patients with CrCl <30 mL/minute, initiate therapy at 0.3
mg daily. Use caution if dose is titrated. Monitor for
adverse effects.
In patients undergoing dialysis, administer 0.3 mg twice
weekly. Monitor closely for adverse effects.
MUSCULO-SKELETAL SYSTEM
Gout flare treatment:
In patients with CrCl of 30–80 mL/minute, dose adjustment
is not required. Monitor closely for adverse effects.
In patients with CrCl <30 mL/minute, consider dosage
reduction. Do not repeat treatment more frequently than
every 14 days.
In patients undergoing dialysis, administer 0.6 mg as a
single dose. Do not repeat treatment more frequently
than every 14 days. Colchicine is not removed by dialysis.
In patients undergoing hemodialysis, avoid chronic use.
Hepatic Impairment:
Dose adjustment may be required. Consult product labeling.
Familial Mediterranean fever:
In mild to moderate impairment, use with caution. Monitor
closely for adverse effects.
In severe impairment, consider dose adjustment.
Gout prophylaxis:
In mild to moderate impairment, monitor closely for adverse
effects.
In severe impairment, consider dose adjustment.
Gout flare treatment:
In mild to moderate impairment, monitor closely for adverse
effects.
In severe impairment, do not repeat treatment course more
frequently than every 14 days.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Blood dyscrasias (e.g., myelosuppression and aplastic
anemia).
Gastrointestinal symptoms (dose reduction is
recommended in patients who develop gastrointestinal
symptoms);
Neuromuscular toxicity (patients with renal dysfunction and
elderly patients are at increased risk);
Renal and hepatic impairment (clearance is decreased;
monitor closely for adverse effects or toxicity; fatal
toxicity has been reported);
Colchicine is not an analgesic and should not be used to
treat pain from other causes;
Accidental and intentional fatal overdoses have been
reported. Dosage associated with fatal toxicity is
variable.
Elderly (consider dose adjustment; more toxic in older
adults, particularly in the presence of renal,
gastrointestinal, or cardiac disease);
Pregnancy;
Lactation (excreted in breast milk).
Adverse Drug Reactions:
Common: GI disease, diarrhea, vomiting, nausea, fatigue,
headache, gout, abdominal cramps, abdominal pain,
pharyngolaryngeal pain
Less Common: Alopecia, aplastic anemia, skin rash,
azoospermia, bone marrow, dermatitis, depression,
granulocytopenia, hepatotoxicity, disseminated IV
coagulation, hypersensitivity reaction, lactose
intolerance, leukopenia, maculopapular rash, myalgia,
myasthenia, myopathy, myotonia, neuropathy,
oligospermia, pancytopenia, peripheral neuritis, purpura,
rhabdomyolysis, thrombocytopenia, toxic neuromuscular
disease
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Colchicine:
Fibric Acid Derivatives e.g. Clofibrate (myopathy),
Diltiazem (myopathic effect; rhabdomyolysis)
Reduces therapeutic effect of Choline C11
Avoid concomitant use with:
Decreases serum concentration of Cyanocobalamin
Increases risk of adverse or toxic effects of Colchicine:
HMG-CoA Reductase Inhibitors e.g., Simvastatin
(myopathic effect; rhabdomyolysis)
Increases serum concentration of Colchicine:
Conivaptan, Fosamprenavir, Fusidic Acid Systemic,
Grapefruit Juice, HMG-CoA Reductase Inhibitors e.g.,
Simvastatin, Idelalisib, Mifepristone, P-glycoprotein /
ABCB1 Inhibitors (increases distribution into certain
tissues, e.g., brain), Stiripentol, Telaprevir, Tipranavir
M
TEST INTERACTION. May cause false-positive results in
urine tests for erythrocytes or hemoglobin.
Administration: Administer with water and maintain
adequate fluid intake. May be administered without
regard to meals.
May be taken without regard to meals. May need to
supplement with vitamin B12. Avoid grapefruit juice.
Pregnancy Category: C
ATC Code: M04AC01
DRUGS FOR TREATMENT OF
BONE DISEASE
Rx ALENDRONATE
Oral: 10 mg and 70 mg tablet (as sodium salt)
A bisphosphonate, which inhibits bone resorption via
actions on osteoclasts or on osteoclast precursors. The
use of this drug can indirectly increase bone mineral
density.
Indications: Treatment and prevention of osteoporosis in
postmenopausal females and males; treatment of
Paget’s disease of the bone in patients who are
symptomatic, at risk for future complications, or with
alkaline phosphatase ≥2 times the upper limit of normal;
treatment of glucocorticoid-induced osteoporosis in
males and females with low bone mineral density who
are receiving a daily dosage ≥7.5 mg of prednisone (or
equivalent)
417

Contraindications: Hypocalcemia; abnormalities of the
esophagus (e.g., stricture, achalasia) which delay
esophageal emptying; inability to stand or sit upright for
at least 30 minutes
Dose:
NOTE: Consider discontinuing after 3–5 years of use in
patients at low-risk for fracture. Patients should receive
supplemental calcium and vitamin D if dietary intake is
inadequate.
Osteoporosis, prophylaxis, by mouth, ADULT
(postmenopausal female), 5 mg once daily or 35 mg
once weekly.
Osteoporosis, treatment, by mouth, ADULT
(postmenopausal female), 10 mg once daily or 70 mg
once weekly; ADULT (male), 10 mg once daily or 70 mg
once weekly.
Paget’s disease of the bone, by mouth, ADULT, 40 mg once
daily for 6 months.
Corticosteroid-induced osteoporosis, by mouth, ADULT, 5
mg daily; ADULT (postmenopausal female not receiving
estrogen) 10 mg daily.
RE-TREATMENT: Following a 6-month post-treatment
M
evaluation period, treatment with alendronate may be
considered in patients who have relapsed based on
increases in serum alkaline phosphatase, which should
be measured periodically. Re-treatment may also be
considered in those who failed to normalize their serum
alkaline phosphatase.
Dose Adjustment:
Renal Impairment:
In patients with CrCl<35 mL/minute, use is not
recommended.
Precautions:
Bone fractures (atypical femur fractures have been
reported, including subtrochanteric femur and
diaphyseal femur; may cause prodromal pain weeks or
months before the fracture occurs); bone, joint, or
muscle pain (symptoms usually resolve upon
discontinuation);
Osteonecrosis of the jaw;
Gastrointestinal mucosa irritation;
Hypocalcemia (has been reported; correct hypocalcemia
prior to therapy initiation; ensure adequate calcium and
vitamin D intake);
Renal impairment;
Elderly (advise patient to report any lower extremity, jaw, or
muscle pain that cannot be explained or lasts longer
than 2 weeks);
Pregnancy (discontinue use in women of reproductive
potential as early as possible prior to a planned
pregnancy; use in premenopausal women should be
reserved for rapid bone loss; monitor exposed infants for
hypocalcemia after birth);
Lactation (not known if excreted into breast milk).
Adverse Drug Reactions:
Common: Headache, hypocalcemia, hypophosphatemia,
abdominal pain, acid regurgitation, dyspepsia, nausea,
flatulence, diarrhea, gastroesophageal reflux disease,
constipation, abdominal distension, gastritis, vomiting,
418
MUSCULO-SKELETAL SYSTEM
dysphagia, gastric ulcer, melena, musculoskeletal pain,
muscle cramps, esophageal ulcer / stricture / erosions
Less Common: Alopecia, anastomotic ulcer, angioedema,
atrial fibrillation, dizziness, duodenal ulcer, dysgeusia,
episcleritis, erythema, erosive esophagitis, esophageal
perforation, esophageal spasm, esophageal ulcer,
esophagitis, exacerbation of asthma, femur fracture,
fever, flu-like symptoms, hypocalcemia (symptomatic),
hypersensitivity reaction, joint swelling,
lymphocytopenia, malaise, malignant neoplasm of
esophagus, myalgia or arthralgia (occasionally severe),
oropharyngeal ulcer; ostealgia, osteonecrosis (jaw),
peripheral edema, pruritus, skin rash, Stevens-Johnson
syndrome, toxic epidermal necrolysis, urticaria, vertigo,
weakness
Rare: Scleritis, skin photosensitivity, uveitis
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Alendronate:
Aminoglycosides e.g. Streptomycin (hypocalcemic
effect), Aspirin (upper GI adverse events), NSAIDs (GI
ulceration; nephrotoxicity), Systemic Angiogenesis
Inhibitors (osteonecrosis of the jaw)
Increases risk of adverse or toxic effects of Deferasirox (GI
ulceration, irritation, or bleeding)
Reduces therapeutic effect of Alendronate:
Proton Pump Inhibitors
Avoid concomitant use with:
Decreases serum concentration of Alendronate [if
concomitant use cannot be avoided, separate
administration times by at least 30 minutes]:
Antacids [except Magaldrate, Sodium Bicarbonate],
Calcium Salts, Iron Salts [except Ferric Carboxymaltose,
Ferric Gluconate, Ferric Pyrophosphate Citrate,
Ferumoxytol, Iron Dextran Complex, Iron Sucrose],
Magnesium Salts, Multivitamins / Minerals with ADEK,
Folate, Iron, Multivitamins / Minerals with AE, no Iron
Reduces therapeutic effect of the following drugs:
Parathyroid Hormone (interferes with normalization of
blood calcium concentrations)
TEST INTERACTIONS. May interfere with diagnostic imaging
agents such as technetium-99m-diphosphonate in bone
scans
Administration: Must be taken with plain water first thing in
the morning and ≥30 minutes before the first food,
beverage, or other medication(s) of the day. All food and
beverages interfere with absorption. Co-administration
with dairy products may decrease alendronate
absorption. Food and beverages (especially orange juice,
coffee, and mineral water) may reduce the absorption of
alendronate as much as 60%. Do NOT take with mineral
water or with other beverages. Instruct patients to stay
upright and not to lie down for at least 30 minutes and
until after first food of the day to reduce esophageal
irritation.
Swallow tablet whole. Do NOT chow or suck.
MUSCULO-SKELETAL SYSTEM

MISSED DOSE (once weekly): If a once-weekly dose is
missed, it should be given the next morning after
remembered. May then return to the original once-
weekly schedule (original scheduled day of the week). Do
NOT give 2 doses on the same day.
Pregnancy Category: C
ATC Code: M05BA04
ALENDRONATE +
Rx
CHOLECALCIFEROL (VIT D3)
Oral: 70 mg (as sodium) + 5,600 IU tablet
Alendronate is a bisphosphonate, which inhibits bone
resorption via actions on osteoclasts or on osteoclast
precursors.
Cholecalciferol is a fat-soluble vitamin D, which helps
increase GI absorption of calcium and its assimilation
into bones.
Indications: Treatment of osteoporosis in postmenopausal
females; to increase bone mass in males with
Elderly (advise patient to report any lower extremity, jaw, or
muscle pain that cannot be explained or lasts longer
than 2 weeks; if on concomitant diuretic therapy, closely
monitor serum electrolytes).
Pregnancy (not known if it crosses the placenta; fetal
exposure is expected; most sources recommend
discontinuation in women of reproductive potential as
early as possible prior to a planned pregnancy; use in
premenopausal women should be reserved for rapid
bone loss; monitor exposed infants for hypocalcemia
after birth);
Lactation (not known if excreted into breast milk).
Adverse Drug Reactions:
Common: Headache, hypocalcemia, abdominal pain,
hypophosphatemia, acid regurgitation, nausea,
dyspepsia, flatulence, diarrhea, constipation, GERD,
esophageal ulcer, abdominal distension, gastritis,
vomiting, dysphagia, gastric ulcer, melena,
musculoskeletal pain, muscle cramps
Less Common: Alopecia, angioedema, anastomotic ulcer,
atrial fibrillation, dizziness, duodenal ulcer, dysgeusia,
episcleritis, erosive esophagitis, erythema, esophageal
perforation, esophageal spasm, esophageal ulcer,
esophagitis, joint swelling, exacerbation of asthma,

M
femur fracture, flu-like symptoms, hypocalcemia
osteoporosis
(symptomatic), hypersensitivity reaction,
lymphocytopenia, malaise, malignant neoplasm of
Contraindications: Hypocalcemia; abnormalities of the
esophagus, oropharyngeal ulcer, myalgia or arthralgia
esophagus (e.g., stricture or achalasia) which delay
(occasionally severe), ostealgia, osteonecrosis (jaw),
esophageal emptying; inability to stand or sit upright for
peripheral edema, pruritus, skin rash, Stevens-Johnson
at least 30 minutes
syndrome, toxic epidermal necrolysis, urticaria, vertigo,
fever, weakness
Dose:
Rare: Scleritis, skin photosensitivity, uveitis
NOTE: Consider discontinuing after 3–5 years of use in
patients at low-risk for fracture. Patients should receive
Drug Interactions:
supplemental calcium and vitamin D if dietary intake is
Monitor closely with:
inadequate.
Increases risk of adverse or toxic effects of Alendronate:
Aminoglycosides (hypocalcemic effect), Aspirin (upper GI
Osteoporosis, by mouth, ADULT, 1 tablet (alendronate 70
adverse events), NSAIDs (GI ulceration; nephrotoxicity),
mg/cholecalciferol 5,600 units) once weekly.
Systemic Angiogenesis Inhibitors (osteonecrosis of the
jaw)
Dose Adjustment:
Renal Impairment:
Increases risk of adverse or toxic effects of Cholecalciferol:
In patients with CrCl<35 mL/minute, use is not
Danazol (hypercalcemic effect)
recommended.
Increases risk of adverse or toxic effects of the following
Precautions:
drugs:
Bone fractures;
Cardiac Glycosides e.g. Digoxin (arrhythmogenic effect),
Bone, joint, or muscle pain (symptoms usually resolve upon
Deferasirox (GI ulceration, irritation, or bleeding)
discontinuation);
Osteonecrosis of the jaw;
Reduces therapeutic effect of Alendronate:
Gastrointestinal mucosa irritation (use with caution);
Proton Pump Inhibitors
Gastrointestinal malabsorption syndrome (increased doses
of vitamin D supplementation may be required; monitor
Avoid concomitant use with:
25-hydroxy vitamin D levels).
Increases risk of adverse or toxic effects of Cholecalciferol:
Hypercalcemia (may exacerbate hypercalcemia and/or
Multivitamins / Fluoride with ADE, Other Vitamin D
hypercalciuria; monitor serum and urine calcium levels);
Analogs
Hypocalcemia or vitamin D deficiency (has been reported;
correct hypocalcemia and/or vitamin D deficiency prior
Reduces therapeutic effect of Parathyroid Hormone
to therapy initiation; ensure adequate calcium and
(interferes with normalization of blood calcium
vitamin D intake).
concentrations)
Renal impairment (use with caution);
Hepatic impairment (cholecalciferol may not be adequately
TEST INTERACTIONS. May interfere with diagnostic imaging
absorbed in patients who have malabsorption due to
agents such as technetium-99m-diphosphonate in bone
inadequate bile production);
scans.

419

Administration: Must be taken with plain water first thing in
the morning and ≥30 minutes before the first food,
beverage, or other medication(s) of the day. All food and
beverages interfere with absorption. Co-administration
with dairy products may decrease alendronate
absorption. Food and beverages (especially orange juice,
coffee, and mineral water) may reduce the absorption of
alendronate as much as 60%. Do NOT take with mineral
water or with other beverages. Instruct patients to stay
upright and not to lie down for at least 30 minutes and
until after first food of the day to reduce esophageal
irritation.
Swallow tablet whole. Do NOT chow or suck.
Ensure adequate calcium and vitamin D intake. If dietary
intake is inadequate, dietary supplementation is
recommended.
Calcium: 1,000 mg daily (men: 50 to 70 years) or 1,200
mg/day (women ≥51 years and men ≥71 years)
Vitamin D: 800 to 1,000 int. units daily (men and women
≥50 years); Recommended Dietary Allowance (RDA):
600 int. units daily (men and women ≤70 years) or 800
int. units daily (men and women ≥71 years)
M
MISSED DOSE (once weekly): If a once-weekly dose is
missed, it should be given the next morning after
remembered; may then return to the original once-
weekly schedule (original scheduled day of the week). Do
NOT give 2 doses on the same day.
Pregnancy Category: C
ATC Code: M05BB03
Rx CONJUGATED ESTROGEN
Oral: 625 micrograms and 1.25 mg tablet
Estrogen products mimic endogenous estrogens in the body
that are responsible for the development and
maintenance of the female reproductive system and
secondary sexual characteristics. Estrogens modulate
the pituitary secretion of luteinizing hormone and follicle-
stimulating hormone through a negative feedback
system thereby reducing elevated levels of these
hormones responsible for symptoms experienced by
postmenopausal women.
Indication: Prevention of progression of osteoporosis
associated with estrogen deficiency in postmenopausal
women
Contraindications: Angioedema or anaphylactic reaction to
estrogen or any component of the formulation;
undiagnosed abnormal genital bleeding; DVT or PE
(current or history of); active or history of arterial
thromboembolic disease (e.g., stroke, MI); breast cancer
(known, suspected or history of); estrogen-dependent
tumor (known or suspected); hepatic impairment or
disease; known protein C, protein S, antithrombin
deficiency or other known thrombophilic disorders;
pregnancy
420
MUSCULO-SKELETAL SYSTEM
Dose:
Prevention of postmenopausal osteoporosis, by mouth,
ADULT, 300 micrograms once a day, continuous or in
cyclical regimens (e.g. 25 days on therapy then 5 days
off); adjust dose based on bone mineral density and
clinical response; lowest effective dose should be used
Administration: To reduce the risk of endometrial cancer,
consider adding progestin in the therapy when
prescribing estrogen for a postmenopausal woman with
a uterus. A woman without a uterus does not need
progestin, however, hysterectomized women with a
history of endometriosis may need a progestin. Use
estrogen-alone, or in combination with a progestin with
the lowest effective dose and for the shortest duration
possible. This drug may be taken without regard to
meals.
See Conjugated Estrogen under Sex Hormones and
Modulators of the Genital System – Estrogens in Chapter
5: Genito Urinary System and Sex Hormones for other
information.
Pregnancy Category: X
ATC Code: G03CA57
OTHER DRUGS FOR DISORDERS OF
THE MUSCULO-SKELETAL SYSTEM
DISEASE MODIFYING ANTIRHEUMATIC
DRUGS (DMARDS)
Rx AZATHIOPRINE
Oral: 50 mg tablet
An imidazolyl derivative of mercaptopurine. This purine
metabolite is incorporated into replicating DNA and halts
replication by blocking purine synthesis. The
6­thioguanine nucleotide metabolites appear to mediate
most of azathioprine’s immunosuppressive and toxic
effects.
Indication: Management of active rheumatoid arthritis
Contraindications: Pregnancy; patients with rheumatoid
arthritis and a history of treatment with alkylating agents
(e.g., cyclophosphamide, chlorambucil, melphalan) may
have a prohibitive risk of malignancy with azathioprine
treatment
Dose:
Rheumatoid arthritis, by mouth, ADULT and CHILD, initially
1 mg/kg daily (50-100 mg) given once daily or divided
twice daily for 6-8 weeks; may increase by 0.5 mg/kg
every 4 weeks until response or up to 2.5 mg/kg daily;
an adequate trial should be a minimum of 12 weeks;
maintenance dose, reduce dose by 0.5 mg/kg (~25 mg
daily) every 4 weeks until lowest effective dose is
reached; may be discontinued abruptly (monitor for
delayed toxicities).
MUSCULO-SKELETAL SYSTEM
Dose Adjustment:
Geriatric:
Start with lowest recommended adult doses. Adjust dose to
creatinine clearance.
Renal Impairment:
For patients with CrCl 10-50 mL/minute, administer 75% of
normal dose.
For patients with CrCl <10 mL/minute, administer 50% of
normal dose.
For patients receiving hemodialysis, administer 50% of
normal dose and supplement with 0.25 mg/kg.
Oliguric patients, particularly those with tubular necrosis in
the immediate post­transplant period (cadaveric
transplant) may have delayed clearance and typically
receive lower doses.
Hepatic Impairment:
Reduce dose.
Precautions:
WARNING: Hazardous agent; use appropriate
precautions for handling and disposal.
WARNING: Chronic use for immunosuppression
increases risk of malignancy, including
posttransplant lymphoma and hepato-splenic T-
cell lymphoma in patients with inflammatory bowel
disease.
Gastrointestinal toxicity (e.g. severe nausea, vomiting,
diarrhea, rash, fever, malaise, myalgia, hypotension, and
liver enzyme abnormalities generally reversible upon
discontinuation).
Hematologic toxicity (dose-related; leukopenia,
thrombocytopenia, and anemias may occur; may be
severe and/or delayed; patients with intermediate
thiopurine methyltransferase (TPMT) activity may be at
increased risk for hematologic toxicity at conventional
azathioprine doses; patients with low or absent TPMT
activity are at risk for severe, life-threatening
myelotoxicity; myelosuppression may be more severe
with renal transplants undergoing rejection; may require
treatment interruption or dose reduction).
Hepatotoxicity (transaminase, bilirubin, and alkaline
phosphatase elevations may occur; usually occurs within
6 months of transplant and is normally reversible with
discontinuation; rarely, hepatic sinusoidal obstruction
syndrome [SOS], formerly called veno-occlusive disease
[VOD] has been reported; discontinue if hepatic SOS is
suspected).
Infections (chronic immunosuppression increases the risk
of serious, sometimes fatal, infections; progressive
multifocal leukoencephalopathy [PML] caused by
reactivation of the JC virus, has been reported).
Hepatic and renal impairment (dosage reductions may be
necessary);
TPMT deficiency (increased sensitivity to myelosuppressive
effects; consider TPMT testing in patients with
abnormally low CBC unresponsive to dose reduction);
Elderly;
Lactation (breast­feeding is not recommended by the
manufacturer due to potential for serious adverse
reactions in the nursing infant).
Adverse Drug Reactions:
Common: Malaise, nausea, vomiting, diarrhea, leukopenia,
neoplasia, thrombocytopenia, hepatotoxicity, increased
susceptibility to infection, myalgia, fever
Less Common: Abdominal pain, acute myelocytic leukemia,
alopecia, anemia, arthralgia, bone marrow depression
(dose-related), hemorrhage, hepatic veno-occlusive
disease, hepatosplenic T-cell lymphomas (HSTCL),
hepatotoxicity (idiosyncratic), hypersensitivity,
hypotension, interstitial pneumonitis (reversible), JC
virus infection, macrocytic anemia, malignant
lymphoma, malignant neoplasm of skin, negative
nitrogen balance, pancreatitis, pancytopenia,
progressive multifocal leukoencephalopathy (potentially
fatal), skin rash, steatorrhea, Sweet's syndrome (acute
febrile neutrophilic dermatosis), post-transplant
lymphoma
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Azathioprine:
ACE Inhibitors, Trimethoprim (myelosuppressive effect),
Trastuzumab (neutropenic effect), (myelosuppressive
effect)
M
Enhances therapeutic effect of Sipuleucel-T
Increases risk of adverse or toxic effects of Azathioprine:
ACE Inhibitors, Co-trimoxazole (hematologic
abnormalities), Denosumab (serious infections)
Increases risk of adverse or toxic effects of
Cyclophosphamide (hepatotoxic effect)
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
Avoid concomitant use with:
Decreases serum concentration of Azathioprine:
Ribavirin
Enhances therapeutic effect of Azathioprine:
Roflumilast (immunosuppressive effect)
Enhances therapeutic effect of the following drugs:
Mercaptopurine (myelosuppressive effect), Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Azathioprine:
Pimecrolimus
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity, such as
pancytopenia, agranulocytosis, and/or
thrombocytopenia), Natalizumab (concurrent infection),
Tacrolimus Topical, Vaccines (Live)
Increases serum concentration of Azathioprine:
Allopurinol [if concomitant use cannot be avoided,
reduce azathioprine dose to 1/3 to ¼ of usual dose],
Febuxostat
421

Reduces therapeutic effect of Azathioprine:
Ribavirin
Reduces therapeutic effect of the following drugs:
BCG, Vaccines, Inactivated [complete all age-appropriate
vaccinations at least 2 weeks prior to starting
azathioprine; if vaccinated during azathioprine therapy,
revaccinate at least 3 months after discontinuation],
Vaccines, Live [avoid azathioprine doses greater than 3
mg/kg daily]
Administration: Administer tablets after meals or in divided
doses to decrease adverse GI events.
Protect from light and moisture and store between 15–
25°C.
Pregnancy Category: D
ATC Code: Not available
Rx HYDROXYCHLOROQUINE
M
Oral: 200 mg tablet (as sulfate)
NOTE: Hydroxychloroquine sulfate 200 mg is equivalent to
155 mg hydroxychloroquine base and 250 mg
chloroquine phosphate.
Indications: Management of systemic lupus erythematosus
(SLE) and rheumatoid arthritis (RA)
Contraindications: Pre-existing maculopathy of the eye;
retinal or visual field changes attributable to
4­aminoquinolines; long-term use in children
Dose:
Rheumatoid arthritis, by mouth, ADULT, initially 400 to 600
mg daily taken with food or milk; increase dose gradually
until optimum response level is reached; usually after 4–
12 weeks dose should be reduced by ½ to a
maintenance dose of 200 to 400 mg daily in 1–2 divided
doses (maximum daily dose, 6.5 mg/kg or 400 mg,
whichever is lower); CHILD, up to 6.5 mg/kg daily or 400
mg, whichever is lower.
Lupus erythematosus, by mouth, ADULT, 400 mg 1–2 times
daily for several weeks to months depending on
response; 200–400 mg daily in 1 to 2 divided doses for
prolonged maintenance therapy (maximum daily dose,
6.5 mg/kg or 400 mg, whichever is lower).
Dose Adjustment:
Renal and Hepatic Impairment:
Dose adjustment may be necessary.
Precautions:
WARNING: Should be prescribed only by physicians
familiar with its use. May cause dizziness and
blurred vision.
Cardiovascular effects e.g. rare cardiomyopathy in long term
use; hematologic effect e.g. agranulocytosis, aplastic
anemia, and thrombocytopenia;
422
MUSCULO-SKELETAL SYSTEM
Neuromuscular effects e.g. myopathy, neuromyopathy, and
progressive weakness;
Ophthalmic effects e.g. loss of visual acuity, macular
pigmentary changes, and loss of foveal reflex;
G6PD deficiency;
Hepatic impairment;
Porphyria and psoriasis;
Pediatric (use caution due to increased sensitivity to
aminoquinolones).
Pregnancy (may decrease the incidence of cardiac
malformations associated with neonatal lupus);
Lactation (excreted into breast milk).
SKILLED TASKS. May impair ability to perform skilled tasks,
such as operating machinery or driving.
Adverse Drug Reactions:
Common: Ataxia, dizziness, emotional disturbance,
headache, irritability, lassitude, nerve deafness,
nervousness, nightmares, psychosis, seizure, suicidal
tendencies, vertigo, alopecia, bleaching of hair, bullous
rash, dyschromia, exacerbation of psoriasis, pruritus,
urticaria, exacerbation of porphyria, weight loss,
anorexia, diarrhea, nausea, stomach cramps, vomiting,
agranulocytosis, anemia, aplastic anemia, hemolysis,
leukopenia, thrombocytopenia, hepatic insufficiency,
angioedema, myopathy, accommodation disturbance,
corneal changes, decreased visual acuity, epithelial
keratopathy, macular degeneration, macular edema,
maculopathy, nystagmus, optic disk disorder
(pallor/atrophy), retinal pigment changes, retinal
vascular disease, retinitis pigmentosa, retinopathy,
scotoma, vision color changes, visual field defect,
tinnitus, bronchospasm, respiratory failure (myopathy-
related)
Less Common: Hypoglycemia (potentially fatal),
keratopathy
Rare: Cardiomyopathy
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Artemether, Dapsone (hemolytic reactions),
Lumefantrine, Mefloquine (convulsions; QTc-
prolongation) [if concomitant use cannot be avoided,
delay administration of mefloquine until at least 12
hours after the last dose of hydrochloroquine]
Administration: Administer with food or milk.
Pregnancy Category: Not classified
ATC Code: Not available
MUSCULO-SKELETAL SYSTEM

NOTE: Optimal intrathecal chemotherapy dosing should be

Rx METHOTREXATE
Oral: 2.5 mg tablet (as base or sodium salt)
Inj.: 5 mg/mL (as sodium salt), 3 mL vial (IM, IV)
25 mg/mL (as base), 2 mL ampule / vial (IM, IV,
intrathecal)
25 mg/mL (as sodium salt, preservative-free), 2 mL
ampule / vial (IM, IV, intrathecal)
100 mg/mL (as base), 10 mL vial
100 mg/mL (as sodium salt, preservative-free), 10
mL vial (IM, IV, intrathecal)
A folate antimetabolite that inhibits DNA synthesis and
repair, and cellular replication. Methotrexate irreversibly
binds to and inhibits dihydrofolate reductase thereby
preventing the formation of reduced folates and
thymidylate synthetase. The use of this drug results to
the inhibition of purine and thymidylic acid synthesis.
based on age rather than on body surface area (BSA) as
CSF volume correlates with age and not to BSA.
Doses ≥250 mg/m2 (≥12 g/m2 in children) are
associated with moderate emetic potential. Antiemetics
may be given to prevent nausea and vomiting.
Doses >500 mg/m2 require leucovorin calcium rescue.
Doses between 100–500 mg/m2 may require leucovorin
calcium rescue.
See Methotrexate under Antineoplastic Agents –
Antimetabolites in Chapter 8: Antineoplastic and
Immunomodulating Agents for other information.
Pregnancy Category: X
ATC Code: Not available

Indications: Severe, active rheumatoid arthritis (RA); active

polyarticular-course juvenile idiopathic arthritis (pJIA)

Contraindications: Breast­feeding; pregnancy; alcoholism;

alcoholic liver disease or other chronic liver disease;

M
immunodeficiency syndrome; preexisting blood
dyscrasias

Dose:
RA, by mouth, ADULT, initially 7.5 mg once weekly or 2.5 mg
every 12 hours for 3 doses per week; adjust dose
gradually to optimal response;
alternatively, 10-15 mg once weekly, increased by 5 mg
every 2-4 weeks (maximum dose, 20-30 mg once
weekly);
by intramuscular injection, 7.5 mg once weekly; adjust
dose gradually to optimal response;
by mouth, ADULT >60 years, initially 5-7.5 mg per week,
not to exceed 20 mg per week.
pJIA, by mouth or IM injection, CHILD, initially 10 mg/m2
once weekly, adjust gradually to optimum response;
doses up to 20-30 mg/m2 once weekly have been used.

NOTE: Doses above 20 mg (20 mg/m2 in children) once

weekly are associated with an increased incidence of
toxicity.
Doses between 100–500 mg/m2 may require leucovorin
calcium rescue. Doses >500 mg/m2 require leucovorin
calcium rescue.

Administration:
For oral administration, administer without regard to
food. This is the preferred route for low doses.

For IV administration, administer as slow IV push at a

rate of 10 mg/minute, as bolus injection, or as 24-hour
continuous infusion. The route and rate of administration
depends on indication and/or protocol.

For intrathecal administration, do NOT prepare during

the preparation of any other agents. After preparation,
store in an isolated location or container clearly marked
with a label "intrathecal" use only. Administer only with
other medications intended for administration into the
central nervous system.

423
 NERVOUS SYSTEM

NERVOUS SYSTEM Note: Minimum Alveolar Concentration (MAC) decreases

with increasing age. Adjust dose accordingly.
Precautions:
Patient with or at risk of raise intracranial pressure; Patients
at risk of QT prolongation; Neuromuscular diseases e.g.
ANESTHETICS Duchenne muscular dystrophy; Chronic renal or hepatic
impairment.
Children (safety has not been investigated in non- intubated
ANESTHETICS, GENERAL patients < 2 years)
Pregnancy and lactation.
HALOGENATED HYDROCARBONS
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
Rx DESFLURANE machinery.

Inhalation: 240 mL bottle Adverse Drug Reactions:

Desflurane is a highly fluorinated, volatile methyl ethyl
esther used for maintenance of general anesthesia. It
enhances inhibitory postsynaptic activity and inhibits
excitatory synaptic activity, resulting in reversible loss of
consciousness and of pain sensations, suppression of
voluntary motor activity, reduction of autonomic reflexes,
and sedation of respiratory and the cardiovascular
system.
Indications: Induction and maintenance of anesthesia.
N
Common: Decreased oxygen saturation, bradycardia,
hypertension (including malignant hypertension), nodal
arrhythmia, shivering, tachycardia, headache, nausea,
vomiting, sialorrhea, laryngospasm, conjunctivitis,
cough, breath-holding, apnea, increased bronchial
secretions, pharyngitis.
Less Common: Abdominal pain, acute pancreatitis,
agitation, asthma, atrial fibrillation, bigeminy, blood
coagulation disorder, bronchospasm, cardiac
arrhythmia, cholestasis, dizziness, dyspnea, erythema,
hemoptysis, hemorrhage, hepatic failure, hepatic
necrosis, fever, hepatitis (including cytolytic hepatitis),

Contraindications: Known or suspected genetic hepatotoxicity, hyperkalemia, hypokalemia, hypokinesia

susceptibility to malignant hyperthermia; induction of
anesthesia in pediatric patients; history of moderate-to-
severe hepatic impairment following anesthesia with
halogenated agents and not otherwise explained; history
of hepatitis or in whom hepatic dysfunction, jaundice,
unexplained fever, leukocytosis, or eosinophilia has
occurred due to a halogenated inhalational anesthetic.
(ventricular), hypoxia, hypotension, shock, ischemic
heart disease, leukocytosis, malaise, malignant
hyperthermia, metabolic acidosis, myalgia, pruritus,
respiratory distress, respiratory failure, rhabdomyolysis,
scleral icterus, seizure, myocardial infarction, torsade de
pointes, urticaria, vasodilatation, ventricular dysfunction,
weakness.

Dose: Drug Interactions:

Anesthesia, induction, by inhalation, ADULT, initially 3%; Avoid concomitant use with:
increase by 0.5–1% increments every 2–3 breaths; end Enhances therapeutic effect of the following drugs:
tidal concentrations 4–11% v/v [NOTE: Inspired Blood pressure-lowering agents; Hypotension-
concentrations >12% have been safely administered associated agents (hypotensive effect); Dopamine;
during induction and may require a reduction of nitrous Epinephrine (nasal; oral inhalation and systemic);
oxide or air]. Norepinephrine (arrhythmogenic effect); Metyrosine;
Anesthesia, maintenance, by inhalation, ADULT, 2.5 to 8.5% Ropinirole, Rotigotine, Pramipexole (sedative effect);
v/v with or without concomitant nitrous oxide; CHILD, Neuromuscular-blocking Agents, Nondepolarizing, e.g.,
5.2–10% with or without nitrous oxide. Atracurium (neuromuscular-blocking effect)
NOTE: Not indicated as induction agent or for maintenance QTc-prolonging Agents (QTc-prolonging effect)
of anesthesia in non-intubated children <6 years.
Increases risk of adverse or toxic effects of Desflurane:
Dosing based on patient’s age and Minimum Alveolar Ephedrine nasal and systemic (arrhythmogenic effect);
Concentration (MAC): Methylphenidate (hypertensive effect); Other CNS
MAC with 100% MAC with 60% Depressants; Rufinamide (sleepiness and dizziness)
Age
Oxygen N2O/ 40% O2
Increases risk of adverse or toxic effects of the following
9 months 10% 7.5%
drugs:
3 years 8.9% 6.4% Amifostine (hypotensive effect); Fenoterol, Formoterol,
25 years 7.3% 4% Isoproterenol, Metaraminol (arrhythmogenic effect);
45 years 6% 2.8% SSRIs (psychomotor impairment)
70 years 5.2% 1.7%
Administration: Inhalation via desflurane-specific calibrated
Dose Adjustment: heated vaporizer
Geriatric: Geriatric dose requires approximately 70% the
adult dose in 100 % oxygen and 40% the adult dose of NOTE: Monitor BP, heart rate and rhythm, temperature,
nitrous oxide oxygen saturation, end-tidal CO2 and end-tidal
desflurane concentration prior to and throughout

424
NERVOUS SYSTEM

procedure. Monitor signs and symptoms of airway Ephedrine nasal and systemic (arrhythmogenic effect);
narrowing for pediatric patients. Methylphenidate (hypertensive effect); Succinylcholine
Assess for malignant hyperthermia, hypercapnia, muscle (malignant hyperthermia)
rigidity, tachycardia, cyanosis, arrhythmias, hypotension
or hypertension. Increases risk of adverse or toxic effects of the following
drugs:
Pregnancy Category: B Fenoterol, Formoterol, Isoproterenol, Metaraminol
(arrhythmogenic effect); Other CNS depressants
ATC Code: N01AB07
Prolongs recovery from anesthesia:
Ketamine
Rx HALOTHANE Administration: Inhalation via halothane-specific calibrated
vaporizer
Inhalation: 250 mL bottle
NOTE: Monitor pulse and BP.
Halothane is a non-flammable, halogenated, hydrocarbon
inhalational anesthetic. It provides relatively rapid Pregnancy Category: C
induction with little or no excitement, though analgesia
may not be adequate. ATC Code: N01AB01

Indication: Induction and maintenance of general

anesthesia.
Rx ISOFLURANE
Contraindications: Known or suspected susceptibility to
malignant hyperthermia; raised cerebrospinal fluid Inhalation: 100 mL and 250 mL bottle
pressure; history of unexplained jaundice or acute
hepatic damage from previous exposure to halothane; Isoflurane is a highly halogenated methyl ester that

N
outpatient dental surgery in children <18 years; produces profound respiratory depression. Inhaled
obstetrical anesthesia except when uterine relaxation is anesthetics alter activity of neuronal ion channels,
required. particularly the fast-synaptic neurotransmitter receptors.
They can also depress myocardial contractility, decrease
Dose: blood pressure and sympathetic nervous activity.
Anesthesia, induction, by inhalation, ADULT, 0.5% v/v in
oxygen or mixture of nitrous oxide and oxygen, increase Indication: Induction and maintenance of general
gradually according to response to a concentration of 2– anesthesia.
4% v/v, CHILD, 1.5–2% v/v.
Anesthesia, maintenance, by inhalation, ADULT, 0.5 to 2% Contraindications: Known or suspected genetic
v/v depending on the flow rate used, CHILD, 0.5–1.5% susceptibility to malignant hyperthermia; history of
v/v. hepatitis following halogenated inhalational anesthetic;
history of liver dysfunction, jaundice or unexplained
Precautions: fever, leucocytosis, or eosinophilia following halogenated
Pheochromocytoma; myasthenia gravis; renal failure; pre- anesthetic administration.
existing hepatic disease.
Children. Dose:
Pregnancy and lactation. Anesthesia, induction, by inhalation, ADULT, 1.5–3% with
oxygen or oxygen-nitrous oxide mixture.
Adverse Drug Reactions: Anesthesia, induction, by inhalation, ADULT, 0.5% v/v with
Rare: Post-operative nausea, vomiting, shivering, oxygen or oxygen and nitrous oxide mixture, increased to
respiratory depression, respiratory arrest, hypotension, 1.5–3% v/v with oxygen or oxygen-nitrous oxide mixture.
skeletal muscle relaxation, hepatic necrosis, Anesthesia, maintenance, by inhalation, ADULT, 1 to 2.5%
hyperpyrexia, bradycardia, cardiac arrest, hypotension. v/v with concomitant oxygen and nitrous oxide mixture,
Potentially fatal: Hepatotoxicity, malignant hyperthermia, then 1.5–3.5% v/v with oxygen alone.
cardiac arrhythmias. Anesthesia, maintenance during caesarian section, ADULT
women, 0.5–0.75% v/v with oxygen and nitrous oxide
Drug Interactions: mixture.
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs: Precautions:
Dopamine, Epinephrine (nasal, oral inhalation and Increased intracranial pressure; Coronary artery disease;
systemic), Norepinephrine (arrhythmogenic effect); Patients at risk of QT prolongation and
Hypotensive Agents, e.g., Hexamethonium Bromide, bronchoconstriction; Hypotension; Hypovolemia;
Trimetaphan Camsilate; Neuromuscular-blocking Neuromuscular disease, e.g., Duchenne muscular
Agents; Nondepolarizing (neuromuscular-blocking dystrophy; myasthenia gravis; mitochondrial disorders;
effect) Addison’s disease; Myxedema; Hepatic impairment:
Carboxyhemoglobinemia (do not allow CO2 absorbents in
Increases risk of adverse or toxic effects of Halothane: anesthetic apparatus to dry out when delivering

425
 NERVOUS SYSTEM

isoflurane to minimize the risk of developing hepatic impairment associated with halogenated
carboxyhemoglobinaemia); Hemodynamically anesthetics.
compromised and debilitated patients.
Children (use with caution in <3 years); Pregnancy and Dose:
lactation. Anesthesia, induction and maintenance, by inhalation,
ADULT, 0.5–3% v/v with or without the concomitant use
Drug Interactions: of nitrous oxide; amnesia and loss of awareness occurs
Avoid concomitant use with: at 0.6%.
Enhances therapeutic effect of the following drugs:
Blood pressure-lowering agents, (hypotensive effect); Patient Age and Minimum Alveolar Concentration
Dopamine; Epinephrine nasal; oral inhalation and (MAC)
systemic, Norepinehrine (arrhythmogenic effect); MAC with
Metyrosine; Pramipexole (sedative effect); MAC with 100% 65%
Neuromuscular-blocking Agents; Nondepolarizing Age
Oxygen N2O/
(neuromuscular-blocking effect); QTc-prolonging Agents 35% O2
(QTc-prolonging effect); Ropinirole; Rotigotine (sedative 0–1 month
effect) old full-
3.3% -
term
Increases risk of adverse or toxic effects of Isoflurane: neonates
Bambuterol; Ephedrine, Nasal and Systemic 1 to <6
(arrhythmogenic effect); Methylphenidate (hypertensive 3% -
months
effect); Rufinamide (sleepiness and dizziness)
6 months to
2.8% 2%
<1 year
Increases risk of adverse or toxic effects of the following
drugs: 1 to <3
2.8% 2%
Fenoterol; Formoterol; Isoproterenol; Metaraminol years
(arrhythmogenic effect); Other CNS depressants; SSRIs 3–12 years 2.5% -
(psychomotor impairment) 25 years 2.6% 1.4%
N

40 years 2.1% 1.1%

Administration: Administer via isoflurane-specific calibrated 60 years 1.7% 0.9%
vaporizer or vaporizer with calculated flow required.
80 years 1.4% 0.7%
Use an ultra-short-acting barbiturate to avoid coughing,
breath-holding, or laryngospasm during induction. Dose Adjustment:
Renal and Hepatic Impairment:
NOTE: Select premedication based on the need of the Use with caution in severe impairment. Safety has not been
individual patient, considering that secretions are weakly established.
stimulated by isoflurane, and the heart rate tends to be
increased. The use of anticholinergic drugs is a matter of Precautions:
choice. Increased intracranial pressure; Neuromuscular disease
e.g. Duchenne muscular dystrophy; mitochondrial
Pregnancy Category: C disorder; Hypovolemia; Hypotension; Hemodynamically
compromised patients; Patients at risk of QT
ATC Code: N01AB06 prolongation; Hepatic and renal impairment
Children; Pregnancy and lactation

Adverse Drug Reactions:

Rx SEVOFLURANE Common: Hypotension, tachycardia, bradycardia,
hypertension, agitation, drowsiness, shivering, dizziness,
Inhalation: 250 mL bottle headache, hypothermia, myoclonus, delirium
(emergence), sialorrhea, cough, airway obstruction,
Sevoflurane is a fluorinated isopropyl esther. It may act by laryngospasm, breath-holding, apnea, fever
interfering with the release and re- uptake of Less Common: Acidosis, albuminuria, amblyopia,
neurotransmitters at post- synaptic terminals and/or anaphylactoid reaction, anaphylaxis, atrial arrhythmia,
alter ionic conduction following receptor activation. It bigeminy, bronchospasm, atrial fibrillation, cardiac
also activates GABA receptors that produces general arrhythmia, chest discomfort, complete AV block,
anesthetic effect, a decrease in myocardial contractility confusion, conjunctivitis, crying, dysgeusia, ST-segment
and mean arterial pressure and increases respiratory depression on ECG, dyspnea, extrasystoles
rate. (supraventricular), facial edema, glycosuria,
hemorrhage, hepatic failure, hepatic insufficiency,
Indication: Induction and maintenance of general hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic),
anesthesia. hiccups, hypertonia, hyperbilirubinemia, hyperglycemia,
hypoxia, hypersensitivity reaction, hyperkalemia
Contraindications: Known or suspected susceptibility to (pediatric; postoperative), hyperventilation,
malignant hyperthermia; history of moderate to severe hypophosphatemia, hypoventilation, insomnia,
jaundice, leukocytosis (transient), malignant

426
NERVOUS SYSTEM
hyperthermia, myoglobinuria, nervousness, oliguria,
pain, pharyngitis, pruritus, second degree
atrioventricular block, skin rash, stridor, syncope,
thrombocytopenia, tooth enamel damage (fluorosis),
urinary retention, urticaria, ventricular premature
contractions, weakness, wheezing, xerostomia
Rare: Seizure
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:
Blood pressure-lowering agents and Hypotensive agents
(hypotensive effect);
Dopamine; Epinephrine nasal, oral inhalation and
systemic; Norepinephrine (arrhythmogenic effect);
Metyrosine, Pramipexole, Ropinirole, Rotigotine
(sedative effect); Neuromuscular-blocking Agents;
Nondepolarizing (neuromuscular-blocking effect); QTc-
prolonging Agents (QTc-prolonging effect)
Increases risk of adverse or toxic effects of Sevoflurane:
Bambuterol; Epinephrine nasal, oral inhalation and
systemic (arrhythmogenic effect); Methylphenidate
(hypertensive effect); Rufinamide (sleepiness and
dizziness)
Increases risk of adverse or toxic effects of the following
drugs:
Fenoterol; Formoterol; Isoproterenol; Metaraminol
(arrhythmogenic effect); Other CNS depressants; SSRIs
(psychomotor impairment)
Administration: Administer via sevoflurane-specific
calibrated vaporizers. Use with caution in low-flow or
closed-circuit systems since sevoflurane is unstable and
may liberate potentially toxic breakdown products.
Pregnancy Category: B
ATC Code: N01AB08
BARBITURATES, PLAIN
Rx THIOPENTAL SODIUM
Inj.: 500 mg vial (IV)
1 g vial + 50 mL diluent (IV)
Thiopental is an ultrashort-acting thiobarbiturate with
anesthetic activity that binds to the chloride site of the
GABAA/chloride receptor complex resulting in inhibitory
actions of GABAA in the brain. This leads to synaptic
inhibition, decreased neuronal excitability, glutamate
response and induction of anesthesia but not analgesia.
Indication: Induction of anesthesia.
Contraindications: Variegate or acute intermittent
porphyria; absence of suitable veins for IV
administration; status asthmaticus; dyspnea or
respiratory obstruction; severe cardiovascular disease or
hypotension; Addison’s disease; hepatic dysfunction;
myxedema.
Dose:
Anesthesia, induction, by IV injection or continuous IV
infusion, ADULT, 100–150 mg of a 2.5 or 5% solution
injected over 10–15 seconds, repeat every 30–60
seconds according to response or as a continuous
infusion of a 0.2 or 0.4% solution (maximum, 500 mg;
maximum dose in pregnancy, 250 mg); CHILD, 2–7
mg/kg over 10–15 seconds, repeat after 1 minute if
needed.
Dose Adjustment:
Geriatric:
Use with caution. Dose reduction or small doses are
advisable.
Renal Impairment:
Use with caution as hypnotic effect may be prolonged or
potentiated. If CrCl<10 mL/minute, administer at 75% of
normal dose.
Hepatic Impairment:
Use with caution. Reduce doses.
Precautions:
Severe CV, respiratory, renal, hepatic, or endocrine disease;
Hypotension; Shock; Hypovolemia; Conditions in which
hypnotic effects may be potentiated; History of severe
asthma; Severe cardiac disease; Severe anemia;
N
Hyperkalemia; Toxemia Myasthenia gravis; Myxedema;
Muscular dystrophies; Adrenocortical insufficiency;
Increased intracranial pressure
Elderly; Pregnant
Lactation (excreted in breastmilk; monitor infant for
possible adverse effects).
Adverse Drug Reactions: Coughing, hiccupping, sneezing,
muscle twitching, laryngospasm, bronchospasm. tissue
necrosis (IV-related). severe arterial spasm with burning
pain (intra-arterial), blanching of forearm and hands and
gangrene of digits (intra-arterial), respiratory depression,
arrhythmias, circulatory failure, anaphylactoid reactions,
myocardial depression, arrhythmias, delirium, headache,
amnesia, seizures, rash, abdominal pain, rectal irritation,
diarrhea, cramping, apnea, hiccups, sneezing, coughing,
thrombophlebitis, pain at injection site, salivation,
shivering.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Thiopental:
Brimonidine (Topical); Doxylamine; Dronabinol;
Hydroxyzine; Magnesium sulphate; Minocycline;
Nabilone
Enhances therapeutic effect of the following drugs:
Diazoxide; Hypotensive agents (hypotensive effect); Ethyl
alcohol; Meperidine (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Enhances absorption of Theophylline Derivatives [except
Dyphylline]
Increases metabolism of Thiopental:
Pyridoxine
Increases metabolism of the following drugs:
427
 NERVOUS SYSTEM

Paracetamol; Calcium Channel Blockers; Propacetamol; NOTE: IV infusion of concentrated solutions (e.g., 5%) may
Rifamycin Derivatives cause thrombophlebitis. Repeated doses may result in
prolonged drug effect because of accumulation.
Increases risk of adverse or toxic effects of Thiopental:
Antipsychotic Agents; Phenothiazines; CNS Depressants Pregnancy Category: C
[except Levocabastine]; Ketamine; Primidone;
Rufinamide (sleepiness and dizziness) ATC Code: N01AF03

Increases risk of adverse or toxic effects of the following

drugs: OTHER GENERAL ANESTHETICS
Paracetamol, Proparacetamol (liver damage); SSRIs
(psychomotor impairment); Thiazide diuretics
(orthostatic hypotension)
Rx KETAMINE

Reduces therapeutic effect of Thiopental: Inj.: 50 mg/mL (as hydrochloride), 10 mL vial (IM, IV)
Aminophylline
Ketamine is a cyclohexane derivative that binds to the
Reduces therapeutic effect of the following drugs: NMDA receptor and blocks glutamate. At low doses, it
Paracetamol; Propacetamol produces analgesia and modulate central sensitization,
hyperalgesia, and opioid tolerance. It also reduces
Avoid concomitant use with: polysynaptic spinal reflexes and produces a cataleptic-
Decreases metabolism of Thiopental: like state in which the patient is dissociated from the
Chloramphenicol surrounding environment.

Decreases serum concentration of Thiopental: Indications: Induction and maintenance of anesthesia;

Mefloquine endotracheal intubation; sedation or analgesia of
critically-ill patients.
Decreases serum concentration of the following drugs:
N

Doxycycline; Lamotrigine; Ulipristal Contraindications: Conditions in which an increase in blood

pressure or intraocular pressure; infants <3 months of
Enhances therapeutic effect of Thiopental: age; known or suspected schizophrenia.
Droperidol (CNS depressant effect); Droperidol,
Sulfisoxazole Dose:
Anesthesia, induction, by IM injection, ADULT, 6.5–13
Enhances therapeutic effect of the following drugs: mg/kg, ADOLESCENT <16 years, CHILD and INFANT ≥3
Buprenorphine [initiate buprenorphine patches at 5 months, 5–10 mg/kg;
micrograms/hour when used concomitantly], by IV infusion, ADULT, 1–4.5 mg/kg, ADOLESCENT <16
Hydrocodone [consider starting with a 20–30% lower years, CHILD, and INFANT ≥3 months, 1–3 mg/kg.
hydrocodone dose when used concomitantly]; Anesthesia, maintenance, by IM injection, ADULT,
Mirtazapine, Orphenadrine, Paraldehydye, Suvorexant, supplemental doses of ½ to full induction dose or by
Thalidomide, Zolpidem (CNS depressant effect) continuous infusion of 0.1 to 0.5 mg/minute;
ADOLESCENTS ≥16 years, supplemental doses of ½ to
Increases metabolism of the following drugs: full induction dose as needed.
Cyclosporine (Systemic); Tricyclic Antidepressants e.g Endotracheal intubation, by IV infusion, ADOLESCENT,
Amytriptyline; Vitamin K Antagonists, e.g., Warfarin CHILD, and INFANT, 1–2 mg/kg as part of rapid
sequence sedation.
Increases risk of adverse or toxic effects of the following Sedation or analgesia, critically-ill patients, by IV infusion,
drugs: ADOLESCENT, CHILD, and INFANT ≥5 months, initially
Azelastine (Nasal) (CNS depressant effect); 0.5–2 mg/kg, then by continuous IV infusion at a rate of
Somatostatin Acetate (barbiturate effects, including 5–20 micrograms/kg per minute; start at lower dose and
sedative effects) titrate to effect.

Reduces therapeutic effect of Thiopental: Dose Adjustment:

Mefloquine Geriatric:
Avoid in older adults with risk factors for coronary artery
Reduces therapeutic effect of the following drugs: disease.
Estrogen and Progestin contraceptives (contraceptive Renal Impairmet:
failure) Reduce dose for moderate impairment. Do not use in severe
impairment.
Administration: Administer by IV infusion. Avoid intra-arterial
administration.

Avoid extravasation.

The patient must always lie supine as even a small

overdose can cause hypotension.

428
NERVOUS SYSTEM
Precautions:
WARNING: Should only be used by experienced
personnel who are not actively engaged in the
procedure or surgery. If used in a non-intubated
and/or nonmechanically ventilated patient,
qualified personnel and appropriate equipment for
rapid institution of respiratory and/or
cardiovascular support must be immediately
available.
Chronic alcoholic or acutely alcohol-intoxicated patients;
Cardiac decompensation; Pre-anesthesia elevated CSF
pressure; Globe injuries; Increased intraocular pressure,
e.g., glaucoma; Neurotic traits or psychiatric illness, e.g.,
schizophrenia, acute psychosis. Acute intermittent
porphyria; Seizures; Hyperthyroidism; Pulmonary or
upper respiratory infection; Intracranial mass lesions;
Head injury or hydrocephalus; Hypovolemia;
Dehydration; Cardiac disease, especially coronary artery
disease, e.g., CHF, MI, myocardial ischemia.
Pregnancy and lactation.
Adverse Drug Reactions:
Common: Confusion, delirium, dreamlike state, excitement,
hallucinations, irrational behavior, vivid imagery,
hypertonia (tonic-clonic; high-dose), sedation,
hypertension or hypotension, bradycardia, cardiac
arrhythmia, increased cerebrospinal fluid pressure,
increased pulse, drug dependence, psychotomimetic
phenomena (euphoria, dysphasia, psychomotor
retardation, vivid dreams, nightmares, impaired
attention, memory and judgment, illusions,
hallucinations, altered body image, blunted affect), CNS
depression, erythema (transient), morbilliform rash
(transient), rash at injection site, central diabetes
insipidus, anorexia, nausea, sialorrhea, bladder
dysfunction (reduced capacity), cystitis (including cystitis
noninfective, cystitis interstitial, cystitis ulcerative,
cystitis erosive, cystitis hemorrhagic), vomiting, dysuria,
hematuria, urinary frequency, urinary incontinence,
urinary urgency, anaphylaxis, pain at injection site,
laryngospasm, diplopia, increased intraocular pressure,
nystagmus, hydronephrosis, airway obstruction, apnea,
respiratory depression, syncope, delirium, dizziness,
blurred vision, altered hearing.
Drug Interactions:
Avoid concomitant use with:
Enhances sedative effect of the following drugs:
Metyrosine; Pramipexole; Ropinirole; Rotigotine
Increases risk of adverse or toxic effects of Ketamine:
Diazepam; Other CNS depressants Rufinamide
(sleepiness and dizziness); Theophylline, Thiopental
(seizures, by reducing the seizure threshold)
Increases risk of adverse or toxic effects of the following
drugs:
Atracurium, Tubocurarine (respiratory depression with
apnea); CNS Depressants, e.g., Phenothiazine, Sedating
H1 Blockers, Skeletal Muscle Relaxants (CNS depression;
respiratory depression); Dextromethorphan;
Halogenated Anesthetics (bradycardia; hypotension;
decreased cardiac output)
Memantine; SSRIs (psychomotor impairment); Thyroid
Hormones (hypertension)
Increases serum concentration of Ketamine:
Diazepam
Reduces therapeutic effect of Ketamine:
Thiopental (antagonistic effect)
Administration:
For deep IM administration, inject into large muscle
mass.
For IV administration, administer bolus or induction
doses over 1 minute or at a rate of 0.5 mg/kg per minute.
A more rapid administration may result in respiratory
depression and enhanced pressor response. May
administer over 2–3 minutes. May be administered as a
continuous IV infusion.
NOTE: May administer atropine, scopolamine, or another
drying agent prior to induction and at appropriate
intervals to decrease hypersalivation. Titrate dose for
desired effect
Pregnancy Category: B
ATC Code: N01AX03
NITROUS OXIDE
N
Rx
Inhalation: Anesthetic gas
Nitrous Oxide is an odorless gas that serves as an
anesthetic and analgesic. At high concentrations, it
causes a narcotic effect and may replace oxygen,
causing asphyxiation.
Indications: Surgical sedation and anesthesia; dental
sedation and anesthesia.
Contraindications: Patients with demonstrable collections
of air in the pleural, pericardial, or peritoneal space;
intestinal obstruction; occlusion of the middle ear;
arterial air embolism; decompression sickness; chronic
obstructive airway disease; emphysema; recent
pneumoencephalography
Dose:
Dental sedation and analgesia, by inhalation, ADULT, 25–
50% nitrous oxide with oxygen.
Surgical sedation and analgesia, by inhalation, ADULT, 25–
50% nitrous oxide with oxygen;
General anesthesia, by inhalation, ADULT, 40–70% via
mask or endotracheal tube.
NOTE: Minimal alveolar concentration (MAC), which can be
considered the ED50 of inhalational anesthetics, is 105%;
delivery in a hyperbaric chamber is necessary to use as
a complete anesthetic. When administered at 70%, MAC
of other anesthetics is reduced by half.
Dose Adjustment:
Renal and Hepatic Impairment:
No information found
429

Precautions:
Addictive (may be associated with abuse and/or addiction);
Body space volume expansion; Bone marrow
suppression (prolonged use may produce bone marrow
suppression; increased risk in vitamin B12 deficiency and
other nutritional deficiencies); Neurologic effects
(increased risk in vitamin B12 deficiency and other
nutritional deficiencies);
Vitreoretinal surgery (may increase intraocular pressure
resulting in retinal artery occlusion, ischemia, or optic
nerve damage and vision loss).
Adverse Drug Reactions: Nausea, vomiting, neurologic
effects (prolonged use)
Rare: Hypotension, CNS stimulation, confusion, dizziness,
headache, nausea, vomiting, apnea
Drug Interactions:
Avoid concomitant use with:
Enhances sedative effect of the following drugs:
Pramipexole; Ropinirole; Rotigotine
Increases risk of adverse or toxic effects of Ketamine:
CNS depressants; Rufinamide (sleepiness and dizziness)
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
N
Administration: For the maintenance of anesthesia, always
mix nitrous oxide with at least 30% oxygen using a
compressed-gas anesthetic machine.
Administer oxygen briefly during emergence from
prolonged anesthesia with nitrous oxide to prevent
diffusion hypoxia.
Pregnancy Category: C
ATC Code: N01AX13
Rx PROPOFOL
Inj.: 10 mg/mL, 20 mL ampule (IV)
10 mg/mL, 50 mL pre-filled syringe (IV)
10 mg/mL, 20 mL and 50 mL vial (IV)
Propofol facilitates inhibitory neurotransmission mediated
by GABA and is associated with minimal respiratory
depression and a short half-life with a duration of action
of 2–10 minutes. It may also reduce glutamatergic
activity through NMDA receptor blockade.
Indications: Induction and maintenance of general
anesthesia; monitored anesthesia care sedation, ICU
sedation in intubated mechanically-ventilated patients.
Contraindications: Hypersensitivity to eggs, egg products,
soybeans, or soy products; hypersensitivity to lipid
emulsions; children ≤18 years of age receiving intensive
care; where general anesthesia or sedation is
contraindicated; pregnancy; lactation.
Dose:
NOTE: Individualize dose, and titrate to response.
430
NERVOUS SYSTEM
ICU sedation in intubated mechanically-ventilated patients,
by IV infusion, ADULT, initially 5 micrograms/kg per
minute or 0.3 mg/kg per hour; increase by 5–10
micrograms/kg per minute or 0.3–0.6 mg/kg per hour
every 5–10 minutes until desired sedation level is
achieved; usual maintenance dose is 5–50
micrograms/kg per minute or 0.3–3 mg/kg per hour;
reduce dose after adequate sedation is established and
adjust to response [NOTE: Daily interruption with re-
titration or a light target level of sedation is
recommended to minimize prolonged sedative effects].
Induction of general anesthesia, by IV push, ADULT <55
years (healthy adults with ASA-PS 1 or 2), 2–2.5 mg/kg
(about 40 mg every 10 seconds until onset of induction),
ADULT (debilitated patients with ASA-PS 3 or 4), use 80%
of healthy adult dose, reduce dose after adequate
sedation is established and adjust to response [NOTE:
Daily interruption with re-titration or a light target level of
sedation is recommended to minimize prolonged
sedative effects];
CHILD 3–16 years (healthy children with ASA-PS 1 or 2),
2.5–3.5 mg/kg over 20–30 seconds; use a lower dose
for children ASA-PS 3 or 4.
Maintenance of general anesthesia, by IV infusion, ADULT
<55 years (healthy adults with ASA-PS 1 or 2), initially
100–200 micrograms/kg per minute or 6–12 mg/kg per
hour for 10–15 minutes; usual maintenance infusion
rate is 50 to 100 micrograms/kg per minute or 3–6
mg/kg per hour to optimize recovery time;
by IV infusion, ADULT >60 years (debilitated with ASA-PS
3 or 4), 50–100 micrograms/kg per minute or 3–6
mg/kg per hour;
by IV push, ADULT (debilitated patients with ASA-PS 3 or
4), 1–1.5 mg/kg (about 20 mg every 10 seconds until
onset of induction);
CHILD 2 months to 16 years (healthy children with ASA-
PS 1 or 2), 125–300 micrograms/kg per minute or 7.5–
18 mg/kg per hour; after 30 minutes, if clinical signs of
light anesthesia are absent, decrease infusion rate;
by IV intermittent bolus, CHILD ≤5 years, 25–50 mg
increments as needed [NOTE: May require larger
infusion rates].
Monitored anesthesia care sedation, by slow IV push and
slow IV infusion, ADULT <55 years (healthy adults with
ASA-PS 1 or 2), 100–150 micrograms/kg per minute or
6–9 mg/kg per hour for 3–5 minutes; alternatively, by
slow IV injection, 0.5 mg/kg over 3–5 minutes followed
by IV infusion of 25–75 micrograms/kg per minute or
1.5–4.5 mg/kg per hour;
by IV infusion, ADULT >60 years (debilitated with ASA-PS
3 or 4), use 80% of healthy adult dose;
by intravenous bolus, ADULT (debilitated or ASA-PS 3 or
4), use 80% of healthy adult dose;
ADULT <55 years (healthy adults with ASA-PS 1 or 2),
incremental bolus doses of 10 or 20 mg;
ADULT (debilitated or ASA-PS 3 or 4), use 80% of healthy
adult dose.
Dose Adjustment:
Geriatric, Debilitated Patients, ASA-PS 3 or 4:
Use a lower induction dose, a slower maintenance rate of
administration, and avoid rapidly delivered boluses to
reduce the incidence of unwanted cardiorespiratory
depressive events.
NERVOUS SYSTEM
Pediatric:
Consult local regulations and individual institutional policies
and procedures. Individualize doses based on total body
weight and titrate to the desired clinical effect. Wait at
least 3–5 minutes between dose adjustments to
clinically assess drug effects. Use smaller doses when
used with opioids.
Alcohol Use:
For general anesthesia, increase dose with chronic
alcoholism and decrease dose with acutely intoxicated
(alcoholic) patients.
Precautions:
WARNING: Should only be used by experienced
personnel who are not actively engaged in the
procedure or surgery. If used in a non-intubated
and/or nonmechanically ventilated patient,
qualified personnel and appropriate equipment for
rapid institution of respiratory and/or
cardiovascular support must be immediately
available.
Hypovolemia; Epilepsy; Lipid disorders; Increased
intracranial pressure.
Elderly; Children.
STORAGE AND STABILITY. Store between 4-25°C. Do NOT freeze.
Adverse Drug Reactions:
Common: Hypotension, hypertension, bradycardia, cardiac
arrhythmia, low cardiac output, tachycardia, involuntary
body movements, skin rash, pruritus,
hypertriglyceridemia, respiratory acidosis (during
weaning), pain at injection site (includes stinging), apnea
Less Common: Agitation, amblyopia, anaphylaxis,
anaphylactoid reaction, anticholinergic syndrome,
asystole, atrial arrhythmia, atrial premature contractions,
bigeminy, chills, cloudy urine, cough, decreased lung
function, delirium, dizziness, drowsiness, fever, flushing,
hair discoloration (green), hemorrhage, hypertonia,
hypomagnesemia, hypoxia, infusion-related reaction
(propofol-related infusion syndrome), infusion site
reaction (including pain, swelling, blisters and/or tissue
necrosis), laryngospasm, leukocytosis, limb pain, loss of
consciousness (postoperative; with or without increased
muscle tone), myalgia, nail discoloration (green
nailbeds), nausea, pancreatitis, paresthesia, phlebitis,
pulmonary edema, rhabdomyolysis, sialorrhea, syncope,
thrombosis, urine discoloration (green), ventricular
premature contractions, visual disturbance, wheezing
Rare: Myoclonus (including seizure and opisthotonos)
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Propofol:
Valproate
Enhances therapeutic effect of the following drugs:
Blood Pressure-lowering Agents (antihypertensive
effect); CNS Depressants (sedative, anesthetic, and
cardiorespiratory effects); Hypotension-associated
Agents (hypotensive effect); Pramipexole, Ropinirole,
Rotigotine (sedative effect); QTc-prolonging Agents (QTc-
prolonging effect)
Increases risk of adverse or toxic effects of Propofol:
Alfentanil (opisthotonos, which is the severe
hyperextension and spasticity resulting in arching or
bridging position, and/or tonic clonic seizures); CNS
depressants; Rifampin (hypotensive effect); Rufinamide
(sleepiness and dizziness)
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
Increases serum concentration of the Ropivacaine
Administration: Administer by IV push or by continuous IV
infusion. Shake well before use. Do not use if there is
evidence of excessive creaming or aggregation, if large
droplets are visible, or if there are other forms of phase
separation indicating that the stability of the product has
been compromised. Slight creaming, which should
disappear after shaking, may be visible upon prolonged
standing.
Avoid rapid bolus injection and large bolus doses in high
risk patients. Emulsion formulation of propofol 2%
should ONLY be used in children >3 years.
Strict aseptic technique must be maintained in handling.
Do NOT use if contamination is suspected. Tubing and
any unused portions of propofol vials should be
N
discarded after 12 hours.
Do NOT administer through the same IV catheter with
blood or plasma. Do NOT use filter <5 micron for
administration.
Use larger veins of forearm or antecubital fossa to
reduce pain associated with injection. One mL of
lidocaine 1% solution may be used prior to
administration or may be added to propofol immediately
prior to administration in a quantity not to exceed 20 mg
lidocaine per 200 mg propofol to reduce pain associated
with injection.
Avoid abrupt discontinuation prior to weaning or daily
wake up assessments as this can result in rapid
awakening, anxiety, agitation, and resistance to
mechanical ventilation. Wean the infusion rate so the
patient awakens slowly. Discontinue opioids and
paralytic agents prior to weaning. Long-term infusions
can result in some tolerance. Taper propofol infusions to
prevent withdrawal.
NOTE: Pain management requires specific use of analgesic
agents, at effective dosages as propofol lacks analgesic
properties. Titrate propofol separately from the analgesic
agent.
Pregnancy Category: B
ATC Code: N01AX10
431

ANESTHETICS, LOCAL
ESTERS OF AMINOBENZOID ACID
Rx TETRACAINE
Inj.: 20 mg sterile powder (as hydrochloride), ampule
(spinal)
Tetracaine prevents the generation and transmission of
impulse along nerve fibers and at nerve endings;
depolarization and ion-exchange are inhibited. In
general, loss of pain occurs before loss of sensory,
autonomic and motor functions.
Indication: Spinal anesthesia
Contraindications: Low plasma cholinesterase
concentrations; complete heart block; bronchoscopy or
cystoscopy.
Dose:
NOTE: Dose varies with the anesthetic procedure, the
degree of anesthesia required, and the individual patient
response.
N
Anesthesia extending up to costal margin, by subarachnoid
injection, ADULT, 15 mg; doses up to 20 mg may be given
but are reserved for exceptional cases.
Low spinal anesthesia, saddle block, by subarachnoid
injection, ADULT and CHILD, 2–5 mg.
Perineal anesthesia, by subarachnoid injection, ADULT and
CHILD, 5 mg.
Perineal and lower extremities, by subarachnoid injection,
ADULT and CHILD, 10 mg.
Spinal anesthesia, by subarachnoid injection, CHILD >15
kg, 0.2–0.3 mg/kg; CHILD 5–15 kg, 0.3–0.4 mg/kg;
NEONATE <5 kg (PCA <60 weeks), 0.4–1 mg/kg
(maximum dose should not exceed usual procedure-
specific adult doses as noted above).
Dose Adjustment:
Elderly, Acutely ill Patients, Debilitated Patients, Obstetric
Patients, and Patients with Increased Intra-abdominal
Pressure:
Use with caution. Dose reduction may be required.
Precautions:
WARNING: Should be used by dental practitioners
and/or clinicians well-trained in the diagnosis and
management of emergencies that may arise from
the use of these agents. Resuscitative equipment,
oxygen, and other resuscitative drugs should be
available for immediate use.
Shock (This should be treated before the administration of
anaesthetic); Cardiovascular disease; Cerebrospinal
diseases; Hypovolemic shock or altered coagulation
status; Epilepsy; Impaired cardiac conduction or
respiratory function; Hepatic impairment; Myasthenia
gravis; Decreased plasma esterase levels;
Hyperthyroidism.
Pregnancy.
432
NERVOUS SYSTEM
Adverse Drug Reactions:
Rare: Hypotension, chills, dizziness, drowsiness, loss of
consciousness, nervousness, seizure, urticaria, nausea,
vomiting, methemoglobinemia, anaphylaxis,
hypersensitivity reaction, tremor, blurred vision, miosis,
tinnitus
Drug Interactions:
Monitor closely with:
Reduces diagnostic effect of Technetium Tc 99m
Tilmanocept
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:
Neuromuscular-blocking agents e.g., Succinylcholine
(neuromuscular-blocking effect)
Increases risk of adverse or toxic effects of Tetracaine:
Hyaluronidase
Increases risk of adverse or toxic effects of the following
drugs:
Bupivacaine (Liposomal) [administer at least 20 minutes
or more apart]
Increases serum concentration of Tetracaine:
Anticholinesterases
Reduces therapeutic effect of Tetracaine:
Aminosalicylic acid, Sulfonamide (antagonistic effect)
Administration: Administer by subarachnoid injection for
spinal anesthesia.
Before injection, withdraw syringe plunger to make sure
injection is not into a vein or an artery.
For spinal anesthesia for adults, dilute to a 1% solution
with an equal volume of CSF immediately prior to
administration; or 5 mg of powder dissolved in 1 mL of
CSF and administer slowly at a rate of 1 mL over 5
seconds.
For low spinal (saddle block) anesthesia in vaginal
delivery, administer 2–5 mg as a hyperbaric solution.
Pregnancy Category: C
ATC Code: N01BA03
AMIDES
Rx BUPIVACAINE
Inj.: 0.5% (as hydrochloride), 5 mL, 10 mL, and 20 mL vial
0.5% (as hydrochloride), 5 mL, 10 mL, 20 mL, and 50
mL ampule /vial (local infiltration)
0.5% (as hydrochloride), 4 mL ampule (spinal) with
8% dextrose
0.5% (as hydrochloride) (isobaric), 5 mL ampule
(spinal)
Bupivacaine blocks the generation and the conduction of
nerve impulses, by binding to the intracellular portion of
NERVOUS SYSTEM
sodium channels and blocks sodium influx into nerve
cells. This leads to lose of sensation for pain,
temperature, touch and proprioception, and eventually
skeletal muscle tone.
Indications: Infiltration of local anesthesia, caudal block
(preservative-free), epidural block (preservative-free),
peripheral nerve block, sympathetic nerve block,
retrobulbar anesthesia, spinal anesthesia.
Contraindications: Obstetrical paracervical block
anesthesia; use as IV regional anesthesia (Bier block).
Dose:
NOTE: Dose varies with anesthetic procedure, area to be
anesthetized, vascularity of tissues, number of neuronal
segments to be blocked, depth of anesthesia, degree of
muscle relaxation required, duration of anesthesia
desired, individual tolerance, and the physical condition
of the patient.
Administer the smallest dose and concentration required
to produce the desired result.
Local anesthesia local infiltration, by SC or IM injection,
ADULT, 0.25% up to a maximum of 175 mg; perform
aspiration prior to each injection, however, absence of
blood in the syringe does not guarantee that IV injection
has been avoided.
Caudal block, by injection into the caudal end of the spinal
canal, ADULT, 15–30 mL of 0.25% or 0.5%.
Epidural block other than caudal block, by epidural
injection, ADULT, 10–20 mL of 0.25% or 0.5% in 3–5 mL
increments, allowing sufficient time to detect toxic
manifestations of inadvertent IV or intrathecal
administration; or 10–20 mL of 0.5% solution, up to 1%;
Non-obstetric surgery, by epidural injection, ADULT, 10–20
mL of 0.75% solution up to 1.5% as a single dose.
Surgical procedures requiring a high degree of muscle
relaxation and prolonged effects only, except obstetrical
cases, by epidural injection, ADULT, 10–20 mL of 0.75%.
Peripheral nerve block, by injection onto or near the nerve,
ADULT, 5 mL of 0.25% or 0.5% (maximum total daily
dose, 400 mg).
Sympathetic nerve block, by injection onto or near the
nerve, ADULT, 20–50 mL of 0.25%.
Retrobulbar anesthesia, by injection into retrobulbar space,
ADULT, 2–4 mL of 0.75%.
Spinal anesthesia, by intrathecal injection, ADULT,
preservative-free solution of 0.75% in 8.25% dextrose;
for lower extremity and perineal procedures, 1 mL;
for lower abdominal procedures, 1.6 mL;
for normal vaginal delivery, 0.8 mL, higher doses may be
required in some patients;
for Caesarean delivery, 1-–1.4 mL.
Dose Adjustment:
Geriatric, Acutely ill Patients, and Debilitated Patients:
Use with caution. Dose reduction may be required.
Hepatic Impairment and/or Cardiac Disease:
Reduce doses.
Precautions:
WARNING: Should be administered by clinicians well-
trained in the diagnosis and management of
emergencies that may arise from the use of these
agents. Resuscitative equipment, oxygen, and
other resuscitative drugs should be available for
immediate use.
The 0.75% concentration is NOT for use as
obstetrical anesthesia. Its use Cardiac arrest with
difficult resuscitation or death has been reported
with its use for epidural anesthesia in obstetrical
patients. Cardiac arrest has occurred after
convulsions resulting from systemic toxicity,
presumably following unintentional IV injection.
Reserve use of 0.75% concentration for surgical
procedures where a high degree of muscle
relaxation and prolonged effect are necessary.
Cardiac arrest and death have occurred with IV
regional anesthesia administration (Bier block).
Delay in proper management of dose-related
toxicity, underventilation from any cause and/or
altered sensitivity may lead to the development of
acidosis, cardiac arrest, and possibly death.
N
Cardiovascular effects; Cardiovascular disease;
Cross-sensitivity (cross-sensitivity with amide type local
anesthetics have been reported);
Chondrolysis (primarily of the shoulder joint, has occurred
following continuous intra-articular infusion; destruction
of articular cartilage has occurred when infused directly
into the shoulder);
Seizures (convulsions due to systemic toxicity leading to
cardiac arrest have been reported);
Respiratory arrest (have been associated with rare
occurrences of sudden respiratory arrest, especially
when administered near the head or neck);
Hepatic impairment; Renal impairment (substantially
excreted by the kidney; increased risk of toxic reactions);
Sulfite allergy (may contain sodium metabisulfite; use with
caution);
Elderly (patients >65 years may be at an increased risk for
developing hypotension while undergoing anesthesia
with bupivacaine);
Children (insufficient data available on the use in patients
<12 years; use with caution);
Pregnancy (no adequate and well-controlled studies);
Lactation (excreted in breastmilk).
Adverse Drug Reactions:
Common: Anxiety, anaphylactoid reaction, apnea,
angioedema, blurred vision, bradycardia, cardiac arrest,
chills, chondrolysis, CNS excitation and/or depression,
constriction of pupils, decreased cardiac output,
depression of myocardium, dizziness, drowsiness
merging into unconsciousness, heart block, hypotension,
hypoventilation, miosis, nausea, palpitations, pruritus,
respiratory arrest, restlessness, tinnitus, tremors,
urticaria, ventricular arrhythmia, vomiting, weakness.
Less Common: Backache, convulsions, cranial nerve palsy,
fecal incontinence, headache, loss of anal sphincter
control, loss of perineal sensation, paralysis of lower
433

extremities, meningismus, paresthesia, persistent
anesthesia, seizure, septic meningitis, sexual disorder
(loss of function), slowing of labor, urinary incontinence,
urinary retention.
Rare: Erythema, angioneurotic edema, tachycardia,
sneezing, syncope, excessive sweating, elevated
temperature, anaphylactoid-like symptoms.
NOTE: Incidence of adverse reactions is difficult to define.
Most effects are dose-related and are often due to
accelerated absorption from the injection site,
unintentional IV injection, or slow metabolic degradation.
The development of any CNS symptoms may be an early
indication of more significant toxicity (seizure).
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Bupivacaine:
Lidocaine, Mexiletine (additive systemic effect)
Increases risk of adverse or toxic effects of Antiarrhythmics
(myocardial depression)
Reduces diagnostic effect of Technetium Tc 99m
Tilmanocept
Avoid concomitant use with:
Enhances therapeutic effect of Neuromuscular-blocking
N
Agents (neuromuscular-blocking effect)
Increases risk of adverse or toxic effects of Bupivacaine:
Hyaluronidase
Increases risk of adverse or toxic effects of the following
drugs:
Blood pressure-lowering agents; Hypotensive agents
(hypotension); Bupivacaine, Liposomal [administer at
least 20 minutes or more apart]; Ergot Alkaloids,
Vasopressor drugs (severe, persistent hypertension or
cerebrovascular accidents)
Administration: Do NOT use solutions containing
preservatives for epidural or caudal blocks. Avoid rapid
injection of large volume. Use fractional (incremental)
doses when feasible.
Use an infusion pump to slowly administer local
anesthetics to or around surgical wound sites and/or
near peripheral nerves for postoperative analgesia.
Avoid IV injections. Perform aspiration prior to
administration. Re-position the needle until no return of
blood can be elicited by aspiration. However, absence of
blood in the syringe does NOT guarantee that IV injection
has been avoided. Intravenous regional anesthesia (Bier
block) is not recommended;
Mixing or the prior or intercurrent use with other local
anesthetic is not recommended due to insufficient data
on the clinical use of such mixtures.
NOTE: A test dose is recommended prior to epidural
administration (prior to initial dose) and all reinforcing
doses with continuous catheter technique.
434
NERVOUS SYSTEM
Duration of anesthetic effect may be prolonged by the addition of
epinephrine.
Pregnancy Category: C
ATC Code: N01BB01
Rx LIDOCAINE
Inj.: 1% (as hydrochloride), 20 mL ampule
2% (as hydrochloride), 2 mL, 5 mL, 20 mL, and 50 mL
ampule/vial (IM/IV)
2% (20 mg/mL) (as hydrochloride), 5 mL and 50 mL
vial (epidural, local infiltration)
2% (as hydrochloride), 1.8 mL carpule (with
epinephrine) (local infiltration)
Topical: 10% spray (as hydrochloride), 50 mL
A moderately long-acting, local anesthetic, which blocks
initiation and transmission of nerve impulses at the site
of application by stabilizing neuronal membrane and
inhibition of Na ion movements.
Indication:
[Injection]: Surface anesthesia of mucous membranes;
infiltration anesthesia; peripheral and sympathetic nerve
block.
[Topical]: Local anesthetic for oral mucous membrane.
Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy
with anticoagulants or an abnormal bleeding tendency;
severe anemia or heart disease; spinal or epidural
anesthesia in dehydrated or hypovolemic patients.
Dose:
NOTE: Dose varies with anesthetic procedure, area to be
anesthetized, vascularity of tissues, number of neuronal
segments to be blocked, depth of anesthesia, degree of
muscle relaxation required, duration of anesthesia
desired, individual tolerance, and the physical condition
of the patient.
Administer the smallest dose and concentration required
to produce the desired result.
Local or percutaneous infiltration and peripheral nerve
block, by SC or ID injection, ADULT, 5–300 mg.
Cutaneous infiltration, by SC injection, ADULT, maximum of
4.5 mg/kg per dose, not to exceed 300 mg; do not repeat
within 2 hours, ADOLESCENT and CHILD, use solutions
<2% for larger volumes (maximum dose, 5 mg/kg per
dose, not to exceed 300 mg/dose); do not repeat within
2 hours.
Intraosseous line or infusion pain, local injectable
anesthesia, by intraosseous injection, ADULT, initially 40
mg of 2% preservative-free solution over 1–2 minutes;
usual dose range is 20–50 mg/dose (maximum dose,
20–50 mg/dose); ADOLESCENT, CHILD, and INFANT,
initially 0.5 mg/kg of 1% or 2% preservative-free solution
over 1–2 minutes; usual dose range is 20–50 mg/dose
(maximum dose, 20–50 mg/dose).
[NOTE: After administration of initial dose, allow
lidocaine to dwell for up to 1 minute then follow with NS
flush, immediately follow with a second lower (50% dose
NERVOUS SYSTEM

reduction) lidocaine dose over 30–60 seconds has occurred following continuous intra-articular
(maximum repeat dose, 20 mg/dose); if discomfort infusion; destruction of articular cartilage has occurred
reoccurs, may repeat doses at a maximum frequency of when infused directly into the shoulder); Seizures
every 45 minutes during intraosseous access, not (convulsions due to systemic toxicity leading to cardiac
exceeding 3 mg/kg in 24 hours. arrest have been reported). Sulfite allergy (may contain
Each intraosseous access device has as specific sodium metabisulfite; use with caution).
minimum weight and age in addition to specific Solutions containing epinephrine should be used with
instruction for insertion and validation. Consult product caution for ring block of digits or appendages to prevent
specific information for more detail]. risk of ischemic necrosis. Increased risk of arrhythmias
Peripheral nerve block, CHILD, 505 micrograms/kg. has been reported.
(maximum safe doses of lidocaine for ADULT and CHILD Elderly (increased sensitivity); Children <6 months (more
are: 4 mg/kg for the 1% lidocaine). sensitive to toxic effects). Pregnancy (avoid large doses
Topical anesthesia, by topical administration, ADULT, apply during third trimester to diminish risk of neonatal
to affected area ≤4 times daily as needed, respiratory depression, hypotonia and bradycardia after
paracervical block); Lactation
Maximum Dose
Usual Procedure Procedures [Topical]:
Route Application to broken or inflamed skin may lead to
Dose <1 >5
minute minutes increased systemic absorption. Do not leave on large
body areas for >2 hours.
20–60
Nasal 600 mg 500 mg Pregnancy (amount absorbed varies by dose administered,
mg
duration of exposure, and site of application; cumulative
20– exposure from all routes of administration should be
Oropharyngeal 500 mg 600 mg
200 mg considered).
Respiratory 50–
400 mg 600 mg
tract 400 mg Adverse Drug Reactions:
Trachea [Injection]:
50– Common: Blurred vision, chest pain, confusion,
Larynx 200 mg 400 mg

N
200 mg disturbances in vision, dizziness, drowsiness, dyspnea,
Bronchi
flushing, headache, lightheadedness, nausea,
Topical anesthesia, by topical administration, ADOLESCENT paresthesia, tinnitus, tremors
and CHILD ≥2 years, Less Common: Arrhythmias, bradycardia, cardiac arrest,
coma, heart block, hypotension, muscle twitching,
recurrence of SVT, respiratory depression, restlessness,
Route Maximum Dose
seizures
Laryngotracheal 3 mg/kg Rare: Bronchospasm, convulsions, hypersensitivity
Nasal reactions, paraplegia, unconsciousness.
4–5 mg/kg
Oropharyngeal
[Topical]:
NOTE: Dose varies with age and weight. Common: Blanching or redness of the skin (temporary)
Rare: Anaphylactic reactions
Dose Adjustment: Application site reactions: Abnormal sensation, altered
Geriatric, Pediatric, Acutely ill, and Debilitated Patients: temperature sensation, burning sensation, edema,
Administer reduced doses commensurate with their age erythema, itching, pallor or blanching (application time
and physical status. >2 hours), rash, redness, sore throat, hoarseness, loss
of voice
Renal Impairment: Systemic reactions: Angioedema, bronchospasm,
Reduce dose during prolonged infusion (>24 hours) or bradycardia, hypotension, CNS excitation and/or
repeated IV doses. depression, confusion, dizziness, double or blurred
vision, drowsiness, nervousness, euphoria, respiratory
Hepatic Impairment: depression, shock, tinnitus, tremors, twitching,
In severe disease, lower doses may be needed. unconsciousness, vomiting
Consider administering ½ of its dose during prolonged NOTE: Systemic reactions are unlikely due to small dose
infusion (>24 hours) or repeated IV doses. absorbed but may occur with repeated doses or
application to large surface areas
Precautions:
[Injection]: Drug Interactions:
Severe bradycardia, heart block or impaired cardiac Monitor closely with:
conduction (local anesthetics enhance conduction Increases risk of adverse or toxic effects of Lidocaine due to
defects); Severe shock; Respiratory impairment; Renal increased serum concentration:
and hepatic impairment; Epilepsy; Porphyria; Beta Blockers e.g., Propranolol
Neuromuscular diseases, e.g., myasthenia gravis
(increases sensitivity to local anesthetics; may increase Avoid concomitant use with:
muscle weakness and depress respiration with central Increases risk of adverse or toxic effects of the following
neural blockade); Neurological disease (may worsen drugs:
condition). Chondrolysis (primarily of the shoulder joint,

435

Bupivacaine [never use in combination]; Drugs that
depresses cardiac contractility and conduction (heart
failure; significant bradyarrhythmia)
Reduces therapeutic effect of Lidocaine:
Diuretics, e.g., Furosemide, Hydrochlorothiazide
Reduces therapeutic effect of the following drugs:
Antiarrhythmics, e.g., Amiodarone, Sotalol, Disopyramide
(antagonistic effect)
Administration:
For parenteral administration, use an infusion pump to
slowly administer lidocaine to or around surgical wound
sites and/or near nerves for pre- or postoperative
regional anesthesia.
Do NOT use solutions containing preservatives for
epidural or spinal anesthesia.
Avoid IV injections. Perform aspiration prior to
administration.
Visually inspect for particulate matter and discoloration
prior to administration whenever the solution and
container permit. Solutions that are discolored and/or
contain particulate matter should NOT be used. Unused
N
portion should be discarded.
For intradermal injection, use only on intact skin and on
skin locations where an adequate seal can be
maintained. Do NOT use on body orifices, mucous
membranes, around the eyes, or on areas with a
compromised skin barrier.
For topical administration, apply a moderately thick layer
to affected area (~1/8 inch thick), and allow time for
numbness to develop, approximately 20–60 minutes.
Reapply if needed. It is unnecessary to dry the site prior
to application.
Do NOT use in large quantities, particularly over raw
surfaces or blistered areas. Avoid contact with eyes, in
case of accidental contact with eyes, rinse immediately
with copious amounts of eyewash and seek treatment by
an eye care specialist.
Keep out of reach of children. If swallowed, get medical
help or contact a Poison Control Center right away.
NOTE: When used in mouth or throat, topical anesthesia
may impair swallowing and increase risk of aspiration.
Avoid food for ≥60 minutes following oral or throat
application, especially in children. Numbness may
increase the danger of tongue or buccal biting trauma.
Avoid ingesting food or chewing gum while mouth or
throat is anesthetized. Excessive doses or frequent
application may result in high plasma levels and serious
adverse effects. Strictly adhere to dosing instructions.
Use measuring devices to measure the correct volume,
if applicable, to ensure accuracy of dose.
Pregnancy Category: B
ATC Code: N01BB02
436
NERVOUS SYSTEM
Rx ROPIVACAINE
Inj.: 10 mg/mL (as hydrochloride), 10 mL ampule (IV)
Ropivacaine is a local anesthetic of the amide type with
analgesic activity. It binds to voltage-gated sodium ion
channels in the neuronal membrane resulting in a
stabilization of the membrane and inhibition of
depolarization. This blocks nerve impulse generation and
propagation, resulting in a reversible loss of sensation.
Indications: Surgical anesthesia, labor pain management,
postoperative pain management.
Contraindications: IV regional anesthesia (Bier block),
obstetric paracervical block anesthesia.
Dose:
NOTE: Dose varies with anesthetic procedure, area to be
anesthetized, vascularity of tissues, number of neuronal
segments to be blocked, depth of anesthesia, degree of
muscle relaxation required, duration of anesthesia
desired, individual tolerance, and the physical condition
of the patient.
Administer the smallest dose and concentration required
to produce the desired result.
Caudal block, central nerve blocks or anesthesia, by
injection into the caudal end of the spinal canal, CHILD
and INFANT, 0.5–1 mL/kg of a 0.2% (2 mg/mL) solution
(maximum volume, 25 mL).
Epidural block, central nerve blocks or anesthesia, by
epidural injection, ADOLESCENT, CHILD, and INFANT, 0.7
mL/kg of a 0.2% (2 mg/mL) solution; for infants requiring
repeat injections, a decreased dose may be necessary to
prevent drug accumulation; if at least 45 minutes since
initial dose, reduce dose to 1/3 of the initial; if at least
90 minutes since initial dose, reduce dose to half of the
initial; if additional doses are necessary, reduce doses to
half of the previous dose.
Epidural, continuous infusion for central nerve blocks or
anesthesia, by epidural injection, INFANT <3 months,
0.5–1 mL/kg of a 0.2% (2 mg/mL) solution as a bolus
injection; a more dilute solution (e.g., 0.1% or 1 mg/mL)
may be required to ensure adequate volume and
minimize toxicity; follow with continuous epidural
infusion of 0.2% (2 mg/mL) solution at 0.2 mg/kg per
hour; ADOLESCENT, CHILD, and INFANT ≥3 months, 0.5–
1 mL/kg of a 0.2% (2 mg/mL) solution as a bolus
injection, administered over 3–5 minutes, followed by
continuous epidural infusion at 0.4 mg/kg per hour.
Field block, surgical anesthesia, by injection onto or near
the nerve, ADULT, 1–40 mL of a 0.5% solution.
Infiltration or minor nerve block, postoperative pain
management, by injection onto or near the nerve, ADULT,
1–100 mL of a 0.2% solution; or 1–40 mL of a 0.5%
solution.
Labor pain management, lumbar epidural, by epidural
injection, ADULT, initially 10–20 mL of a 0.2% solution;
the continuous infusion dose is 6–14 mL/hour of a 0.2%
solution with incremental injections of 10–15 mL/hour
of a 0.2% solution.
NERVOUS SYSTEM
Lumbar epidural block, cesarean section, by epidural
injection, ADULT, 20–30 mL dose of a 0.5% solution; or
15–20 mL dose of a 0.75% solution.
Lumbar epidural block, surgical anesthesia, by epidural
injection, ADULT, 15–30 mL of a 0.5% solution; 15–25
mL of a 0.75% solution; or 15 to 20 mL of a 1% solution.
Lumbar or thoracic epidural, postoperative pain
management, by epidural injection, ADULT, the
continuous infusion dose is 6–14 mL/hour of a 0.2%
solution.
Major nerve block, surgical anesthesia, by injection onto or
near the nerve, ADULT, 35–50 mL of a 0.5% solution; or
10–40 mL of a 0.75% solution
Peripheral nerve block, postoperative pain management, by
injection onto or near the nerve, ADULT, the continuous
infusion dose is 5–10 mL/hour of a 0.2% solution.
Peripheral nerve blocks or local anesthesia, single injection,
by injection onto or near the nerve, ADOLESCENT, CHILD,
and INFANT ≥6 months, extrapolate dosing based on
adult experience (maximum dose, 3 mg/kg per dose
based on lean body mass); for infants <6 months, reduce
dose by 30%; volume of dose (mL/kg) and concentration
of solution are site-specific based on anatomy and
variable among patients and procedure, using a 0.2%-
0.5% (2-5 mg/mL) solution,
Site Dose
Head and neck blocks 0.05 mL/kg
Maxillary nerve 0.15 mL/kg
Brachial plexus 0.2–0.3 mL/kg
Digital nerve 0.05 mL/kg
Transversus abdominis plane 0.2–0.5 mL/kg
Ilioinguinal nerve 0.075 mL/kg
Rectus sheath 0.1–0.2 mL/kg
Femoral nerve 0.2–0.4 mL/kg
Sciatic nerve 0.2–0.3 mL/kg
Peripheral nerve blocks or local anesthesia, continuous
peripheral nerve block infusion, by injection onto or near
the nerve, ADOLESCENT, CHILD, and INFANT ≥6 months,
administer a bolus dose dependent on the nerve
catheter location using a 0.2% (2 mg/mL) solution; usual
dose range is 0.5–1.32 mg/kg; higher bolus dose may
be required; for continuous peripheral nerve block
infusion, 0.2–0.25 mg/kg per hour of a 0.2% (2 mg/mL)
solution.
Spinal anesthesia, by intrathecal injection, ADOLESCENT
≤17 years, CHILD, and INFANT, 0.5 mg/kg of
preservative-free 0.5% (5 mg/mL) isobaric solution via
the LP site at L 3–5 (maximum dose, 20 mg/dose).
Thoracic epidural block, surgical anesthesia, by epidural
injection, ADULT, 5–15 mL dose of a 0.5% or 0.75%
solution.
Dose Adjustment:
Geriatric:
Use with caution. Initial dose reductions may be necessary.
Precautions:
WARNING: Should be administered by clinicians well-
trained in the diagnosis and management of
emergencies that may arise from the use of these
agents. Resuscitative equipment, oxygen, and
other resuscitative drugs should be available for
immediate use.
CNS toxicity (restlessness, anxiety, tinnitus, dizziness,
blurred vision, tremors, depression, or drowsiness may
be early warning signs of CNS toxicity); Seizures
(convulsions due to systemic toxicity leading to cardiac
arrest have been reported); Neurological and psychiatric
disorders (may be at greater risk for toxicity).
Chondrolysis (primarily of the shoulder joint, has
occurred following continuous intra-articular infusion;
destruction of articular cartilage has occurred when
infused directly into the shoulder); Respiratory arrest
(have been associated with rare occurrences of sudden
respiratory arrest). Cardiovascular disease (may be at
greater risk for toxicity); Porphyria; Hepatic impairment
(undergoes hepatic metabolism; at an increased risk for
developing toxic drug levels); Renal impairment (renally
excreted; may be at greater risk for toxicity); Acutely ill
and debilitated patients (may be at greater risk for
toxicity).
Elderly (may be at greater risk for toxicity; cardiovascular
adverse events may be age-related; more common in
patients >61 years of age); Children (use extra
precaution to ensure accuracy and minimize potential
toxicity).
N
Adverse Drug Reactions:
Common and Less Common: Bradycardia, chest pain,
hypertension, hypotension (dose-related; age-related),
tachycardia, anxiety, dizziness, headache, hypoesthesia,
paresthesia, rigors, chills, shivering, pruritus,
hypokalemia, nausea, oral paresthesia, vomiting,
oliguria, urinary retention, urinary tract infection, anemia,
back pain, dyspnea, fever.
Rare: Angioedema, apnea (associated with epidural block in
head/neck region), bronchospasm, cardiac insufficiency,
chondrolysis (continuous intra-articular administration),
circulatory shock, dyskinesia, hypersensitivity reaction,
seizure, hallucination, hyperthermia, laryngeal edema,
myocardial infarction, skin rash, syncope, tinnitus,
urticaria, ventricular arrhythmia.
Drug Interactions:
Monitor closely with:
Reduces diagnostic effect of Technetium Tc 99m
Tilmanocept
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:
Blood Pressure-lowering Agents (antihypertensive
effect); Hypotension-associated Agents (hypotensive
effect); Neuromuscular-blocking Agents e.g.,
Succinylcholine
Increases risk of adverse or toxic effects of Ropivacaine:
Hyaluronidase
Increases risk of adverse or toxic effects of Bupivacaine
(Liposomal)
Administration: Administered by local infiltration, epidural
block and epidural infusion, or intermittent bolus.
437

Do NOT administer large volume of anesthetic rapidly,
including emergency situations where rapid
administration is necessary.
Use an infusion pump to slowly administer local
anesthetics to or around surgical wound sites and/or
near peripheral nerves for postoperative analgesia.
Avoid IV injections. Perform aspiration prior to
administration. Re-position the needle until no return of
blood can be elicited by aspiration. However, absence of
blood in the syringe does NOT guarantee that IV injection
has been avoided. IV regional anesthesia (Bier block) is
not recommended.
NOTE: A test dose of short-acting local anesthetic containing
epinephrine (e.g., 3–5 mL) is recommended prior
administration. Incremental ropivacaine dosing is
recommended.
Pregnancy Category: B
ATC Code: N01BB09
ANALGESICS
N
OPIOIDS
NATURAL OPIUM ALKALOIDS
General Information
Natural opium alkaloids are opioid analgesics extracted
from Papaver somniferum. It belongs to a class of
medicines used to provide relief from moderate-to-
severe acute or chronic pain.
Mode of Action: Pre-synaptically, opioids block calcium
channels on nociceptive afferent nerves to inhibit
release of neurotransmitters such as substance P and
glutamate, which contribute to nociception. Post-
synaptically, opioids open potassium channels which
hyperpolarize cell membranes, increasing the required
action potential to generate nociceptive transmission.
Precautions:
WARNING: Addiction, abuse, and misuse. Exposes
patients and other users to the risks of opioid
addiction, abuse, and misuse, which can lead to
overdose and death. Assess each patient's risk
prior to prescribing. Monitor all patients regularly
for development of these behaviors or
conditions. Risk of opioid abuse is increased in
patients with a history or family history of alcohol
or drug abuse or mental illness.
438
NERVOUS SYSTEM
Life-threatening respiratory depression. Serious,
life-threatening, or fatal respiratory depression
may occur. Monitor closely for respiratory
depression, especially during initiation or dose
escalation. Carbon dioxide retention from opioid-
induced respiratory depression can exacerbate
the sedating effects of opioids.
Neonatal opioid withdrawal syndrome.
Prolonged use during pregnancy can result in
neonatal opioid withdrawal syndrome, which
may be life-threatening if not recognized and
treated. If opioid use is required for a prolonged
period in a pregnant woman, advise the patient
of the risk of neonatal opioid withdrawal
syndrome and ensure that appropriate
treatment will be available.
Risks from concomitant use with
benzodiazepines or other CNS depressants.
Concomitant use with benzodiazepines or other
CNS depressants, including alcohol, may result
in profound sedation, respiratory depression,
coma, and death. Reserve concomitant
prescribing with benzodiazepines or other CNS
depressants in patients for whom alternative
treatment options are inadequate.
Accidental ingestion. Accidental ingestion of
even 1 dose, especially by children, can result in
a fatal overdose.
Safety and handling. Accidental dermal
exposure should be treated by the removal of
any contaminated clothing and rinsing the
affected area with water.
CNS depression or coma (may cause CNS depression;
increased susceptibility to intracranial effects of CO2
retention);
Delirium tremens; Head trauma and increased intracranial
pressure (exaggerated elevation of ICP may occur);
Seizure disorders (may cause or exacerbate seizures);
Constipation (may cause or aggravate constipation; chronic
use may result in obstructive bowel disease; may also be
problematic in patients with unstable angina and/or
post-myocardial infarction);
Abdominal conditions (may obscure diagnosis or clinical
course of patients with acute abdominal conditions; may
worsen GI ileus due to reduced GI motility);
Biliary tract impairment (may cause constriction of
sphincter of Oddi diminishing biliary and pancreatic
secretions);
Inflammatory bowel disorders;
Pancreatitis;
Hepatic and renal impairment;
Hypotension with or without hypovolemia (may cause
severe hypotension, including orthostatic hypotension
and syncope);
Cardiac arrhythmias;
Severe bronchial asthma;
Sleep-disordered breathing;
NERVOUS SYSTEM
Phenanthrene hypersensitivity (cross-sensitivity may occur);
Sulfite allergy (may contain sulfites);
Obesity;
Thyroid dysfunction;
Adrenocortical insufficiency (long-term opioid use may
cause secondary hypogonadism, which may lead to
sexual dysfunction, infertility, mood disorders, and
osteoporosis);
Prostatic hyperplasia or urinary stricture;
Mental health conditions, e.g., depression, anxiety
disorders, post-traumatic stress disorder (increased risk
for opioid use disorder and overdose); Psychosis; Acute
alcoholism; History of substance abuse;
Cachectic or debilitated patients (greater potential for
critical respiratory depression, even at therapeutic
dosages);
Opioid depended patient;
Elderly (may be more sensitive to adverse effects, including
life-threatening respiratory depression; may be
particularly susceptible to the CNS depressant and
constipating effects; increased potential for risks and
overdose);
Children (increased sensitivity to respiratory depression;
infants <3 months are more susceptible to respiratory
depression and/or apnea);
Pregnancy (prolonged use can result in neonatal opioid
withdrawal syndrome, which may be life-threatening if
not recognized and treated; has been shown to have
embryolethal and fetotoxic effects in animal studies;
adverse events have been observed in some animal
reproduction studies; crosses the placenta; use if
parenteral morphine during labor have the potential to
interfere with a newborn's natural reflex to nurse within
the first few hours after birth);
Lactation (excreted in breastmilk; maternal use can
potentially lead to serious adverse events, including
death, in nursing infants; monitor nursing infant for
apnea and sedation).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Opioids:
Somatostatin Analogs e.g. Octreotide
Enhances therapeutic effect of Opioids:
Amphetamines (analgesic effect); Brimonidine, Topical;
Cannabis; Doxylamine, Dronabinol; Magnesium sulfate;
Minocycline; Nabilone; Tetrahydrocannabinol (CNS
depressant effect);
Domperidone
Enhances therapeutic effect of the following drugs:
Ethyl alcohol; Mirtazapine (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect);
SSRIs (serotonergic effect)
Increases excretion of Opioids:
Ammonium Chloride
Increases risk of adverse or toxic effects of Opioids:
CNS Depressants; Rufinamide (sleepiness and
dizziness); Succinylcholine (bradycardic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Anticholinergic Agents (constipation and urinary
retention); Antipsychotic Agents; Phenothiazines
(hypotensive effect); Desmopressin; Diuretics;
Ramosetron (constipating effect); SSRIs (serotonin
syndrome; psychomotor impairment)
Reduces therapeutic effect of the following drugs:
Pegvisomant
Avoid concomitant use with:
Decreases serum concentration of Opioids:
Clopidogrel
Enhances therapeutic effect of Opioids:
Anesthetics; Antipsychotics; Anxiolytics; Hypnotics;
Tricyclic antidepressants (depressant effects);
Droperidol
Enhances therapeutic effect of the following drugs:
Hydrocodone [consider starting at a 20–30% lower
hydrocodone dose when used concomitantly];
Orphenadrine, Paraldehyde, Perampanel, Tapentadol
[start tapentadol at one-third to one-half of the normal
dose when used concomitantly], Thalidomide, Zolpidem
(CNS depressant effect)
N
Increases risk of adverse or toxic effects of Opioids:
MAO Inhibitors e.g. Selegeline
Increases risk of adverse or toxic effects of Azelastine
(Nasal) (CNS depressant effect)
Reduces therapeutic effect of the following drugs:
Clopidogrel (antiplatelet effect); Mixed Agonist /
Antagonist Opioids; Naltrexone
FOOD INTERACTONS. Alcoholic beverages or ethanol-
containing products may result in a rapid release of the
entire dose.
Administration: Inspect parenteral drug products visually for
particulate matter before opening the ampule. Inspect
after removing contents from the ampule for color. Do
NOT use if the solution contains a precipitate, which does
not disappear upon shaking.
Patients taking opioids chronically may become tolerant
and require doses higher than the usual dosage range to
maintain the desired effect. Tolerance can be managed
by appropriate dose titration. There is no optimal or
maximal dose for opioids in chronic pain. The
appropriate dose is one that relieves pain throughout its
dosing interval without causing unmanageable side
effects. Consider total daily dose, potency, prior opioid
use, degree of opioid experience and tolerance,
conversion from previous opioid (including formulation),
patient’s general condition, concurrent medications, and
type and severity of pain during prescribing.
Initiate therapy at the lowest effective dosage using
immediate-release opioids. Tailor opioid-containing
analgesic regimen to each patient's needs based on the
type of pain being treated, route of administration,
439

degree of tolerance for opioids, age, weight, and medical
condition. Titrate doses to pain relief or prevention.
Opioid tolerance is defined as patients already taking at
least 60 mg oral morphine daily, 25 micrograms
transdermal fentanyl per hour, 30 mg oral oxycodone
daily, 8 mg oral hydromorphone daily, 25 mg oral
oxymorphone daily, or an equivalent dose of another
opioid for at least 1 week.
Abrupt discontinuation following prolonged use may lead
to withdrawal symptoms. Gradually titrate dose
downward when discontinuing. Do NOT discontinue
abruptly.
NOTE: Opioids should not be used as first-line therapy for
chronic pain management (pain >3 months or beyond
time of normal tissue healing) due to limited short-term
benefits, undetermined long-term benefits, and
association with serious risks.
Opioids decrease bowel motility. Consider preventative
measures (e.g., stool softener, increased fiber) to reduce
the potential for constipation.
Concurrent use of mixed agonist / antagonist (e.g.,
pentazocine, nalbuphine, butorphanol) or partial agonist
(e.g. buprenorphine) analgesics may precipitate
N
withdrawal symptoms and/or reduced analgesic efficacy
in patients following prolonged therapy with mu opioid
agonists.
Rx CODEINE
Oral: 30 mg MR capsule (as phosphate)
10 mg/5 mL suspension, 60 mL
Codeine alters the perception of and response to pain by
binding to opiate receptors in the CNS, blocking the
ascending pain pathways. It also helps suppress cough
by direct action in the medulla.
Indication: Relief of mild to moderately severe pain when
use of an opioid analgesic is appropriate.
Contraindications: Children <12 years; postoperative
management in children <18 years who have undergone
tonsillectomy and/or adenoidectomy; significant
respiratory depression; acute or severe bronchial
asthma in an unmonitored setting or in the absence of
resuscitative equipment; known or suspected GI
obstruction, including paralytic ileus; acute ulcerative
colitis; acute alcoholism; head injury; raised intracranial
pressure; concurrent use with MAOIs or use of MAOIs
within the last 14 days; children <1 year.
Dose:
Relief of mild to moderately severe pain, by mouth, ADULT
(opioid-naive patients),
MR capsule, initially 50 mg every 12 hours; titrate at
intervals of ≥48 hours until adequate analgesia has been
achieved (maximum daily dose, 600 mg), patients
requiring higher doses should be switched to an opioid
approved for use in severe pain;
440
NERVOUS SYSTEM
suspension, initially 15–60 mg every 4 hours as needed,
titrate as needed to pain relief or prevention (maximum
total daily dose, 360 mg); patients with prior opioid
exposure may require higher initial doses; for moderate
pain, initiate dose at 30–60 mg; CHILD <12 years, 0.5–
1 mg/kg every 4–6 hours daily (maximum 240 mg daily).
Dose Adjustment:
Geriatric:
Use with caution. Consider initiation at the low end of the
dosing range. Reduced initial dosages may be necessary.
Renal Impairment:
For GFR >50 mL/minute, dose adjustment is not necessary.
For GFR 10–50 mL/minute and in patients receiving
continuous renal replacement therapy (CRRT),
administer 75% of dose.
For GFR <10 mL/minute, administer 50% of dose.
Hepatic Impairment:
Lower initial doses or longer dosing intervals followed by
careful titration are recommended.
Precautions:
WARNING: Risk of medication errors. Ensure
accuracy when prescribing, dispensing, and
administering codeine suspension. Dosing
errors due to confusion between mg and mL
and can result in accidental overdose and
death.
Ultra-rapid metabolism and other risk factors
for life-threatening respiratory depression in
children. Life-threatening respiratory
depression and death have occurred in
children, mostly following tonsillectomy and/or
adenoidectomy. Many of the children had
evidence of being ultra-rapid metabolizers of
codeine due to a CYP-450 2D6 polymorphism.
Interactions with drugs affecting CYP-450
isoenzymes. The use of CYP-450 3A4
inducers, 3A4 inhibitors, or 2D6 inhibitors with
codeine requires careful consideration of the
effects on the parent drug, codeine, and the
active metabolite morphine.
CYP2D6 ultra-rapid metabolizers (may have extensive
conversion to morphine and thus increased opioid-
mediated effects).
Adverse Drug Reactions:
Common: Physical dependence, tolerance, opioid-induced
hyperalgesia, increased biliary tract pressures and/or
spasm, opioid-induced constipation, nausea, vomiting,
respiratory depression (dose-related), drowsiness (dose-
related), delirium, bradycardia, cardiac arrest, circulatory
depression, flushing, hypertension, hypotension,
palpitations, shock, syncope, tachycardia, abnormal
dreams, agitation, anxiety, apprehension, ataxia, chills,
depression, disorientation, dizziness, dysphoria,
euphoria, fatigue, hallucination, headache, increased
intracranial pressure, insomnia, nervousness,
paresthesia, sedation, shakiness, taste disorder, vertigo,
diaphoresis, pruritus, skin rash, urticaria, abdominal
NERVOUS SYSTEM
cramps, abdominal pain, anorexia, diarrhea,
pancreatitis, xerostomia, urinary hesitancy, urinary
retention, hypersensitivity reaction, laryngospasm,
muscle rigidity, tremor, weakness, blurred vision,
diplopia, miosis, nystagmus, visual disturbance,
bronchospasm, dyspnea, respiratory arrest
Administration:
For oral suspensions, shake well before use. Administer
with an accurate measuring device, such as a calibrated
oral syringe or a measuring cup. Do NOT use a household
teaspoon or tablespoon to measure dose.
For MR tablets, swallow whole. Do NOT chew, dissolve,
or crush. All strengths may be halved, except the 50 mg
tablets. Half tablets should also be swallowed intact.
Pregnancy Category: C
See General Information on Natural Opium Alkaloids under
Analgesics – Opioids in Chapter 10: Nervous System for
other information.
ATC Code: Not available
Rx MORPHINE
Oral: 10 mg, 20 mg, and 30 mg tablet / capsule (as sulfate)
10 mg, 30 mg, and 60 mg MR tablet (as sulfate)
Inj.: 10 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
16 mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
Morpine is a mu receptor agonist in the CNS and PNS. It
binds to opioid receptors in the CNS, causing inhibition
of ascending pain pathways, altering the perception of
and response to pain, as well as producing generalized
CNS depression.
Indication:
[Oral]: Relief of moderate to severe acute and chronic pain
for which use of an opioid analgesic is appropriate;
management of pain severe enough to require daily,
around-the-clock, long-term opioid treatment and for
which alternative treatment options are inadequate.
[Injection]: Relief of severe pain, such as MI and severe
injuries; relief of dyspnea of acute left ventricular failure
and pulmonary edema; preanesthetic medication;
management of pain for extended periods without
attendant loss of motor, sensory, or sympathetic
function.
Contraindications:
[Oral]: GI obstruction and hypercarbia.
[Injection]: Severe respiratory depression; acute or severe
asthma (in an unmonitored setting or without
resuscitative equipment); known or suspected paralytic
ileus; presence of infection at infusion site; concomitant
anticoagulant therapy; uncontrolled bleeding diathesis;
heart failure due to chronic lung disease; cardiac
arrhythmias; increased intracranial pressure; head
injuries; brain tumors; acute alcoholism; deliriums
tremens; seizure disorders; use during labor when a
premature birth is anticipated.
NOTE: Some contraindications are product specific. See
detailed product prescribing information.
Dose:
NOTE: Tailor dosing based on patient's needs, type of pain
being treated, route of administration, degree of
tolerance for opioids, age, weight, and medical condition.
The optimal analgesic dose varies widely among
patients. Titrate doses to pain relief/prevention.
Acute pain, moderate to severe, by mouth, ADULT (opioid
naïve), as immediate-release tablet or capsule, initially
15–30 mg every 4 hours as needed; patients with prior
opioid exposure may require higher initial doses; CHILD
>6 months and <50 kg, as immediate-release tablet or
capsule, 0.15–0.3 mg/kg every 3–4 hours as needed; if
pain is severe, an initial dose of 0.3 mg/kg may be
administered;
by IM or SC injection, ADULT (opioid naïve), initially 5–10
mg every 4 hours as needed; usual range, 5–15 mg
every 4 hours as needed; patients with prior opioid
exposure may require higher initial doses; CHILD >6
months and <50 kg, 0.1–0.2 mg/kg;
by IV injection, ADULT (opioid naïve), initially 2.5–5 mg
every 3–4 hours; patients with prior opioid exposure may
require higher initial doses.
[NOTE: Administer 2–3 mg every 5 minutes until pain
relief or if associated sedation, oxygen saturation <95%,
N
or serious adverse event occurs, may be appropriate in
treating acute moderate-to-severe pain in immediate
postoperative period or the emergency department;
maximum cumulative dose prompting reevaluation of
continued morphine use and/or dose should be included
as part of any medication order intended for short-term
use.]; CHILD >6 months and <50 kg, 0.05–0.3 mg/kg
every 3–4 hours as needed, not to exceed 10 mg per
dose;
by continuous IV or SC infusion, ADULT, 0.8–10
mg/hour; usual range is up to 80 mg/hour; may
administer a loading dose prior to initiating the infusion;
ADULT (critically ill patients), usual range Is 2–30
mg/hour; ADULT (patient-controlled analgesia), usual
concentration is 1 mg/mL; usual demand dose is 1 mg,
ranging from 0.5–2.5 mg; lockout interval is 5–10
minutes; CHILD >6 months and <50 kg, initially 10–30
micrograms/kg per hour, titrate as needed to control
pain; CHILD >6 months and <50 kg (patient-controlled
analgesia; opioid-naive), consider using lower end of
dosing range; usual concentration is 1 mg/mL; usual
demand dose is 0.02 mg/kg per dose ranging from
0.01–0.03 mg/kg per dose; lockout interval is 8–10
minutes; usual basal rate is 0–0.03 mg/kg per hour.
Chronic pain, by mouth, ADULT (opioid-tolerant), as MR
tablet, 90–120 mg once daily at the same time each day;
ADULT (opioid naïve), initially 30 mg once daily; adjust in
increments ≤30 mg daily every 3–4 days (maximum
dose, 1,600 mg daily).
Dose Adjustment:
Geriatric and Debilitated Patients:
Use with caution. May require reduced doses.
Renal Impairment:
For CrCl 10–50 mL/minute and patients on CRRT,
administer 75% of normal dose.
441

For CrCl <10 mL/minute and patients on peritoneal dialysis,
administer 50% of normal dose.
Hepatic Impairment:
Substantial extrahepatic metabolism may occur.
In cirrhosis, increases in half-life and AUC may require dose
adjustment.
Precautions:
WARNING: Risk of overdose. NOT recommended for
single-dose IV, IM, or SC administration because of
the very large amount of morphine in the ampule
and the associated risk of overdosage.
Naloxone injection and resuscitative equipment
should be immediately available for use in case of
life-threatening or intolerable side effects and
whenever therapy is being initiated, the reservoir is
being refilled, or any manipulation of the reservoir
system is taking place.
Each ampule contains a large amount of a potent
narcotic which has been associated with abuse and
dependence among healthcare providers. Due to
the limited indications for this product, the risk of
overdosage and the risk of its diversion and abuse,
it is recommended that special measures be taken
to control this product within the hospital or clinic,
N
including wastage and access.
Adverse Drug Reactions:
Common: Circulatory depression, flushing, shock,
bradycardia, hypotension, atrial fibrillation, chest pain,
edema, hypertension, palpitation, syncope, tachycardia,
vasodilation, dysphonia, physical and psychological
dependence, sedation, drowsiness, dizziness, confusion,
amnesia, fever, agitation, anxiety, apathy, apprehension,
ataxia, chills, coma, delirium, depression, dream
abnormalities, euphoria, false sense of well-being,
hallucination, hypoesthesia, insomnia, lethargy, malaise,
nervousness, restlessness, seizure, slurred speech,
somnolence, vertigo, pruritus (dose related), dry skin,
rash, urticaria, antidiuretic hormone release,
hypogonadism, gynecomastia, hypokalemia,
hyponatremia, decreased libido, constipation, nausea,
vomiting, abdominal distension, abdominal pain,
anorexia, biliary colic, diarrhea, dyspepsia, dysphagia,
flatulence, gastroenteritis, GERD, GI irritation, paralytic
ileus, rectal disorder, taste perversion, weight loss,
xerostomia, bladder spasm, dysuria, abnormal
ejaculation, impotence, decreased urination,
leukopenia, thrombocytopenia, pain at injection site,
decreased bone mineral density, weakness, arthralgia,
back pain, bone pain, foot drop, gait abnormalities,
paresthesia, rigors, skeletal muscle rigidity, amblyopia,
conjunctivitis, tremor, eye pain, vision problems or
disturbance, decreased oxygen saturation, oliguria,
asthma, atelectasis, dyspnea, hiccups, pulmonary
edema (noncardiogenic), hypoxia, hypercapnia,
respiratory depression, rhinitis, flulike syndrome,
diaphoresis, infection, thirst, histamine release, voice
alteration, withdrawal syndrome.
Less Common: Amenorrhea, anaphylaxis, apnea, biliary
tract spasm, bronchospasm, blurred vision, cardiac
arrest, decreased cough reflex, dehydration, intestinal
obstruction, diplopia, disorientation, hemorrhagic
442
NERVOUS SYSTEM
urticaria, intracranial pressure increased, laryngospasm,
menstrual irregularities, miosis, myoclonus, nystagmus,
paradoxical CNS stimulation, respiratory arrest, sepsis,
thermal dysregulation, toxic psychoses, urinary tract
spasm.
Administration:
For oral administration, swallow MR tablets whole. Do
NOT crush, chew, or dissolve to prevent the rapid release
of a potentially fatal dose of morphine. Take consistently
with regards to meals.
Administration with food may increase bioavailability.
Morphine may cause GI upset. Take with food if GI upset
occurs.
Avoid alcohol. Do NOT administer with alcoholic
beverages or ethanol-containing prescription or
nonprescription products.
Establish a patient's morphine requirement using
immediate-release tablets or capsules. Conversion to
MR tablets may be considered when chronic, continuous
treatment is required. Reserve the use of higher doses in
opioid-tolerant patients only. Reserve use of MR tablets
in patients for whom alternative treatment options are
ineffective, not tolerated, or would be otherwise
inadequate to provide sufficient management of pain.
When administering by IV push, dilute with sterile water
or NS to a concentration of 1 mg/mL in adults or 0.1–1
mg/mL in children. Administer slowly over 4–5 minutes.
Repeated SC administration causes local tissue
irritation, pain, and induration.
The use of IM injections is no longer recommended for
repeated administration due to painful administration,
variable absorption, and lag time to peak effect.
Do NOT use unless the solution is colorless or pale
yellow.
Protect from light.
NOTE: Conversion from parenteral to MR tablet. Substantial
interpatient variability exists in relative potency.
Therefore, it is safer to underestimate a patient's daily
oral morphine requirement and provide breakthrough
pain relief with immediate-release morphine. Consider
the parenteral to oral morphine ratio.
Parenteral to oral morphine ratio. Between 2–6 mg of
oral morphine may be required for analgesia equivalent
to 1 mg of parenteral morphine. An oral dose 3 times the
daily parenteral dose may be sufficient in chronic pain
settings.
Pregnancy Category: C
See General Information on Natural Opium Alkaloids
under Analgesics – Opioids in Chapter 10: Nervous
System for other information.
ATC Code: N02AA01
NERVOUS SYSTEM
Rx OXYCODONE
Oral: 10 mg, 20 mg, 40 mg, and 80 mg (as hydrochloride)
tablet/prolonged-release or controlled release tablet
5 mg capsule
Inj.: 10 mg/mL, 1 mL and 2 mL ampule (IV infusion)
Oxycodone binds to opiate receptors in the CNS, causing
inhibition of ascending pain pathways, altering the
perception of and response to pain and produces
generalized CNS depression.
Indication: Persistent moderate-to-severe acute and chronic
pain.
Contraindications: Significant respiratory depression;
hypercarbia; acute or severe bronchial asthma in an
unmonitored setting or in the absence of resuscitative
equipment; known or suspected GI obstruction, including
paralytic ileus; suspected surgical abdomen; any disease
or condition that affects bowel transit; mild, intermittent,
or short duration pain that can be managed with other
pain medications; acute pain (controlled release);
chronic obstructive airway; status asthmaticus; cor
pulmonale; acute alcoholism; delirium tremens;
convulsive disorders; severe CNS depression; increased
cerebrospinal or intracranial pressure; head injury; MAO
inhibitors (concomitant use within 14 days of each
other); pregnancy; use during labor and delivery;
breastfeeding.
Dose:
Persistent moderate-to-severe acute and chronic pain, by
mouth, ADULT, as immediate release form, initially 5–15
mg every 4–6 hours as needed with an average dosing
range of 5–10 mg per dose; for severe chronic pain,
administer on a regularly scheduled basis, every 4–6
hours, at the lowest dose that will achieve adequate
analgesia;
ADULT (opioid naïve), as controlled release form, initially
5–10 mg every 12 hours (maximum, 400 mg daily);
by IV injection, ADULT, 1–10 mg over 1–2 minutes, may
repeat nor more often than every 4 hours;
by IV infusion, ADULT, initially 2 mg per hour, increase as
needed.
Patient-controlled analgesia (PCA), by IV infusion, ADULT,
0.03 mg/kg, administer with a minimum lock-out time of
5 minutes.
NOTE: Oxycodone ER capsules are not bioequivalent to ER
tablets. Doses of ER capsules is expressed as oxycodone
base. Doses of ER tablets is expressed as oxycodone
hydrochloride.
Dose Adjustment:
Geriatric:
Initiate therapy at low end of dosing range and use caution.
Renal Impairment:
For CrCl <60 mL/minute, initiate at the low end of the
dosing range and adjust dose as clinically indicated.
Doses 33–50% of usual initial dose have been
recommended.
Hepatic Impairment:
Initiate at doses 33–50% of usual initial dose have been
recommended. If reduced dose is less than smallest
available dosage form, consider alternative analgesic.
Precautions:
WARNING: Cytochrome P450 3A4 Interaction. The
concomitant use of oxycodone with all CYP-450 3A4
inhibitors may result in an increase in oxycodone
plasma concentrations, which could increase or
prolong adverse drug effects and may cause
potentially fatal respiratory depression.
Discontinuation of a concomitantly used CYP3A4
inducer may result in an increase in oxycodone
plasma concentration.
Adverse Drug Reactions:
Common: Physical dependence, tolerance, opioid-induced
hyperalgesia, hypogonadism, opioid-induced
constipation, increased biliary tract pressures and/or
spasm, respiratory depression (dose-related), delirium,
hypogonadism, urinary retention, edema, itching,
sweating, injection site reaction, allergic reaction,
nausea, vomiting, drowsiness (dose-related), edema,
flushing, hypertension, children and adolescents may
experience the following: tachycardia, headache, fatigue,
lethargy, pain, decreased oxygen saturation,
N
hypochloremia, hyponatremia, weight loss, GERD, febrile
neutropenia, limb pain and seroma. Orthostatic
hypotension, drowsiness, dizziness, abnormal dreams,
abnormality in thinking, anxiety, confusion, drug
withdrawal, dysphoria, euphoria, chills, insomnia,
irritability, nervousness, twitching, withdrawal syndrome,
migraine, depression, hypoesthesia, agitation,
paresthesia pruritus, diaphoresis, excoriation,
hyperhidrosis, skin rash, hyperglycemia, xerostomia,
diarrhea, anorexia, dyspepsia, abdominal pain, gastritis,
hiccups, upper abdominal pain, nausea, vomiting,
dysuria, urinary retention, constipation, weakness,
arthralgia, back pain, musculoskeletal pain, myalgia,
tremor, blurred vision, cough, dyspnea, oropharyngeal
pain, fever, cardiac failure, vasodilatation, neuralgia,
personality disorder, thrombophlebitis, skin
photosensitivity, gout, gingivitis, glossitis, urinary tract
infection, anemia, leukopenia, hypersensitivity, infection,
hemorrhage, arthritis, laryngospasm, neck pain,
pathological fracture, bronchitis, ostealgia, sepsis,
epistaxis, respiratory depression, pharyngitis, pulmonary
disease, rhinitis, sinusitis, accidental injury.
Less Common: Abnormal gait, abnormal stools, aggressive
behavior, amenorrhea, amnesia, anaphylactoid reaction,
anaphylaxis, chest pain, choking sensation; gag reflex
and dysphagia (controlled release tablets), cholestasis,
cough, dehydration, dental caries, depersonalization,
diverticulitis (exacerbation), drug abuse, disturbed sleep,
drug dependence, dysgeusia, emotional lability,
exfoliative dermatitis, flatulence, eructation,
hallucination, hematuria, histamine release,
hyperkinesia, hypertonia, hypogonadism, increased
appetite, hyperalgesia, hyponatremia, hypotonia,
impotence, rase, increased heart rate, increased
intracranial pressure, increased thirst, intestinal
obstruction, lymphadenopathy, memory impairment,
mood changes, malaise, neonatal withdrawal, night
sweats, palpitations, pharyngeal edema, polyuria,
443

restlessness, seizure, SIADH, speech disturbance,
stomatitis, stupor, suicidal ideation, suicidal tendencies,
syncope, tinnitus, urticaria, vasodilatation, vertigo, visual
disturbance, voice disorder, xeroderma.
Administration: For oral administration, may be taken with
or without food. Administering with food may delay its
onset.
Swallow tablet whole. Do NOT moisten, dissolve, cut,
crush, break, or chew. Administer controlled release
tablets one at a time and each followed with water
immediately after placing in the mouth.
NOTE: Reserve use of 80 mg tablets for opioid-tolerant
patients only.
Pregnancy Category: B
See General Information on Natural Opium Alkaloids
under Analgesics – Opioids in Chapter 10: Nervous
System for other information.
ATC Code: N02AA05
PHENYLPIPERIDINE
N
Rx FENTANYL
Inj.: 50 micrograms/mL (as citrate), 2 mL and 10 mL
ampule (IV)
NOTE: The 50 mcg/mL, 10 mL prep is restricted to
pain management of terminal cancer patients.
80- 100 times more potent than morphine and has high
lipid solubility and quickly crosses the blood-brain
barrier, producing a rapid but short-onset of analgesia. It
increases pain threshold, alters pain reception and
inhibits ascending pain pathways by binding to
stereospecific receptors w/in the CNS.
Indication: Adjunct to general or regional anesthesia.
Contraindications: Septicemia; severe hemorrhage or
shock; local infection at proposed injection site;
disturbances in blood morphology and/or anticoagulant
therapy.
Dose:
Surgery, premedication, by slow IV infusion, ADULT, 50–100
micrograms 30–60 minutes prior to surgery; or 25–50
micrograms given shortly before induction.
Surgery adjunct to general anesthesia, by slow IV infusion,
ADULT,
low dose, 1–2 micrograms/kg depending on indication;
moderate dose with a sedative / hypnotic, 25–50
micrograms every 15–30 minutes (0.5–2
micrograms/kg per hour), discontinue infusion 30–60
minutes prior to the end of surgery to allow adequate
ventilation upon emergence from anesthesia;
Surgery adjunct to general anesthesia, by IV bolus, ADULT,
high dose, 4–20 micrograms/kg, then 2–10
micrograms/kg per hour.
444
NERVOUS SYSTEM
Surgery adjunct to regional anesthesia, by slow IV infusion,
ADULT, 50–100 micrograms over 1–2 minutes.
Surgery adjunct to anesthesia, by IV infusion, ADOLESCENT
and CHILD ≥2 years; 2–3 micrograms/kg per dose every
1–2 hours as needed.
Surgery, postoperative recovery, by slow IV infusion, ADULT,
50–100 micrograms every 1–2 hours as needed.
Dose Adjustment:
Geriatric patients are twice as sensitive as younger patients
to the effects of fentanyl. Determine dose based on age,
weight, physical status, underlying disease states, other
drugs used, type of anesthesia used, and the surgical
procedure to be performed.
Precautions:
WARNING: Cytochrome P450 3A4 Interaction. Use
with strong or moderate CYP3A4 inhibitors may
result in increased effects and potentially fatal
respiratory depression. Discontinuation of a
concomitant CYP3A4 inducer may result in
increased fentanyl concentrations. Monitor
patients receiving any CYP 3A4 inhibitor or
inducer.
Life-threatening respiratory depression. Serious,
life-threatening, or fatal respiratory depression
may occur. Monitor closely for respiratory
depression, especially during initiation or dose
escalation. Carbon dioxide retention from opioid-
induced respiratory depression can exacerbate
the sedating effects of opioids.
Abuse, misuse, and diversion. Users are exposed
to the risks of addiction, abuse, and misuse,
potentially leading to overdose and death. Assess
each patient’s risk prior to prescribing. Monitor all
patients for development of these behaviors or
conditions. Risk for opioid abuse is increased in
patients with a personal or family history of
substance abuse, including drug or alcohol abuse
or addiction, or mental illness.
See General Information on Natural Opium Alkaloids
under Analgesics – Opioids in Chapter 10: Nervous
System for other precautions.
SKILLED TASKS. May impair a bility to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Bradycardia, chest wall rigidity (high dose),
edema, cardiac arrhythmia, cardiorespiratory arrest,
chest pain, deep vein thrombosis, flushing, hypertension,
hypotension, orthostatic hypotension, palpitations,
peripheral edema, sinus tachycardia, syncope,
tachycardia, vasodilatation, CNS depression, confusion,
dizziness, drowsiness, fatigue, headache, sedation,
abnormal dreams, abnormal gait, abnormality in
thinking, agitation, altered sense of smell, amnesia,
anxiety, ataxia, chills, depression, disorientation,
dysphoria, euphoria, hallucination, hypoesthesia,
insomnia, irritability, lack of concentration, lethargy,
NERVOUS SYSTEM
malaise, mental status changes, migraine, nervousness,
neuropathy, paresthesia, restlessness, rigors, paranoia,
speech disturbance, stupor, vertigo, withdrawal
syndrome, diaphoresis, alopecia, cellulitis, decubitus
ulcer, hyperhidrosis, night sweats, erythema, pallor,
papule, pruritus, skin rash, dehydration, hot flash,
hypercalcemia, hyperglycemia, hypocalcemia,
hypokalemia, hypoalbuminemia, hypomagnesemia,
hyponatremia, weight loss, constipation, nausea,
vomiting, xerostomia, abdominal distention, abdominal
pain, anorexia, biliary tract spasm, decreased appetite,
diarrhea, dysgeusia, dyspepsia, flatulence, gastritis,
gastroenteritis, GERD, GI hemorrhage, hematemesis,
hiccups, intestinal obstruction, rectal pain, dysuria,
erectile dysfunction, mastalgia, UTI, urinary
incontinence, urinary retention, vaginitis, vaginal
hemorrhage, anemia, lymphadenopathy, bruise,
leukopenia, neutropenia, thrombocytopenia, ascites,
jaundice, hypersensitivity reaction, application site
erythema, application site pain or irritation, muscle
rigidity, weakness, arthralgia, back pain, limb pain,
myalgia, tremor, miosis, blepharoptosis, blurred vision,
diplopia, dry eye syndrome, strabismus, swelling of eye,
renal failure, dyspnea, respiratory depression, apnea,
asthma, asthma, atelectasis, bronchitis, cough, dyspnea
(exertional), epistaxis, hemoptysis, flu-like symptoms,
hypoventilation, laryngitis, hypoxia, nasopharyngitis,
pharyngolaryngeal pain, pharyngitis, pneumonia, rhinitis,
sinusitis, upper respiratory tract infection, wheezing,
fever.
Less Common: Amblyopia, anaphylaxis, angina pectoris,
anorgasmia, aphasia, bladder pain, bronchospasm, CNS
stimulation, cold and clammy skin, decreased libido,
delirium, depersonalization, dizziness (paradoxical), drug
dependence (physical and psychological; with prolonged
use), dysesthesia, emotional lability, eructation,
esophageal stenosis, exfoliative dermatitis, falling, fecal
impaction, flank pain, genitourinary tract spasm,
hematuria, hostility, hypertonia, hypogonadism,
hypotonia, increased bronchial secretions,
laryngospasm, joint swelling, nocturia, oliguria,
pancytopenia, pleural effusion, polyuria, myasthenia,
pustules, seizure, stertorous breathing, urticaria, vertigo,
voice disorder.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Fentanyl:
Amphetamines (analgesic effect); Brimonidine (Topical);
Doxylamine; Dronabinol, Hydroxyzine; Magnesium
sulfate; Minocycline, Nabilone (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Beta- blockers e.g. Propranolol; Non- dihydropyridine
Calcium channel blockers e.g. Verapamil; (bradycardic
effect; antihypertensive effect); Ethyl alcohol (CNS
depressant effect); Pramipexole, Ropinirole, Rotigotine
(sedative effect)
Increases excretion of Fentanyl:
Ammonium Chloride
Increases risk of adverse or toxic effects of Fentanyl:
Antipsychotic Agents, Phenothiazines (hypotensive
effect); CNS Depressants; Rufinamide (sleepiness and
dizziness);
Succinylcholine (bradycardic effect)
Reduces diagnostic effect of Ioflupane I123
Increases risk of adverse or toxic effects of the following
drugs:
Anticholinergic Agents e.g., Atropine (constipation and
urinary retention); Antipsychotic Agents (neuroleptic
malignant syndrome); Desmopressin; Diuretics,
Metoclopramide (symptoms consistent with serotonin
syndrome; neuroleptic malignant syndrome);
Ramosetron (constipating effect)
Avoid concomitant use with:
Enhances therapeutic effect of Fentanyl:
Droperidol
Enhances therapeutic effect of the following drugs:
Eluxadoline (constipating effect); Hydrocodone [consider
starting at a 20–30% lower hydrocodone dose when
used concomitantly], Methotrimeprazine, Orphenadrine,
Paraldehyde, Perampanel, Suvorexant, Tapentadol [start
tapentadol at one-third to one-half of the normal dose
when used concomitantly], Thalidomide, Zolpidem (CNS
depressant effect)
Increases risk of adverse or toxic effects of the following
drugs:
N
Nasal (CNS depressant effect); Dapoxetine; MAO
Inhibitors (serotonergic effect; serotonin syndrome);
Serotonin Modulators [except Tedizolid] (serotonin
syndrome)
Increases serum concentration of Fentanyl:
Conivaptan; Crizotinib; Dasabuvir; Fusidic Acid,
Systemic; Mifepristone [do NOT administer within 2
weeks of each other]; Ritonavir
Reduces therapeutic effect of Fentanyl:
Mixed Agonist / Antagonist Opioids (analgesic effect);
Naltrexone
Reduces therapeutic effect of the following drugs:
Clopidogrel (antiplatelet effect)
Mixed Agonist / Antagonist Opioids e.g.
Naltrexone
FOOD INTERACTONS. Fentanyl concentrations may be
increased by grapefruit juice. Avoid concurrent intake of
large quantities (>1 quart daily) of grapefruit juice.
Administration: Administer by slow IV infusion over 3–5
minutes.
Rapid IV infusion may result in skeletal muscular and
chest wall rigidity, impaired ventilation, or respiratory
distress or arrest. Nondepolarizing skeletal muscle
relaxant may be required.
Prolonged use may cause tolerance, psychological and
physical dependence.
Tailor each opioid-containing analgesic regimen based
on patient's needs, type of pain being treated, route of
administration, degree of tolerance for opioids, age,
weight, and medical condition. The optimal analgesic
445

dose varies widely among patients. Titrate doses to pain
relief or prevention.
Concurrent use of mixed agonist / antagonist analgesics
or partial agonist analgesics may precipitate withdrawal
symptoms and/or reduced analgesic efficacy in patients
following prolonged therapy with mu opioid agonists.
Abrupt discontinuation following prolonged use may lead
to withdrawal symptoms. Gradually taper dose to avoid
this risk.
Pregnancy Category: C
ATC Code: N02AB03
Rx PETHIDINE (MEPERIDINE)
Inj.: 50 mg/mL (as hydrochloride), 2 mL ampule (IM, IV,
SC)
Meperidine binds to the opioid receptors in the CNS,
causing inhibition of ascending pain pathways, altering
the perception of and response to pain and producing
generalized CNS depression.
N
Indications: Management of moderate-to-severe pain;
adjunct to anesthesia and preoperative sedation.
Contraindications: Use with or within 14 days of MAO
inhibitors; severe respiratory insufficiency.
Dose:
Pain, analgesic, by IM or SC injection, ADULT, 50–150 mg
every 3–4 hours as needed; CHILD, 1.1–1.8 mg/kg per
dose every 3–4 hours as needed (maximum, 50–150
mg/dose).
Pain, preoperative, by IM or SC injection, ADULT, 25-100 mg
given 1 hour before surgery;
by IM injection, CHILD, 1–2 mg/kg given 1 hour before
surgery.
Pain, postoperative, by IM or SC injection, ADULT, 25–100
mg every 2–3 hours if necessary;
by IM injection, CHILD, 0.5–2 mg/kg every 2–3 hours if
necessary.
Pain, moderate to severe acute pain, by IM or SC injection,
ADULT, 25–100 mg; CHILD 2 months to 12 years, 0.5–2
mg/kg; CHILD 12–18 years, 20–100 mg, repeat dose
every 4–6 hours if needed;
by slow IV injection, ADULT, 25–50 mg, repeat after 4
hours; ADOLESCENT 12–18 years, 25–50 mg every 4–6
hours if needed CHILD ≥12 years and NEONATE, 0.5–1
mg/kg every 10–12 hours, if needed in those up to 2
months and every 4–6 hours if needed in older children;
by IV injection, CHILD ≥1 month, 1 mg/kg as loading dose
followed by 100–400 micrograms/kg per hour by
continuous IV infusion adjusted according to response.
Pain, obstetrical analgesia, by IM or SC injection, ADULT,
50–100 mg when pain or contraction becomes regular,
may repeat every 1–3 hours if needed (maximum, 400
mg in 24 hours).
446
NERVOUS SYSTEM
NOTE: NOT recommended for use in children as an
analgesic. NOT recommended for the management of
chronic pain.
Dose Adjustment:
Geriatric:
Avoid use. If used for acute pain, limit to 1–2 doses.
Renal Impairment:
Avoid use.
Hepatic Impairment:
Use with caution in severe impairment. Consider lower initial
dose when initiating therapy. An increased opioid effect
may be seen in patients with cirrhosis.
Sickle-cell Disease:
Use with caution and decrease initial dose. NOT
recommended for use in this population and should only
be used if vaso-occlusive crisis occurs and only if it is the
only effective opioid for the patient.
Precautions:
WARNING: Abuse, misuse, and diversion. Users are
exposed to the risks of addiction, abuse, and
misuse, potentially leading to overdose and death.
Monitor all patients for development of these
behaviors or conditions. Risk for opioid abuse is
increased in patients with a personal or family
history of substance abuse, including drug or
alcohol abuse or addiction, or mental illness.
Hypovolemia (Use with caution); Cardiovascular disease;
Supraventricular tachycardia; Pre-existing respiratory
compromise, e.g., hypercapnia, hypoxia; COPD or other
obstructive airway disease. Adrenal insufficiency; Thyroid
dysfunction; History of drug abuse or acute alcoholism;
Morbidly obese; Sickle-cell disease; Biliary tract disorder;
Hepatic or renal impairment (Avoid use); Prostatic
hyperplasia. CNS depression (Avoid use); Coma (Avoid
use); Head injury (Use with extreme caution); Intracranial
lesions; Elevated intracranial pressure; Toxic psychoses;
Elderly and debilitated patients;
Pregnancy (avoid prolonged use or high doses at term);
Lactation
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Bradycardia, cardiac arrest, circulatory
depression, flushing, hypotension, palpitations, syncope,
tachycardia, agitation, confusion, shock, delirium,
disorientation, dizziness, drug dependence (physical),
hallucination, headache, habituation, increased
intracranial pressure, seizure, involuntary muscle
movements (muscle twitching, myoclonus), mood
changes (euphoria, dysphoria), sedation, serotonin
syndrome, skin rash, diaphoresis, pruritus, urticaria,
biliary colic, constipation, nausea, spasm of sphincter of
Oddi, vomiting, xerostomia, urinary retention,
anaphylaxis, histamine release, injection site reaction
(pain, wheal, flare), hypersensitivity reaction, tremor,
weakness, visual disturbance, respiratory arrest,
respiratory depression, dyspnea.
NERVOUS SYSTEM
Less Common: Hypogonadism
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Pethidine:
Amphetamines (analgesic effect); Barbiturates e.g.
Phenobarbital, Brimonidine (Topical);
Tetrahydrocannabinol, Doxylamine; Dronabinol,
Magnesium sulfate; Minocycline, Nabilone (CNS
depressant effect)
Enhances therapeutic effect of the following drugs:
Antiemetics 5HT3 Antagonists e.g., Ondansetron
(serotonin syndrome); Ethyl alcohol (CNS depressant
effect); Pramipexole, Ropinirole (sedative effect)
Increases excretion of Pethidine:
Ammonium Chloride; Barbiturates e.g. Phenobarbital
Increases risk of adverse or toxic effects of Pethidine:
Anticholinergic Agents e.g., Atropine (constipation and
urinary retention); Antipsychotic Agents, Phenothiazines
(hypotensive effect); CNS Depressants; Rufinamide
(sleepiness and dizziness); Succinylcholine (bradycardic
effect)
Increases risk of adverse or toxic effects of the following
drugs:
Antipsychotic Agents (neuroleptic malignant syndrome);
Desmopressin; Diuretics; Metoclopramide (serotonin
syndrome; neuroleptic malignant syndrome);
Ramosetron (constipating effect)
Avoid concomitant use with:
Decreases serum concentration of Pethidine:
Protease Inhibitors e.g. Lopinavir
Enhances therapeutic effect of Pethidine:
Droperidol, Hydroxyzine Methotrimeprazine (CNS
depressant effect) [reduce codeine dose by 50% with
concomitant use] (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Hydrocodone (CNS depressant effect) [consider starting
at a 20–30% lower hydrocodone dose when used
concomitantly], Paraldehyde, Sodium oxybate,
Suvorexant, Tapentadol [start tapentadol at one-third to
one-half of the normal dose when used concomitantly],
Thalidomide, Zolpidem (CNS depressant effect)
Increases risk of adverse or toxic effects of Pethidine:
MAO Inhibitors (serotonin syndrome);
Protease Inhibitors e.g. Lopinavir
Increases risk of adverse or toxic effects of the following
drugs:
Azelastine(Nasal) (CNS depressant effect); Dapoxetine;
Serotonin Modulators [Except Tedizolid] (serotonin
syndrome)
Increases serum concentration of toxic metabolites of
Pethidine:
Protease Inhibitors e.g. Lopinavir
Reduces therapeutic effect of Pethidine:
Mixed Agonist / Antagonist Opioids (analgesic effect);
Naltrexone
Reduces therapeutic effect of Clopidogrel (antiplatelet
effect)
Administration: May be administered by IM, SC, or IV
injection. IV push should be administered slowly using a
diluted solution. 10 mg/mL has been recommended.
Abrupt discontinuation following prolonged use may also
lead to withdrawal symptoms.
NOTE: IM administration is preferred when repeated doses
are required.
Pregnancy Category: C
ATC Code: N02AB02
MORPHINAN DERIVATIVES
Rx BUTORPHANOL
Inj.: 2 mg/mL (as tartrate), 1 mL and 2 mL ampule/vial
(IM, IV)
N
Butorphanol causes inhibition of the ascending pain
pathways, altering the perception of and response to
pain, producing analgesia, respiratory depression, and
sedation similar to opioids.
Indication: Management of pain when the use of an opioid
analgesic is appropriate.
Contraindication: Hypersensitivity to butorphanol or any
component of the formulation.
Dose:
Pain, by IM injection, ADULT, initially 2 mg, may repeat every
3–4 hours as needed; usual range, 1–4 mg every 3–4
hours as needed;
by IV injection, ADULT, initially 1 mg, may repeat every 3–
4 hours as needed; usual range, 0.5–2 mg every 3–4
hours as needed.
Preoperative medication, by IM injection, ADULT, 2 mg 60–
90 minutes before surgery.
Supplement to balanced anesthesia, by IV injection, ADULT,
2 mg shortly before induction and/or an incremental
dose of 0.5–1 mg (up to 0.06 mg/kg), depending on
previously administered sedative, analgesic, and
hypnotic medications.
Pain during labor, by IM or IV injection, ADULT (female with
fetus >37 weeks gestation and no signs of fetal distress),
1–2 mg, may repeat in 4 hours during early labor.
Dose Adjustment:
Geriatric and Renal and Hepatic Impairment:
Initiate at ½ of the recommended dose, repeat doses must
be based on initial response rather than fixed intervals,
but should generally be 6 hours apart.
Precautions:
447

WARNING: Abuse, misuse, and diversion. Users are
exposed to the risks of addiction, abuse, and
misuse, potentially leading to overdose and death.
Monitor all patients for development of these
behaviors or conditions. Risk for opioid abuse is
increased in patients with a personal or family
history of substance abuse, including drug or
alcohol abuse or addiction, or mental illness.
Head injury (Use with extreme caution); Increased
intracranial pressure; CNS depression; Acute MI;
Ventricular dysfunction; Coronary insufficiency;
Hypercapnia or hypoxia; COPD; Adrenal insufficiency;
Biliary tract dysfunction; Prostatic hyperplasia; Thyroid
dysfunction; Renal and hepatic impairment. Obese
patients; Patients at risk for drug abuse.
Elderly (may be more sensitive to adverse effects).
Pregnancy (may cause neonatal withdrawal syndrome may
occur in the newborn with prolonged use during
pregnancy);
Lactation.
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
N
Common: Palpitations, vasodilatation, drowsiness,
dizziness, anxiety, burning sensation, confusion,
euphoria, floating feeling, headache, lethargy,
nervousness, paresthesia, cold and clammy skin,
diaphoresis, pruritus, nausea, vomiting, anorexia,
constipation, unpleasant taste, stomach pain,
xerostomia, tremor, weakness, blurred vision, otalgia,
tinnitus, bronchitis, cough, dyspnea, nasal discomfort,
pharyngitis, rhinitis, epistaxis, sinus congestion,
sinusitis, upper respiratory tract infection.
Less Common: Abnormal dreams, agitation, apnea, chest
pain, convulsions, delusions, depression, drug
dependence, dysphoria, hallucination, edema, hostility,
hypertension, hypogonadism, hypotension, respiratory
depression, seizure, shallow respiration, speech
disturbance, skin rash, syncope, tachycardia, urination
disorder, urticaria, vertigo, withdrawal syndrome.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Ethyl alcohol, Mirtazapine (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect);
SSRIs (serotonergic effect)
Enhances therapeutic effect of Butorphanol:
Amphetamines (analgesic effect); Brimonidine (Topical);
Doxylamine; Dronabinol; Hydroxyzine; Magnesium
sulfate; Minocycline, Nabilone; Tetrahydrocannabinol
(CNS depressant effect)
Increases excretion of Butorphanol:
Ammonium Chloride
Increases risk of adverse or toxic effects of Butorphanol:
Anticholinergic Agents e.g., Atropine (constipation and
urinary retention); Antipsychotic Agents, Phenothiazines
(hypotensive effect);
448
NERVOUS SYSTEM
CNS Depressants [except Levocabastine];
Rufinamide (sleepiness and dizziness); Succinylcholine
(bradycardic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Desmopressin; Diuretics; Ramosetron (constipating
effect); SSRIs (serotonin syndrome; psychomotor
impairment)
Avoid concomitant use with:
Enhances therapeutic effect of Butorphanol:
Droperidol
Enhances therapeutic effect of the following drugs:
Buprenorphine, Orphenadrine, Paraldehyde,
Thalidomide, Zolpidem (CNS depressant effect)
Increases risk of adverse or toxic effects of Nasal Azelastine
(CNS depressant effect)
Reduces therapeutic effect of Butorphanol:
Naltrexone; Other Opioid Analgesics [except
Buprenorphine, Butorphanol, Nalbuphine, Pentazocine]
Administration: Administer by IM or IV injection.
Abrupt discontinuation following prolonged use may also
lead to withdrawal symptoms.
Pregnancy Category: C
ATC Code: N02AF01
Rx NALBUPHINE
Inj.: 10 mg/mL (as hydrochloride), 1 mL ampule (IM, IV,
SC)
Nalbuphine is a synthetic morphine opioid agonist-
antagonist analgesic and a phenanthrene derivative that
is a potent analgesic essentially equivalent to morphine
on a milligram basis and may produce the same degree
of respiratory depression.
Indications: Management of pain severe enough to require
an opioid analgesic; supplement to balanced anesthesia;
preoperative and postoperative analgesia; obstetrical
analgesia during labor and delivery.
Contraindications: Significant respiratory depression; acute
or severe bronchial asthma in an unmonitored setting or
in the absence of resuscitative equipment; known or
suspected GI obstruction, including paralytic ileus.
Dose:
NOTE: Individualize doses based on severity of pain, patient
response, prior analgesic treatment experience, and risk
factors for addiction, abuse, and misuse.
Moderate to severe pain, by IM or SC injection, or by IV
infusion, ADULT, 10 mg every 3-6 hours as needed based
on a 70 kg patient; may titrate dose to appropriate effect
NERVOUS SYSTEM
(maximum single dose in nonopioid-tolerant patients, 20
mg; maximum daily dose, 160 mg).
Dose Adjustment:
Geriatric:
Initiate therapy with reduced doses and use with caution.
Renal and Hepatic Impairment:
Reduce dose.
Precautions:
WARNING: Life-threatening respiratory depression.
Serious, life-threatening, or fatal respiratory
depression may occur, particularly when used
concomitantly with other opioids or CNS
depressants. Monitor for respiratory depression,
especially during initiation of nalbuphine or
following a dose increase.
Risks from concomitant use with benzodiazepines
or other CNS depressants. May result in profound
sedation, respiratory depression, coma, and
death. Reserve concomitant prescribing of
nalbuphine and benzodiazepines or other CNS
depressants for use in patients for whom
alternative treatment options are inadequate.
Limit doses and durations to the minimum
required. Follow patients for signs and symptoms
of respiratory depression and sedation.
Should be administered by personnel trained in
the use of IV anesthetics and the management of
the respiratory effects of potent opioids.
Resuscitative and intubation equipment and
oxygen should be readily available.
Abuse, misuse, and diversion. Users are exposed
to the risks of addiction, abuse, and misuse,
potentially leading to overdose and death. Monitor
all patients for development of these behaviors or
conditions. Risk for opioid abuse is increased in
patients with a personal or family history of
substance abuse, including drug or alcohol abuse
or addiction, or mental illness.
Chronic pulmonary disease (monitor for decreased
respiratory drive including apnea); Adrenal insufficiency
(monitor for nausea, vomiting, anorexia, fatigue,
weakness, dizziness, and low blood pressure); Head
injury and increased intracranial pressure (may obscure
the clinical course of patients with head injuries); Renal
or hepatic impairment; Biliary tract surgery (may cause
spasm of the sphincter of Oddi); Myocardial infarction;
Cardiovascular effects (monitor for bradycardia);
Cachectic or debilitated patients (life-threatening
depression is more likely to occur);
Elderly (life-threatening depression is more likely to occur);
Children (safety and effectiveness in patients <18 years
have not been established); Pregnancy (severe fetal
bradycardia has been reported when used during labor;
sinusoidal fetal heart rate pattern associated with the
use of nalbuphine has been reported); Lactation
(monitor nursing infants for excess sedation and
respiratory depression).
Adverse Drug Reactions:
Common: Sedation, sweaty or clammy, nausea, vomiting,
dizziness or vertigo, dry mouth, headache.
Less Common: Nervousness, restlessness, crying,
depression, euphoria, floating, hostility, unusual dreams,
confusion, faintness, dysphoria, feeling of heaviness,
hallucinations, numbness, tingling, unreality,
bradycardia, tachycardia, hypotension, hypertension,
cramps, dyspepsia, bitter taste, depression, dyspnea,
asthma, itching, burning, urticaria, speech difficulty,
urinary urgency, blurred vision, flushing and warmth,
anaphylactic or anaphylactoid and other serious
hypersensitivity reactions.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Butorphanol:
Amphetamines (analgesic effect)
Enhances therapeutic effect of the following drugs:
Pramipexole, Ropinirole, Rotigotine (sedative effect);
Selective Modulators (serotonergic effect)
Reduces therapeutic effect of the following drugs:
Buprenorphine; Prokinetics
Increases risk of adverse or toxic effects of the following
drugs:
N
Buprenorphine (opioid withdrawal); Desmopressin;
Diuretics; Ramosetron (constipating effect); Selective
Modulators (serotonin syndrome); SSRIs (psychomotor
impairment)
Increases risk of adverse or toxic effects of Butorphanol:
Anticholinergic Agents (constipation and urinary
retention); CNS Depressants; Rufinamide (sleepiness
and dizziness); Succinylcholine (bradycardic effect)
Avoid concomitant use with:
Reduces therapeutic effect of Butorphanol:
Nalmefene; Naltrexone; Other Opioid Analgesics [except
Buprenorphine, Butorphanol, Nalbuphine, Pentazocine]
Administration: For IM or SC injection, administer undiluted.
For IV infusion, administer undiluted over at least 2–3
minutes. Larger induction doses should be administered
over 10–15 minutes.
Inspect visually for particulate matter and discoloration
prior to administration whenever solution and container
permit.
NOTE: When discontinuing therapy, decrease dose by 25–
50% every 2–4 days. Monitor carefully for signs or
symptoms of withdrawal. If patient displays withdrawal
symptoms, increase dose to previous level and then
reduce dose more slowly by increasing interval between
dose reductions, decreasing amount of daily dose
reduction, or both.
Pregnancy Category: B
ATC Code: N02AF02
449
 NERVOUS SYSTEM

OTHER OPIOIDS Renal Impairment:

Immediate Modified
CrCl Parenteral
release release
Rx TRAMADOL
≥30
Reduce dose
mL/min
Oral: 50 mg capsule (as hydrochloride) 50–100 50–100 mg
100 mg, 150 mg, and 200 mg MR tablet (as 10–30 mg every every 12
hydrochloride) mL/min 12 hours Do not hours
50 mg dispersible tablet (as hydrochloride) (maximum, administer
Inj.: 50 mg/mL (as hydrochloride), 1 mL and 2 mL ampule <10 200 mg Not
(IM, IV, SC) mL/min daily) recommended

Tramadol is a centrally-acting, synthetic opioid analgesic. It Hepatic Impairment:

alters perception and response to pain by binding to mu-
Modified
opiate receptors in the CNS. Severity Immediate release
release
Mild-to-
Indications: Relief of moderate to moderately-severe pain; Reduce dose
moderate
around-the-clock management of moderate to
moderately-severe pain; management of postoperative Do not
Severe
pain. administer
50 mg every 12
Cirrhosis
Contraindications: Acute intoxication with alcohol, hours
hypnotics, centrally-acting analgesics, opioids, or
psychotropic drugs; severe or acute bronchial asthma; Precautions:
hypercapnia; significant respiratory depression in the WARNING: Neonatal opioid withdrawal syndrome.
absence of appropriately monitored setting and/or Prolonged use during pregnancy can result in
resuscitative equipment; uncontrolled seizures; use neonatal opioid withdrawal syndrome, which may
within 14 days of a MAO inhibitor e.g. Selegeline; use for
N

be life-threatening if not recognized and treated. If

narcotic withdrawal treatment.
Dose:
Moderate-to-severe pain, by mouth, ADULT, ADOLESCENT,
and CHILD >12 years,
as capsule, 50–100 mg every 4 hours as needed
(maximum, 400 mg daily);
as MR tablet, initially 50–100 mg once or twice daily
(maximum daily dose, 400 mg);
as dispersible tablet, 50–100 mg every 4–6 hours
(maximum, 400 mg daily);
by IV or IM injection, ADULT, ADOLESCENT, and CHILD
>12 years, 50–100 mg every 4–6 hours (maximum 600
mg daily).
Postoperative pain, by IV injection, ADULT, initially 100 mg
as a single dose, followed by 50 mg every 10–20
minutes for the first hour (maximum cumulative initial
dose, 250 mg/hour, including the first dose); administer
subsequent doses at 50–100 mg every 4–6 hours
(maximum cumulative dose, 600 mg daily).
Dose Adjustment:
Geriatric:
Use with caution. Initiate at the low end of the dosing range.
When administering immediate release formulations, do
not exceed 300 mg daily.
Avoid use of MR tablets in elderly patients >75 years. If
used, increase dosing interval and use with great
caution.
opioid use is required for a prolonged period in a
pregnant woman, advise the patient of the risk of
neonatal opioid withdrawal syndrome and ensure
that appropriate treatment will be available.
Emotional disturbance or depression; History of epilepsy or
risk of seizure; Head injury; Increased intracranial
pressure; Renal and hepatic impairment.
Elderly (may be more sensitive to adverse effects);
Children (opioid withdrawal syndrome in neonates, may be
life-threatening).
Pregnancy (may cause neonatal withdrawal syndrome with
prolonged use during pregnancy);
Lactation.
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Flushing, orthostatic hypotension, chest pain,
hypertension, peripheral edema, vasodilation, dizziness,
headache, drowsiness, CNS stimulation, insomnia,
agitation, anxiety, apathy, chills, confusion,
depersonalization, depression, euphoria, hypertonia,
hypoesthesia, ataxia, lethargy, malaise, nervousness,
pain, paresthesia, restlessness, rigors, sleep disorder,
withdrawal syndrome, fatigue, vertigo, pruritus,
diaphoresis, dermatitis, skin rash, hot flash,
hyperglycemia, constipation, nausea, vomiting, weight
loss, xerostomia, dyspepsia, diarrhea, anorexia,
abdominal pain, decreased appetite, flatulence, sore
throat, menopausal symptoms, pelvic pain, prostatic
disease, urine abnormality, urinary tract infection,
urinary frequency, urinary retention, weakness,
arthralgia, back pain, myalgia, neck pain, tremor, blurred
vision, miosis, visual disturbance, cough, dyspnea,

450
NERVOUS SYSTEM
nasopharyngitis, bronchitis, pharyngitis, respiratory
congestion, rhinitis, rhinorrhea, sinusitis, sneezing,
upper respiratory tract infection, accidental injury, fever,
flu-like syndrome.
Less Common: Abnormal dreams, abnormal gait, amnesia,
anaphylactoid reaction, anaphylaxis, anemia,
angioedema, appendicitis, bradycardia, bronchospasm,
cataract, cellulitis, cholecystitis, cholelithiasis, cold and
clammy skin, convulsions, deafness, cognitive
dysfunction, delirium, disorientation, diverticulitis,
dysgeusia, dysphagia, dysuria, ECG abnormality, edema,
decreased libido, fecal impaction, gout, GI hemorrhage,
gastroenteritis, hematuria, hepatic failure, hallucination,
hepatitis, hypersensitivity, hypersensitivity reaction,
hypotension, hypoglycemia, irritability, ischemic heart
disease, joint stiffness, lack of concentration, menstrual
disease, migraine, movement disorder, muscle cramps,
muscle spasm, muscle twitching, mydriasis, myocardial
infarction, night sweats, palpitations, pancreatitis,
peripheral edema, otitis, peripheral ischemia,
pneumonia, proteinuria, pulmonary embolism, sedation,
pulmonary edema, seizure, serotonin syndrome,
shivering, skin vesicle, speech disturbance, Stevens-
Johnson syndrome, stomatitis, suicidal tendencies,
tachycardia, thrombocytopenia, syncope, tinnitus, toxic
epidermal necrolysis, urticaria.
Drug Interactions:
Monitor closely with:
Increases excretion of Tramadol:
Ammonium Chloride
Enhances therapeutic effect of Tramadol:
Amphetamines (analgesic effect); Brimonidine (Topical);
Doxylamine; Dronabinol; Hydroxyzine; Magnesium
sulfate; Minocycline; Nabilone
Enhances therapeutic effect of the following drugs:
Antipsychotic Agents, Phenothiazines (hypotensive
effect); Ethyl alcohol (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect);
Vitamin K Antagonists, e.g., Warfarin (anticoagulant
effect)
Increases risk of adverse or toxic effects of Tramadol:
Anticholinergic Agents (constipation and urinary
retention); CNS Depressants; Rufinamide (sleepiness
and dizziness); Succinylcholine (bradycardic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Antipsychotic Agents (neuroleptic malignant syndrome;
serotonin syndrome); Desmopressin; Diuretics;
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome); Ramosetron (constipating effect)
Reduces therapeutic effect of Tramadol:
Antiemetics (5HT3 Antagonists)
Reduces therapeutic effect of Buprenorphine
Avoid concomitant use with:
Decreases serum concentration of Tramadol:
Carbamazepine; Dabrafenib; Mitotane
Enhances therapeutic effect of Tramadol:
Droperidol, Sodium oxybate (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Carbamazepine, Hydrocodone [start with a 20–30%
lower hydrocodone dose when using together with any
other CNS depressant]; Orphenadrine; Paraldehyde,
Suvorexant; Tapentadol [start tapentadol at one-third to
one-half of normal dose if used concomitantly];
Thalidomide; Zolpidem (CNS depressant effect); MAO
Inhibitors (neuroexcitatory and/or seizure-potentiating
effect; serotonergic effect); SSRIs [except Tedizolid]
(serotonergic effect); Tricyclic Antidepressants
(serotonergic effect; seizure)
Increases risk of adverse or toxic effects of Tramadol:
SSRIs (neuroexcitatory and/or seizure-potentiating
effect; serotonin syndrome); Tricyclic Antidepressants
(neuroexcitatory and/or seizure-potentiating effect)
Increases risk of adverse or toxic effects of the following
drugs:
Dapoxetine; MAO Inhibitors (serotonin syndrome;
seizures); Mixed Agonist / Antagonist Opioids (analgesic
effect); Selective Modulators [except Tedizolid]
(serotonin syndrome)
Reduces therapeutic effect of Tramadol:
N
Naltrexone
Reduces therapeutic effect of Carbamazepine
TEST INTERACTION. May produce a false-positive result in
the urine detection of phencyclidine.
Administration:
For oral administration, swallow whole. Do not crush,
chew, or split. May be taken without regard to meals but
administer consistently either with or without meals.
Parenteral administration may be administered by IM or
IV injection. For IV administration, inject slowly over 2–3
minutes or further dilute in LR or D5W and administer as
an infusion.
Pregnancy Category: C
ATC Code: N02AX02
451

OTHER ANALGESICS AND ANTIPYRETICS
NON-OPIOID ANALGESICS
Rx DICLOFENAC
Oral: 25 mg and 50 mg (as sodium or potassium salt)
tablet/capsule
50 mg (as sodium salt) enteric coated tablet or MR
tablet
100 mg (as sodium or potassium salt) MR
tablet/capsule
Inj.: 25 mg/mL (as sodium salt), 3 mL ampule (IM, IV)
A reversible cyclooxygenase1 and 2 (COX1 and 2) enzyme
inhibitor resulting in decreased formation of
prostaglandin precursors. It exhibits antipyretic,
analgesic, and anti-inflammatory properties.
Indication: Management of mild to moderate acute pain and
moderate to severe acute pain.
Contraindications: Patients who have experienced asthma,
urticaria, or other allergic-type reactions after taking
aspirin or other NSAIDs; treatment of perioperative pain
in the setting of coronary artery bypass graft (CABG)
N
surgery; moderate to severe renal impairment in the
perioperative period and who are at risk for volume
depletion.
Dose:
Analgesia, by IV injection, ADULT, 37.5 mg every 6 hours as
needed (maximum daily dose, 150 mg).
Dose Adjustment:
Geriatric:
Initiate therapy using the lowest recommended dose and
frequency.
Renal Impairment:
In patients with advanced renal disease or significant renal
impairment, use is not recommended.
Hepatic Impairment:
May require dose adjustment. Drug undergoes extensive
hepatic metabolism.
In moderate to severe impairment, use of injectables is not
recommended (has not been studied).
Administration: Administer as an IV bolus over 15 seconds.
NOT indicated for long-term use.
NOTE: Some products may contain phenylalanine.
See Diclofenac under Antiinflammatory and
Antirheumatic Products – Non-selective COX
Inhibitors in Chapter 9: Musculo-Skeletal System for
other information.
Pregnancy Category: C; D (≥30 weeks’ gestation)
ATC Code: Not Available
452
NERVOUS SYSTEM
OTC IBUPROFEN
Oral: 200 mg and 400 mg tablet
100 mg/5 mL syrup / suspension, 60 mL
200 mg/5 mL suspension, 60 mL
Inhibits synthesis of prostaglandins in body tissuesby
inhibiting cyclooxygenase-1 and 2 resulting prevention of
inflammation useful for pain management. It has anti-
inflammatory, analgesic and antipyretic properties.
Indications: Acute pain and inflammation in rheumatic
diseases and other musculoskeletal disorders; mild-to-
moderate pain, including dysmenorrhea and headache;
pain in children; acute migraine attack.
Contraindications: Active or history of peptic ulceration.
Dose:
Mild-to-moderate pain, pyrexia and inflammatory
musculoskeletal disorders, by mouth, ADULT, 1.2–1.8 g
daily in 3–4 divided doses, increased if necessary to
maximum 2.4 g daily (3.2 g daily in inflammatory
disease); maintenance dose of 0.6–1.2 g daily may be
sufficient.
Pain, by mouth, CHILD, 20–40 mg/kg daily in divided doses
(maximum, 1.2 g daily); CHILD 8–12 years, 200 mg 3–4
times daily; CHILD 3–7 years, 100 mg 3–4 times daily;
CHILD 1–2 years, 50 mg 3–4 times daily. [NOTE: NOT
recommended for children <7 kg].
Dose Adjustment:
Renal and Hepatic Impairment:
Keep dose as low as possible.
Precautions:
WARNING: Cardiovascular risks. NSAIDs are
associated with an increased risk of adverse
cardiovascular thrombotic events, including fatal
MI and stroke.
Gastrointestinal events. NSAIDs may increase risk
of GI irritation, inflammation, ulceration, bleeding,
and perforation.
Renal impairment (monitor renal function;); Hepatic
impairment (increased risk of GI bleeding and can cause
fluid retention; avoid use in severe liver disease); Allergic
disorders; Cardiac disease; Coagulation defects.
Elderly; Pregnancy (avoid use unless the potential benefit
outweighs risk; third trimester); Lactation (amount is too
small to be harmful; short courses safe in usual doses).
Adverse Drug Reactions:
Common: Diarrhea, dizziness, dyspepsia, headache, GI
ulceration or bleeding, hypertension, nausea,
hemorrhage, raised liver enzymes, salt and fluid
retention, vomiting.
Less Common: Bronchospasm, esophageal ulceration,
heart failure, hyperkalemia, rash, confusion, renal
impairment.
Rare: Acute renal failure, aseptic meningitis, blood
dyscrasias, blurred vision, colitis, cystitis, fluid retention,
anaphylactic and anaphylactoid reactions, hepatitis,
NERVOUS SYSTEM
interstitial nephritis, MI, nephrotic syndrome,
photosensitivity reaction, Stevens-Johnson syndrome,
stroke, tinnitus, toxic epidermal necrolysis, vertigo.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Ibuprofen:
ACE Inhibitors (renal impairment and hyperkalemia);
Angiotensin II Receptor Blockers (significant decrease in
renal function)
Increases risk of adverse or toxic effects of the following
drugs:
Atenolol; Ciprofloxacin; Levofloxacin (convulsions);
Digoxin (exacerbation of heart failure; reduced renal
function); Diuretics, e.g., Loop Diuretics, Thiazide
Diuretics (reduced renal function; nephrotoxicity); Oral
Corticosteroids, e.g., Hydrocortisone (gastric ulceration);
Other NSAIDs
Reduces therapeutic effect of the following drugs:
ACE Inhibitors, Angiotensin II Receptor Blockers
(antihypertensive effect); Aspirin (antiplatelet activity;
cardioprotective effect); Diuretics (diuretic effect)
Avoid concomitant use with:
Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Ibuprofen:
Alendronate (gastric ulceration); Drugs Affecting Clotting
Process, e.g., Ketorolac (bleeding; GI bleeding); Drugs
that increase Potassium Concentration, e.g., Amiloride,
Triamterene (hyperkalemia)
Increases risk of adverse or toxic effects of the following
drugs:
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
(increased BP); Drugs that are renally excreted, e.g.,
Calcineurin Inhibitors; Vitamin K Antagonists, e.g.,
Warfarin (serious bleeding)
Reduces therapeutic effect of the following drugs:
Antihypertensives, e.g., Beta Blockers, ARBs, Nitrates
(antihypertensive effect)
Administration: Should be taken with food.
Pregnancy Category: C, prior to 30 weeks gestation;
D, ≥30 weeks gestation
ATC Code: Not available
Rx KETOPROFEN
Oral: 100 mg tablet
Inj.: 50 mg/mL, 2 mL ampule (IM)
Reversibly inhibits COX-1 and COX-2 resulting in decreased
formation of prostaglandin precursors and induces a
decrease of prostaglandin synthesis in CNS and PNS. It
also inhibits lipoxygenase, resulting in a decreased
leukotriene production and decreased
polymorphonuclear neutrophil activation.
Indications: Management of painful conditions, including
rheumatoid arthritis, osteoarthritis, ankylosing
spondylitis, acute gout, and inflammation or pain
following surgery.
Contraindications: Perioperative pain in coronary artery
bypass graft (CABG) surgery; active peptic ulcer or
cerebrovascular bleeding; history of NSAID-induced GI
bleeding or perforation; concomitant use with high-dose
methotrexate (≥15 mg/week) or ciprofloxacin; severe
edema; severe hepatic or renal impairment; use in third
trimester of pregnancy; use in children.
Dose:
NOTE: Use the lowest effective dose for the shortest
duration of time, consistent with individual patient goals,
to reduce risk adverse events.
Avoid long-term administration. Transition to oral therapy
to oral therapy after initial improvement.
Pain, by IM injection, ADULT, 50–100 mg daily in 1 or 2
divided doses; may administer up to 100 mg twice daily
for severe pain (maximum, 200 mg in 24 hours for up to
3 days).
Dose Adjustment:
N
Geriatric:
Start at lower end of dosing range. Use with caution.
Renal and Hepatic Impairment:
Use with caution in mild-to-moderate impairment. Use is
contraindicated in severe impairment.
Precautions:
WARNING: Cardiovascular risks. NSAIDs are
associated with an increased risk of adverse
cardiovascular thrombotic events, including fatal
MI and stroke. Use is contraindicated for the
treatment of perioperative pain in CABG surgery.
Gastrointestinal events. NSAIDs may increase risk
of GI irritation, inflammation, ulceration, bleeding,
and perforation.
History of GI disease, e.g. bleeding or ulcer;
Hypertension;
Renal or hepatic impairment;
Elderly (at greater risk of serious GI events, hyperkalemia,
and renal toxicity);
Pregnancy (crosses the placenta; cardiovascular anomalies
and cleft palate following use in the first trimester;
myocardial degenerative changes, prenatal constriction
of the ductus arteriosus, fetal tricuspid regurgitation,
failure of the ductus arteriosus to close postnatally
following use in the third trimester);
Lactation (excreted in breastmilk).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Peripheral edema, headache, depression,
dizziness, abnormal dreams, insomnia, malaise,
nervousness, somnolence, rash, dyspepsia, abdominal
453

pain, constipation, diarrhea, flatulence, nausea, GI
hemorrhage, peptic ulcer, anorexia, stomatitis, vomiting,
urinary tract irritation, abnormal hepatic function tests,
visual disturbance, tinnitus, renal insufficiency.
Less Common: Agranulocytosis, allergic reaction, allergic
rhinitis, alopecia, anaphylaxis, anemia, angioedema,
arrhythmia, aseptic meningitis, blurred vision, bone
marrow suppression, bronchospasm, buccal necrosis,
bullous rash, chills, cholestatic hepatitis, confusion, CHF,
conjunctivitis, diabetes mellitus (aggravated), cystitis,
drowsiness, dysphoria, dyspnea, eczema, edema,
epistaxis, erythema multiforme, exfoliative dermatitis,
facial edema, fecal occult blood, fluid retention, gastritis,
GI perforation, GI ulceration, gynecomastia, decreased
hearing, hallucinations, hematemesis, hemolytic
anemia, hematuria, hemoptysis, hepatic dysfunction,
hepatitis, hepatotoxicity (idiosyncratic), hot flashes,
hypertension, hyponatremia, impotence, intestinal
ulceration, interstitial nephritis, infection, leukopenia,
laryngeal edema, libido disturbance, jaundice,
microvesicular steatosis, melena, migraine, MI,
nephrotic syndrome, onycholysis, palpitation,
pancreatitis, peptic ulcer, peripheral neuropathy,
peripheral vascular disease, photosensitivity, polydipsia,
polyuria, pruritus, purpura, purpuric rash, renal failure,
renal papillary necrosis, retinal hemorrhage, septicemia,
shock, Stevens-Johnson syndrome, tachycardia,
thrombocytopenia, toxic amblyopia, toxic epidermal
N
necrolysis, ulcerative colitis, tubulopathy, urticaria,
vasodilation, xerostomia.
Drug Interactions:
Monitor closely with:
Decreases bioavailability of Ketoprofen:
Aminoglycosides (in premature infants)
Enhances therapeutic effect of Ketoprofen:
Antidepressants; Tricyclic and Tertiary Amine;
Glucosamine; Multivitamins / Fluoride with ADE,
Multivitamins / Minerals with ADEK, Folate, Iron,
Multivitamins / Minerals with AE, No iron, Omega 3 fatty
acids, Pentoxiflylline, Prostacyclin analogues, Serotonin
/ Norepinephrine Re- Uptake Inhibitors, Tipranavir,
Vitamin E (antiplatelet effect); Pentosan Polysulfate
Sodium (bleeding)
Enhances therapeutic effect of the following drugs:
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs (antiplatelet effect);
Anticoagulants, Thrombolytic agents (anticoagulant
effect); Prostaglandins, Ophthalmic, Vitamin K
antagonists (anticoagulant effect [consider therapy
modifications])
Increases risk of adverse or toxic effects of Ketoprofen:
Angiotensin II Receptor Blockers (significant decrease in
renal function); Corticosteroids, Systemic; Other NSAIDS
Increases risk of adverse or toxic effects of the following
drugs:
5-ASA Derivatives (nephrotoxic effect); ACE Inhibitors
(decrease in renal function); Aliskiren (nephrotoxic
effect;); Bisphosphonate Derivatives (GI ulceration;
nephrotoxicity); Collagenase, Systemic (injection site
bruising and/or bleeding); Dasatinib (anticoagulant
454
NERVOUS SYSTEM
effect); Deferasirox (GI ulceration or irritation; GI
bleeding)
Increases risk of adverse or toxic effects of the following
drugs:
Deoxycholic Acid (bleeding or bruising in the treatment
area); Desmopressin;
Drospirenone; Eplerenone, Potassium- sparing diuretics
(hyperkalemic effect); Haloperidol (drowsiness and
confusion); Ibrutinib; Iodine I131 Tositumomab, (bleeding-
related adverse events); Obinutuzumab (serious
bleeding-related events); Porfimer, Verteporfin
(photosensitizing effect); Quinolone Antibiotics
(neuroexcitatory and/or seizure-potentiating effect);
Tacrolimus, Systemic (nephrotoxic effect)
Reduces therapeutic effect of the following drugs:
ACE Inhibitors; Aliskiren; Angiotensin II Receptor
Blockers; Eplerenone, Hydralazine, Potassium- sparing
diuretics; Thiazide Diuretics (antihypertensive effect);
Prostaglandins, Ophthalmic.
Agents with Antiplatelet Properties may enhance the
effect of Urokinase.
Risk X: Avoid combination
NSAID (Nonselective) may enhance the anticoagulant
effect of Vitamin K Antagonists.
Risk D: Consider therapy modification
Avoid concomitant use with:
Decreases absorption of Ketoprofen:
Bile Acid Sequestrants
Enhances therapeutic effect of Ketoprofen:
SSRIs (antiplatelet effect)
Enhances therapeutic effect of the following drugs:
Dabigatran Etexilate, Rivaroxaban, Urokinase, Vitamin K
antagonists e.g., Warfarin (anticoagulant effect)
Increases risk of adverse or toxic effects of Ketoprofen:
Dexketoprofen; Diclofenac, Systemic; Ketorolac, Nasal and
Systemic; Sodium Phosphates (nephrotoxic effect,
specifically, acute phosphate nephropathy)
Increases risk of adverse or toxic effects of the following
drugs:
Apixaban (bleeding); COX2 Inhibitor; Cyclosporine,
Systemic (nephrotoxic effect); Herbs with Anticoagulant
or Antiplatelet Properties, e.g., Alfalfa, Anise, Bilberry
(bleeding); Omacetaxine (bleeding-related events);
Salicylates [except Choline Magnesium Trisalicylate]
(bleeding); Tenofovir
Increases serum concentration of Ketoprofen:
Cyclosporine, Systemic
Increases serum concentration of the following drugs:
Cyclosporine, Systemic; Dabigatran Etexilate; Lithium;
Methotrexate; Pemetrexed [avoid NSAIDs for 2–5 days
prior to, and 2 days after pemetrexed]
NERVOUS SYSTEM
Reduces therapeutic effect of the following drugs:
Loop Diuretics (diuretic effect); Salicylates [except
Choline Magnesium Trisalicylate] (cardioprotective
effect); SSRIs
TEST INTERACTION. May interfere with urine tests that rely
on acid precipitation as an endpoint or on color reactions
for carbonyl groups, including detection of albumin, bile
salts, 17ketosteroids or 17hydroxycorticosteroids in
urine.
Administration: To be administered by deep IM injection into
the gluteal muscle every 4 hours.
Pregnancy Category: C
ATC Code: Not available
Rx KETOROLAC
Inj.: 30 mg/mL (as tromethamol), 1 mL ampule (IM, IV)
Reversibly and non-selectively inhibits COX-1 and COX-2
enzymes, resulting in decreased formation of
prostaglandin precursors. It exhibits minimal anti-
inflammatory effect at its analgesic dose.
Indication: Short-term (≤5 days) management of moderately
severe acute pain requiring analgesia at the opioid level,
usually in a postoperative setting.
Contraindications: Active or history of peptic ulcer disease;
recent or history of GI bleeding or perforation; advanced
renal impairment; patients at risk for renal failure due to
volume depletion; use in labor and delivery; use in
nursing mothers; use as prophylactic analgesic before
any major surgery; intra-operative use when hemostasis
is critical; suspected or confirmed cerebrovascular
bleeding, hemorrhagic diathesis, incomplete
hemostasis, and those at high risk of bleeding;
concomitant use with aspirin, NSAIDs, or probenecid;
neuraxial administration.
Dose:
Short-term management of moderate-to-severe acute pain,
by IM injection, ADULT ≥50 kg, initially 10 to 30 mg as a
single dose, then every 4–6 hours as needed (maximum
total daily dose, 90 mg for up to 2 days); utilize lowest
effective dose;
ADULT <50 kg, initially 10 mg as a single dose, then the
lowest effective dose every 4–6 hours as needed
(maximum total daily dose, 60 mg for not more than 5
days);
by IV bolus, ADULT ≥50 kg, 30 mg single dose over a
minimum of 15 seconds; or 30 mg every 6 hours
(maximum total daily dose, 120 mg for not more than 5
days); ADULT <50 kg or ≥65 years, 15 mg as a single
dose over a minimum of 15 seconds; or 15 mg every 6
hours (maximum total daily dose, 60 mg for not more
than 5 days).
Single-dose treatment, by IM injection, ADULT <65 years, 60
mg single dose; ADULT ≥65 years, renally impaired
and/or <50 kg (110 lbs), 30 mg single dose;
by IV injection, ADULT <65 years, 30 mg single dose;
ADULT ≥65 years, renally impaired and/or <50 kg (110
lbs), 15 mg single dose.
Multiple-dose treatment, by IM or IV injection, ADULT <65
years, 30 mg every 6 hours (maximum daily dose, 120
mg); ADULT ≥65 years, renally impaired and/or <50 kg
(110 lbs), 15 mg every 6 hours (maximum daily dose, 60
mg).
NOTE: For breakthrough pain, do not increase dose or
frequency. Consider supplementing regimen with low
doses of opioids “prn” unless otherwise contraindicated.
Dose Adjustment:
Geriatric:
For IM injection, initially 10 mg single dose, then administer
the lowest effective dose every 4–6 hours as needed
(maximum total daily dose, 60 mg for not more than 5
days).
For IV bolus, 15 mg single dose over a minimum of 15
seconds, or 15 mg every 6 hours (maximum total daily
dose, 60 mg for not more than 5 days).
Renal Impairment:
In moderately elevated serum creatinine, reduce daily dose
by half, not to exceed 60 mg daily.
In advanced renal impairment, use is contraindicated.
N
Hepatic Impairment:
In mild-to-moderate impairment, use with caution as it may
cause elevation of liver enzymes. Discontinue if clinical
signs and symptoms of liver disease develop.
In severe impairment or active hepatic disease, use is
contraindicated.
Precautions:
WARNING: Ketorolac is indicated for the short-term
(up to 5 days) management of moderately severe
acute pain that requires analgesia at the opioid
level. It is NOT indicated for minor or chronic
painful conditions. It is a potent NSAID analgesic,
and its administration carries many risks. NSAID-
related adverse events can be serious, especially
when used inappropriately. Increasing dose
beyond what is recommended will not provide
better efficacy but will result in an increased risk
of serious adverse events.
Gastrointestinal Effects. Can cause peptic ulcers,
GI bleeding and/or perforation. It is
contraindicated in active peptic ulcer disease,
recent GI bleeding or perforation, and in a history
of peptic ulcer disease or GI bleeding.
Risk of Bleeding. Inhibits platelet function. May
cause increased risk of bleeding.
Hypersensitivity. Hypersensitivity reactions,
ranging from bronchospasm to anaphylactic
shock, have occurred. Contraindicated in patients
with previously demonstrated hypersensitivity to
ketorolac or allergic manifestations to aspirin or
other NSAIDs.
455

Intrathecal or Epidural Administration. NOT for
intrathecal or epidural administration due to its
alcohol content.
Concomitant Use with NSAIDs. Has cumulative
risks of inducing serious NSAID-related adverse
events.
Special populations. Adjust doses for patients ≥65
years, patients <50 kg (110 lbs), and patients with
moderately elevated serum creatinine. Total dose
should NOT exceed 60 mg daily.
Labor, Delivery, and Nursing. Has prostaglandin
synthesis inhibitory effect. May adversely affect
fetal circulation and inhibit uterine musculature or
contraction, increasing the risk of uterine
hemorrhage. Use in nursing mothers has potential
adverse effects of prostaglandin-inhibiting drugs
on neonates.
History of hypertension and/or heart failure;
Predisposition to reduced blood volume and/or renal blood
flow;
Mild renal or hepatic impairment;
Patient weighing <50 kg;
Elderly (more susceptible to hyperkalemia and GI
N
complications, e.g., GI ulcerations, bleeding, and
perforation);
Children (safety and efficacy in patients <16 years have not
been established);
Pregnancy (no adequate and well-controlled studies of its
use in pregnant women);
Lactation (may have possible adverse effects of
prostaglandin-inhibiting drugs on neonates).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Edema, hypertension, pruritus, rash, nausea,
dyspepsia, GI fullness, diarrhea, GI pain, constipation,
vomiting, stomatitis, purpura, flatulence, headache,
drowsiness, dizziness, sweating, injection site pain.
Less Common: Weight gain, infections, asthenia, fever,
palpitation, pallor, syncope, urticaria, gastritis, rectal
bleeding, eructation, anorexia, increased appetite,
epistaxis, anemia, tremors, eosinophilia, abnormal
dreams, hallucinations, euphoria, extrapyramidal
symptoms, vertigo, paresthesia, insomnia, nervousness,
excessive thirst, depression, dry mouth, abnormal
thinking, inability to concentrate, hyperkinesis, stupor,
dyspnea, pulmonary edema, rhinitis, abnormal taste,
cough, abnormal vision, blurred vision, tinnitus, hearing
loss, hematuria, proteinuria, oliguria, urinary retention,
polyuria, increased urinary frequency, hypersensitivity
reactions, myalgia, hypotension, flushing, Stevens-
Johnson syndrome, Lyell’s syndrome, exfoliative
dermatitis, maculo-papular rash, urticaria, peptic
ulceration, GI hemorrhage, GI perforation, acute
pancreatitis, melena, thrombocytopenia, liver failure,
hepatitis, cholestatic jaundice, psychosis, leukopenia,
convulsions, aseptic meningitis, asthma, bronchospasm,
acute renal failure, flank pain with or without hematuria
456
NERVOUS SYSTEM
and/or azotemia, nephritis, hyponatremia,
hyperkalemia, hemolytic uremic syndrome.
Rare: Postoperative wound hemorrhage.
Drug Interactions:
Monitor closely with:
Decreases excretion of the following drugs:
Aminoglycosides [in premature infants]
Pralatrexate
Enhances therapeutic effect of Ketorolac:
Dasatinib, Glucosamine, Limaprost, Multivitamins /
Minerals with ADEK, Folate, Iron, Multivitamins /
Minerals with AE, no Iron, Omega- 3 fatty acids,
Prostacyclin analogues, SNRIs, SSRIs, Tricyclic anti-
depressants, Tertiary amine, Vitamin E, Systemic
(anticoagulant effect)
Enhances therapeutic effect of the following drugs:
Prostaglandins, Ophthalmic; Thrombolytic agents;
Urokinase; Vitamin K antagonists e.g., Warfarin
(anticoagulant effect)
Increases risk of adverse or toxic effects of Ketorolac:
ACE Inhibitors (significant decrease in renal function);
Agents with Antiplatelet Properties, e.g., P2Y12
Inhibitors, NSAIDs, SSRIs (antiplatelet effect);
Angiotensin II Receptor Blockers (significant decrease in
renal function); Corticosteroids, Systemic; Diclofenac,
Systemic; Ethyl alcohol, Flunarizine (GI bleeding); Loop
Diuretics, Thiazide diuretics, Thiazide- like diuretics
(nephrotoxic effect); Pentosan Polysulfate Sodium
(bleeding); Sodium Phosphates (nephrotoxic effect,
specifically, acute phosphate nephropathy)
Increases risk of adverse or toxic effects of the following
drugs:
5-Aminosalicylic Acid Derivatives; Aliskiren; Cyclosporine,
Systemic; Tacrolimus, Systemic; Tenofovir (nephrotoxic
effect); Aminolevulinic Acid, Systemic and Topical;
Porfimer; Verteporfin (photosensitizing effect);
Angiotensin II Receptor Blockers (decrease glomerular
filtration and renal function); Apixaban; Dabigatran;
Bisphosphonate Derivatives (GI ulceration;
nephrotoxicity); Deferasirox (GI ulceration, irritation, or
bleeding); Deoxycholic Acid (bleeding or bruising in the
treatment area); Desmopressin; Drospirenone,
Eplerenone, Potassium- sparing diuretics (hyperkalemic
effect); Haloperidol (drowsiness and confusion);
Iodine I131; Neuromuscular-blocking Agents,
Nondepolarizing (apnea); Quinolones (neuroexcitatory
and/or seizure-potentiating effect)
Reduces absorption of Ketorolac:
Bile Acid Sequestrants; Cholestyramine
Reduces therapeutic effect of the following drugs:
ACE Inhibitors; Aliskiren; Angiotensin II Receptor
Blockers; Beta- blockers; Eplerenone, Potassium-
sparing diuretics (antihypertensive effect); Loop
Diuretics (diuretic effect); Prostaglandins, Ophthalmic;
SSRIs; Thiazide Diuretics; Thiazide-like Diuretics
Avoid concomitant use with:
Decreases serum concentration of Ketorolac:
NERVOUS SYSTEM

Salicylates e.g. Aspirin Rx (Inj.) PARACETAMOL

OTC (Oral; Rectal) (ACETAMINOPHEN)
Enhances therapeutic effect of the following drugs:
Anticoagulants (anticoagulant effect)
Oral: 300 mg and 500 mg tablet
100 mg/mL drops (alcohol-free), 15 mL
Increases risk of adverse or toxic effects of Ketorolac:
120 mg/5 mL (125 mg/5 mL) syrup / suspension
Dexketoprofen; Ketorolac, Nasal; Phenylbutazone
(alcohol-free), 30 mL, 60 mL, and 120 mL
250 mg/5 mL syrup / suspension (alcohol-free), 30
Increases risk of adverse or toxic effects of the following
mL, 60 mL, and 120 mL
drugs:
Rectal: 125 mg and 250 mg suppository
Aspirin (bleeding); Pentoxifylline (bleeding); NSAIDs; COX-
Inj.: 150 mg/mL solution for injection, 2 mL ampule (IM,
2 Selective; Salicylates (bleeding)
IV)
10 mg/mL solution for infusion, 50 mL and 100 mL
Increases serum concentration of Ketorolac:
vial (IV)
Probenecid
Inhibits COX-1 and COX-2 and has no significant anti-
Reduces therapeutic effect of the following drugs:
inflammatory activity and is particularly useful for
Aspirin, Salicylates (cardioprotective effect)
treating mild-to-moderate pain, for reducing fever, and in
patients where salicylates and other NSAIDs are
Administration: May be used as a single or multiple dose on
contraindicated.
a regular or “prn” schedule.
Indications: Management of mild- moderate pain, fever.
For IV bolus, administer over a minimum of 15 seconds.
Contraindications: Severe hepatic impairment or severe
For IM injection, administer slowly and deeply into the
active liver disease.
muscle.
Dose:
Inspect visually for particulate matter and discoloration
Mild-to-moderate pain, pyrexia, by mouth, ADULT, 0.5–1 g

prior to administration.
Peel back needle wrapping and expose needle hub.
Avoid touching the hub. Aseptically remove rubber
protective cap from the syringe. Attach needle to syringe
hub with a twist, keeping needle sheath intact. Remove
needle sheath and inject medication. Do NOT recap
needles, purposely bend, or break by hand to prevent
needle-stick injuries. Dispose of used syringe in
accordance with applicable medical waste regulations
and guidelines.
NOTE: The analgesic effect begins in approximately 30
minutes with maximum effect in 1–2 hours after
injection. Duration of analgesic effect is usually 4–6
hours.
Do NOT mix in a small volume with morphine sulfate,
meperidine hydrochloride, promethazine hydrochloride,
or hydroxyzine hydrochloride. This will result in
precipitation of ketorolac from solution.
Correct hypovolemia prior to administration. Switch
patients to alternative analgesics as soon as possible.
Do NOT administer for more than 5 days.
Post-immunization pyrexia, by mouth, INFANT 2–3 months,
Pregnancy Category: C; D in 3rd trimester
ATC Code: Not available
Treatment of acute migraine attack, by mouth, ADULT, 0.5–
Pain or fever, by mouth, pediatric dosing:
N
every 4–6 hours (maximum, 4 g daily); CHILD 6–12
years, 250–500 mg; CHILD 1–5 years, 120–250 mg;
CHILD 3 months to 1 year, 60–125 mg or 10–15 mg/kg
per dose; may repeat doses in children every 4–6 hours
if necessary (maximum, 4 doses in 24 hours);
by rectum, ADULT, ADOLESCENT, and CHILD ≥12 years,
650 mg every 4–6 hours (maximum daily dose, 3,900
mg); CHILD >6 up to 12 years, 325 mg every 4–6 hours
(maximum daily dose, 1,625 mg); CHILD >3 to 6 years,
120 mg every 4–6 hours (maximum daily dose, 600 mg);
CHILD and INFANT 12–36 months, 80 mg every 4–6
hours (maximum daily dose, 400 mg); INFANT 6–11
months, 80 mg every 6 hours (maximum daily dose, 320
mg daily);
by IV injection, ADULT ≥50 kg, 650 mg every 4 hours or
1,000 mg every 6 hours (maximum single dose, 1,000
mg per dose; maximum daily dose, 4 g daily); ADULT <50
kg, 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours
(maximum single dose, 15 mg/kg per dose or 750
mg/dose; maximum daily dose, 75 mg/kg or 3.75 g);
CHILD 2–12 years, 15 mg/kg every 6 hours or 12.5
mg/kg every 4 hours (maximum single dose, 15 mg/kg
per dose or 750 mg; maximum daily dose, 75 mg/kg or
3.75 g).
10–15 mg/kg per dose followed by a second dose, if
necessary, 4–6 hours later [NOTE: Warn parents to seek
medical advice if pyrexia persists after the second dose].
1 g at first sign of attack, repeated every 4 to 6 hours if
necessary, (maximum, 4 g daily); CHILD 6–12 years,
250–500 mg at the first sign of attack, repeated every
4–6 hours if necessary (maximum, 4 doses in 24 hours).

457
 NERVOUS SYSTEM

Weight Weight Dosage [Inj.]

Age Common: Hypertension, hypotension, peripheral edema,
(kg) (lbs) (mg)
2.7–5.3 6–11 0–3 months 40 tachycardia, headache, insomnia, agitation, anxiety,
4–11 fatigue, trismus, pruritus, skin rash, hypervolemia,
5.4–8.1 12–17 80 hypoalbuminemia, hypokalemia, hypophosphatemia,
months
nausea, vomiting, hypomagnesemia, constipation,
8.2–10.8 16–23 1–2 years 120
abdominal pain, diarrhea, oliguria, anemia, infusion site
10.9– reaction, limb pain, muscle spasm, periorbital edema,
24–35 2–3 years 160
16.3 atelectasis, abnormal breath sounds, dyspnea, hypoxia,
16.4– pleural effusion, pulmonary edema, stridor, wheezing,
36–47 4–5 years 240
21.7 fever
21.8– Less Common: Anaphylaxis, hepatic injury (dose-related),
48–59 6–8 years 320
27.2 hypersensitivity reaction, severe dermatological reaction
27.3– (acute generalized exanthematous pustulosis, Stevens-
60–71 9–10 years 400
32.6 Johnson syndrome, toxic epidermal necrolysis)
32.7–
72–95 11 years 480
43.2 Drug Interactions:
Monitor closely with:
NOTE: Infants <3 months should not be given paracetamol Enhances therapeutic effect of Vitamin K Antagonists, e.g.,
unless advised by a doctor. A dose of 10 mg/kg (5 mg/kg Warfarin (anticoagulant effect)
if jaundiced) is suitable.
Increases metabolism of Paracetamol:
Dose Adjustment: Barbiturates e.g. Phenobarbital; Carbamazepine
Renal Impairment:
Longer dosing intervals and reduce total doses. Avoid Increases risk of adverse or toxic effects of Paracetamol:
prolonged or repeated use. Barbiturates; Carbamazepine; Ethyl alcohol (liver
damage); Isoniazid
Hepatic Impairment:
N

Use with caution and avoid prolonged or repeated use in any
type of liver disease. Contraindicated in severe active
liver disease
Precautions:
WARNING: Massive overdose may cause hepatic
necrosis and, less frequently, renal damage. Less
overdoses can frequently cause reversible
jaundice.
Has been associated with cases of acute liver
failure, at times resulting in liver transplant and
death. Most are associated with the doses that
exceed the maximum daily limits, and often
involve more than 1 paracetamol-containing
product.
Sodium restriction (soluble paracetamol products may
contain large amounts of sodium);
Phenylketonuria (soluble products of paracetamol may
contain aspartame);
Alcohol dependence; overdosage;
G6PD deficiency;
Hepatic impairment and renal impairment; (dose-related
toxicity;
Avoid large doses, e.g., >4 g daily);
Pregnancy (not known to be harmful);
Lactation (small amount is present in milk; short courses
are safe in usual dosage; monitor infant).
Increases risk of adverse or toxic effects of the following
drugs:
Dapsone, Topical; Fosphenytoin-Phenytoin; Imatinib;
Sorafenib (hepatotoxic effect); Nitric Oxide, Prilocaine,
Sodium nitrite (significant methemoglobinemia)
Reduces therapeutic effect of Paracetamol:
Barbiturates, Carbamazepine
Avoid concomitant use with:
Decreases absorption of Paracetamol:
Cholestyramine Resin [administer 1 hour apart to
minimize this effect]
Increases risk of adverse or toxic effects of Dasatinib
(hepatotoxic effect)
Increases serum concentration of Paracetamol:
Dasatinib; Probenecid (increases the potential for
formation of the toxic NAPQI metabolite); Sorafenib
TEST INTERACTION. May cause false-positive urinary 5-
hydroxyindoleacetic acid.
Administration:
For oral administration, may be taken with or without
food. Taking with food may decrease GI upset. When
administering suspensions, shake well before use.

Adverse Drug Reactions:
[Oral, Rectal]
Common and Less Common: Skin rash, nephrotoxicity
(chronic overdose), anemia, hyperuricemia, leukopenia,
neutropenia, renal disease, pancytopenia
Rare: Hypersensitivity reaction
For rectal administration, remove the wrapper and insert
the suppository well up into the rectum.
For IV administration, administer by IV infusion only.
Administer undiluted over 15 minutes. Use within 6
hours of opening vial or transferring to another container.

For doses <1,000 mg (<50 kg), withdraw the appropriate

dose from the vial and place in a separate empty, sterile

458
NERVOUS SYSTEM
container prior to administration. Small volume pediatric
doses (up to 600 mg [60 mL]) may be placed in a syringe
and infused over 15 minutes via syringe pump.
For 1,000 mg doses (≥50 kg), insert a vented IV set
through vial stopper.
Pregnancy Category: C
ATC Code: N02BE01
DRUGS FOR NEUROPATHIC PAIN
Rx CARBAMAZEPINE
Oral: 200 mg tablet
200 mg and 400 mg MR tablet
100 mg/5 mL syrup, 120 mL
Carbamazepine is an anti-seizure drug also used for
neuropathic pain. It limits the firing of action
potentials evoked by a sustained depolarization in
cortical neurons by slowing the rate of recovery of
voltage-activated Na+ channels from inactivation.
Indication: Idiopathic trigeminal neuralgia and painful
diabetic neuropathy.
Contraindications: Atrioventricular block; bone marrow
depression; acute intermittent porphyria; combination
with MAO Inhibitors e.g. Selegeline
Dose:
NOTE: MR tablets are designed to be taken twice daily due
to the controlled release of the active substance.
Idiopathic trigeminal neuralgia, by mouth, ADULT, initially
100 mg 2 times daily, slowly raise the dosage until
freedom from pain is achieved (normally at 200 mg 3–4
times daily), then gradually reduce dose to the lowest
possible maintenance level; usual maintenance dose is
400–800 mg daily in divided doses (maximum, 1.2 g
daily).
Painful diabetic neuropathy, by mouth, ADULT, initially 100
mg 1–2 times a day, gradually increase depending on
response; average dose is 200 mg 2–4 times daily.
Dose Adjustment:
Geriatric:
Select doses with caution. Generally, lower doses are
started.
Renal Impairment:
Use with caution. In moderate to severe impairment, reduce
doses.
Hepatic Impairment:
Drug is primarily metabolized in the liver. Use with caution
in advanced liver disease as metabolism is impaired.
Precautions:
WARNING: Neurologic. Must be used with caution in
patients with mixed seizures, including absences,
which can be exacerbated by carbamazepine. In
case of exacerbation, the drug must be
discontinued.
Hematologic effects (Obtain pretreatment complete blood
counts with platelet counts at baseline and periodically
thereafter; discontinue if there is significant bone
marrow depression); Dermatologic effects (discontinue if
signs and symptoms of severe skin reaction appear);
psychosis (may activate latent psychosis); Hepatic
effects (evaluate baseline and periodic hepatic function
particularly in those with a history of liver disease; may
cause or aggravate liver disease; withdraw immediately
in case of aggravated liver dysfunction or active liver
disease); Breakthrough bleeding (may be seen in women
taking oral contraceptives); may affect reliability of oral
contraceptives, women of childbearing age must be
advised to use alternative forms of birth control.
Elderly (increased risk for adverse effects, including liver
dysfunction, and confusion and agitation); Pregnancy
(increased risk for developmental disorders has been
reported; rare reports of developmental disorders,
including spina bifida, has been reported; can aggravate
folic acid deficiency so supplementation is
N
recommended before and during pregnancy; administer
Vitamin K1 to the mother during the last weeks of
pregnancy and to the newborn to prevent bleeding
disorders in the offspring); lactation (excreted in
breastmilk; monitor infants closely for adverse
reactions).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Ataxia, dizziness, drowsiness, fatigue, headache
diplopia, blurred vision, allergic reactions, urticaria (may
be severe), leucopenia, thrombocytopenia, eosinophilia,
elevated gamma-GT (usually not clinically relevant),
elevated alkaline phosphatase, nausea, vomiting, mouth
dryness, edema, increase in weight, hyponatremia,
reduced plasma osmolality.
Less Common: Abnormal involuntary movements,
exfoliative dermatitis, erythroderma, diarrhea,
constipation.
Rare: Orofacial dyskinesia, oculomotor disorders, slurred
speech, peripheral neuritis, paresthesia, muscle
weakness, hallucinations, depression, restlessness,
agitation, confusion, loss of appetite, lupus-
erythematosus like syndrome, pruritus, Stevens-Johnson
syndrome, acne, purpura, leukocytosis,
lymphadenopathy, folic acid deficiency, hypertension or
hypotension, delayed multiorgan hypersensitivity,
disturbance in cardiac conduction, agranulocytosis,
aplastic anemia, pure red cell aplasia, megaloblastic
anemia, pancreatitis, anaphylactic reactions,
arrhythmias, renal or urinary dysfunction.
NOTE: Particularly at the start of treatment, or if the initial
dose is too high, or in the elderly, certain adverse
459

reactions (e.g., CNS and GI symptoms, allergy) commonly
occur.
Drug Interactions:
Monitor closely with:
Decreases bioavailability of Paracetamol
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics, e.g., Hydrochlorothiazide, Furosemide
(symptomatic hyponatremia)
Isoniazid (isoniazid-induced hepatotoxicity)
Neuroleptics, e.g., Haloperidol (neurological adverse
reactions)
Avoid concomitant use with:
Decreases serum concentration of Oral Contraceptives
Incompatible with the following products:
MAO Inhibitors e.g. Phenelzine
Reduces therapeutic effect of Oral Contraceptives
Administration: May be taken during, after, or between
meals. For the syrup formulation, shake well before use.
Administer tablets with little liquid. Swallow MR tablets
unchewed with a little liquid.
N
Pregnancy Category: D
ATC Code: N03AF01
Rx GABAPENTIN
Oral: 100 mg and 300 mg capsule
Gabapentin selectively binds to α2δ subunits of voltage-
sensitive calcium channels, causing closure of N and P/Q
presynaptic calcium channels that diminishes excessive
neuronal activity and neurotransmitter release.
Indication: Management of postherpetic neuralgia (PHN) in
adults; neuropathic pain.
Contraindication: Hypersensitivity to gabapentin or any
component of the formulation.
Dose:
Postherpetic neuralgia, by mouth, ADULT, Day 1: 300 mg;
Day 2: 300 mg twice daily; Day 3: 300 mg 3 times daily;
titrate dose as needed for pain relief, usually ranging
from 1,800–3,600 mg daily in divided doses.
Neuropathic pain, by mouth, ADULT, initially, 300 mg on the
1st day, 300 mg twice a day on the 2nd day and 300 mg
3 times a day on the 3rd day; alternatively, 900 mg daily
in 3 divided doses; dose may increase in increments of
300 mg every 2–3 days (maximum 3,600 mg daily).
Dose Adjustment:
Geriatric:
Dose reductions may be needed based on renal function.
Renal Impairment:
Adjust doses for renal function.
460
NERVOUS SYSTEM
In CrCl ≥60 mL/minute, administer 300–1,200 mg 3 times
daily.
In CrCl >30 to 59 mL/minute, administer 200–700 mg
twice daily.
In CrCl >15 to 29 mL/minute, administer 200–700 mg once
daily.
In CrCl 15 mL/minute, administer 100–300 mg once daily.
In CrCl <15 mL/minute, reduce daily dose in proportion to
creatinine clearance based on dose for CrCl 15
mL/minute (e.g., reduce dose by one-half [range: 50–
150 mg daily] for CrCl 7.5 mL/minute).
In ESRD requiring hemodialysis, adjust dose based on CrCl
plus a single supplemental dose of 125–350 mg after
each 4 hours of hemodialysis.
Precautions:
Mixed seizures including absences; Acute pancreatitis
(discontinue if acute pancreatitis develops); Renal
impairment; Hemodialysis; Not recommended for
patients who need to sleep during daytime and remain
awake at night.
Elderly; Children; Pregnancy (crosses the placenta; adverse
events have been observed in animal reproduction
studies); Lactation (use only if the benefits to the mother
outweigh the potential risk to the infant).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Peripheral edema, dizziness, drowsiness,
vasodilatation, ataxia, fatigue, hostility, tremor,
emotional lability, hyperkinesia, abnormality in thinking,
headache, abnormal gait, depression, amnesia,
nervousness, hyperesthesia, lethargy, pain, twitching,
vertigo, pruritus, weight gain, skin rash, hyperglycemia,
diarrhea, nausea and vomiting, xerostomia, constipation,
abdominal pain, dyspepsia, dry throat, dental disease,
flatulence, increased appetite, urinary tract infection,
impotence, decreased white blood cell count,
leukopenia, infection, weakness, back pain, dysarthria,
myalgia, bone fracture, limb pain, viral infection,
nystagmus, diplopia, blurred vision, conjunctivitis,
nasopharyngitis, rhinitis, otitis media, bronchitis,
pharyngitis, respiratory tract infection, cough, fever.
Less Common: Acute renal failure, altered serum glucose,
anemia, angina pectoris, angioedema, aphasia,
aspiration pneumonia, blindness, blood coagulation
disorder, bradycardia, brain disease, breast hypertrophy,
bronchospasm, cardiac arrhythmia (various),
cerebrovascular accident, cardiac failure, colitis,
confusion, Cushingoid appearance, CNS neoplasm,
DRESS syndrome, drug abuse, dyspnea, erythema
multiforme, drug dependence, facial paralysis, fecal
incontinence, gastroenteritis, glaucoma, glycosuria,
hearing loss, hematemesis, hematuria, hemiplegia,
heart block, hemorrhage, hepatitis, hepatomegaly,
herpes zoster, hyperlipidemia, hypertension,
hyperthyroidism, hyponatremia, hypotension,
hyperventilation, hypoventilation, hypothyroidism,
jaundice, leukocytosis, lymphadenopathy, joint swelling,
lymphocytosis, memory impairment, meningism,
migraine, movement disorder, myocardial infarction,
myoclonus (local), nerve palsy, nephrolithiasis,
nephrosis, non-Hodgkin's lymphoma, palpitations,
NERVOUS SYSTEM
pancreatitis, ovarian failure, paresthesia, peptic ulcer,
pericardial effusion, pericardial rub, pericarditis,
peripheral vascular disease, pneumonia, psychosis,
pulmonary thromboembolism, retinopathy, purpura,
rhabdomyolysis, seasonal allergy, skin necrosis, status
epilepticus, Stevens-Johnson syndrome, subdural
hematoma, suicidal ideation, suicidal tendencies,
syncope, tachycardia, thrombophlebitis, tumor growth,
thrombocytopenia, withdrawal syndrome.
Drug Interactions:
Monitor closely with:
Enhances CNS Depressant effect of Gabapentin:
Brimonidine (Topical); Doxylamine; Dronabinol;
Hydroxyzine; Minocycline; Nabilone
Enhances therapeutic effect of the following drugs:
Ethyl alcohol; Mirtazapine (CNS depressant effect);
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Increases risk of adverse or toxic effects of Gabapentin:
CNS Depressants [except Levocabastine, Nasal];
Rufinamide (sleepiness and dizziness)
Increases risk of adverse or toxic effects of SSRIs e.g.
Fluoxetine (psychomotor impairment)
Avoid concomitant use with:
Decreases serum concentration of Gabapentin:
Antacids [administer gabapentin at least 2 hours after
antacid]; Magnesium Salts [administer gabapentin at
least 2 hours after magnesium salts]; Mefloquine
Enhances therapeutic effect of Gabapentin:
Droperidol; Magneisum salts; Methotrimeprazine
[reduce gabapentin dose by 50% with concomitant use];
Perampanel; Sodium oxybate; Tapentadol [start
tapentadol at one-third to one-half of normal dose if used
concomitantly] (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Azelastine, Nasal; Buprenorphine; Hydrocodone [start
with a 20–30% lower hydrocodone dose when used
concomitantly]; Methotrimeprazine [reduce gabapentin
dose by 50% with concomitant use]; Orphenadrine;
Paraldehyde; Suvorexant; Thalidomide; Zolpidem (CNS
depressant effect)
Reduces therapeutic effect of Gabapentin:
Mefloquine; Mianserin
TEST INTERACTION. May cause a false positive result with
the Ames N-Multistix SG® dipstick test for urine protein.
Administration: May be taken with or without food.
Administer first dose on first day at bedtime to avoid
somnolence and dizziness. When given 3 times daily, the
maximum time between doses should not exceed 12
hours.
Do NOT discontinue abruptly because of the possibility of
increasing seizure frequency. Withdraw gradually to
minimize the potential of increased seizure frequency,
unless safety concerns require a more rapid withdrawal.
Pregnancy Category: C
ATC Code: N03AX12
ANTIMIGRAINE PREPARATIONS
ERGOT ALKALOIDS
Rx ERGOTAMINE
Oral: 1 mg tablet (as tartrate)
Ergotamine is an ergot alkaloid with partial agonist and/or
antagonist activity against tryptaminergic, dopaminergic
and alpha-adrenergic receptors. It stimulates uterine
contraction, peripheral and cranial vasoconstriction and
depression of central vasomotor center.
Indication: Management and prophylaxisof vascular
headaches (e.g. migraine, migraine variants, or so-called
“histaminic cephalalgia”).
Contraindications: Peripheral vascular disease; hepatic or
renal impairment; coronary artery disease; hypertension;
sepsis; concomitant use with strong CYP3A4 inhibitors;
pregnancy.
N
Dose:
Vascular headache, by mouth, placed under the tongue,
ADULT, initially 2 mg at first sign of migraine, then 2 mg
every 30 minutes if needed (maximum dose, 6 mg per
24 hours, or 10 mg per week).
Dose Adjustment:
Geriatric:
Use is not recommended.
Precautions:
WARNING: Concomitant use with CYP3A Inhibitors.
Serious and/or life-threatening peripheral
ischemia has been associated with concomitant
use of potent CYP 3A4 inhibitors, including
protease inhibitors e.g. Lopinavir and macrolide
antibiotics e.g. Erythromycin..Concomitant use of
these medications is contraindicated.
Cardiac valvular fibrosis; cardiovascular effectse. g
vasoconstriction, hypertension and direct myocardial
toxicity; anemia; ergotism; pleural or retroperitoneal
fibrosis.
Elderly (may precipitate angina, MI, or aggravate
intermittent claudication).
Pregnancy (may cause prolonged constriction of the uterine
vessels and/or increased myometrial tone leading to
reduced placental blood flow); lactation (excreted in
breastmilk; may cause vomiting, diarrhea, weak pulse,
and unstable blood pressure in the nursing infant).
Adverse Drug Reactions:
Common and Less Common: Absence of pulse, bradycardia,
cardiac valvular fibrosis, cyanosis, edema, ECG changes,
gangrene, hypertension, ischemia, tachycardia,
vasospasm, vertigo, precordial distress and pain, itching,
nausea, vomiting, retroperitoneal fibrosis, muscle pain,
461

paresthesia, weakness, cold extremities,
pleuropulmonary fibrosis.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Ergotamine:
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Agents, Tedizolid (serotonergic effect)
Increases risk of adverse or toxic effects of Ergotamine:
Antipsychotic Agents (possibly increasing the risk for
neuroleptic malignant syndrome; serotonin syndrome)
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome)
Tedizolid (serotonin syndrome)
Avoid concomitant use with:
Enhances therapeutic effect of Ergotamine:
Beta Blockers e.g., Metoprolol, Serotonin 5­HT1D
Receptor Agonists (vasoconstricting effect)
Enhances therapeutic effect of the following drugs:
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive;
vasoconstricting effects) Serotonin 5­HT1D Receptor
Agonists (vasoconstricting effect)
Decreases serum concentration of Ergotamine:
Enzalutamide
N
Increases risk of adverse or toxic effects of Ergotamine:
Other Serotonin Modulators [except Tedizolid] (serotonin
syndrome)
Increases risk of adverse or toxic effects of Dapoxetine
Increases serum concentration of Ergotamine:
Anti-hepaciviral Combination Products, Boceprevir,
Clarithromycin, Cobicistat, Fusidic Acid (Systemic),
Itraconazole, Ketoconazole (Systemic), Macrolide
Antibiotics [except Systemic Azithromycin, Fidaxomicin,
Spiramycin], Mifepristone [avoid ergotamine during and
2 weeks following mifepristone use], Nitroglycerin,
Posaconazole, Protease Inhibitors, Voriconazole
Reduces therapeutic effect of Nitroglycerin (vasodilatory
effect)
FOOD INTERACTION. Grapefruit juice may cause increased
blood levels of ergotamine, leading to increased toxicity.
Administration: Administer sublingually, by placing under
the tongue until it dissolves. Do NOT crush or swallow.
Discontinuation even after limited use may result in
withdrawal symptoms, e.g., rebound headache, nausea,
vomiting.
NOTE: Use for ≥10 days per month may lead to worsening
of headaches due to medication overuse headache.
Withdrawal treatment may be necessary in the setting of
overuse.
Pregnancy Category: X
ATC Code: N02CA02
462
NERVOUS SYSTEM
SELECTIVE SEROTONIN (5HT1) AGONISTS
Rx SUMATRIPTAN
Oral: 50 mg tablet
A selective serotonin agonist that acts at 5-HT1B/1D receptor,
causing vasoconstriction of meningeal vessels and/or
inhibition of neurogenic inflammatory processes in the
CNS. Its nociceptive effect is likely due to blocking the
pain transmission signals at trigeminal nerve terminals
and synapses of second-order neurons in trigeminal
nucleus caudalis.
Indication: Acute treatment of migraine with or without aura.
NOTE: NOT for the prevention of migraine attacks
Contraindications: Hypersensitivity to sumatriptan or any
component of the formulation; Severe hepatic
impairment; ischemic coronary artery disease or
coronary artery vasospasm, including Prinzmetal’s
angina; uncontrolled hypertension; Wolff-Parkinson-
White syndrome or arrhythmias associated with other
cardiac accessory conduction pathway disorders; history
of stroke or transient ischemic attack; history of
hemiplegic or basilar migraine; peripheral vascular
disease; ischemic bowel disease; recent use (within 24
hours) of ergotamine-containing medication or another
5-HT1 agonist; concurrent or recent (within 2 weeks) use
of a MAOA inhibitor.
Dose:
Acute treatment of migraine, by mouth, ADULT >18 years,
initially a single dose 50 mg tablet; if the migraine has
not resolved by 2 hours after administration, or returns
after a transient improvement, administer a second dose
at least 2 hours after the first dose (maximum daily dose,
200 mg in a 24-hour period).
Dose Adjustment:
Geriatric:
Administer first dose at physician’s office, if needed.
Hepatic Impairment:
Reduce doses, in mild-to-moderate hepatic impairment, the
maximum single dose should not exceed 50 mg.
Precautions:
Cardiac events (e.g., coronary artery vasospasm, transient
ischemia, MI, ventricular tachycardia or fibrillation,
cardiac arrest, and death); arrhythmias (life-
threatening); elevated blood pressure (hypertensive
crisis) Cerebrovascular events (e.g., cerebral
hemorrhage, subarachnoid hemorrhage, and stroke;
some fatal); vasospasm reactions; CNS depression;
seizures; ocular effects.
Serotonin syndrome; anaphylactic or anaphylactoid
reactions (may be fatal); hepatic impairment.
Elderly (may be at increased cardiovascular risk); children
(safety and effectiveness have not been established).
Pregnancy; (has been associated with embryolethality, fetal
abnormalities, and pup mortality in animal studies);
lactation (excreted in breastmilk; use with caution).
NERVOUS SYSTEM
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Hot and cold flashes, chest pain, chest pressure,
chest tightness, pain, sensation of pressure,
paresthesia, malaise, fatigue, feeling of heaviness,
sensation of tightness, heaviness of chest, sore throat,
jaw pain, jaw pressure, jaw tightness, pharyngeal edema,
neck pain, local pain
Less Common: Hypotension, palpitations, dystonia, tremor,
vertigo
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Sumatriptan:
Antipsychotic Agents (serotonergic effect)
Increases risk of adverse or toxic effects of Sumatriptan:
Antipsychotic Agents (enhances dopamine blockade,
possibly increasing the risk for neuroleptic malignant
syndrome; serotonin syndrome)
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome)
Avoid concomitant use with:
Enhances therapeutic effect of Sumatriptan:
Beta Blockers Ergot Derivatives [except Nicergoline]
(vasoconstricting effect)
Metaxalone, Methylene blue, Methylphenidate, Opioid
Analgesics, Tramadol
(serotonergic effect)
Other Serotonin 5­HT1D Receptor Agonists
Enhances therapeutic effect of the following drugs:
Ergot Derivatives [except Nicergoline], Serotonin 5­HT1D
Receptor Agonists (vasoconstricting effect)
Increases risk of adverse or toxic effects of Sumatriptan:
Other Serotonin Modulators [except Tedizolid]
Metaxalone, Methylene blue (serotonin syndrome)
Methylphenidate (serotonin toxicity)
Opioid Analgesics, Tramadol
Increases risk of adverse or toxic effects of the following
drugs:
Dapoxetine
Tramadol (seizures)
Increases serum concentration of Sumatriptan:
MAO Inhibitors
Administration: Administer as soon as symptoms appear.
Pregnancy Category: C
ATC Code: N02CC01
Rx ZOLMITRIPTAN
Oral: 2.5 mg tablet
Zolmitriptan is a selective 5-HT1B/1D/1F receptor agonist that
causes vasoconstriction of cranial arteries and sensory
nerves of the trigeminal system. This causes
vasoconstriction and reduces inflammation associated
with relief of migraine.
Indication: Acute treatment of migraine with or without aura.
Contraindications: Ischemic coronary artery disease;
coronary artery vasospasm, including Prinzmetal variant
angina, or other significant underlying cardiovascular
disease; Wolff-Parkinson-White syndrome or arrhythmias
associated with other cardiac accessory conduction
pathway disorders; peripheral vascular disease;
ischemic bowel disease; uncontrolled hypertension;
recent use (within 24 hours) of other 5-HT1 agonist or an
ergotamine-containing medication; history of stroke,
transient ischemic attack, or history of hemiplegic or
basilar migraine; co-administration or use within 2 weeks
of MAOA inhibitor therapy
Dose:
Migraine, by mouth, ADULT >18 years, 1.25–2.5 mg
N
(maximum single dose, 5 mg), may repeat in 2 hours if
the migraine headache has not resolved or returns after
transient improvement (maximum daily dose 10 mg).
Dose Adjustment:
Geriatric:
Initiate therapy at the low end of the dosing range.
Renal Impairment:
Zolmitriptan clearance is reduced in patients with severe
renal impairment (CrCl 5–25 mL/min.)
Hepatic Impairment:
For moderate to severe impairment, initial dose is 1.25 mg.
Maximum daily dose in severe impairment is 5 mg.
Precautions:
Cardiac events (coronary artery vasospasm, transient
ischemia, MI, ventricular tachycardia or fibrillation,
cardiac arrest, and death have been reported within a
few hours’ administration); elevated blood pressure;
coronary artery disease (administer first dose in the
healthcare provider's office).
Cerebrovascular events (cerebral or subarachnoid
hemorrhage and stroke have been reported, some fatal);
visual effects; vasospasm-related events (have been
reported); hepatic impairment; serotonin syndrome.
Elderly, Pregnancy; lactation.
Adverse Drug Reactions:
Common: Chest pain, cardiac arrhythmia, syncope,
hypertension, tachycardia, dizziness, local alterations in
temperature sensations, vertigo, paresthesia,
drowsiness, sensation of pressure, hyperesthesia,
headache, agitation, amnesia, anxiety, depression,
emotional lability, insomnia, diaphoresis, pruritus,
urticaria, nausea, skin rash, xerostomia, dyspepsia,
vomiting, urinary frequency, urinary urgency, dysphagia,
463
 NERVOUS SYSTEM

local pain at the neck, throat, or jaw, hypersensitivity Withdrawal treatment may be necessary in the setting of
reaction, weakness, tinnitus, polyuria. overuse.
Less Common: Abnormal dreams, abnormality in thinking, If a patient does not respond to the first dose, the
altered sense of smell, amblyopia, anaphylactoid diagnosis of migraine should be reconsidered.
reaction, anaphylaxis, back pain, angina pectoris,
angioedema, apathy, ataxia, atrial fibrillation, Pregnancy Category: C
bradycardia, breast carcinoma, breast neoplasm, bruise,
cellulitis, cerebral ischemia, confusion, conjunctivitis, ATC Code: N02CC03
constipation, colitis, convulsions, coronary artery
vasospasm, cyanosis, cyst, cystitis, diarrhea,
dysmenorrhea, dry eye syndrome, eructation, erythema, OTHER ANTIMIGRAINE PREPARATIONS
eye pain, eczema, erythema multiforme, euphoria,
fibrocystic breast disease, flu­like symptoms, fever,
gastritis, GI carcinoma, GI infarction, GI necrosis, Rx FLUNARIZINE
genitourinary neoplasm, gingivitis, hallucination, hepatic
neoplasm, hiccups, hypertensive crisis, hyperthyroidism,
Oral: 5 mg capsule (as hydrochloride)
hypertonia, hyperventilation, increased appetite,
increased bronchial secretions, increased thirst,
Flunarizine is a selective calcium channel blocker that
infection, intestinal obstruction, irritability, ischemic
prevents cellular calcium overload by reducing excessive
colitis, ischemic heart disease, lacrimation, laryngitis,
transmembrane calcium influx. It has calmodulin binding
leukopenia, mania, menorrhagia, MI, neoplasm,
properties and histamine H1 blocking activity. It also
neuropathy, otalgia, photophobia, pneumonia,
appears to act by blocking dopamine D2 receptors in a
psychosis, pyelonephritis, renal pain, salivation, seizure,
manner similar to antipsychotics.
serotonin syndrome, sialadenitis, skin neoplasm, splenic
infarction, stomatitis, tardive dyskinesia, tenosynovitis,
Indication: Prophylactic treatment of migraine, with or
thrombophlebitis, thyroid edema, tongue edema, tremor,
without aura, in patients with frequent severe attacks
twitching, UTI, uterine hemorrhage, uterine fibroid
who have not responded satisfactorily to other
enlargement, vasodilatation, vaginitis, ventricular
treatments and/or do not tolerate other therapy.
N

fibrillation, ventricular tachycardia, visual field defect,

voice disorder, yawning.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Zolmitriptan:
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Agents (serotonergic effect)
Increases risk of adverse or toxic effects of Zolmitriptan
(serotonergic syndrome)
5HT3 Antagonists e.g., Ondansetron, Antipsychotic
Agents
Increases risk of adverse or toxic effects of the following
drugs:
Antipsychotic Agents (enhances dopamine blockade,
possibly increasing the risk for neuroleptic malignant
syndrome) Metoclopramide (serotonin syndrome;
neuroleptic malignant syndrome)
Avoid concomitant use with:
Decreases metabolism of Zolmitriptan:
MAO Inhibitors e.g Phenelzine
Enhances therapeutic effect of Zolmitriptan:
Ergot Derivatives (vasoconstricting effect)
Increases risk of adverse or toxic effects of Zolmitriptan:
Dapoxetine, Other Serotonin Modulators [except
Tedizolid] (serotonin syndrome)
Administration: Administer as soon as migraine headache
starts. May be broken in half to achieve a smaller initial
dose.
NOTE: Use for ≥10 days per month may lead to worsening
of headaches, e.g., medication overuse headache.
Contraindications: History of depression, preexisting
symptoms of Parkinson’s disease or other
extrapyramidal disorders.
Dose:
Migraine prophylaxis, by mouth, ADULT <65 years, 10 mg
once daily.
Dose Adjustment:
Hepatic Impairment:
Use with caution. Undergoes hepatic metabolism.
Precautions:
CNS effects e.g. (CNS depression); extrapyramidal
symptoms,
Endocrine effects e.g. mild but significant increase in
serum prolactin levels and menstrual irregularities;
Elderly (risk of extrapyramidal symptoms is increased).
Pregnancy (adverse events have been observed in animal
studies); lactation (not known if excreted in breastmilk).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common and Less Common: Drowsiness, anxiety,
depression, dizziness, extrapyramidal reaction, fatigue,
insomnia, motor dysfunction, sedation, sleep disorder,
vertigo, skin rash, weight gain, galactorrhea, menstrual
disease, heartburn, increased appetite, nausea,
stomach pain, vomiting, xerostomia, myalgia weakness.
Drug Interactions:
Monitor closely with:
Enhances CNS depressant effect of Flunarizine:

464
NERVOUS SYSTEM
Doxylamine, Dronabinol, Hydroxyzine, Magnesium
Sulfate, Minocycline, Mirtazapine, Nabilone
Enhances therapeutic effect (sedative effect) of the
following drugs:
Ethyl Alcohol Pramipexole, Ropinirole, Rotigotine
Increases risk of adverse or toxic effects of Flunarizine:
CNS Depressants, Rufinamide (sleepiness and
dizziness)
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
Avoid concomitant use with:
Enhances therapeutic effect of Flunarizine:
Droperidol, Methotrimeprazine [reduce flunarizine dose
by 50% with concomitant use] (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Hydrocodone [consider starting at a 20–30% lower
hydrocodone dose when used concomitantly],
Methotrimeprazine [reduce flunarizine dose by 50% with
concomitant use], Orphenadrine, Paraldehyde,
Perampanel, Sodium Oxybate, Tapentadol [start
tapentadol at one-third to one-half of the normal dose
when used concomitantly], Thalidomide Zolpidem (CNS
depressant effect)
Increases risk of adverse or toxic effects of the following
drugs:
Alvimopan [administer at least 7 days apart], Azelastine
(Nasal) (CNS depressant effect) Buprenorphine
Administration: Take with water at bedtime.
Allow 2 consecutive medication-free days each week to
decrease incidence of adverse effects. Discontinue use
if no significant improvement is seen after 3 months of
therapy.
Pregnancy Category: C
ATC Code: N07CA03
Rx PROPRANOLOL
Oral: 10 mg and 40 mg tablet (as hydrochloride)
Propranolol is a non-selective beta-adrenergic blocker that
competitively blocks response to beta1­ and
beta2­adrenergic stimulation. These result in decrease in
heart rate, myocardial contractility, blood pressure, and
myocardial oxygen demand.
Indication: Prophylaxis for migraine headache.
Contraindications: BP <50/30 mmHg; uncompensated CHF
(unless the failure is due to tachyarrhythmias being
treated with propranolol); cardiogenic shock; severe
sinus bradycardia; sick sinus syndrome or heart block
greater than first degree (except in the presence of a
functioning artificial pacemaker) ; heart rate <80 bpm;
bronchial asthma; bronchospasm.
Dose:
Migraine headache prophylaxis, by mouth, ADULT, initially
80 mg daily divided every 6–8 hours, increase by 20–40
mg/dose every 3–4 weeks to a maximum of 160–240
mg daily given in divided doses every 6–8 hours; if
satisfactory response is not achieved within 6 weeks of
starting therapy, withdraw drug gradually over several
weeks; CHILD >12 years, initially, 40 mg twice or thrice
daily, increase to weekly intervals up to 160 mg daily
(maximum, 240 mg daily); CHILD ≤12 years, 10–20 mg
twice or thrice daily.
Precautions:
WARNING: Do NOT withdraw abruptly, particularly in
patients with CAD. Gradually taper dose to avoid
acute tachycardia, hypertension, and/or ischemia.
Administration: To be taken on an empty stomach.
See Propranolol under Cardiac Therapy – Antiarrhythmics
(Class II Antiarrhythmics) in Chapter 3: Cardiovascular
System for other information.
Pregnancy Category: C
ATC Code: Not available
N
ANTIEPILEPTICS
BARBITURATES AND DERIVATIVES
Rx PHENOBARBITAL
Oral: 15 mg, 30 mg, 60 mg, and 90 mg tablet
Inj.: 120 mg/mL (130 mg/mL) (as sodium salt), 1 mL
ampule (IM, IV)
Phenobarbital is a long-acting barbiturate with sedative,
hypnotic, and anticonvulsant properties. It depresses the
sensory cortex, decrease motor activity, alter cerebellar
function, and produce drowsiness, sedation, and
hypnosis. In high doses, barbiturates exhibit
anticonvulsant activity.
Indications: Management of generalized tonic-clonic (grand
mal), status epilepticus, and partial seizures.
Contraindications: Marked hepatic impairment; dyspnea or
airway obstruction; porphyria (manifest and latent); intra-
arterial and SC administration; history of sedative /
hypnotic addiction; nephritic patients (large doses).
Dose:
NOTE: Individualize doses based on clinical response and
serum concentration. Once daily doses are usually
administered at bedtime in children and adolescents.
Status epilepticus, by IV infusion, ADULT, 20 mg/kg at 50 to
100 mg/minute, may repeat once after 10 minutes with
an additional 5–10 mg/kg if needed; may administer
additional boluses if in ICU [NOTE: Additional respiratory
support may be required particularly when maximizing
465

loading dose or if on concurrent sedative therapy. Repeat
doses administered sooner than 10–15 minutes may
not allow adequate time for peak CNS concentrations to
be achieved and may lead to CNS depression];
ADOLESCENT, CHILD, and INFANT, 20 mg/kg over 10
minutes or 50–100 mg/minute (maximum dose, 1,000
mg), may repeat dose after 15 minutes if needed
(maximum total dose, 40 mg/kg); or may administer an
additional 5–10 mg/kg once after 10 minutes.
Seizures, maintenance, by mouth, ADULT, 50–100 mg 2–3
times daily; ADOLESCENT, CHILD, and INFANT, 3–6
mg/kg daily; or
by mouth or IV injection, ADOLESCENT, 1–3 mg/kg daily
in 1–2 divided doses; CHILD >5 years, 2–3 mg/kg daily
in 1–2 divided doses; CHILD ≤5 years and INFANT, 3–5
mg/kg daily in 1–2 divided doses.
Dose Adjustment:
Geriatric:
Initiate at the lowest recommended dose.
Renal Impairment:
In CrCl <10 mL/minute, administer ever 12–16 hours.
In patients under hemodialysis, administer dose before
dialysis and 50% of the dose after dialysis.
In patients under peritoneal dialysis, administer 50% of
normal dose.
N
Hepatic Impairment:
Reduce doses. Phenobarbital exposure is increased with
hepatic impairment. Use with caution.
Precautions:
NOTE: Phenobarbital requires an S-2 license for physicians
to be able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense it. To
be prescribed and dispensed through Yellow Rx. Only one
(1) drug preparation shall be prescribed in one single
prescription form. Partial filling allowed. STRICTLY NO
REFILL.
CNS depression; paradoxical stimulatory response (e.g.,
agitation and hyperactivity); depression; suicidal
tendencies; Hypotension; Respiratory depression;
Hepatic and Renal impairment; hypoadrenalism;
Substance abuse (e.g., drug dependence; tolerance)
Use with caution in
Debilitated patients; Elderly (at risk of overdose at low
doses; increased risk of developing tolerance to sleep
effects; increased risk of physical dependence; may
induce paradoxical stimulation, cause or aggravate
depression and confusion); Children (increased risk for
paradoxical stimulatory response).
Pregnancy (Incidence of fetal abnormalities), lactation
(infantile spasms and other withdrawal symptoms may
occur)
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common and Less Common: Bradycardia, syncope,
hypotension, agitation, anxiety, ataxia, CNS excitation or
depression, confusion, dizziness, drowsiness,
466
NERVOUS SYSTEM
hallucinations, “hangover” effect, headache,
hyperkinesia, impaired judgment, insomnia, lethargy,
nervousness, nightmares, somnolence, exfoliative
dermatitis, rash, Stevens-Johnson syndrome, nausea,
vomiting, constipation, agranulocytosis, megaloblastic
anemia, thrombocytopenia, pain at injection site,
thrombophlebitis (IV), oliguria, laryngospasm, respiratory
depression, hypoventilation, apnea (rapid IV), gangrene.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect (CNS depressant effect) of
Phenobarbital:
Antihistamines, Brimonidin (Topical), Doxylamine,
Dronabinol, Fosphenytoin, Magnesium Sulfate,
Minocycline, Nabilone, Phenytoin, Sedative / Hypnotics
Enhances therapeutic effect of the following drugs:
Ethyl Alcohol, Meperidin (CNS depressant effect)
Hypotensive Agents (hypotensive effect)
Pramipexole, Rotigotine (sedative effect)
Increases metabolism of Phenobarbital:
Pyridoxine, Rifamycin Derivatives
Increases metabolism of the following drugs:
Paracetamol, Propacetamol
Increases risk of adverse or toxic effects of Phenobarbital:
CNS Depressants
Cosyntropin (hepatotoxic effect)
Dapsone (Topical), Primidone
Increases risk of adverse or toxic effects of the following
drugs:
Paracetamol, Propacetamol (liver damage)
Nitric Oxide, Prilocaine, Sodium Nitrite
(methemoglobinemia)
Quinidine (hepatotoxic effect)
SSRIs (psychomotor impairment),
Thiazide Diuretics (orthostatic hypotensive effect)
Reduces therapeutic effect of the following drugs:
Paracetamol, Propacetamol
Avoid concomitant use with:
Decreases metabolism of Phenobarbital:
Chloramphenicol
Decreases serum concentration of Phenobarbital:
Cholestyramine Resin [administer phenobarbital at least
1 hour before or 4­6 hours after cholestyramine],
Mefloquine.
Decreases serum concentration of the following drugs:
Abiraterone Acetate, Afatinib [increase dose by 10mg as
tolerated then reduce to original dose 2–3 days after
stopping phenobarbital], Anti-hepaciviral Combination
Products, Apixaban, Aripiprazole [double oral dose and
closely monitor clinical response then reduce dose to
10–15 mg daily after discontinuing phenobarbital; avoid
concomitant use for more than 14 days with extended-
release injectable aripiprazole], Artemether
[dihydroartemisinin], Axitinib, Bedaquiline, Boceprevir,
Bortezomib, Cabozantinib, Canagliflozin [increase dose
to 300 mg daily in GFR >60 mL/min/1.73 m2 who
NERVOUS SYSTEM
tolerate canagliflozin 100 mg daily and require greater
glycemic control; consider alternatives in GFR 45–60
mL/min/1.73 m2], Ceritinib, Clarithromycin, Clozapine,
Cobicistat, Dabigatran Etexilate, Daclatasvir, Dasabuvir,
Dasatinib [consider increasing dose and monitor clinical
response and toxicity closely], Deferasirox [consider a
50% increase in initial dose], Dexamethasone
(Systemic), Dienogest [avoid use within 28 days of
phenobarbital], Dolutegravir, Doxorubicin
(Conventional), Doxycycline, Enzalutamide, Erlotinib [If
concomitant use cannot be avoided, increase dose by 50
mg increments every 2 weeks as tolerated, to a
maximum of 450 mg daily], Etoposide, Everolimus
[consider gradually increasing dose in 5 mg increments
from 10 mg daily to 20 mg daily], Exemestane [consider
using an increased dose of 50 mg daily when used
concomitantly], Felbamate [initiate at 1,200 mg daily in
3–4 divided doses and reduce phenobarbital dose by
20%], Gefitinib [increase dose to 500 mg daily when
used concomitantly, then resume 250 mg dose 7 days
after discontinuation of phenobarbital], Imatinib
[increase dose by at least 50% and closely monitor
clinical response], Irinotecan, Itraconazole, Ivabradine,
Ivacaftor, Ixabepilone [if concomitant use cannot be
avoided, gradually increase dose from 40 mg/m2 to 60
mg/m2 given as a 4-hour infusion]
Decreases serum concentration of the following drugs:
Lamotrigine, Lapatinib [if concomitant use cannot be
avoided, titrate lapatinib gradually from 1,250 mg daily
up to 4,500 mg daily for HER2 positive metastatic breast
cancer, or 1,500 mg daily up to 5,500 mg daily for HER2
positive breast cancer], Ledipasvir, Linagliptin,
Lopinavir, Lumefantrine, Macitentan,
Methylprednisolone, Mifepristone, Netupitant,
Nifedipine, Nilotinib, Nimodipine, Nintedanib,
Nisoldipine, Olaparib, Oxcarbazepine, Palbociclib,
Paliperidone, Pazopanib, Perampanel [increase starting
dose to 4 mg daily], Praziquantel, Quetiapine, Quinine,
Ranolazine, Regorafenib, Rilpivirine, Ritonavir,
Rivaroxaban, Roflumilast, Simeprevir, Sofosbuvir,
Sorafenib, Sunitinib, Tadalafil, Ticagrelor, Tofacitinib,
Tolvaptan, Ulipristal, Vemurafenib, Vincristine
(Liposomal), Voriconazole, Vortioxetine [consider
increasing dose to not more than 3 times the original
dose when used concomitantly for >14 days, return dose
to normal within 14 days of stopping phenobarbital]
Enhances therapeutic effect of Phenobarbital:
Droperidol Hydroxyzine, Sodium Oxybate, Tapentadol
[start at one-third to one-half of the normal dose] (CNS
depressant effect)
Enhances therapeutic effect of the following drugs:
Buprenorphine, Hydrocodone [consider starting with a
20–30% lower dose when used concomitantly],
Orphenadrine, Paraldehyde, Thalidomide, Zolpidem
(CNS depressant effect)
Increases metabolism of the following drugs:
Chloramphenicol, Cyclosporine (Systemic), TCAs, Vitamin
K Antagonists [e.g., Warfarin]
Increases risk of adverse or toxic effects of Phenobarbital:
Somatostatin Acetate (sedative effects)
Increases risk of adverse or toxic effects of the following
drugs:
Azelastine, Nasal (CNS depressant effect)
Increases serum concentration of Phenobarbital:
Clarithromycin, Felbamate [initiate at 1,200 mg daily in
3–4 divided doses and reduce phenobarbital dose by
20%], Oxcarbazepine, Quinine
Increases serum concentration of Clarithromycin
Reduces therapeutic effect of Phenobarbital:
Mefloquine
Reduces therapeutic effect of the following drugs:
Contraceptives [Estrogens, Progestins], Steroidal
Hormones
TEST INTERACTION. Interferes with assay of LDH.
Administration:
For oral administration, may be taken with or without
food.
For IM administration, inject deep into muscle. Do NOT
exceed 5 mL per injection site due to potential for tissue
irritation.
N
For IV administration, administer at 50–100 mg/minute
Avoid rapid IV administration at >60 mg/minute in adults
and >30 mg/minute in children.
Avoid extravasation.
Do NOT administer by SC or intra-arterial injection.
Do NOT discontinue abruptly because of the possibility of
increasing seizure frequency. Withdraw therapy
gradually to minimize the potential of increased seizure
frequency, unless safety concerns require a more rapid
withdrawal.
NOTE: May cause loss in vitamin D due to malabsorption.
Increase intake of food rich in vitamin D. Vitamin D
and/or calcium supplementation may be necessary.
Pregnancy Category: B / D (product-specific)
ATC Code: N03AA02
HYDANTOIN DERIVATIVES
Rx PHENYTOIN
Oral: 100 mg capsule (as sodium salt)
30 mg/5 mL suspension, 120 mL (as sodium salt)
125 mg/5 mL suspension, 120 mL (as sodium salt)
Inj.: 50 mg/mL solution (as sodium salt), 2 mL and 5 mL
ampule (IV)
A hydantoin antiepileptic drug that works primarily through
the reduction of hyperexcitability on sodium channels. It
stabilizes neuronal membranes and decreases seizure
activity.
467

Indications: Management of generalized tonic-clonic (grand
mal), complex partial seizures; prevention of seizures
following neurosurgery.
Contraindications: Concurrent use of delavirdine; sinus
bradycardia, sinoatrial block, second­ and third-degree
heart block, Adams-Stokes syndrome (IV).
Dose:
Status epilepticus, by IV injection, ADULT, initially 10 to 15
mg/kg loading dose at a maximum rate of 50
mg/minute, may give an additional 5–10 mg/kg 10
minutes after the loading dose; or 10–15 mg/kg at a
maximum rate of 50 mg/minute;
ADOLESCENT, CHILD, and INFANT, initially 15–20 mg/kg
loading dose at a maximum rate of 1–3 mg/kg/minute
or 50 mg/minute, whichever is slower, may give an
additional 5–10 mg/kg 10 minutes after the loading
dose; or 15–20 mg/kg loading dose, followed by
maintenance therapy.
Anticonvulsant, by IV injection, ADULT, 20 mg/kg loading
dose at a maximum rate of 50 mg/minute, may give an
additional dose of 5–10 mg/kg 10 minutes after the
loading dose; or 10 to 15 mg/kg at a max. rate of 50
mg/minute;
Anticonvulsant, maintenance, by mouth or by IV injection,
ADULT and ADOLESCENT, 100 mg every 6–8 hours;
N
CHILD and INFANT, initially 5 mg/kg daily in 2–3 divided
doses; usual dose range, 4–8 mg/kg daily (maximum
daily dose, 300 mg or 8–10 mg/kg daily in divided
doses).
Dose Adjustment:
NOTE: Phenytoin base (e.g., oral suspension) contains ~8%
more drug than phenytoin sodium (~92 mg base is
equivalent to 100 mg phenytoin sodium). Dosage
adjustments and closer serum monitoring may be
necessary when switching dosage forms.
Geriatric:
Clearance is decreased in the elderly. Lower doses or lessen
dosing frequency.
Hepatic Impairment:
In cirrhosis, clearance may be substantially reduced and
plasma level monitoring with dose adjustment is
advisable. Free phenytoin levels should be monitored
closely.
Obesity:
Loading dose = 14 mg/kg IBW + 19 mg/kg weight in excess
of IBW
468
NERVOUS SYSTEM
Precautions:
WARNING: Cardiovascular risk. The rate of IV
administration should not exceed 50 mg/min in
adults and 1–3 mg/kg per min (or 50 mg/min,
whichever is slower) in pediatric patients because
of the risk of severe hypotension and cardiac
arrhythmias. Careful cardiac monitoring is needed
during and after administering IV phenytoin.
Reduction in rate of administration or
discontinuation of dosing may be needed if
cardiovascular toxicities are observed below the
recommended infusion rate.
Hazardous agent. Use appropriate precautions for
handling and disposal.
Blood dyscrasias (may be fatal); porphyria; bone effects
(e.g., decreased bone mineral density and bone
fractures); cardiovascular events (e.g., hypotension and
severe cardiac arrhythmias with rapid administration);
cardiovascular disease; dermatologic reactions;
hypersensitivity; suicidal ideation; hepatic impairment;
hypoalbuminemia; hypothyroidism; Asian ancestry
(variant HLA-B*1502 may be at an increased risk of
developing SJS and/or TEN); debilitated patients.
Elderly (higher incidence of adverse effects; avoid use in
older adults with a history of falls or fractures as it may
cause syncope, impaired psychomotor function, or
ataxia).
Pregnancy (may cause fetal hydantoin syndrome; crosses
the placenta; increased risk of congenital malformations
and adverse outcomes may occur following in utero
phenytoin exposure); lactation (excreted in breastmilk;
use with caution).
Adverse Drug Reactions:
Common: Atrial conduction depression (IV), bradycardia (IV),
circulatory shock (IV), cardiac arrhythmia (IV),
hypotension (IV), periarteritis nodosa, ventricular
conduction depression (IV), ventricular fibrillation (IV),
confusion, dizziness, ataxia, drowsiness, decreased
coordination, nystagmus, headache, slurred speech,
mood changes, insomnia, nervousness, paresthesia,
peripheral neuropathy (chronic treatment), twitching,
vertigo, bullous dermatitis, exfoliative dermatitis,
hypertrichosis, morbilliform rash, scarlatiniform rash,
skin or other tissue necrosis (IV administration), skin
rash, toxic epidermal necrolysis, hyperglycemia, vitamin
D deficiency (chronic treatment), constipation, dysgeusia
(metallic taste), gingival hyperplasia, nausea,
enlargement of facial features (lips), vomiting, Peyronie's
disease, granulocytopenia, Hodgkin lymphoma,
agranulocytosis, immunoglobulin abnormality,
leukopenia, lymphadenopathy, macrocytosis,
megaloblastic, anemia, malignant lymphoma,
pancytopenia, pseudolymphoma, purpuric dermatitis,
thrombocytopenia, acute hepatic failure, hepatitis,
anaphylaxis, DRESS syndrome, Injection site reaction
("purple glove syndrome"; edema, discoloration, and pain
distal to injection site), local inflammation, irritation,
tissue necrosis (IV), localized tenderness (IV), coarsening
of facial features, osteomalacia, systemic lupus
erythematosus, tremor, fever, tissue sloughing (IV)
Less Common: Dyskinesia, hepatotoxicity (idiosyncratic)
NERVOUS SYSTEM
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect (CNS depressant effect) of
Phenytoin:
Doxylamine, Dronabinol, Ethosuximide, Hydroxyzine,
Magnesium Sulfate, Minocycline, Nabilone
Enhances therapeutic effect of the following drugs:
Ethyl Alcohol, Phenobarbital (CNS depressant effect)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Neuromuscular-Blocking Agents, Nondepolarizing
(neuromuscular-blocking effect)
Increases metabolism of Phenytoin:
Pyridoxine
Increases metabolism of Primidone
Increases risk of adverse or toxic effects of Phenytoin:
Carbonic Anhydrase Inhibitors [except Brinzolamide]
(osteomalacia or rickets)
CNS Depressants, Dapsone (Topical), Dexketoprofen
Cosyntropin (hepatotoxic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Paracetamol, Propacetamol (hepatotoxicity) Lithium,
Nitric Oxide, Prilocaine, Sodium Nitrite
(methemoglobinemia)
SSRIs (psychomotor impairment)
Reduces therapeutic effect of Phenytoin:
Ciprofloxacin (Systemic)
Avoid concomitant use with:
Paracetamol, Levodopa, Loop Diuretics, Neuromuscular-
Blocking Agents (Nondepolarizing), Propacetamol
Decreases serum concentration of Phenytoin:
Carbamazepine, Dexamethasone (Systemic),
Enzalutamide, Mefloquine, Rifampin, Ritonavir,
Theophylline Derivatives [except Dyphylline],
Decreases serum concentration of the following drugs:
Abiraterone Acetate, Afatinib [increase dose by 10 mg as
tolerated then reduce to original dose 2–3 days after
stopping phenytoin], Antihepaciviral Combination
Products, Apixaban, Aripiprazole [double oral dose and
closely monitor clinical response then reduce the dose to
10–15 mg daily after discontinuing phenytoin; avoid
concomitant use for >14 days with extended-release
injectable aripiprazole], Artemether, Axitinib,
Bedaquiline, Boceprevir, Bortezomib, Cabozantinib,
Canagliflozin [increase dose to 300 mg daily in GFR >60
mL/min/1.73 m2 who tolerate canagliflozin 100 mg daily
and require greater glycemic control; consider
alternatives in GFR 45–60 mL/min/1.73 m2],
Carbamazepine, Caspofungin, Ceritinib, Clarithromycin,
Clozapine, Cobicistat, Crizotinib, Dabigatran Etexilate,
Daclatasvir, Dasabuvir, Dasatinib [consider increasing
dose and monitor clinical response and toxicity closely],
Deferasirox [consider a 50% increase in initial dose],
Dexamethasone (Systemic), Dienogest [avoid use within
28 days of phenobarbital], Disulfiram, Dolutegravir,
Doxorubicin (Conventional)
Decreases serum concentration of the following drugs:
Everolimus [consider gradually increasing dose in 5 mg
increments from 10 mg daily to 20 mg daily],
Exemestane [consider using an increased dose of 50 mg
daily when used concomitantly], Felbamate [reduce
phenytoin dose by 20%], Gefitinib [increase dose to 500
mg daily when used concomitantly, then resume 250 mg
dose 7 days after discontinuation of phenytoin],
[consider increasing guanfacine dose by 2-fold when
used concomitantly, titrate the guanfacine dose up to a
maximum of 8 mg daily], HMG-CoA Reductase Inhibitors
[except Pitavastatin, Rosuvastatin], Imatinib [increase
dose by at least 50% and closely monitor clinical
response], Irinotecan, Itraconazole, Ivabradine,
Ivacaftor, Ixabepilone [if concomitant use cannot be
avoided, gradually increase dose from 40 mg/m2 to 60
mg/m2 given as a 4-hour infusion], Lamotrigine,
Lapatinib [if concomitant use cannot be avoided, titrate
gradually from 1,250 mg daily up to 4,500 mg daily for
HER2 positive metastatic breast cancer, or 1,500 mg
daily up to 5,500 mg daily for hormone receptor/HER2
positive breast cancer], Ledipasvir, Linagliptin, Lopinavir,
Lumefantrine, Lurasidone, Macitentan, Maraviroc
[increase dose to 600 mg twice daily when used with
phenobarbital], Methylprednisolone, Metyrapone,
Mianserin, Mifepristone, Netupitant, Nifedipine,
Nilotinib, Nimodipine, Nintedanib, Nisoldipine, Olaparib,
Oxcarbazepine, Palbociclib, Paliperidone, Panobinostat,
N
Paritaprevir, Pazopanib, Perampanel [increase starting
dose to 4 mg daily], Ponatinib, Praziquantel, Quetiapine
[reduce dose within 7–14 days of phenytoin], Quinine,
Ranolazine, Regorafenib, Rilpivirine, Ritonavir,
Rivaroxaban, Roflumilast, Simeprevir, Sirolimus,
Sofosbuvir, Sorafenib, Sunitinib, Tadalafil, Temsirolimus
[if concomitant use cannot be avoided, consider
increasing dose to 50 mg weekly], Teniposide,
Theophylline Derivatives [except Dyphylline], Ticagrelor,
Tipranavir, Tofacitinib, Tolvaptan, Topotecan, Toremifene
Decreases serum concentration of the following drugs:
Trimethoprim, Ulipristal, Vandetanib, Vemurafenib,
Vincristine (Liposomal), Voriconazole, Vortioxetine
[consider increasing dose to no more than 3 times the
original dose when used concomitantly for more than 14
days, return dose to normal within 14 days of stopping
phenobarbital]
Enhances therapeutic effect of Phenytoin:
Droperidol, Sodium Oxybate, Tapentadol [start at one-
third to one-half of the normal dose] (CNS depressant
effect)
Enhances therapeutic effect of the following drugs:
Buprenorphine Hydrocodone [consider starting with a
20–30% lower dose when used concomitantly], Metho
[reduce codeine dose by 50% with concomitant use],
Orphenadrine, Paraldehyde, Thalidomide, Vitamin K
Antagonists e.g., Warfarin (anticoagulant effect),
Zolpidem (CNS depressant effect)
Increases metabolism of Cyclosporine (Systemic)
Increases risk of adverse or toxic effects of Phenytoin:
Cimetidine
469

Increases risk of adverse or toxic effects of the following
drugs:
Azelastine, Nasal (CNS depressant effect)
Increases serum concentration of Phenytoin:
Capecitabine, Cimetidine, Clarithromycin,
Dexamethasone (Systemic), Efavirenz, Felbamate
[reduce phenytoin dose by 20%], Fluconazole,
Fluorouracil (Systemic), Isoniazid, Nifedipine,
Oxcarbazepine, Sulfamethoxazole, Tegafur,
Trimethoprim, Vitamin K Antagonists [e.g., Warfarin]
Increases serum concentration of Clarithromycin
Reduces therapeutic effect of Phenytoin:
Mefloquine
Reduces therapeutic effect of the following drugs:
Contraceptives [Estrogens, Progestins]
FOOD INTERACTION
Ethanol. Inhibits metabolism of phenytoin and may also
increase CNS depression. Chronic ethanol use
stimulates metabolism of phenytoin.
Folic acid. May decrease mucosal uptake of folic acid.
Administer prophylactic doses of folic acid and
cyanocobalamin to avoid folic acid deficiency and
N
megaloblastic anemia. 0.5 mg folic acid daily has been
shown to reduce the incidence of phenytoin-induced
gingival overgrowth in children. However, folate
supplementation may increase seizures in some patients
(dose dependent).
Calcium. Hypocalcemia has been reported in patients
taking prolonged high-dose therapy. administer an
additional 4000 units/week of vitamin D to prevent
hypocalcemia.
Vitamin D. Phenytoin interferes with vitamin D
metabolism and osteomalacia. Consider vitamin D
supplementation.
Administration:
For oral administration, preferably take on an empty
stomach. Taking with food may decrease phenytoin
serum concentrations. For oral suspension, shake well
prior to use.
Tube feedings decrease bioavailability. Absorption is
impaired when given concurrently to patients who are
receiving continuous nasogastric feedings. Hold tube
feedings 1–2 hours before and 1–2 hours after
phenytoin. Divide daily dose and withhold administration
of supplements for 1–2 hours before and after each
phenytoin dose to resolve this interaction.
For IV administration, may be administered by direct IV
injection. Administer by infusion pump either undiluted
or diluted in normal saline as an IV piggyback (IVPB) to
prevent exceeding the maximum infusion rate. The
maximum rate of IV administration is 50 mg/minute in
adults and 0.5 to 1 mg/minute in neonates. An in­line
0.22 to 0.55-micron filter is recommended for IVPB
solutions due to the potential for precipitation of the
solution.
470
NERVOUS SYSTEM
Avoid extravasation. Ensure proper needle or catheter
placement prior to and during IV infusion. Following IV
administration, inject NS through the same needle or IV
catheter to prevent irritation.
If extravasation occurs, stop infusion immediately and
disconnect. Leave needle or cannula in place. Gently
aspirate extravasated solution. Do NOT flush the line.
Remove needle or cannula and elevate the extremity
Pregnancy Category: D
ATC Code: N03AB02
BENZODIAZEPINE DERIVATIVES
Rx CLONAZEPAM
Oral: 500 mcg and 2 mg tablet
A benzodiazepine derivative that suppresses the spike-and-
wave discharge in absence seizures by depressing nerve
transmission in the motor cortex. It enhances the activity
of GABA in the CNS.
Indications: Monotherapy or adjunct therapy in the
treatment of Lennox-Gastaut syndrome (petit mal
variant), akinetic, and myoclonic seizures; absence
seizures (petit mal) unresponsive to succinimides.
Contraindications: Significant liver disease; acute narrow-
angle glaucoma.
Dose:
Seizure disorders, by mouth, ADULT, ADOLESCENT, and
CHILD >10 years or ≥30 kg, initially 1.5 mg daily in 3
divided doses, may increase by 0.5–1 mg every third day
until seizures are controlled or adverse effects seen
(maximum, 20 mg daily); usual maintenance dose, 2–8
mg daily in 1–2 divided doses (maximum, 20 mg daily);
CHILD <10 years or <30 kg, initially 0.01–0.03 mg/kg
daily in 3 divided doses (maximum: 0.2 mg/kg daily).
Dose Adjustment:
Geriatric:
Initiate with low doses and observe closely.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Anterograde amnesia; CNS depression; paradoxical
reactions; suicidal ideation; depression; drug abuse;
Post-traumatic Stress Disorder.
Renal and hepatic impairment; respiratory disease (e.g.,
respiratory depression and increase in salivation);
glaucoma.
Debilitated patients; fall risk.
Elderly (increased risk of impaired cognition, delirium, falls,
fractures, and motor vehicle accidents); children
(increased risk for paradoxical reactions).
NERVOUS SYSTEM
Pregnancy (possible increased risk of birth defects when
taken during pregnancy, especially during the first
trimester; infants may experience withdrawal effects
when administered late in pregnancy; neonatal
flaccidity); lactation (excreted in breastmilk; drowsiness,
lethargy, or weight loss in nursing infants have been
observed following maternal use).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Edema (ankle or facial), palpitation, amnesia,
ataxia, behavior problems, coma, confusion, impaired
coordination, depression, dizziness, drowsiness,
emotional lability, fatigue, fever, headache, hysteria,
insomnia, reduced intellectual ability, hallucinations,
memory disturbance, nervousness, paradoxical
reactions (including agitation, anxiety, excitability,
hostility, aggressive behavior, irritability, nightmares,
sleep disturbance, vivid dreams), psychosis, slurred
speech, somnolence, vertigo, hair loss, hirsutism, skin
rash, dysmenorrhea, increased or decreased libido,
abdominal pain, anorexia, increased or decreased
appetite, dehydration, constipation, diarrhea,
encopresis, coated tongue, gastritis, gum soreness,
nausea, weight changes, xerostomia, Colpitis, dysuria,
delayed ejaculation, enuresis, micturition frequency,
nocturia, urinary retention, UTI, impotence, anemia,
eosinophilia, leukopenia, thrombocytopenia,
hepatomegaly, Choreiform movements, dysarthria,
hypotonia, muscle weakness, myalgia, tremor, blurred
vision, diplopia, abnormal eye movements, nystagmus,
bronchitis, chest congestion, cough, hypersecretions,
pharyngitis, respiratory depression, rhinitis, respiratory
tract infection, rhinorrhea, sinusitis, shortness of breath,
allergic reaction, dysdiadochokinesis, “glassy-eyed”
appearance, lymphadenopathy, flu-like syndrome,
aphonia, hemiparesis.
Less Common: Apathy, burning skin, chest pain,
depersonalization, hyperactivity, excessive dreaming,
dyspnea, hypoesthesia, increased oppositional behavior,
postural hypotension, infection, migraine, organic
disinhibition, pain, paresthesia, paresis, periorbital
edema, polyuria, suicidal attempt, suicide ideation, thick
tongue, twitching, visual disturbance, xerophthalmia.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Clonazepam:
Brimonidine (Topical), Doxylamine, Dronabinol,
Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone,
Vigabatrin (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Ethyl Alcohol, Mirtazapine (CNS depressant effect)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Increases risk of adverse or toxic effects of Clonazepam:
CNS Depressants
Cosyntropin (hepatotoxic effect)
Rufinamide (sleepiness and dizziness)
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
Avoid concomitant use with:
Decreases serum concentration of Clonazepam:
Dafrafenib, Deferasirox, Mitotane
Enhances therapeutic effect of the following drugs:
Buprenorphine, Hydrocodone [consider starting with a
20–30% lower dose when used concomitantly],
Methadone, Orphenadrine, Paraldehyde, Perampanel,
Sodium Oxybate, Thalidomide, Zolpidem (CNS
depressant effect)
Enhances therapeutic effect of Clonazepam:
Droperidol
Tapentadol (CNS depressant effect) [start at one-third to
one-half of the normal dose]
Increases risk of adverse or toxic effects of Clonazepam:
Olanzapine
Increases risk of adverse or toxic effects of the following
drugs:
Azelastine (Nasal), Clozapine (CNS depressant effect)
Increases serum concentration of Clonazepam:
Fusidic Acid (Systemic), Idelalisib, Mifepristone
Reduces therapeutic effect of Clonazepam:
Theophylline Derivatives
N
Administration: Swallow whole with water. Administer one
dose at bedtime to reduce somnolence.
Pregnancy Category: D
ATC Code: N03AE01
NOTE: Clonazepam requires an S-2 license for physicians to
be able to prescribe it and an S-1 license with a triplicate
prescription for pharmacists to dispense it.
CARBOXAMIDE DERIVATIVES
Rx CARBAMAZEPINE
Oral: 200 mg tablet
200 mg and 400 mg MR tablet
100 mg/5 mL syrup, 120 mL
Carbamazepine is an iminostilbene that limits the firing of
action potentials evoked by a sustained depolarization in
cortical neurons. It acts by limiting influx of sodium ions
or by slowing the rate of recovery of Na+ channels.
Indications: Management of epilepsy; complex or simple
partial seizures with or without secondary generalization;
generalized tonic-clonic seizures; mixed forms of
seizures.
NOTE: NOT effective in absence seizures (petit mal) and
myoclonic seizures.
Contraindications: Atrioventricular block; bone marrow
depression; acute intermittent porphyria; combination
with MAO Inhibitors e.g., Phenezline, Selegeline.
471
 NERVOUS SYSTEM

Dose: 29.1–39 kg 1,200 mg daily

NOTE: MR tablets are designed to be taken twice daily due >39 kg 1,800 mg daily
to the controlled release of the active substance. CHILD <20 kg, initiate at 16–20 mg/kg, titrate to the
maximum maintenance dose over 2–4 weeks, not to
Epilepsy, by mouth, ADULT, initially 100–200 mg once or
exceed 60 mg/kg daily twice daily.
twice daily, slowly raise until an optimal response is
Seizures, monotherapy, by mouth, ADULT, initially 600 mg
obtained (generally at 400 mg twice or thrice daily);
twice daily, may increase by 300 mg daily every third day
ADOLESCENT >12 years, 5–10 mg/kg daily divided every
to a dose of 1,200 mg daily;
12 hours then increase gradually to maintenance of 10– CHILD 4–16 years, initially 8–10 mg/kg daily twice daily,
30 mg/kg daily divided every 8 or 6 hours (maximum, 1 increase by 5 mg/kg daily every third day to the
g daily for 12–15 years old and 1.2 g daily if >16 years recommended daily dose as follows:
old); CHILD 6–12 years, initially 10 mg/kg daily in 2–4
divided doses, increase by 5 mg/kg weekly until
From dose To dose
therapeutic levels; CHILD <5 years, initially 5 mg/kg daily Weight in kg
(mg daily) (mg daily)
in 2–4 divided doses, increase every 5–7 days by 5
20 600 900
mg/kg based on response.
25 900 1,200
Administration: May be taken during, after, or between 30 900 1,200
meals. For the syrup formulation, shake well before use. 35 900 1,500
Administer tablets with little liquid. Swallow MR tablets 40 900 1,500
unchewed with a little liquid.
45 1,200 1,500
For existing anticonvulsant therapy, add carbamazepine 50 1,200 1,800
gradually while existing anticonvulsant is maintained or 55 1,200 1,800
gradually decreased, except with phenytoin, which may 60 1,200 2,100
need to be increased or decreased depending on 65 1,200 2,100
phenytoin serum levels.
70 1,500 2,100
N

See Carbamazepine under Analgesics – Other Analgesics

and Antipyretics: Drugs for Neuropathic Pain in Chapter
10: Nervous System for other information.
Pregnancy Category: D
ATC Code: N03AF01
Rx OXCARBAZEPINE
Oral: 300 mg and 600 mg tablet
60 mg/mL, 100 mL and 250 mL suspension
Oxcarbazepine is a prodrug related to carbamazepine. It
works by binding to the open channel conformation of
voltage-sensitive sodium channels at a site within the
channel itself at the α subunit.
Indication: Management of partial-onset seizure in adults
and children and partial seizure with secondary
generalization.
Dose:
NOTE: Oral suspension and tablets may be interchanged at
equal doses.
Seizures, adjunct therapy, by mouth, ADULT, initially 600 mg
twice daily, may increase up to a maximum of 600 mg
daily at weekly intervals if clinically indicated;
recommended daily dose is 1,200 mg;
CHILD 2–16 years, initially 8–10 mg/kg twice daily, not
to exceed 600 mg daily, titrate gradually over 2 weeks to
the target maintenance dose, as follows:
Weight Target maintenance dose
20–29 kg 900 mg daily
Dose Adjustment:
Renal Impairment:
In CrCl <30 mL/minute, initiate at ½ the usual starting dose
and increase slowly to achieve the desired clinical
response.
Precautions:
Hyponatremia; anaphylactic reactions and angioedema
(eg., laryngeal edema can be fatal); serious
dermatological reactions (some fatal); bone metabolism.
Suicidal behavior and ideation; neuropsychiatric adverse
events; DRESS or multi-organ hypersensitivity (some
fatal); hematologic events; glaucoma; hyponatremia.
HLA-B*1502 allele carrier (e.g., SJS or toxic epidermal
necrolysis (SJS/TEN) during treatment).
Elderly (increased incidence of adverse effects).
Pregnancy (no adequate and well-controlled studies);
lactation (excreted in breastmilk).
Adverse Drug Reactions:
Common: Dizziness, somnolence, diplopia, fatigue, nausea,
vomiting, abdominal pain, abnormal vision, ataxia,
tremor, dyspepsia, abnormal gait, nystagmus,
maculopapular rash, convulsions, rash, status
epilepticus, fatigue, edema, weight gain, asthenia,
diarrhea, hypotension, hyponatremia, sprains, strains,
muscle weakness, gastritis, constipation, acne,
headache, nervousness, agitation, dysmetria, abnormal
coordination, speech disorder, rhinitis, dry mouth,
toothache, lymphadenopathy, rectal hemorrhage,
infection, thirst, emotional lability, hypoesthesia,
pharyngitis, purpura, earache, ear infection, vaginitis,
micturition frequency.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of CNS Depressants

472
NERVOUS SYSTEM

Avoid concomitant use with: mg/kg daily [NOTE: In patients previously receiving
Decreases serum concentration of Hormonal valproic acid therapy, divalproex sodium is initiated at
contraceptives the same daily dose and dosing schedule].
Dose Adjustment:
Increases risk of adverse or toxic effects of the following Geriatric:
drugs: Lower initial dose and slower increase in dosage. Regularly
MAO Inhibitors (serotonin syndrome) monitor fluid and nutritional intake and increased
somnolence and other side effects.
Reduces therapeutic effect of Hormonal contraceptives
Renal Impairment:
Administration: May be taken with or without food. No dose adjustment necessary. May cause misleading
Administer in a twice-a-day regimen. results in therapeutic drug monitoring due to substantial
reduction of protein binding.
Keep out of sight and reach of children.
Hepatic Impairment:
Pregnancy Category: C Avoid if possible, hepatotoxicity and hepatic failure may
occasionally occur, usually in the first six months.
ATC Code: N03AF02
Precautions:
WARNING: Hepatotoxicity. Hepatic failure resulting in
FATTY ACID DERIVATIVES fatalities has occurred, usually during the first six
months of treatment. Increased risk for fatal
hepatotoxicity is seen in children <2 years old,
Rx VALPROIC ACID patients on multiple anticonvulsants, congenital
metabolic disorders, severe seizure disorders
Oral: 250 mg and 500 mg tablet (as divalproex sodium) accompanied by mental retardation, or organic
250 mg and 500 mg extended release tablet (as brain disease, hereditary neurometabolic
divalproex sodium) syndromes. Monitor for and immediately report

N
500 mg controlled release tablet (333 mg sodium non-specific symptoms such as malaise,
valproate + 145 mg valproic acid) weakness, lethargy, facial edema, anorexia, and
200 mg/5 mL syrup, 100 mL bottle (as sodium vomiting that may precede hepatotoxicity. Loss of
valproate) seizure control may also be seen. Discontinue
250 mg/5 mL syrup, 120 mL (as valproic acid) immediately in the presence of suspected or
Inj.: 500 mg/5 mL, 5 mL vial (IV infusion) (as valproic acid) apparent significant hepatic dysfunction.
Pancreatitis. May be life-threatening, some
Valproate is a simple branched-chain carboxylic acid that hemorrhagic and progressed rapidly from initial
inhibits sustained repetitive firing of cortical neurons by symptoms to death. Monitor for and immediately
prolonging recovery of voltage-activated Na+ channels report symptoms of abdominal pain, nausea,
from inactivation. Its activity is thought to be related to vomiting, and/or anorexia. Measure plasma
the elevated concentrations of gamma-aminobutyric amylase immediately if with abdominal pain.
acid (GABA) in the brain. Discontinue drug immediately.
Teratogenicity. May cause neural tube defects. Do
Indications: Management of status epilepticus and other NOT use in women of child-bearing age unless
epilepsies when oral dosage forms cannot be utilized or essential.
when IV anticonvulsants are warranted.
Hepatotoxicity (liver function tests, e.g., SGPT/ALT,
NOTE: It is an effective and safe alternative (less
prothrombin time, must be done pre-treatment and
hypotension, cardiac arrhythmia, sedation) for status
periodically especially within the first 6 months and in at-
epilepticus.
risk patients).
Urea cycle disorders (hyperammonemic encephalopathy,
Contraindications: Hepatic disease or significant hepatic
sometimes fatal)
dysfunction; urea cycle disorders; hereditary
Thrombocytopenia (platelet counts and coagulation tests,
neurometabolic syndromes caused by DNA mutations of
should be done before treatment and periodically
the mitochondrial DNA polymerase-gamma (POLG) gene
thereafter particularly during the first six months of
(e.g., Alpers Huttenlocher Syndrome); active pancreatitis.
therapy, and prior to surgery or anticoagulant therapy;
discontinue at first signs of hemorrhage, bruising, or
Dose:
disordered coagulation).
Epilepsy, by mouth, ADULT, initiate at 10–15 mg/kg daily
Suicidal thoughts and behavior (monitor and immediately
(give in 2–3 divided doses if total daily dose exceeds 250
report any unusual change in mood or behavior).
mg), gradually increase by 5–10 mg/kg per week to
Children (children <2 years are at increased risk for fatal
achieve optimal clinical response; usual maintenance
hepatotoxicity; use with extreme caution in this age
dose is 20–30 mg/kg daily; doses above 60 mg/kg daily
group and as a sole agent).
is not recommended (therapeutic serum range, 50 to
Pregnancy (may cause teratogenic effects, such as neural
100 micrograms/mL); ADULT and CHILD >12 years,
tube defects, e.g., spina bifida; must be considered in
maximum dose is 2.5 grams daily in divided doses;
women of child-bearing age only after the risks have
CHILD <12 years and >20 kg, maximum dose is 35

473

been carefully weighed against the benefits; immediately
refer to a specialist).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
NOTE: The frequency of adverse effects, particularly
elevated liver enzymes and thrombocytopenia, can be
dose-related.
Common: Nausea, vomiting, abdominal pain, diarrhea,
anorexia, dyspepsia, elevated AST or ALT, somnolence,
dizziness, tremor, insomnia, nervousness, depression,
anxiety, amnesia, mood changes, hallucinations,
nystagmus, blurred vision, amblyopia, ataxia, vertigo,
thrombocytopenia, increased bleeding time, petechiae
or ecchymosis, asthenia, flu syndrome infection,
bronchitis, pharyngitis, rhinitis, headache, transient
alopecia, skin rash, increased appetite, weight gain,
tinnitus.
Less Common: Irregular menses, secondary amenorrhea.
Rare: Hepatic failure (may be fatal), pancreatitis,
hyperammonemia, SJS, toxic epidermal necrolysis.
Drug Interactions:
Monitor closely with:
N
Decreases metabolism of the following drugs:
Diazepam, Phenobarbital, Phenytoin
Decreases plasma clearance of the following drugs:
Amitriptyline, Nortriptyline
Increases plasma clearance of Valproate Disodium:
Rifampin
Increases risk of adverse or toxic effects of Phenobarbital
(neurologic toxicity, including CNS depression)
Avoid concomitant use with:
Reduces therapeutic effect of Valproate Disodium:
Carbapenem Antibiotics e.g., Imipenem, Meropenem,
Ertapenem (loss of seizure control)
Administration: Swallow tablets whole. Do not chew or
crush. Taken preferably after food intake. If dose is
skipped, do not double the next dose.
CONVERSION TO MONOTHERAPY. Reduce concomitant anti-
epilepsy drug dose by approximately 25% every 2 weeks.
Reduction may be started at initiation of therapy or
delayed by 1–2 weeks if there is a concern that seizures
are likely to occur with a reduction.
AS ADJUNCT TO THERAPY. May be added to the regimen at
an initial oral dose of 10–15 mg/kg daily (give in 2–3
divided doses if total daily dose exceeds 250 mg), may
increase dose 5–10 mg/kg daily at 1-week intervals to
achieve optimal clinical response (maximum 60 mg/kg
daily or less with a therapeutic serum range of 50 to 100
micrograms/mL).
Pregnancy Category: D
ATC Code: N03AG01
474
NERVOUS SYSTEM
OTHER ANTIEPILEPTICS
Rx DIAZEPAM
Oral: 5 mg tablet
Inj.: 5 mg/mL, 2 mL ampule (IM, IV)
Diazepam is a long-acting benzodiazepine with
anticonvulsant, anxiolytic, sedative, muscle relaxant and
amnestic properties. It increases neuronal membrane
permeability to Chloride ions by binding to
benzodiazepine receptors on the postsynaptic GABA
neuron within the CNS and enhancing the GABA
inhibitory effects resulting in hyperpolarization and
stabilization.
Indications: Management of initial and immediate
suppression of convulsive and non-convulsive status
epilepticus prior to transfer to hospital; recurrent or
prolonged febrile convulsions; recurrent generalized or
grand mal seizures associated with poisoning and drug
and acute alcohol withdrawal.
Contraindications: Respiratory depression; marked
neuromuscular respiratory weakness, including unstable
myasthenia gravis; acute pulmonary insufficiency; sleep
apnea syndrome; phobic or obsessional states;
hyperkinesis; severe hepatic impairment.
NOTE: Oral diazepam is NOT recommended for chronic
psychosis. NOT to be used alone in depression or in
anxiety with depression.
Dose:
Status epilepticus, convulsive and non-convulsive, by slow
IV injection, ADULT and CHILD >12 years, 5–10 mg at a
rate not exceeding 2 mg/minute, repeated as necessary
every 5–10 minutes until seizures stop or up to a
maximum total dose of 30 mg, may repeat in 2–4 hours
if needed; CHILD up to 12 years and INFANT >1 month,
300–400 micrograms/kg at a rate not exceeding 1
mg/minute every 15–30 minutes up to a maximum total
dose of 5 mg in infants, and 10 mg for older children.
Prolonged or recurrent febrile convulsions, by slow IV
injection, CHILD and INFANT, 300–400 micrograms/kg
at a rate not exceeding 1 mg/minute every 15–30
minutes up to a maximum total dose of 5 mg in infants,
and 10 mg for older children.
Seizures associated with poisoning, by slow IV injection,
ADULT, 100–150 micrograms/kg at a rate not exceeding
2 mg/minute.
Dose Adjustment:
Geriatric or Debilitated Patients:
Reduce dose.
Renal Impairment:
Reduce dose in prolonged periods.
Hepatic Impairment:
Reduce maintenance dose.
NERVOUS SYSTEM
Precautions:
WARNING: Overdose may produce coma and
respiratory depression.
Agents for correcting hypotension and facilities for
supporting ventilation (e.g., AMBU bag, oxygen) in
cases of respiratory depression should be
available. In such cases, the patient should be
referred to the nearest hospital immediately.
Hepatic impairment and renal impairment (can precipitate
coma in cases of severe hepatic and renal impairment);
avoid prolonged use and abrupt withdrawal;
Respiratory disease (e.g., compromised respiratory drive
and sleep apnea may lead to hypoventilation and
hypoxemia); muscle weakness; (may worsen); history of
alcohol or drug abuse, marked personality disorder; use
only if the indication is clear; porphyria.
Pregnancy (high doses during late pregnancy or labor may
cause neonatal hypothermia, hypotonia, and respiratory
depression); lactation (monitor infant for drowsiness).
Adverse Drug Reactions:
Common: Coma or sensorial depression, hypotension,
respiratory depression.
Rare: Allergic reactions (including anaphylaxis), jaundice.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Diazepam:
Azole Derivatives, e.g., Fluconazole
Enhances therapeutic effect of the following drugs:
Amlodipine, Enalapril, Furosemide, Hydrochlorothiazide,
Methyldopa, Nitrates, e.g., Isosorbide Dinitrate
(hypotensive effect)
Chlorpromazine (sedative effect)
CNS Depressants, e.g., Alcohol, Sedatives, Tranquilizers
(CNS depression; sedative effect)
Increases risk of adverse or toxic effects of Diazepam:
Azole Derivatives, e.g., Fluconazole
Increases risk of adverse or toxic effects of the following
drugs:
Chlorphenamine (sedative effect)
Seizure-inducing Drugs
Reduces therapeutic effect of Diazepam:
Theophylline (sedative effects)
Avoid concomitant use with:
Decreases metabolism of Diazepam:
Isoniazid
Reduces therapeutic effect of Diazepam due to decreased
serum concentration:
Rifampicin (increases metabolism of Diazepam)
Administration: Give by slow IV injection at a rate not faster
than 2 mg/minute.
NOTE: Avoid extravasation, intra-arterial and IM injection.
Avoid dilution and infusion of injection, as diazepam has
a low solubility and adsorbs to PVC-giving sets
Diazepam 5 mg requires an S-2 license for physicians to be
able to prescribe it and an S-1 license with a triplicate
prescription for pharmacists to dispense it.
Pregnancy Category: D
ATC Code: N05BA01
Rx GABAPENTIN
Oral: 100 mg and 300 mg capsule
Gabapentin is a leucine analog of GABA. Its therapeutic
properties are due to its selective binding to α2δ subunits
of voltage-sensitive calcium channels, causing closure of
N and P/Q presynaptic calcium channels that diminishes
excessive neuronal activity and neurotransmitter
release.
Indications: Adjunct therapy in the treatment of partial
seizures with and without secondary generalization in
adults and pediatric patients 3 years and older.
N
Dose:
Seizures, partial onset, by mouth, ADULT or CHILD ≥12
years, initially 300 mg on the 1st day, 300 mg twice a day
on the 2nd day, and 300 mg 3 times a day on the 3rd day;
or 300 mg 3 times daily on the 1st day, increase dose
based on response and tolerability; usual dose range is
900–1,800 mg daily administered in 3 divided doses;
CHILD 5–11 years, initially 10–15 mg/kg daily in 3
divided doses, titrate to effective dose over
approximately 3 days, increase dosage based on
response and tolerability; usual dose range is 25–35
mg/kg daily in 3 divided doses with maximum interval of
12 hours (maximum, 50 mg/kg daily); CHILD 3–4 years,
initially 10–15 mg/kg daily in 3 divided doses, titrate to
effective dose over approximately 3 days, increase
dosage based on response and tolerability; usual dose
range is 40 mg/kg daily in 3 divided doses.
NOTE: If gabapentin is discontinued or if another
anticonvulsant is added to therapy, it should be done
slowly over a minimum of 1 week.
Administration: May be taken with or without food.
Administer first dose on first day at bedtime to avoid
somnolence and dizziness. When given 3 times daily, the
maximum time between doses should not exceed 12
hours.
Do NOT discontinue abruptly because of the possibility of
increasing seizure frequency. Withdraw gradually to
minimize the potential of increased seizure frequency,
unless safety concerns require a more rapid withdrawal.
See Gabapentin under Analgesics – Other Analgesics and
Antipyretics: Drugs for Neuropathic Pain in Chapter 10:
Nervous System for other information.
475

Pregnancy Category: C
ATC Code: N03AX12
Rx LAMOTRIGINE
Oral: 50 mg and 100 mg tablet
Lamotrigine is a synthetic phenyltriazine anticonvulsant and
mood stabilizer used in seizures and bipolar depression.
It blocks the open channel conformation of voltage-
sensitive sodium channels and decreases the release of
glutamate and aspartate.
Indication: Antiepileptic drug of choice for pregnant
patients.
Dose:
Seizures, by mouth, ADULT and CHILD >12 years, weeks 1
and 2: initially 25 mg once daily at night; weeks 3 and 4:
50 mg once daily at night; week 5 onwards: increase by
50 mg daily every 1–2 weeks to a maintenance dose of
225–375 mg daily in 2 divided doses; CHILD 2–12
years, weeks 1 and 2: 0.3 mg/kg daily in 1 or 2 divided
doses, rounded down to the nearest whole tablet; weeks
3 and 4: 0.6 mg/kg daily in 2 divided doses, rounded
N
down to the nearest whole tablet; weeks 5 onwards:
increase dose every 1–2 weeks by 0.6 mg/kg daily,
rounded to the nearest whole tablet to a maintenance
dose of 4.5–7.5 mg/kg daily (maximum daily dose, 300
mg in 2 divided doses). [NOTE: In patients <30 kg, may
need to increase dose by as much as 50% based on
clinical response].
Dose Adjustment:
Geriatric:
Select doses with caution. Start at the low end of the dosing
range, reflecting greater frequency of decreased hepatic,
renal, or cardiac function, and of concomitant disease or
other drug therapy.
Renal Impairment:
Reduce maintenance dose in patients with significant
impairment.
Hepatic Impairment:
In moderate and severe impairment without ascites, reduce
maintenance doses by 25%.
In severe impairment with ascites, reduce maintenance
dose by 50%.
Precautions:
WARNING: Serious skin rashes. Can cause serious
rashes requiring hospitalization and
discontinuation of treatment, including SJS. Nearly
all cases of life-threatening rashes occurred within
2–8 weeks of treatment initiation.
Aseptic meningitis; blood dyscrasias (e.g., neutropenia,
leukopenia, thrombocytopenia, pancytopenia, and
anemias); CNS depression; seizures; suicidal ideation.
476
NERVOUS SYSTEM
Multiorgan hypersensitivity reactions, i.e., drug reaction with
eosinophilia and systemic symptoms [DRESS];
photosensitivity; hepatic impairment; renal impairment.
Children (at increased risk for developing serious skin
rashes during therapy).
Pregnancy (weigh potential benefits to the mother against
the risks to the fetus; increased risk of isolated cleft
palate or cleft lip deformity with first trimester exposure);
lactation (monitor infant for possible adverse effects).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common or Less Common: Aggression, ataxia, arthralgia,
agitation, blurred vision, back pain, diarrhea, dizziness,
drowsiness, diplopia, dry mouthm, headache, nausea,
vomiting, insomnia, nystagmus.
Rare: conjunctivitis
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
CNS Depressants (central effects)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Increases metabolism of Lamotrigine:
Carbamazepine, Rifampin
Increases risk of adverse or toxic effects of Lamotrigine:
Rufinamide (sleepiness and dizziness)
Valproate (rash)
Increases risk of adverse or toxic effects of the following
drugs:
Carbamazepine, Desmopressin
SSRIs (psychomotor impairment)
Avoid concomitant use with:
Decreases serum concentration of Lamotrigine:
Estrogen Derivatives, Estrogen-containing Products,
Mefloquine, UGT Inducers, UGT Substrates
Decreases serum concentration of Progestins
(Contraceptive)
Enhances therapeutic effect of Olanzapine (sedative effect)
Increases serum concentration of Lamotrigine:
UGT Inhibitors
Increases serum concentration of the following drugs:
Organic Cation Transporter 2 Substrates, Procainamide
Reduces therapeutic effect of Lamotrigine:
Mefloquine
Administration: May be taken with or without food.
Pregnancy Category: C
ATC Code: N03AX09
NERVOUS SYSTEM
Rx MAGNESIUM SULFATE
Inj.:250 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IM, IV)
250 mg/mL (as heptahydrate), 10 mL, 20 mL, and 50
mL vial (IV)
500 mg/mL (as heptahydrate), 2 mL and 10 mL
ampule (IM, IV)
Magnesium sulfate decreases levels of acetylcholine in
motor nerve terminals. It also acts on the myocardium by
decreasing the rate of SA node impulse formation and
prolonging the conduction time.
Indication: Drug of choice for the prevention of seizures in
women with severe preeclampsia, and for controlling
seizures or preventing their recurrence among eclamptic
patients.
Contraindications: Heart block; myocardial infarction;
hypermagnesemia; deranged renal function; myasthenia
gravis.
Dose:
Prevention of recurrent seizures, by IV injection, ADULT, 4 g
as loading dose over 5–15 minutes followed by an IV
infusion of 1 g/hour as maintenance dose for at least 24
hours after the last seizure or delivery, whichever occurs
later;
by deep IM injection, ADULT (special situations; when IV
lines are not available), 5 g into each buttock, then 5 g
every 4 hours into alternate buttocks for at least 24
hours after the last seizure or delivery; treat recurrent
seizure by further IV bolus of 2 g, or 4 g if body weight is
over 70 kg.
NOTE: Continue therapy until paroxysms cease. A serum
magnesium level of 6 mg/100mL is considered optimal
for seizure control. NOT to exceed 30–40 g per 24 hours.
Administration: Administer at a concentration not exceeding
20%. Dilute according to manufacturer’s instructions.
For IM route, solutions may need dilution prior to
administration. 25% or 50% for adults or ≤20% for
children.
For IV route, solutions must be diluted to ≤20% for IV
infusion and may be administered by IV push, IVPB, or
continuous IV infusion.
For IV push, dilute first and do not administer faster than
150 mg/minute.
May be administered over 1–2 minutes in patients with
persistent pulseless VT or VF with known
hypomagnesemia. Administer over 15 minutes in
patients with torsade de pointes.
Maximum rate of infusion is 1 g/hour in asymptomatic
patients. For doses <6 g, infuse over 8–12 hours. For
larger doses, infuse over 24 hours.
If patient is severely symptomatic or has conditions such
as preeclampsia or eclampsia, more aggressive therapy
(≤4 g over 4-5 minutes) may be required.
See Magnesium Sulfate under I.V. Solutions Additives in
Chapter 2: Blood and Blood Forming Organs for other
information.
Pregnancy Category: D
ATC Code: Not available
Rx MIDAZOLAM
Oral: 15 mg tablet
Inj.: 1 mg/mL, 5 mL ampule/vial (IM, IV)
5 mg/mL, 1 mL, 2 mL, 3 mL, 5 mL, and 10 mL ampule
(IM, IV)
Midazolam is a short-acting benzodiazepine that binds to
stero-specific receptors on the postsynaptic GABA
neuron at several sites within the CNS. This results to an
enhanced inhibitory effect of GABA on neuronal
excitability.
Indications: Management of seizures and status
epilepticus.
Contraindications: Intrathecal or epidural injection; acute
N
narrow-angle glaucoma; concurrent use of potent
inhibitors of CYP3A4 (e.g., amprenavir, atazanavir,
ritonavir)
[Oral]: Severe respiratory insufficiency; severe hepatic
insufficiency; sleep apnea syndrome; myasthenia gravis;
use in children and adolescents.
Dose:
NOTE: Individualize dose based on patient’s age, underlying
diseases, and concurrent medications. Initial dose for
sedation should not exceed 2.5 mg in a healthy adult.
Consider reducing dose by 20–50% in patients receiving
opioids or other CNS depressants.
Seizures, by IM injection, ADOLESCENT and CHILD, 0.2
mg/kg (maximum dose, 6 mg), may repeat every 10–15
minutes.
Status epilepticus, convulsions >5 minutes or convulsions
occurring after intermittent seizures without regaining
consciousness for >5 minutes, by IM injection, ADULT,
ADOLESCENT, and CHILD >40 kg, 10 mg once; or 0.2
mg/kg once (maximum dose, 10 mg); ADOLESCENT and
CHILD 13–40 kg, 5 mg once.
Status epilepticus, refractory, by IV injection, ADULT,
ADOLESCENT, CHILD, and INFANT, 0.2 mg/kg as loading
dose followed by a continuous IV infusion, 0.05–2 mg/kg
per hour (0.83–33.2 micrograms/kg per minute), titrate
to cessation of electrographic seizures or burst
suppression; if patient experiences breakthrough status
epilepticus while on the continuous infusion, administer
a bolus of 0.1–0.2 mg/kg and increase infusion rate by
0.05–0.1 mg/kg per hour (0.83–1.66 micrograms/kg
per minute) every 3–4 hours. [NOTE: Withdraw
continuous infusion after a period of at least 24–48
hours of electrographic control; withdraw gradually to
prevent recurrent status epilepticus]; or
ADOLESCENT, CHILD, and INFANT, 0.15–0.2 mg/kg
followed by a continuous infusion of 1 microgram/kg per
477

minute, titrated every 15 minutes by increments of 1
microgram/kg per minute until the cessation of seizures
(maximum dose, 5 micrograms/kg per minute).
Dose Adjustment:
Geriatric, Chronically Ill, or Debilitated Patients:
Consider reducing dose by 20–50%. Initial doses should be
conservative. Initiate treatment at the low end of the
dosing range. Titrate subsequent doses slowly.
Renal Impairment:
Lower doses may be needed. Patients with renal failure
receiving continuous infusion cannot adequately
eliminate the active hydroxylated metabolites, which may
cause prolonged sedation.
Hepatic Impairment:
Lower doses as needed.
Precautions:
WARNING: Respiratory Depression. Has been
associated with respiratory depression and
respiratory arrest, especially when used for
sedation in noncritical care settings. The immediate
availability of specific reversal agents (e.g.,
flumazenil) and size appropriate equipment for
intubation and ventilation is highly recommended.
Monitor vital signs continuously during the recovery
N
period. For deeply sedated patients, a dedicated
individual, other than the practitioner performing
the procedure, should monitor the patient
throughout the procedure.
Sedation precaution. Administer over at least 2
minutes and allow an additional 2 or more minutes
to fully evaluate the sedative effect. Use 1 mg/mL
formulation or dilution of the 1 mg/mL or 5 mg/mL
formulation to facilitate slower injection. Doses of
sedative medications in pediatric patients must be
calculated on a mg/kg basis. Initial pediatric dose
for sedation, anxiolysis, or amnesia is dependent
on age, procedure, and route.
Neonates [injection]. Do NOT administer by rapid
injection in neonates. Rapid IV injection (<2
minutes) in neonates has been associated with
seizures and severe hypotension, particularly when
used concomitantly with fentanyl. Severe
hypotension has also been observed in neonates
receiving a continuous infusion of midazolam who
then receive a rapid IV injection of fentanyl.
Anterograde amnesia; CNS depression; paradoxical
reactions (e.g., hyperactive behavior, particularly in
adolescent and pediatric patients; consider treatment
with flumazenil).
Hypotension; hemodynamic events are more common in
pediatric patients or patients with hemodynamic
instability); heart failure.
Impaired gag reflex; renal impairment (half-life may be
prolonged); respiratory disease; fall risk; obesity (may
have prolonged action when discontinued).
Elderly; neonates (e.g., severe hypotension and seizures;
risk may be increased with concomitant fentanyl use).
Pregnancy; (teratogenic effects have been observed;
incidence of premature birth and low birth weights may
478
NERVOUS SYSTEM
be increased with use; neonatal withdrawal symptoms
may occur within days to weeks after birth; “floppy infant
syndrome” has been reported); lactation.
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Hypotension, drowsiness, over-sedation,
headache, seizure-like activity (children), pain and local
reactions at injection site, nausea, vomiting, myoclonic
jerks (preterm infants), nystagmus, decreased tidal
volume and/or decreased respiratory rate, apnea,
cough, physical and psychological dependence
(prolonged use), hiccups, paradoxical reaction (children).
Less Common: Acid taste, agitation, amnesia, bigeminy,
bronchospasm, confusion, dyspnea, bradycardia,
emergence delirium, euphoria, hallucinations,
hyperventilation, laryngospasm, excessive salivation,
PVC, rash, tachycardia, wheezing, respiratory arrest (life-
threatening), cardiac arrest (life-threatening).
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect (CNS depressant effect) of
Midazolam:
Brimonidine (Topical), Doxylamine, Dronabinol,
Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone
Enhances therapeutic effect of the following drugs:
Ethyl Alcohol, Mirtazapine (CNS depressant effect)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Increases risk of adverse or toxic effects of Midazolam:
Other CNS Depressants
Rufinamide (sleepiness and dizziness)
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
Avoid concomitant use with:
Decreases serum concentration of Midazolam:
Dabrafenib, Mitotane
Enhances therapeutic effect of Midazolam:
Droperidol, Methotrimeprazine [reduce dose by 50%
when used concomitantly], Tapentadol (CNS depressant
effect) [start at one-third to one-half of the normal dose]
Enhances therapeutic effect of the following drugs:
Buprenorphine, Hydrocodone [consider starting with a
20–30% lower dose when used concomitantly],
Methadone, Methotrimeprazine [reduce dose by 50%
when used concomitantly], Orphenadrine, Paraldehyde,
Perampanel, Sodium Oxybate, Thalidomide, Zolpidem
(CNS depressant effect)
Increases risk of adverse or toxic effects of Midazolam:
Olanzapine
Increases risk of adverse or toxic effects of the following
drugs:
Azelastine (Nasal), Clozapine (CNS depressant effect)
NERVOUS SYSTEM
Increases serum concentration of Midazolam:
Anti-hepaciviral Combination Products, Boceprevir,
Cobicistat, Fusidic Acid (Systemic), Idelalisib,
Itraconazole, Ketoconazole (Systemic), Macrolide
Antibiotics [except Systemic Azithromycin, Fidaxomicin,
Spiramycin], Mifepristone [avoid midazolam during and
2 weeks following use], Protease Inhibitors, Telaprevir
Increases serum concentration of Amodiaquine
Reduces therapeutic effect of Midazolam:
Theophylline Derivatives
FOOD INTERACTION. Grapefruit juice may increase serum
concentrations of midazolam.
Administration:
For IM route, administer by deep IM injection into a large
muscle.
For IV route, administer by slow IV injection over at least
2–5 minutes at a concentration of 1–5 mg/mL or by IV
infusion via an infusion pump. For induction of
anesthesia, administer IV bolus over 5–30 seconds.
For oral administration, swallow tablet whole with
adequate fluid.
Rebound or withdrawal symptoms may occur following
abrupt discontinuation or large decreases in dose.
Decrease doses slowly and monitor for withdrawal
symptoms.
NOTE: Midazolam 15 mg requires an S-2 license for
physicians to be able to prescribe it and an S-1 license
with a triplicate prescription for pharmacists to dispense
it.
Pregnancy Category: D
ATC Code: N05CD08
Rx THIOPENTAL SODIUM
Rx
Inj.: 500 mg vial (IV)
1 g vial + 50 mL diluent (IV)
Thipental is an ultrashort-acting thiobarbiturate with
anesthetic activity. It acts by binding to the chloride
site of the GABAA/chloride receptor complex, thereby
enhancing the inhibitory actions of GABAA in the brain.
This leads to synaptic inhibition, decreased neuronal
excitability and induction of anesthesia, as well as
decreased glutamate responses.
Indication: Treatment of convulsive states.
Contraindications: Variegate or acute intermittent
porphyria; absence of suitable veins for IV
administration; status asthmaticus; dyspnea or
respiratory obstruction; severe cardiovascular
disease or hypotension; Addison’s disease; hepatic
dysfunction; myxedema.
Dose:
Seizures, by IV injection, ADULT, 75–125 mg per dose as a
2.5% solution, repeated as needed; convulsions
following use of local anesthetic may require 125–
250 mg given over 10 minutes; dose depends on the
amount of local anesthetic given and its convulsant
properties.
Administration: Administer by IV infusion. Avoid intra-arterial
administration.
Avoid extravasation.
The patient must always lie supine as even a small
overdose can cause hypotension.
NOTE: IV infusion of concentrated solutions (e.g., 5%) may
cause thrombophlebitis. Repeated doses may result
in prolonged drug effect because of accumulation.
See Thiopental Sodium under Anesthetics, General –
Barbiturates, Plain in Chapter 10: Nervous System for
other information.
Pregnancy Category: C
ATC Code: N05CA19
N
Rx TOPIRAMATE
Oral: 25 mg, 50 mg, and 100 mg tablet
Topiramate is a sulfamate-substituted monosaccharide that
potentiates GABA action and inhibits glutamate release
through interfering with both calcium and sodium
channels.
Indications: Initial monotherapy or adjunct therapy in
patients ≥2 years with partial onset or primary
generalized tonic-clonic seizures.
Dose:
Partial-onset seizure and primary generalized tonic-clonic
seizure, monotherapy, by mouth, ADULT and CHILD ≥10
years, initially 25 mg twice daily, may increase weekly by
50 mg daily up to 100 mg twice daily (week 4 dose), may
further increase weekly by 100 mg daily up to the
recommended dose of 200 mg twice daily;
CHILD 2 to <10 years, initially 25 mg once daily in the
evening, may increase to 25 mg twice daily in week 2,
may further increase by 25–50 mg daily at weekly
intervals over 5–7 weeks up to the minimum
recommended maintenance dose; if additional seizure
control is needed and therapy is tolerated, may further
increase weekly by 25–50 mg daily up to the maximum
recommended maintenance dose:
Minimum
Maximum
Maintenance
Maintenance
Weight Dose
Dose (in 2
(in 2
divided doses)
divided doses)
≤11 kg 150 mg daily 250 mg daily
479

12–22 kg 200 mg daily 300 mg daily
23–31 kg 200 mg daily 350 mg daily
32–38 kg 250 mg daily 350 mg daily
≥39 kg 250 mg daily 400 mg daily
Partial-onset seizure, primary generalized tonic-clonic
seizure, or Lennox-Gastaut syndrome, adjunct therapy,
by mouth, ADULT, initially 25 mg once or twice daily for 1
week, may increase weekly by 25–50 mg daily until
response; usual maintenance dose, 100–200 mg twice
daily for partial-onset seizures or 200 mg twice daily for
primary generalized tonic-clonic seizures; ADOLESCENT
<17 years and CHILD ≥2 years, initially 25 mg once daily
(1–3 mg/kg daily) in the evening for 1 week, may
increase every 1–2 weeks in increments of 1–3 mg/kg
daily to the recommended dose of 5–9 mg/kg daily in 2
divided doses.
Dose Adjustment:
Geriatric:
An initial dose of 25 mg daily may be recommended,
followed by incremental increases of 25 mg at weekly
intervals until an effective dose is reached.
Renal Impairment:
In CrCl <70 mL/minute, administer 50% of the dose and
titrate more slowly.
N
In hemodialysis, supplemental dose may be needed.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
CNS effects (e.g., cognitive dysfunction, psychiatric
disturbances, and sedation); paresthesia, dizziness, and
ataxia); suicidal ideation; hyperammonemia or
encephalopathy; oligohidrosis or hyperthermia.
Metabolic acidosis (hyperchloremic non-anion gap
metabolic acidosis; metabolic acidosis); ophthalmic
effects (acute myopia and secondary angle-closure
glaucoma); visual field defects; renal calculus (e.g.,
kidney stones); renal and hepatic impairment (clearance
may be reduced); eating disorders (may develop or
exacerbate anorexia nervosa and bulimia).
Elderly (use with caution).
Pregnancy (hypospadia cleft lip or palate with use during
pregnancy); lactation (use with caution).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Flushing, chest pain, paresthesia, memory
impairment, drowsiness, dizziness, lack of
concentration, mood disorder, depression, ataxia,
insomnia, cognitive dysfunction, anxiety, hypoesthesia,
nervousness, UTI, psychomotor retardation, confusion,
behavioral problems, hypertonia, vertigo, alopecia,
pruritus, skin rash, acne vulgaris, increased gamma-
glutamyl transferase, intermenstrual bleeding, weight
loss, dysgeusia, constipation, gastritis, xerostomia,
anorexia, diarrhea, GERD, decreased libido, urinary
frequency, vaginal hemorrhage, cystitis, urinary
incontinence, dysuria, anemia, viral infection, infection,
480
NERVOUS SYSTEM
weakness, muscle spasm, leg pain, nephrolithiasis,
rhinitis, bronchitis, sinusitis, epistaxis, dyspnea, fever,
upper respiratory tract infection.
Less Common: Abnormal electroencephalogram, abnormal
dreams, abnormal hair texture, acute myopia with
secondary angle-closure glaucoma, albuminuria, alcohol
intolerance, altered sense of smell, angina pectoris,
apraxia, AV block, blepharoptosis, bone marrow
depression, brain disease, bullous rash, cerebellar
syndrome, chloasma, deep vein thrombosis,
dehydration, delirium, delusions, dyskinesia, dystonia,
diabetes mellitus, enlargement of abdomen, ejaculatory
disorder, erythema multiforme, hepatitis,
hyperchloremic metabolic acidosis (non-anion gap),
hepatic failure, hyperesthesia, hyperglycemia,
hyperlipidemia, hypernatremia, hypocholesterolemia,
hypothermia (with valproic acid, with or without
hyperammonemia), hyperthermia, hypohidrosis,
hypocalcemia, hyponatremia, hypotension, increased
libido, impotence, iritis, lymphadenopathy,
lymphocytosis, maculopathy, lymphocytopenia, melena,
mydriasis, manic reaction, neuropathy, nipple discharge,
oliguria, orthostatic hypotension, ostealgia, pancreatitis,
pancytopenia, paranoia, pemphigus, phlebitis,
photophobia, polycythemia, polyuria, psychosis,
pulmonary embolism, renal pain, scotoma, skin
photosensitivity, SJS, stomatitis, strabismus, suicidal
ideation, suicidal tendencies, tongue edema, tongue
paralysis, toxic epidermal necrolysis, upper motor
neuron lesion, urinary retention, urticaria, vasodilation,
vasospasm, visual field defect, voice disorder,
xerophthalmia.
Drug Interactions:
Monitor closely with:
Decreases excretion of the following drugs:
Memantine, Quinidine
Enhances therapeutic effect of Topiramate:
Brimonidine (Topical), Doxylamine, Dronabinol,
Hydroxyzine, Magnesium Sulfate, Minocycline, Nabilone
(CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Amitriptyline, Mirtazapine (CNS depressant effect)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
Increases risk of adverse or toxic effects of Topiramate:
Anticholinergics
Loop Diuretics (hypokalemic effect)
Other CNS Depressants
Rufinamide (sleepiness and dizziness)
Increases risk of adverse or toxic effects of the following
drugs:
SSRIs (psychomotor impairment)
Primidone (osteomalacia and rickets)
Valproate Products
Avoid concomitant use with:
Decreases serum concentration of Topiramate:
Carbamazepine, Mefloquine
Decreases serum concentration of the following drugs:
Aripiprazole [double dose when used concomitantly;
reduce dose to 10–15 mg daily when topiramate is
NERVOUS SYSTEM
discontinued], Contraceptives [Estrogens and
Progestins], Ulipristal
Enhances therapeutic effect (CNS depressant effect) of
Topiramate:
Droperidol, Ethyl Alcohol, Methotrimeprazine [reduce
midazolam dose by 50% when used concomitantly]
Tapentadol [start at one-third to one-half of the normal
dose]
Enhances therapeutic effect (CNS depressant effect) of the
following drugs:
Buprenorphine, Hydrocodone [consider starting with a
20–30% lower dose when used concomitantly],
Methotrimeprazine [reduce midazolam dose by 50%
when used concomitantly], Orphenadrine, Paraldehyde,
Perampanel, Sodium Oxybate, Thalidomide, Zolpidem
Increases risk of adverse or toxic effects of Topiramate:
Other Carbonic Anhydrase Inhibitors (acid-base
disorders; kidney stones; metabolic acidosis)
Salicylates
Thiazide Diuretics (hypokalemic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Azelastine, Nasal (CNS depressant effect)
Metformin
Salicylates (salicylate toxicity)
Increases serum concentration of Topiramate:
Ethyl Alcohol, Thiazide Diuretics
Reduces therapeutic effect of Topiramate:
Mefloquine
Reduces therapeutic effect of the following drugs:
Contraceptives, Estrogens and Progestins (contraceptive
failure is possible)
Methenamine
FOOD INTERACTION. Ketogenic diet may increase the
possibility of acidosis and/or kidney stones.
Administration: May be taken with or without food.
Administer in divided doses. Do NOT crush, break, or
chew tablets due to bitter taste.
Do NOT abruptly discontinue therapy because of the
possibility of increasing seizure frequency. Taper dosage
gradually to prevent rebound effects and to minimize the
potential of increased seizure frequency, unless safety
concerns require a more rapid withdrawal.
Pregnancy Category: D
ATC Code: N03AX11
ANTI-PARKINSON DRUGS
ANTICHOLINERGICS
Rx BIPERIDEN
Oral: 2 mg tablet (as hydrochloride)
Inj.: 5 mg/mL (as lactate), 1 mL ampule (IM, IV)
A tertiary-amine, centrally-acting anticholinergic drug, used
in the management of Parkinsonism and is effective for
the treatment of acute EPS.
Indication: Management of drug-induced extrapyramidal
symptoms (except tardive dyskinesia) by phenothiazines,
butyrophenones or reserpine; adjunctive treatment of
post-encephalitic, idiopathic or arteriosclerotic
Parkinson’s disease.
Contraindications: Angle-closure glaucoma; untreated
urinary retention; prostatic hypertrophy; myasthenia
gravis; and GI obstruction or atony; toxic megacolon.
Dose:
Parkinsonism, by mouth, ADULT, 2 mg every 8 or 6 hours,
N
with initial dose of 0.5–1 mg daily, gradually increase by
0.5 mg every 5–6 days until optimum dose (maximum,
16 mg daily).
Drug-induced extrapyramidal disorders, by mouth, ADULT,
1–4 mg daily, in single or 2 divided doses; CHILD >3
years, 0.02–0.05 mg/kg per dose every 8–12 hours; by
IM injection or slow IV infusion, ADULT, 10 to 20 mg once
daily.
Dose Adjustment:
Geriatric:
Start with low dose and increase slowly to the lowest
effective dose.
Hepatic Impairment:
For mild-to-moderate hepatic impairment, dose reduction is
warranted.
For severe impairment, the patient should be referred to a
specialist.
Precautions:
Avoid abrupt withdrawal in Parkinson’s disease (to prevent
acute exacerbation); tardive dyskinesia; fever or high
ambient temperature (hyperthermia).
Heart diseases e.g., arrhythmias, coronary heart disease,
and heart failure (may be exacerbated); hepatic
impairment.
Inflammatory bowel disease (paralytic ileus); dementia
(anticholinergics are best avoided; may worsen
symptoms and antagonize therapeutic effects of
anticholinesterases); GERD (may be aggravated).
Elderly (more sensitive to anticholinergic adverse effects;
confusion may be precipitated or worsened); children
(more susceptible to anticholinergic side effects).
Pregnancy; lactation (use with caution).
481

SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Blurred vision, confusion, constipation,
decreased sweating, disorientation, dizziness,
drowsiness, flushing, lightheadedness, dryness of
mouth, mydriasis, nausea, nervousness, reduced
bronchial secretions, thirst, urinary hesitancy and
retention, vomiting.
Less Common or Rare: Agitation, angle-closure glaucoma,
arrhythmias, delirium, delusions, diplopia, excitement,
hallucinations, epigastric distress, hypotension, memory
impairment, muscular cramping and weakness,
palpitations, paralytic ileus, paresthesia, rash,
psychiatric disturbances, urticaria, bradycardia followed
by tachycardia.
Drug Interactions:
NOTE: Concomitant use of two or more drugs having
antimuscarinic effects can increase side-effects, such as
constipation, urine retention and dryness of mouth, and
can also lead to confusion especially in the elderly.
Monitor closely with:
Enhances therapeutic effect of Fluphenazine
(antimuscarinic effects)
N
Increases risk of adverse or toxic effects of Biperiden:
Antipsychotic Drugs, e.g., Phenothiazines, Haloperidol
(masking of extrapyramidal symptoms; tardive
dyskinesia; long-term therapy)
Reduces therapeutic effect of the following drugs:
Isosorbide Dinitrate, Sublingual (failure to dissolve under
the tongue owing to dry mouth)
Avoid concomitant use with:
Decreases bioavailability of Levodopa
Enhances therapeutic effect of Alcohol (CNS depression)
Increases risk of adverse or toxic effects of Biperiden:
Anticholinergics (including central anticholinergic
delirium)
Drugs with Anticholinergic Effects (including central
anticholinergic delirium)
Reduces therapeutic effect of Biperiden:
Anticholinesterases, e.g., Neostigmine, Pyridostigmine
Cisapride
Reduces therapeutic effect of the following drugs:
Haloperidol
Metoclopramide
Administration: Should be taken with food.
Do NOT discontinue abruptly to prevent acute
exacerbation. Gradually taper dose.
Pregnancy Category: C
ATC Code: N04AA02
482
NERVOUS SYSTEM
DOPAMINERGIC AGENTS
Rx BROMOCRIPTINE
Oral: 2.5 mg tablet (as mesilate)
Bromocriptine is a semisynthetic ergot alkaloid and
dopamine agonist with high affinity for the D2 receptor
and weak α-agonist activity. The dopamine receptor
agonist activity also causes inhibition of prolactin-
secreting cells in the anterior pituitary for the treatment
of hyperprolactinemia and for reducing tumor sizes in
prolactin- and growth hormone-secreting pituitary
adenomas.
Indication: Management of hyperprolactinemia.
Contraindications: Uncontrolled hypertension; eclampsia;
preeclampsia; pregnancy-induced hypertension; post-
partum patients with coronary artery disease or other
severe cardiovascular conditions.
Dose:
Hyperprolactinemia, by mouth, ADULT, initially 0.5 to 2.5 mg
once daily at bedtime to increase tolerance; slowly
increase the daily dose by 1.25 to 2.5 mg every 1–2
weeks up to an average of 20–30 mg once daily
(maximum, 100 mg once daily).
Dose Adjustment:
Hepatic Impairment:
May require dose adjustment. Undergoes extensive hepatic
metabolism. Use with caution.
Precautions:
Cardiac valvular fibrosis; cardiovascular effects (e.g.,
symptomatic hypotension; seizures, hypertension, MI,
and stroke).
Visual or auditory hallucinations; impulse control disorders;
sedation (e.g., sudden sleep onset and somnolence);
dementia; psychosis.
Melanoma; pleural or retroperitoneal fibrosis (prolonged
and high-dose daily use); peptic ulcer disease (severe GI
bleeding; may be fatal).
Acromegaly (digital vasospasm); diabetic ketoacidosis;
macroadenomas; pituitary irradiation; prolactin-
secreting adenomas.
Elderly (concomitant diseases or drug therapy may
complicate therapy).
Pregnancy (a pregnancy test every 4 weeks is
recommended as long as no menses occur); lactation.
Adverse Drug Reactions:
Common: Hypotension, Raynaud’s phenomenon, syncope,
vasospasm (digital), dizziness, fatigue, headache,
drowsiness, hypoglycemia, nausea, lightheadedness,
constipation, anorexia, GI hemorrhage, abdominal
cramps, dyspepsia, diarrhea, vomiting, xerostomia,
increased susceptibility to infection weakness,
amblyopia, rhinitis, flu-like symptoms, nasal congestion,
sinusitis.
Less Common: Abdominal distress, acquired valvular heart
disease, alopecia, anxiety, ataxia, blepharospasm,
blurred vision, bradycardia, cardiac arrhythmia,
cerebrovascular accident (postpartum), cold extremities,
NERVOUS SYSTEM
cold intolerance, confusion, constrictive pericarditis,
delusions, depression, dyskinesia, dysphagia, dyspnea,
epileptiform seizures, ergot alkaloids toxicity,
erythromelalgia, GI ulcer, hallucination, heavy
headedness, MI (postpartum), hypersensitivity reaction,
hypertension (postpartum), increased cerebrospinal
fluid pressure, increased libido, insomnia, lassitude,
lethargy, muscle cramps, narcolepsy, nervousness,
nightmares, on­off phenomenon, pallor, paranoia,
paresthesia, pericardial effusion, peripheral edema,
pleural effusion, psychomotor agitation, psychosis,
pulmonary fibrosis, retroperitoneal fibrosis, pleurisy,
seizure (postpartum), skin mottling, skin rash, status
epilepticus (postpartum), sleep disorder, tachycardia,
tingling of the ears, tinnitus, transient blindness, urinary
frequency, urinary incontinence, vasodepressor syncope,
urinary retention, ventricular tachycardia, vertigo, visual
disturbance.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect (hypoglycemic effect) of
Bromocriptine:
Alpha-Lipoic Acid, Androgens [except Danazol],
Hypoglycemia-Associated Agents, MAO Inhibitors
[Linezolid, Tedizolid], Pegvisomant, Quinolone Antibiotics
e.g., Ciprofloxacin, Salicylates e.g. Aspirin
Enhances therapeutic effect of the following drugs:
5HT3 Antagonists e.g., Ondansetron (serotonergic effect)
MAO Inhibitors [except Linezolid, Tedizolid] (hypotensive
effect)
Tedizolid (serotonergic effect)
Increases risk of adverse or toxic effects of Bromocriptine:
Ethyl Alcohol, Methylphenidate
Quinolone Antibiotics (loss of blood sugar control)
Increases risk of adverse or toxic effects of the following
drugs:
5HT3 Antagonists (serotonin syndrome), Tedizolid
(serotonin syndrome)
Bupropion, Ethyl Alcohol, Methylphenidate
MAO Inhibitors [Linezolid] (orthostatic hypotensive)
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome)
Reduces therapeutic effect of Bromocriptine:
Hyperglycemia-Associated Agents, Metoclopramide,
Thiazide Diuretics
Quinolone Antibiotics (loss of blood sugar control)
Avoid concomitant use with:
Enhances therapeutic effect of Bromocriptine:
Beta Blockers e.g., Propranolol, Serotonin 5­HT1D
Receptor Agonists (vasoconstricting effect)
Enhances therapeutic effect of the following drugs:
Alpha / Beta Agonists, Alpha1 Agonists (hypertensive
effect; vasoconstricting effect)
Serotonin 5­HT1D Receptor Agonists (vasoconstricting
effect)
Increases risk of adverse or toxic effects of Bromocriptine:
Beta Blockers (vasoconstricting effect)
Dapoxetine, Other Serotonin Modulators [except
Tedizolid]
Increases risk of adverse or toxic effects of the following
drugs:
Dapoxetine, Tizanidine
Serotonin Modulators [except Tedizolid] (serotonin
syndrome)
Increases serum concentration of Bromocriptine:
Anti-hepaciviral Combination Products, CYP3A4
Inhibitors, Fusidic Acid (Systemic), Idelalisib, Macrolide
Antibiotics [except Systemic Azithromycin, Fidaxomicin,
Spiramycin], Mifepristone [if concomitant use cannot be
avoided, minimize Bromocriptine doses], Nitroglycerin,
Protease Inhibitors
Increases serum concentration of the following drugs:
Tizanidine [if concomitant use cannot be avoided, initiate
at 2 mg and increase in 2–4 mg increments based on
patient response]
Reduces therapeutic effect of Bromocriptine:
Amisulpride, Antipsychotic Agents (First Generation /
Typical), Antipsychotic Agents (Second Generation /
Atypical)
Reduces therapeutic effect of the following drugs:
N
Amisulpride, Antipsychotic Agents (First Generation /
Typical)
Nitroglycerin (vasodilatory effect)
Administration: Administer with food to decrease GI
distress.
Do NOT discontinue abruptly to prevent acute
exacerbation. Discontinue gradually over a period of 1
week.
Pregnancy Category: B
ATC Code: N04BC01
Rx LEVODOPA + CARBIDOPA
Oral: 100 mg levodopa + 25 mg carbidopa per tablet
250 mg levodopa + 25 mg carbidopa per tablet
200 mg levodopa + 50 mg carbidopa extended-
release tablet
Levodopa is an aromatic amino acid and the naturally-
occurring form of dihydroxyphenylalanine. It is the
immediate precursor to dopamine and can pass through
the blood-brain barrier, where it is immediately taken up
by dopaminergic neurons and converted into dopamine.
It is administered with carbidopa, a peripheral
decarboxylase inhibitor that prevents gut metabolism of
levodopa, thereby increasing dopamine in the CNS.
Indication: Management of Parkinson’s disease, including
idiopathic parkinsonism, post-encephalitic
parkinsonism, and symptomatic parkinsonism.
483

Contraindications: Narrow angle glaucoma; history of
melanoma.
Dose:
Parkinson’s disease, by mouth, ADULT,
Immediate-release, initially 300 mg/75 mg daily in 3
divided doses, may be increased by 100 mg/25 mg every
other day (maximum, 800 mg/200 mg daily in divided
doses);
Extended-release, initially 400 mg/100 mg daily in 2
divided doses, may be increased by 100 mg/25 mg to
200 mg/50 mg every other day (maximum, 2,450
mg/612.5 mg daily in divided doses).
Precautions:
Abnormal thinking or behavioral changes e.g. aggresive
behavior, agitation, confusion, delirium, disorientation,
delusion, paranoid ideation and psychotic like behavior;
hallucinations (typically presents shortly after initiation of
therapy; may require dose reduction); psychotic
disorders (use with extreme caution; at risk of
exacerbating psychosis; depression with concomitant
suicidal tendencies).
Dyskinesias (may require dosage reduction); impulse
control disorders.
Leukopenia; melanoma (monitor closely; perform periodic
skin examinations).
Neuroleptic malignant syndrome (rapid dose reduction, or
N
abrupt withdrawal; monitor closely for this reaction;
discontinue immediately if signs and symptoms arise);
peripheral neuropathy.
Cardiovascular disease (use with caution); orthostatic
hypotension (monitor closely for signs and symptoms of
postural hypotension, especially during dose escalation).
Somnolence (evaluate for factors that may increase these
risks such as concomitant sedating medications, and the
presence of sleep disorders; monitor for drowsiness or
sleepiness).
Endocrine disease (use with caution in patients with
endocrine disease and when interpreting plasma or
urine catecholamine levels; falsely diagnosed
pheochromocytoma).
Glaucoma (use with caution; monitor IOP carefully);
respiratory disease.
Peptic ulcer disease (use with caution); hepatic and renal
impairment.
Elderly (use with caution; may be more sensitive to CNS
effects, e.g., hallucinations).
Pregnancy (safety has not been established); lactation (can
cause reduced serum prolactin levels, resulting in
reversible suppression of lactation).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Abnormal dreams, anorexia, anxiety, arrhythmias,
chorea, confusion, dementia, depression, dizziness,
drowsiness, dry mouth, dyskinesia, dystonia, euphoria,
fatigue, insomnia, nausea, palpitations, postural
hypotension, psychosis, syncope, taste disturbances,
vomiting.
Less Common: Ataxia, chest pain, constipation, diarrhea,
dysphagia, flatulence, hand tremor, hoarseness,
hypersalivation, hypertension, malaise, muscle cramps,
484
NERVOUS SYSTEM
edema, reddish discoloration of the urine and other body
fludis, weakness, weight changes.
Rare: Abdominal pain, activation of malignant melanoma,
agitation, alopecia, blurred vision.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Blood Pressure Lowering
Agents (hypotensive effect)
Increases absorption of Levodopa + Carbidopa:
TCAs
Increases bioavailability of Levodopa + Carbidopa:
Antacids, Anticholinergics, TCAs e.g., Amytriptylline
Increases risk of adverse or toxic effects of Levodopa +
Carbidopa:
Biperiden (choreic movements or dyskinesias),
Methylphenidate, Papaverine (hypotensive effect),
Sapropterin
Increases risk of adverse or toxic effects of the following
drugs:
Antihypertensives (orthostatic hypotension)
Bupropion
Duloxetine (hypotensive effect)
MAOIs (hypertensive reactions)
Selegiline (severe orthostatic hypotension)
Reduces diagnostic effect of Macimorelin
Reduces therapeutic effect of Levodopa + Carbidopa:
Benzodiazepines, Dopamine Receptor Antagonists,
Fosphenytoin, Isoniazid
Methionine [with large doses], Metoclopramide,
Multivitamins / Fluoride with ADE [pyridoxine when used
in the absence of a dopa decarboxylase inhibitor],
Multivitamins / Minerals e.g., ADEK, Folate, Iron, (Oral),
Multivitamins / Minerals with AE, no Iron [pyridoxine
when used in the absence of a dopa decarboxylase
inhibitor], Papaverine, Phenytoin, Pyridoxine, Spiramycin
Reduces therapeutic effect of Antipsychotics
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Non-selective
MAOIs (hypertensive crisis)
Administration: Should be taken on an empty stomach.
Pregnancy Category: C
ATC Code: N04BA02
NERVOUS SYSTEM
Rx SELEGILINE
Oral: 5 mg tablet (as hydrochloride)
Selegeline is a phenethylamine selective MAO-B inhibitor
used as an adjunct to levodopa in managing Parkinson’s
disease. It increases dopaminergic activity by intervening
w/ the reuptake of dopamine at the synapse. It also
irreversibly inhibits monoamine oxidase (MAO)-B which is
involved in the metabolism of dopamine in the brain.
Indication: Adjunctive therapy for the symptomatic
treatment of parkinsonian syndrome.
Contraindications: Pheochromocytoma; elective surgery
requiring general anesthesia; active duodenal
ulceration, active gastric ulceration, avoid or use with
great caution in postural hypotension (when used in
combination with levodopa).
Dose:
Parkinson’s disease, by mouth, ADULT, initially 2.5 mg twice
daily; slowly increase to 5 mg twice daily and reduce the
dose of levodopa after 2–3 days; avoid doses greater
than 10 mg daily.
Dose Adjustment:
Geriatric:
Increase doses with caution.
Renal Impairment:
Use with caution. May require a lower dose to prevent
accumulation in the plasma.
Hepatic Impairment:
May require a lower dose.
Precautions:
WARNING: Antidepressants increase the risk of
suicidal thoughts and behaviors in pediatric and
young adult patients. Closely monitor for clinical
worsening and for emergence of suicidal thoughts
and behaviors.
Blood pressure effects (e.g., hypertension and orthostatic
hypotension); CNS depression; dyskinesia; impulse
control disorders.
Melanoma; psychosis; serotonin syndrome; hepatic and
renal impairment; hypoglycemia; surgery patients.
Elderly (orthostatic hypotension when titrating dose);
children (monitor for activation of suicidal ideation).
Pregnancy (use is not recommended, especially during the
first trimester); lactation.
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: hypertension, hypotension, chest pain,
peripheral edema, body pain, confusion, hallucination,
vivid dream, lethargy, abnormality in thinking, agitation,
amnesia, paresthesia, headache, dizziness, insomnia,
skin rash, acne vulgaris, diaphoresis, pruritus, weight
loss, diarrhea, xerostomia, abdominal pain, nausea,
dyspepsia, constipation, vomiting, dysgeusia, flatulence,
anorexia, gastroenteritis, urinary retention,
dysmenorrhea, sexual disorder, UTI, urinary frequency,
uterine hemorrhage, bruise, leg cramps, myalgia,
tinnitus, pharyngitis, sinusitis, bronchitis, cough.
Less Common: Agitation, ankle edema, arrthymias, anxiety,
dyspnea, angina, blurred vision, loss of appetite,
palpitation, micturition difficulties, leukocytopenia,
postural hypotension, skin reactions, thrombocytopenia,
supraventricular tachycardia.
Rare: Activation of suicidal ideation and behavior.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Selegiline:
Dihydrocodeine, Fentanyl, Metaxalone, Opioids,
Oxycodone, Tapentadol, Oxcarbazepine (serotonergic
effect)
Diphenoxylate (hypertensive effect)
Pheniramine (anticholinergic effect)
Spinal Anesthesia (combined hypotensive effects)
Enhances therapeutic effect of the following drugs:
Alpha / Beta Agonists (Indirect-Acting), Alpha1 Agonists,
Amphetamines, Dopamine, Epinephrine, Bupropion,
Norepinephrine (hypertensive effect)
Anticholinergics, Pizotifen (anticholinergic effects)
N
Blood Glucose Lowering Agents (hypoglycemic effect)
Blood Pressure Lowering Agents, Pindolol (hypotensive
effect)
CNS depressants (sedation and hypotension)
Mequitazine (anticholinergic effect)
SSRIs, Serotonin Modulators, SNRIs, TCAs (serotonergic
effect)
Increases risk of adverse or toxic effects of Selegiline:
Antipsychotics (serotonin syndrome)
Increases risk of adverse or toxic effects of Selegiline:
Antipsychotics, Second Generation / Atypical, Spinal
Anesthesia, Blood Pressure Lowering Agents (Topical)
(hypotensive effect)
Buprenorphine, Cerebrolysin, Chlorphenesin,
Carbamate, COMT Inhibitors, Dapoxetine, Ethyl Alcohol,
Oxymorphone, Tryptophan, Heroin, Hydrocodone,
Hydromorphone
Buspirone (blood pressure elevations)
Fentanyl, Opioids, Oxycodone (serotonin syndrome)
Disulfiram (acute delirium)
L-tryptophan, L–tyrosine, Phenylalanine (hypertensive
crisis)
Levodopa (hypertensive reactions)
Tapentadol (adverse cardiovascular effects; serotonin
syndrome)
Increases risk of adverse or toxic effects of the following
drugs:
Antipsychotics (neuroleptic malignant syndrome)
Atomoxetine (neurotoxic / central effect)
Atropine (Ophthalmic), Methylphenidate,
Tetrahydrozoline (Nasal) (hypertensive effect)
Beta2 Agonists, Codeine, Domperidone, Lithium,
Methyldopa, Moclobemide, Morphine, Serotonin
Reuptake Inhibitor or Antagonists
Hypotension-Associated Agents (hypotensive effect)
485

Iohexol, Iomeprol, Iopamidol (seizures)
Metoclopramide (serotonin syndrome; neuroleptic
malignant syndrome)
Mirtazapine (neurotoxic effect)
Reserpine (paradoxical effects, e.g., excitation,
hypertension)
SSRIs, Serotonin Modulators, SNRIs, TCAs (serotonin
syndrome)
Reduces diagnostic effect of I123
Reduces therapeutic effect of Selegiline:
Domperidone
Reduces therapeutic effect of Domperidone
Avoid concomitant use with:
Enhances therapeutic effect of Selegiline:
Alcohol (central effects)
Tyramine (additive sympathomimetic effects)
Increases risk of adverse or toxic effects of Selegiline:
Alcohol, Carbamazepine
Antidepressants, Ginseng, Linezolid, MAOB Inhibitors,
Methadone, Methylene Blue, Sibutramine,
Propoxyphene (serotonin syndrome)
Dextromethorphan, Meperidine, Non-selective MAOIs
(severe agitation, stupor, muscle rigidity, elevated
N
temperatures, hallucinations, death)
Sympathomimetics (severe agitation, stupor, muscle
rigidity, elevated temperatures, hallucinations,
hypertensive crisis, death)
Tramadol (serotonin syndrome; seizures)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics, Guanethidine (combined hypotensive effects)
Increases serum concentration of Selegiline:
Carbamazepine
Administration: Should be taken with food.
Do NOT discontinue abruptly. Gradually taper dose.
When discontinuing selegiline, wait 2 weeks (wash-out
period) before starting another antidepressant to allow
enough time for the body to regenerate MAO enzyme.
NOTE: Abrupt discontinuation or interruption of
antidepressant therapy has been associated with a
discontinuation syndrome, which may resemble
neuroleptic malignant syndrome; symptoms may include
elevated temperature, muscular rigidity, altered
consciousness and autonomic instability.
Pregnancy Category: C
ATC Code: N04BD01
486
NERVOUS SYSTEM
OTHER DRUGS FOR PARKINSONISM
Rx DIPHENHYDRAMINE
Oral: 25 mg and 50 mg capsule (as hydrochloride)
12.5 mg/5 mL, 30 mL and 60 mL syrup
Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
Diphenhydramine is a monoethanolamine-derived, first-
generation H1 receptor antagonist, which exhibits anti-
muscarinic and pronounced sedative property, with low
incidence of GI side effects.
Indications: Management of Parkinsonism; drug-induced
dystonic reaction (Extrapyramidal Syndrome).
Contraindications: Acute asthma; neonates or premature
infants (increased susceptibility to antimuscarinic
effects); breastfeeding; use of the parenteral form as a
local anesthetic.
Dose:
Parkinsonism, by mouth, ADULT, 25–50 mg 3 or 4 times
daily and reassess need for continued administration
after 1–2 weeks;
by IV infusion, ADULT, 10–50 mg per dose at a rate not
exceeding 25 mg/minute, may use doses up to 100
mg/dose (maximum, 400 mg daily); CHILD ≥12 years, 5
mg/kg every 24 hours; or 150 mg every 24 hours at a
rate not exceeding 25 mg/minute (maximum daily dose,
300 mg divided into 4 doses);
by deep intramuscular injection, ADULT, 10–50 mg per
dose (maximum daily dose, 400 mg); CHILD ≥12 years,
5 mg/kg every 24 hours; or 150 mg every 24 hours
(maximum daily dose, 300 mg divided into 4 doses).
Drug-induced dystonic reaction (extrapyramidal syndrome),
by IM or IV injection, ADULT, 25–50 mg single dose, may
repeat in 20–30 minutes if necessary; CHILD, 0.5–1
mg/kg per dose.
Dose Adjustment:
Geriatric:
If used, consider lower doses.
Use only smallest effective dose, 25 mg oral or IV every 8–
12 hours due to usual association with reduced
clearance of drug.
Hepatic Impairment:
In severe impairment, refer patient to a specialist.
Precautions:
WARNING: May cause sedation. Serious adverse drug
interactions are quite common, potentially fatal in
some. Antihistamines can cause hypersensitivity
reactions themselves.
CNS depression (caution in performing tasks requiring
mental alertness); prostatic hypertrophy, urinary
retention, susceptibility to angle-closure glaucoma, and
pyloroduodenal obstruction; asthma; thyroid
dysfunction; cardiovascular disease; epilepsy.
Elderly (associated with reduced drug clearance, and
increased risk of confusion, dryness of mouth,
constipation or other anticholinergic effects, and
NERVOUS SYSTEM
toxicity); children (may cause excitation; more
susceptible to side-effects).
Pregnancy (use during the latter part of third trimester may
cause irritability, paradoxical excitability, and tremor in
neonates).
Adverse Drug Reactions:
Common: Anxiety, blurred vision, constipation, cough,
diarrhea, dizziness, dryness of mouth, nose and throat,
epigastric discomfort, euphoria, incoordination,
insomnia, nausea, nervousness, psychomotor
impairment, sedation, sleepiness, thickening of
bronchial secretions, tinnitus, tremor, vomiting.
Less Common: Hallucinations, hypotension, headache,
palpitations, psychosis, restlessness, urinary retention,
vertigo.
Rare: Agranulocytosis, arrhythmias, blood dyscrasias,
convulsions, EPS, hemolytic anemia, hepatitis,
hypersensitivity reactions, leukopenia, liver disorders,
excitation, hallucination, seizures, paralysis.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Diphenhydramine:
CNS Depressants, e.g., Alcohol, Anxiolytic Sedatives,
Barbiturates, Hypnotics, Neuroleptics, Opioid Analgesics
(sedative effect)
Enhances therapeutic effect of the following drugs:
Beta Blockers, e.g., Labetalol, Metoprolol, Propranolol
(cardiovascular effects)
Administration:
For oral administration, may be taken with or without
food.
For IV administration, do NOT exceed a rate of 25
mg/minute.
IM administration must be deep. Local necrosis may
result with SC or intradermal use.
Pregnancy Category: B
ATC Code: Not available
PSYCHOLEPTICS
ANTIPSYCHOTICS
Rx ARIPIPRAZOLE
Oral: 10 mg, 15 mg, 20 mg, and 30 mg tablet
10 mg and 15 mg orally disintegrating tablet (ODT)
Aripiprazole is a quinolinone derivative and an atypical
antipsychotic agent, which acts as a partial agonist at
dopamine D2 and serotonin 5-HT21A receptors and as an
antagonist at 5-HT22A receptors.
Indications: Management of Schizophrenia; acute mania or
mixed mania; adjunct treatment of major depressive
disorder; bipolar disorder; autism-related irritability;
Tourette syndrome.
Dose:
Acute mania or mixed mania, by mouth, ADULT, initially 10–
15 mg once daily, slowly titrate dose based on efficacy
and tolerability (maximum, 30 mg once daily), CHILD ≥10
years, initially 2 mg once daily for 2 days, increase to 5
mg once daily for 2 days, further increase to a target dose
of 10 mg once daily, slowly titrate dose in 5 mg
increments based on efficacy and tolerability (maximum,
30 mg once daily).
Autism-related irritability, by mouth, CHILD ≥6 years, initially
2 mg once daily for 7 days, then increase to 5 mg once
daily, slowly titrate dose in 5 mg increments at intervals
of ≥1 week based on efficacy and tolerability (maximum,
15 mg once daily).
Major depressive disorder, adjunct, by mouth, ADULT,
initially 2–5 mg once daily, may increase by 5 mg daily at
intervals of ≥1 week based on efficacy and tolerability
(maximum, 15 mg once daily).
Schizophrenia, by mouth, ADULT, initially 10–15 mg once
daily, slowly titrate dose based on efficacy and
tolerability (maximum, 30 mg once daily); CHILD ≥13
years, initially 2 mg once daily, slowly titrate dose based
on efficacy and tolerability (maximum, 30 mg once daily).
Tourette syndrome, by mouth, CHILD ≥6 years or <50 kg,
initially 2 mg once daily for 2 days, then increase to a
N
target dose of 5 mg once daily, slowly titrate dose at
intervals of no less than 1 week based on efficacy and
tolerability (maximum, 10 mg once daily); assess the
need for ongoing treatment periodically; CHILD ≥50 kg,
initially 2 mg once daily for 2 days, then increase to 5 mg
once daily for 5 days with a target dose of 10 mg once
daily on day 8, slowly titrate dose in 5 mg increments at
intervals of no less than 1 week based on efficacy and
tolerability (maximum, 20 mg once daily).
Dose Adjustment:
Geriatric:
May tolerate lower doses better. Antipsychotics are
considered potentially inappropriate in in the elderly.
Avoid in patients 65 years and older with dementia due
to an increased risk of mortality, cerebrovascular
accidents (stroke), a greater rate of cognitive decline with
use, and potential to cause or exacerbate or
hyponatremia unless all nonpharmacologic options have
failed or are not possible or the patient is threatening
substantial harm to self or to others.
Precautions:
WARNING: Elderly patients with dementia-related
psychosis are at an increased risk of death.
Aripiprazole is NOT approved for the treatment of
dementia-related psychosis.
Closely monitor for clinical worsening and for the
emergence of suicidal thoughts and behaviors.
Cardiovascular disease; Parkinson disease (may aggravate
motor disturbances); seizures.
Elderly (may be at increased risk of seizures; increased risk
of mortality and cerebrovascular accidents; potential to
cause or exacerbate SIADH or hyponatremia); children
487

(increased risk of suicidal thoughts and behavior; safety
and efficacy have not been established).
Pregnancy (risk of abnormal muscle movements and
withdrawal symptoms in newborns with use during the
third trimester); lactation (excreted in breastmilk;
monitor infant for possible adverse effects).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
TEST INTERACTION. May give false positive urine
immunoassay screening tests for amphetamines.
Adverse Drug Reactions:
Common: Malaise, hypersalivation, peripheral edema,
headache, dizziness, insomnia, drowsiness, sedation
(dose-related), lethargy, fatigue (dose-related),
extrapyramidal reaction (dose-related), akathisia (dose-
related), agitation, activation, anxiety, restlessness, pain,
dystonia, irritability, ataxia, tremor (dose-related),
anorexia, weight gain, weight loss, decreased HDL
cholesterol, nausea, vomiting, constipation, dyspepsia,
decreased or increased appetite, xerostomia,
toothache, diarrhea, gastric distress, stomach
discomfort, upper abdominal pain, abdominal distress,
urinary incontinence, dysmenorrhea, arthralgia, limb
pain, myalgia, stiffness, muscle cramps, muscle rigidity,
N
weakness, asthenia, muscle spasm, dyskinesia, blurred
vision, nasopharyngitis, upper respiratory tract infection,
cough, pharyngolaryngeal pain, epistaxis, aspiration
pneumonia, dyspnea, fever.
Less Common: Depression, dry mouth, anticholinergic
effects, hypersomnia, orthostatic hypotension, nasal
congestion, changes in body thermoregulation,
aggressive behavior, agranulocytosis, akinesia,
alopeciaamenorrhea, anaphylaxis, angina pectoris,
angioedema, anorgasmia, atrial fibrillation, atrial flutter,
AV block, altered serum glucose, bradycardia,
bradykinesia, bruxism, cardiac arrhythmia, catatonia,
cerebrovascular accident, change in libido, chest
discomfort, chest pain, choreoathetosis, cogwheel
rigidity, delayed ejaculation, delirium, depression,
diabetes mellitus, diabetic ketoacidosis, diplopia, drug-
induced Parkinson disease, dysgeusia, dysphagia,
dystonia (oromandibular), edema, erectile dysfunction,
esophagitis, extrasystoles, eyelid edema, facial edema,
falling, GERD, glycosuria, gynecomastia, heatstroke,
hepatotoxicity, hepatic failure, hepatitis, hirsutism,
homicidal ideation, hostility, hyperglycemia,
hyperhidrosis, hyperinsulinism, hyperlipidemia,
hypersensitivity reaction, hypertension, hypertonia,
hypokalemia, hypoglycemia, hypokinesia, hypothermia,
joint stiffness, hyponatremia, hypotonia, impulse control
disorder, MI, panic attack, intentional injury, ischemic
heart disease, jaundice, laryngospasm, skin
photosensitivity, leukopenia, mastalgia, memory
impairment, mobility disorder, muscle twitching,
myasthenia, menstrual disease, myoclonus, nocturia,
obesity, oropharyngeal spasm, oculogyric crisis,
palpitations, pancreatitis, photophobia, photopsia,
pollakiuria, polydipsia, polyuria, presyncope, priapism,
prolonged QT interval, pruritus, psychosis,
rhabdomyolysis, seizure, sleep apnea syndrome
(obstructive), sleep talking, somnambulism, SVT, speech
disturbance, suicidal tendencies, tics, suicidal ideation,
488
NERVOUS SYSTEM
swollen tongue, syncope, tardive dyskinesia,
thrombocytopenia, tongue spasm, tonic-clonic seizures,
torsades de pointes, transient ischemic attacks, trismus,
uncontrolled diabetes mellitus, urinary retention,
urticaria, venous thromboembolism, ventricular
tachycardia.
Rare: Neuroleptic malignant syndrome, seizures, theoretical
risk of tardive dyskinesia, dysphagia, blood dyscrasias
(leukopenia, neutropenia, agranulocytosis), increased
risk of death and cerebrovascular events (elderly with
dementia-related psychosis).
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Aripiprazole:
Antidepressants (serotonergic effect)
Antihypertensives
CNS Depressants (central effects)
Increases risk of adverse or toxic effects of Aripiprazole:
Lithium (neurotoxic effect)
Methylphenidate, Metoclopramide
(sleepiness; dizziness)
Increases risk of adverse or toxic effects of the following
drugs:
Acetylcholinesterase Inhibitors (extrapyramidal
symptoms)
Antidepressants (serotonin syndrome; neuroleptic
malignant syndrome)
Iohexol, Iomeprol, Iopamidol (seizures)
Mequitazine (arrhythmogenic effect)
Serotonin Modulators (serotonin syndrome; neuroleptic
malignant syndrome)
SSRIs (psychomotor impairment)
Methylphenidate
Reduces therapeutic effect of the following drugs:
Amphetamines, CNS Stimulants (stimulant effect)
Antidiabetics, Dopamine Agonists
Guanethidine (antihypertensive effect)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Aripiprazole:
Other Antipsychotics (increased side effect burden, high
dose prescribing, increased hospitalization rates and
length of stay, higher treatment costs, and increased
mortality)
Administration: May be taken with or without food
Orally disintegrating tablets must be removed from the
foil blister by peeling back. Do NOT push the tablet
through the foil. Place tablet in mouth immediately upon
removal. Tablet dissolves rapidly in saliva and may be
swallowed without liquid. If needed, can be taken with
liquid. Do NOT split the tablet.
NOTE: Do NOT discontinue abruptly because of the
possibility of withdrawal and rebound psychosis.
Discontinue gradually to avoid physical withdrawal
symptoms, including anorexia, anxiety, diaphoresis,
diarrhea, dizziness, dyskinesia, headache, myalgia,
nausea, paresthesia, restlessness, tremulousness, and
vomiting.
NERVOUS SYSTEM
Pregnancy Category: C
ATC Code: N05AX12
Rx CHLORPROMAZINE
Oral: 50 mg, 100 mg, and 200 mg tablet (as hydrochloride)
Inj.: 25 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
Chlorpromazine is a dimethylamine derivative of
phenothiazine. It has weak anticholinergic and strong
antiadrenergic activity and possesses slight ganglionic,
antihistaminic, and anti-serotonin activity. It blocks at
least 60% of D2 receptors in the mesolimbic pathway of
the brain to produce a therapeutic effect on the positive
symptoms of schizophrenia.
Indications: Management of schizophrenia; bipolar mania;
nausea; vomiting; restlessness and apprehension before
surgery; acute intermittent porphyria; manifestations of
manic type of manic-depressive illness; tetanus
(adjunct); intractable hiccups; combativeness and/or
explosive hyperexcitable behavior (children); hyperactive
children who show excessive motor activity with
accompanying conduct disorders consisting impulsivity,
difficulty sustaining attention, aggressivity, mood lability,
poor frustration tolerance, and/or psychosis.
Contraindications: Hypersensitivity to chlorpromazine, other
phenothiazines, sulfites, or any component of the
formulation; comatose states; Reye’s syndrome; blood
dyscrasias; bone marrow suppression; subcortical brain
injury, CNS depression, pheochromocytoma,
hypothyroidism.
Dose:
Acute intermittent porphyria, by mouth, ADULT, 25–50 mg
3 or 4 times daily;
by IM injection, ADULT, 25 mg 3 or 4 times daily until
patient can tolerate oral administration.
Behavior problems, severe, by mouth, CHILD ≤45.5 kg and
INFANT ≥6 months, initially 0.55 mg/kg every 4–6 hours
as needed, slowly titrate dose based on efficacy and
tolerability (maximum, 500 mg once daily); CHILD ≥45.5
kg, initially 30–40 mg daily in 3–4 divided doses or 50–
75 mg daily in 2–3 divided doses, slowly titrate dose
based on efficacy and tolerability; usual dose is 200 mg
once daily.
Bipolar mania, by mouth, ADULT, initially 30–40 mg daily in
3–4 divided doses or 50–75 mg daily in 2–3 divided
doses; an initial dose of 100–200 mg once daily is
reserved for severe inpatient cases, slowly titrate dose
based on efficacy and tolerability (maximum, 1,000 mg
once daily);
by IM injection, ADULT, initially 25 mg, a second 25-mg
or 50-mg dose may be administered after 1 hour, slowly
titrate dose based on efficacy and tolerability (maximum,
400 mg every 4–6 hours).
Intractable hiccups, by mouth, ADULT, 25–50 mg 3 or 4
times daily for 2–3 days, if symptoms are persistent
beyond 2–3 days, administer parenterally;
by IM injection, ADULT, if refractory to oral treatment,
25–50 mg;
by slow IV infusion, ADULT, if refractory to IM treatment,
25–50 mg in 500–1,000 mL normal saline; CHILD 1–12
years, 500 micrograms/kg every 4–6 hours (maximum
daily dose, 75 mg if 5 years old, 40 mg if 1–5 years old).
Nausea and vomiting, non-CINV (chemotherapy-induced
nausea and vomiting), by mouth, ADULT, 10–25 mg
every 4–6 hours as needed;
by IM injection, ADULT, initially 25 mg; if no hypotension
occurs, 25–50 mg every 3–4 hours may be given until
vomiting stops; during surgery, initially administer 12.5
mg and repeat in 30 minutes if necessary and if no
hypotension occurs;
by IV injection, ADULT, during surgery, 2 mg per fractional
injection at 2-minute intervals using a 1 mg/mL solution,
not to exceed 25 mg;
by mouth, IM or IV injection, CHILD ≥5 years or >22.7 kg
but <45.5 kg, initially 0.55 mg/kg every 6–8 hour as
needed; in severe cases, higher doses may be needed
up to a maximum of 75 mg once daily; CHILD <5 years or
<22.7 kg and INFANT ≥6 months, initially 0.55 mg/kg
every 6 to 8 hours as needed; in severe cases, higher
doses may be needed up to a maximum of 40 mg once
daily; CHILD ≥45.5 kg, initially 25 mg; if no hypotension
occurs, administer 25–50 mg every 4–6 hours as
needed.
Schizophrenia, by mouth, ADULT (outpatient), 10 mg 3–4
times daily, or 25 mg 3 times daily; for more severe
cases, may increase the initial dose after 1–2 days by
N
20–50 mg at semi-weekly intervals until patient
becomes calm and cooperative;
ADULT (hospitalized), 25 mg 3 times daily, increase
gradually until effective dose is reached (usually 400 mg
daily); for patients in acute schizophrenic state, once
patient is quiet and cooperative, oral doses may be
substituted for IM and increased, usually to 500 mg
daily, may gradually increase to 2,000 mg daily may be
needed, although doses greater than 1,000 mg daily for
extended periods generally do not provide therapeutic
gain.
by IM injection, ADULT, initially 25 mg, a second 25-mg
to 50-mg dose may be administered after 1 hour; slowly
titrate dose based on efficacy and tolerability until
patient is controlled, usually within 24–48 hours at
which time oral doses may be substituted (maximum,
400 mg every 4–6 hours).
Tetanus adjunct, by IM injection, ADULT, usually in
combination with barbiturates, initially 25–50 mg 3 or 4
times daily, slowly titrate dose to response;
by IV injection, ADULT, usually in conjunction with
barbiturates, 25–50 mg at a rate of 1 mg/minute, initiate
with low dose and gradually increase;
by IM or IV injection, CHILD ≥5 years or >22.7 kg but
<45.5 kg, initially 0.55 mg/kg every 6–8 hour as needed;
in severe cases, higher doses may be needed up to a
maximum of 75 mg once daily; CHILD <5 years or <22.7
kg and INFANT ≥6 months, initially 0.55 mg/kg every 6–
8 hour as needed; in severe cases, higher doses may be
needed up to a maximum of 40 mg once daily; CHILD
≥45.5 kg, initially 25 mg; if no hypotension occurs, 25–
50 mg 3 or 4 times daily, slowly titrate dose to response.
Dose Adjustment:
Geriatric:
Start with small doses in severe renal impairment because
of increased cerebral sensitivity.
489

Hepatic Impairment:
Can precipitate coma; phenothiazines are hepatotoxic.
Precautions:
WARNING: Elderly patients with dementia-related
psychosis are at an increased risk of death.
Closely monitor for clinical worsening and for the
emergence of suicidal thoughts and behaviors.
Cardiovascular disease; anticholinergic effects (e.g.,
constipation, xerostomia, blurred vision, urinary
retention); blood dyscrasias (e.g., leukopenia,
neutropenia, and agranulocytosis, some fatal); seizures.
Hepatic impairment; masking (may mask signs of other
disorders or overdose); renal impairment; respiratory
disease; Reye syndrome; ocular effects (pigmentary
retinopathy, and lenticular and corneal deposits);
photosensitivity (mild urticarial-type rash or
photosensitivity); glaucoma.
Elderly (tardive dyskinesia; mortality and cerebrovascular
accidents; SIADH or hyponatremia); children (suicidal
thoughts and behavior; safety and efficacy have not
been established).
Pregnancy (abnormal muscle movements and withdrawal
symptoms in newborns with use during the third
trimester); lactation (monitor infant for possible adverse
effects).
N
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Neuroleptic-induced deficit syndrome, akathisia,
priapism, extrapyramidal symptoms, parkinsonism,
acute dystonia, galactorrhea, dry mouth, amenorrhea,
gynecomastia, dizziness, sedation, impaired memory,
constipation, urinary retention, blurred vision, decreased
sweating, sexual dysfunction, hypotension, tachycardia,
syncope, tardive dyskinesia, maculopapular rash, weight
gain, erythema multiforme, urticaria, photosensitivity
reactions, urine discoloration (red to red-brown),
photosensitivity, cholestatic jaundice, long-term skin
pigmentation changes.
Less Common: Jaundice, changes in body
thermoregulation.
Rare: Cornea and lens pigmentation, retinitis pigmentosa,
blood dyscrasias (leukocytosis or leukopenia,
eosinophilia, thrombocytopenia, agranulocytosis),
seizures, increased risk of death and cerebrovascular
events (elderly with dementia-related psychosis),
neuroleptic malignant syndrome.
Drug Interactions:
Monitor closely with:
Decreases metabolism of Phenytoin
Enhances therapeutic effect of the following drugs:
Antihypertensives [except Guanethidine]
Beta Blockers [except Atenolol, Nadolol]
CNS Depressants (central effects)
Vasopressors, e.g. Epinephrine (lowers blood pressure)
Thiopental (hypotensive effect; CNS excitatory effect)
Increases risk of adverse or toxic effects of Chlorpromazine:
490
NERVOUS SYSTEM
Methylphenidate, Metoclopramide, Lithium (neurotoxic
effect)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics, Hypotension-associated Agents (hypotension)
Glucagon (GI adverse effects)
Iohexol, Iomeprol, Iopamidol (seizures)
Mequitazine (arrhythmogenic effect)
Methylphenidate, Mirabegron
Photosensitizing Agents (photosensitizing effect)
QTc-prolonging Agents (torsades de pointes)
Serotonin Modulators (neuroleptic malignant syndrome;
serotonin syndrome)
SSRIs (psychomotor impairment)
Topiramate (hyperthermia)
Reduces absorption of Chlorpromazine:
Antacids
Reduces absorption of Nitroglycerin (decreases dissolution
of sublingual nitroglycerin tablets)
Reduces therapeutic effect of Chlorpromazine:
Anticholinergics (anticholinergic effect)
Methylphenidate (inhibits antipsychotic and mood-
stabilizing activity)
Reduces therapeutic effect of the following drugs:
Anticoagulants, Dopamine Agonists, Prokinetics,
Secretin
Amphetamines (stimulant effect)
Guanethidine (antihypertensive effects)
Methylphenidate (inhibits stimulatory effects)
Avoid concomitant use with:
Decreases serum concentration of Tamoxifen
Delayed gastric emptying with Potassium Salts (Oral)
Increases risk of adverse or toxic effects of the following
drugs:
Nilotinib (QTc prolongation; torsades de pointes)
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration:
For oral administration, may be taken with or without
food. May be taken with meals to reduce GI discomfort.
For direct IV injection, admqinister diluted solution by
slow IV at a rate not to exceed 0.5 mg/minute in children
and 1 mg/minute in adults. Patients must remain lying
down during and for 30 minutes after administration to
reduce the risk of hypotension.
For IM administration, inject slowly, deep into the upper
outer quadrant of buttock.
Do NOT administer by SC injection to prevent tissue
damage and irritation. Avoid skin contact with solution to
prevent contact dermatitis.
NOTE: Do NOT discontinue abruptly because of the
possibility of withdrawal and rebound psychosis.
NERVOUS SYSTEM
Discontinue gradually to avoid physical withdrawal
symptoms, including anorexia, anxiety, diaphoresis,
diarrhea, dizziness, dyskinesia, headache, myalgia,
nausea, paresthesia, restlessness, tremulousness, and
vomiting.
For the treatment of intractable hiccups, infuse as a slow
IV infusion.
Pregnancy Category: C
ATC Code: N05AA01
Rx CLOZAPINE
Oral: 25 mg and 100 mg tablet
Clozapine is a tricyclic dibenzodiazepine and an atypical
antipsychotic with weak D2 blocking action. It is the only
antipsychotic documented to reduce suicide risk in
patients with schizophrenia. It has 5-HT2A antagonism
which gives it little to no EPS and tardive dyskinesia risk,
and dose not elevate prolactin. It is often reserved as a
last-line option due to the risk of developing life-
threatening and occasionally fatal agranulocytosis, as
well as an increased risk of seizures.
Indications: Management of clozapine-resistant
schizophrenia; for reducing the risk of recurrent suicidal
behavior in patients with schizophrenia and
schizoaffective disorder.
Contraindications: Uncontrolled epilepsy, paralytic ileus,
myoproliferative disorders, history of clozapine-induced
agranulocytosis or severe granulocytopenia; severe CNS
depression; coma, bone-marrow disorders, alcoholic and
toxic psychoses, severe cardiac disorders (e.g.,
myocarditis), history of circulatory collapse.
Dose:
Treatment-resistant schizophrenia and for reducing risk of
recurrent suicidal behavior in patients with
schizophrenia and schizoaffective disorder, by mouth,
ADULT, initially 25 mg daily in 2 divided doses, slowly
increase by 25–50 mg daily each day to a target dose of
300–450 mg daily in divided doses by the end of 2
weeks; administer doses above 300 mg once daily in
divided doses; dose increases beyond 450 mg once daily
should be done no more frequently than once or twice
weekly in increments not exceeding 100 mg daily up to a
maximum dose of 900 mg once daily; if dosing is
interrupted for ≥48 hours, re-initiate therapy at 12.5 mg
once or twice daily to minimize the risk of hypotension,
bradycardia, and syncope.
NOTE: Recommended dose is between 300–800 mg once
daily for at least 8 weeks as an adequate trial in
treatment-resistant schizophrenia. If despite adequate
dosing and adherence there is no adequate response,
perform therapeutic drug monitoring. Plasma levels
above 350 nanograms/mL have been associated with
treatment response.
Dose Adjustment:
Geriatric:
May tolerate lower doses better. Initiate with 12.5 mg once
daily for 3 days, then increase to 25 mg once daily for 3
days as tolerated, may further increase, as tolerated, in
increments of 12.5–25 mg daily every 3 days to desired
response, up to a maximum of 700 mg daily.
Renal Impairment:
Avoid in severe impairment.
Hepatic Impairment:
Avoid in symptomatic liver disease, progressive liver disease
and hepatic failure. Monitor hepatic function regularly.
Precautions:
WARNING: Agranulocytosis. Associated with a
significant risk of potentially life-threatening
agranulocytosis. Reserved use in the treatment of
severely-ill patients with schizophrenia who fail to
show an acceptable response to adequate courses
of standard antipsychotic drug treatment, or for
reducing the risk of recurrent suicidal behavior in
patients with schizophrenia and schizoaffective
disorder who are judged to be at risk of re-
experiencing suicidal behavior. Patients must have
a baseline absolute neutrophil count (ANC) before
initiation of treatment, as well as regular ANCs
N
during treatment and for at least 4 weeks after
discontinuation of treatment.
Seizures. Use caution when administering to
patients with a history of seizures or other
predisposing factors. Advise patients not to engage
in any activity where sudden loss of consciousness
could cause serious risk to themselves or others.
Fatal myocarditis and cardiomyopathy.
Discontinue immediately when myocarditis is
suspected. Re-challenge with clozapine patients
with clozapine-related myocarditis or
cardiomyopathy.
Orthostatic hypotension, with or without
syncope, can occur. Rarely, collapse can be
profound and be accompanied by respiratory
and/or cardiac arrest. In case of a brief interval off
clozapine, i.e. 2 or more days since the last dose,
resume treatment with 12.5 mg once or twice daily.
Use with caution when administered concurrently
with benzodiazepine or any other psychotropic drug
since collapse, respiratory arrest and cardiac arrest
has occurred in this combination.
Elderly patients with dementia-related psychosis
treated with antipsychotic drugs are at an
increased risk of death. Clozapine is not approved
for use in patients with dementia-related
psychosis.
Anticholinergic effects (e.g., constipation, xerostomia,
blurred vision, urinary retention; use is associated with
491
 NERVOUS SYSTEM

increased risk of paralytic ileus, bowel obstruction, fecal dysphagia, enlargement of salivary glands, erythema
impaction, bowel perforation, and in rare cases death); multiforme, fecal impaction, gastroenteritis,
fever (benign transient temperature elevation >38°C or granulocytopenia, esophageal dysmotility, hepatic
100.4°F); neuroleptic malignant syndrome; impared cirrhosis, hepatic fibrosis, hepatic insufficiency, hepatic
temperature regulation. necrosis, hepatitis, hypersensitivity reaction,
CNS depression; extrapyramidal symptoms e.g. acute hepatotoxicity, hyperglycemia associated with
dystonic reactions, pseudoparkinsonism, akathisia, and ketoacidosis or hyperosmolar coma or death,
tardive dyskinesia; risk of dystonia may be greater with hyperuricemia, hyponatremia, interstitial nephritis
increased doses); falls; suicidal ideation; QT prolongation (acute), intestinal obstruction, jaundice, ketoacidosis,
(ventricular arrhythmias; cardiac arrest and sudden leukocytosis, liver injury, liver steatosis, lower respiratory
death). tract infection, mitral valve insufficiency, myasthenia
Dyslipidemia; eosinophilia; hyperglycemia (associated with syndrome, myocardial infarction, myocarditis,
ketoacidosis, hyperosmolar coma, or death); sialorrhea myoclonus, neuroleptic malignant syndrome, nocturnal
(drooling, skin irritation and infections, aspiration enuresis, obsessive compulsive disorder, obstructive
pneumonia, chronic sleep disturbances with daytime orthostatic hypotension, palpitations, sleep apnea,
fatigue and somnolence, painful swelling of the salivary pancreatitis (acute), paralytic ileus, paresthesia,
glands, and symptomatic aerophagia with resultant gas pheochromocytoma (pseudo), periorbital edema, pleural
bloating, pain, and flatus may also develop); effusion, pneumonia, priapism, pulmonary embolism,
thromboembolism (deep vein thrombosis and pulmonary prolonged QT interval (dose-dependent), renal failure,
embolism, some fatal). psychosis (exacerbated), retrograde ejaculation,
Esophageal dysmotility or aspiration; hepatotoxicity (severe, rhabdomyolysis, sepsis, skin photosensitivity,
life-threatening, sometimes fatal, including hepatic sialadenitis, status epilepticus, SJS, systemic lupus
failure, hepatic necrosis, and hepatitis); weight gain. erythematosus, syncope, tardive dyskinesia,
Acute infectious or inflammatory processes; benign ethnic thrombocytopenia, thrombocytosis, torsade de pointes,
neutropenia; cardiovascular disease; glaucoma; vasculitis, weight loss.
prostate; renal impairment. Rare: Changes in body thermoregulation.
Smokers (decreases clozapine concentration; may require
twice the daily dose to obtain an equivalent Drug Interactions:
N

concentration; smoking cessation may cause toxicity in Monitor closely with:

patients stabilized on clozapine; monitor change in
smoking patterns).
Elderly (more susceptible to adverse effects; potentially
inappropriate in the elderly; avoid use in patients ≥65
years with dementia due to an increased risk of mortality
and cerebrovascular accidents, a greater rate of
cognitive decline, and potential to cause or exacerbate
SIADH or hyponatremia, unless all non-pharmacologic
options have failed or are not possible or the patient is
threatening substantial harm to self or to others).
Pregnancy (risk of abnormal muscle movements and
withdrawal symptoms in newborns with fetal exposure
during the third trimester); lactation (monitor infant for
possible adverse effects).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Tachycardia, hypotension, hypertension, syncope,
drowsiness, sedation, dizziness, insomnia, headache,
agitation, restlessness, vertigo, akinesia, disturbed
sleep, nightmares, akathisia, confusion, seizure (dose
related), fatigue, tremor, hypersalivation (can be severe),
diaphoresis, skin rashweight gain, sialorrhea, weight
gain, constipation, nausea, vomiting, dyspepsia,
xerostomia, abdominal distress, heartburn, diarrhea,
leukopenia, neutropenia, eosinophilia, urine
abnormality, hypokinesia, muscle rigidity, visual
disturbance.
Less Common: Agranulocytosis, abnormal
electrocephalogram, angioedema, aspiration,
bradycardia, cardiac arrhythmia, cardiac failure,
cardiomyopathy (usually dilated), cataplexy,
cerebrovascular accident, cholestasis, colitis, deep vein
thrombosis, delirium, diabetes mellitus, dyschromia,
Enhances therapeutic effect of the following drugs:
Antihypertensives
CNS Depressants (central effects)
Increases risk of adverse or toxic effects of Clozapine:
Methylphenidate, Metoclopramide (sleepiness and
dizziness)
Lithium (neurotoxic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Acetylcholinesterase Inhibitors (extrapyramidal
symptoms), Antihypertensives (hypotension)
Glucagon (GI adverse effects)
Iohexol, Iomeprol, Iopamidol (seizures)
Mequitazine (arrhythmogenic effect)
Mirabegron, Topiramate, Myelosuppressive Agents
(bone marrow suppression)
QTc-prolonging Agents (torsades de pointes) Saquinavir
(arrhythmogenic effect)
Serotonin Modulators (neuroleptic malignant syndrome;
serotonin syndrome)
SSRIs (psychomotor impairment)
Reduces absorption of Nitroglycerin (decreases dissolution
of sublingual nitroglycerin tablets)
Reduces therapeutic effect of the following drugs:
Antidiabetics, Phenylephrine, Prokinetics, Secretin
Amphetamines (stimulant effect)
Anticholinergics (anticholinergic effect)
Epinephrine (reverses pressor effect)
Guanethidine (antihypertensive effects)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:

492
NERVOUS SYSTEM
Agranulocytosis-inducing Drugs (agranulocytosis)
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration: May be taken with or without food.
Do NOT discontinue abruptly because of the possibility of
withdrawal and rebound psychosis. Perform
discontinuation or cross-titration gradually over 1–2
weeks to minimize the potential of withdrawal, rebound
psychosis, extrapyramidal side effects, cholinergic
rebound, rebound insomnia, and unwanted pregnancy,
unless safety concerns require a more rapid withdrawal.
Pregnancy Category: B
ATC Code: N05AH02
Rx FLUPENTIXOL
Inj.: 20 mg/mL (as decanoate), 1 mL ampule and 10 mL
vial (IM)
Flupentixol is a thioxanthene typical antipsychotic that
inhibits dopamine-mediated effects by blocking
postsynaptic dopamine receptors in the CNS. It was
formulated as a long-acting injectable for use in patients
with schizophrenia who have difficulty with adherence to
oral medications.
Indication: Management of chronic schizophrenia whose
main manifestations do not include excitement, agitation
or hyperactivity; bipolar disorder
Contraindications: Acute intoxication with ethanol,
barbiturate, or opioid; psychoneurotic patients or
geriatric patients with confusion and/or agitation;
suspected or established subcortical brain damage; CNS
depression; blood dyscrasias; comatose or brain
damage; pheochromocytoma; liver damage; severe
cardiovascular disorder; cerebrovascular insufficiency;
renal insufficiency.
Dose:
Maintenance therapy of schizophrenia and reduces
symptoms of acute psychotic mania but not proven as a
mood stabilizer or as an effective maintenance
treatment in bipolar disorder, by IM injection, ADULT
(stabilized on oral flupentixol), 20 mg into the gluteal
muscle; continue oral flupentixol until 1 week after first
injection while slowly tapering; administer second 20 mg
dose not earlier than 4–10 days after the first injection,
followed by 20–40 mg every 2–3 weeks maintenance
dose; maximum of 200 mg every 1-4 weeks
NOTE: Conversion of oral flupentixol to long-acting injectable
maintenance dose:
x mg once daily is equivalent to
4x mg decanoate every 2 weeks; or
8x mg decanoate every 4 weeks
Slowly titrate dose at maximum increments of ≤20 mg
based on efficacy and tolerability up to a maximum
maintenance dose of 200 mg every 1–4 weeks.
Dose Adjustment:
Geriatric:
Initially 5 mg by IM injection into the gluteal muscle.
Recommended maintenance dose is 10–20 mg every 15
days.
Renal Impairment:
Recommended maintenance dose is 10–20 mg every 15
days.
Hepatic Impairment:
Can precipitate coma. Consider serum-flupentixol
concentration monitoring
Precautions:
WARNING: Neuroleptic malignant syndrome. Has been
associated with use. Monitor for mental status
changes, fever, muscle rigidity and/or autonomic
instability, elevated creatine phosphokinase (CPK),
myoglobinuria, and/or acute renal failure.
Discontinue treatment immediately with onset of
NMS. Recurrence has been reported when re-
challenged with antipsychotic therapy.
N
Elderly patients with dementia-related psychosis
treated with antipsychotic drugs are at an increased
risk of death.
Anticholinergic effects (e.g., constipation, xerostomia,
blurred vision, urinary retention; use is associated with
increased risk of paralytic ileus, bowel obstruction, fecal
impaction, bowel perforation, and in rare cases death);
Impaired temperature regulation
CNS depression; extrapyramidal symptoms (e.g., acute
dystonic reactions, pseudoparkinsonism, akathisia, and
tardive dyskinesia; risk of dystonia may be greater with
increased doses); dementia; Parkinson disease; seizure
disorder; ocular effects (lens opacity has been reported
rarely).
Esophageal dysmotility or aspiration; masking of toxicity of
other drugs or conditions; diabetic ketoacidosis
Altered cardiac conduction (life-threatening arrhythmias);
cardiovascular disease; orthostatic hypotension; blood
dyscrasias (agranulocytosis, neutropenia, leukopenia,
and granulocytopenia); venous thromboembolism.
Glaucoma; hepatic impairment; renal impairment; prolactin-
dependent tumors.
Surgical patients (monitor closely for hypotension).
Elderly (increased risk of tardive dyskinesia, especially
among women; potentially inappropriate in the elderly;
avoid use in patients ≥65 years with dementia due to an
increased risk of mortality and cerebrovascular
accidents, a greater rate of cognitive decline, and
potential to cause or exacerbate SIADH or hyponatremia,
unless all nonpharmacologic options have failed or are
not possible or the patient is threatening substantial
harm to self or to others).
Pregnancy (risk of abnormal muscle movements and
withdrawal symptoms in newborns with fetal exposure
during the third trimester); lactation (excreted in
breastmilk; tardive dyskinesia, dystonia, and sedation
have been observed in nursing infants).
493
 NERVOUS SYSTEM

SKILLED TASKS. May impair ability to perform tasks, which Reduces absorption of Nitroglycerin (decreases dissolution
require mental alertness, like driving or operating of sublingual nitroglycerin tablets)
machinery.
Reduces therapeutic effect of the following drugs:
Adverse Drug Reactions: Antidiabetics, Dopamine Agonists, Prokinetics, Secretin
Common: Neuroleptic-induced deficit syndrome, Amphetamines (stimulant effect) Anticholinergics
extrapyramidal symptoms, Parkinsonism, tardive (anticholinergic effect) Epinephrine (reverses pressor
dyskinesia (duration and dose dependent), acute effect)
dystonia, insomnia, restlessness, agitation, Guanethidine (antihypertensive effects)
galactorrhea, gynecomastia, amenorrhea, weight gain,
sedation, tachycardia, hypomania, photosensitivity, long- Avoid concomitant use with:
term skin pigmentation changes. Enhances therapeutic effect of CNS Depressants [high
Less Common: ECG changes (broadened, flattened T waves, dose] (CNS depression)
QT and PR interval prolongation, ST segment
depression), palpitations, syncope, depression, Increases risk of adverse or toxic effects of the following
dizziness, drowsiness, headache, hyperreflexia, drugs:
hypertonia, hypomania, insomnia, opisthotonos, Other Antipsychotics (increased hospitalization rates
psychomotor agitation, contact dermatitis, diaphoresis, and length of stay; increased mortality; QTc
eczema, erythema, exfoliative dermatitis, pruritus, prolongation; torsades de pointes)
seborrhea, skin rash, urticaria, amenorrhea, decreased
libido, hyperprolactinemia, increased libido, fatigue, Administration: Administer by deep IM injection into the
weight changes, constipation, nausea, paralytic ileus, gluteal muscle or deltoid muscle.
sialorrhea, xerostomia, impotence, urination disorder,
eosinophilia, jaundice, tremor, blurred vision, cataract, Do NOT discontinue abruptly because of the possibility of
oculogyric crisis, accommodation disturbance, withdrawal and rebound psychosis. Discontinue or cross-
abdominal pain, confusion, diarrhea, dyspepsia, titrate gradually to minimize the potential of withdrawal,
dyspnea, ejaculation failure, erectile dysfunction, rebound psychosis, extrapyramidal side effects,
flatulence, hot flash, hyperglycemia, impaired glucose cholinergic rebound, rebound insomnia, and unwanted
N

tolerance, increased appetite, muscle rigidity, myalgia, pregnancy, unless safety concerns require a more rapid
nervousness, prolonged QT interval, priapism, speech withdrawal.
disturbance, torsades de pointes, urinary retention,
ventricular arrhythmia, ventricular fibrillation, ventricular Pregnancy Category: C
tachycardia, vomiting, weakness.
Rare: Cholestatic jaundice, jaundice, neuroleptic malignant ATC Code: N05AF01
syndrome, seizures, changes in body thermoregulation,
blood dyscrasias (eosinophilia, leukocytosis or
leukopenia, granulocytopenia, agranulocytosis,
thrombocytopenia).
Rx FLUPHENAZINE

NOTE: Patients taking this drug may experience weight gain Inj.: 25 mg/mL (as decanoate), 1 mL ampule and 10 mL
and/or sedation. vial (IM)

Drug Interactions: Fluphenazine is a phenothiazine typical antipsychotic

Monitor closely with: formulated as a long-acting injectable for use in patients
Enhances therapeutic effect of the following drugs: with schizophrenia who have difficulty with adherence to
Antihypertensives oral medications. It blocks brain dopamine (D2) receptors
CNS Depressants (central effects) in the mesolimbic system and decreases the release of
hypothalamic and hypophyseal hormones.
Increases risk of adverse or toxic effects of Flupentixol:
Methylphenidate, Metoclopramide (sleepiness and Indication: Management of psychotic disorders.
dizziness)
Lithium (neurotoxic effect) Contraindications: Comatose state; CNS depression;
children <12 years; hepatic disease; blood dyscrasias;
Increases risk of adverse or toxic effects of the following bone marrow suppression; subcortical brain injury with
drugs: or without hypothalamic damage; marked cerebral
Acetylcholinesterase Inhibitors (extrapyramidal atherosclerosis; pheochromocytoma; pregnancy (third
symptoms) trimester); lactation.
Antihypertensives (hypotension)
Glucagon (GI adverse effects) Dose:
Iohexol, Iomeprol, Iopamidol (seizures) Psychotic disorders, by IM injection, ADULT (stabilized on
Mequitazine (arrhythmogenic effect), Mirabegron, oral fluphenazine), 12.5 mg/0.5 mL to 25 mg/1 mL into
Topiramate the deltoid or gluteal muscle; determine subsequent
QTc-prolonging Agents (torsades de pointes) Serotonin doses and intervals based on patient’s response;
Modulators (neuroleptic malignant syndrome; serotonin average dosing is usually 6.25–25 mg every 2 weeks or
syndrome) 50 mg/2 mL not longer than every 4 weeks; if doses >50
SSRIs (psychomotor impairment)

494
NERVOUS SYSTEM
mg are needed, increase cautiously in 12.5 mg up to a
maximum of 100 mg per dose.
Dose Adjustment:
Geriatric:
Use with caution and initiate with lower dose
Renal Impairment:
Use with caution and titrate slower. Monitoring is
recommended.
Hepatic Impairment:
Avoid in hepatic failure. Can precipitate coma.
Phenothiazines are hepatotoxic.
Precautions:
WARNING: NOT approved for the treatment of
patients with dementia-related psychosis. Elderly
patients with dementia-related psychosis treated
with antipsychotic drugs are at an increased risk
of death, mostly associated with cardiovascular
diseases (e.g. heart failure, sudden death) or
infections (e.g. pneumonia).
Altered cardiac conduction (life-threatening arrhythmias);
orthostatic hypotension; cardiovascular disease;
respiratory disorder; blood dyscrasias (agranulocytosis,
neutropenia, and leukopenia, some fatal).
Anticholinergic effects (e.g., constipation, xerostomia,
blurred vision, urinary retention); pheochromocytoma;
hyperprolactinemia; temperature regulation (impaired
core body temperature regulation); neuroleptic
malignant syndrome.
CNS depression; extrapyramidal symptoms
(pseudoparkinsonism, acute dystonic reactions,
akathisia, and tardive dyskinesia; risk of dystonia may be
greater with increased doses); Parkinson’s disease;
seizure disorder; ocular effects (cause pigmentary
retinopathy, and lenticular and corneal deposits);
glaucoma.
Esophageal dysmotility or aspiration; hepatic effects (liver
damage and jaundice of the cholestatic type of
hepatitis); hepatic impairment; renal impairment;
masking.
Elderly (increased risk of tardive dyskinesia, especially
among women; potentially inappropriate in the elderly;
avoid use in patients ≥65 years with dementia due to an
increased risk of mortality and cerebrovascular
accidents, a greater rate of cognitive decline, and
potential to cause or exacerbate SIADH or hyponatremia,
unless all nonpharmacologic options have failed or are
not possible or the patient is threatening substantial
harm to self or to others).
Pregnancy (risk of abnormal muscle movements and
withdrawal symptoms in newborns with fetal exposure
during the third trimester); lactation (tardive dyskinesia,
dystonia, and sedation have been observed in nursing
infants).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Neuroleptic-induced deficit syndrome, akathisia,
priapism, extrapyramidal symptoms, parkinsonism,
tardive dyskinesia, tardive dystonia, galactorrhea,
amenorrhea, sedation, dry mouth, urinary retention,
decreased sweating, sexual dysfunction, syncope, red to
red-brown urine, photosensitivity, long-term skin
pigmentation changes.
Less Common: Jaundice, cardiac arrhythmia, edema,
hypertension, hypotension, tachycardia, variable blood
pressure, akathisia, bizarre dream, cerebral edema,
depression, disruption of body temperature regulation,
dizziness, drowsiness, dystonia, excitement, headache,
hyperreflexia, lethargy, Parkinsonian-like syndrome,
tardive dyskinesia, restlessness, dermatitis, eczema,
erythema, pruritus, skin photosensitivity, seborrhea, skin
pigmentation, skin rash, urticaria, amenorrhea, change
in libido, galactorrhea, gynecomastia, menstrual
disease, SIADH (syndrome of inappropriate antidiuretic
hormone secretion), weight gain anorexia, constipation,
paralytic ileus, salivation, xerostomia, bladder paralysis,
ejaculatory disorder, impotence, mastalgia,
agranulocytosis, eosinophilia, leukopenia, lens disease,
nonthrombocytopenic purpura, urinary incontinence,
pancytopenia, thrombocytopenia hepatotoxicity muscle
spasm (neck), systemic lupus erythematosus, tremor
(fingers), blurred vision, corneal changes, glaucoma,
retinitis pigmentosa, polyuria, asthma, laryngeal edema,
N
nasal congestion.
Rare: Cholestatic jaundice, cornea and lens pigmentation,
blood dyscrasias (leukocytosis or leukopenia,
eosinophilia, thrombocytopenia, agranulocytosis),
seizures, changes in body thermoregulation, neuroleptic
malignant syndrome.
NOTE: Patients taking this drug may experience weight gain
and/or sedation.
Drug Interactions:
Monitor closely with:
Additive effect of drugs with:
CNS depressants
Additive cholinergic effects with:
Atropine or related compounds
Enhances therapeutic effect of Fluphenazine:
Anticholinergics (anticholinergic effects)
Enhances therapeutic effect of the following drugs:
Antihypertensives [except Guanethidine], Beta Blockers
[except Atenolol, Nadolol]
Vasopressors, e.g. Epinephrine (lowers blood pressure)
Thiopental (hypotensive effect; CNS excitatory effect)
Increases risk of adverse or toxic effects of Fluphenazine:
Diuretics (hypotension)
Epinephrine (low blood pressure)
Methylphenidate, Metoclopramide (sleepiness and
dizziness)
Lithium (neurotoxic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics (hypotension)
Glucagon (GI adverse effects)
495

Hypotension-associated Agents (hypotension) Iohexol,
Iomeprol, Iopamidol (seizures) Mequitazine
(arrhythmogenic effect) Methylphenidate, Mirabegron
Photosensitizing Agents (photosensitizing effect)
QTc-prolonging Agents (torsades de pointes) Serotonin
Modulators (neuroleptic malignant syndrome; serotonin
syndrome)
SSRIs (psychomotor impairment)
Topiramate (hyperthermia)
Reduces absorption of Fluphenazine:
Antacids
Reduces absorption of Nitroglycerin (decreases dissolution
of sublingual nitroglycerin tablets)
Reduces therapeutic effect of the following drugs:
Amphetamines (stimulant effect)
Guanethidine (antihypertensive effects)
Methylphenidate (inhibits stimulatory effects) Levodopa,
Dopamine Agonists, Prokinetics, Secretin
Reduces therapeutic effect of Fluphenazine:
Methylphenidate (inhibits antipsychotic and mood-
stabilizing activity)
Avoid concomitant use with:
Delayed gastric emptying with Potassium Salts (Oral)
N
Enhances therapeutic effect of Fluphenazine:
CNS Depressant [high dose] (CNS depression)
Increases risk of adverse or toxic effects of the following
drugs:
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration: Administer by IM injection using a dry
syringe and needle of ≥21 gauge. A wet needle or syringe
may cause the solution to become cloudy. Z-track
injection techniques are recommended to limit leakage
after injections.
Do NOT discontinue abruptly because of the possibility of
withdrawal and rebound psychosis. Discontinue or cross-
titrate gradually to minimize the potential of withdrawal,
rebound psychosis, extrapyramidal side effects,
cholinergic rebound, rebound insomnia, and unwanted
pregnancy, unless safety concerns require a more rapid
withdrawal.
Pregnancy Category: C
ATC Code: N05AB02
496
NERVOUS SYSTEM
Rx HALOPERIDOL
Oral: 2 mg, 5 mg, and 10 mg tablet
Inj.: 5 mg/mL, 1 mL ampule (IM)
50 mg/mL (as decanoate), 1 mL (oily) ampule (IM)
Haloperidol is a butyrophenone typical antipsychotic that
blocks postsynaptic dopamine D1 and D2 receptors in the
mesolimbic system and decreases the release of
hypothalamic and hypophyseal hormones. It has the
lowest relative risk for sedation, anticholinergic effects,
and hypotension, but conversely a very high relative risk
for extrapyramidal symptoms. It is also formulated as a
long-acting injectable in the form of its decanoate salt.
Indications: Management of manifestations of psychotic
disorders; tics and vocal utterances in Tourette
syndrome; second-line treatment of severe behavior
problems in children of combative, explosive
hyperexcitability; second-line short-term treatment of
hyperactive children; treatment of schizophrenic
patients who require prolonged parenteral antipsychotic
therapy.
Contraindications: Comatose state, CNS depression,
Parkinson’s disease, blood dyscrasias, bone marrow
suppression, subcortical brain injury, IV administration,
significant depressive states, previous spastic diseases,
young children.
Dose:
Behavior disorders, by mouth, CHILD 3–12 years and 15–
40 kg, initially 0.5 mg daily in 2–3 divided doses, slowly
increase by 0.5 mg once daily every 5–7 days to an
average maintenance dose of 0.05–0.075 mg/kg daily
in 2–3 divided doses; no benefit is seen with doses
greater than 6 mg once daily.
Manifestations of psychotic disorders, by mouth, ADULT,
initially 1–6 mg daily in 2–3 divided doses for moderate
cases or 6–15 mg daily in 2 to 3 divided doses for severe
cases, slowly titrate dose based on efficacy and
tolerability up to a maximum of 100 mg once daily; usual
maintenance is 3–10 mg daily; CHILD 3–12 years and
15–40 kg, initially 0.5 mg daily in 2–3 divided doses,
slowly increase by 0.5 mg once daily every 5–7 days to
an average maintenance dose of 0.05–0.15 mg/kg daily
in 2–3 divided doses; no benefit is seen with doses >6
mg once daily;
by IM injection (immediate-release), ADULT, initially 2–5
mg every hour, may administer subsequent doses as
often as every 60 minutes, although 4- to 8-hour
intervals may be satisfactory until symptoms are
controlled (maximum, 18 mg daily) switch to oral
formulation as soon as possible.
Schizophrenia requiring prolonged parenteral antipsychotic
therapy, by IM injection (long-acting), ADULT (stabilized
on oral haloperidol), 10–15 times the oral daily dose
(oral haloperidol ≤10 mg daily for elderly or debilitated)
or 20 times the oral daily dose (oral haloperidol >10 mg
daily for high risk of relapse) into the deltoid or gluteal
muscle, not exceeding 100 mg every 4 weeks; if dose
conversion exceeds 100 mg, administer a second
injection in 3–7 days; following initial dose, taper the oral
dose and discontinue following the subsequent 2 or 3
NERVOUS SYSTEM
injections; administer the total dose every 4 weeks with
a maximum dose of 450 mg.
Tourette syndrome, by mouth, ADULT, initially 0.5 mg 2 or 3
times daily, slowly titrate dose based on efficacy and
tolerability up to a maintenance dose of 0.5–3 mg daily
or 0.25–15 mg daily, up to a maximum of 100 mg once
daily, CHILD 3-12 years, initially 0.5 mg daily in 2–3
divided doses, slowly increase by 0.5 mg once daily every
5–7 days to an average maintenance dose of 0.05 to
0.075 mg/kg daily in 2–3 divided doses; no benefit is
seen with doses >6 mg once daily.
Dose Adjustment:
Geriatric:
Use with caution and initiate with lower dose.
Precautions:
WARNING: Elderly patients with dementia-related
psychosis treated with antipsychotic drugs are at
an increased risk of death.
Altered cardiac conduction (cases of sudden death, QT
prolongation, and torsades de pointes); orthostatic
hypotension; cardiovascular disease; respiratory
disorder; blood dyscrasias; some fatal)
Anticholinergic effects (e.g., constipation, xerostomia,
blurred vision, urinary retention); hyperprolactinemia;
neuroleptic malignant syndrome; temperature regulation
(impaired core body temperature regulation); thyroid
dysfunction.
CNS depression; extrapyramidal symptoms (e.g.,
pseudoparkinsonism, acute dystonic reactions,
akathisia, and tardive dyskinesia; risk of dystonia may be
greater with increased doses); falls; bipolar disorder;
Parkinson disease; seizure disorder; glaucoma.
Esophageal dysmotility or aspiration.
Elderly (tardive dyskinesia, especially among women;
potentially inappropriate; avoid use in patients ≥65 years
with dementia (mortality and cerebrovascular accidents,
cognitive decline, and SIADH or hyponatremia, unless all
nonpharmacologic options have failed or are not
possible or the patient is threatening substantial harm to
self or to others).
Pregnancy (abnormal muscle movements and withdrawal
symptoms in newborns with fetal exposure during the
third trimester); lactation (tardive dyskinesia, dystonia,
and sedation).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Syncope, extrapyramidal reaction, parkinsonian-
like syndrome, dystonia, dry mouth, hypertonia,
drowsiness, akathisia, headache, dizziness, neuroleptic-
induced deficit syndrome, decreased sweating,
galactorrhea, amenorrhea, constipation, abdominal
pain, xerostomia, sialorrhea, constipation, urinary
retention, hyperkinesia, tremor, bradykinesia, oculogyric
crisis, long-term skin pigmentation changes, depression,
weight loss, tardive dyskinesia (long term use,
irreversible).
Less Common: Dyspnea, edema
Rare: Cholestatic jaundice, blood dyscrasias (leukocytosis
or leukopenia, eosinophilia, thrombocytopenia,
agranulocytosis), neuroleptic malignant syndrome,
seizures, changes in body thermoregulation.
NOTE: Patients taking this drug may experience weight gain
and/or sedation.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Haloperidol:
Anticholinergics (anticholinergic effects)
Enhances therapeutic effect of the following drugs:
Antihypertensives [except Guanethidine], Beta Blockers
[except Atenolol, Nadolol] (antihypertensive effect)
CNS Depressants (central effects)
Vasopressors, e.g. Epinephrine (lowers blood pressure)
Increases risk of adverse or toxic effects of Haloperidol:
Methylphenidate, Metoclopramide, NSAIDs
Lithium (encephalopathic syndrome)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics, Hypotension-associated Agents (hypotension)
Glucagon (GI adverse effects)
Iohexol, Iomeprol, Iopamidol (seizures)
N
Mequitazine (arrhythmogenic effect)
Methylphenidate, Mirabegron
Photosensitizing Agents (photosensitizing effect)
QTc-prolonging Agents (torsades de pointes)
Serotonin Modulators (neuroleptic malignant syndrome;
serotonin syndrome)
SSRIs (psychomotor impairment)
Topiramate (hyperthermia)
Reduces absorption of Nitroglycerin
Reduces therapeutic effect of Haloperidol:
Methylphenidate (inhibits antipsychotic and mood-
stabilizing activity)
Reduces therapeutic effect of the following drugs:
Prokinetics, Secretin
Amphetamines (stimulant effect)
Dopamine Agonists (antagonism)
Guanethidine (antihypertensive effect)
Methylphenidate (stimulatory effect)
Urea Cycle Disorder Agents (increases plasma ammonia
concentrations)
Avoid concomitant use with:
Delayed gastric emptying with Potassium Salts (Oral)
Increases risk of adverse or toxic effects of the following
drugs:
Nilotinib (QT prolongation; torsades de pointes)
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration:
For oral administration, may be taken with or without
food, but preferably taken with meals to minimize GI
irritation.
497
 NERVOUS SYSTEM

In End-stage renal disease (ESRD) with hemodialysis,

For IM injection as decanoate formulation, administer by administer dose after dialysis.
IM only, using a 21-gauge needle. Do NOT administer by
IV injection. The maximum volume per injection site is 3 Precautions:
mL. Z-track injection techniques are recommended to
limit leakage after injections.
WARNING: Lithium toxicity is closely related to serum
lithium levels and can occur at doses close to
Do NOT discontinue abruptly because of the possibility of
therapeutic levels. Facilities for prompt and
withdrawal and rebound psychosis. Discontinue or cross-
accurate serum lithium determinations should be
titrate gradually to minimize the potential of withdrawal,
available before initiating therapy. Monitor trough
rebound psychosis, extrapyramidal side effects,
lithium plasma levels frequently (1.0 and 1.5
cholinergic rebound, rebound insomnia, and unwanted
mEq/L for acute treatment and 0.6 and 1.2 mEq/L
pregnancy, unless safety concerns require a more rapid
for chronic treatment)
withdrawal.

Pregnancy Category: C CNS depression; depression; suicidal ideation;

heart failure, e.g., reversible myocardial toxicity;
ATC Code: N05AB02 cardiovascular disease; hypercalcemia; hypothyroidism;
thyroid disease; renal effects e.g. renal impairment,
dehydration.

Rx LITHIUM CARBONATE Debilitated patients and Elderly (lithium toxicity); women

(hypothyroidism).
Oral: 450 mg MR tablet
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
The mechanism of action of Lithium Carbonate is unclear,
machinery.
but is effective in managing mania, bipolar disorder, and
recurrent unipolar depression.
N

Adverse Drug Reactions:

Common: AV block or other conduction issues,
Indications: First-line treatment of manic episodes of bipolar
bradyarrhythmia, ECG changes, arrhythmias, QTc
disorder; maintenance treatment for bipolar disorder
prolongation, ataxia, dysarthria, delirium, tremor,
with a history of mania; maintenance treatment for
memory problems, diarrhea, acne, psoriasis, alopecia,
manic-depressive patients with a history of mania; manic
hypothyroidism, weight gain, nausea, dry mouth,
episodes of manic-depressive illness.
polyuria, benign leukocytosis.
Less Common: End stage renal disease, hypothyroidism
Contraindications: Severe kidney disease; severe
(children, adolescents), abnormal T waves, bradycardia,
cardiovascular disease; Brugada syndrome; severe
chest tightness, circulatory shock, cold extremities,
debilitation; severe dehydration; sodium depletion.
edema, hypotension, myxedema, startled response,
sinus node dysfunction, syncope, ataxia, blackout spells,
Dose:
cogwheel rigidity, coma, confusion, dizziness,
Treatment for bipolar disorder I (acute mania, acute
drowsiness, dystonia, EEG pattern changes,
depression),, by mouth, ADULT, initially 450 mg twice
extrapyramidal reaction, fatigue, hallucination,
daily, slowly titrate dose based on efficacy, tolerability,
headache, hyperactive deep tendon reflex, hypertonia,
and serum lithium concentrations to an average of 900–
involuntary choreoathetoid movements, lethargy,
1,800 mg daily in 2 divided doses; maintenance
memory impairment, local anesthesia, loss of
treatment of bipolar disorders I and II, initially 500 mg
consciousness, metallic taste, pseudotumor cerebri,
daily, increase gradually every 7 days until target blood
psychomotor retardation, reduced intellectual ability,
level is reached; maximum of 600-1200 mg daily.
restlessness, salty taste, sedation, seizure, slowed
Manic episodes of bipolar disorder, by mouth, ADULT,
intellectual functioning, slurred speech, stupor, tics,
initially 450 mg twice daily, slowly titrate dose based on
vertigo, worsening of organic brain syndromes, blue-gray
efficacy, tolerability, and serum lithium concentrations to
skin pigmentation, dermal ulcer, exacerbation of
an average of 1,800 mg daily in 2 divided doses; CHILD
psoriasis, folliculitis, pruritus, skin rash, xerosis,
≥12 years, initially 1.8 g daily in 2–3 divided doses.
albuminuria, dehydration, diabetes insipidus, euthyroid
goiter, glycosuria, hypercalcemia, hyperparathyroidism,
Dose Adjustment:
increased radioactive iodine uptake, hyperthyroidism,
Geriatric:
polydipsia, weight loss, abdominal pain, anorexia, dental
Lower doses and lower serum lithium concentrations are
caries, diarrhea, dysgeusia, dyspepsia, excessive
often adequate and advisable.
salivation, flatulence, gastritis, vomiting, sialadenitis,
sialorrhea, swelling of lips, xerostomia, impotence,
Renal Impairment:
incontinence, leukocytosis, angioedema, joint swelling,
Not recommended for use in patients with severe renal
muscle hyperirritability, neuromuscular excitability,
impairment.
polyarthralgia, tremor, blurred vision, exophthalmos,
In CrCl 10–50 mL/minute and in patients on continuous
nystagmus, transient scotoma, tinnitus, oliguria,
renal replacement therapy (CRRT), administer 50–75%
polyuria, fever.
of dose.
In CrCl <10 mL/minute, administer 25–50% of dose.

498
NERVOUS SYSTEM
Rare: Lithium toxicity, renal impairment (interstitial
nephritis), nephrogenic diabetes insipidus, acute tubular
necrosis, cardiovascular changes, sick sinus syndrome,
bradycardia, hypotension, nephrotic syndrome, T wave
flattening and inversion, pseudotumor cerebri, seizures,
chronic kidney disease, syndrome of irreversible lithium-
effectuated neurotoxicity (SILENT), myasthenia gravis.
NOTE: Patients taking this drug may experience weight gain and/or
sedation.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Linezolid, Methylene Blue, Opioids, SSRIs e.g., Fluoxetine
(serotonergic effect)
Neuromuscular Blockers (prolonged effects) Potassium
Iodide (hypothyroid effect)
QTc-prolonging Agents
Increases risk of adverse or toxic effects of lithium
carbonate
Antipsychotics, CCBs e.g., Amlodipine, Carbamazepine,
Fosphenytoin, MAOIs [except Moclobemide],
Methyldopa, Phenytoin, Metronidazole, Sargramostim
(myeloproliferative effects)
Increases risk of adverse or toxic effects of the following
drugs:
Dapoxetine, Haloperidol (encephalopathic syndrome),
Linezolid, Opioids,
Serotonin Modulators [except Nicergoline, Tedizolid]
(serotonin syndrome)
Methylphenidate, SSRIs e.g. Fluoxetine (serotonin
syndrome) Metoclopramide (serotonin syndrome;
neuroleptic malignant syndrome)
TCAs e.g., Amytriptylline (neurotoxic effect)
Tramadol (seizures)
Reduces therapeutic effect of the following drugs:
Amphetamines (stimulatory effect)
Desmopressin
Administration: Should be taken with food.
Maintain normal fluid and salt intake during therapy.
Pregnancy Category: D
ATC Code: N05AN01
Rx OLANZAPINE
Oral: 5 mg and 10 mg tablet
10 mg orodispersible tablet (ODT)
Olanzapine is a thienobenzodiazepine structurally related to
clozapine. It is more potent and less sedating than
clozapine. It also has low risk for extrapyramidal
symptoms, even at high doses. However, it has the
greatest known cardiometabolic risks, because it
increases triglyceride levels and promotes insulin
resistance.
Indications: Management of schizophrenia; maintaining
response in schizophrenia, acute phase schizophrenia;
acute agitation associated with schizophrenia, acute
mania or mixed mania; bipolar maintenance; acute
agitation associated with bipolar I mania, bipolar
depression; treatment-resistant depression (in
combination with fluoxetine).
Contraindications: Psychosis in Parkinson’s disease.
Dose:
Acute mania or mixed mania, by mouth, ADULT and CHILD
≥13 years, as monotherapy, initially 10 to 15 mg once
daily, increase by 5 mg once daily at intervals of not less
than 1 week until desired efficacy is reached (maximum
dose, 20 mg once daily).
Acute mania/mixed mania, by mouth, ADULT and CHILD
≥13 years, as adjunct to lithium or valproate, initially 10
mg once daily, increase by 5 mg once daily at intervals of
not less than 1 week until desired efficacy is reached
(maximum dose, 20 mg once daily).
Bipolar I disorder maintenance, by mouth, ADULT, continue
therapy at the lowest effective dose and adjust dose
depending on clinical response and tolerability.
Depression associated with bipolar 1 disorder, by mouth,
ADULT, in combination with fluoxetine, initially 5 mg once
daily in the evening, slowly titrate dose based on efficacy
and tolerability up to a maximum of 12.5 mg once daily
N
in the evening; CHILD ≥10 years, initially 2.5 mg once
daily in the evening, slowly titrate dose based on efficacy
and tolerability.
Schizophrenia, by mouth, ADULT and CHILD ≥13 years,
initially 5–10 mg once daily, increase by 5 mg once daily
once a week until desired efficacy is reached (maximum
dose, 20 mg once daily).
Treatment-resistant depression, by mouth, ADULT, in
combination with fluoxetine, initially 5 mg once daily in
the evening, slowly titrate dose based on efficacy and
tolerability (maximum, 12.5 mg once daily in the
evening).
Dose Adjustment:
Geriatric:
May tolerate lower doses better.
Hepatic Impairment:
For moderate to severe hepatic impairment, consider initial
dose of 5 mg daily. When used in combination with
fluoxetine, limit initial dose to 2.5–5 mg once daily.
Increase dose with caution.
Debilitated Patients with a predisposition to Hypotensive
reactions, who exhibit a combination of factors that may
result in slower metabolism, e.g., nonsmoking female
patients ≥65 years), or who may be more
pharmacodynamically sensitive to olanzapine:
Initiate at 5 mg once daily, increase dose with caution as
clinically indicated.
Precautions:
WARNING: NOT approved for treatment of dementia-
related psychosis (increased risk of death)
Altered cardiac conduction, e.g., life-threatening
arrhythmias; orthostatic hypotension; cardiovascular
499

disease; blood dyscrasias, e.g., leukopenia, neutropenia,
and agranulocytosis; dyslipidemia; hyperglycemia;
hyperprolactinemia (dose-related); Anticholinergic
effects, e.g., constipation, xerostomia, blurred vision,
urinary retention; esophageal dysmotility or aspiration;
multiorgan hypersensitivity reactions (drug reaction with
eosinophilia and systemic symptoms [DRESS]);
neuroleptic malignant syndrome; temperature
regulation, e.g., impaired core body temperature
regulation; cerebrovascular effects; CNS depression;
extrapyramidal symptoms, e.g., dystonic reactions,
pseudoparkinsonism, akathisia, and tardive dyskinesia;
greater risk for dystonia with increased doses; greater
risk for falls; suicidal ideation; Parkinson disease;
seizures; weight gain; hepatic impairment; renal
impairment
Smokers (decreases olanzapine concentration; may require
daily doses 30% higher to obtain an equivalent
concentration); Elderly (more susceptible to adverse
effects; potentially inappropriate in the elderly; avoid use
in patients ≥65 years with dementia due to an increased
risk of mortality and cerebrovascular accidents, a greater
rate of cognitive decline, and potential to cause or
exacerbate SIADH or hyponatremia, unless all non-
pharmacologic options have failed or are not possible or
the patient is threatening substantial harm to self or to
others); children (safety of doses >12 mg in combination
N
with doses >50 mg of fluoxetine has not been studied;
use in adolescents ≥13 years of age may result in
increased weight gain, sedation, and increases in LDL
cholesterol, total cholesterol, triglycerides, prolactin, and
liver transaminase levels).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
Adverse Drug Reactions:
Common: Arthralgia, hypercholesterolemia,
hypertriglyceridemia, increased appetite, malaise,
edema.
Less Common: Alopecia, amnesia, bradycardia, epistaxis.
Rare: Hepatitis, pancreatitis, rhabdomyolysis.
NOTE: Patients taking this drug may experience weight gain
and/or sedation.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Antihypertensives [except Guanethidine], CNS
Depressants (sedative effect), QTc-prolonging Agents
(QTc-prolonging effect)
Increases risk of adverse or toxic effects of Olanzapine:
Methylphenidate, Metoclopramide
Increases risk of adverse or toxic effects of the following
drugs:
Glucagon (GI adverse effects)
Hypotension- associated Agents (hypotension)
Iohexol, Iomeprol, Iopamidol (seizures)
Mequitazine (arrhythmogenic effect)
Methylphenidate, Mirabegron
Potassium Chloride (ulcerogenic effect)
500
NERVOUS SYSTEM
Serotonin Modulators (neuroleptic malignant syndrome;
serotonin syndrome)
SSRIs (psychomotor impairment)
Topiramate (hyperthermia)
Reduces absorption of Nitroglycerin (decreases dissolution
of sublingual nitroglycerin tablets)
Reduces therapeutic effect of Olanzapine:
Methylphenidate (antipsychotic and mood- stabilizing
actions)
Reduces therapeutic effect of the following drugs:
Phenylephrine, Prokinetics, Secretin, Antidiabetics,
Anticholinergics
Methylphenidate (stimulant effect)
Dopamine Agonists (antagonism)
Guanethidine (antihypertensive effects)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration:
Olanzapine orodispersible tablet may be placed on the
tongue and allowed to dissolve, or dispersed in water,
orange juice, apple juice, milk or coffee. May be taken
with or without food.
Do NOT discontinue abruptly because of the possibility of
withdrawal and rebound psychosis. Perform
discontinuation or cross-titration gradually to minimize
the potential of withdrawal, rebound psychosis,
extrapyramidal side effects, cholinergic rebound,
rebound insomnia, and unwanted pregnancy, unless
safety concerns require a more rapid withdrawal.
Pregnancy Category: C
ATC Code: N05AH03
Rx PALIPERIDONE
Inj.: 50 mg/0.5 mL, 75 mg/0.75 mL, 100 mg/mL, and
150 mg/1.5 mL prolonged-release suspension for
injection (IM)
Paliperidone is a benzisoxazole atypical antipsychotic, and
a metabolite of risperidone. It is an antagonist at
dopamine (D2), serotonin (5-HT2A), adrenergic (α1 and
α2), and histamine (H1) receptors. Paliperidone is not
hepatically metabolized and is eliminated via the urine,
giving it less drug interactions.
Indications: Maintenance in schizophrenia; maintaining
stability in schizophrenia; schizoaffective disorder;
Contraindications: History of QTc prolongation or cardiac
arrhythmia; recent acute myocardial infarction;
uncompensated heart failure; preexisting severe GI
narrowing.
NERVOUS SYSTEM

Administer second dose of

Dose: 100 mg by intramuscular
Maintaining stability in schizophrenia, by intramuscular injection into the deltoid
injection, ADULT, stabilize service user/patient on oral muscle as soon as possible,
paliperidone. Initially, 150 mg injected into the deltoid 4-7 weeks since first followed by another 100 mg
muscle, followed after 1 week (±4 days) by 100 mg injection by intramuscular injection
injected into the deltoid muscle. Monthly maintenance into the deltoid muscle one
doses (±7 days) may be administered after the second week after the second dose.
loading dose in the gluteal muscle or the deltoid muscle Resume regular monthly
and dosed based on the oral dose the service dosing after.
user/patient is stabilized on: >7 weeks since first Restart with recommended
12 mg by mouth once daily = 150 mg by intramuscular injection initiation dosing schedule.
injection once a month Missed Doses – Maintenance Dose
9 mg by mouth once daily = 100 mg by intramuscular Resume previous schedule
injection once a month 4-6 weeks since last
and dose as soon as
6 mg by mouth once daily = 75 mg by intramuscular dose
possible.
injection once a month If maintenance dose <150
3 mg by mouth once daily = 25-50 mg by intramuscular mg, administer the dose by
injection once a month. intramuscular injection into
Schizoaffective disorder, by intramuscular injection, ADULT, the deltoid muscle as soon
stabilize service user/patient on oral paliperidone. as possible and administer a
Initially, 150 mg injected into the deltoid muscle, second previously stabilized
followed after 1 week (±4 days) by 100 mg injected into dose after 1 week
the deltoid muscle. Monthly maintenance doses (±7
days) ranging from 25-150 mg may be administered >6 weeks and ≤6 If maintenance dose is 150
after the second loading dose in the gluteal muscle or months since last mg, administer a 100 mg
the deltoid muscle and dosed based on the oral dose the injection dose by intramuscular
service user/patient is stabilized on: injection into the deltoid

N
12 mg by mouth once daily = 150 mg by intramuscular muscle as soon as possible
injection once a month and administer a second 100
9 mg by mouth once daily = 100 mg by intramuscular mg dose after 1 week
injection once a month
6 mg by mouth once daily = 75 mg by intramuscular Continue with the previously
injection once a month stabilized dose 1 week after
3 mg by mouth once daily = 25-50 mg by intramuscular the second injection.
injection once a month. Restart with the
Schizophrenia, by intramuscular injection, >6 months since last
recommended initiation
ADULT/CHILD≥12 years, stabilize service user/patient injection
dosing schedule.
on oral paliperidone. Initially, 150 mg injected into the
deltoid muscle, followed after 1 week (±4 days) by 100 NOTE: Antipsychotics should not be discontinued abruptly because of
mg injected into the deltoid muscle. Monthly the possibility of withdrawal and rebound psychosis;
maintenance doses (±7 days) may be administered after discontinuation or cross-titration should be done gradually to
the second loading dose in the gluteal muscle or the minimize the potential of withdrawal, rebound psychosis and
deltoid muscle and dosed based on the oral dose the extrapyramidal side effects, cholinergic rebound, rebound
insomnia, and unwanted pregnancy, unless safety concerns
service user/patient is stabilized on:
require a more rapid withdrawal.
12 mg by mouth once daily = 150 mg by intramuscular
injection once a month Dose Adjustment:
9 mg by mouth once daily = 100 mg by intramuscular Geriatric:
injection once a month Some patients may tolerate lower doses better;
6 mg by mouth once daily = 75 mg by intramuscular antipsychotics are considered to be potentially
injection once a month inappropriate in in the elderly. and to be avoided in
3 mg by mouth once daily = 25-50 mg by intramuscular service patients 65 years and older with dementia due to
injection once a month. an increased risk of mortality, cerebrovascular accidents
(stroke), a greater rate of cognitive decline with use, and
Missed Doses – Second Initiation Dose potential to cause or exacerbate or hyponatremia unless
Administer second dose of all nonpharmacologic options have failed or are not
100 mg by intramuscular possible or the service user/patient is threatening
injection into the deltoid substantial harm to self or to others. It may be
muscle as soon as possible, appropriate for use in schizophrenia.
<4 weeks since first followed by a third dose of
injection 75 mg by intramuscular Renal Impairment:
injection into the deltoid or For mild renal impairment (CrCl≥50 mL/min and <80
gluteal muscle 5 weeks after mL/min), reduce initiation doses to 100 mg by
the first injection (regardless intramuscular injection on day 1 and 75 mg by
of timing of second dose) intramuscular injection after 1 week. Administer a

501

maintenance dose of 50 mg by intramuscular injection
once a month.
Not recommended for use in service patients with moderate
to severe renal impairment (CrCl<50 mL/min).
Hepatic Impairment:
No dose adjustment necessary in mild to moderate hepatic
impairment. Not studied in severe hepatic impairment.
Precautions:
WARNING: NOT approved for treatment of dementia-
related psychosis (increased risk of death)
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C. Protect from moisture.
Adverse Drug Reactions:
Common: Dose-dependent extrapyramidal symptoms,
hyperprolactinemia, anxiety, appetite changes,
arthralgia, depression, epistaxis, hypertension, infection,
malaise, myalgia, edema, respiratory disorders, sleep
disorders, toothache, urinary disorders; may increase
risk for diabetes and dyslipidemia.
Less Common: Alopecia, hypoesthesia, paresthesia, taste
disturbances, tinnitus, visual disorders.
Rare: Inappropriate antidiuretic hormone secretion-
obstruction, intra-operative floppy iris syndrome,
N
pancreatitis, pulmonary embolism, rhabdomyolysis.
NOTE: Patients taking this drug may experience weight gain
and/or sedation.
Drug Interactions:
Monitor closely with:
Reduces the therapeutic effects of the following drugs:
Amphetamines, Antidiabetics, Dopamine agonists,
Levodopa
Enhances the therapeutic effects of CNS depressants e.g.
Alcohol
Increases risk adverse/toxic effect of Paliperidone:
Metoclopramide
Increases risk of adverse or toxic effects of the following
drugs:
Iohexol, Iomeprol, Iopamidol (seizures)
QTc-prolonging agents, Methylphenidate
Mequitazine (arrhythmogenic effect)
Serotonin modulators (neuroleptic malignant syndrome;
serotonin syndrome)
SSRIs (psychomotor impairment)
Acetylcholinesterase inhibitors (neurotoxic effect; severe
extrapyramidal symptoms)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Other Antipsychotics (increased hospitalization rates
and length of stay; increased mortality; QTc
prolongation; torsades de pointes)
Administration: Administer by IM route only as a single
injection (do not divide); do not administer by any other
route. Avoid inadvertent injection into vasculature.
502
NERVOUS SYSTEM
Do not mix with any other product or diluent. Prior to
injection, shake syringe for at least 10 seconds to ensure
a homogenous suspension. Administer using only the
needles that are provided in the kit. The 2 initial
injections should be administered in the deltoid muscle
using a 11/2 inch, 22-gauge needle for service patients
≥90 kg, and a 1 inch, 23-gauge needle for service
patients <90 kg. The 2 initial deltoid intramuscular
injections help attain therapeutic concentrations rapidly.
Alternate deltoid injections (right and left deltoid
muscle). The second dose may be administered 4 days
before or after the weekly time point. Monthly
maintenance doses can be administered in either the
deltoid or gluteal muscle. Administer injections in the
gluteal muscle using a 11/2 inch, 22-gauge needle
(regardless of service user/patient weight) in the upper-
outer quadrant of the gluteal area. Alternate gluteal
injections (right and left gluteal muscle). The monthly
maintenance dose may be administered 7 days before
or after the monthly time point.
Pregnancy Category: C
ATC Code: N05AX13
QUETIAPINE
Rx
Oral: 25 mg, 100 mg, 200 mg, and 300 mg tablet (as
fumarate)
Quetiapine is dibenzothiazepine atypical antipsychotic
structurally related to clozapine. It is a dopamine D1,
dopamine D2, 5-HT2 alpha1-adrenoceptor, and
histamine-1 receptor antagonist.
Indications: Management of acute schizophrenia,
schizophrenia maintenance, acute bipolar mania,
bipolar maintenance, bipolar depression, bipolar
maintenance, depression (as an adjunct only)
Dose:
Acute bipolar mania, by mouth, ADULT, monotherapy and
adjunct to lithium/valproate: initially 50 mg twice daily.
Increase by 50 mg twice daily each day up to 200 mg
twice daily. Further dose increases up to a maximum of
400 mg twice daily should be done in increments of no
greater than 100 mg twice daily, CHILD≥10 years,
monotherapy: initially 25 mg twice daily. Increase to 50
mg twice daily on day 2, then increase by 50 mg twice
daily each day up to 200 mg twice daily on day 5. Further
dose adjustments may be done in increments of ≤100
mg/day up to a maximum of 600 mg/day in 2-3 divided
doses.
Acute schizophrenia, by mouth, ADULT, initially 25 mg twice
daily. Increase in increments of 25-50 mg/day twice or
thrice daily each day until an average of 300-400
mg/day in 2-3 divided doses on day 4. Further dose
adjustments should be done at intervals of no less than
2 days in increments of 25-50 mg twice daily up to a
maximum dose of 400 mg twice daily, CHILD≥13 years,
initially 25 mg twice daily. Increase to 50 mg twice daily
on day 2 then further increase by 100 mg/day divided
into 2 doses until 400 mg/day divided into 2 doses is
NERVOUS SYSTEM
reached on day 5. Further dose increases may be done
in increments of ≤100 mg/day up to a maximum of 800
mg/day in 2-3 divided doses.
Bipolar depression, by mouth, ADULT, initially 50 mg once
daily at bedtime. Increase to 100 mg once daily at
bedtime on day 2. Increase by 100 mg/day as needed
up to a maximum of 300 mg once daily at bedtime on
day 4.
Bipolar maintenance, by mouth, ADULT, continue therapy at
the lowest effective dose and adjust dose depending on
clinical response and tolerability.
Schizophrenia maintenance, by mouth, 150–750 mg/day
(in divided doses)
Depression, adjunct to any antidepressant, by mouth, 25
mg once daily
NOTE: Antipsychotics should not be discontinued abruptly
because of the possibility of withdrawal and rebound
psychosis; discontinuation or cross-titration should be
done gradually to minimize the potential of withdrawal,
rebound psychosis and extrapyramidal side effects,
cholinergic rebound, rebound insomnia, and unwanted
pregnancy, unless safety concerns require a more rapid
withdrawal.
Dose Adjustment:
Geriatric:
Lower doses are generally used, but higher doses may be
used if tolerated; initially 50 mg once daily and may
increase in increments of 50 mg/day to an effective dose
based on efficacy and tolerability
Hepatic Impairment:
Initially 25 mg once daily or in 2 divided doses. Slowly
increase by 25-50 mg once daily to effective dose.
Precautions:
WARNING: NOT approved for treatment of dementia-
related psychosis (increased risk of death)
Cerebrovascular disease; elderly patients at risk of
aspiration pneumonia; treatment of depression in
patients under 25 years (increased risk of suicide)
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C.
Adverse Drug Reactions:
Common: Asthenia, dysarthria, dyspnea, increased
appetite, irritability, peripheral edema, sleep disorders,
dizziness, increased risk for diabetes and dyslipidemia
Less Common: Hyponatremia, hypothyroidism, restless legs
syndrome, rhinitis.
Rare: Angioedema, inappropriate secretion of antidiuretic
hormone, rhabdomyolysis, SJS.
NOTE: Patients taking this drug may experience weight gain and/or
sedation.
Drug Interactions:
Monitor closely with:
Reduces the therapeutic effects of the following drugs:
Amphetamines, Guanethidine
Reduced drug clearance with:
Lorazepam (by 20%)
Enhances the therapeutic effects of the following drugs:
CNS depressants, Antihypertensives [except
guanethidine]
Increases risk adverse/toxic effect of Quetiapine:
Metoclopramide
Increases risk of adverse or toxic effects of the following
drugs:
Iohexol, Iomeprol, Iopamidol (seizures)
Mequitazine (arrhythmogenic effect)
Serotonin modulators (neuroleptic malignant syndrome)
SSRIs (psychomotor impairment)
Lorazepam – quetiapine may reduce the clearance of
lorazepam by 20%
Serotonin modulators – may enhance the risk of
neuroleptic malignant syndrome and serotonin
syndrome with antipsychotics
Avoid concomitant use with:
Increases risk of adverse or toxic effects of other
Antipsychotics (increased hospitalization rates and
length of stay; increased mortality)
N
Administration: May be taken with or without food.
Pregnancy Category: C
ATC Code: N05AH04
Rx RISPERIDONE
Oral: 1 mg, 2 mg, 3 mg, and 4 mg tablet
1 mg and 2 mg orodispersible tablet
1 mg/mL oral solution, 100 mL
Inj.: 25 mg and 37.5 mg MR powder for suspension, vial
+ 2 mL diluent in pre-filled syringe (IM)
50 mg prolonged-release powder for suspension for
injection (IM) + 2 mL diluent
Risperidone is a benzisoxazole atypical antipsychotic that
gains typical properties such as extrapyramidal
symptoms when given in higher doses. It has a moderate
risk of inducing weight gain and dyslipidemia.
Indications: Treatment of schizophrenia; delaying relapse in
schizophrenia; other psychotic disorders; treatment of
acute and long term mania/mixed mania (monotherapy
and adjunct to lithium or valproate); autism-related
irritability in children; bipolar maintenance (monotherapy
and adjunct to lithium or valproate)
Dose:
Acute mania/mixed mania, monotherapy and adjunct to
lithium or valproate, by mouth, ADULT, initially 2-3 mg
once daily or in two divided doses. Slowly increase by 1
mg once daily each day until desired efficacy is reached
up to a maximum of 6 mg once daily, CHILD≥10 years,
initially 0.5 mg once daily or in two divided doses. Slowly
increase by 0.5-1 mg once daily each day until desired
503

efficacy is reached up to a maximum of 6 mg once daily,
with doses >2.5 mg daily not conferring additional
benefit and are associated with increased adverse
events.
Autism-related irritability, by mouth, CHILD≥5 years (15 to
<20 kg), initially 0.25 mg once daily or in two divided
doses. Increase dose to 0.5 mg once daily after at least
4 days and maintain dose for at least 14 days. If
response is insufficient, slowly increase dose by 0.25 mg
once daily not earlier than every 2 weeks up to a
maximum of 3 mg once daily or in two divided doses,
CHILD≥5 years (≥20 kg), initially 0.5 mg once daily or in
two divided doses. Increase dose to 1 mg once daily after
at least 4 days and maintain dose for at least 14 days. If
response is insufficient, slowly increase dose by 0.5 mg
once daily not earlier than every 2 weeks up to a
maximum of 3 mg once daily or in two divided doses.
Bipolar maintenance, monotherapy and adjunct to lithium
or valproate, by intramuscular injection, ADULT, initially
stabilize service user/patient on oral risperidone.
Administer 12.5-25 mg into the deltoid or gluteal muscle.
Continue oral risperidone for 3 weeks before
discontinuing and administer maintenance doses based
on the oral dose the service user/patient is stabilized on:
≤3 mg by mouth once daily = 25 mg by intramuscular
injection every 2 weeks
3-≤5 mg by mouth once daily = 37.5 mg by intramuscular
injection every 2 weeks
N
>5 mg by mouth once daily = 50 mg by intramuscular
injection every 2 weeks.
Continue therapy at the lowest effective dose and adjust
dose depending on clinical response and tolerability at
intervals of no more than 4 weeks.
Delaying relapse in schizophrenia, by mouth, ADULT, initially
1 mg/day in two divided doses. Slowly increase by 1 mg
once daily each day until desired efficacy is reached up
to a maximum of 6 mg once daily. Clinical benefit and
risk of EPS beyond 6 mg usually does not warrant
exceeding 6 mg once daily up to 16 mg once daily.
Psychosis, by mouth, initialy 1 mg daily, gradually increase
to 2-6 mg daily; for a maximum of 10 mg.
Other psychotic disorders, by mouth, ADULT, initially 1
mg/day in two divided doses. Slowly increase by 1 mg
once daily each day until desired efficacy is reached up
to a maximum of 6 mg once daily. Clinical benefit and
risk of EPS beyond 6 mg usually does not warrant
exceeding 6 mg once daily up to 16 mg once daily.
Schizophrenia, by mouth, ADULT, initially 1 mg/day in two
divided doses. Slowly increase by 1 mg once daily each
day until desired efficacy is reached up to a maximum of
6 mg once daily. Clinical benefit and risk of EPS beyond
6 mg usually does not warrant exceeding 6 mg once daily
up to 16 mg once daily, CHILD≥13 years, initially 0.5 mg
once daily or in two divided doses. Slowly increase by 0.5-
1 mg once daily each day until desired efficacy is reached
up to a maximum of 6 mg once daily, by intramuscular
injection, ADULT, initially stabilize service patient on oral
risperidone. Administer 12.5-25 mg into the deltoid or
gluteal muscle. Continue oral risperidone for 3 weeks
before discontinuing and administer maintenance doses
based on the oral dose the service user/patient is
stabilized on:
≤3 mg by mouth once daily = 25 mg by intramuscular
injection every 2 weeks
3-≤5 mg by mouth once daily = 37.5 mg by intramuscular
injection every 2 weeks
504
NERVOUS SYSTEM
>5 mg by mouth once daily = 50 mg by intramuscular
injection every 2 weeks.
Continue therapy at the lowest effective dose and adjust
dose depending on clinical response and tolerability at
intervals of no more than 4 weeks.
NOTE: Antipsychotics should not be discontinued abruptly
because of the possibility of withdrawal and rebound
psychosis; discontinuation or cross-titration should be
done gradually to minimize the potential of withdrawal,
rebound psychosis and extrapyramidal side effects,
cholinergic rebound, rebound insomnia, and unwanted
pregnancy, unless safety concerns require a more rapid
withdrawal.
Dose Adjustment:
Geriatric:
Initially 0.5 mg twice daily. Slowly increase by 0.5 mg twice
daily and increase dose not more than once a week for
doses above 1.5 mg twice daily.
Renal Impairment:
Initially 0.5 mg by mouth twice daily for the first week.
Increase to 1 mg by mouth twice daily on the second
week. Slowly increase doses beyond 1.5 mg by mouth
twice daily at intervals of 1 week or longer.
For long-acting injectable formulation, do not administer
unless service user/patient has demonstrated
tolerability to at least 2 mg by mouth once daily or in
divided doses. An initial dose of 12.5 mg may be more
appropriate. Maintenance doses should be 25 mg every
two weeks, with oral risperidone being continued for 3
weeks after the first injection.
Hepatic Impairment:
Initially 0.5 mg by mouth twice daily for the first week.
Increase to 1 mg by mouth twice daily on the second
week. Slowly increase doses beyond 1.5 mg by mouth
twice daily at intervals of 1 week or longer.
For long-acting injectable formulation, do not administer
unless service user/patient has demonstrated
tolerability to at least 2 mg by mouth once daily or in
divided doses. An initial dose of 12.5 mg may be more
appropriate. Maintenance doses should be 25 mg every
two weeks, with oral risperidone being continued for 3
weeks after the first injection.
Precautions:
WARNING: NOT approved for treatment of dementia-
related psychosis (high risk of cardiovascular and
infectious-related deaths).
Pregnancy: There is a risk of abnormal muscle movements
and withdrawal symptoms in newborns during the third
trimester.
Hypersensitivity
STORAGE AND STABILITY: Tablet: store between 20-25°C.
Excursions permitted to 15-30°C. Protect from light and
moisture. Orodispersible tablet: No special storage
conditions. Oral solution: store between 15-25°C.
Excursions permitted to 15-30°C. Protect from light and
freezing. Long-acting injectable: The entire dose pack
should be stored in the refrigerator between 2–8°C and
protected from light. If refrigeration is unavailable, it can
be stored at temperatures not exceeding 25°C for no
NERVOUS SYSTEM

more than 7 days prior to administration. Do not expose ANXIOLYTICS

unrefrigerated product to temperatures above 25°C.

Adverse Drug Reactions: Rx ALPRAZOLAM

Common: Anxiety, appetite changes, arthralgia, depression,
dose-dependent extrapyramidal symptoms, dose-related
Oral: 250 micrograms, 500 micrograms, and 1 mg tablet
hyperprolactinemia, dose-dependent dizziness,
insomnia, anxiety, sedation, epistaxis, hypertension,
Alprazolam is a short-acting benzodiazepine which causes a
infection, malaise, myalgia, edema, respiratory
dose-related CNS depressant activity varying from mild
disorders, sleep disorders, toothache, urinary disorders,
impairment of task performance to hypnosis.
weight gain, sedation, dizziness, hypotension, motor side
Indications: Acute treatment of generalized anxiety disorder,
effect, dose-dependent extrapyramidal symptoms, dose-
acute treatment of panic disorder with or without
dependent hyperprolactinemia
agoraphobia. Adjunct for acute mania and acute
Less Common: Alopecia, hypoesthesia, paresthesia, taste
psychosis, generalized anxiety disorder, panic disorder.
disturbances, tinnitus, visual disorders.
Rare: Inappropriate antidiuretic hormone secretion,
NOTE: Alprazolam does not have analgesic, antidepressant,
intestinal obstruction, intra-operative floppy iris
or antipsychotic properties.
syndrome, pancreatitis, pulmonary embolism,
rhabdomyolysis.
Contraindications: Narrow-angle glaucoma, myasthenia
gravis, history of substance use disorder, respiratory
NOTE: Patients taking this drug may experience weight gain
disorders (e.g. chronic obstructive pulmonary disease,
and/or sedation.
sleep apnea), significant hepatic disease, pregnancy,
labor, lactation.
Drug Interactions:
Monitor closely with:
Dose:
Reduces the therapeutic effects of the following drugs:
NOTE: Treatment >4 weeks should be reevaluated to
Amphetamines, Dopamine agonists, Levodopa
determine the service user/patient's continued need for
the drug.

N
Enhances the therapeutic effects of the following drugs:
Antihypertensives [except Guanethidine]
Generalized anxiety disorder, by mouth, ADULT, Immediate
Increases therapeutic effects of Risperidone:
release: initially 0.75-1.5 mg/day in 3 divided doses.
Anticholinergics
Slowly titrate dose every 3-4 days until desired efficacy is
reached with a maximum dose of 4 mg/day. Assess need
Increases risk adverse/toxic effect of Risperidone:
for continued treatment regularly as benzodiazepines
Acetylcholinesterase inhibitors, Metoclopramide,
should generally be used for not more than 4 weeks for
Valproate (increase the risk of generalized edema with
anxiety disorders.
and the clearance of risperidone)
Panic disorder, by mouth, ADULT:
Increases risk of adverse or toxic effects of the following
Immediate release: initially 1.5 mg/day in 3 divided
drugs:
doses. Slowly increase by ≤1 mg/day every 3-4 days until
CNS depressants, Methylphenidate
desired efficacy is reached. Slowly increase by small
Iohexol, Iomeprol, Iopamidol (seizures)
amounts for dosages beyond 4mg/day. Doses as high as
Mequitazine (arrhythmogenic effect)
10 mg/day may be required for difficult cases. Assess
QTc-prolonging agents
need for continued treatment regularly as
SSRIs (psychomotor impairment)
benzodiazepines should generally be used for not more
than 4 weeks for anxiety disorders.
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
Extended release: initially 0.5-1 mg once daily in the
drugs:
morning. Slowly increase by ≤1 mg/day every 3-4 days
Other Antipsychotics (increased hospitalization rates
until desired efficacy is reached up to a maximum dose
and length of stay; increased mortality)
of 10 mg once daily. Assess need for continued
treatment regularly as benzodiazepines should generally
Administration: May be taken with or without food.
be used for not more than 4 weeks for anxiety disorders.
Intramuscular injection into the deltoid or gluteal muscle.
Switching from immediate release to extended release:
Pregnancy Category: C
Service patients may be switched to extended release
tablets by taking the total daily dose of the immediate
ATC Code: N05AX08
release tablets and giving it once daily using the
extended release preparation.

Adjunct for acute mania and acute psychosis in patients

who are in acute agitation, by mouth, 250 mcg-1mg
every hour (maximum of 3 doses) provided that vital
signs are monitored

505

NOTE: Dose reduction: Abrupt discontinuation should be
avoided. Generally, the dose is reduced by 25% per week
until 50% of the dose is reached, then the dose is
reduced by one-eighth every 4-7 days. If therapy is >8
weeks, slowly taper over 2-3 weeks. If therapy is >6
months, slowly taper over 4-8 weeks. If therapy is >1
year, slowly taper over 2-4 months.
Dose Adjustment:
Geriatric:
Immediate release: Initial 0.25 mg twice or thrice daily.
Extended release: Initial: 0.5 mg once daily.
NOTE: Elderly service patients may be more sensitive to the
effects of alprazolam including ataxia and oversedation.
The elderly may also have impaired renal function
leading to decreased clearance. Titrate gradually, if
needed and tolerated.
Renal Impairment:
Start with small doses in severe impairment.
Hepatic Impairment:
For service patients with advanced liver disease:
Immediate release: 0.25 mg twice or thrice daily; titrate
slowly if needed and tolerated.
Extended release: 0.5 mg once daily; titrate slowly if needed
and tolerated.
N
Precautions:
NOTE:
Muscle weakness;
Organic brain changes
Personality disorder (within the fearful group) dependent,
avoidant, obsessive-compulsive)
Patients may develop dependence/tolerance with long-term
use.
Pregnancy (not recommended as treatment for anxiety
during pregnancy, especially during the first trimester).
MONITORING PARAMETERS: Respiratory and
cardiovascular status.
STORAGE AND STABILITY: Immediate release tablets: Store
at 20°C to 25°C (68°F to 77°F). Extended release
tablets: Store at 25°C (77°F); excursions permitted to
15°C to 30°C (59°F to 86°F). Orally disintegrating
tablet: Store at room temperature of 20°C to 25°C
(68°F to 77°F). Protect from moisture. Seal bottle tightly
and discard any cotton packaged inside bottle.
Adverse Drug Reactions:
Common: Amnesia, ataxia (especially in the elderly),
confusion (especially in the elderly), dependence,
depression, drowsiness the next day, fatigue,
forgetfulness, hyperexcitability, lightheadedness the
next day, muscle, nervousness, weakness, paradoxical
increase in aggression, slurred speech.
Less Common: Changes in libido, dizziness, dysarthria,
gastrointestinal disturbances, gynecomastia, headache,
hypotension, incontinence, salivation changes, slurred
speech, tremor, urinary retention, vertigo, visual
disturbances.
Rare: Apnea, blood disorders, jaundice, respiratory
depression, skin reactions.
506
NERVOUS SYSTEM
NOTE: Patients taking this drug may experience sedation.
Drug Interactions:
Monitor closely with:
Enhances the therapeutic effects of CNS Depressants e.g.,
Alcohol
Increases risk of adverse or toxic effects of SSRIs e.g.
Fluoxetine (psychomotor impairment)
Avoid concomitant use with:
Increases the serum concentration of Alprazolam:
Itraconazole, Ketoconazole (Systemic), Estrogen-
containing hormonal contraceptives
Administration:
NOTE: May be administered with or without food. If drug
upsets stomach, take with food.
Immediate release preparations: Can be administered
sublingually if oral administration is not possible;
absorption and onset of effect are comparable to oral
administration.
Extended release tablet: Should be taken once daily in the
morning; do not crush, break, or chew.
Orally disintegrating tablets: Do not remove tablets from the
container until just prior to administration. Do not push
the tablet out of the foil when opening. Using dry hands,
place tablet on top of tongue and allow to disintegrate. If
using one half of tablet, immediately discard remaining
half (may not remain stable). Administration with water
is not necessary. Do not swallow it whole. Do not chew,
break, or crush it. Discard any cotton included in the
container and reseal the container tightly after opening
to prevent introduction of moisture.
Pregnancy Category: D
BREAST-FEEDING CONSIDERATIONS: Benzodiazepines are
present in milk, and should be avoided if possible during-
breast feeding.
PATIENT ADVICE: May impair judgement and increase
reaction time, and so affect ability to drive or operate
machinery; they increase the effects of alcohol.
Moreover, the hangover effects of a night dose may
impair driving on the following day. Take only as
prescribed; do not increase dosage or duration of
therapy unless otherwise instructed by a clinician. Do
not abruptly discontinue therapy. For women, inform
clinicians if they are or planning to become pregnant or
plan to breast-feed. Inform clinicians of any concomitant
illness, particularly depression; behavioral or mental
changes, memory impairment, tolerance, or
dependence/withdrawal symptoms.
SPECIAL CONSIDERATIONS: In adolescent with psychotic or
bipolar disorder, Risperidone can be offered as a
treatment option only under supervision of a specialist,
if treatment with Risperidone is not feasible,
Haloperidol or Chlopromazine may be used only under
supervision of a specialist.
ATC Code: N05BA12
NERVOUS SYSTEM
Rx BROMAZEPAM
Oral: 1.5 mg tablet
Bromazepam is a benzodiazepine. It has been used in the
short-term treatment of anxiety disorders occurring
alone or associated with insomnia.
Indications: Short-term relief of symptoms of excessive
anxiety.
NOTE: Bromazepam does not have analgesic,
antidepressant, or antipsychotic properties.
Contraindications: Myasthenia gravis; narrow-angle
glaucoma; severe hepatic or respiratory disease; sleep
apnea; history of substance use disorder; pregnancy,
labor, or lactation
Dose:
Anxiety, by mouth, ADULT, Initial: 6 to 18 mg/day in equally
divided doses. Initial course of treatment should not last
longer than 1 week without reassessment of the need for
a limited extension. Optimal dosage range: 6 to 30
mg/day. Limited experience with doses up to 60 mg/day.
For debilitated service patients: Initial dose: 3 mg/day in
divided doses; may adjust dose cautiously based on
response and tolerance.
Dose Adjustment:
Geriatric:
Anxiety, by mouth, Initial dose: 3 mg/day in divided doses;
may adjust dose cautiously based on response and
tolerance.
Renal Impairment:
No dosage adjustments; initiate therapy conservatively and
titrate cautiously.
Hepatic Impairment:
Mild to moderate impairment: No dosage adjustments;
initiate therapy conservatively and titrate cautiously.
Severe impairment: Use of bromazepam is contraindicated.
Precautions:
WARNING: Patients must be cautioned about performing
tasks which require mental alertness (e.g., operating
machinery or driving).
Concerns related to adverse effects:
Anterograde amnesia; CNS depression; paradoxical
reactions (e.g., hyperactive or aggressive behavior);
sleep-related activities.
Use with caution in:
Depression (not recommended in patients with depressive
disorders or psychosis);
Drug abuse (dependence and tolerance); Withdrawal (use
caution when reducing dose or withdrawing therapy;
decrease slowly and monitor for withdrawal symptoms);
Post-traumatic Stress Disorder;
Hepatic and renal impairment;
Respiratory depression;
Elderly (impaired cognition, delirium, falls, fractures, and
motor vehicle accidents. (avoid use for treatment of
insomnia, agitation, or delirium);
Pregnancy (not recommended as treatment for anxiety
during pregnancy, especially during the first trimester;
drug should be tapered if discontinued); Lactation (use
while breastfeeding is not recommended).
MONITORING PARAMETERS: Respiratory, cardiovascular,
and mental status; periodic CBC and liver function tests.
STORAGE AND STABILITY: Store at room temperature of
15°C to 30°C (59°F to 86°F).
Adverse Drug Reactions:
Common: Cardiac arrest, hypotension, palpitations,
tachycardia; Ataxia, confusion, depression, dizziness,
drowsiness, emotional lability, euphoria, fatigue,
headache, impaired consciousness, myasthenia,
seizure, Pruritus, skin rash, change in libido,
Gastrointestinal distress, nausea, vomiting, xerostomia;
urinary incontinence, muscle spasm, Blurred vision,
diplopia, respiratory depression.
Drug Interactions:
Monitor closely with:
Reduces the therapeutic effect of Bromazepam:
Theophylline Derivatives e.g., Aminophylline
N
Enhances the therapeutic effects of CNS depressants e.g.
Alcohol
Increases risk of adverse or toxic effects of the following
drugs:
Flumazenil (precipitate seizures)
Pramipexole, Ropinirole, Rotigotine (sedative effect)
SSRIs (psychomotor impairment)
Administration: May be administered with or without food.
Pregnancy Category: C
NOTE: Bromazepam requires an S-2 license for physicians
to be able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense it.
ATC Code: N05BA08
Rx CLONAZEPAM
Oral: 500 micrograms and 2 mg tablet
A benzodiazepine derivative that is used both as an
anticonvulsant and for the short-term treatment of panic
disorder with or without agoraphobia.
Indication: Second-line treatment for panic disorder, with or
without agoraphobia; Lennox-Gastaut syndrome (petit
mal variance); akinetic seizure; myoclonic seizure;
absence seizure (petit mal)
NOTE: Clonazepam does not have analgesic,
antidepressant, or antipsychotic properties. Worsening
of seizures may occur when added to service patients
507

with multiple seizure types. Periodically re-evaluate the
long-term usefulness of clonazepam for the individual
service user/patient.
Contraindications: Severe liver disease, angle-closure
glaucoma, myasthenia gravis, current alcohol abuse and
drug abuse, respiratory depression, coma.
Dose:
Panic disorder with or without agoraphoia, by mouth,
ADULT, initially 0.25 mg/day in 2 divided doses. Slowly
increase in increments of 0.25 to 0.5 mg/day in 2
divided doses every 3 days until an average dose of 1
mg/day in 2 divided doses daily is reached or the desired
efficacy is reached, whichever comes first, with a
maximum dose of 4 mg/day. Discontinuation of
treatment: To discontinue, treatment should be
withdrawn gradually. Decrease dose by 0.25 mg/day in
2 divided doses every 3 days until medication is
completely withdrawn.
Seizures, by mouth, 1.5 mg into three divided doses, raise
by 0.5 mg every 3 days until desired effect is reached;
divide into three even doses or else give largest dose at
bedtime; maximum dose generally 20 mg/day.
Panic disorder, by mouth, 0.25 mg twice daily; increase in
increments of 0.125 to 0.25 mg twice daily every 3 days;
target dose: 1 mg daily (maximum: 4 mg daily).
N
Discontinuation of treatment: To discontinue, treatment
should be withdrawn gradually. Decrease dose by 0.125
mg twice daily every 3 days until medication is
completely withdrawn.
Dose Adjustment:
Geriatric:
Refer to adult dosing. Initiate with low doses and observe
closely for signs of CNS and pulmonary toxicity.
Renal Impairment:
Start with small doses in severe impairment.
Hepatic Impairment:
Start with smaller initial doses or reduce dose. Can
precipitate coma. Avoid in severe impairment.
Precautions:
WARNING: Concomitant use of benzodiazepines and
opioids may result in profound sedation,
respiratory depression (monitor), coma, and
death. Reserve concomitant prescribing of these
drugs for use in service patients for whom
alternative treatment options are inadequate.
Limit dosages and durations to the minimum
required.
Acute porphyrias, airways obstruction, brain damage,
cerebellar ataxia, depression, spinal ataxia, suicidal
ideation.
Disease-related concerns:
Drug abuse
Post-traumatic Stress Disorder
Special populations:
508
NERVOUS SYSTEM
Elderly (Increase the risk of impaired cognition, delirium,
falls, fractures, and motor vehicle accidents (avoid use
for treatment of insomnia, agitation, or delirium) though
use may be appropriate for seizure disorders, rapid eye
movement sleep disorders, benzodiazepine withdrawal,
ethanol withdrawal, severe generalized anxiety disorder,
and periprocedural anesthesia.)
Pregnancy (Not recommended as treatment for anxiety
during pregnancy, especially during the first trimester.
Drug should be tapered if discontinued.)
Breastfeeding (should be avoided if possible during breast-
feeding.)
Other precautions:
Opioids and skeletal muscle relaxants
Tolerance (The effectiveness of clonazepam may decrease
significantly after weeks or months of continuous
therapy.)
Withdrawal
MONITORING PARAMETERS: CBC, liver and renal function
tests (periodically with long-term therapy) suicidality
(e.g., suicidal thoughts, depression, behavioral changes).
STORAGE AND STABILITY: Tablets: Store at 20°C to 25°C
(68°F to 77°F). Orally disintegrating tablets: Store at
25°C (77°F) ; excursions permitted between 15°C and
30°C (59°F and 80°F).
Adverse Drug Reactions:
Common: Amnesia, bronchial hypersecretion and salivary
hypersecretion in infants and small children,
coordination disturbances, confusion, dependence,
dizziness, drowsiness, fatigue, muscle hypotonia,
nystagmus, poor concentration, restlessness, withdrawal
syptoms (in children).
Rare: Aggression, anxiety, blood disorders, dysrthria,
gastrointestinal symptoms, headache, paradoxical
effects, pruritus, respiratory depression.
Drug Interactions:
Monitor closely with:
Increases risk adverse/toxic effect of Clonazepam:
(sleepiness and dizziness)
Decreases the therapeutic effects of Clonazepam:
Theophylline derivatives, Yohimbine, CNS Depressants
Increases risk of adverse or toxic effects of the following
drugs:
Flumazenil (precipitate seizures)
Ropinirole, Pramipexole, Rotigotine (sedative effect)
SSRIs (psychomotor impairment)
Increases plasma concentration of Clonazepam:
Disulfiram (reduce Clonazepam dosage as necessary)
Decreases plasma concentration of Clonazepam:
Propantheline
Administration: Administer in 3 equally divided doses for the
treatment of seizure disorders; if doses are not equally
divided, give the largest dose at bedtime. Administer in 2
equally divided doses for the management of panic
disorder; alternatively, administer the entire dosage at
bedtime to reduce the inconvenience of somnolence.
NERVOUS SYSTEM
Orally disintegrating tablet: Just prior to administration,
remove blister from aluminum pouch. Open pouch and
peel back foil on the blister; do not push tablet through
foil. Use dry hands to remove tablet and place in mouth.
May be swallowed with or without water. Use
immediately after removing from package.
Tablet: Swallow whole with water.
See Clonazepam under Benzodiazepine Derivatives in
Chapter 10: Antiepileptics for other information.
Pregnancy Category: D
PREGNANCY
BREAST-FEEDING: Present in milk, and should be avoided if
possible during breast-feeding. All infants should be
monitored for sedation, feeding difficulties, adequate
weight gain, and developmental milestones.
PATIENT ADVICE: Inform clinicians and pharmacists of
existing or contemplated concomitant therapy, including
prescription and OTC drugs, and alcohol consumption.
Inform clinician of any of these health problems:
glaucoma or very bad liver disease. Take only as
prescribed; do not increase dosage or duration of
therapy unless otherwise instructed by a clinician. Do
not abruptly discontinue therapy, this could cause
seizures. If the drug has been taken for a long time or at
high doses, it may not work as well and higher doses may
be needed to get the same effect—this is known as
tolerance, inform the clinician it the drug stops working
well.
Avoid driving and doing other tasks or actions that needs
alertness. Avoid alcohol or other drugs and natural
products that slow down actions. Inform the clinician of
any side effect (e.g., behavioral or mental changes,
memory impairment, tolerance, or
dependence/withdrawal symptoms) experienced with
taking the drug. If seizures have been experienced in the
past, the drug may cause you to pass out. Do not do
activities that may be unsafe to you or others if you pass
out, like driving or swimming. For women, inform
clinicians if they are or planning to become pregnant or
plan to breast-feed. Do not breast-feed while taking this
drug.
ATC Code: N03AE01
Clonazepam requires an S-2 license for physicians to be
able to prescribe it and an S-1 license with a triplicate
prescription for pharmacists to dispense it.
Rx DIAZEPAM
Oral: 5 mg tablet
Inj.: 5 mg/mL, 2 mL ampule (IM, IV)
Diazepam is a benzodiazepine that exerts anxiolytic,
sedative, muscle- relaxant, anticonvulsant and
amnestic effects due to its facilitation of the action of
gamma aminobutyric acid (GABA), an inhibitory
neurotransmitter in the central nervous system.
Indications: Short-term management of anxiety disorders,
symptoms of anxiety, ethanol withdrawal symptoms,
skeletal muscle relaxant, convulsive disorders (adjunct),
preoperative or preprocedural sedation and amnesia or
perioperative anxiety (injection only), anxiety during
endoscopic procedures (adjunct, injection only), anxiety
relief prior to cardioversion (IV), acute agitation, tremor,
impending or acute delirium tremens, hallucinosis in acute
alcohol withdrawal, skeletal muscle spasm due to reflex
spasm to local pathology, spasticity caused by upper motor
neuron disorder, athethosis, Stiffman syndrome, initial
treatment of status epilepticus
NOTE: Diazepam does not have analgesic, antidepressant,
or antipsychotic properties.
Contraindications: Myasthenia gravis; severe respiratory
insufficiency; severe hepatic insufficiency; sleep apnea
syndrome; acute narrow-angle glaucoma; not for use in
infants <6 months of age (oral).
Dose:
NOTE: Oral absorption is more reliable than IM.
Acute ethanol withdrawal, by mouth, ADULT, 10 mg 3 to 4
times during first 24 hours, then decrease to 5 mg 3 to
4 times daily and continue treatment as needed, by
intravenous infusion, ADULT, initially administer 10 mg
N
at a rate of 5 mg/minute, followed by 5-10 mg 3-4 hours
later at a rate of 5 mg/minute, if needed, by
intramuscular injection, ADULT, initially administer 10
mg, followed by 5-10 mg 3-4 hours later, if needed.
Anxiety (symptoms/disorders), by mouth, ADULT, 2 to 10 mg
2-4 times daily if needed, by intravenous infusion,
ADULT, initially administer 2-10 mg at a rate of
5mg/minute. Repeat in 3-4 hours at a rate of 5
mg/minute, if needed, by intramuscular injection,
ADULT, initially administer 2-10 mg. Repeat in 3-4 hours,
if needed.
Conscious sedation for procedures, by mouth, CHILD, 0.2 to
0.3 mg/kg (maximum dose: 10 mg) 45 to 60 minutes
prior to procedure; Adolescents: 10 mg. by intravenous
infusion, Adolescents: 5 mg; may repeat with 2.5 mg if
needed.
Perioperative anxiety, by intramuscular injection, ADULT,
administer 10 mg prior to surgery.
Rapid tranquilization of agitated service user/patient
(administer every 30 to 60 minutes), by mouth, ADULT,
5 to 10 mg; average total dose for tranquilization: 20-60
mg; by iInjection:5 mg per mL, 0.5 mL-1 mL every 30-60
minutes provided that the vital signs are monitored
Sedation or muscle relaxation or anxiety, by mouth, CHILD,
0.12 to 0.8 mg/kg/day in divided doses every 6 to 8
hours. IV or IM, CHILD, 0.04 to 0.3 mg/kg/dose every 2
to 4 hours to a maximum of 0.6 mg/kg within an 8-hour
period if needed.
Sedation in the ICU service user/patient, by intravenous
infusion, ADULT, Loading dose: 5 to 10 mg; Maintenance
dose: 0.03 to 0.1 mg/kg every 30 minutes to 6 hours.
Skeletal muscle relaxant (adjunct therapy), by mouth,
ADULT, 2-10 mg 3-4 times daily.
Dose Adjustment:
Debilitated Patients/Geriatric:
Oral: Initially 2-2.5 mg once or twice daily. Slowly increase
as needed and tolerated.
509

NOTE: Due to its long-acting metabolite, diazepam is not
considered a drug of choice in the elderly. Long-acting
benzodiazepines have been associated with falls in the
elderly.
Renal Impairment:
Initially 2-2.5 mg once or twice daily. Slowly increase as
needed and tolerated.
NOTE: Hemodialysis – Not dialyzable (0%-5%); supplemental dose is
not necessary.
Hepatic Impairment:
Initially 2-2.5 mg once or twice daily and slowly increase as
needed and tolerated for mild to moderate hepatic
impairment. Contraindicated in severe hepatic
impairment. If treatment is necessary, benzodiazepines
with shorter half lives are safer, such as temazepam or
oxazepam.
Precautions:
WARNING: Concomitant use of benzodiazepines and
opioids may result in profound sedation, respiratory
depression, coma, and death. Reserve concomitant
prescribing of these drugs for use in patients for
whom alternative treatment options are
inadequate. Limit dosages and durations to the
minimum required. Follow patients for signs and
N
symptoms of respiratory depression and sedation.
When given IV, there is a risk of propylene glycol
toxicity; monitor closely if using for prolonged
periods or at high doses.
To be prescribed and dispensed through Yellow Rx.
Only one (1) drug preparation shall be prescribed in
one single prescription form. Partial filling allowed.
STRICTLY NO REFILL.
Diazepam 5 mg requires an S-2 license for physicians
to be able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense
it.
Anterograde amnesia;
CNS depression;
Opioids–should be reduced by approximately one third
when diazepam is added;
Psychiatric and paradoxical reactions (discontinue if
reactions occur);
Convulsive disorders (abrupt withdrawal - seizures);
Depression;
Drug abuse; tolerance, psychological and physical
dependence may occur with prolonged used (generally
>10 days);
Hepatic and renal impairment;
Impaired gag reflex;
Post-traumatic Stress Disorder;
Respiratory disease (lower dose is recommended for
chronic insufficiency).
Special populations:
Debilitated/elderly patients; Obese patients (prolonged
action when discontinued).
Psychotic patients (use of diazepam is not recommended in
place of appropriate therapy.
Pregnancy (not recommended during pregnancy, especially
during the first trimester. Drug should be tapered if
510
NERVOUS SYSTEM
discontinued. Women who have seizures in the second
half of pregnancy should be assessed for eclampsia
before any change is made to antiepileptic treatment.
Lactation (Because diazepam and its metabolites may be
present in breast milk for prolonged periods following
administration, it is recommended to discontinue breast-
feeding for an appropriate period of time.).
Benzyl alcohol and derivatives (potentially fatal toxicity
“gasping syndrome” in neonates).
MONITORING PARAMETERS: Respiratory, cardiovascular,
and mental status; check for orthostasis. /For critically ill
mechanically-ventilated service patients: Monitor depth
of sedation with either the Richmond Agitation Sedation
Scale (RASS) or Sedation-Agitation Scale (SAS).
STORAGE AND STABILITY: Injection: Store at 20°C to 25°C
(68°F to 77°F) ; excursions permitted to 15°C to 30°C
(59°F to 86°F). Protect from light. Potency is retained for
up to 3 months when kept at room temperature. Most
stable at pH 48; hydrolysis occurs at pH <3. Tablet: Store
at 15°C to 30°C (59°F to 86°F).
Adverse Drug Reactions:
NOTE: Adverse reactions may vary by route of
administration.
Common: Localized phlebitis, vasodilatation, amnesia,
ataxia, confusion, depression, drowsiness the next day,
lightheadedness the next day, dysarthria, muscle
weakness, constipation, diarrhea, nausea, pain at
injection site; tremor, asthma, bradypnea; paradoxical
increase in aggression.
Less common: Changes in libido (in adults), dizziness,
dysarthria, gastro-intestinal disturbances, gynecomastia,
headache, hypotension (in adults), incontinence,
salivation changes, slurred speech, tremor, urinary
retention, vertigo, visual disturbances.
Rare: Apnea, changes in libido (in children) respiratory
depression (overdose), hepatic dysfunction, renal
dysfunction, blood disorders, hallucinations, mania,
hypotension (in children), jaundice, skin reactions.
Drug Interactions:
Monitor closely with:
Enhances the toxic/adverse effects of SSRIs (psychomotor
impairment)
Enhances the toxic/adverse effects of diazepam:
Cosyntropin (hepatotoxic)
CNS depressants (central effects)
Flumazenil (precipitate seizures)
Enhances the sedative effect of the following drugs:
Pramipexole, Ropinirole, Rotigotine
Decreases therapeutic effect of diazepam:
Theophylline derivatives e.g. Aminophylline
FOOD INTERACTIONS: Diazepam serum concentrations may
be decreased if taken with food. Grapefruit juice may
increase diazepam serum concentrations. Avoid
concurrent use of grapefruit juice. Maintain adequate
hydration, unless instructed to restrict fluid intake.
NERVOUS SYSTEM
TEST INTERACTIONS: False-negative urinary glucose
determinations when using Clinistix® or Diastix®.
Administration:
Note: Do not mix IV product with other medications. When
given intravenously, continuous infusion is not
recommended because of precipitation in IV fluids and
absorption of drug into infusion bags and tubing. In
children, do not exceed 1 to 2 mg/minute IVP; in adults
5 mg/minute.
WARNING: Parenterally administered diazepam may
cause hypotension and/or respiratory depression,
particularly if the drug is administered too rapidly
IV.
When given IV, diazepam should be administered directly
into a large vein to avoid thrombosis; if this is not
feasible, the drug should be given into the tubing of a
flowing IV solution as close as possible to the vein
insertion. Small veins such as those of the wrist or the
dorsum of the hand should not be used. Care should be
taken to avoid intra-arterial administration or
extravasation. Alternatively, some clinicians have
suggested IV administration of dilute solutions of the
drug to avoid extravasation; however, the drug may
precipitate when diluted and the manufacturers do not
recommend this method of administration.
Although diazepam may also be given by deep IM injection,
this route of administration of the drug is rarely justified
because absorption is slow and erratic.
Therapy with oral diazepam should replace parenteral
administration as soon as possible.
WARNING: Diazepam is a vesicant; ensure proper
needle or catheter placement prior to and during
infusion; avoid extravasation. Extravasation
management: If extravasation occurs, stop IV
administration immediately and disconnect (leave
cannula/needle in place) ; gently aspirate
extravasated solution (do NOT flush the line) ;
remove needle/cannula; elevate extremity. Apply
dry cold compresses.
See Diazepam under Other Antiepileptics in Chapter 10:
Antiepileptics for other information.
Pregnancy Category: D
ATC Code: N05BA01
HYPNOTICS AND SEDATIVES
Rx MIDAZOLAM
Oral: 15 mg tablet
Inj.: 1 mg/mL, 5 mL ampule / vial (IM, IV)
5 mg/mL, 1 mL, 2 mL, 3 mL, 5 mL, and 10 mL ampule
(IM, IV)
Midazolam is a short-acting benzodiazepine with general
properties similar to those of diazepam, except that it
has a more potent amnestic action. It is mainly used for
sedation in minor surgical or investigative procedures
and in intensive care, for premedication, and for
induction of general anaesthesia.
Indications: Sedation in minor surgical or investigative
procedures; ICU sedation (continuous infusion);
preoperative sedation, conscious prior to short
diagnostics or endoscopic procedures; preoperative
anxiolytic; drug-induced amnesia premedication and
sedation, and for induction and maintenance of general
anesthesia; moderate sedation prior to diagnostic or
radiographic procedures. Sedation in pediatric patients
WARNING: Use only when adequate treatment
N
facilities for appropriate management of therapy
and complications are available.
NOTE: Midazolam does not have analgesic, antidepressant,
or antipsychotic properties. Does not protect against
increases in heart rate or blood pressure during
intubation. Should not be used in shock, coma, or acute
alcohol intoxication.
Contraindications: Intrathecal or epidural injection of
parenteral forms containing preservatives (i.e., benzyl
alcohol); acute narrow angle glaucoma; Severe
respiratory depression; severe hepatic insufficiency;
sleep apnea syndrome; myasthenia gravis, CNS
depression.
Dose:
NOTE: The dose of midazolam needs to be individualized
based on the patient's age, underlying diseases, and
concurrent medications. Consider reducing dose by 20%-
50% in elderly, chronically ill, or debilitated patients and
those receiving opioids or other CNS depressants.
Preoperative/preprocedural sedation, by mouth,
ADULT<60 years, 7.5-15 mg 30-60 minutes prior to
surgery/procedure, by intramuscular injection,
ADULT<60 years, 0.07 to 0.08 mg/kg 30-60 minutes
prior to surgery/procedure; usual dose: 5 mg, by
intravenous infusion, ADULT<60 years, 0.02 to 0.04
mg/kg; repeat every 5 minutes as needed to desired
effect or up to 0.1 to 0.2 mg/kg.
Conscious sedation, by intravenous infusion, ADULT<60
years, Initial: Some service patients respond to doses as
low as 1 mg; no more than 2.5 mg should be
administered over a period of 2 minutes. Additional
doses of midazolam may be administered after a 2
minute waiting period and evaluation of sedation after
each dose increment. A total dose >5 mg is generally not
511

needed. Maintenance: 25% of dose used to reach
sedative effect. ADULT ≥60 years, debilitated, or
chronically ill, Refer to geriatric dosing. Alternate
recommendations (American Society for
Gastrointestinal Endoscopy): Initial: 0.5 to 2 mg slow IV
over at least 2 minutes; slowly titrate to effect by
repeating doses every 2 to 3 minutes if needed; usual
total dose: 2.5 to 5 mg.
Anesthesia, by intravenous infusion, ADULTS<55 years,
Induction: Unpremedicated service patients: 0.3 to 0.35
mg/kg over 20-30 seconds; after 2 minutes, may repeat
if necessary at 25% of initial dose every 2 minutes, up to
a total dose of 0.6 mg/kg in resistant cases.
Premedicated patients: Usual dosage range: 0.05-0.2
mg/kg. Use of 0.2 mg/kg administered over 5 to 10
seconds has been shown to safely produce anesthesia
within 30 seconds and is recommended for ASA physical
status P1 and P2 patients. When used with other
anesthetic drugs (i.e., coinduction), the dose is <0.1
mg/kg. ASA physical status >P3 or debilitation: Reduce
dose by at least 20%. Maintenance: 0.05 mg/kg as
needed, or continuous infusion 0.015 to 0.06
mg/kg/hour (0.25 to 1 mcg/kg/minute).
Sedation in mechanically-ventilated service patients, by
intravenous infusion, ADULT, Initial dose: 0.01 to 0.05
mg/kg (~0.5 to 4 mg); may repeat at 5-15 minute
intervals until adequate sedation achieved; maintenance
infusion: 0.02 to 0.1 mg/kg/hour (0.3 to 1.7
N
mcg/kg/minute). Titrate to reach desired level of
sedation. Titration to maintain a light rather than a deep
level of sedation is recommended unless clinically
contraindicated. May consider a trial of daily awakening;
if agitated after discontinuation of drip, then restart at
50% of the previous dose.
WARNING: Initial IV dose for healthy adults should not
exceed 2.5 mg. Lower dosages are necessary in
patients >60 years of age, debilitated service
patients, and service patients receiving
concomitant opiates or other CNS depressants.
Titrate initial and subsequent dosages slowly;
administer the appropriate dose over ≥2 minutes
and wait an additional 2 or more minutes to fully
evaluate the sedative effect.
NOTE: For pediatric patients: The dose of midazolam needs
to be individualized based on the patient's age,
underlying diseases, and concurrent medications.
Decrease dose (by ~30%) if opioids or other CNS
depressants are administered concomitantly. Children
<6 years may require higher doses and closer monitoring
than older children; in children with obesity, calculate
dose based on ideal body weight.
Conscious sedation for procedures or preoperative
sedation, CHILD≥6 months, Children, and Adolescents
≤16 years: oral (solution only), 0.25 to 0.5 mg/kg
(maximum: 20 mg) as a single dose 20 to 30 minutes
prior to procedure. Children <6 years or less cooperative
patients may require as much as 1 mg/kg as a single
dose; 0.25 mg/kg may suffice for children 6-16 years of
age or for cooperative patients. Doses of 0.5-0.75 mg/kg
administered 20-30 minutes prior to procedure have
also been suggested; however, doses above 0.5 mg/kg
typically do not improve the sedative and anxiolytic
effects but increase side effects during recovery. by
512
NERVOUS SYSTEM
intramuscular injection, 0.1-0.15 mg/kg 30 to 60
minutes before surgery or procedure; range: 0.05-0.15
mg/kg; doses up to 0.5 mg/kg have been used in more
anxious patients; maximum total dose: 10 mg.
Conscious sedation for procedures or preoperative
sedation, by intravenous infusion, CHILD<6 months,
Limited information is available in nonintubated infants;
dosing recommendations not clear; infants <6 months
are at higher risk for airway obstruction and
hypoventilation; titrate dose in small increments to
desired effect. CHILD 6 months-5 years, Initial: 0.05-0.1
mg/kg; total dose of 0.6 mg/kg may be required;
maximum total dose: 6 mg, CHILD 6-12 years: Initial:
0.025 to 0.05 mg/kg; total doses of 0.4 mg/kg may be
required; maximum total dose: 10 mg, CHILD 12-16
years: Dose as adults; maximum total dose: 10 mg.
Conscious sedation during mechanical ventilation, by
intravenous infusion, CHILD<18 years, Loading dose:
0.05 to 0.2 mg/kg, followed by initial continuous
infusion: 0.06 to 0.12 mg/kg/hour (1 to 2
mcg/kg/minute).
USUAL INFUSION CONCENTRATIONS: Adult: IV infusion: 100
mg in 100 mL (concentration: 1 mg/mL) of D5W or NS.
Pediatric: IV infusion: 0.5 mg/mL or 1 mg/mL.
WARNING: Calculate pediatric dosage on a mg/kg
basis. Initial dose is dependent on age, procedure,
and route; titrate subsequent dosages slowly.
Dose Adjustment:
Geriatric:
NOTE: The dose of midazolam needs to be individualized
based on the patient's age, underlying diseases, and
concurrent medications. Consider reducing dose by 20%-
50% in elderly, chronically ill, or debilitated patients and
those receiving opioids or other CNS depressants.
Anesthesia, by intravenous infusion, ADULT >55 years,
Induction: Unpremedicated service patients: Initial dose:
0.3 mg/kg; Premedicated service patients: Reduce dose
by at least 20%. Maintenance: Refer to adult dosing.
Conscious sedation, by intravenous infusion, ADULT, Initial:
0.5 mg slow IV; give no more than 1.5 mg in a 2 minute
period; if additional titration is needed, give no more than
1 mg over 2 minutes, waiting another 2 or more minutes
to evaluate sedative effect; a total dose of >3.5 mg is
rarely necessary.
Preoperative/pre-procedural sedation, ADULT >60 years
(without concomitant opioid administration): by
intramuscular injection, 2 to 3 mg (or 0.02 to 0.05
mg/kg) 30 to 60 minutes prior to surgery/procedure;
some may only require 1 mg (or 0.01 mg/kg) if
anticipated intensity and duration of sedation is less
critical. By mouth, 7.5 mg 30 to 60 minutes prior to
surgery/procedure.
Renal Impairment:
Oral: 7.5 mg; consider lower doses as needed.
IV, and Oral (Solution): There are no dosage adjustments
provided; however, patients with renal failure receiving a
continuous infusion cannot adequately eliminate the
active hydroxylated metabolites (e.g., 1-
hydroxymidazolam) contributing to prolonged sedation
sometimes for days after discontinuation. Intermittent
NERVOUS SYSTEM
hemodialysis: Supplemental dose is not necessary.
Continuous venovenous hemofiltration (CVVH):
Unconjugated 1-hydroxymidazolam not effectively
removed; 1-hydroxymidazolamglucuronide effectively
removed; sieving coefficient = 0.45. Peritoneal dialysis:
Significant drug removal is unlikely based on
physiochemical characteristics.
Hepatic Impairment:
Oral: Mild to moderate impairment: 7.5 mg; consider lower
doses as needed. Severe impairment: Use is
contraindicated.
IV, and Oral (solution): Severe hepatic impairment (e.g.,
cirrhosis): Note: Use with caution in patients with any
degree of hepatic impairment; patients with hepatic
encephalopathy likely to be more sensitive to
midazolam. Single dose (e.g., induction): No dosage
adjustment recommended; patients with hepatic
impairment may be more sensitive compared to patients
without hepatic impairment; anticipate longer duration of
action. Multiple dosing or continuous infusion: Expect
longer duration of action and accumulation; based on
patient response, dosage reduction likely to be
necessary.
Precautions:
WARNING: Associated with respiratory depression
and respiratory arrest, especially when used for
sedation in noncritical-care settings. Death or
hypoxic encephalopathy has resulted when
respiratory depression was not recognized
promptly and treated effectively.
Initial doses in debilitated and elderly patients should
be conservative; start at the lower end of dosing
range.
Do not administer by rapid IV injection in neonates;
severe hypotension and seizures have been
reported; risk may be increased with concomitant
fentanyl use.
Midazolam 15 mg requires an S-2 license for
physicians to be able to prescribe it and an S-1
license with a triplicate prescription for
pharmacists to dispense it.
Cardiac disease; children (particularly if cardiovascular
impairment); concentration of midazolam in children
<15kg not to exceed 1 mg/mL.
Debilitated patients (reduce dose) (in children);
hypothermia; hypovolemia (hypotension); neonates;
airways obstruction and hypoventilation in children <6
months (monitor respiratory rate and oxygen saturation);
vasocontriction.
Impaired gag reflex.
Renal impairment (use with caution).
Respiratory disease (use with caution).
Tolerance; withdrawal.
Pregnancy; Lactation (avoid breast-feeding for 24 hours
after administration).
Concurrent drug therapy issues:
NOTE: See Drug Interactions Section for further information.
CNS depressants/psychoactive medications
CYP3A4 Inhibitors/Protease inhibitors (consider reducing
midazolam dose; is contraindicated with both oral and
parenteral forms of midazolam)
Opioids and skeletal muscle relaxants (CNS depression;
avoid)
Elderly/Debilitated patients (start at the lower end of dosing
range); fall risk
Obese patients (use with caution; may have prolonged
action when discontinued)
Neonates (do not administer by rapid IV injection in
neonates; increased risk with concomitant fentanyl use)
Benzyl alcohol and derivatives (potentially fatal toxicity
(“gasping syndrome”) in neonates; avoid or use dosage
forms containing benzyl alcohol with caution in
neonates.)
MONITORING PARAMETERS: Respiratory and
cardiovascular status, blood pressure, blood pressure
monitor required during IV administration. For critically ill
patients: Monitor depth of sedation with either the
Richmond Agitation-Sedation Scale (RASS) or Sedation--
Agitation Scale (SAS).
STORAGE/STABILITY: Oral: Store at 25°C (77°F);
excursions permitted to 15°C to 30°C (59°F to 86°F).
Injection: Store at 20°C to 25°C (68°F to 77°F),
excursions permitted to 15°C to 30°C (59°F to 86°F).
The manufacturer states that midazolam, at a final
concentration of 0.5 mg/mL, is stable for up to 24 hours
when diluted with D5W or NS. A final concentration of 1
mg/mL in NS has been documented to be stable for up
N
to 10 days. Admixtures do not require protection from
light for short-term storage.
Adverse Drug Reactions:
Common: Decreased tidal volume and/or respiratory rate
decrease, apnea; hypotension; drowsiness,
oversedation, impaired recall, agitation, headache,
seizurelike activity; nausea, vomiting; pain and local
reactions at injection site; myoclonic jerks (preterm
infants); nystagmus; cough; physical and psychological
dependence with prolonged use, hiccups, paradoxical
reaction; vital sign fluctuations.
Less Common: Acid taste, agitation, amnesia, bigeminy,
bradycardia, bronchospasm, confusion, dyspnea,
emergence delirium, euphoria, excessive salivation,
hallucinations, hyperventilation, laryngospasm, PVC,
rash, tachycardia, wheezing, respiratory arrest, cardiac
arrest.
Drug Interactions:
Monitor closely with:
Decrease therapeutic effect of Midazolam:
Aminophylline
Anesthetic agents, inhalation (patients who have
received midazolam as an induction agent may require
reduced amounts of inhalation agents during
maintenance of anesthesia)
Anticonvulsants e.g., carbamazepine, phenobarbital,
phenytoin; Use with caution; consider dosage
adjustments, if necessary
CCBs e.g., diltiazem, nifedipine, verapamil); use oral or
parenteral midazolam with caution; reduce oral
midazolam dosage.
Clozapine (consider therapy modification; consider
decreasing the dose of (or possibly discontinuing)
benzodiazepines prior to initiating clozapine)
CNS Depressants
Ketamine
513

Opiates e.g., fentanyl (use with caution; adjust
midazolam dosage appropriately to avoid overdosage)
Quinupristin and Dalfopristin
SSRIs (psychomotor impairment)
Thiopental (induction of anesthesia reduced by about
15% in patients who received preoperative sedation with
IM midazolam)
Enchances the sedative effect of the following drugs:
Pramipexole, Ropinirole, Rotigotine
Decrease the therapeutic effect of midazolam:
Theophylline derivatives, Yohimbine
Avoid concomitant use with:
FOOD INTERACTIONS: Grapefruit juice may increase serum
concentrations of midazolam. Management: Avoid
concurrent use of grapefruit juice with oral midazolam
Administration:
WARNING: For deeply sedated pediatric service
patients, an individual other than the clinician
performing the procedure should be dedicated to
monitoring the service user/patient throughout
the procedure.
IM: Give deep IM into large muscle.
IV: Administer by slow IV injection over at least 2 to 5
N
minutes at a concentration of 1 to 5 mg/mL or by IV
infusion. For induction of anesthesia, administer IV bolus
over 5to 30 seconds. Continuous infusions should be
administered via an infusion pump.
Oral: Swallow tablet whole with adequate fluid.
Avoid intra-arterial injection or extravasation of the drug. Do
not administer intrathecally or epidurally. It is advisable
to keep the service user/patient supine during
intravenous use and throughout the procedure.
WARNING: Administer by direct IV injection as the 1-
mg/mL solution or dilute the 1 or 5mg/mL
solution to facilitate slower administration. Rapid
IV administration may result in respiratory
depression, airway obstruction, and/or respiratory
arrest. Do not administer by rapid IV injection in
neonates. Severe hypotension and seizures have
been reported following rapid IV administration,
particularly with concomitant administration of
fentanyl.
DIETARY CONSIDERATIONS: Avoid grapefruit juice with oral
syrup.
COMPATIBILITY: Stable in D5NS, D5W, NS; incompatible
with LR. Y-site administration: Compatible: Abciximab,
amikacin, amiodarone, anidulafungin, argatroban,
atracurium, bivalirudin, calcium gluconate, caspofungin,
cefazolin, cimetidine, ciprofloxacin, cisatracurium,
clindamycin, digoxin, diltiazem, doripenem, epinephrine,
eptifibatide, erythromycin lactobionate, esmolol,
etomidate, famotidine, fenoldopam, fentanyl,
fluconazole, gentamicin, heparin, hetastarch in lactate
electrolyte injection (Hextend®), hydromorphone, insulin
(regular), labetalol, linezolid, lorazepam, methadone,
metronidazole, milrinone, morphine, nicardipine,
514
NERVOUS SYSTEM
nitroglycerin, nitroprusside, norepinephrine,
palonosetron, pancuronium, piperacillin, ranitidine,
remifentanil, , theophylline, tirofiban, tobramycin,
vancomycin, vecuronium. Incompatible: Albumin,
amphotericin B cholesteryl sulfate complex, ampicillin,
bumetanide, butorphanol, cefepime, ceftazidime,
cefuroxime, dexamethasone sodium succinate,
drotrecogin alfa, foscarnet, fosphenytoin, furosemide,
hydrocortisone sodium succinate, imipenem/cilastatin,
methotrexate, micafungin, nafcillin, sodium bicarbonate,
thiopental, trimethoprim/sulfamethoxazole. Variable
(consult detailed reference): Cefotaxime, clonidine,
dobutamine, haloperidol, methylprednisolone sodium
succinate, metoclopramide, pantoprazole, potassium
chloride, propofol. Compatibility in syringe: Compatible:
Alfentanil, atracurium, atropine, buprenorphine,
butorphanol, chlorpromazine, cimetidine,
diphenhydramine, dopamine, droperidol, fentanyl,
glycopyrrolate, hydromorphone, hydroxyzine, ketamine,
meperidine, metoclopramide, morphine, nalbuphine,
ondansetron, promethazine, rocuronium, scopolamine,
trimethobenzamide. Incompatible: Dimenhydrinate,
heparin, pantoprazole, pentobarbital, prochlorperazine
edisylate, ranitidine. Variable (consult detailed
reference): Dexamethasone sodium phosphate,
methylprednisolone sodium succinate.
See Midazolam under Other Antiepileptics in Chapter 10:
Antiepileptics for other information.
Pregnancy Category: D
PREGNANCY CONSIDERATIONS: Hypoglycemia and
respiratory problems in the neonate may occur following
exposure late in pregnancy. Neonatal withdrawal
symptoms may occur within days to weeks after birth and
“floppy infant syndrome” (which also includes withdrawal
symptoms).
BREAST-FEEDING CONSIDERATIONS: Midazolam and
hydroxymidazolam can be detected in breast milk. The
manufacturer recommends that caution be exercised
when administering midazolam to nursing women.
PATIENT ADVICE: Inform clinicians and pharmacists of
existing or contemplated concomitant therapy, including
prescription and OTC drugs, and alcohol consumption.
Inform clinician of any breathing problems experienced.
Take only as prescribed; do not increase dosage or
duration of therapy unless otherwise instructed by a
clinician.
Avoid driving and doing other tasks or actions that needs
alertness. Avoid alcohol or other drugs and natural
products that slow down actions. Inform the clinician of
any side effect (e.g., feeling sleepy, tired or weak, or
memory problems or loss) experienced with taking the
drug. For women, inform clinicians if they are or planning
to become pregnant or plan to breast-feed.
ATC Code: N05CD08
NERVOUS SYSTEM
Rx ZOLPIDEM
Oral: 10 mg tablet
Zolpidem tartrate, a type A, γ-aminobutyric acid (GABAA) -
receptor agonist of the imidazopyridine class, is a
sedative and hypnotic agent. As conventional tablets,
zolpidem tartrate is used as a hypnotic agent in the short-
term management of insomnia characterized by
difficulties with sleep initiation.
Indications: Short-term treatment of insomnia; as needed
for the treatment of insomnia when a middle-of the-night
awakening is followed by a difficulty returning to sleep
and there are at least 4 hours of bedtime remaining
before planned time of wakening; short-term treatment
of insomnia.
Contraindications: obstructive sleep apnea and acute
and/or severe impairment of respiratory function;
unstable myasthenia gravis; severe hepatic impairment;
personal or family history of sleepwalking, psychotic
illness
Dose:
Short-term treatment of insomnia, by mouth, ADULT,
Note: The lowest effective dose should be used; higher
doses may be more likely to impair next morning
activities.
Immediate release tablet: 5 mg (females) or 5 to 10 mg
(males) immediately before bedtime for 7-10 days;
maximum dose: 10 mg daily.
Extended release tablet: 6.25 mg (females) or 6.25 to
12.5 mg (males) immediately before bedtime; maximum
dose: 12.5 mg daily.
For debilitated patients:
Immediate release tablet: 5 mg immediately before
bedtime.
Extended release tablet: 6.25 mg immediately before
bedtime.
Dose Adjustment:
Geriatric:
Immediate release tablet: 5 mg immediately before
bedtime.
Extended release tablet: 6.25 mg immediately before
bedtime.
Renal Impairment:
No dosage adjustment necessary. Use with caution and
monitor
Hepatic Impairment:
Immediate release tablet, 5 mg immediately before
bedtime.
Extended release tablet: 6.25 mg immediately before
bedtime.
WARNING: For severe hepatic impairment, use is
contraindicated.
Zolpidem requires an S-2 license for physicians to be
able to prescribe it and an S-1 license with a
triplicate prescription for pharmacists to dispense
it.
Precautions:
Avoid prolonged use (and abrupt withdrawal thereafter),
CNS depression, elderly, history of alcohol abuse, history
of drug abuse, muscle weakness, myasthenia gravis
Hypersensitivity e.g., anaphylactic reactions
Behavior changes
Neuropsychiatric symptoms e.g., amnesia, anxiety
Temporary memory loss at doses >10 mg/night
Insomnia may be a symptom of a primary disorder, rather
than a primary disorder itself.
Depression (suicide or suicidal ideation)
History of drug dependence (abuse)
Elderly (dose adjustment; closely monitor elderly or
debilitated patients for impaired cognitive and/or motor
performance, confusion, and potential for falling; avoid
chronic use (>90 days) ; adverse events e.g., delirium,
falls, fractures.
Females (dose adjustment)
Pregnancy (avoid regular use (neonatal withdrawal
symptoms); high doses during late pregnancy or labor
(neonatal hypothermia, hypotonia, respiratory
depression); Lactation (avoid)
Sleep disturbance (failure of sleep disturbance to resolve
N
after 7 to 10 days may indicate the need for psychiatric
and/or medical illness reevaluation).
TEST INTERACTIONS: Increased aminotransferase
[ALT/AST], bilirubin (S); decreased RAI uptake.
MONITORING PARAMETERS: Daytime alertness; fall risk,
respiratory rate; behavior profile; tolerance, abuse, and
dependence; reevaluate if insomnia persists after 7 to
10 days of use.
STORAGE AND STABILITY: Store at 15°C to 25°C (59°F to
77°F) ; limited excursions permitted up to 30°C (86°F).
Adverse Drug Reactions:
Common: Agitation, amnesia, asthenia, ataxia, changes in
libido, confusion, dependence, depression, diarrhea,
diplopia, dizziness, drowsiness, falls, hallucination,
headache.
Less Common: Abnormal hepatic function tests, acute renal
failure, aggressive behavior, agitation, anaphylaxis,
anemia, angina pectoris, anorexia, arteritis, arthritis,
breast fibroadenosis, breast neoplasm, bronchitis,
cardiac arrhythmia, cerebrovascular disease, circulatory
shock, cognitive dysfunction, corneal ulcer, cough,
cystitis, decreased libido, delusions, dementia,
dermatitis, diaphoresis, drug tolerance, dysarthria,
dysgeusia, dysphagia, dyspnea, edema, extrasystoles,
eye irritation, falling, glaucoma, hepatic insufficiency,
hyperbilirubinemia, hyperlipidemia, hypertension,
hypotension, hysteria, illusion, impotence, increased
thirst, leg cramps, leukopenia, localized erythema,
lymphadenopathy, menstrual disease, migraine,
myocardial infarction, nervousness, neuralgia, neuritis,
neuropathy.
Rare: Hallucinations, angioedema
515

Drug Interactions:
Monitor closely with:
Chlorpromazine (additive effects)
Diminish the sedative effect of the zolpidem:
Flumazenil
Enhances the sedative effect of the following drugs:
Pramipexole, Ropinirole, Rotigotine
Enhances the toxic/adverse effects of SSRIs (psychomotor
impairment)
Avoid concomitant use with:
FOOD INTERACTIONS: Grapefruit juice may decrease the
metabolism of zolpidem. Avoid grapefruit juice.
Administration: To be given orally, ingest immediately before
bedtime due to rapid onset of action. Zolpidem tartrate
should be taken only once per night immediately before
bedtime and at least 7–8 hours before the planned time
of awakening; patients should be advised of the
importance of only taking the drug at such time. In
addition, because food can reduce both the rate and
extent of GI absorption of zolpidem tartrate, the drug
should not be administered with or immediately after a
meal in order to facilitate the onset of sleep; should be
N
taken on an empty stomach. Swallow tablet as a whole.
Do not chew, crush, or break tablet.
Pregnancy Category: B
PATIENT ADVICE: Inform clinicians and pharmacists of
existing or contemplated concomitant therapy, including
prescription and OTC drugs, and alcohol consumption.
Take only as prescribed; do not start, stop, or change the
dose of any drug unless otherwise instructed by a
clinician. When sleep drugs are used nightly for more
than a few weeks, they may not work as well to help sleep
problems. This is known as tolerance. Only use sleep
drugs for a short time. Do not take naps.
Avoid driving and doing other tasks or actions that needs
alertness. Avoid alcohol or other drugs and natural
products that slow down actions. To lower the chance of
feeling dizzy or passing out, rise slowly over a few
minutes when sitting or lying down. Be careful climbing
stairs. Inform the clinician of any side effect (e.g., allergy,
trouble swallowing, shortness of breath) experienced
with taking the drug. For women, inform clinicians if they
are or planning to become pregnant or plan to breast-
feed.
ATC Code: N05CF02
516
NERVOUS SYSTEM
OTHER PSYCHOLEPTIC AGENTS
Rx ATROPINE
Inj.: 500 micrograms/mL, 600 micrograms/mL and 1
mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
An alkaloid from Atropa belladonna, that competitively
blocks acetylcholine action in central and peripheral
muscarinic autonomic receptors.
Indications: To relieve pylorospasm, hypertonicity of the
small intestine, and hypermotility of the colon; To relieve
biliary and ureteral colic; neuromuscular blockade
reversal; bradycardia in children; antidote to overdosage
with cholinergic drugs, poisoning with organophosphate
and n-methyl carbamate pesticides, and mushroom
poisoning; as a pre-operative medication to reduce
salivary, bronchial, gastric, pancreatic, and nasal
secretions and to prevent bradycardia; Treatment of
symptomatic sinus bradycardia, syncope from Stokes-
Adams syndrome, and high-degree atrioventricular block
with profound bradycardia, symptomatic sinus
bradycardia.
Contraindications: Angle-closure glaucoma; severe
inflammatory GI disease or GI obstruction; prostatic
hypertrophy; prostatism and urinary obstruction;
myasthenia gravis; thyrotoxicosis; organochlorine
poisoning; pyloric stenosis; poisoning caused by CNS
adrenergic stimulants, phenothiazines, TCAs and other
anticholinergics.
NOTE: No contraindications exist in the treatment of life-
threatening organophosphate or carbamate
insecticides, and nerve agent poisoning.
Dose:
WARNING: Fatal dose of atropine in pediatric patients
may be as low as 10 mg.
Bradyarrhythmia, IM or IV, ADULT, American Heart
Association (AHA) recommendation: 0.5 mg every 3 to 5
minutes as needed, the total dose not to exceed 0.04
mg/kg (3 mg). Use of shorting dose intervals (3 minutes)
and higher maximum dose range (0.04 mg/kg) is
suggested in severe clinical conditions. Subsequent
doses of 0.5 to 1 mg may be given at 4- to 6-hour
intervals. Doses under 0.5 mg may cause paradoxical
slowing of HR, IV or IO, CHILD, 0.02 mg/kg with a
maximum single dose of 0.5 mg that may be repeated
once in 3-5 minutes and a maximum total dose of 1 mg.
Smooth muscle relaxation and suppression of secretions,
IM or IV or SC, ADULT, 0.4-0.6 mg 30-60 minutes
minutes preoperatively and repeat every 4 to 6 hours as
needed, CHILD<5 kg, 0.02 mg/kg 30-60 minutes
preoperatively and every 4-6 hours as needed. Usually
given SC., CHILD≥5 kg, 0.01-0.02 mg/kg 30-60 minutes
preoperatively and every 4-6 hours as needed with a
minimum dose of 0.1 mg and a maximum single dose of
0.4 mg.
Neuromuscular blockade reversal, by intravenous infusion,
ADULT, administer 15-30 mcg/kg of atropine with
neostigmine or 7-10 mcg/kg atropine with edrophonium.
NERVOUS SYSTEM
Dose Adjustment:
Geriatric:
Reduced dose
Renal Impairment:
For mild-to-moderate renal impairment, dose reduction, or
less frequent doses, after initial atropinization is
warranted (since atropine may be eliminated more
slowly); for severe impairment, the patient should be
referred to a specialist.
Administration:
Rate of administration - 1 mg or fraction thereof over 1
minute.
See Atropine under Anticholinergics in Chapter 1: Drugs for
Functional Gastrointestinal Disorders, and Other Cardiac
Preparations in Chapter 3: Cardiac Therapy for other
information.
Pregnancy Category: C
ATC Code: Not available
Rx CARBAMAZEPINE
Oral: 200 mg tablet
200 mg and 400 mg modified-release (MR) tablet
100 mg/5 mL syrup, 120 mL
An iminostilbene that limits the firing of action potentials
evoked by a sustained depolarization in cortical neurons
mediated by a slowing of the rate of recovery of voltage-
sensitive Na+ channels from inactivation. It stimulates
the release of antidiuretic hormone (ADH) and
potentiates its action in promoting reabsorption of water.
Indications: Second line treatment of acute and long term
mania.
Contraindications: AV conduction abnormalities (unless
paced); history of bone marrow suppression; positive test
for HLA-B*1502 allele; acute porphyrias.
Dose:
NOTE: Dosage must be adjusted according to patients’
response and serum concentrations. As a result of slow,
controlled release of the active substance from the
controlled-release (modified-release) tablets, these are
designed to be taken in a twice-daily dosage regimen.
Administer suspension in 4 divided doses daily.
Acute mania/mixed mania, by mouth, ADULT/CHILD≥13
years, start 200 mg daily (Increase by 200 mg weekly to
400 – 600 mg daily in 2 divided doses, maximum of
1200 mg daily).
NOTE: Anticonvulsants should not be discontinued abruptly
because of the possibility of increasing seizure
frequency; therapy should be withdrawn gradually to
minimize the potential of increased seizure frequency,
unless safety concerns require a more rapid withdrawal.
Dose Adjustment:
Geriatric:
Use with caution. Generally, lower dosages are started;
monitor sodium closely with initiation or dosage
adjustments in older adults.
Renal Impairment:
Use with caution; dose reduction in moderate to severe
impairment. If GFR <10 mL/minute, administer 75% of
dose. For patients undergoing hemodialysis or peritoneal
dialysis, administer 75% of dose postdialysis. For
patients undergoing continuous renal replacement
therapy (CRRT), there are no dosage adjustment
recommendation for adults; for children, administer 75%
of dose.
Hepatic Impairment:
Metabolism impaired in advanced liver disease.
Precautions:
WARNING:
Serious dermatologic reactions and HLA-B*1502
allele: Serious and sometimes fatal dermatologic
reactions, including toxic epidermal necrolysis
(TEN) and SJS. Studies in patients of Chinese
ancestry have found a strong association between
the risk of developing SJS/TEN and the presence
of HLA-B*1502, an inherited allelic variant of the
N
HLA-B gene. HLA-B*1502 is found almost
exclusively in patients with ancestry across broad
areas of Asia. Test for HLA-B*1502 prior to
initiating treatment with carbamazepine in with an
increased likelihood of carrying this allele. Avoid
use of carbamazepine in patients testing positive
for the allele unless the benefit clearly outweighs
the risk. Discontinue carbamazepine if the patient
is suspected of having a serious dermatologic
reaction.
Aplastic anemia and agranulocytosis: Obtain
complete pretreatment hematological testing as a
baseline and monitor complete blood cell count
periodically. If a patient in the course of treatment
exhibits low or decreased WBC or platelet counts,
monitor the patient closely. Consider
discontinuation of the drug if any evidence of
significant bone marrow depression develops.
Patient w/ history of cardiac disease and haematological
reactions to other drugs; Not effective in absence,
myoclonic, or akinetic seizures; Avoid abrupt withdrawal;
Skin reactions; susceptibility to angle-closure glaucoma;
Hyponatremia (consider discontinuing therapy in
patients with symptomatic hyponatremia); Multi-organ
hypersensitivity reactions (monitor for signs and
symptoms of possible disparate manifestations
associated with lymphatic, hepatic, renal, and/or
hematologic organ systems; gradual discontinuation and
conversion to alternate therapy may be required);
Psychiatric effects; Anticholinergic sensitivity; Hepatic
and renal impairment (monitor renal function at baseline
and periodically thereafter).
Pregnancy (doses should be adjusted on the basis of
plasma-drug concentration monitoring); Lactation.
Elderly.
517

SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, like driving or operating
machinery.
STORAGE AND STABILITY: Tablet: Store between 20-25°C.
Excursions permitted to 15-30°C. Protect from light and
moisture. Modified-release tablet: Store at 25°C.
Excursions permitted to 15-30°C. Protect from moisture.
Syrup: Store between 20-25°C. Excursions permitted to
15-30°C. Protect from light.
Adverse Drug Reactions:
NOTE: Particularly at the start of treatment, or if the initial
dose is too high, or in the elderly, certain adverse
reactions (e.g., central nervous system and
gastrointestinal symptoms, and allergy) commonly occur.
Common: Allergic skin reactions, urticaria, dermatitis,
vomiting, thrombocytopenia, leucopenia, nausea,
edema, headache, hemolytic anemia, weakness,
eosinophilia, dry mouth, dizziness, drowsiness, blurring
of vision, blood disorders, ataxia, aplastic anemia.
Less Common: involuntary movements e.g., nystagmus,
exfoliative dermatitis, erythroderma, diarrhea,
constipation, visual disturbances.
Rare: Abdominal pain, aggression, agitation, anorexia,
cardiac conduction disorders, confusion, delayed multi-
organ hypersensitivity disorder, depression, dysarthria,
N
hallucinations, hepatitis, hypertension, hypotension,
jaundice, lymph node enlargement, muscle weakness,
paresthesia, peripheral neuropathy, restlessness, SLE,
vanishing bile duct syndrome.
Drug Interactions:
Monitor closely with:
Enhances the toxic/adverse effects of the following drugs:
Desmopressin (hyponatremia)
Diuretics e.g., hydrochlorothiazide and furosemide
(symptomatic hyponatremia)
Dipyrone, CNS depressants
Lacosamide (AV blocking effect)
Lithium (neurotoxic effects)
MAOIs (serotonin syndrome; contraindicated within 14
days of MAOI use)
Adenosine (high degree heart block)
Anticonvulsants (thyroid function)
Hormonal contraceptives (bleeding and failure of
contraception; alternative or backup contraceptive
methods are recommended)
Warfarin (possibly requiring an increase in the dose of
warfarin; carefully monitor INR)
Paracetamol (reduce bioavailability)
Avoid concomitant use with:
Liquid medications or diluents – may result in the formation
of a precipitate
Administration: The tablets and the syrup (to be shaken
before use) may be taken during, after, or between
meals. Tablets should be taken with little liquid. The
modified-release tablets should be swallowed unchewed
with a little liquid. Administer tablets in 2-3 divided doses
daily and syrup in 4 divided doses daily. Avoid grapefruit
juice.
518
NERVOUS SYSTEM
NOTE: Drug may cause GI upset, take with large amount of
water or food to decrease GI upset. May need to split
doses to avoid GI upset. The suspension may contain
sorbitol; avoid use in service patients with hereditary
fructose intolerance.
See Carbamazepine under Analgesics, and Antiepileptics in
Chapter 10: Nervous System; for other information.
Pregnancy Category: D
ATC Code: N03AF01
Rx VALPROIC ACID
Oral: 250 mg and 500 mg tablet (as divalproex sodium)
250 mg and 500 mg extended release tablet (as
divalproex sodium)
500 mg controlled release tablet (333 mg sodium
valproate + 145 mg valproic acid)
200 mg/5 mL syrup, 100 mL bottle (as sodium
valproate)
250 mg/5 mL syrup, 120 mL (as valproic acid)
Inj.: 500 mg/5 mL IV infusion, 5 mL vial (as valproic acid)
A simple branched-chain carboxylic acid with mood-
stabilizing properties that are hypothesized to be
mediated by one or a combination of the following:
reduction of excessive neurotransmission; GABA
action enhancement; downstream actions on
complex signal transduction cascades, and activating
various signals that promote neuroprotection and
long-term plasticity.
Indication: First-line treatment for acute mania (divalproex),
mixed episodes (divalproex, divalproex ER).
Contraindications: Family history of severe hepatic
dysfunction; active liver disease; mitochondrial and
urea cycle disorders; pregnancy when used
exclusively for migraine prophylaxis;
thrombocytopenia; acute porphyrias; Hepatic
impairment.
Dose:
Acute mania, by mouth, ADULT, immediate release: for less
acute mania, initially 250-500 mg once daily on the
first day and slowly titrate dose based on efficacy and
tolerability. For more severe cases, initially 750-1000
mg/day in divided doses and increase dose rapidly to
desired clinical effect up to a maximum of 60
mg/kg/day. Due to half-life, the immediate release
formulation is ideally dosed as twice daily, while the
extended-release formulation may be given once daily
with a corresponding dose increase of about 8-20%
when converting from the immediate release
formulation due to decreased bioavailability
compared to the immediate release formulation,
controlled release: initially 25 mg/kg once daily and
increase dose rapidly to desired clinical effect up to a
maximum of 60 mg/kg/day.
Start 500 mg daily (Increase slowly to 1000 – 2000
mg daily, maximum of 60 mg/kg/day)
NERVOUS SYSTEM
Dose Adjustment:
Geriatric:
Reduce initial dose and titrate slowly.
Renal Impairment:
No dose adjustment necessary; may cause misleading
results in therapeutic drug monitoring due to substantial
reduction of protein binding.
Precautions:
WARNING:
Liver toxicity; Liver dysfunction (including fatal hepatic
failure) especially in children <3 years and in those
with metabolic or degenerative disorders, organic
brain disease or severe seizure disorders
associated with mental retardation) usually in first
6 months and usually involving multiple
antiepileptic therapy. Raised liver enzymes are
usually transient (patients should be reassessed
clinically and liver function (including prothrombin
time) monitored until return to normal –
discontinue if abnormally prolonged prothrombin
time (particularly in association with other relevant
abnormalities).
Mitochondrial disease: valproate-induced acute liver
failure and resultant deaths. Valproate is
contraindicated in patients known to have
mitochondrial disorders caused by POLG
mutations and children <2 years who are clinically
suspected of having a mitochondrial disorder. In
patients >2 years who are clinically suspected of
having a hereditary mitochondrial disease, only
use after other anticonvulsants have failed.
Closely monitor this older group of patients during
treatment for the development of acute liver injury
with regular clinical assessments and serum liver
testing. Perform POLG mutation screening in
accordance with current clinical practice.
Pancreatitis: (life-threatening) Warn patients and
guardians that abdominal pain, nausea, vomiting,
and/or anorexia can be symptoms of pancreatitis
that require prompt medical evaluation. If
pancreatitis is diagnosed, ordinarily discontinue
valproate. Initiate alternative treatment for the
underlying medical condition as clinically
indicated.
Administration: Take with food. Extended-release
formulations should be taken whole and not crushed,
chewed, or split.
See Valproic Acid under Fatty Acid Derivatives in Chapter
10: Antiepileptics for other information.
Pregnancy Category: D
ATC Code: N03AG01
PSYCHOANALEPTICS
ANTIDEPRESSANTS
SELECTIVE SEROTONIN REUPTAKE
INHIBITORS
GENERAL PRECAUTIONS:
Concerns related to adverse effects:
Bleeding risk (Use with caution in hemodynamically
unstable patients or if used concomitantly with aspirin,
NSAIDs, warfarin, or other anticoagulants).
Cardiovascular effects e.g., QTc prolongation (Use with
caution in service users/patients with 1 or more risk
factors for torsades de pointes).
CNS depression (Caution operating hazardous machinery or
driving).
Fractures (Consider the possibility of a fragility fracture if an
antidepressant-treated patient presents with
unexplained bone pain, point tenderness, swelling, or
bruising).
Ocular effects e.g. mild pupillary dilation can lead to an
episode of narrow-angle glaucoma. (Consider evaluating
service users/patients who have not had an iridectomy
for narrow-angle glaucoma risk factors).
N
Serotonin syndrome (Potentially life-threatening serotonin
syndrome (SS) has occurred with serotonergic agents
(e.g., SSRIs, SNRIs), particularly when used in
combination with other serotonergic agents (e.g.,
triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St
John's wort, tryptophan) or agents that impair
metabolism of serotonin (e.g., MAO inhibitors intended to
treat psychiatric disorders, other MAO inhibitors [i.e.
linezolid and intravenous methylene blue]). Monitor
patients closely for signs of SS such as mental status
changes (e.g. agitation, hallucinations, delirium, coma);
autonomic instability (e.g., tachycardia, labile blood
pressure, diaphoresis); neuromuscular changes (e.g.,
tremor, rigidity, myoclonus); GI symptoms (e.g., nausea,
vomiting, diarrhea); and/or seizures. Discontinue
treatment (and any concomitant serotonergic agent)
immediately if signs/symptoms arise.).
Sexual dysfunction: May cause or exacerbate sexual
dysfunction.
SIADH and hyponatremia: SSRIs and SNRIs have been
associated with the development of SIADH and rarely,
hyponatremia predominantly in the elderly.
Hyponatremia is reversible with discontinuation of
treatment.
Disease-related concerns:
Cardiovascular disease (Use with caution in patients with a
recent history of MI or unstable heart disease).
Hepatic impairment (Use with caution in service
users/patients with hepatic impairment; a lower dosage
may be needed.)
Mania/hypomania (May precipitate a shift to mania or
hypomania in patients with bipolar disorder.
Monotherapy in service users/patients with bipolar
disorder should be avoided. Patients presenting with
depressive symptoms should be screened for bipolar
disorder. Escitalopram is not FDA approved for the
treatment of bipolar depression.)
519

Metabolic disease (Use with caution patients with altered
metabolism.)
Renal impairment (Use with caution in service patients with
severe renal impairment.)
Seizure disorders (Use with caution in patients with a
previous seizure disorder or condition predisposing to
seizures such as brain damage or alcoholism.)
Special populations:
Elderly (Bioavailability and half-life are increased by 50% in
the elderly; May also cause agitation, sleep disturbances
and excessive CNS stimulation.)
Lactation: Must weigh benefits of breast feeding with risks
and benefits of antidepressant treatment versus
nontreatment to both the infant and the mother.
Pediatric: When treating children, carefully weigh the risks
and benefits of pharmacological treatment against the
risks and benefits of nontreatment with antidepressants
and make sure to document this in the service
user/patient’s chart.
Pregnancy: Not generally recommended for use during
pregnancy, especially during the first trimester;
nonetheless, continuous treatment during pregnancy
may be necessary and has not been proven to be harmful
to the fetus; At delivery there may be more bleeding in
the mother and transient irritability or sedation in the
newborn; Must weigh the risk of treatment (first trimester
fetal development, third trimester newborn delivery) to
N
the child against the risk of no treatment (recurrence of
depression, maternal health, infant bonding) to the
mother and child; For many service users/patients this
may mean continuing treatment during pregnancy.
Other warnings/precautions:
Discontinuation syndrome: Abrupt discontinuation or
interruption of antidepressant therapy has been
associated with a discontinuation syndrome. Symptoms
arising may vary with antidepressant however commonly
include nausea, vomiting, diarrhea, headaches, light-
headedness, dizziness, diminished appetite, sweating,
chills, tremors, paresthesias, fatigue, somnolence, and
sleep disturbances (e.g., vivid dreams, insomnia).
Rx ESCITALOPRAM
Oral: 10 mg tablet (as oxalate)
Escitalopram is a furancarbonitrile and S-stereoisomer of
citalopram. It induces allosteric serotonin transporter
(SERT) inhibition which results in a significant increase
of serotonin.
Indications: Management of major depressive disorder,
generalized anxiety disorder.
Contraindications: Known QTc prolongation, congenital long
QTc syndrome.
Dose:
Generalized anxiety disorder, by mouth, ADULT, initially 10
mg once daily. May increase to 20 mg once daily if
necessary. Continue treatment for up to 12 months after
initial response.
520
NERVOUS SYSTEM
Major depressive disorder, by mouth, ADULT/CHILD> 12
years, initially 10 mg once daily. May increase to 20 mg
once daily after at least 1 week (ADULT) or at least 3
weeks (CHILD>12 years) if necessary. Continue
treatment for at least 6 months to 1 year.
NOTE: For all indications, allow a sufficient duration of
therapy for around 4-8 weeks on the maximum tolerable
dose before switching the antidepressant.
Dose Adjustment:
Geriatric:
10 mg once daily; use with caution as per the Beers Criteria
due to association of SSRIs with falls and fractures in
service users/patients 65 years and older and should be
avoided such service users/patients who have a history
of falls or fractures, as well as having the potential to
cause or exacerbate syndrome of inappropriate
antidiuretic hormone secretion (SIADH) or hyponatremia
monitor sodium concentration closely when initiating or
adjusting the dose in older adults.
Renal Impairment:
Use with caution
Hepatic Impairment:
Initially 5 mg once daily. Increase to 10 mg once daily after
2 weeks
Precautions:
WARNING: Antidepressants increased the risk of
suicidal thinking and behavior (suicidality) in
children, adolescents, and young adults with major
depressive disorder (MDD) and other psychiatric
disorders. Balance the risk with the clinical need.
Appropriately monitor patients of all ages who are
started on antidepressant therapy and closely
observe for clinical worsening, suicidality, or
unusual changes in behavior. Advise families and
caregivers of the need for close observation and
communication with the health care provider.
Escitalopram is not approved for use in pediatric
service users/patients younger than 12 years.
Electroconvulsive therapy (ECT): Use with caution; no
clinical studies have assessed the combined use of
escitalopram and electroconvulsive therapy; may
increase the risks (e.g., cognitive adverse effects)
associated with electroconvulsive therapy; consider
discontinuing, when possible, prior to ECT treatment.
Use with caution in patients with history of seizures.
Use with caution in patients with bipolar disorder unless
treated with concomitant mood stabilizing agent.
Monitor patients for activation of suicidal ideation,
especially children and adolescents.
Do not use use if patients is taking a MAO inhibitor
STORAGE AND STABILITY: Store at 25°C. Excursions
permitted to 15-30°C. Protect from light.
See General Precautions under Selective Serotonin
Reuptake Inhibitors in Chapter 10: Nervous System for
other precautions.
NERVOUS SYSTEM
Adverse Drug Reactions:
Common: Abnormal dreams, fatigue, paresthesia, pyrexia,
restlessness, sinusitis, yawning.
Less Common: Alopecia, bruxism, confusion, epistaxis,
menstrual disturbances, mydriasis, edema, pruritus,
syncope, tachycardia, taste disturbance, tinnitus.
Rare: Aggression, bradycardia, depersonalization.
Drug Interactions:
Monitor closely with:
Tramadol, buspirone, tryptophan (serotonin syndrome)
NSAIDs (bleeding)
Oral anticoagulants (altered anticoagulant effects)
Drug-induced hypokalaemia/hypomagnesaemia
(malignant arrhythmias)
Concomitant administration or w/in 14 days of MAOIs
withdrawal (serotonin syndrome; fatal)
QTc prolonging agents e.g., pimozide (additive effect;
fatal; monitor)
Avoid concomitant use with:
Linezolid (may cause serotonin syndrome)
MAOIs (may cause serotonin syndrome)
Methylene blue (may cause serotonin syndrome)
Pimozide (may precipitate torsades de pointes)
Administration: May be taken with or without food
Pregnancy Category: Category C
ATC Code: N06AB10
Rx FLUOXETINE
Oral: 20 mg dispersible tablet / capsule
Fluoxetine is a propylamine with a long half-life that, in
addition to blocking SERT, also has antagonistic
properties at the 5-HT2C receptor and weak
norepinephrine reuptake blockade. It blocks SERT and
possesses antagonistic properties at the 5-HT2C leading
to disinhibition of dopamine and norepinephrine release
resulting to precognitive effects.
Indications: Management of major depressive disorder,
depression associated with bipolar 1 disorder in
combination with olanzapine, treatment-resistant
depression in combination with olanzapine, obsessive
compulsive disorder, premenstrual dysphoric disorder,
bulimia nervosa, panic disorder with or without
agoraphobia.
Contraindications: Hypersensitivity to fluoxetine.
Dose:
Bulimia nervosa, by mouth, ADULT, initially 60 mg once daily
in the morning. Some patients may need to begin at
lower dose and titrate over several days
Depression associated with bipolar 1 disorder, by mouth,
ADULT, initially 20 mg once daily in the evening or with
the fixed-dose combination, 25 mg once daily in the
evening. Slowly titrate dose based on efficacy and
tolerability up to a maximum of 50 mg once daily in the
evening, CHILD≥10 years, initially 20 mg once daily in the
evening or with the fixed-dose combination, 25 mg once
daily in the evening. Slowly titrate dose based on efficacy
and tolerability. Safety of fluoxetine doses >50 mg in
combination with doses >12 mg of olanzapine has not
been studied in pediatrics.
Major depressive disorder, by mouth, ADULT, initially 20 mg
once daily in the morning. Allow a few weeks to assess
effects before titrating dose slowly up to a maximum of
80 mg once daily in the morning. Continue treatment for
up to 4 to 9 months, CHILD≥8 years, initially 10 mg once
daily in the morning. Allow at least 1 week to assess
effects before titrating dose slowly up to a maximum of
20 mg once daily in the morning. Continue treatment for
at least 4 to 9 months.
Obsessive compulsive disorder, by mouth, ADULT, initially
20 mg once daily in the morning. Allow a few weeks to
assess effects before titrating dose slowly up to a
maximum of 80 mg once daily in the morning. Continue
treatment for at least 1 to 2 years after initial response.
Panic disorder with or without agoraphobia, by mouth,
ADULT, initially 10 mg once daily in the morning. Increase
to 20 mg once daily in the morning after 1 week. Allow a
few weeks to assess effects before titrating dose slowly
up to a maximum of 60 mg once daily in the morning.
Continue treatment for at least 12 months after initial
response.
Premenstrual dysphoric disorder, by mouth, ADULT, initially
N
20 mg once daily in the morning through the menstrual
cycle or limited to the luteal phase.
Treatment-resistant depression, in combination with
olanzapine, by mouth, ADULT, initially 20 mg once daily
in the evening or with the fixed-dose combination, 25 mg
once daily in the evening. Slowly titrate dose based on
efficacy and tolerability up to a maximum of 50 mg once
daily in the evening.
NOTE: For all indications, allow a sufficient duration of
therapy for around 4-8 weeks on the maximum tolerable
dose before switching the antidepressant.
Dose Adjustment:
Geriatric:
Decrease initial dose and increase dose intervals; some
service users/patients may require an initial dose of 10
mg/day with dosage increases of 10 mg and 20 mg every
several weeks as tolerated; should not be taken at night
unless service user/patient experiences sedation.
NOTE: Use with caution in patients >65 years, patients with
history of falls or fractures and patients with a potential
to cause SIADH or hyponatremia.
Renal Impairment:
No dosage adjustment necessary. Accumulation of
fluoxetine or norfluoxetine is possible due to chronic
administration in patients with severely impaired renal
function.
Hepatic Impairment:
Decrease initial dose and increase dose intervals; for
service users/patients with cirrhosis, administer a lower
dose or less frequent dosing interval; for service
users/patients with compensated cirrhosis without
ascites, administer 50% of normal dose.
521

Precautions:
WARNING: Antidepressants increased the risk
compared with placebo of suicidal thinking and
behavior (suicidality). Appropriately monitor and
closely observe service users/patients of all ages
who are started on antidepressant therapy for
clinical worsening, suicidality, or unusual changes
in behavior. Advise families and caregivers of the
need for close observation and communication
with the prescriber
Fluoxetine should not be discontinued abruptly.
Therapy should be withdrawn gradually to
minimize unwanted effects. For long- term
patients gradually taper the dose within 4- 6
months.
Caution operating hazardous machinery or driving.
Monotherapy in service users/patients with bipolar
disorder should be avoided. Patients presenting
with depressive symptoms should be screened for
bipolar disorder. Fluoxetine monotherapy is not
FDA approved for the treatment of bipolar
depression.
Allergic events e.g., rash, lupus-like syndrome, larynospasm,
anaphylactoid reactions and pulmonary inflammatory
N
disease
See General Precaution under Selective Serotonin
Reuptake Inhibitors in Chapter 10: Nervous System for
other precautions.
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C. Protect from light.
Adverse Drug Reactions:
Common: delayed ejaculation, erectile dysfunction; men
and women: anorgasmia, urinary frequency, urination
disorder decreased/increased appetite, nausea,
vomiting, diarrhea, constipation, flatulence, dry mouth,
dyspepsia, dysgeusia, insomnia, sedation, drowsiness,
sleep disorder, agitation, personality disorder,
abnormality in thinking, tremors, chills, emotional lability,
headache, dizziness, headaches, anxiety, nervousness,
yawning, fatigue, anorexia, abnormal dreams, amnesia,
confusion, QTc prolongation, palpitations, vasodilation,
chest pain, hypertension, sweating, skin rash, pruritis,
hypermenorrhea, increased thirst, weight loss, weight
gain, decreased sexual desire, bruising, pharyngitis,
hyperkinesia, asthenia, weakness , visual disturbance,
otalgia, tinnitus, flu-like symptoms, sinusitis, epistaxis.
Rare: bleeding, hyponatremia and SIADH, seizures,
induction of mania, suicidality, falls, fractures and
osteoporosis (long-term use), abnormal hepatic function
tests, acne vulgaris, acute abdominal condition,
akathisia, albuminuria, alopecia, amenorrhea,
anaphylactoid reaction, anemia, angina pectoris, angle-
closure glaucoma, aphthous stomatitis, aplastic anemia,
arthritis, asthma, ataxia, atrial fibrillation, bruise,
bruxism, bursitis, cardiac arrhythmia, cataract,
cerebrovascular accident, cholelithiasis, cholestatic
jaundice, colitis, congestive heart failure, dehydration,
delusions, depersonalization, dyskinesia, dysphagia,
dysuria, ecchymoses, edema, eosinophilic pneumonitis,
522
NERVOUS SYSTEM
equilibrium disturbance, erythema multiforme, erythema
nodosum, esophagitis, euphoria, exfoliative dermatitis,
extrapyramidal reaction, gastritis, gastroenteritis,
gastrointestinal ulcer, glossitis, gout, gynecological
gynecomastia, hallucination, hemolytic anemia, hepatic
failure, hepatic necrosis, hepatitis, hiccups, hostility,
hypersensitivity reaction, hypertonia, hyperventilation,
hypoglycemia, hypokalemia, hypotension,
hypothyroidism, immune thrombocytopenia, laryngeal
edema, laryngospasm, leg cramps, lupus-like syndrome,
malaise, melena, memory impairment, migraine,
mydriasis, myocardial infarction, myoclonus, neuroleptic
malignant syndrome, optic neuritis, orthostatic
hypotension, ostealgia, pancreatitis, pancytopenia,
paranoia, petechia, priapism, pulmonary embolism,
pulmonary fibrosis, pulmonary hypertension, purpuric
rash, renal failure, serotonin syndrome, sexual disorder
(may persist after discontinuation), skin photosensitivity,
Stevens-Johnson syndrome, syncope, tachycardia,
thrombocytopenia, toxic epidermal necrolysis, vasculitis,
ventricular tachycardia (including torsades de pointes),
violent behavior
Drug Interactions:
Monitor closely with:
Enhances effect of the following:
Anti- platelet agents e.g. Aspirin, Glucosamine,
Multivitamins/Minerals [with With Vitamins ADEK,
Folate, Iron], NSAID, Omega-3 Fatty Acids, Prostacyclin
analogues, Vitamin E (anti-platelet effect), Blood
glucose- lowering agents
Thiazide diuretics (hyponatremic effect), Anti-coagulants
e.g. Vitamin K antagonists (anti- coagulant effect)
Enhances effect of Fluoxetine:
Anti-emetics, Anti- psychotic agents, Opioid analgesics,
(serotonin syndrome)
Reduces the therapeutic effect of the following:
Codeine, Thyroid products
Reduces the therapeutic effect of Fluoxetine:
Cyproheptadine, Non-selective NSAID, Ioflupane I123
Increases adverse effects of Fluoxetine:
Bupropion, CNS depressants e.g. Alcohol (psychomotor
impairment), Desmopressin
Tositumomab (bleeding), Iodine I131
Increases adverse effects of the following drugs:
Antipsychotic agents (neuroleptic malignant syndrome);
Metyrosine; Nifedipine, Obinituzumab (bleeding)
Avoid concomitant use with:
Increase serum concentration of the following:
Abiraterone acetate, Atomoxetine, Brexpiprazole
Dabigatran etexilate, Dosulepin, Doxorubicin
Metoprolol, Mequitazine, Propafenone, Thioridazine,
Tizanidine, Tricyclic anti- depressants e.g.
Amytriptylline
Increase serum concentration of Fluoxetine:
Fosphenytoin, Haloperidol, Pimozide (QTc prolonging
effect), Darunavir
May enhance adverse effects of the following drugs:
NERVOUS SYSTEM
Apixaban (bleeding), Aripiprazole, Metoclopramide
(neuroleptic malignant syndrome), Metoclopramide
(extrapyramidal symptoms)
Enhances the adverse effects of Fluoxetine:
Ethyl Alcohol (psychomotor impairment), Dapoxetine,
non-selective NSAID (anti- platelet effect); Serotonin
modulators [except Tedizolid], Tedizolid, (serotonin
syndrome), Tricyclic anti- depressants e.g.
Amaytriptylline
Enhances effects of the following drugs:
Dextrometorphan (serotonin syndrome), Dabigatran
etexeilate (anti-coagulant effect), Fosphenytoin,
Haloperidol, Highest Risk QTc prolonging agents,
Ivabradine, Mifepristone, Moderate Risk QTc Prolonging
agents, Pimozide, Thioridazine, Ziprasidone (QTc
prolonging effect), Tramadol (neuroexcitatory effect),
Urokinase (bleeding)
Enhances effects of Fluoxetine:
Antidepressants, Aripiprazole, Bupropion, Linezolid,
Lithium, MAO inhibitors [except Linezolid, Methylene
blue and Tedizolid], Methylene blue, Metoclopramide,
Tramadol, Tryptophan, Ziprasidone (serotonin
syndrome)
Propafenone (QTc prolonging effect)
Decreases the metabolism of the following drugs:
Bupropion, Carbamazepine, Cimetidine, Clopidogrel,
Mexiletine
Increase the metabolism of Fluoxetine
Carbamazepine, Cobicistat
Decrease therapeutic effect of the following:
Iobenguane I123
Decreases effect of Fluoxetine
NSAID [non- selective]
Administration: May be taken with or without food.
Pregnancy Category: Category C
ATC Code: N06AB03
Rx SERTRALINE
Oral: 50 mg tablet (as hydrochloride)
Sertraline inhibits SERT and weak dopamine transporter
that is necessary to create an antidepressant used in
various types of psychiatric disorders.
Indications: Major depressive disorder; premenstrual
dysphoric disorder; anxiety disorders (social anxiety
disorder, panic disorder with or without agoraphobia);
obsessive compulsive disorder; post-traumatic stress
disorder
Contraindications: Hypersensitivity to sertraline
Dose:
Major depressive disorder, by mouth, ADULT, initially 50 mg
once daily. Allow a few weeks to assess effects before
increasing the dose, but may increase the dose by 25-50
mg once a week. Slowly titrate to a maximum of 200 mg
once daily. Continue treatment for at least 4 to 9 months.
Obsessive compulsive disorder, by mouth, ADULT and
CHILD≥13 years, initially 50 mg once daily. Allow a few
weeks to assess effects before increasing the dose, but
may increase the dose by 25-50 mg once a week. Slowly
titrate to a maximum of 200 mg once daily. Continue
treatment for up to 12 months after initial response,
CHILD 6-12 years, initially 25 mg once daily. Allow a few
weeks to assess effects before increasing the dose, but
may increase the dose by 25-50 mg once a week. Slowly
titrate to a maximum of 200 mg once daily. Continue
treatment for up to 12 months after initial response.
Panic disorder with or without agoraphobia, by mouth,
ADULT, initially 25 mg once daily. Increase to 50 mg once
daily after 1 week. Allow a few weeks to assess effects
before increasing the dose again, but may increase the
dose by 25-50 mg once a week. Slowly titrate to a
maximum of 200 mg once daily. Continue treatment for
at least 12 months after initial response.
Post-traumatic stress disorder, by mouth, ADULT, initially 25
mg once daily. Increase to 50 mg once daily after 1 week.
Allow a few weeks to assess effects before increasing the
dose again, but may increase the dose by 25-50 mg once
N
a week. Slowly titrate to a maximum of 200 mg once
daily. Continue treatment for at least 12 months after
initial response.
Premenstrual dysphoric disorder, by mouth, ADULT, initially
50 mg once daily through the menstrual cycle or limited
to the luteal phase.
Social anxiety disorder, by mouth, ADULT, initially 25 mg
once daily. Increase to 50 mg once daily after 1 week.
Allow a few weeks to assess effects before increasing the
dose again, but may increase the dose by 25-50 mg once
a week. Slowly titrate to a maximum of 200 mg once
daily. Continue treatment for at least 12 months after
initial response.
NOTE: For all indications, allow a sufficient duration of
therapy for around 4-8 weeks on the maximum tolerable
dose before switching the antidepressant.
Dose Adjustment:
Geriatric:
No dose adjustment necessary
NOTE: Use with caution in patients >65 years, patients with history of
falls or fractures and patients with a potential to cause SIADH or
hyponatremia.
Renal Impairment:
No dose adjustment necessary; not removed by
hemodialysis.
Hepatic Impairment:
Decrease initial dose and increase dose intervals; for mild
hepatic impairment, reduce dose by 50% of the normal
dose; for moderate to severe impairment, use is not
recommended.
523

Precautions:
WARNING:
Suicidal risk
Antidepressants increased the risk of suicidal
thinking and
behavior (suicidality). Monitor and closely observe
service users/patients of all ages who are started on
antidepressant therapy for clinical worsening
suicidality, or unusual changes in behavior. Advise
families and caregivers of the need for close
observation and communication with the prescriber.
Withdrawal syndrome
Sertraline should not be discontinued abruptly.
Therapy
should be withdrawn gradually to minimize unwanted
effects. For long- term patients gradually taper the
dose
within 4- 6 months.
CNS Depression
Caution operating hazardous machinery or driving.
Monotherapy
Monotherapy in service users/patients with bipolar
disorder
should be avoided. Patients presenting with
N
depressive symptoms should be screened for bipolar
disorder. Sertraline monotherapy is not FDA
approved for the treatment of bipolar depression.
See General Precautions under Selective Serotonin
Reuptake Inhibitors in Chapter 10: Nervous System for
other precautions.
STORAGE AND STABILITY: Store between 20-25°C. Excursions
permitted to 15-30°C.
Adverse Drug Reactions:
Common:
Palpitations, edema, hypertension, syncope, tachycardia,
vasodilation, insomnia, sedation, drowsiness, lethargy,
psychomotor agitation, seizure, yawning, agitation,
irritability, malaise, tremors, dizziness, headaches,
anxiety, nervousness, fatigue, anorexia, abnormal gait,
ataxia, coma, confusion, euphoria, hallucination,
hypertonia, hypoesthesia, impaired consciousness,
hyperhidrosis, sweating, alopecia, bullous dermatitis,
dermatitis, diaphoresis, erythematous rash, follicular
rash, maculopapular rash, pruritus, urticaria, weight loss,
weight gain, diabetes mellitus, galactorrhea,
hypercholesterolemia, hypoglycemia, hypothyroidism,
decreased sexual desire, decreased appetite, increased
appetite, nausea, vomiting, diarrhea, constipation,
dyspepsia, abdominal pain, dry mouth, bruxism,
hematochezia, melena, ejaculation failure, ejaculatory
disorder, erectile dysfunction, priapism, vaginal
haemorrhage, anorgasmia, hematuria, bruising,
hemorrhage, rectal hemorrhage, anaphylaxis,
hyperkinesia, muscle spasm, asthenia, visual
disturbance, blurred vision, mydriasis, tinnitus,
bronchospasm.
Rare: bleeding, hyponatremia and SIADH, induction of
mania, hypotension, suicidality, falls, fractures and
524
NERVOUS SYSTEM
osteoporosis, aggressive behavior, purpura, arthralgia,
muscle twitching, epistaxis, fever, acute renal failure,
agranulocytosis, angioedema, angle-closure glaucoma,
aplastic anemia, atrial arrhythmia, atrioventricular block,
blindness, bradycardia, cataract, cerebrovascular
spasms, coagulation time increased, diabetes mellitus,
edema, extrapyramidal reaction, gynecomastia, hepatic
failure, hepatitis, hyperglycemia, hyperprolactinemia,
hypersensitivity reaction, jaundice, leukopenia, lupus-
like syndrome, menstrual disease, neuroleptic malignant
syndrome nightmares, oculogyric crisis, optic neuritis,
pancreatitis, pancytopenia, prolonged Q-T interval on
ECG, psychosis, pulmonary hypertension,
rhabdomyolysis, serotonin syndrome, serum sickness,
skin photosensitivity, Stevens-Johnson syndrome,
thrombocytopenia, torsades de pointes, toxic epidermal
necrolysis, trismus, vasculitis, ventricular tachycardia,
withdrawal syndrome
Drug Interactions:
Monitor closely with:
Enhances the effects of the following:
Anti-platelet agents e.g Aspirin, Glucosamine,
Multivitamins/Minerals, NSAIDs., COX-2 inhibitor,
Pentoxifylline, Prostacyclin analogues, Tipranavir,
Vitamin E, Vitamin E, Oral (anti- platelet effect),
Analgesics, Opioid, Anti- emetics, 5HT3 antagonists,
Tedizolid (serotonin syndrome), Anticoagulants,
Dasatinib, Rivaroxaban, Thrombolytic agents, Vitamin K
antagonists (anti- coagulant effect), Blood glucose
lowering agents (hypoglycemic effect)
Limaprost, Propafenone (QTc prolonging effect)
Thiazide diuretics e.g Hydrochlorothiazide (hyponatremic
effect), Tositumomab, Iodine I131 Tositumomab
(bleeding)
Enhances the effects of Sertraline:
Antipsychotic agents (serotonin syndrome)
Enhance adverse effects of the following:
Antipsychotic agents (neuroleptic malignant syndrome),
CNS depressants e.g., Alcohol (psychomotor
impairment)
Collagenase, Systemic, Deoxycholic acid (injection site
reaction), Desmopressi, Ibritumomab, Obinituzumab,
Pentosan Polysulfate Sodium, Salicylates (bleeding),
Ibrutinib, Metyrosine, Omega- 3 Fatty Acids
Reduces the therapeutic effect of the following:
Codeine, Cyproheptadine, Ioflupane I123
Thyroid products
Decreases the metabolism of the following:
Risperidone
Decreases the metabolism of Sertraline:
Macrolide antibiotics [except Azithromycin, Systemic,
Fidaxomicin, Spiramycin]
Avoid concomitant use with:
Increases the serum concentration of the following:
Amodiaquine, Aripiprazole, Cilostazol, Citalopram,
Clozapine, Dabigatran etexilate, Dextrometorphan,
Dosulepin, Doxorubicin, Eliglustat, Metoprolol,
Thioridazine, Tizanidine
Tricyclic antidepressants e.g. Amytriptylline
NERVOUS SYSTEM
Decreases serum concentration of the following drugs:
Clopidogrel, Tamoxifen
Decreases serum concentration of Sertraline:
Darunavir, Efavirenz, Phenytoin
Enhances effects of the following drugs:
Antidepressants, Dextrometorphan (serotonin
syndrome), Dabigatran etexilate, Urokinase (anti-
coagulant effect), QTc prolonging Agents (QTc prolonging
effect), Mifepristone, non-selective NSAID (anti- platelet
effect)
Tramadol (neuroexcitatory effect)
Enhances the effects of Sertraline:
Buspirone, Linezolid, Lithium, MAO Inhibitors [except
Linezolid, Methylene blue, Tedizolid], Methylene blue,
Tramadol, Tryptophan (serotonin syndrome)
Enhances adverse effects of the following:
Apixaban (bleeding), Aripiprazole, Pimozide
Tricyclic antidepressants
Reduces the therapeutic effect of the following:
Iobenguane I123
Enhances adverse effects of the Sertraline:
Ethyl Alcohol (psychomotor impairment), Dapoxetine,
Disulfiram, Metoclopramide, Serotonin modulators
[except Tedizolid] (serotonin syndrome)
Increases the metabolism of Sertraline:
Carbamazepine
Decreases the metabolism of the following:
Buspirone, Carbamazepine, Methadone
Decrease the metabolism of Sertraline:
Cimetidine
Administration: May be taken with or without food.
Pregnancy Category: Category C
ATC Code: N06AB06
PSYCHOTIMULANTS, AGENTS USED FOR ADHD AND
NOOTROPICS
Rx METHYLPHENIDATE
Oral: 10 mg tablet
18 mg, 27 mg, and 36 mg modified release (MR)
tablet
20 mg MR capsule
Methylphenidate helps correct neurotransmitter levels for
norepinephrine and dopamine synapses in the prefrontal
cortex, which brings prefrontal activity back to optimal
levels.
Indications: Attention deficit hyperactive disorder (ADHD)
and narcolepsy.
Contraindications: Extreme anxiety or agitation, motor tics
or Tourette’s syndrome, family history of Tourette’s
syndrome or tics, glaucoma, structural cardiac
abnormalities, advanced atherosclerosis, symptomatic
cardiovascular disease, moderate to severe
hypertension, cardiac arrhythmias, heart failure, recent
myocardial infarction, hyperthyroidism and
thyrotoxicosis, gastrointestinal obstruction or severe GI
narrowing (specific for Concerta formulation), history of
substance use disorders.
Dose:
Attention deficit hyperactive disorder, by mouth, ADULT,
initially 18 mg once daily in the morning. Increase by 9-
18 mg each week up to a maximum dose of 72 mg once
daily in the morning, CHILD 13-17 years, initially 18 mg
once daily in the morning. Increase by 9-18 mg each
week up to a maximum dose (≥40 kg) of 54-72 mg once
daily in the morning, CHILD<13 years, initially 18 mg
once daily in the morning. Increase by 9-18 mg each
week up to a maximum dose (≤40 kg) of 54 mg once
daily in the morning.
Narcolepsy, by mouth, 20-60 mg/day in 2-3 divided doses.
Dose Adjustment:
Geriatric:
Lower doses may be better tolerated.
N
Renal Impairment:
No dose adjustment necessary.
Hepatic Impairment:
No dose adjustment necessary.
Precautions:
WARNING: The use of methylphenidate-containing
products and amphetamines have a high potential
for abuse and dependence. Assess the risk of
abuse prior to prescribing, and monitor for signs
of abuse and dependence while on therapy. Long-
term abusive use can lead to marked tolerance
and psychological dependence with varying
degrees of abnormal behavior. Frank psychotic
episodes can occur, especially with parenteral
abuse. Methylphenidate requires an S-2 license
for physicians to be able to prescribe it and an S-
1 license with a triplicate prescription for
pharmacists to dispense it.
Monotherapy in service users/patients with bipolar
disorder should be avoided. Patients presenting
with depressive symptoms should be screened for
bipolar disorder. Methylphenidate monotherapy is
not FDA approved for the treatment of bipolar
depression.
Caution operating hazardous machinery or driving.
Take caution in switching formulations of
methylphenidate, as bioequivalence does not
automatically translate into clinical equivalence.
Not an appropriate first-line treatment for depression
or for normal fatigue.
Cardiovascular events (serious structural cardiac
abnormalities, cardiomyopathy, serious heart rhythm
abnormalities); Chemical leukoderma; Hypersensitivity
(angioedema and anaphylactic reactions); Peripheral
525

vasculopathy (Raynaud’s phenomenon, digital
ulceration); Priapism; Visual disturbance (difficulty in
accommodation and blurred vision); Adrenal tumors.
Cardiovascular disorders; Hyperthyroidism; Psychiatric
disorders; Seizure disorder; Tourette syndrome/tics.
Lactation; Children (appetite suppression, weight loss,
slowing of growth rate); Pregnancy (infants whose
mothers took methylphenidate during pregnancy may
experience withdrawal symptoms); Neonates (Gasping
syndrome may occur with benzyl alcohol and derivatives
containing preparation.)
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C. Protect from light and
moisture.
Adverse Drug Reactions:
Common: insomnia, sedation, headache, exacerbation of
tics, nervousness, anxiety, restlessness, irritability,
emotional lability (1%-, depressed mood, depression,
agitation, overstimulation, aggressive behavior, tremor,
dizziness, anorexia, hypertonia, lack of emotion, vertigo,
confusion, tension, tension headache, paresthesia,
hyperhidrosis, excoriation, skin rash, weight loss,
decreased libido, temporary slowing of normal growth in
children, nausea, vomiting, upper abdominal pain,
decreased appetite, dry mouth, bruxism, dyspepsia,
motion sickness, constipation, blurred vision, eye pain,
N
nasopharyngitis, cough, upper respiratory tract infection,
oropharyngeal pain, fever.
Rare: Priapism; dysphoria; “zombie-like” state; psychotic
episodes; seizures; palpitations; tachycardia;
hypertension; neuroleptic malignant syndrome;
activation of hypomania, mania, or suicidal ideation;
cardiovascular adverse effects; Gilles de la Tourette
syndrome; hypervigilance; jitteriness; mood changes;
outbursts of anger; panic attack; psychomotor agitation;
sleep disorder; toxic psychosis; macular eruption; growth
suppression; hot flash; increased thirst; abdominal
distress; diarrhea; erectile dysfunction; anemia;
leukopenia; muscle spasm; weakness; dry eye
syndrome; dyspnea; sinusitis; accommodation
disturbance; allergic contact dermatitis; allergic contact
sensitivity; alopecia; angina pectoris; application site
reaction; arthralgia; auditory hallucination; bradycardia;
cerebral arteritis; cerebrovascular occlusion; change in
libido; chest discomfort; chest pain; decreased platelet
count; decreased therapeutic response; diplopia;
disorientation; drowsiness; dyskinesia; erythema;
extrasystoles; fatigue; hallucination; hepatic failure
(acute); hepatic injury (severe); hyperpyrexia;
hypersensitivity reaction; immune thrombocytopenia;
lethargy; leukoderma; loss of scalp hair; muscle
twitching; myalgia; mydriasis; neuroleptic malignant
syndrome; pancytopenia; peripheral vascular
insufficiency; priapism; Raynaud phenomenon;
rhabdomyolysis; seizure; supraventricular tachycardia;
talkativeness; thrombocytopenia; thrombotic
thrombocytopenic purpura; urticaria; ventricular
premature contractions; visual disturbance; sudden
death in service users/patients with preexisting cardiac
structural abnormalities.
526
NERVOUS SYSTEM
Drug Interactions:
Monitor closely with:
Enhances the effects of the following:
Atomoxetine (anti-hypertensive effects)
Reduces therapeutic effect of the following:
Antihypertensives, Ioflupane I123
Enhance adverse effects of the following:
Anti-Parkinson’s agents e.g., Levodopa, Antipsychotic
agents, Clonidine, Doxofylline
Sympathomimetics, Tricyclic anti- depressants
Enhances the adverse effects of Methylphenidate:
Antipsychotic agents
Avoid concomitant use with:
Increases the serum concentration of the following:
Methylphenidate
Enhance adverse effects of Methylphenidate:
Alcohol, Ethyl
Enhances effects of the following:
Inhalational anaesthetic (anti-hypertensive effect)
Enhances effects of Methylphenidate:
MAO Inhibitors (anti- hypertensive effects)
Enhances adverse effects of the following:
Iobenguane I123
Administration: May be taken with or without food. Swallow
whole and do not chew, divide, or crush.
Pregnancy Category: Category C
ATC Code: N06BA04
ANTI-DEMENTIA DRUGS
ANTICHOLINESTERASES
Rx DONEPEZIL
Oral: 5 mg and 10 mg tablet/orodispersible tablet (ODT)
Donepezil inhibits acetylcholinesterase resulting in an
increase of acetylcholine availability at the remaining
sites that slows the decline in function of dementia
service users/patients without memory improvement to
enhanced memory.
Indications: Management of Alzheimer dementia (mild,
moderate, and severe)
Dose:
Alzheimer dementia (mild, moderate, severe), by mouth,
ADULT, mild to moderate: initially 5 mg by mouth once
daily at bedtime. May increase to 10 mg once daily at
bedtime after 4-6 weeks, moderate to severe: initially 5
mg by mouth once daily at bedtime. May increase to 10
mg once daily at bedtime after 4-6 weeks. May increase
further after ≥3 months to 23 mg once daily at bedtime.
NERVOUS SYSTEM
Dose Adjustment:
Geriatric:
Some service users/patients may tolerate lower doses
better; for elderly women ≥85 years with low body weight,
a maximum of 5 mg once daily at bedtime is
recommended.
Renal Impairment:
Few data available; dose adjustment may not be necessary.
Hepatic Impairment:
Few data available; dose may need to be lowered.
Precautions:
Altered cardiac conduction (QTc prolongation and torsades
de pointes, bradycardia); Anorexia/weight loss; Bladder
obstruction; GI effects (dose-related diarrhea, nausea,
and/or vomiting); Neuroleptic malignant syndrome;
Rhabdomyolysis.
Peptic ulcer disease; Respiratory disease e.g. COPD and/or
asthma; Seizure disorder; Urinary tract obstruction.
Lactation; Low-weight service users/patients; Pregnancy
(NOT recommended for use in pregnant women or
women of childbearing potential).
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C.
Adverse Drug Reactions:
Common: hypertension, chest pain, syncope, atrial
fibrillation, bradycardia, cardiac failure, ECG abnormality,
edema, hypotension, peripheral edema, vasodilation,
insomnia, dizziness, headache, pain, tremor, fatigue,
depression, abnormal dreams, hallucination, hostility,
nervousness, confusion, drowsiness, emotional lability,
personality disorder, abnormal gait, aggressive behavior,
agitation, anxiety, aphasia, ataxia, convulsions,
delusions, irritability, paresthesia, restlessness, vertigo,
wandering, anorexia, ecchymosis, eczema, dermal ulcer,
diaphoresis, pruritus, skin rash, urticaria, weight loss,
hyperlipidemia, dehydration, glycosuria, hot flash,
increased libido, nausea, vomiting, diarrhea, appetite
loss, increased gastric acid secretion, abdominal pain,
bloating, constipation, dyspepsia, epigastric pain, fecal
incontinence, gastroenteritis, gastrointestinal
hemorrhage, sore throat, toothache, urinary frequency,
cystitis, hematuria, nocturia, urinary tract infection,
bruise, hemorrhage, anemia, infection, fungal infection,
influenza, muscle cramps, back pain, arthritis,
weakness, bone fracture blurred vision, cataract, eye
irritation bronchitis, dyspnea), flu-like symptoms,
increased cough, pharyngitis , pneumonia, accidental
injury (13%), fever (2%).
Rare: seizures, syncope, bladder incontinence, abnormal
lacrimation, abnormal vision, abscess, acute rhinitis,
albuminuria, alopecia, angina pectoris, apathy, arteritis,
arthralgia, arthropathy, asthma, atelectasis, atrophic
striae, benign prostatic hypertrophy, blepharitis, breast
fibroadenosis, cachexia, cardiomegaly, cellulitis,
cerebral hemorrhage, cerebral infarction, cerebral
ischemia, cerebrovascular accident, chills, cholecystitis,
cholelithiasis, conjunctival hemorrhage, conjunctivitis,
convulsions, decreased libido, deep vein thrombosis,
dementia, dermatitis, diabetes mellitus, diverticulitis,
duodenal ulcer, dysarthria, dysgeusia, dysphagia,
dysphoria, dysuria, emotional disturbance, eosinophilia,
epigastric distress, epistaxis, eructation, erythema,
erythrocytopenia, esophagitis, euphoria, extrapyramidal
reaction, facial edema, fasciculations, fibrocystic breast
changes, first degree atrioventricular block, flatulence,
fungal dermatitis, gastritis, gastric ulcer, gingivitis,
glaucoma, goiter, gout, hearing loss, heart block,
hemiplegia, hemolytic anemia, hemorrhoids, hepatitis,
hernia, herpes zoster, hiatal hernia, hirsutism,
hyperbilirubinemia, hyperglycemia, hyperkeratosis,
hypersensitivity reaction, hypertonia, hypokalemia,
hypokinesia, hyponatremia, hypoproteinemia, hypoxia,
increased appetite, intestinal obstruction, intracranial
hemorrhage, iron deficiency anemia, irritable bowel
syndrome, jaundice, leg cramps, leukocytosis, localized
coldness, malaise, mastitis, melena, motion sickness,
muscle spasm, myalgia, myasthenia, myocardial
infarction, neuralgia, neurodermatitis, neuroleptic
malignant syndrome, night sweats, nystagmus,
orthostatic hypotension, osteoporosis, otalgia, otitis
externa, otitis media, pacing, pancreatitis, paranoia,
peptic ulcer disease, periodontal abscess, periodontitis,
periorbital edema, peripheral vascular disease,
pernicious anemia, pleurisy, polydipsia, post nasal drip,
prolonged Q-T interval on ECG, psoriasis, pulmonary
congestion, pyelonephritis, pyuria, rectal hemorrhage,
renal failure, retinal hemorrhage, rhabdomyolysis,
rhinitis, seeing spots, sensation of cold, sepsis, severe
depression, sialorrhea, skin discoloration, sleep apnea,
N
snoring, supraventricular extrasystole, supraventricular
tachycardia, thrombocythemia, thrombocytopenia,
tinnitus, tongue edema, tonic-clonic seizures, torsades
de pointes, transient ischemic attacks, urinary urgency,
uterine hemorrhage, vaginitis, vasodilation, ventricular
premature contractions, ventricular tachycardia, vertigo,
vesiculobullous dermatitis, weight gain, wheezing,
xeroderma, xerophthalmia, xerostomia.
Drug Interactions:
Monitor closely with:
Amifampridine – may enhance the therapeutic effect and
side effects of acetylcholinesterase inhibitors;
acetylcholinesterase inhibitors may enhance the
therapeutic effect and side effects of amifampridine.
Anesthetics – donepezil may enhance the effects of
anesthetics; donepezil should be discontinued before
surgery.
Anticholinergics – may decrease the efficacy of each other
due to opposite physiologic effects.
Benoxinate – acetylcholinesterase inhibitors may prolong
the effects of benoxinate.
Beta-blockers – acetylcholinesterase inhibitors may
enhance the bradycardic effect of beta-blockers except
for levobunolol and metipranolol.
Bradycardia-causing agents – may enhance the bradycardic
effect of other bradycardia-causing agents.
Bretylium – may enhance the bradycardic effect of other
bradycardia-causing agents; bretylium may also enhance
atrioventricular (AV) blockade in service users/patients
receiving AV blocking agents.
Ceritinib – may enhance the bradycardic effect of ceritinib.
Cholinergics – may have a synergistic effect if administered
simultaneously.
Corticosteroids (systemic) – may enhance the adverse/toxic
effect of acetylcholinesterase inhibitors; increased
muscular weakness may occur.
527

Dipyridamole – may diminish the therapeutic effect of
acetylcholinesterase Inhibitors.
Ivabradine – bradycardia-causing agents may enhance the
bradycardic effect of ivabradine.
Lacosamide – bradycardia-causing agents may enhance the
AV-blocking effect of lacosamide.
Levodopa – efficacy may be theoretically reduced by
donepezil.
Neuromuscular-blocking agents (nondepolarizing) –
acetylcholinesterase inhibitors may diminish the
neuromuscular-blocking effect of neuromuscular-
blocking agents (nondepolarizing).
QTc-prolonging agents – QTc-prolonging agents may
enhance the QTc-prolonging effect of QTc-prolonging
agents.
Ruxolitinib – may enhance the bradycardic effect of
bradycardia-causing agents.
Succinylcholine – acetylcholinesterase inhibitors may
increase the serum concentration of succinylcholine.
Terlipressin – may enhance the bradycardic effect of
bradycardia-causing agents.
Tofacitinib – may enhance the bradycardic effect of
bradycardia-causing agents.
Administration: May be taken with or without food. Allow
tablet to dissolve completely on tongue and follow with
water.
N
Pregnancy Category: Category C
ATC Code: N06DA02
Rx RIVASTIGMINE
Oral: 1.5 mg, 3 mg, and 6 mg capsule (as hydrogen
tartrate)
A carbamate pseudoirreversible (self-reversing over hours),
intermediate-acting agent that is selective for inhibiting
acetylcholinesterase over butyrylcholinesterase and for
inhibiting acetylcholinesterase in the cortex and
hippocampus over other areas of the brain. It also
inhibits butyrylcholinesterase in the glia, which may be
even more important when Alzheimer’s disease service
users/patients develop gliosis when cortical neurons die.
Indications: Alzheimer dementia (mild to moderate);
Parkinson’s disease dementia (mild to moderate)
Contraindications: hypersensitivity to rivastigmine or other
carbamates
Dose:
Alzheimer dementia, mild to moderate, by mouth, ADULT,
initially 1.5 mg twice daily. Increase by 3 mg every 2
weeks and titrate to tolerability with a maximum dose of
6 mg twice daily.
Parkinson’s disease dementia, mild to moderate, by mouth,
ADULT, initially 1.5 mg twice daily. Increase by 3 mg every
4 weeks and titrate to tolerability with a maximum dose
of 6 mg twice daily.
528
NERVOUS SYSTEM
Dose Adjustment:
Geriatric:
Some service users/patients may tolerate lower doses
better.
Renal Impairment:
Dose adjustment not necessary; titrate to point of
tolerability.
Hepatic Impairment:
Dose adjustment not necessary; titrate to point of
tolerability.
Precautions:
Caution operating hazardous machinery or driving.
Systemic exposure may be increased in service
users/patients <50 kg and decreased in service
users/patients >100 kg
Concerns related to adverse effects:
Allergic dermatitis; CNS depression; Extrapyramidal effects
GI effects (nausea/vomiting/diarrhea or
anorexia/weight loss/decreased appetite); Vagotonic
effects (bradycardia and/or heart block with or without a
history of cardiac disease); Weight loss.
Peptic ulcer disease; Respiratory disease (use with caution
in service users/patients with COPD and/or asthma);
Seizure disorder; Urinary tract obstruction e.g. bladder
outlet obstruction or prostatic hyperplasia.
Lactation (not recommended for use in nursing women);
Pregnancy (not recommended for use in pregnant
women or women of childbearing potential).
NOTE: Should be started at lowest dose and titrated; if
treatment is interrupted for >3 days, reinstate at the
lowest daily dose. Severe vomiting with esophageal
rupture may occur if rivastigmine therapy is resumed
without retitrating the drug from the beginning (i.e. 1.5
mg by mouth twice daily).
STORAGE AND STABILITY: Store between 20-25°C.
Excursions permitted to 15-30°C.
Adverse Drug Reactions:
Common: hypertension, syncope, nausea, vomiting,
diarrhea, abdominal pain, appetite loss, weight loss,
dyspepsia, increased gastric acid secretion, upper
abdominal pain, sialorrhea, anorexia, headache,
dizziness, falling, tremor, fatigue, insomnia, confusion,
depression, drowsiness, malaise, anxiety, hallucination,
aggressive behavior, exacerbation of Parkinson’s
disease, cogwheel rigidity, restlessness, drug-induced
Parkinson’s disease, diaphoresis, dehydration, urinary
tract infection, urinary incontinence, asthenia,
weakness, bradykinesia, hypokinesia, dyskinesia
Rare: seizures, syncope, severe vomiting with esophageal
rupture, rhinitis, urogenital infection, fever, injury,
dyspnea, abnormal hepatic function tests, allergic
dermatitis, atrial fibrillation, atrioventricular block,
bradycardia, dystonia, edema, extrapyramidal reaction,
gastrointestinal hemorrhage, hepatic failure, hepatitis,
hyperacidity, hypersensitivity reaction, nightmares,
pancreatitis, sick-sinus syndrome, skin blister, Stevens-
Johnson syndrome, tachycardia, urticaria
NERVOUS SYSTEM
Drug Interactions:
Monitor closely with:
Enhances the effect of the following:
Antipsychotic agents (severe extrapyramidal symptoms)
Bradycardia-causing agents, Bretylium, Ivabradine
(bradycardic effect) Lacosamide (AV blockade effect)
Enhances effect of Rivastigmine:
Ruxolitinib, Tofacitinib (bradycardic effect)
Enhances adverse effect of the following:
Cholinergic agonists e.g., Betanechol
Enhances adverse effects of Rivastigmine:
Corticosteroids, Systemic (muscular weakness)
Reduces the therapeutic effect of the following drugs:
Anticholinergic agents
Neuromuscular- blocking agents, Nondepolarizing
Reduces the therapeutic of Rivastigmine:
Dipyridamole
Avoid concomitant use with:
Increases serum concentration of the following:
Succinylcholine (neuromuscular blockade)
Enhances effect of the following:
Beta-blockers, Ceritinib (bradycardic effect)
Enhances adverse effect of the following:
Metoclopramide (extrapyramidal reactions)
Administration: Take with food
Pregnancy Category: Category B
ATC Code: N06D
OTHER NERVOUS SYSTEM DRUGS
PARASYMPATHOMIMETICS
ANTICHOLINESTERASES
Rx NEOSTIGMINE
Inj.: 500 micrograms/mL, 1 mL ampule and 10 mL vial
Neogstigmine inhibits the destruction of acetylcholine by
acetylcholinesterase.
Indications: Management of myasthenia gravis, reversal of
non-depolarizing neuromuscular blockade after surgery;
paralytic ileus and postoperative bladder
distention/urinary retention and diagnosis of myasthenia
gravis.
Contraindications: peritonitis or mechanical obstruction of
the intestinal or urinary tract, hypersensitivity to
neostigmine or any component of the formulation.
Dose:
NOTE: Pretreatment with atropine is recommended, and
atropine should be available if a cholinergic reaction occurs.
Myasthenia gravis, diagnosis, by intramuscular injection,
ADULT, 0.022 mg/kg as a single dose. If test is
inconclusive, retesting can be done on a different day
with a single dose of 0.031 mg/kg, CHILD<2 years
(limited data available), 0.04 mg/kg once. If results are
equivocal or negative, may be repeated once in 4 hours.
Typical dose is 0.5-1.5 mg.
Myasthenia gravis, treatment, by intramuscular or
intravenous or subcutaneous injection, ADULT, 0.5-2.5
mg. Dosing based on individual patient response, CHILD
AND ADOLESCENT (limited data available), 0.01-0.04
mg/kg every 2-6 hours.
NOTE: An anticholinergic agent (atropine or glycopyrrolate)
should be given intravenously prior to or in conjunction
with neostigmine; in the presence of bradycardia,
administer the anticholinergic prior to neostigmine.
Peripheral nerve stimulation delivering train-of-four (TOF)
stimulus must also be used to determine time of
neostigmine initiation and need for additional doses.
Prior to administration, there must be a twitch response
to the first stimulus in the TOF of at least 10% of
baseline.
Reversal of nondepolarizing neuromuscular blockade after
N
surgery, by intravenous injection, ADULT/CHILD,
Bioxiverz: The usual dose is 0.03-0.07 mg/kg, which
generally achieves a TOF twitch ratio of 90% within 10-
20 minutes of administration. The maximum total dose
is 0.07 mg/kg or 5 mg, whichever is less. The 0.03
mg/kg dose is recommended for reversal of NMBAs with
shorter half-lives (e.g. rocuronium); or when the first
twitch response to the TOF stimulus is substantially
>10% of baseline or when a second twitch is present.
The 0.07 mg/kg dose is recommended for NMBAs with
longer half-lives (e.g. vecuronium, pancuronium); or
when the first twitch response is relatively weak (i.e. not
substantially >10% of baseline); or rapid recovery is
needed, NEONATE, Bloxiverz: Note: An anticholinergic
agent (atropine or glycopyrrolate) should be given prior
to or in conjunction with neostigmine; in the presence of
bradycardia, administer the anticholinergic prior to
neostigmine. Peripheral nerve stimulation delivering
train-of-four (TOF) stimulus must also be used to
determine time of neostigmine initiation and need for
additional doses.
Dose Adjustment:
Geriatric:
No dose adjustment necessary.
Renal Impairment:
ADULT, CrCl >50 mL/minute: No dosage adjustment
necessary.
CrCl 10 to 50 mL/minute: Administer 50% of normal dose.
CrCl <10 mL/minute: Administer 25% of normal dose.
Hemodialysis: No dosage adjustment necessary.
Peritoneal dialysis: No dosage adjustment necessary.
Continuous renal replacement therapy (CRRT): Administer
50% of normal dose.
Hepatic Impairment:
Has not been studied
529

Precautions:
Concerns related to adverse effects:
Cardiovascular effects (bradycardia, hypotension,
dysrhythmias); Cholinergic crisis (extreme muscle
weakness and potentially fatal respiratory paralysis);
Hypersensitivity; Neuromuscular effects;
Asthma; Cardiovascular disease; Hyperthyroidism;
Megacolon/GI dysfunction; Myasthenia gravis; Peptic
ulcer disease; Seizure disorder; Vagotonia
Pediatric; Elderly (Elderly patients experience slower
spontaneous recovery from neuromuscular blocking
agents.);
NOTE: Adequate facilities should be available for
cardiopulmonary resuscitation when testing and
adjusting dose for myasthenia gravis.
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Protect from light. Store in carton
until time of use.
Adverse Drug Reactions:
Atrioventricular block, cardiac arrhythmia (especially
bradycardia), flushing, hypotension, nodal arrhythmia,
syncope, tachycardia, thrombophlebitis (IV), dizziness,
drowsiness, dysarthria, headache, loss of
consciousness, seizure, voice disorder, diaphoresis, skin
rash, urticaria, diarrhea, dysphagia, flatulence,
N
increased peristalsis, nausea, salivation, stomach
cramps, vomiting, urinary urgency, anaphylaxis,
hypersensitivity reaction, arthralgia, fasciculations,
laryngospasm, muscle cramps, muscle spasm,
weakness, lacrimation, miosis, bronchospasm, dyspnea,
exacerbation of asthma, increased bronchial secretions,
respiratory depression, respiratory paralysis
Drug Interactions:
Monitor closely with:
Amifampridine – may enhance the therapeutic effect of
acetylcholinesterase inhibitors; acetylcholinesterase
inhibitor side effects may also be increased;
acetylcholinesterase inhibitors may enhance the
therapeutic effect of amifampridine; amifampridine side
effects may also be increased.
Anticholinergics – may diminish the therapeutic effect of
acetylcholinesterase inhibitors. acetylcholinesterase
inhibitors may diminish the therapeutic effect of
anticholinergics.
Benoxinate – acetylcholinesterase inhibitors may enhance
the therapeutic effect of Benoxinate; specifically, the
effects of benoxinate may be prolonged.
Beta-blockers – acetylcholinesterase inhibitors may
enhance the bradycardic effect of beta-blockers except
for levobunolol and metipranolol.
Cholinergic agonists – acetylcholinesterase inhibitors may
enhance the adverse/toxic effect of cholinergic agonists.
Corticosteroids (systemic) – may enhance the adverse/toxic
effect of acetylcholinesterase inhibitors; increased
muscular weakness may occur.
Dipyridamole – may diminish the therapeutic effect of
acetylcholinesterase inhibitors.
Neuromuscular-blocking agents (nondepolarizing) –
acetylcholinesterase inhibitors may diminish the
neuromuscular-blocking effect of neuromuscular-
blocking agents (nondepolarizing).
530
NERVOUS SYSTEM
Succinylcholine – acetylcholinesterase inhibitors may
increase the serum concentration of Succinylcholine.
Management: Consider alternatives to this combination
due to a risk of prolonged neuromuscular blockade.
Administration: Neostigmine Omega, Prostigmin: May be
administered IM, IV, or SC. Bloxiverz: Administer by slow
IV injection over at least 1 minute.
Pregnancy Category: Category
ATC Code: N07AA01
Rx PYRIDOSTIGMINE
Oral: 60 mg tablet (as bromide)
Pyridostigmine is a quaternary pyridinium carbamate. It
inhibits destruction of acetylcholine by
acetylcholinesterase.
Indications: Management of myasthenia gravis; paralytic
ileus; Soman nerve gas exposure, pretreatment (military
use)
Contraindications: Mechanical intestinal or urinary
obstruction
Dose:
Myasthenia gravis, by mouth, ADULT, highly individualized
dosing ranges from 60-1500 mg/day. The usual dose is
600 mg/day divided into 5-6 doses, spaced to provide
maximum relief, CHILD 6-12 years, 60 mg, CHILD<6
years, initially 30 mg. Dosage should increase gradually,
in increments of 15-30 mg daily, until maximum
improvement is obtained. Total daily requirements are
usually in the range of 30-360 mg.
NOTE: Do not administer pyridostigmine after Soman
exposure; if taken immediately before exposure (e.g.
when gas attack alarm is given) or at the same time, it is
not expected to be effective and may exacerbate the
effects of a sub-lethal exposure to Soman.
Soman nerve gas exposure, pretreatment (military use), by
mouth, ADULT, 30 mg every 8 hours beginning several
hours prior to exposure. Discontinue at first sign of
Soman exposure, then immediately begin atropine and
pralidoxime.
Dose Adjustment:
Geriatric:
No dose adjustment necessary.
Renal Impairment:
Lower initial doses dosages may be required due to
prolonged elimination in renal impairment.
Hepatic Impairment:
No dose adjustment necessary.
Precautions:
Cholinergic effects; Hypersensitivity reactions;
NERVOUS SYSTEM

Cardiovascular disease; Glaucoma; Renal impairment; Beta-blockers – acetylcholinesterase inhibitors may

Respiratory disease (use with extreme caution in
patients with asthma, bronchospastic disease, COPD)
Bromide sensitivity;
Pediatrics (gasping syndrome due to benzyl alcohol and
derivaitves);
Military use (Only for pretreatment for exposure to Soman;
discontinue pyridostigmine at the first sign of Soman
exposure (do not administer pyridostigmine after Soman
exposure); atropine and pralidoxime must be
administered after Soman exposure. Use in conjunction
with protective garments, including gas mask, hood and
overgarments.)
NOTE: Must be administered by trained personnel; use of
peripheral nerve stimulation to monitor neuromuscular
function recovery and continuous patient observation. To
counteract anticholinergic effects, use of glycopyrrolate
or atropine sulfate simultaneously with or prior to
administration is recommended until recovery of normal
respiration is recommended.
Inadequate reversal induced by nondepolarizing muscle
relaxants is possible; manage with manual or
mechanical ventilation until recovery is adequate
(additional doses not recommended).
Pyridostigmine pretreatment offers no benefit against
Soman unless atropine and pralidoxime are
administered once symptoms of poisoning appear.
enhance the bradycardic effect of beta-blockers except
levobunolol and metipranolol.
Cholinergic agonists – acetylcholinesterase inhibitors may
enhance the adverse/toxic effect of cholinergic agonists.
Corticosteroids (systemic) – may enhance the adverse/toxic
effect of acetylcholinesterase inhibitors; increased
muscular weakness may occur.
Dipyridamole – may diminish the therapeutic effect of
acetylcholinesterase inhibitors.
Methocarbamol – may diminish the therapeutic effect of
pyridostigmine.
Neuromuscular-blocking agents (nondepolarizing) –
acetylcholinesterase inhibitors may diminish the
neuromuscular-blocking effect of neuromuscular-
blocking agents (nondepolarizing).
Succinylcholine – acetylcholinesterase inhibitors may
increase the serum concentration of succinylcholine.
Administration: Should be taken with food.
Pregnancy Category: Category B/C (manufacturer
dependent)
ATC Code: N07AA02
DRUGS USED IN ADDICTIVE DISORDERS

N
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Dispense in original container. Rx NALTREXONE
Adverse Drug Reactions:
Oral: 50 mg tablet (as hydrochloride)
Common: twitching, hyperesthesia, xeroderma, abdominal
pain, diarrhea, dysmenorrhea, urinary frequency,
Naltrexone blocks mu opioid receptors, preventing
myalgia, neck pain, amblyopia, epistaxis
exogenous opioids from binding and thus preventing the
Rare: bradycardia (transient), chest tightness, decreased
pleasurable effects of opioid consumption. It also
heart rate, increased blood pressure, confusion,
reduces alcohol consumption through modulation of
depressed mood, disturbed sleep, drowsiness,
opioid systems, thereby reducing the reinforcing effects
headache, hypertonia, lack of concentration, lethargy,
of alcohol.
localized warm feeling, numbness of tongue, tingling of
extremities, vertigo, alopecia, diaphoresis, skin rash,
Indications: Management of alcohol dependence, blockade
abdominal cramps, bloating, borborygmi, flatulence,
of effects of exogenously administered opioids
increased peristalsis, nausea, salivation, vomiting,
fasciculations, muscle cramps, weakness, eye pain,
Contraindications: Concurrent opioid dependence or opiate
lacrimation, miosis, visual disturbance, acute bronchitis
withdrawal, failure in naloxone challenge test, positive
(exacerbation), exacerbation of asthma, increased
urine screening for opioids, acute hepatitis, liver failure
bronchial secretions, fecal incontinence, loss of
or liver function tests greater than 3 times the upper limit
consciousness, pallor (postsyncopal), stiffness (arms or
of normal, hypersensitivity to naltrexone
upper torso), thrombophlebitis, urinary incontinence
Dose:
Drug Interactions:
NOTE: Do not initiate therapy until service user/patient is
Monitor closely with:
opioid-free (including tramadol) for at least 7-10 days as
Amifampridine – may enhance the therapeutic effect of
determined by urinalysis; consider naloxone challenge
acetylcholinesterase inhibitors; acetylcholinesterase
test to confirm service user/patient is opioid-free if there
inhibitor side effects may also be increased;
is any suspicion since urinary opioid screen may not be
acetylcholinesterase inhibitors may enhance the
sufficient proof.
therapeutic effect of amifampridine; amifampridine side
effects may also be increased.
Alcohol dependence, by mouth, ADULT, 50 mg once daily.
Anticholinergics – may diminish the therapeutic effect of
Titration is not required. Alternative maintenance
acetylcholinesterase inhibitors. acetylcholinesterase
regimens may be used and include: 50 mg on weekdays
inhibitors may diminish the therapeutic effect of
with a 100 mg dose on Saturday; 100 mg every other
anticholinergics.
day; or 150 mg every 3 days (degree of blockade may be
Benoxinate – acetylcholinesterase inhibitors may enhance
reduced with extended dosing interval regimens and
the therapeutic effect of benoxinate; specifically, the
doses >50 mg may increase risk of hepatocellular injury).
effects of benoxinate may be prolonged.

531

Opioid dependence, by mouth, ADULT, initially 25 mg. If no
withdrawal signs occur, administer 50 mg once daily
thereafter. Alternative maintenance regimens may be
used and include: 50 mg on weekdays with a 100 mg
dose on Saturday; 100 mg every other day; or 150 mg
every 3 days (degree of blockade may be reduced with
extended dosing interval regimens and doses >50 mg
may increase risk of hepatocellular injury).
Dose Adjustment:
Geriatric:
Some service users/patients may tolerate lower doses
better.
Renal Impairment:
Dose adjustment not necessary for mild impairment;
Hepatic Impairment:
Dose adjustment not generally necessary for mild
impairment; has the potential to cause hepatocellular
injury when given in excessive doses and is
contraindicated in acute hepatitis and liver failure.
Precautions:
Patients who had been treated with naltrexone may
respond to lower opioid doses than previously used.
This could result in potentially life-threatening
opioid intoxication. Patients should be aware that
N
they may be more sensitive to lower doses of
opioids after naltrexone treatment is discontinued.
Discontinue therapy if signs/symptoms of acute
hepatitis develop. Clinicians should note that
elevated transaminases may be a result of pre-
existing alcoholic liver disease, hepatitis B and/or C
infection, or concomitant use of other hepatotoxic
drugs; abrupt opioid withdrawal may also lead to
acute liver injury.
Increase risk of suicidal thinking and behavior
(suicidality).
Patients should be opioid-free (including tramadol) for
a minimum of 7-10 days; a naloxone challenge test
may be helpful to confirm service user/patient is
opioid-free prior to therapy if there is any suspicion
since urinary opioid screen may not be sufficient
proof.
Patients transitioning from buprenorphine or
methadone may be vulnerable to precipitation of
withdrawal symptoms for as long as 2 weeks
In naltrexone-treated service users/patients requiring
emergency pain management, consider
alternatives to opioid therapy. Seek direct care of a
trained anesthesia provider
For naltrexone- treated patients requiring surgery;
discontinue oral naltrexone at least 72 hours before
scheduled elective surgery if opioid use is
anticipated; extended-release IM naltrexone should
be discontinued at least 30 days prior to scheduled
surgery
Naltrexone should be avoided in opioid- dependent
patients as an acute withdrawal may be
precipitated.
Accidental opioid overdose, Acute opioid withdrawal (pain,
hypertension, sweating, agitation, and irritability; in
532
NERVOUS SYSTEM
neonates: shrill cry, failure to feed); Eosinophilic
pneumonia; Hepatocellular injury (dose-related
hepatocellular injury); Hypersensitivity; Injection site
reactions (cellulitis, induration, hematoma, abscess,
necrosis); Suicidal thoughts/depression.
Bleeding disorders; Hepatic and renal impairment;
Detoxified opioid addiction.
Lactation.
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Protect from light.
Adverse Drug Reactions:
Common: Syncope, hypertension, headache, insomnia,
dizziness, anxiety, decreased energy, nervousness,
suicidal ideation, delayed ejaculation, depression,
drowsiness, fatigue, chills, depressed mood, increased
energy, irritability, skin rash, increased gamma-glutamyl
transferase, increased thirst, polydipsia, nausea,
vomiting, decreased appetite, diarrhea, abdominal pain,
abdominal cramps, xerostomia, toothache, constipation,
impotence, influenza, injection site reaction, arthralgia,
myalgia, muscle cramps, back pain, pharyngitis.
Rare: Hepatocellular injury (excessive doses), dysphoria,
abnormality in thinking, acne vulgaris, acute ischemic
stroke, agitation, alopecia, altered blood pressure,
angina pectoris, anorexia, atrial fibrillation, blurred
vision, burning sensation of eyes, cardiac failure,
cerebral aneurysm, chest pain, chest tightness,
cholecystitis, cholelithiasis, chronic obstructive
pulmonary disease, cold extremities, colitis, confusion,
cough, decreased libido, deep vein thrombosis,
dehydration, delirium, diaphoresis, disorientation,
dyspnea, dysuria, ECG changes, edema, eosinophilia
(transient), eosinophilic pneumonitis, epistaxis,
euphoria, eye pain, fever, flatulence, gastrointestinal
hemorrhage, groin pain, hallucination, hemorrhoids,
hepatic insufficiency, hepatitis, herpes labialis,
hoarseness, hot flash, hypercholesterolemia,
hyperkinesia, hypersensitivity reaction, increased
appetite, increased bronchial secretions, increased
libido, knee pain, leg pain, leukocytosis,
lymphadenopathy, malaise, myocardial infarction, nasal
congestion, nightmares, oily skin, opioid withdrawal
syndrome, otalgia, palpitations, pancreatitis, paralytic
ileus, paranoia, perirectal abscess, photophobia,
pneumonia, pulmonary embolism, restlessness,
rhinorrhea, rigors, seizure, shoulder pain, sinusitis,
sneezing, sore throat, swelling of eye, tachycardia,
thrombocytopenia, tinea pedis, tinnitus, tremor,
twitching, ulcer, urinary frequency, urinary tract infection,
visual disturbance, weakness, weight gain, weight loss,
yawning
NOTE: May cause cross- reactivity with some immunoassay
methods
Drug Interactions:
Monitor closely with:
Acamprosate – naltrexone may increase the serum
concentration of acamprosate.
Cannabinoids – naltrexone may enhance or diminish the
therapeutic effect of cannabinoids.
Codeine – naltrexone may block the effects of codeine.
Glyburide – may increase the serum concentration of
naltrexone.
NERVOUS SYSTEM
Loperamide – naltrexone may block the effect of
loperamide.
Avoid concomitant use with:
Reduces therapeutic effect of the following:
Analgesics, Opioid
Enhances adverse effects of Naltrexone:
Methylnaltrexone (increased risk of opioid withdrawal),
Disulfiram (hepatotoxicity), Phenothiazines (lethargy)
Buprenorphine – may precipitate withdrawal if used within
the last 14 days.
Methadone – may precipitate withdrawal if used within the
last 14 days.
Methylnaltrexone – opioid antagonists may enhance the
adverse/toxic effect of naloxegol; specifically, the risk for
opioid withdrawal may be increased.
Naldemedine – opioid antagonists may enhance the
adverse/toxic effect of naloxegol; specifically, the risk for
opioid withdrawal may be increased.
Naloxegol – opioid antagonists may enhance the
adverse/toxic effect of naloxegol; specifically, the risk for
opioid withdrawal may be increased.
Opioid analgesics – may precipitate withdrawal if used
within the last 7 days except for buprenorphine or
methadone.
Administration: May be administered with or without food.
Administration with food or after meals may minimize
adverse gastrointestinal effects. Advise service
user/patient not to self-administer opioids while
receiving naltrexone therapy.
Pregnancy Category: Category C
ATC Code: N07BB04
ANTIVERTIGO PREPARATIONS
Rx BETAHISTINE
Oral: 8 mg, 16 mg, and 24 mg tablet (as hydrochloride/
dihydrochloride)
Betahistine is a partial agonist of histamine at H1 receptors
and antagonist at H3 receptors. It produces excitatory
effects on neuronal activity of cortical and subcortical
structures agonism and decrease vestibular sensory
input and increases release of histamine from the
hypothalamus via H3-receptor antagonism.
Indications: Management of Ménière disease
Contraindications: Presence or history of active peptic ulcer
disease, pheochromocytoma
Dose:
Ménière disease (to decrease episodes of vertigo), by
mouth, ADULT, 8-16 mg thrice daily or 24 mg twice daily.
The usual dosage range is 24-48 mg daily in divided
doses.
Dose Adjustment:
Geriatric:
Use with caution due to likelihood of decreased
hepatic/renal function.
Renal Impairment:
Has not been studied; use with caution.
Hepatic Impairment:
Has not been studied, but betahistine primarily undergoes
hepatic metabolism; use with caution.
Precautions:
Disease-related concerns:
Asthma; Cardiovascular disease (ventricular extrasystoles,
hypotension, tachycardia); Hepatic impairment; Peptic
ulcer;
STORAGE AND STABILITY: Do not store above 25°C. Store
the tablets in the original package.
Adverse Drug Reactions:
Common: headache, nausea, dyspepsia.
Rare: confusion, convulsions, drowsiness, hallucination,
paresthesia, hypotension, tachycardia, ventricular
premature contractions, pruritus, skin rash, Stevens-
Johnson syndrome, urticaria, abdominal distension,
abdominal pain, bloating, peptic ulcer, vomiting,
anaphylaxis, angioedema, hypersensitivity reaction,
dyspnea.
Drug Interactions:
Monitor closely with:
N
Reduces therapeutic effect of the following:
Beta-2 agonists e.g. Salbutamol
Reduces therapeutic effect of Betahistine:
Antihistamine [except Levocabastine]
Administration: Administer with or without meals;
administer with meals if adverse GI effects occur. Food
intake slows down absorption of betahistine.
ATC Code: N07CA01
Rx CINNARIZINE
Oral: 25 mg tablet
Inhibits contractions of vascular smooth muscle cells by
blocking calcium channels. It also decreases the
contractile activity of vasoactive substances (e.g.
norepinephrine and serotonin) by blocking receptor-
operated calcium channels.
Indications: Cerebral circulatory disorders, migraine
prophylaxis, motion sickness, vestibular disorders
Contraindications: Hypersensitivity to cinnarizine or any
component of the formulation
Dose:
NOTE: Do not exceed 225 mg daily; suggested maximum
daily doses for specific indications are noted, when
available.
Cerebral circulatory disorders, by mouth, ADULT, 25 mg
thrice daily.
533
 NERVOUS SYSTEM

Migraine prophylaxis, by mouth, ADULT, 25-50 mg thrice Administration: Administer after meals to reduce gastric
daily with a maximum dose of 150 mg/day. irritation.
Motion sickness, by mouth, ADULT/CHILD>12 years, 25 mg
30 minutes before traveling. May repeat every 6 hours if Pregnancy Category: Not available
needed, CHILD 5-12 years, 12.5 mg about 30 minutes
before traveling. May repeat every 6 hours if needed. ATC Code: N07CA02
Vestibular disorders, by mouth, ADULT/CHILD>12 years,
25-30 mg thrice daily with a maximum dose of 90
mg/day, CHILD 5-12 years, 12.5-15 mg thrice daily with OTHER NERVOUS SYSTEM DRUGS
a maximum dose of 45 mg/day.
ADJUNCTS TO ANESTHETIC
Dose Adjustment:
Geriatric:
No dose adjustment necessary. Rx EPHEDRINE
Renal Impairment:
Has not been studied; use with caution. Inj.: 30 mg/mL, 1 mL ampule solution for injection
50 mg/mL (as sulfate), 1 mL ampule (IM, IV)
Hepatic Impairment:
Has not been studied; use with caution. Ephedrine is a phenethylamine alpha and beta adrenergic
agonist. It may also enhance the release of
Precautions: norepinephrine.
Caution operating hazardous machinery or driving.
Indications: Anesthesia-induced hypotension
Use with caution in patients with Parkinson’s disease
and/or when considering long-term therapy. Contraindications: Angle-closure glaucoma; co-
Prolonged therapy (>6 months) may increase risk administration with myocardial sensitizing anesthetics
and resolution of symptoms may take >1 year (cyclopropane or halothane)
after discontinuation or may not be reversible.
N

CNS depression; Stomach discomfort; Hepatic impairment;
Hypotension
Parkinson’s disease (aggravation of parkinsonian
symptoms); Porphyria; Renal impairment
Dose:
Hypotension, anesthesia-induced, by slow intravenous
push, ADULT/CHILD>15 years, 5-25 mg/dose. Repeat as
needed to maintain blood pressure up to a maximum
total dose of 50 mg.

STORAGE AND STABILITY: Store between 15-30°C. Dose Adjustment:

Geriatric:
Adverse Drug Reactions: No dose adjustment necessary.
Common: Drowsiness, weight gain, dyspepsia, nausea
Rare: Dyskinesia, extrapyramidal disorders, fatigue, Renal Impairment:
hyperhidrosis, hypersomnia, lethargy, lichenoid Use with caution.
keratosis, lichen planus, muscle rigidity, parkinsonism,
stomach discomfort, subacute cutaneous lupus Hepatic Impairment:
erythematosus, tremor, upper abdominal pain, vomiting No dose adjustment necessary.

Drug Interactions: Precautions:

Monitor closely with: Concerns related to adverse effects:
Enhances the effects of the following: Cardiovascular effects (may cause hypertension
Alcohol, Ethyl, Brimonidine, Topical, Cannabis, resulting in intracranial haemorrhage, anginal pain in
Doxylamine, Dronabinol, Magnesium sulfate, ischemic heart disease, fatal arrythmia); Decreased
Mirtazapine (CNS depression), Metyrosine, Ropinirole, urine output; Tolerance (Temporary cessation of therapy
Rotigotine, Rufinamide (sedative effect), SSRIs restores its effectiveness.)
(psychomotor impairment) Anxiety and symptoms of paranoid schizophrenia
(Repeated use).
Enhances the effects of Cinnarizine:
Hydroxyzine, Minocycline, Nabilone (CNS depression) Use caution in:
Cardiovascular disease e.g. Hypertension, angina
Avoid concomitant use with: pectoris (Ephedrine should not ordinarily be used.)
Enhances effects of the following: Diabetes Mellitus; Prostatic hyperplasia/urinary
Azelastine, Nasal, Buprenorphine, Droperidol, stricture; Renal impairment; Thyroid dysfunction;
Hydrocodone, Methotrimeprazine, Orphenadrine, Patients with unstable vasomotor symptoms; Elderly
Paraldehyde, Suvorexant, Thalidomide (CNS depression)
NOTE: Blood volume depletion should be corrected before
Enhances effects of Cinnarizine: IV therapy is instituted.
Perampanel, Sodium oxybate, Tapentadol, Thalidomide
(CNS depression)

534
NERVOUS SYSTEM
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Protect from light. Store in carton
until time of use.
Adverse Drug Reactions:
Angina pectoris, bradycardia, cardiac arrhythmia,
hypertension, palpitations, pulse irregularity,
tachycardia, ventricular ectopy, visceral vasoconstriction
(renal), anxiety, confusion, delirium, dizziness,
hallucination, headache, insomnia, intracranial
hemorrhage, nervousness, precordial pain, restlessness,
tension, vertigo, diaphoresis, pallor, anorexia, nausea,
vomiting, dysuria, oliguria, urinary retention (males with
prostatism), tremor, vesicle sphincter spasm, weakness,
dyspnea, tachyphylaxis
Drug Interactions:
Monitor closely with:
May decrease therapeutic effect of the following drugs:
Alpha1-blockers (vasoconstricting effect), Iobenguane
I123, Quinidine
May increase the therapeutic effect (hypertensive effect) of
ephedrine
Atomoxetine, Atropine (systemic), Beta-blockers e.g.,
Metoprolol Chloroprocaine, Clonidine, Guanethidine,
Linezolid, Tedizolid, MAOi e.g., Phenelzine, Oxytocin,
Propofol, Ergot derivatives, SNRIs e.g., Duloxetine, TCA
e.g., Amytryptilline
May diminish the therapeutic effect of ephedrine:
Clozapine, Quinidine, Spironolactone
May enhance the adverse/toxic effect of Doxofylline
May enhance the effect of the following drugs:
Droxidopa, Rocuronium
May enhance the adverse/toxic effect of Ephedrine:
Guanethidine, Inhalational anesthetics (arrythmogenic
effects)
Other sympathomimetics
Avoid concomitant use with:
May enhance the adverse/toxic effect of Ephedrine:
Cyclopropane, Halothane (arrythmogenic effects)
Administration: Administer diluted solution as a slow IV
push.
Pregnancy Category: Category C
ATC Code: Not available
Rx ESMOLOL
Inj.: 10 mg/mL (as hydrochloride), 10 mL vial (IV)
100 mg/mL (as hydrochloride), 10 mL vial (IV)
Indications: Intraoperative and postoperative tachycardia
and/or hypertension
Contraindications: Severe sinus bradycardia; heart block
greater than first degree (except in patients with a
functioning artificial ventricular pacemaker); sick sinus
syndrome; cardiogenic shock; decompensated heart
failure; IV administration of calcium channel blockers
(e.g. verapamil) in close proximity to esmolol (i.e. while
effects of other drug are still present); pulmonary
hypertension; patients requiring inotropic agents and/or
vasopressors to maintain cardiac output and systolic
blood pressure; hypotension; right ventricular failure
secondary to pulmonary hypertension; untreated
pheochromocytoma; hypersensitivity to esmolol or any
component of the formulation
Dose:
Intraoperative and postoperative tachycardia and/or
hypertension, by intravenous bolus and intravenous
infusion. ADULT, immediate control: initial bolus of 1000
mcg/kg over 30 seconds, followed by a 150
mcg/kg/minute infusion, if necessary. Adjust infusion
rate as needed to maintain desired heart rate and/or
blood pressure (up to 300 mcg/kg/minute). Gradual
control: Initial bolus of 500 mcg/kg over 1 minute,
followed by a 50 mcg/kg/minute infusion for 4 minutes.
Infusion may be continued at 50 mcg/kg/minute or, if
the response is inadequate, titrated upward in 50
mcg/kg/minute increments (increased no more
frequently than every 4 minutes) to a maximum of 300
N
mcg/kg/minute; may administer an optional loading
dose equal to the initial bolus (500 mcg/kg over 1
minute) prior to each increase in infusion rate.
Dose Adjustment:
Geriatric:
No dose adjustment necessary.
Renal Impairment:
No dose adjustment necessary; not removed by hemo- or
peritoneal dialysis. Supplemental dose is not necessary.
Hepatic Impairment:
No dose adjustment necessary.
Precautions:
If hyperthyroidism is suspected, carefully manage
and monitor; abrupt withdrawal may exacerbate
symptoms of hyperthyroidism or precipitate
thyroid storm.
Calcium channel blockers are contraindicated when
IV calcium channel blockers have been
administered in close proximity to esmolol
Beta-blocker therapy should not be withdrawn
abruptly. Gradually taper the dose to prevent
exacerbation of withdrawal symptoms.
Concerns related to adverse effects:
Hyperkalemia (monitor serum potassium during
therapy), Hypotension (Close blood pressure monitoring
needed. If an unacceptable drop in blood pressure
occurs, reduction in dose or discontinuation may reverse
hypotension (usually within 30 minutes)).
Use with caution in:
History of severe anaphylaxis to allergens;
Bronchospastic disease; Conduction abnormality;
535

Diabetes; Heart failure; Myasthenia gravis; Peripheral
vascular disease (PVD) and Raynaud's disease;
Untreated pheochromocytoma (Adequate alpha-
blockade is required prior to use of any beta-blocker.)
Renal impairment (monitor serum potassium), Thyroid
disease (If hyperthyroidism is suspected, carefully
manage and monitor; abrupt withdrawal may exacerbate
symptoms of hyperthyroidism or precipitate thyroid
storm.); Hypertension associated with hypothermia
(monitor vital signs closely and titrate esmolol slowly),
Hypovolemic patients (Avoid use; treat hypovolemia
first).
Elderly (Bradycardia may be observed more frequently in
elderly patients (>65 years of age); dosage reductions
may be necessary.
STORAGE AND STABILITY: Store at 20-25°C. Excursions
permitted to 15-30°C. Avoid excessive heat. Protect
from freezing.
Adverse Drug Reactions:
Common: Decreased blood pressure, asymptomatic
hypotension, symptomatic hypotension, peripheral
ischemia, dizziness, drowsiness, agitation, confusion,
headache, nausea, vomiting, infusion site reaction
Rare: Abdominal distress, abnormality in thinking,
angioedema, anorexia, anxiety, asystole (rare),
N
bradycardia, bronchospasm, cardiac failure
(decompensated), constipation, coronary artery
vasospasm, depression, dizziness, dyspepsia, flushing,
heart block, hyperkalemia, pallor, paresthesia, psoriasis,
renal tubular acidosis, seizure, severe bradycardia (rare),
syncope, urinary retention, urticaria, xerostomia
Drug Interactions:
Monitor closely with:
Enhance effects of Esmolol:
Acetylcholinesterase inhibitors, Amiodarone,
Anilidopiperidine opiods, Bretylium, Dipyridamole,
Disopyramide, Regorafenib (bradycardic effect)
Antihypertensives, Antipsychotic agents, Barbiturates,
Calcium channel blockers, Non- dihydropyridine [except
Bepridil], Diazoxide, Ivabradine, Molsidomine,
Nicorandil, Nifedipine, Pentoxifylline, Prostacyclin
analogues, Reserpine (hypotensive effect)
Bretylium, Lacosamide (AV blocking effect)
Brimonidine, Topical, Phosphodiesterase 5 inhibitors
(antihypertensive effect)
Duloxetine, Levodopa, MAO Inhibitors [except Linezolid,
Tedizolid] (orthostatic hypotensive effect)
Nifedipine (negative inotropic effect)
Enhances effects of the following:
Disopyramide (negative inotropic effect)
Fingolimod, Midodrine (bradycardic effect)
Insulin, Sulfonylureas (hypoglycemic effect)
Risperidone, Tofacitinib (hypotensive effect)
Enhance the adverse effects of the following:
Cholinergic agonists (bronchoconstriction)
Reduces therapeutic effect of Esmolol:
Herbs, Hypertensive properties
Methylphenidate
Non- steroidal anti- inflammatory agents
536
NERVOUS SYSTEM
Yohimbine
Reduces therapeutic effect of the following:
Theophylline derivatives (bronchodilatory effect)
Decreases the metabolism of Esmolol:
Aminoquinolines, Anti-malarial
Avoid concomitant use with:
Increases serum concentration of Esmolol:
Dronedarone
Enhance the effects of the following medicines:
Alpha/Beta Agonists, Direct- acting [except Dipivefrin]
(vasopressor effect)
Alpha- 1 blockers (orthostatic hypotension)
Amifostine, Obinituzumab, Rituximab (hypotensive
effect)
Ceritinib (bradycardic effect)
Ergot derivatives (vasoconstricting effect)
Enhance the effect of Esmolol:
Alpha- 2 agonists [except Apraclonidine] (AV blocking
effect)
Dronedarone, Rivastigmine (bradycardic effect)
Enhance adverse effects of the following:
Floctafenine
Grass pollen allergen extract, 5 grass extract
Methacholine
Administration: Loading doses may be administered over 30
seconds to 1 minute depending on how urgent the need
for effect. Infusion into small veins or through a butterfly
catheter should be avoided (can cause
thrombophlebitis). Medication port of premixed bags
should be used to withdraw only the initial bolus, if
necessary (not to be used for withdrawal of additional
bolus doses). Ensure proper needle or catheter
placement prior to and during infusion; avoid
extravasation. If extravasation occurs, stop infusion
immediately and disconnect (leave cannula/needle in
place); gently aspirate extravasated solution (do NOT
flush the line); remove needle/cannula; elevate
extremity.
Pregnancy Category: Category C
ATC Code: Not available
NERVOUS SYSTEM
DRUGS TO REDUCE CEREBRAL EDEMA
Rx DEXAMETHASONE
Oral: 500 micrograms, 750 micrograms, 3 mg, and 4 mg
tablet
Inj.: 4 mg/mL (as sodium phosphate), 1 mL and 2 mL
ampule / vial (IM, IV)
5 mg/mL (as sodium phosphate), 1 mL ampule (IM,
IV)
Crosses cell membranes and binds with glucocorticoid
receptors, then bind to DNA glucocorticoid response
elements that in turn modify the protein synthesis
required for inflammation
Indications: Cerebral edema associated with brain tumor or
craniotomy
Contraindications: Systemic fungal infections
Dose:
Cerebral edema associated with brain tumor or craniotomy,
by mouth or by intramuscular injection or by intravenous
infusion, ADULT, 10 mg intravenously immediately,
followed by 4 mg intramuscularly every 6 hours until
cerebral edema subsides, then switch to oral regimen.
Dosage may be reduced after 2-4 days and gradually
discontinued over 5-7 days, CHILD, initially administer a
loading dose of 1-2 mg/kg/dose as a single dose. The
maintenance dose is 1-1.5 mg/kg/day in divided doses
every 4-6 hours up to a maximum dose of 16 mg/day.
Dose Adjustment:
Geriatric:
Use with caution and with the smallest possible dose.
Renal Impairment:
Use with caution; Supplemental doses are not necessary for
patients undergoing hemodialysis or peritoneal dialysis.
Hepatic Impairment:
No dose adjustment necessary.
Precautions:
Withdrawal and discontinuation of a corticosteroid
should be done slowly and carefully. Particular
care is required when patients are transferred
from systemic corticosteroids to inhaled products
due to possible adrenal insufficiency or
withdrawal from steroids, including an increase in
allergic symptoms.
Corticosteroids should not be used for cerebral
malaria, fungal infections, or viral hepatitis. Close
observation is required in patients with latent
tuberculosis and/or TB reactivity; restrict use in
active TB
Amebiasis should be ruled out in any patient with
recent travel to tropic climates or unexplained
diarrhea prior to initiation of corticosteroids. Use
with extreme caution in patients with
Strongyloides infections
Corticosteroid use may cause psychiatric
disturbances, including depression, euphoria,
insomnia, mood swings, personality changes,
severe depression to psychotic manifestations.
Preexisting psychiatric conditions may be
exacerbated by corticosteroid use.
Long term use may lead to water retention, increased
bone loss, osteoporotic fractures
Immunosuppressants may diminish the diagnostic
effect of Coccidioides immitis skin test
Administration: Tablets should be taken with food. Ampules
are administered via intramuscular injection or
intravenous infusion.
See Dexamethasone under Glucocorticoids in Chapter 6:
Systemic Hormonal Preparation for other information.
Pregnancy Category: Category C
ATC Code: Not available
Rx GLYCEROL (GLYCERIN)
Oral: USP grade (liquid)
N
Elevates blood plasma osmolality, resulting in enhanced
flow of water from extravascular spaces into plasma.
Reduction of intracranial pressure is attributed to the
establishment of an osmotic gradient between blood,
cerebrospinal fluid (CSF), and brain, resulting in
withdrawal of fluid from the brain and CSF
Indications: Management of cerebral edema
Contraindications: Acute abdominal pain
Dose:
Cerebral edema, by mouth, ADULT, 1-1.5 g/kg as a single
dose. Initial doses up to 2 g/kg have been used.
Additional doses of 500 mg/kg may be administered at
approximately 6-hour intervals, if necessary, CHILD, 1-
1.5 g/kg or 40 g/m2 as a single dose. Dose may be
repeated in 4-8 hours, if necessary.
Precautions:
Use with caution in:
Diabetes mellitus, type II (may increase risk of dehydration);
Confused mental states; heart disease; Kidney disease,
Hypervolemia (circulatory overload).
Pregnancy and lactation (no adequate studies in women for
determining infant risk).
Adverse Drug Reactions:
Common: Headache, nausea, vomiting.
Less Common: Confusion, diarrhea, dizziness, dryness of
mouth, increased thirst
Rare: Arrhythmias
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Glycerol:
537

Tetracyclines
Avoid concomitant use with:
Enhances therapeutic effect of Glycerol:
ACE inhibitors e.g. Enalapril (additive effect),
Acetazolamide, Bumetanide (potentiated effect), Other
Diuretics
Enhances therapeutic effect of Diuretics (potentiated
effect)
Increases risk of adverse or toxic effects of Glycerol:
ACE inhibitors (hypovolemia)
Acetazolamide, Bumetanide, Other diuretics (significant
loss of fluid and electrolytes), Carbamazepine
(hyponatremia), Drugs that prolong QT Interval
(electrolyte loss)
Increases risk of adverse or toxic effects of the following
drugs:
ACE inhibitors e.g. Enalapril (hypotension),
Corticosteroids (significant loss of electrolytes;
hypokalemia), Digoxin (arrhythmias), QT prolonging
drugs (torsade de pointes), Ondansetron (irregular heart
rhythm)
Administration: For use as an oral demulcent. Do NOT
swallow excessive amounts.
N
Mix it with a small amount of unsweetened lemon, lime,
or orange juice, pour over cracked ice, and sip through a
straw to mask its unpleasant taste. Lie down when taking
this medicine and for a short time after taking it to
prevent or relieve headaches.
NOTE: When used preoperatively, administer 60–90
minutes prior to surgery. Precautions should be taken to
avoid acute urinary retention.
Pregnancy Category: C
ATC Code: Not available
Rx MANNITOL
Inj.: 20%, 250 mL and 500 mL bottle (IV)
Mannitol is a naturally-occurring sugar alcohol. It reduces
ICP by reducing blood viscosity which transiently
increases cerebral blood flow and oxygen transport and
constricts pial arterioles which in turn reduces cerebral
blood volume and ICP and withdraws water from the
brain parenchyma and excretes water in the urine.
Indications: Reduction of intracranial pressure associated
with cerebral edema
Contraindications: Severe renal disease (anuria); severe
dehydration; active intracranial bleeding except during
craniotomy; progressive heart failure, pulmonary
congestion, or renal dysfunction after mannitol
administration; severe pulmonary edema or congestion
538
NERVOUS SYSTEM
Dose:
Intracranial pressure (ICP), reduction, by intravenous
infusion, ADULT, 0.25 to 2 g/kg as a 15-20% solution
over at least 30 min administered not more frequently
than every 6-8 hours, INFANT, CHILD, AND ADOLESCENT,
the usual range is 0.25-1 g/kg/dose infused over 20-30
minutes. Repeat as needed to maintain serum osmolality
<300 to 320 mOsm/kg. The manufacturer's labeling
allows for higher single doses up to 2 g/kg/dose.
Dose Adjustment:
Geriatric:
Consider initiation at lower end of dosing range.
Renal Impairment:
Contraindicated in severe renal impairment. Use caution in
patients with underlying renal disease. May be used to
reduce the incidence of acute tubular necrosis when
administered prior to revascularization during kidney
transplantation.
Precautions:
Fluid/electrolyte loss (Watch for and correct electrolyte
disturbance; adjust dose to avoid dehydration);
Nephrotoxicity;
Cerebral edema (rebound increases in intracranial
pressure);
Adequate renal function.
NOTE: Should not be administered until adequacy of renal
function and urine flow is established; use 1 to 2 test
doses to assess renal response.
Adverse Drug Reactions:
Chest pain, cardiac failure, hypertension, hypotension,
local thrombophlebitis, peripheral edema, tachycardia,
chills, dizziness, headache, seizure, bullous rash,
urticaria, dehydration (secondary to rapid diuresis),
dilutional hyponatremia, electrolyte disturbance
(increased osmolar gap), fluid and electrolyte
disturbance, hypovolemia (secondary to rapid diuresis),
hyperglycemia, hyperkalemia (hyperosmolality-induced),
hypernatremia, hypervolemia, metabolic acidosis
(dilutional), water intoxication, nausea, vomiting,
xerostomia, dysuria, hypersensitivity reaction, local pain,
blurred vision, acute renal failure, tubular necrosis (adult
dose: >200 g/day; serum osmolality >320 mOsm/L),
polyuria, pulmonary edema, rhinitis, fever, tissue
necrosis.
Drug Interactions:
Monitor closely with:
Aminoglycosides – mannitol (systemic) may enhance the
nephrotoxic effect of aminoglycosides.
Diacerein – may enhance the therapeutic effect of diuretics;
specifically, the risk for dehydration or hypokalemia may
be increased.
Opioid analgesics – may enhance the adverse/toxic effect
and diminish the therapeutic effect of diuretics.
Sodium phosphates – diuretics may enhance the
nephrotoxic effect of sodium phosphates; specifically,
the risk of acute phosphate nephropathy may be
enhanced.
Tobramycin (oral inhalation) – mannitol (systemic) may
enhance the nephrotoxic effect of tobramycin (oral
inhalation).
NERVOUS SYSTEM

Administration: Concentration and rate of administration

depends on indication/severity or may be adjusted to
urine flow. For cerebral edema or elevated ICP,
administer over 30-60 minutes. Inspect for crystals prior
to administration. If crystals are present, redissolve by
warming solution. Use filter-type administration set (≤5
micron) for infusion solutions containing mannitol ≥20%
(WHO 2011). Do not administer with blood. Crenation
and agglutination of red blood cells may occur if
administered with whole blood. Mannitol may act as a
vesicant at concentrations >5%. Ensure proper catheter
or needle position prior to and during IV infusion. Avoid
extravasation of IV infusions. If extravasation occurs,
stop infusion immediately and disconnect (leave
needle/cannula in place). Gently aspirate extravasated
solution (do NOT flush the line), initiate hyaluronidase
antidote, remove needle/cannula, apply dry cold
compresses, and elevate extremity.

See drug name under category name in Chapter number:

chapter title for other information.

Pregnancy Category: Category C

539
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

inadequate for reliable protection against malaria in the

ANTIPARASITIC PRODUCTS, breastfed infant; avoid breastfeeding when used for
INSECTICIDES, AND REPELLENTS rheumatic disease).

NOTE: If patient continues to deteriorate after chloroquine

ANTIPROTOZOALS medication – suspect resistance and administer quinine
IV as emergency measure.

AGENTS AGAINST AMOEBIASIS AND Adverse Drug Reactions:

OTHER PROTOZOAL DISEASES Common: GI disturbances, itch, lack of appetite, pruritus,
skin eruptions, weight loss
Less Common: Anxiety, confusion, dizziness, drowsiness,
Rx/OTC CHLOROQUINE headache, hypotension, irreversible retinopathy,
paresthesia, personality changes, psychotic episodes,
reversible corneal opacities, sleep disorders, vertigo,
Oral: 250 mg tablet (as phosphate or diphosphate) (150 visual disturbances
mg base) Rare: Hypersensitivity reactions, pancytopenia, porphyria,
Inj.: 50 mg/mL (as phosphate or diphosphate), 20 mL vial prolonged QT interval, psoriasis, neuromyopathy,
(IM, IV) seizure, rash, Steven-Johnsons Syndrome,
thrombocytopenia, tinnitus, toxic epidermal necrolysis,
An aminoquinoline antimalarial, found effective in extra CV collapse (potentially fatal); convulsions (potentially
intestinal amoebiasis fatal); coma (potentially fatal)
Indication: Treatment of extraintestinal amoebiasis Drug Interactions:
NOTE: Chloroquine has a long half-life; consequently, the
Contraindications: Presence of retinal or visual field potential for drug interactions may persist for weeks
changes either attributable to 4­aminoquinoline after it has been stopped.
compounds or to any other etiology; patients with
epilepsy Monitor closely with:
Reduces the absorption of Chloroquine: Antacids (e.g.
Dose: Aluminum or Magnesium Hydroxide)
P

Extraintestinal amoebiasis, by mouth, ADULT, 1 g (600 mg

base) on day 1, followed by 500 mg (300 mg base) after Avoid concomitant use with:
6 hours, 24 hours, and 48 hours following first dose, may Increases risk of adverse or toxic effects of the following
be combined with an intestinal amebicide. drugs:
Hepatic amoebiasis, by mouth, ADULT, 600 mg (as base) Artemether + Lumefantrine (potentially hazardous
daily for 2 days, then 300 mg daily for 2 or 3 weeks given interactions), Drugs which prolong QT Interval
with emetine or dehydroemetine; CHILD, up to 3 mg/kg (arrhythmia; prolonged QT interval), Other Antimalarials
daily (maximum daily dose, 300 mg). e.g. Mefloquine (arrhythmia; prolonged QT interval)
Dose Adjustment: Administration: To avoid nausea and vomiting, tablets
Renal Impairment: should be administered after meals.
For mild-to-moderate renal impairment, dose reduction is
warranted. NOTE: If part or all of a dose is vomited, re-administer the
For severe impairment, the patient should be referred to a same amount.
specialist.
Pregnancy Category: C
Precautions:
G6PD deficiency; Psoriasis may be worsened. ATC Code: P01BA01
Porphyria cutanea tarda
Epilepsy; May aggravate myasthenia gravis; neurological
disorders.
QT interval Rx DILOXANIDE
Renal impairment; hepatic impairment (avoid concurrent
therapy with hepatotoxic drugs); severe GI disorders.
Oral: 500 mg tablet (as furoate)
Pregnancy (in the first trimester of pregnancy, quinine in
125 mg/5 mL syrup / suspension (as furoate), 30 mL
combination with clindamycin for 7 days is the treatment
and 60 mL
of choice – this combination can be used throughout
pregnancy; in acute malaria and third trimester: benefit
A dichloroacetamide-derived luminal amoebicide acting
of prophylaxis and treatment outweighs risk).
mainly in the bowel lumen. It is given alone in
asymptomatic cyst passers. For patients with active
NOTE: If clindamycin is not available, then quinine should be
amoebic infections, it can be administered with a 5-
given as monotherapy.
nitroimidazole e.g. metronidazole or tinidazole.
Breastfeeding (at doses used for malaria prophylaxis;
amount in milk is probably too small to be harmful, and

540
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Indications: Second line agent for luminal infection;
amebicide; intestinal amoebiasis; for hepatic abscess
secondary to E. histolytica
Dose:
Asymptomatic and symptomatic amoebiasis, by mouth,
ADULT, 500 mg 3 times daily for 10 days (may repeat
course if needed), CHILD, 20 mg/kg daily in 3 divided
doses for 10 days (may repeat if necessary).
Dose Adjustment: No information found
Precautions:
Pregnancy and lactation (use with caution).
Adverse Drug Reactions:
Common: Flatulence
Less Common: Vomiting, pruritus, urticaria, anorexia
Liver abscess with positive amoeba serology, by mouth or
IV, ADULT, 750 mg 3 times daily for 10 days.
Trichomoniasis, first-line, by mouth, ADULT (women and
pregnant women), 2 g single dose; ADULT (women with
HIV infection), 500 mg 2 times daily for 7 days.
Trichomoniasis, second-line, by mouth, ADULT, 500 mg 2
times daily for 7 days.
Administration:
For Oral: Tablets should be swallowed whole with water,
during or after a meal; oral suspension should be taken
one hour before a meal or on an empty stomach.
For IV: Infuse intravenously over 30 to 60 minutes; Avoid
contact of drug solution with equipment containing
aluminum.
See Metronidazole under Chapter 7: Anti-Infectives under
other Antibacterials or other information

Drug Interactions: No information found Pregnancy Category: B

Administration: Swallow with water. ATC Code: P01AB01

Do NOT break, crush, or chew tablets.

ANTIMALARIALS
Pregnancy Category: Not classified
ARTEMETHER + LUMEFANTRINE
ATC Code: P01AC01 Rx
(AL)
Oral: 20 mg artemether + 120 mg lumefantrine per tablet

P
Rx METRONIDAZOLE
A fixed-dose, antimalarial combination of an oil-soluble,
artemisinin analog and a fluorene-derived aryl alcohol
Oral: 250 mg and 500 mg tablet (as base)
that is used for uncomplicated P. falciparum malaria.
125 mg base/5 mL (200 mg/5 mL (as benzoate)
suspension, 60 mL Indication: For acute, uncomplicated malaria caused by P.
5 mg/mL, 100 mL vial (IV infusion) falciparum, P. malariae, or P. knowlesi alone or with
Plasmodium spp. in areas with significant drug
A nitroimidazole, antiprotozoal drug, which has potent resistance; 2nd line drug for uncomplicated P. vivax or P.
antibacterial activity against anaerobes, including ovale infections.
Bacteroides and Clostridium spp.
Contraindications: Family history of sudden death or
Indications: Management of acute invasive amebic congenital prolongation of QT interval; history of
dysentery; trichomonal vaginitis; amoebiasis; giardiasis arrhythmias, clinically-relevant bradycardia, or CHF
accompanied by reduced left ventricular ejection
Contraindications: Chronic alcohol dependence
fraction; pregnancy (first trimester); breastfeeding
(during and for 1 week after stopping treatment; present
Dose:
in milk in animal studies)
Amoebiasis, by mouth, ADULT, 35–50 mg/kg per day in 3
divided doses for 7–10 days or 800 mg 3 times daily for Dose:
5 days (intestinal infection); 5–10 days (extra-intestinal Uncomplicated malaria due to P. falciparum or P. malariae
infection), (maximum, 2.4 g daily); CHILD 35 – 50 mg/ (in combination with primaquine tablet, 15 mg (0.24 mg
kg per day in 3 divided doses for 7 – 10 days. base per kg) on day 1; 3 tablets for adults >60 kg), by
Giardiasis, by mouth, ADULT, 15 mg/kg per day in 3 divided mouth,
doses for 5–7 days or 2 g once daily for 3 days, 400 mg
3 times daily for 5 days, or 500 mg twice daily for 7–10
days; CHILD 1–3 years, 500 mg once daily; CHILD 3–7 DAY 1 DAY 2 DAY 3
years, 600–800 mg once daily; CHILD 7–10 years, 1 g ADULT and 4 tablets followed
once daily; doses are given for 3 days. 4 tablets 2 times a
CHILD >35 by 4 tablets after 8
Suspected antibiotic-associated colitis presenting as severe day
kg hours
disease or with prolonged symptoms, by mouth, ADULT
and CHILD, 30 mg/kg per day in 4 divided doses for 10– 3 tablets followed
CHILD 25 3 tablets 2 times a
14 days. by 3 tablets after 8
to <35 kg day
Severe diarrhea due to Entamoeba histolytica, by mouth, hours
ADULT, 500–750 mg 3 times a day for 7–10 days.

541
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

2 tablets followed SKILLED TASKS. May cause dizziness. Avoid performing

CHILD 15 2 tablets 2 times a tasks, which require mental alertness, e.g., operating
by 2 tablets after 8
to <25 kg day machinery or driving.
hours
CHILD 5 to
<15 kg 1 tablet followed Adverse Drug Reactions:
1 tablet 2 times a Common: Abdominal pain, anorexia, arthralgia, asthenia,
and by 1 tablet after 8
day cough, diarrhea, dizziness, fatigue, headache, itch,
INFANT 6– hours
11 months myalgia, nausea, palpitations, prolonged QT interval,
pruritus, pyrexia, rash, sleep disorder, vomiting,
weakness
Uncomplicated malaria due to P. vivax or P. ovale (in
Less Common: Ataxia, clonus, hypesthesia, paresthesia
combination with primaquine tablet, 0.25 mg base per
Rare: Hepatitis, hypersensitivity reactions
kg starting on day 1), or Malaria due to P.
knowlesi (alone), plus primaquine tablet 0.25mg base
Drug Interactions:
per kg on day 1-14, by mouth,
Monitor closely with:
DAY 1 DAY 2 DAY 3 Increases risk of adverse or toxic effects
4 tablets followed Drugs which prolong QT Interval (arrhythmia), Other
4 tablets 2 times a Antimalarials (arrhythmia)
ADULT by 4 tablets after
day
8 hours
Reduces therapeutic effect of Hormonal Contraceptives
3 tablets followed
CHILD 25 3 tablets 2 times a
by 3 tablets after
to <35 kg day Avoid concomitant use with:
8 hours
Reduces therapeutic effect of Artemether + Lumefantrine:
2 tablets followed
CHILD 15 2 tablets 2 times a CYP3A4 Inducers (potential loss of antimalarial efficacy)
by 2 tablets after
to <25 kg day
8 hours
Increases risk of adverse or toxic effects of CYP2D6
CHILD 5 to Substrates (QT prolongation)
<15 kg 1 tablet followed
1 tablet 2 times a
and by 1 tablet after 8 Administration: Take the tablets with food or high-fat meal
day
INFANT 6– hours to increase absorption.
11 months
P

NOTE: If patient vomits out the dose within 1 to 2 hours, give

Mixed malarial infection due to P. falciparum and P. vivax another dose.
with or without P. malariae (in combination with
primaquine tablet, 0.25 mg base per kg on day 1–14), Pregnancy Category: C
by mouth,
DAY 1 DAY 2 DAY 3 ATC Code: P01BF01
4 tablets followed
4 tablets 2 times a
ADULT by 4 tablets after
day
8 hours Rx ARTESUNATE
3 tablets followed
CHILD 25 3 tablets 2 times a
by 3 tablets after
to <35 kg day Inj.: 60 mL vial
8 hours Rectal: 50 mg suppository
2 tablets followed
CHILD 15 2 tablets 2 times a
by 2 tablets after A potent artemisinin-derived, rapidly-acting blood
to <25 kg day
8 hours schizontocide effective against P. vivax and P. falciparum
1 tablet followed malaria.
CHILD 5 to 1 tablet 2 times a
by 1 tablet after 8
<15 kg day
hours Indication: For use by the National Malaria Program as pre-
referral drug for managing severe malaria cases both
Dose Adjustment: within the highly endemic and at-risk areas of the country
Renal and Impairment:
For mild-to-moderate impairment, use same dosage as in Dose:
patients with normal function. Severe malaria due to P. falciparum or P. malariae, by IV or
For severe impairment, refer patient to a specialist. IM injection, ADULT, 2.4 mg/kg per dose; give 3 IV or IM
doses 12 hours apart (shift to oral artemether-
Precautions: lumefantrine and primaquine once patient can tolerate;
Concomitant administration of drugs that prolong the QT by IV drip or IM injection into the anterior thigh, CHILD
interval; Acute porphyria and severe and/or complicated <20 kg, 3 mg/kg per dose, dissolved in 5% NaHCO3,
malaria (avoid use); Electrolyte disturbances; monitor diluted in 5 mL D5W.
patients unable to take; severe renal and hepatic Severe malaria due to P. falciparum or P. malariae, second-
impairment (monitor ECG and plasma potassium line (for pre-referral to hospital), by rectum, CHILD, 10
concentration) mg/kg
Pregnancy (avoid use in first trimester); lactation. Severe malaria due to P. vivax or P. ovale, first-line /
preferred treatment, by IV or IM injection, ADULT, 2.4

542
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
mg/kg per dose for at least 24 hours (shift to oral
artemether-lumefantrine once patient can tolerate; by IV
drip or IM injection into the anterior thigh, CHILD <20 kg,
3 mg/kg per dose, dissolved in 5% NaHCO3, diluted in 5
mL D5W.
NOTE: Artesunate suppository is a last-resort drug
NOT recommended for older children and adults.
Precautions:
Hepatic and renal impairment.
Pregnancy and lactation (use with caution)
Adverse Drug Reactions:
Common and Less Common: Drug fever, transient
reticulocytopaenia (reversible), bradycardia, rash,
transient first-degree heart block.
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Artesunate:
Chloroquine, Mefloquine, Primaquine, Tetracycline
Reduces therapeutic effect of Artesunate:
Pyrimethamine, Sulfonamides
Administration: When administering the rectal suppository,
wash hands thoroughly. You may use a disposable glove
if desired. Remove the wrapper prior to insertion. Lie on
your side with the lower leg straightened out and the
upper leg bent towards the torso. Lift the upper buttock
to expose rectal area. Insert the suppository, pointed end
first with your finger until it passes the muscular
sphincter of the rectum. Hold buttocks together for a few
seconds. Remain lying on your side for at least 5
minutes. Discard all used materials and wash hands
thoroughly.
Pregnancy Category: Not classified
ATC Code: P01BE03
Rx CHLOROQUINE
Oral: 250 mg tablet (as phosphate or diphosphate) (150
mg base)
Inj.: 50 mg/mL (as phosphate or diphosphate), 20 mL vial
(IM, IV)
An aminoquinoline antimalarial, which has rapid
schizontocidal activity against blood forms of
Plasmodium ovale and P. malariae, and against
susceptible strains of P. vivax and P. falciparum. It
influences hemoglobin digestion by increasing
intravesicular pH in malaria parasite cells and interferes
with the nucleoprotein synthesis of the patient.
Indications: Prophylaxis of malaria; treatment of non-
chloroquine-resistant acute malaria caused by P. vivax
and P. ovale (followed in P. vivax and P. ovale infections
by primaquine to eliminate intrahepatic forms).
Contraindications: In patients with history of epilepsy;
retinal damage or impaired visual field
Dose:
Prophylaxis of malaria, by mouth, ADULT, 300 mg as base,
once weekly, starting 1 week before exposure,
continuing throughout on a weekly basis and for at least
4 weeks after exposure; CHILD, 5 mg/kg weekly.
Uncomplicated malaria due to P. vivax or P. ovale, by mouth,
ADULT, initially 600 mg as base, followed by 300 mg 6–
8 hours later on day 1, then single doses of 300 mg daily
on days 2 and 3; CHILD, initially 10 mg base/kg
(maximum 600 mg base), followed by 5 mg base/kg after
6 hours (maximum 300 mg base), then single doses of 5
mg base/kg on days 2 and 3.
Congenital and neonatal malaria, by mouth, CHILD, 10
mg/kg on day 1 and 2, and 5 mg/kg on day 3.
Relapse malaria, by mouth, ADULT and CHILD, 10 mg/kg on
day 1 and 2, and 5 mg/kg on day 3.
Mixed malarial infection due to P. vivax and P. malariae, by
mouth, ADULT and CHILD, 10 mg/kg on day 1 and 2, and
5 mg/kg on day 3 (in combination with primaquine 0.25
mg (as base) per kg per day taken as a single dose for
day 1 to 14).
Administration: Administer tablets after meals to avoid
nausea and vomiting.
NOTE: If part or all of a dose is vomited, the same amount
should be re-administered.
See Chloroquine under Antiprotozoals – Agents against
ameobiasis and other protozoal diseases in this chapter
for other information.
P
Pregnancy Category: C
ATC Code: P01BA01
Rx MEFLOQUINE
Oral: 250 mg tablet (as hydrochloride)
A quinoline-methanol compound structurally similar to
quinine, capable of destroying the asexual blood forms
of Plasmodium falciparum and P. vivax.
Indication: Prophylaxis for chloroquine resistant malaria
NOTE: Not recommended for treatment of malaria acquired
in Southeast Asia due to drug resistance
Contraindications: Prophylactic use in patients with a history
of seizures or psychiatric disorder including active or
recent history of depression, generalized anxiety
disorder, psychosis, schizophrenia, or other major
psychiatric disorders; hypersensitivity to mefloquine,
related compounds, e.g., quinine and quinidine, or any
component of the formulation
Dose:
Malaria, chemoprophylaxis, by mouth, ADULT, 250 mg
weekly starting 1 week before arrival in endemic area,
continue weekly during travel and for 4 weeks after
leaving endemic area; CHILD, 5 mg/kg per dose weekly
starting 1 week before arrival in endemic area, continue
weekly during travel and for 4 weeks after leaving
543
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
endemic area [NOTE: Prophylaxis may begin 2­3 weeks
prior to travel to ensure tolerance].
Precautions:
Agranulocytosis or aplastic anemia; Cardiovascular disease
(use with caution); Hypersensitivity reactions;
Neuropsychiatric effects (e.g. anxiety, paranoia,
depression, hallucinations, and psychosis may develop
early during therapy; suicidal ideation and suicide have
been reported; dizziness or vertigo, tinnitus, and loss of
balance); Seizure disorder; Hepatic impairment (use with
caution)
Children (early vomiting leading to treatment failure has
been reported; consider alternate therapy if a second
dose is not tolerated).
Pregnancy (crosses the placenta); lactation (excreted in
breast milk in small quantities).
SKILLED TASKS. May cause drowsiness or blurred vision.
Avoid performing tasks, which require mental alertness,
e.g., operating machinery or driving. Warn patient not to
operate machinery nor drive during treatment or for 24
hours after treatment.
Adverse Drug Reactions:
Common: Chills, dizziness, fatigue, fever, headache, rash,
vomiting, abdominal pain, decreased appetite, diarrhea,
nausea, myalgia, tinnitus
Less Common: Alopecia, bradycardia, emotional lability,
extra-systoles, pruritus, seizure, syncope, weakness,
abnormal dreams, abnormal T-waves, ataxia, aggressive
P
behavior, agitation, anxiety, arrhythmia, arthralgia, AV
block, cardiac arrest (with concomitant use of
propranolol), chest pain, conduction abnormalities
(transient), confusion, depression, diaphoresis
increased, dyspepsia, dyspnea, edema, encephalopathy,
erythema, erythema multiforme, exanthema, flushing,
forgetfulness, hallucinations, hearing impairment,
hematocrit decreased, hypertension, hypotension,
insomnia, irregular pulse, leukocytosis, leukopenia,
increased liver function tests, loss of balance, malaise,
mood changes, muscle cramps/weakness, palpitation,
panic attacks, paranoia, paresthesia, pneumonitis
(allergic etiology), psychosis, QT prolongation,
restlessness, somnolence, Stevens-Johnson syndrome,
suicidal ideation and behavior (causal relationship not
established), tachycardia, thrombocytopenia, tremor,
urticaria, vertigo, visual disturbances
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Mefloquine:
Amiodaquine (vision problems)
Increases risk of adverse or toxic effects of QTc-prolonging
agents (QTc-prolonging effect)
Avoid concomitant use with:
Decreases serum concentration of Mefloquine:
Dabrafenib, Mitotane,
Decreases serum concentration of Anticonvulsants e.g.
Phenytoin, Barbiturates
Increases risk of adverse or toxic effects of Mefloquine:
544
Antimalarial Aminoquinolines e.g. Chloroquine (QTc-
prolongation; convulsions) [if concomitant use cannot be
avoided, delay Mefloquine administration at least 12
hours after the last dose of aminoquinoline antimalarial]
Artemether, Dapsone (hemolytic reactions),
Lumefantrine, Quinidine (QTc-prolongation; convulsions)
[if concomitant use cannot be avoided, delay Mefloquine
administration at least 12 hours after the last dose of
Quinidine], Quinine (QTc-prolongation; convulsions) [if
concomitant use cannot be avoided, delay Mefloquine
administration at least 12 hours after the last dose of
Quinidine]
Increases risk of adverse or toxic effects of the following
drugs:
Halofantrine (QTc-prolonging effect), Highest Risk QTc-
prolonging Agents, Mifepristone (QTc-prolonging effect)
Increases serum concentration of Mefloquine:
Conivaptan, Fusidic Acid, Idelalisib, Mifepristone,
Stiripentol
Increases serum concentration of the following drugs:
Afatinib [if concomitant use cannot be avoided, reduce
Afatinib by 10 mg if not tolerated], Bosutinib, Colchicine
(enhances distribution to specific tissues, e.g., brain),
Dabigatran Etexilate [active metabolite/s], Doxorubicin
(Conventional), Edoxaban, Everolimus, Pazopanib,
Silodosin, Topotecan, Vincristine (Liposomal)
Reduces therapeutic effect of Anticonvulsants
Administration: Administer with food and with at least 8 oz.
of water. Tablets may be crushed and suspended in a
small amount of water, milk, or another beverage for
persons unable to swallow tablets.
When used for malaria prophylaxis, dose should be taken
once weekly on the same day each week.
If vomiting occurs within 30 minutes after the dose,
administer an additional full dose. If it occurs within 30–
60 minutes after dose, administer an additional half-
dose.
Pregnancy Category: B
ATC Code: P01BC02
Rx PRIMAQUINE
Oral: 26.3 mg tablet (as diphosphate) (15 mg base)
An 8-aminoquinoline antimalarial used for the radical cure
and terminal prophylaxis of infections with P. vivax and
P. ovale. It eliminates the exoerythrocytic form of malarial
parasite by disrupting the mitochondria and binding to
DNA.
Indications: Radical cure in relapsing infections of P. vivax
and P. ovale malaria; elimination of intrahepatic forms of
P. vivax and P. ovale (after standard chloroquine
therapy); elimination of P. falciparum gametocytes (after
standard therapy with a blood schizontocide)
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
Contraindications: G6PD deficiency in infants (risk of
hemolysis); infants <1 year (methemoglobinemia);
patients with conditions that predispose to
granulocytopenia, including active rheumatoid arthritis
and systemic lupus erythematosus; pregnancy (delay
treatment until after delivery; breastfeeding
Dose:
Uncomplicated malaria due to P. falciparum or P. malariae
(in combination with artemether-lumefantrine), ADULT
and CHILD, 0.25 mg base per kg per day as a single dose
per day 1.
Uncomplicated malaria due to P. vivax or P. ovale, first-line
treatment (in combination with chloroquine 10 mg/kg on
day 1–2, then 5 mg/kg on day 3), by mouth, ADULT and
CHILD, 0.25 mg base/kg per day as a single dose for day
1 to 14.
Relapse malaria due to hypnozoites of P. vivax (in
combination with chloroquine 10 mg/kg on day 1–2,
then 5 mg/kg on day 3; or with artemether-lumefantrine),
by mouth, ADULT and CHILD, 0.75 mg/kg per day on day
1–14 (maximum dose, 30–45 mg/day).
Severe malaria due to P. vivax or P. ovale (in combination
with artemether-lumefantrine).
Mixed malarial infection due to P. falciparum and P. vivax
with or without P. malariae (in combination with
artemether-lumefantrine).
Mixed malarial infection due to P. vivax and P. malariae (in
combination with chloroquine tablet 10 mg/kg on day 1–
2, then 5 mg/kg on day 3), by mouth, ADULT and CHILD,
0.25 mg base/kg per day as a single dose for day 1 to
14.
Relapse malaria due to P. vivax (in combination with
chloroquine (150 mg base tablet), 2 tablets weekly for 8
weeks, by mouth, ADULT (lactating women), 0.25 mg/kg
daily on day 1–14 (maximum, 30–45 mg daily).
See National Antibiotic Guidelines for other dosing
information.
Dose Adjustment:
G6PD Deficiency:
For mild deficiency, administer 0.75 mg/kg once a week for
8 weeks.
Precautions:
G6PD deficiency (exclude before radical treatment for P.
vivax and P. ovale malaria; but, not necessary before
single-dose gametocytocidal treatment); Concomitant
use with other potentially hemolytic drugs that depress
myeloid elements of the bone marrow (monitor if either
methemoglobinemia or hemolysis occurs, withdraw
treatment and consult a physician).
Pregnancy (withhold during entire pregnancy; neonatal
hemolysis and methemoglobinemia have been reported
with use during the third trimester); lactation (excreted
in breast milk in amounts not harmful to the nursing
infant and in insufficient amounts to provide protection
against malaria).
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, dizziness, headache,
leukocytosis, nausea, vomiting
Less Common: Hemolytic anemia, methemoglobinemia
Rare: Agranulocytosis, anemia, arrhythmias,
granulocytopenia, hypertension, interference with visual
accommodation, hemoglobinuria, leukopenia, pruritus
Drug Interactions:
Monitor closely with:
Increases risk of hematological adverse effects of the
following drugs:
Bone Marrow Depressants, Hemolytics
Administration: Take with food to avoid stomach upset and
pain.
Do NOT give to patients with G6PD deficiency.
Pregnancy Category: C
ATC Code: P01BA03
Rx PYRIMETHAMINE
Oral: 25 mg and 75 mg tablet
A diaminopyrimidine that inhibits parasitic dihydrofolate
reductase, resulting in inhibition of vital tetrahydrofolic
acid synthesis. It is active against pre-erythrocytic forms
and is also a slow-acting schizontocide.
Indications: Treatment of toxoplasmosis or pneumocystosis
P
(in combination with sulfonamide)
Contraindications: Megaloblastic anemia secondary to
folate deficiency; pregnancy; lactation
Dose:
Toxoplasmosis treatment (in combination with a
sulfonamide and leucovorin calcium), by mouth, ADULT,
50–75 mg daily for 1–3 weeks depending on patient's
tolerance and response, then dose may be reduced by
50% and continue for 4–5 weeks, with 1–4 g
sulfadiazine daily; CHILD, initially 1 mg/kg daily divided
into 2 equal daily doses for 2 to 4 days, may decrease
dose to 0.5 mg/kg daily divided into 2 doses for 4 weeks,
with usual pediatric dose of sulfadiazine.
Precautions:
Hematologic effects (most commonly with high doses;
monitor CBC and platelets twice weekly in high-dose
therapy); Folate deficiency (use with caution); G6PD
deficiency (use with caution); renal impairment; hepatic
impairment; Seizure disorders (use with caution).
Pregnancy (adverse events have been observed in animal
reproduction studies; supplementation of folate is
strongly recommended); lactation (excreted in breast
milk; may result in significant systemic concentrations in
breast­fed infants).
Adverse Drug Reactions: Arrhythmias (large doses), rash,
anorexia, atrophic glossitis, vomiting, leukopenia,
megaloblastic anemia, pancytopenia, pulmonary
eosinophilia, thrombocytopenia, hematuria, anaphylaxis
Potentially Fatal: Cutaneous reactions (e.g., erythema
multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis (with sulfadoxine at large doses)
545
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Bone marrow suppression: Proguanil, Sulfonamides e.g.
Co-trimoxazole, Zidovudine, Cytostatic Agents
Co-trimoxazole (pancytopenia; megaloblastic anemia),
Lorazepam (hepatotoxicity)
Reduces therapeutic effect of Pyrimethamine:
Methylfolate
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Pyrimethamine:
Artemether
Increases risk of adverse or toxic effects of the following
drugs:
Dapsone (hemolytic reactions), Lumefantrine
Administration: Administer with meals to minimize GI
distress.
Pregnancy Category: C
ATC Code: Not available
Rx QUININE
P
Oral: 325 mg tablet (as sulfate) (300 mg base)
Inj.: 250 mg/mL (as dihydrochloride). 1 mL ampule (IV)
300 mg/mL (as dihydrochloride). 1 mL ampule (IV)
A methanolquinoline that intercalates into the DNA
structure of susceptible Plasmodium spp., disrupting the
parasite’s replication and transcription.
Indications: 1st line treatment of uncomplicated
chloroquine-resistant P. falciparum malaria (in
conjunction with other antimalarial agents) in pregnant
and lactating women and infants less than 6 months old;
2nd line treatment of severe malaria.
Contraindications: Prolonged QT interval; myasthenia
gravis; optic neuritis; G6PD deficiency; hypersensitivity to
quinine, mefloquine, quinidine, or any component of the
formulation;
Dose:
Uncomplicated malaria due to P. falciparum or P. malariae
(in combination with clindamycin, 10 mg/kg twice daily
for 7 days; and primaquine tablet, 15 mg (0.25 mg base
per kg) on day 1 and 3 tablets for adults >60 kg), by
mouth, ADULT (pregnant and lactating women), INFANT
<6 months, 10 mg/kg every 8 hours for 7 days.
2nd line drug for severe malaria, by IV drip, ADULT, 20
mg/kg in 500 mL D5W or 0.9 NaCl for 4 hours ass
loading dose (maximum total dose, 2,000 mg), then 10
mg/kg in 0.9 NaCl or D5W for 4 hours every 8 hours as
maintenance dose; shift to oral artemether-lumefantrine
plus clindamycin once patient can tolerate; CHILD 8–16
years (in combination with clindamycin, 10 mg/kg twice
daily for 7 days), 15 mg/kg for 4 hours in 10 mL/kg D5W
or 0.9 NaCl as loading dose (maximum infusion rate, 5
546
mg/kg per hour), then 10 mg/kg for 4 hours every 8
hours as maintenance dose; CHILD ≤7 years, 10 mg/kg
for 4 hours as loading dose, then 10 mg/kg every 12
hours as maintenance dose.
See National Antibiotic Guidelines for other dosing
information.
Dose Adjustment:
Renal Impairment:
For patients with severe chronic impairment but not on
dialysis, initiate dose at 648 mg, followed by 324 mg
every 12 hours.
Hepatic Impairment:
For patients with mild-to-moderate impairment, no dosage
adjustment needed. Monitor closely.
For patients with severe impairment, avoid use or reduce
maintenance dose to 5–7 mg/kg of quinine salt every 8
hours.
Precautions:
Hypersensitivity reactions (discontinue following any signs
of sensitivity); Hypoglycemia; Thrombocytopenia (re-
exposure may result in increased severity of
thrombocytopenia and faster onset); Altered cardiac
conduction (use with caution); Hepatic impairment (use
with caution); renal impairment (use with caution; dose
adjustment recommended in severe chronic
impairment)
Elderly (use with caution).
Pregnancy (crosses the human placenta in amounts not
therapeutic to the infant; teratogenic effects, optic nerve
hypoplasia, and deafness have been reported in the
infant following maternal use of very high doses);
lactation.
Adverse Drug Reactions:
Common and Less Common: Atrial fibrillation,
atrioventricular block, bradycardia, cardiac arrest, chest
pain, hypotension, irregular rhythm, nodal escape beats,
orthostatic hypotension, palpitation, QT prolongation,
syncope, tachycardia, torsade de pointes, unifocal
premature ventricular contractions, U waves,
vasodilation, ventricular fibrillation, ventricular
tachycardia, aphasia, ataxia, chills, coma, confusion,
disorientation, dizziness, dystonic reaction, fever,
flushing, headache, mental status altered, restlessness,
seizure, suicide, vertigo, acral necrosis, allergic contact
dermatitis, bullous dermatitis, bruising, cutaneous rash,
cutaneous vasculitis, exfoliative dermatitis, erythema
multiforme, petechiae, photosensitivity, pruritus,
Stevens-Johnson syndrome, toxic epidermal necrolysis,
hypoglycemia, abdominal pain, anorexia, diarrhea,
esophagitis, gastric irritation, nausea, vomiting,
agranulocytosis, aplastic anemia, coagulopathy,
disseminated intravascular coagulation, hemolytic
anemia, hemolytic uremic syndrome, hemorrhage,
hypoprothrombinemia, immune thrombocytopenia,
leukopenia, neutropenia, pancytopenia,
thrombocytopenia, thrombotic thrombocytopenic
purpura, granulomatous hepatitis, hepatitis, jaundice,
myalgia, tremor, weakness, blindness, blurred vision,
color vision disturbance, diminished visual fields,
diplopia, night blindness, optic neuritis, photophobia,
pupillary dilation, vision loss (sudden), deafness, hearing
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

impaired, tinnitus, acute interstitial nephritis,, renal Pitavastatin, Pravastatin, Red Yeast Rice, Rosuvastatin],
failure, renal impairment, asthma, dyspnea, pulmonary Metoprolol, Pazopanib, Phenobarbital, Ritonavir,
edema, black water fever, diaphoresis, hypersensitivity Silodosin, Thioridazine, Topotecan, Vincristine
reaction, lupus anticoagulant, lupus-like syndrome (Liposomal)

Drug Interactions: Administration: Take with food to decrease incidence of

Monitor closely with: gastric upset. Swallow dose whole to avoid bitter taste.
Enhances therapeutic effect of the following drugs:
Antihypertensive Herbs, Vitamin K Antagonists [e.g., Avoid use of aluminum- or magnesium-containing
Warfarin (anticoagulant effect)] antacids because of drug absorption problems.

Increases risk of hypoglycemic adverse effects of Quinine: Pregnancy Category: C

Androgens [except Danazol], Antidiabetic Agents, Herbs
with Hypoglycemic Properties, MAO Inhibitors, Other ATC Code: P01BC01
hypoglycemia-associated Agents, Pegvisomant,
Salicylates, Selective Serotonin Reuptake Inhibitors
OTHER ANTIMALARIALS
Increases risk of the following drugs:
Herbs with Hypotensive Properties (excessive blood
pressure lowering), Rx DOXYCYCLINE
Significant methemoglobinemia: Nitric Oxide, Prilocaine,
Sodium Nitrite
Oral: 100 mg capsule (as hyclate)
Reduces therapeutic effect of the following drugs:
A broad-spectrum, long-acting tetracycline antibiotic used
Codeine, Tramadol
for infections caused by chlamydia, spirochetes and
other pathogens, and for malarial prophylaxis.
Avoid concomitant use with:
Decreases serum concentration of Quinine:
Indications: Prophylaxis and treatment (supplement to
Antacids [except Calcium Carbonate, Sodium
quinine or artesunate) of multi-drug-resistant P.
Bicarbonate], Carbamazepine, Dabrafenib,
falciparum malaria
Fosphenytoin, Lopinavir, Mitotane, Phenobarbital,

P
Phenytoin, Rifampin, Ritonavir,
Contraindications: Children <8 years (deposition of
tetracyclines in growing bones and teeth causes
Decreases serum concentration of Tamoxifen [active
deformation and inhibit bone growth) except for cholera
metabolite/s]
or leptospirosis but not to be given for > 7 days;
pregnancy (first trimester, effects on skeletal
Enhances therapeutic effect of Neuromuscular-blocking
development in animal studies; 2nd and 3rd trimesters,
Agents
dental discoloration; maternal hepatotoxicity with large
doses); breastfeeding; porphyria; SLE
Increases risk of adverse or toxic effects of Quinine:
Artemether, Dapsone (hemolytic reactions), Ivabradine
Dose:
(QTc-prolonging effect), Mifepristone (QTc-prolonging
2nd line treatment for Uncomplicated malaria due to P.
effect), QTc-prolonging Agents
falciparum or P. malariae, second-line treatment (in
combination with quinine sulfate, 10 mg/ kg every 8
Increases risk of adverse or toxic effects of the following
hours for 7 days and primaquine tablet, 15 mg (0.24 mg
drugs:
base per kg) on day 1; 3 tablets for adults >60 kg), by
Dapsone (hemolytic reactions), Halofantrine,
mouth, ADULT, 100 mg 2 times daily for 7 days.
Lumefantrine, Mefloquine (QTc-prolongation;
Prophylaxis of chloroquine-resistant malaria, beginning 1-2
convulsions)
days before travel to malarious area up to 4 weeks after
leaving, ADULT, 100 mg daily CHILD ≥ 8 years, 2.2 mg
Increases serum concentration of Quinine:
∙base/ kg daily.
Antihepatitis C viral Combination Products, Cimetidine,
Chloroquine-resistant falciparum malaria acute attack,
Conivaptan, CYP3A4 Inhibitors, Fusidic Acid, Idelalisib,
ADULT, 200 mg daily for at least 7 days, with or after
Macrolide Antibiotics e.g. Erythromycin [except
treatment with quinine.
Fidaxomicin], Mefloquine [delay Mefloquine
administration at least 12 hours after the last dose of
NOTE: Refer to DOH Public Health Program on Malaria for
Quinine], Stiripentol
more details.
Increases serum concentration of the following drugs:
Administration: Capsules should be swallowed whole with
Afatinib [if concomitant use cannot be avoided, reduce
plenty of fluid (a full glass of water). Remain sitting or
Afatinib dose by 10 mg if not tolerated], Amodiaquine,
standing (for at least 30 minutes) to prevent esophageal
Bosutinib, Carbamazepine, Colchicine (enhances
irritation or damage.
distribution into certain tissues, e.g., brain), Dabigatran
Etexilate [active metabolite/s], Doxorubicin
May be given with food to counter gastric irritation. Do NOT
(Conventional), Edoxaban, Everolimus, Halofantrine,
give with milk
HMG-CoA reductase inhibitors [except Fluvastatin,

547
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
See Doxycycline under Antibacterials for Systemic Use –
Tetracyclines in Chapter 7: Antiinfectives for Systemic
Use for other information.
Pregnancy Category: D
ATC Code: J01AA02
Rx TETRACYCLINE
Oral: 250 mg and 500 mg capsule
A tetracycline antibiotic that inhibits bacterial synthesis by
binding with the 30s ribosomal subunit(s) of
susceptible microorganisms.
Indication: For chloroquine-resistant falciparum malaria (in
combination with other antimalarials)
Dose:
2nd line treatment for uncomplicated malaria due to P.
falciparum or P. malariae (in combination with quinine
sulfate, 10 mg/kg every 8 hours for 7 days; and
primaquine tablet, 15 mg (0.25 mg base per kg) on day
1 and 3 tablets for adults >60 kg), by mouth, ADULT, 3
mg/kg once daily for 7 days.
Severe malaria due to P. falciparum or P. malariae, second-
line treatment (in combination with artemether-
lumefantrine), by mouth, ADULT, 3 mg/kg once daily for
P
7 days.
Dose Adjustment:
Renal Impairment:
If CrCl is 50–80 mL/minute, administer every 8–12 hours.
If CrCl is 10–50 mL/minute, administer every 12–24 hours.
If CrCl <10 mL/minute, administer every 24 hours.
Hepatic Impairment:
Use with caution. Maximum dose is 1 g daily.
Administration: Should be given on an empty stomach (1
hour prior to, or 2 hours after meals) to increase total
absorption.
Administer at least 1–2 hours prior to, or 4 hours after
antacid because aluminum and magnesium cations may
chelate with tetracycline and reduce its total absorption.
Administer around-the-clock to promote less variation in
peak and trough serum levels.
See Tetracycline under Antibacterials for Systemic Use –
Tetracyclines in Chapter 7: Antiinfectives for Systemic
Use for other information.
Pregnancy Category: D
ATC Code: J01AA07
548
ANTHELMINTICS
ANTITREMATODALS
Rx PRAZIQUANTEL
Oral: 600 mg tablet (available under DOH program)
NOTE: Available at the DOH Central Office and government
health facilities in endemic areas.
A quinoline-derived, broad-spectrum anthelmintic, which is
effective, as a single dose, in the treatment of
schistosome infections of all species, and other
trematode and cestode infections, including
cysticercosis. It increases the cell permeability to Ca in
schistosomes, causing contractions and paralysis of
worm musculature leading to detachment of suckers
from the blood vessel walls and to dislodgement.
Indications: For fluke and tapeworm infections including
Cysticercus cellulosae; intestinal schistosomiasis;
urinary schistosomiasis
Contraindications: Ocular cysticercosis
Dose:
Schistosomiasis (selective treatment), by mouth, ADULT
and CHILD >4 years, 40–60 mg/kg as a single dose; or
in 3 divided doses of 20 mg/kg at intervals of 4–6 hours.
Dose Adjustment:
Hepatic Impairment:
Consider reducing dose due to increased concentration and
half-life.
Precautions:
Cardiovascular disease; cerebral cysticercosis (it is
recommended to hospitalize patients for the duration of
treatment)
Ocular cysticercosis (severe eye damage due to death of
parasites may occur)
Undiagnosed neurocysticercosis (seizures may result if
praziquantel is used to treat another systemic infection).
Paragonimus infections (may have CNS involvement);
severe hepatic disease
Areas endemic for cysticercosis (possible risk of edematous
reaction)
Reduced liver drug metabolism may result in higher and
longer lasting plasma concentration of unmetabolized
praziquantel.
Pregnancy (Taenia solium infections should be treated
immediately; benefit of treatment in schistosomiasis
outweighs the risk; if treatment is not essential, it should
be delayed until after delivery); breastfeeding (low
excretion in breastmilk; avoid breastfeeding during, and
for 72 hours, after treatment; considered safe to
continue breastfeeding during treatment).
SKILLED TASKS. Avoid performing tasks, which require
mental alertness, e.g., operating machinery or driving.
Warn patient not to operate machinery or drive during
treatment or for 24 hours after treatment.
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, appetite loss, colic,
diarrhea, dizziness, drowsiness, fever, headache,
malaise, myalgia, nausea, reversible rises in hepatic
aminotransferases, somnolence, urticaria, vertigo,
vomiting
Rare: Arrhythmias, bloody diarrhea, hypersensitivity
reactions, rectal bleeding, seizures, eosinophilia,
pruritus
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Praziquantel:
Carbamazepine, Chloroquine, Dexamethasone,
Phenytoin
Avoid concomitant use with:
Reduces therapeutic effect of Praziquantel due to
decreased serum concentration of active metabolite/s:
CYP450 Inducers (e.g., Rifampicin)
Increases serum concentration of Praziquantel:
CYP Inhibitors (e.g., Cimetidine, Erythromycin,
Itraconazole)
Administration: Should be taken on a full stomach. Swallow
with water, without chewing, to lessen its bitter taste.
Pregnancy Category: B
ATC Code: P02BA01
Rx TRICLABENDAZOLE
Oral: 250 mg tablet
A benzimidazole compound that is active against immature
and adult Fasciola parasites.
Indications: For the treatment of paragonimiasis; primary or
alternate agent to praziquantel; for implementation of
the DPCB – Food and Waterborne Disease Program in
identified endemic areas in the Philippines
Contraindications: Breastfeeding
Dose:
Fascioliasis, by mouth, ADULT and ADOLESCENT, 10 mg/kg
as a single dose, may be repeated after 2 weeks or 6
months if necessary; CHILD, 10 mg/kg as a single dose.
Fascioliasis, severe, by mouth, ADULT and ADOLESCENT, 20
mg/kg in 2 divided doses 12 hours apart.
Paragonimiasis, by mouth, ADULT and ADOLESCENT, 5
mg/kg once daily for 3 days; or 10 mg/kg as a single
dose; CHILD, 10 mg/kg as a single dose; or 20 mg/kg in
2 divided doses for 1 day.
Precautions:
Pregnancy (studies in humans have not been conducted);
lactation (excreted in breast milk).
Adverse Drug Reactions:
Common and Less Common: Transient self-limiting biliary
obstruction, gastrointestinal disturbance, abdominal
cramps, diarrhea
Drug Interactions: No information found
Administration: To be taken with fatty food to increase
absorption.
MISSED DOSE. Take missed dose as soon as remembered.
Do NOT take if near time for next dose. Do NOT take 2
doses at once.
Pregnancy Category: D
ATC Code: P02BX04
ANTINEMATODAL AGENTS
Rx ALBENDAZOLE
Oral: 400 mg chewable tablet
200 mg/5 mL suspension, 10 mL and 60 mL
A benzimidazole-derived, broad-spectrum, oral
anthelmintic, which is used for long-term treatment of
tissue helminth infections, including hydatid disease and
cysticercosis.
P
Indications: Management of filariasis; treatment of
intestinal helminths
Contraindications: Pregnancy (first trimester, avoid in
nematode infections); hepatic cirrhosis; cestode
infections due to Taenia solium occurring during
pregnancy; ocular cysticercosis (severe eye damage due
to death of parasites may occur)
Dose:
Filariasis (selective treatment for patients positive for
microfilariae in nocturnal blood examination, 12-day
treatment), by mouth, ADULT,
Day 1, 400 mg albendazole and 6 mg/kg body weight
diethylcarbamazine citrate (DEC) in 3 divided doses;
Day 2 to 12, 6 mg/kg body weight of DEC only, given in 3
divided doses daily.
NOTE: Refer to DOH National Filariasis Elimination Program
for more details
Intestinal Helminths, by mouth, ADULT and CHILD> 2 years,
400 mg single dose.
Dose Adjustment:
Hepatic Impairment:
Consider dose reduction during extended treatment.
Precautions:
Liver disease; Liver function tests, clinical signs of hepatic
toxicity and blood count should be monitored twice
during each cycle before a longer-term treatment.
Pregnancy (exclude pregnancy before starting the
treatment; advise patients to use non-hormonal
549
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
contraception during and for one month after treatment);
breastfeeding.
Adverse Drug Reactions:
Common: Abdominal pain, headache, nausea, vomiting
Less Common: Abnormal liver function tests, diarrhea,
dizziness, fever, increased intracranial pressure,
meningeal signs, vertigo
Rare: Agranulocytosis, allergic shock (if with cyst leakage),
aplastic anemia, bone marrow suppression, jaundice,
convulsions, erythema multiforme, hepatitis,
hypersensitivity reactions, proteinuria, Stevens-Johnson
syndrome
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Albendazole due to
decreased serum concentration of active metabolite/s:
Phenobarbital, Phenytoin
Administration: To be taken with food. Oral absorption may
be increased 4–5 times with fatty meal
Pregnancy Category: C
ATC Code: P02CA03
Rx DIETHYLCARBAMAZINE
P
Oral: 50 mg and 100 mg tablet (available under DOH
program)
NOTE: Refer to DOH National Filariasis Elimination Program
for more details
A piperazine-derived, filarial medicine, which renders
microfilariae susceptible to destruction by the host’s
defense mechanism through parasite immobilization,
normal habitat dislocation and surface membrane
alteration.
Indication: Management of filariasis
Contraindications: Pregnancy (delay medication until after
delivery)
Dose:
Filariasis (selective treatment for patients positive for
microfilariae in nocturnal blood examination, 12-day
treatment), by mouth, ADULT,
Day 1, 6 mg/kg body weight diethylcarbamazine citrate
(DEC) in 3 divided doses and 400 mg albendazole;
Day 2 to 12, 6 mg/kg body weight of DEC only, given in 3
divided doses daily.
Dose Adjustment:
Renal Impairment:
Consider reducing dose. Plasma half-life is prolonged, and
urinary excretion is considerably reduced.
Precautions:
Cardiac disorders; other severe acute diseases (delay
treatment until after recovery); Treatment should be well
supervised since allergic reaction is common and usually
550
severe (especially in onchocerciasis and loiasis); Monitor
for eye changes.
PATIENT ADVICE. Complete the prescribed course as
directed to minimize allergic reactions to dying parasites.
Adverse Drug Reactions:
Common: Allergic reactions
Less Common: Anorexia, asthmatic attacks, dizziness,
drowsiness, fever, headache, joint pain, malaise,
transient hematuria, urticaria, vomiting
Rare: Convulsions, exacerbation of lymphedema, transient
lymphangitis
Drug Interactions: No information found.
Administration: To be taken after meals. Rigorous hygiene
is essential.
Total cumulative dose for W. bancrofti infections should be
72 mg/kg. Treatment is best initiated with smaller doses
for 2–3 days to avoid potential risk of immunological
reactions.
NOTE: Before treatment with diethylcarbamazine citrate
(DEC), patients should be assessed for co-infection with
Loa loa and Onchocerca volvulus because DEC can
cause serious reactions in these patients.
May be co-administered with dexamethasone, 0.8
mg/kg daily to reduce intensity of Mazzotti reactions.
Administer prior to initiating diethylcarbamazine and
maintained for 5 days prior to gradual withdrawal.
Pregnancy Category: X
ATC Code: P02CB02
Rx MEBENDAZOLE
Oral: 100 mg tablet / capsule
500 mg tablet / chewable tablet
50 mg/mL suspension, 10 mL
100 mg/5 mL suspension, 30 mL and 60 mL
A benzimidazole derivative that inhibits the formation of
helminth microtubules. It selectively and irreversibly
blocks glucose uptake and other nutrients in susceptible
adult intestine-dwelling helminths.
Indication: Management of common roundworm infections
Dose:
Ascaris lumbricoides (roundworm), Strongyloides
stercoralis (roundworm), mixed infection, by mouth,
ADULT, ADOLESCENT, and CHILD ≥2 years, 500 mg as
single dose of 100 mg twice daily for 3 days, repeat in 3
weeks if not cured with initial treatment.
Precautions:
Bone marrow suppression; Hepatic impairment (undergoes
extensive hepatic metabolism);
Children (experience with use in children <2 years of age is
limited)
ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS
Pregnancy (use with caution; consider postponing therapy
until the third trimester when possible).
Adverse Drug Reactions: Dizziness, drowsiness, headache,
seizure, alopecia, angioedema, exanthema, itching, rash,
Stevens-Johnson syndrome, toxic epidermal necrolysis,
urticaria, abdominal pain, diarrhea, vomiting,
agranulocytosis, eosinophilia, decreased hemoglobin,
leukopenia, neutropenia, increased alkaline
phosphatase, hepatitis, cylindruria, glomerulonephritis,
hematuria, hypersensitivity reactions (anaphylactic,
anaphylactoid)
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects Mebendazole:
Metronidazole (Stevens-Johnson syndrome or toxic
epidermal necrolysis)
Administration: May be administered with or without food.
Tablets may be chewed, swallowed whole, or crushed
and mixed with food.
Pregnancy Category: C
ATC Code: P02CA01
ECTOPARASITICIDES, INCLUDING SCABICIDES,
INSECTICIDES, AND REPELLENTS
ECTOPARASITICIDES,
INCLUDING SCABICIDES
OTC BENZYL BENZOATE
Topical: 25% lotion, 60 mL and 120 mL bottle
An acaricide that is used in the treatment of scabies
Indication: For the treatment of scabies
Contraindications: Broken or irritated skin; neonates;
pregnancy
Dose:
Scabies, by topical application, ADULT, apply 3 times over
the whole body once daily for 2 consecutive nights. May
repeat 1 application at night 3 days later.
Dose Adjustment: No information found
Precautions:
Prevent drug from entering the eyes.
Elderly (increased risk of drying effects).
Adverse Drug Reactions: Irritant to eyes and mucous
membranes, allergic dermatitis reactions, drying effects
(elderly)
Drug Interactions: No information found
Administration: For external use only. Apply to intact skin
only. Do NOT apply to broken or irritated skin.
Pregnancy Category: Not classified
ATC Code: P03AX01
Rx CROTAMITON
Topical: 10% lotion, 60 mL bottle
A scabicidal and antipruritic agent for topical use only.
Indications: For eradication of scabies (Sarcoptes scabiei);
symptomatic treatment of pruritic skin
Contraindications: Sensitive skin
Dose:
Scabies, by topical application, ADULT, CHILD >3 years,
thoroughly massage into the skin of the whole body from
the chin down, paying attention to all folds and creases,
re-apply after 24 hours, wash all clothing and bed linen
the next morning, take cleansing bath 48 hours after the
last application; CHILD <3 years, apply once daily with
medical supervision.
Pruritus, by topical application, ADULT, massage gently into
affected areas until medication is completely absorbed,
repeat as needed; CHILD <3 years, apply once daily with
P
medical supervision.
Dose Adjustment: No information found
Precautions:
WARNING: If severe irritation or sensitization
develops, treatment with this product should be
discontinued and appropriate therapy instituted.
Pregnancy (use with caution; use only when clearly needed).
Adverse Drug Reactions: Dermatitis, pruritus, rash, allergic
sensitivity reactions
Administration: For external use only. Shake well before use.
Take a routine bath or shower. Thoroughly massage the
lotion into the skin from the chin to the toes including
folds and creases, as well as under fingernails after
trimming the fingernails short. A toothbrush can be used
to apply the lotion under the fingernails. Immediately
after use, the toothbrush should be wrapped in paper
and thrown away. Use of the same brush in the mouth
could lead to poisoning. One bottle is sufficient for 2
applications. Clothing and bed linen should be changed
the next day. Contaminated clothing and bed linen may
be dry-cleaned, or washed in the hot cycle of the washing
machine.
Do NOT apply in the eyes or mouth because it may cause
irritation. Do NOT apply to acutely inflamed skin or raw or
weeping surfaces until the acute inflammation has
subsided.
551
 ANTIPARASITIC PRODUCTS, INSECTICIDES, AND REPELLENTS

Pregnancy Category: C Avoid contact with eyes, mucous membrane, and broken
skin.
ATC Code: Not available
Pregnancy Category: B

ATC Code: P03AC04

Rx PERMETHRIN

Topical: 1% lotion, 125 mL bottle

5% lotion, 30 mL and 60 mL bottle
OTC SULFUR
1% shampoo (crème rinse), 30 mL and 60 mL
bottle Topical: 10% cream / ointment, 15 g and 30 g tube

A topical scabicidal agent. It acts on the nerve cell A keratolytic, mild antiseptic, mild antifungal, and
membrane to disrupt the sodium channel current by parasiticide.
which the polarization of the membrane is regulated,
resulting to paralysis. Indication: Treatment of scabies

Indications: Treatment of scabies (Sarcoptes scabiei); head
pediculosis
Dose:
For scabies, by topical application, ADULT and CHILD >2
months, apply 5% lotion to entire skin from chin down to
and including toes and under fingernails and toenails,
leave on for 8–14 hours, repeat in 1–2 weeks.
Pediculosis pubis, by topical application, ADULT and CHILD
>2 months, apply 1% crème rinse to affected areas and
wash off after 10 minutes.
Contraindications: Children <2 years
Dose:
Scabies, by topical application, ADULT, apply a thin layer
uniformly and massage gently into all skin surfaces from
the neck to the toes (including the soles), leave on for 24
hours before washing, repeat application for 2–3
successive days, 30 g is sufficient for each application;
CHILD, use a smaller proportion of adult dose.
Dose Adjustment: No information found

Dose Adjustment: No information found Precautions:

P

Precautions:
Dermatological effects (may temporarily exacerbate
pruritus, edema, and erythema associated with scabies
infestation).
Children (safety and effectiveness in children <2 months
have not been established).
Lactation (excreted in breast milk; withhold drug while
mother is nursing)
Adverse Drug Reactions:
Common: Mild and transient burning and stinging, pruritus,
erythema, numbness, tingling, rash, skin and scalp
irritation, eczema, localized edema
May stain the skin black and give off a foul smell when
applied concomitantly with mercurial compounds.
Adverse Drug Reactions: Skin irritation, dermatitis
Drug Interactions:
Enhances therapeutic effect of Sulfur:
Resorcinol
Administration: For external use only.
Cleanse skin thoroughly. Cover the entire affected area with
a thin layer and leave on for 24 hours. Thoroughly
remove with water.

Drug Interactions: No information found
Administration: Treat close contacts. Wash and dry linens to
prevent re-infection. Re-apply to hands after
handwashing.
Avoid contact with eyes, mouth and other mucous
membranes. Do NOT use on broken skin.
Do NOT use concurrently with other topical acne
medications unless otherwise directed by physician.

Thoroughly massage the product into the skin from the head Pregnancy Category: Not classified
to the soles of the feet. Scabies rarely infests the scalp
of adults, although the hairline, neck, temple, and ATC Code: Not available
forehead may be infested in infants and geriatric
patients. Remove the product by washing (shower or
bath) after 8 to 14 hours. Infants should be treated on
the scalp, temple, and forehead. ONE APPLICATION IS
GENERALLY CURATIVE.

Patients may experience persistent pruritus after treatment.

This is rarely a sign of treatment failure and is NOT an
indication for retreatment. Demonstrable living mites
after 14 days indicate that retreatment is necessary.

552
RESPIRATORY SYSTEM

Precautions:
RESPIRATORY SYSTEM WARNING: Discontinuation of Therapy. Withdraw
systemic therapy with gradual tapering of dose. There
have been reports of systemic corticosteroid
withdrawal symptoms (e.g., joint or muscle pain,
NASAL PREPARATIONS lassitude, depression) when withdrawing oral
inhalation therapy.

DECONGESTANTS AND OTHER NASAL Adrenal suppression; Bronchospasm (if this occurs, stop
PREPARATIONS FOR TOPICAL USE steroid and treat with a fast-acting bronchodilator);
Asthma (not to be used in status asthmaticus or for the
relief of acute bronchospasm); Immunosuppression (use
Rx BUDESONIDE is restricted in active TB); Local oral infections; Kaposi's
sarcoma (if noted, discontinue therapy); myopathy
Inhalation: (monitor creatine kinase; recovery may be delayed);
DPI: myasthenia gravis; Psychiatric disturbances; seizure
100 micrograms/dose x 200 doses with appropriate disorders; Cardiovascular disease (myocardial
accompanying dispenser infarction); Diabetes; gastrointestinal disease; Hepatic
200 micrograms/dose x 100 doses and 200 doses with impairment (long-term use has been associated with
appropriate accompanying dispenser fluid retention); renal impairment (fluid retention may
occur); Thyroid disease (changes in thyroid status may
MDI: necessitate dose adjustments); Ocular disease;
200 micrograms/dose x 120 actuations Osteoporosis; Elderly; children (routinely monitor
growth); lactation (excreted in breast milk).
Respiratory solution for nebulization:
250 micrograms/mL respiratory solution (for Adverse Drug Reactions:
nebulization), 2 mL (unite dose) Common: Syncope, headache, pain, hypertonia, insomnia,
voice disorder, weight gain, emotional lability, fatigue,
A corticosteroid with potent glucocorticoid activity and weak skin rash, contact dermatitis, eczema, pruritus, pustular
mineralocorticoid activity. It controls the rate of protein rash, dyspepsia, nausea, gastroenteritis, diarrhea,
synthesis, depresses the migration of vomiting, abdominal pain, dysgeusia, xerostomia,
polymorphonuclear leukocytes, fibroblasts, and reverses anorexia, cervical purpura, bruise, lymphadenopathy,
capillary permeability and lysosomal stabilization at the hypersensitivity reaction, candidiasis, viral infection,

cellular level to prevent or control inflammation.
Indications: For seasonal allergic and non-allergic perennial
rhinitis; treatment of nasal polyps; prevention of nasal
polyps after polypectomy
Contraindications: Primary treatment of status asthmaticus,
acute episodes of asthma
NOTE: NOT for the relief of acute bronchospasm.
Dose:
NOTE: Dose should be individualized and tapered to the
smallest dose maintaining symptom control.
Rhinitis, into the nostril, ADULT and CHILD ≥6 years, initially
256 micrograms daily once daily in the morning or in 2
divided doses (morning and evening).
Nasal polyps, into the nostril, ADULT, 64–100 micrograms
into each nostril twice daily for up to 3 months.
Dose Adjustment:
Geriatric:
Administer the smallest possible effective dose for the
shortest duration.
Pediatric:
Titrate to lowest effective dose to minimize systemic effects.
R
herpes simplex infection, infection, bone fracture,
hyperkinesia, myalgia, arthralgia, weakness, back pain,
conjunctivitis, eye infection, otitis media, otic infection,
otalgia, otitis externa, cough, epistaxis, flu-like
symptoms, stridor, nasopharyngitis, respiratory infection,
rhinitis, chest pain, sinusitis, nasal congestion,
pharyngitis, fever
Less Common: Adrenocortical insufficiency, aggressive
behavior, anxiety, avascular necrosis of femoral head,
bronchitis, bruise, cataract, depression, glaucoma,
growth suppression, headache, hypercorticolism,
hypersensitivity (including angioedema, bronchospasm,
urticaria), increased intraocular pressure, irritability,
nervousness, osteoporosis, pain, pharyngitis, psychosis,
restlessness, skin irritation (facial), throat irritation,
wheezing (patients with severe milk allergy)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Budesonide:
Trastuzumab (neutropenic effect)
Increases risk of adverse or toxic effects of Budesonide:
Denosumab (serious infections)
Increases risk of adverse or toxic effects of the following
drugs:
Amphotericin B (hypokalemic effect), Deferasirox (GI
ulceration, irritation, or bleeding), Loop Diuretics
(hypokalemic effect), Thiazide Diuretics (hypokalemic
effect)

Reduces therapeutic effect of the following drugs:

553

Corticorelin, Sipuleucel-T
Avoid concomitant use with:
Enhances therapeutic effect of Tofacitinib
(immunosuppressive effect)
Increases risk of adverse or toxic effects of Budesonide:
Pimecrolimus, Tacrolimus (Topical)
Increases risk of adverse or toxic effects of the following
drugs:
Leflunomide (hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia), Loxapine,
Natalizumab (concurrent infection)
Increases serum concentration of Budesonide:
Conivaptan (CYP3A4 Inhibitors), Fusidic Acid (Systemic),
Grapefruit Juice, Mifepristone, Stiripentol, Telaprevir
Reduces diagnostic effect of Coccidioides immitis Skin Test
Reduces therapeutic effect of the following drugs:
Aldesleukin (antineoplastic effect), BCG (Intravesical),
Hyaluronidase, Vaccines (Inactivated) [complete all age-
appropriate vaccinations at least 2 weeks prior to
starting budesonide; if vaccinated during budesonide
therapy, revaccinate at least 3 months after
discontinuation]
Administration: Shake well before use. If using for the first
time, remove the protective cap from the tip and prime
metered pump by depressing the pump firmly several
times. To spray, hold bottle with thumb at base and
nozzle between first and second fingers. Without tilting
R
your head, insert the nozzle into nostril. Fully depress rim
with a firm, even stroke and sniff deeply. Wipe nozzle
clean after use.
Pregnancy Category: B
ATC Code: R01AD08
OTC OXYMETAZOLINE
Topical: 0.05% nasal spray (as hydrochloride), 10 mL
and 15 mL bottle
0.025% nasal drops solution (as
hydrochloride), 10 mL bottle
A direct-acting sympathomimetic with vasoconstrictor effect
on mucosal blood vessels when applied topically,
reducing edema of the nasal mucosa.
Indications: Temporarily relieves nasal congestion due to
common cold, hay fever, upper respiratory allergies
Contraindications: Glaucoma; hyperthyroidism; heart
disease, including angina; hypertension; advanced
arteriosclerotic conditions; children <6 years
Dose:
Nasal congestion, into the nostril, ADULT and CHILD ≥6
years, spray 0.05% solution 1–3 times into each nostril
twice daily.
554
RESPIRATORY SYSTEM
Dose Adjustment: No information found
Precautions:
Difficulty in urination secondary to prostate enlargement;
heart disease; high blood pressure; thyroid disease;
diabetes mellitus; Lactation
Adverse Drug Reactions:
Common and Less Common: Local stinging or burning,
sneezing, dryness of mouth and throat, rebound
congestion (prolonged use), headache, insomnia,
tachycardia, hypertension, nervousness, nausea,
dizziness, palpitation, arrhythmia
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of MAO Inhibitors
e.g. Phenelzine (potentially fatal hypertensive crisis)
Administration: Do NOT ingest. Keep out of reach of
children.
Shake well before use. If using for the first time, remove
the protective cap from the tip and prime metered pump
by depressing the pump firmly several times. To spray,
hold bottle with thumb at base and nozzle between first
and second fingers. Without tilting your head, insert the
nozzle into nostril. Fully depress rim with a firm, even
stroke and sniff deeply. Wipe nozzle clean after use.
Administer each dose 10–12 hours apart. Do NOT
exceed 2 doses in any 24-hour period.
For children under 6 years of age, ask a doctor prior to
administration.
Use only as directed. Do NOT use more than directed. Do
NOT use for more than 3 days. Frequent or prolonged use
may cause nasal congestion to recur or worsen.
Do not share containers with other persons to prevent
the spread of infection
Pregnancy Category: C
ATC Code: R01AB07
THROAT PREPARATIONS
OTC POVIDONE–IODINE
Oral: 1% antiseptic solution, 60 mL, 120 mL, and
240 mL bottle
An iodophore with a powerful broad-spectrum germicidal
activity against a wide range of bacteria, viruses, fungi,
protozoa and spores.
Indications: oral hygiene; oral candidiasis
RESPIRATORY SYSTEM
Contraindications: prolonged use in patients with thyroid
disorders or on lithium therapy; premature neonates or
neonates weighing <1.5 kg
Dose:
Oral hygiene, by mouth or throat, ADULT and CHILD >6
years, rinse mouth with 10 mL 0.1% solution, undiluted
or diluted with an equal amount of warm water for 30
seconds 4 times daily for 14 days.
Oral candidiasis, by mouth or throat, ADULT, rinse with 1%
solution.
Precautions:
Avoid contact with eyes; lactation; neonates.
Adverse Drug Reactions:
Rare: Local irritation, sensitivity
Drug Interactions:
Monitor closely with:
Incompatible with the following products:
Bupivacaine (Liposomal) [allow the site to dry completely
before administering bupivacaine], Fibrin Sealant
(Human) [thoroughly rinse and dry prior to application of
sealant]
Avoid concomitant use with:
Incompatible with the following products:
Benzalkonium Chloride, Collagenase
TEST INTERACTIONS. May interfere with thyroid function test
results and interpretation if used for prolonged periods.
Administration: Do NOT ingest. Ensure to spit out the
solution after thorough rinsing. May color teeth and
mucous membranes.
Pregnancy Category: D
ATC Code: R02AA15
DRUGS FOR OBSTRUCTIVE AIRWAY
DISEASE
ADRENERGICS, INHALANTS
Rx SALBUTAMOL
Inhalation:
DPI:
200 micrograms per dose (as sulfate) with appropriate
accompanying dispenser
MDI:
100 micrograms per dose (as sulfate) x 200 doses
Breath Actuated MDI:
100 micrograms per dose (as sulfate) x 200 doses
Respiratory solution for nebulization:
1 mg/mL (as sulfate), 2.5 mL (unit dose)
2 mg/mL (as sulfate), 2.5 mL (unit dose)
A short-acting, beta2-adrenergic agonist used in the
treatment or prevention of bronchospasm.
Indications: Prophylaxis and treatment of asthma;
bronchospasm in patients with reversible obstructive
airway disease; prevention of exercise-induced
bronchospasm
Contraindications: Severe pre-eclampsia and eclampsia;
intrauterine infection; intrauterine fetal death; ante-
partum hemorrhage, placenta previa; cord compression;
threatened miscarriage; cardiac disease
Dose:
Chronic asthma (as adjunct in stepped treatment), by
aerosol inhalation, ADULT, 100–200 micrograms (1–2
puffs) up to 3–4 times daily; CHILD, 100 micrograms (1
puff) 3–4 times daily, increased to 200 micrograms (2
puffs) 3–4 times daily if necessary.
Prophylaxis of exercise-induced bronchospasm, by aerosol
inhalation, ADULT, 200 micrograms (2 puffs); CHILD,
100 micrograms (1 puff) increased to 200 micrograms
(2 puffs) if required.
Relief of acute bronchospasm, by aerosol inhalation,
ADULT, 100–200 micrograms (1–2 puffs); CHILD, 100
micrograms (1 puff) increased to 200 micrograms (2
puffs) if necessary.
Severe acute asthma, chronic bronchospasm
(unresponsive to conventional treatment), by inhalation
of nebulized solution, ADULT and CHILD >18 months, 2.5
mg repeated up to 4 times daily; may be increased to 5
mg if necessary (consider medical assessment since
alternative therapy may be indicated); CHILD <18
months, clinical efficacy uncertain (transient hypoxemia
R
may occur – consider oxygen supplementation).
Dose Adjustment:
Geriatric:
Start with a lower dose than the usual adult dose. Gradually
increase if needed.
Precautions:
WARNING: Excessive use and reliance on beta2-
agonists for the treatment of asthma without an anti-
inflammatory agent have been associated with an
increased incidence of sudden deaths. Beta2-
agonists inhalation can occasionally cause
paradoxical bronchospasm and hypoxemia.
Paradoxical bronchospasm (should be treated immediately
with alternative therapy); discontinue treatment if the
patient develops signs of pulmonary edema; Myocardial
insufficiency, arrhythmias, susceptibility to QT-interval
prolongation, hypertension; Diabetes mellitus, especially
IV administration (monitor blood glucose);
hyperthyroidism; renal and hepatic impairment (use with
caution in high-dose treatments); Pregnancy (high doses
should be given through inhalation only); lactation
(monitor breastfeeding infant).
Adverse Drug Reactions:
Common: Cough, headache, musculoskeletal pain,
palpitations, throat irritation, tremor, upper respiratory
inflammation, viral respiratory infections
555
 RESPIRATORY SYSTEM

Less Common: Agitation, hyperactivity in children, Pregnancy Category: C

hyperglycemia (high doses), insomnia, tachycardia
Rare: Allergic reactions, hypokalemia, lactic acidosis, ATC Code: R03AC03
paradoxical bronchospasm

Drug Interactions:
Monitor closely with: Rx FORMOTEROL
Increases risk of adverse or toxic effects of Methyldopa
(acute hypotension) Inhalation:
DPI:
Avoid concomitant use with: 12 mcg dry powder for inhalation
Increases risk of adverse or toxic effects of Salbutamol:
Corticosteroids (serious hypokalemia), Diuretics (serious Formoterol is a long acting beta 2 agonist. It relaxes
hypokalemia), Drugs that increase blood glucose bronchial smooth muscle with little effect on heart rate.
concentration e.g., Glucocorticoids, Antipsychotics,
Calcineurin Inhibitors, high-dose Thiazide Diuretics, Indication: Maintenance treatment of chronic obstructive
Somatropin (hyperglycemia), Drugs that reduce pulmonary disease (COPD).
potassium concentration e.g., Amphotericin B, Diuretics
(hypokalemia), Theophylline (serious hypokalemia) Contraindications: Treatment of status asthmaticus or other
acute episodes of asthma or COPD; monotherapy
Increases risk of adverse or toxic effects of the following treatment in asthma; tachyarrhythmias.
drugs:
Sympathomimetic Amines e.g., Ephedrine, Dose:
Phenylephrine, Pseudoephedrine (sympathetic adverse Chronic obstructive pulmonary disease, by dry powder
effects e.g., tremor, tachycardia, headache) inhalation, ADULT and CHILD, 12 mcg every 12 hours
(maximum dose: 24 mcg/ day).
Reduces therapeutic effect of Beta Blockers e.g.,
Propranolol (may precipitate asthma) Dose Adjustment:
Renal and Hepatic impairment:
Administration: Multi-dose solution for nebulization may No dosage adjustments provided in the manufacturer’s
need dilution with 0.9% sodium chloride to obtain final labeling.
volume for the nebulizer.
Precautions:
Pregnancy Category: C
R

Asthma-related deaths, bronchospasm, hypersensitivity,

ATC Code: R03AC02
Rx TERBUTALINE
Inhalation:
Respiratory solution for nebulization:
2.5 mg/mL (as sulfate), 2 mL (unit dose)
A direct acting sympathomimetic drug with beta-adrenergic
activity, selectively on beta2 receptors.
Indications: Bronchodilator in reversible airway obstruction
and bronchial asthma
Contraindications: Acute or chronic use in the prevention,
treatment, or management of preterm labor
Dose:
Severe bronchospasm, by inhalation of nebulized solution,
as 1% solution, ADULT, 2.5–10 mg 2 to 4 times daily;
CHILD ≥25 kg: 5 mg 2–4 times daily.
Administration: Keep out of reach of children and pets.
Consult with pharmacist on discarding unused drugs.
See Terbutaline under Other Gynecologicals –
Sympathomimetics, Labor Repressants in Chapter 5:
Genito Urinary System and Sex Hormones for other
information.
serious effects/fatalities;
Use in caution in patients with asthma, cardiovascular
disease, COPD, diabetes, exercise-induced
bronchospasm, hyperthyroidism, hypokalemia,
pheochromocytoma, and seizure disorders.
Adverse Drug Reactions:
Less Common: Chest pain, anxiety, dizziness, insomnia,
voice disorder, headache, pruritus, skin rash, diarrhea,
nausea, xerostomia, vomiting, abdominal pain,
dyspepsia, gastroenteritis, muscle cramps, tremor,
respiratory infection, exacerbation of asthma, acute
deterioration, bronchitis, pharyngitis, sinusitis, dyspnea,
tonsillitis, and fever.
Rare: Agitation, anaphylaxis, angina pectoris, atrial
fibrillation, behavioral changes, cardiac arrhythmia,
cough, decreased glucose tolerance, dermatitis,
disturbed sleep, dysgeusia, fatigue, hyperglycemia,
hypertension, hypokalemia, malaise, metabolic acidosis,
muscle spasm, nervousness, palpitations, paradoxical
bronchospasm, prolonged Q-T interval on ECG,
restlessness, tachycardia, urticarial, variable blood
pressure, and ventricular premature contractions.
Drug Interactions:
Monitor closely with:
Decreases serum potassium when given with the following
drugs:
Salbutamol, Aspirin, Atenolol, Betaxolol, Bisoprolol,
Bumetanide, Ephedrine, Epinephrine, Esmolol,
Furosemide, Gentamicin, Hydrochlorothiazide,
Indapamide, Norepinephrine, Propranolol, Terbutaline

556
 RESPIRATORY SYSTEM

Decreases sedation: diabetes, hyperthyroidism, hypokalemia, and seizure

Salbutamol, Alprazolam, Aripiprazole, Caffeine, disorders.
Ephedrine, Epinephrine, Haloperidol, Hydroxyzine,
Norepinephrine, Risperidone, Terbutaline Adverse Drug Reactions:
Common: Nasopharyngitis
Increases QTc interval: Less Common: Skin rash, urinary tract infection, back pain,
Azithromycin, Fluoxetine, Goserelin, Levofloxacin, arthralgia, and bronchitis.
Ofloxacin, Quinine, Risperidone, Co-trimoxazole, Rare: Asthma-related death, constipation, cough,
Voriconazole depression of ST segment on ECG, diarrhea, dizziness,
fever, hypersensitivity reaction, hypokalemia, rhinorrhea,
Increases adrenergic effects of Formoterol: and upper respiratory tract infection.
Ephedrine, Epinephrine, Norepinephrine, Olodaterol,
Terbutaline, Salbutamol Drug Interactions:
Monitor closely with:
Decreases effects of Formoterol: Increases QTc interval:
Atenolol, Betaxolol, Bisoprolol, Carvedilol, Esmolol, Alfuzosin, Amiodarone, Artemether/Lumefantrine,
Metoprolol, Propranolol. Azithromycin, Chlorpromazine, Ciprofloxacin,
Clarithromycin, Erythromycin, Escitalopram, Fluconazole,
Avoid concomitant use with: Fluoxetine, Fluphenazine, Haloperidol, Levofloxacin,
Increases QTc interval: Moxifloxacin, Octreotide, Ofloxacin, Quetiapine, Quinine,
Amiodarone, Artemether/Lumefantrine, Risperidone, Tacrolimus, Voriconazole
Chlorpromazine, Clarithromycin, Epinephrine,
Erythromycin, Fluconazole, Fluphenazine, Haloperidol, Decreases serum potassium when given with the following
Ketoconazole, Moxifloxacin, Octreotide, Ondansetron drugs:
Betamethasone, Bumetanide, Dexamethasone,
Increases effect of Formoterol: Linezolid Furosemide, Hydrochlorothiazide, Hydrocortisone,
Prednisone
Administration: Remove capsule from foil blister
immediately before use. Capsules must not be Increases adrenergic effects:
swallowed whole; must only use the aerolizer inhaler. Dobutamine, Dopamine, Ephedrine, Epinephrine,
Formoterol, Indacaterol, Norepinephrine, Phenylephrine,
Pregnancy Category: C Terbutaline.

ATC Code: R03AC13 Antagonizes the effects of Olodaterol:

R
Carvedilol, Propranolol

Administration: For oral inhalation only; administer at the

Rx OLODATEROL same time each day. Prime inhaler prior to initial use or
if not used >21 days by pointing inhaler towards ground
Inhalation: 2.5 mcg/puff solution for inhalation, inhaler and actuating until aerosol cloud is seen, then repeat 3
with 4 mL cartridge x 60 puffs (equivalent to 30 additional times before use. If not used for >3 days,
medicinal doses) actuate once before use.

Oladeterol is long acting beta2-receptor agonist. It induces Pregnancy Category: C

bronchodilation by relaxation of airway smooth muscle
cells. ATC Code: R03AC19

Indication: Long term maintenance treatment of airflow

obstruction in chronic obstructive pulmonary disease
(COPD).

Contraindication: Monotherapy in the treatment of asthma

Dose:
Chronic obstructive pulmonary disease, by oral inhalation,
ADULT, 2 inhalations once daily.

Dose Adjustment:
Renal and Hepatic impairment:
No adjustment necessary.

Precautions:
May cause asthma-related deaths, bronchospasm,
hypersensitivity reactions, serious effects/fatalities; use
in caution in patients with cardiovascular disease, COPD,

557

Rx BUDESONIDE + FORMOTEROL
Inhalation:
DPI:
80 micrograms budesonide + 4.5 micrograms formoterol
(as fumarate dihydrate) x 60 doses with appropriate
accompanying dispenser
160 micrograms budesonide + 4.5 micrograms
formoterol (as fumarate dihydrate) x 60 doses with
appropriate accompanying dispenser
320 micrograms budesonide + 9 micrograms formoterol
(as fumarate) x 60 doses with appropriate accompanying
dispenser
MDI:
80 micrograms budesonide + 4.5 micrograms formoterol
(as fumarate dihydrate) x 120 doses and 120 doses with
appropriate accompanying dispenser
160 micrograms budesonide + 4.5 micrograms
formoterol (as fumarate dihydrate) x 120 doses with
appropriate accompanying dispenser
A combination product containing a corticosteroid and a
long-acting beta2-adrenergic agonist.
Indications: Treatment of asthma in patients ≥12 years of
age where combination therapy is indicated;
maintenance treatment of airflow obstruction associated
with chronic obstructive pulmonary disease (COPD),
including chronic bronchitis and emphysema
Contraindications: As primary treatment of status
asthmaticus, acute episodes of asthma or COPD
R
requiring intensive measures, and potentially worsening
or rapidly deteriorating asthma or COPD.
Dose:
NOTE: Recommended starting dose combination is
determined according to asthma severity. Consider
higher dose combination if not adequately controlled on
the lower combination dose following 1–2 weeks of
therapy.
Asthma, by aerosol inhalation, ADULT, 2 inhalations
(80/4.5mcg or 160/4.5mcg) twice daily (maximum, 4
inhalations daily).
COPD, by aerosol inhalation, ADULT, 2 inhalations
(160mcg/4.5mcg) twice daily (maximum, 4 inhalations
daily).
Precautions:
WARNING: Long-acting beta2-adrenergic agonists (LABAs)
increase the risk of asthma-related death and asthma-
related hospitalization in pediatric and adolescent
patients. Use only in patients not adequately controlled
on a long-term asthma control medication or if disease
severity clearly warrants treatment with both an inhaled
corticosteroid and a LABA. Once asthma control is
achieved and maintained, assess the patient at regular
intervals and step-down therapy if possible without loss
of asthma control, and maintain the patient on a long-
term asthma control medication.
Adrenal suppression; diabetes; Bone density; osteoporosis;
Bronchospasm; asthma (not for acute bronchospasm);
558
RESPIRATORY SYSTEM
COPD (not use for acute episodes of COPD);
Hypersensitivity reactions; immunosuppression (restrict
use in active TB); lower respiratory infections (monitor
patients closely); oral candidiasis; Serious effects or
fatalities; Vasculitis; cardiovascular disease; Renal
impairment; hepatic impairment (monitor closely due to
hepatic metabolism of both agents); Hypokalemia;
Ocular disease (consider routine eye exams in chronic
users); Seizure disorders; Thyroid disease (changes in
thyroid status may necessitate dose adjustments;
metabolic clearance of corticosteroids increases in
hyperthyroid patients and decreases in hypothyroid
ones); Children (titrate to lowest effective dose to
minimize the systemic effects; growth should be
routinely monitored); Pregnancy and lactation (refer to
individual agents).
Adverse Drug Reactions:
Common: Headache, dizziness, abdominal distress, oral
candidiasis, vomiting, influenza, back pain, upper and
lower respiratory tract infection, pharyngolaryngeal pain,
sinusitis, bronchitis, nasal congestion
Less Common: Agitation, anaphylaxis, angina pectoris,
angioedema, anxiety, atrial arrhythmia, behavioral
changes, bronchospasm, bruise, cataract, cough,
decreased linear skeletal growth rate (children),
depression, dermatitis, extrasystoles, glaucoma,
hypercorticoidism signs and symptoms, hyperglycemia,
hypersensitivity reaction, hypertension, hypokalemia,
hypotension, immunosuppression, increased intraocular
pressure, insomnia, muscle cramps, nausea,
nervousness, palpitations, pruritus, restlessness, skin
rash, tachycardia, throat irritation, tremor, urticaria,
ventricular arrhythmia, voice disorder
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Budesonide + Formoterol:
Atomoxetine (tachycardia; hypertensive effect),
Cannabinoid [except Cannabidiol] (tachycardia),
Tedizolid (tachycardia; hypertensive effect)
Increases risk of adverse or toxic effects of Budesonide +
Formoterol:
Amphotericin B (hypokalemic effec), Caffeine
(hypokalemic effect), Inhalational Anesthetics
(arrhythmogenic effect), MAO Inhibitors, Other
Sympathomimetics, Tricyclic Antidepressants
Increases risk of adverse or toxic effects of the following
drugs:
Atosiban (pulmonary edema and/or dyspnea), Ceritinib
(hyperglycemic effect), Deferasirox (GI ulceration,
irritation, or bleeding), Doxofylline, Loop Diuretics
(hypokalemic effect), Moderate Risk QTc-prolonging
Agents (QTc-prolonging effect), Theophylline Derivatives
(hypokalemic effect), Thiazide Diuretics (hypokalemic
effect)
Reduces therapeutic effect of Budesonide + Formoterol:
Beta1 Blockers (bronchodilator effect), Betahistine
Avoid concomitant use with:
Enhances therapeutic effect of Budesonide + Formoterol:
Linezolid (hypertensive effect) [reduce initial doses
Budesonide + Formoterol]
RESPIRATORY SYSTEM
Increases risk of adverse or toxic effects of Budesonide +
Formoterol:
Mifepristone (QTc-prolonging effect), Other Long-acting
Beta2 Agonists
Increases risk of adverse or toxic effects of the following
drugs:
Highest Risk QTc-prolonging Agents (QTc-prolonging
effect), Loxapine
Increases serum concentration of Budesonide: Telaprevir
Reduces therapeutic effect of Budesonide + Formoterol:
Beta Blockers, Nonselective (bronchodilator effect)
Reduces therapeutic effect of the following drugs:
Aldesleukin (antineoplastic effect), Hyaluronidase,
Iobenguane I 123
Administration: Prior to first use, “load” the inhaler by
turning the grip on the inhaler as far as it will move in 1
direction, then turning in the opposite direction as far as
it will go. The inhaler is “loaded” with a dose, indicated
by a “click”. Loading procedure should be done twice. It
does not need to be repeated with subsequent uses even
when not used regularly.
Place mouthpiece gently between teeth, closing lips
around inhaler. Inhale deeply and hold breath for 5–10
seconds. The amount of drug delivered is small, and the
individual will not sense the medication as it is inhaled.
Remove mouthpiece prior to exhalation. Do NOT breathe
out through the mouthpiece. After use of the inhaler,
rinse mouth or oropharynx with water and spit out rinse
solution.
Withdrawal and discontinuation of a corticosteroid
should be done slowly and carefully. Use with caution
when transferring from systemic to inhaled
corticosteroids.
Pregnancy Category: B
ATC Code: R03AK07
Rx FLUTICASONE + FORMOTEROL
Inhalation:
MDI:
50 micrograms (as propionate) + 5 micrograms (as
fumarate) x 120 actuations
125 micrograms (as propionate) + 5 micrograms (as
fumarate) x 120 actuations
250 micrograms (as propionate) + 10 micrograms (as
fumarate) x 120 actuations
A combination product containing a corticosteroid with
glucocorticoid activity and a long-acting beta2-adrenergic
agonist.
Indication: Management of adult asthma
Contraindication: acute asthma attack
Dose:
Asthma, by aerosol inhalation, ADULT and CHILD ≥12 years,
initially 2 puffs twice daily, titrated to the lowest effective
dose; may be increased by switching to next highest
strength combination, depending on patient’s response.
Dose Adjustment: No information found
Precautions:
Patient with active or quiescent pulmonary TB, untreated
systemic infections, ocular herpes simplex, or with
fungal, viral or airway infections, thyrotoxicosis,
pheochromocytoma, diabetes mellitus, hypokalemia,
cardiovascular disorders; hepatic impairment;
Pregnancy and lactation.
Adverse Drug Reactions: Hypokalemia, paradoxical
bronchospasm, increased wheezing, shortness of
breath, QTc interval prolongation, insomnia, headache,
tremor, dizziness, abnormal dreams, agitation, asthenia,
palpitations, ventricular extra-systoles, angina pectoris,
tachycardia, hypertension, peripheral edema, oral
candidiasis or fungal infections, hoarseness, stomatitis,
dry mouth, diarrhea, dyspepsia, nausea, asthma
exacerbation, dysphonia, throat irritation, sinusitis,
hyperglycemia, increased blood lactate levels, decrease
BMD, cataract, glaucoma, rash, pruritus, contusion, skin
atrophy, anaphylaxis reactions, arrhythmia (potentially
fatal), cardiac arrest (potentially fatal)
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Fluticasone +
Formoterol:
R
Alcohol (impaired cardiac tolerance)
Antihistamines e.g. Diphenhydramine (prolonged QTc-
interval)
Antipsyschotic Agents (prolonged QTc-interval)
Digitalis Glycoside e.g. Digoxin (ventricular arrhythmias)
Disopyramide (prolonged QTc-interval)
Halogenated Hydrocarbon Anesthetics (ventricular
arrhythmias)
L-dopa (impaired cardiac tolerance)
L-thyroxine (impaired cardiac tolerance)
MAO Inhibitors e.g. Phenelzine (prolonged QTc-interval)
Oxytocin (impaired cardiac tolerance)
Procainamide (prolonged QTc-interval)
Quinidine (prolonged QTc-interval)
Tricyclic Antidepressants (prolonged QTc-interval)
Increases risk of adverse or toxic effects of the following
drugs:
Diuretics (hypokalemia)
Steroids (hypokalemia)
Xanthine Derivatives e.g. Theophylline (hypokalemia)
Increases serum concentration of Fluticasone:
CYP3A4 Inhibitors e.g., Ketoconazole, HIV Protease
Inhibitors, Clarithromycin, Ketoconazole
Reduces therapeutic effect of Fluticasone + Formoterol:
Beta Blockers e.g. Propranolol
Administration: Rinse mouth thoroughly every after
inhalation.
559

Avoid abrupt withdrawal.
Pregnancy Category: C
ATC Code: R03AK11
Rx FLUTICASONE + SALMETEROL
Inhalation:
DPI:
100 micrograms fluticasone (as propionate) + 50
micrograms salmeterol (as xinafoate) x 28 doses and 60
doses with appropriate accompanying dispenser
250 micrograms fluticasone (as propionate) + 50
micrograms salmeterol (as xinafoate) x 28 doses and 60
doses with appropriate accompanying dispenser
500 micrograms fluticasone (as propionate) + 50
micrograms salmeterol (as xinafoate) x 28 doses and 60
doses with appropriate accompanying dispenser
MDI:
50 micrograms fluticasone (as propionate) + 25
micrograms salmeterol (as xinafoate) x 120 actuations
(with dose counter*)
125 micrograms fluticasone (as propionate) + 25
micrograms salmeterol (as xinafoate) x 120 actuations
(*)
250 micrograms fluticasone (as propionate) + 25
micrograms salmeterol (as xinafoate) x 120 actuations
(*)
R
A combination product containing an inhaled corticosteroid,
and a long-acting beta2-adrenoceptor agonist, which is
used for controlling the symptoms of asthma.
Indications: For asthma patients aged 4 years and older;
maintenance treatment of airflow obstruction, and
reduction of exacerbations in patients with COPD
NOTE: This should be used only if the asthma is deemed to
be not well-controlled with a long-term asthma control
medicine (e.g., inhaled corticosteroids).
Contraindications: As primary treatment of status
asthmaticus, acute episodes of asthma or COPD
requiring intensive measures, and potentially worsening
or rapidly deteriorating asthma or COPD.
Dose:
Treatment of asthma, by aerosol inhalation, ADULT and
CHILD ≥12 years, 1 inhalation (100/50 or 250/50) twice
daily; start dose based on asthma severity; CHILD 4–11
years, 1 inhalation (100/50) twice daily.
Maintenance treatment of COPD, by aerosol inhalation,
ADULT, 1 inhalation (250/50) twice daily.
Precautions:
Deterioration of disease and acute episodes: do not initiate
in acutely deteriorating asthma or to treat acute
symptoms; Do NOT combine LABAs because of risk of
overdose; Localized infections; Immunosuppression;
Pneumonia; Cardiovascular and CNS disorders;
Hypercorticolism and adrenal suppression; Decreased
bone mineral density; Growth effects; Glaucoma and
560
RESPIRATORY SYSTEM
cataracts; Metabolic effects (be alert to eosinophilic
conditions, hypokalemia and hyperglycemia); Patients
with convulsive disorders, thyrotoxicosis, diabetes
mellitus and ketoacidosis.
Adverse Drug Reactions:
Common: Dizziness, dysphonia, headache, nausea,
palpitations, throat irritation, upper respiratory tract
infection and inflammation, tremor, vomiting
Less Common: Agitation, hyperactivity in children,
hyperglycemia (high doses), insomnia, tachycardia
Rare: Allergic reactions (including urticaria, angioedema,
anaphylaxis), hypokalemia, lactic acidosis, paradoxical
bronchospasm
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Fluticasone + Salmeterol:
CYP450 3A4 Inhibitors e.g. Ritonavir (may cause
systemic corticosteroid and cardiovascular effects)
Increases risk of adverse or toxic effects of Fluticasone +
Salmeterol:
Corticosteroids (serious hypokalemia), Diuretics e.g.,
Furosemide, Hydrochlorothiazide (serious hypokalemia),
Drugs that increase blood glucose concentration e.g.,
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors
e.g., Tacrolimus, high-dose Thiazide Diuretics e.g.
Hydrochlorothiazide, Somatropin (hyperglycemia), Drugs
that reduce potassium concentration e.g., Amphotericin
B, Theophylline (serious hypokalemia)
Increases risk of adverse or toxic effects of the following
drugs:
Sympathomimetic Amines e.g., Ephedrine,
Phenylephrine, Pseudoephedrine (sympathetic adverse
effects e.g., tremor, tachycardia, headache)
Increases serum concentration of Fluticasone + Salmeterol:
CYP450 3A4 Inhibitors e.g. Ritonavir
Reduces therapeutic effect of Beta Blockers (may
precipitate asthma)
Administration: Should be administered twice daily every
day by the orally inhaled route only. After inhalation, the
patient should rinse the mouth with water and spit out
the water without swallowing.
Pregnancy Category: C
ATC Code: R03AK06
Rx IPRATROPIUM + FENOTEROL
Inhalation:
MDI:
20 micrograms ipratropium (as bromide) + 50
micrograms fenoterol (as hydrobromide) x 10 mL doses
A combination product containing an inhaled nonselective
competitive antimuscarinic agent, and a direct acting
beta2 sympathomimetic agent. They collectively cause
RESPIRATORY SYSTEM

bronchodilation and bronchial smooth muscle Reduces therapeutic effect of Ipratropium + Fenoterol:
relaxation. Beta Blockers (bronchodilator effect)

Indications: For acute asthma attacks; maintenance Administration: Rinse mouth every after inhalation.
treatment of airflow obstruction, and reduction of
exacerbations in patients with COPD; intermittent and Avoid contact with eyes.
long-term treatment of asthma and COPD
Pregnancy Category: C
Contraindications: Hypersensitivity to atropine or any of its
derivatives; Hypertrophic obstructive cardiomyopathy; ATC Code: R03AL01
tachyarrhythmia;

Dose:
Acute asthma attack, by aerosol inhalation, ADULT, 1 puff
for prompt relief, if there is no improvement after 5
minutes, 1 additional dose may be given; if there is no
relief after 2 administrations, further doses may be
required.
Asthma and COPD, intermittent and long-term treatment, by
aerosol inhalation, ADULT, 1 to 2 puffs, up to 3 times
daily (maximum, 8 puffs daily).
Dose Adjustment: No information found
Rx IPRATROPIUM + SALBUTAMOL
Inhalation:
MDI:
20 micrograms ipratropium (as bromide) + 100
micrograms salbutamol x 200 doses x 10 mL
Respiratory solution for nebulization:
500 micrograms ipratropium (as bromide anhydrous) +
2.5 mg salbutamol (as base) x 2.5 mL (unit dose)

Precautions: A combination of a cholinergic antagonist and a short-

Cardiovascular disease; cystic fibrosis; diabetes mellitus; acting, beta2-adrenoceptor agonist, which is used for the
narrow-angle glaucoma; pheochromocytoma; prostatic treatment of chronic obstructive pulmonary diseases; in
hyperplasia or bladder-neck obstruction; which monotherapy is deemed to be insufficient.
hyperthyroidism; seizure disorder; Children; Lactation.
Indications: Treatment of COPD in patients who are
SKILLED TASKS. May cause dizziness, tremor and visual currently on a regular bronchodilator, who continue to
disturbances. Do NOT drive or operate machinery. have evidence of bronchospasm and require a second
bronchodilator
Adverse Drug Reactions:

R
Common and Less Common: Hypokalemia, atrial fibrillation, Contraindications: Tachyarrhythmias; hypertrophic
cardiac arrhythmia, ischemic heart disease, palpitations, obstructive cardiomyopathy; Hypersensitivity to atropine
QT prolongation, supraventricular tachycardia, or any of its derivatives
tachycardia, headache, nervousness, tremor, weakness,
dizziness, hypertension, palpitation, hot flushes, Dose:
hypotension, glossitis, xerostomia, nausea, stomatitis, Bronchospasm, by aerosol inhalation, ADULT, 1 inhalation
constipation, diarrhea, vomiting, throat irritation, cough, 4 times a day, should not exceed 6 inhalations in 24
pharyngitis, hoarseness, urinary retention, hours.
hyperglycemia, muscle cramps, myalgia, visual Treatment of acute attacks, by inhalation of nebulized
accommodation disturbance, eye pain, increased solution using a suitable nebulizer or an intermittent
intraocular pressure, mydriasis, acute angle-closure positive pressure ventilator, ADULT, 1 unit-dose vial; 2
glaucoma, diaphoresis, paradoxical bronchospasm unit-dose vials may be required for severe cases, which
(potentially fatal) have not been relieved by 1 unit-dose vial; consult the
Rare: Anaphylaxis (e.g., urticaria, angioedema, rash, physician immediately.
bronchospasm) Maintenance treatment of acute attacks, by inhalation of
nebulized solution using a suitable nebulizer or an
Drug Interactions: intermittent positive pressure ventilator, ADULT, 1 unit-
Avoid concomitant use with: dose vial 3–4 times daily.
Enhances therapeutic effect of Ipratropium + Fenoterol:
Βeta Agonists, Salbutamol (bronchodilator effect) NOTE: Do NOT administer unit-dose vial orally or
MAO Inhibitors e.g. Phenelzine parenterally. The content does not need to be diluted for
Tricyclic Antidepressants e.g. Amitryptilline nebulization.
Xanthine Derivatives e.g. Theophylline (bronchodilator
effect) Dose Adjustment:
Renal and Hepatic Impairment:
Increases risk of adverse or toxic effects of Ipratropium + For mild-to-moderate impairment, use with caution.
Fenoterol: For severe impairment, refer patient to a specialist.
Corticosteroids (hypokalemia)
Diuretics (hypokalemia) Precautions:
Halogenated Hydrocarbons e.g. Halothane Some preparations contain soya lecithin (do NOT use in
(cardiovascular effects) patients allergic to soya lecithin or related food products,
Xanthine Derivatives e.g. Theophylline (hypokalemia) such as soybean and peanut); Patients with

561

cardiovascular system disorders (use with caution due to
beta-adrenergic stimulation); urinary retention (use with
caution in patients with prostatic hyperplasia or bladder
neck obstruction); paradoxical bronchospasm
(discontinue immediately and treat with alternative
therapy); Ocular effects (avoid spraying into the eyes;
contact a physician if blurred vision, halos, or other visual
disturbances occur); Carefully monitor patients with
narrow-angle glaucoma; Hypersensitivity reactions
(discontinue treatment); hyperthyroidism; diabetes
mellitus; convulsive disorders; Children; (safety and
efficacy have not been established).
Pregnancy (restricted to those where the benefits clearly
outweigh the risk).
Adverse Drug Reactions:
Common: Back pain, bronchitis, cough, dryness of mouth,
dyspepsia, dyspnea, headache, influenza-like symptoms,
musculoskeletal pain, myalgia, nasopharyngitis, nausea,
pharyngitis, sinusitis, taste disturbance, throat irritation,
tremor, upper respiratory inflammation and infection,
urinary tract infection
Less Common: Agitation, blurred vision, diarrhea, dizziness,
fatigue, hyperactivity in children, hyperglycemia (high
doses), insomnia, vomiting
Rare: Acute closed-angle glaucoma, arrhythmias, asthenia,
atrial fibrillation, chest discomfort, constipation, dental
caries, dryness of skin, eye pain, hypersensitivity
reactions (including anaphylaxis, angioedema,
bronchospasm, rash, urticaria and oropharyngeal
edema), hypokalemia, palpitations, paradoxical
bronchospasm, tachycardia, urinary retention, wheezing
Drug Interactions:
R
Monitor closely with:
Enhances therapeutic effect of Salbutamol on the vascular
system:
MAO Inhibitors e.g. Phenelzine, Tricyclic Antidepressants
e.g. Amitryptilline
Increases risk of adverse or toxic effects (hypokalemia) of
Ipratropium + Salbutamol:
Corticosteroids e.g. Hydrocortisone, Diuretics e.g.,
Hydrochlorothiazide, Furosemide, Drugs reducing
Potassium Concentration e.g., Amphotericin B,
Theophylline
Avoid concomitant use with:
Enhances therapeutic effect of Ipratropium + Salbutamol:
Anticholinergic Drugs
Other Drugs with Anticholinergic Effects
Increases risk of adverse or toxic effects of Ipratropium +
Salbutamol:
Anticholinergic Drugs (central anticholinergic delirium),
Drugs increasing Blood Glucose Concentration e.g.,
Glucocorticoids, Antipsychotics, Calcineurin Inhibitors,
high-dose Thiazide Diuretics, Somatropin
(hyperglycemia)
Other Drugs with Anticholinergic Effects (central
anticholinergic delirium)
Increases risk of adverse or toxic effects of the following
drugs:
562
RESPIRATORY SYSTEM
Sympathomimetic Amines e.g., Ephedrine,
Phenylephrine (sympathetic adverse effects e.g., tremor,
tachycardia, headache)
Reduces therapeutic effect of Ipratropium + Salbutamol:
Anticholinesterases e.g. Neostigmine (anticholinergic
effect), Beta Blockers e.g. Propranolol (may precipitate
asthma)
Administration: Metered-dose inhalers require good hand-
breath coordination (unsuitable for use alone in children
<8 years or for people with poor dexterity).
The respiratory solution for nebulization should be
administered via a mouth piece. If this is not available, a
nebulizer mask should be used, and it should fit
perfectly. Patients who may be predisposed to glaucoma
should be warned specifically to protect their eyes.
Pregnancy Category: C
ATC Code: R03AL02
ADRENERGICS IN COMBINATION WITH
ANTICHOLINERGICS INCL. TRIPLE COMBINATIONS
WITH CORTICOSTERIODS
Rx INDACATEROL+ GLYCOPYRRONIUM
Inhalation: 110 mcg Indacaterol + 50 mcg
Glycopyrronium inhalation powder in hard
capsules
Indacaterol is a long-acting beta 2 agonist while
glycopyronium is a long-acting muscarinic antagonist.
Indication: Long-term maintenance treatment of chronic
obstructive pulmonary disease (COPD).
Contraindications: Hypersensitivity to indacaterol,
glycopyrrolate, or any component of the formulation;
monotherapy in patients with asthma.
Dose:
Chronic obstructive pulmonary disease (COPD), by powder
inhalation, ADULT, one capsule (indacaterol 110
mcg/glycopyrrolate 50 mcg) inhaled once daily
(maximum: 1 capsule/day); CHILD, safety and efficacy
not established.
Dose Adjustment:
Renal and Hepatic impairment:
No dosage adjustment necessary; use with caution.
Precautions:
Asthma-related deaths (Indacaterol/glycopyrrolate is not
indicated for the treatment of asthma);
CNS depression (Patient must be cautioned about
performing tasks which require mental alertness);
Hypersensitivity (Discontinue immediately if signs and
symptoms of an allergic reaction occur);
Cardiovascular disease (Use with caution in patients with
cardiovascular disease);
RESPIRATORY SYSTEM
Beta-agonists may cause elevation in blood pressure and
heart rate;
Diabetes (aggravate preexisting diabetes and ketoacidosis
and increase serum glucose);
Severe hepatic function impairment;
Hyperthyroidism;
Hypokalemia (decrease serum potassium);
Narrow angle glaucoma;
Prostatic hyperplasia/bladder neck obstruction (may
worsen urinary retention;
Renal function impairment (Use with caution in patients with
severe renal impairment (GFR <30 mL/minute/1.73 m2)
or end-stage renal disease (ESRD) on dialysis; monitor
closely);
Seizure disorders (CNS stimulation/excitation)
Adverse Drug Reactions:
Less Common: Hypertension, headache, hyperglycemia,
diarrhea, gastroesophageal reflux disease, back pain,
nasopharyngitis, lower and upper respiratory tract
infection, pneumonia, rhinitis, and oropharyngeal pain.
Rare: Atrial fibrillation, bladder outflow obstruction, chest
pain, dizziness, dyspepsia, fatigue, gastroenteritis,
hypersensitivity reaction, insomnia, palpitations,
peripheral edema, pruritus, skin rash, tachycardia, and
urinary retention.
Drug Interactions:
Monitor closely with:
Increases toxicity of the following drugs:
Long Acting Beta2-Agonists e.g. Salbutamol, Systemic
Corticosteroids, Glucagon, Loop Diuretics e.g.
Furosemide, Opioid Analgesics, Potassium Chloride,
Potassium Citrate, QT-Prolonging Agents,
Sympathomimetics, Thiazide And Thiazide-Like Diuretics,
Tiotropium, Topiramate.
Administration: For oral inhalation only; do not swallow
capsules. Administer at the same time each day. Do not
remove capsules from blister until immediately before
use. Discard any capsules that are exposed to air and not
used immediately. Use the new inhaler device included
with each prescription.
Pregnancy Category: C
ATC Code: R03AL04
OTHER DRUGS FOR OBSTRUCTIVE
AIRWAY DISEASES, INHALANTS
Rx BUDESONIDE
Inhalation:
DPI:
100 micrograms/dose x 200 doses with appropriate
accompanying dispenser
200 micrograms/dose x 100 doses and 200 doses with
appropriate accompanying dispenser
Respiratory solution for nebulization:
250 micrograms/mL, 2 mL (unit dose)
A corticosteroid with potent glucocorticoid activity and weak
mineralocorticoid activity. It controls the rate of protein
synthesis, depresses the migration of
polymorphonuclear leukocytes, fibroblasts, and reverses
capillary permeability and lysosomal stabilization at the
cellular level to prevent or control inflammation.
Indications: Maintenance and prophylactic treatment of
asthma; includes patients who require oral
corticosteroids and those who may benefit from systemic
dose reduction or elimination
Contraindications: Primary treatment of status asthmaticus
and acute episodes of asthma
NOTE: NOT for the relief of acute bronchospasm.
R
Dose:
NOTE: A low-dose inhaled corticosteroid (in addition to an
as-needed short acting beta 2­agonist) is the initial
preferred long-term control medication for children,
adolescents, and adult patients with persistent asthma
who are candidates for treatment according to a step-
wise treatment approach.
Asthma, by inhalation, ADULT, initially 360 micrograms
twice daily, some patients may be initiated at 180
micrograms twice daily (maximum, 720 micrograms
twice daily), may increase dose after 1–2 weeks of
therapy in patients who are not adequately controlled;
CHILD ≥6 years, initially 180 micrograms twice daily,
some patients may be initiated at 360 micrograms twice
daily (maximum: 360 micrograms twice daily), may
increase dose after 1–2 weeks of therapy in patients
who are not adequately controlled;
by nebulization, CHILD 12 months – 8 years, initially
0.25 mg daily;
If previously on bronchodilators alone, 0.5 mg daily
administered as a single dose or divided twice daily
(maximum daily dose, 0.5 mg);
If previously on inhaled corticosteroids, 0.5 mg daily
administered as a single dose or divided twice daily
(maximum daily dose, 1 mg);
If previously on oral corticosteroids, 1 mg/day
administered as a single dose or divided twice daily
(maximum daily dose, 1 mg).
NOTE: Titrate to lowest effective dose once patient is stable.
563

Conversion from oral systemic to orally inhaled
corticosteroid. Initiation of oral inhalation therapy should
begin in patients whose asthma is reasonably stabilized
on oral corticosteroids (OCS). A gradual dose reduction
of OCS should begin ~7 to 10 days after starting inhaled
therapy.
Administration:
For dry powder inhalers (DPI):
Hold inhaler in upright position (mouthpiece up) to load
dose. Do NOT shake prior to use. Unit should be primed
prior to first use only. It will not need to be primed again,
even if not used for a long time. Place mouthpiece
between lips and inhale forcefully and deeply. Do NOT
exhale through inhaler. Do NOT use a spacer. Dose
indicator does NOT move with every dose, usually only
after 5 doses. Discard when dose indicator reads “0”.
Rinse mouth with water after each use to reduce
incidence of candidiasis.
For respiratory solutions for nebulization:
Shake well before use. Use with jet nebulizer connected
to an air compressor. Administer with mouthpiece or
facemask. Do NOT use ultrasonic nebulizer. Do NOT mix
with other medications in the nebulizer. Rinse mouth
following treatments to decrease risk of oral candidiasis.
Wash face if face mask was used.
See Budesonide under Nasal Preparations – paradoxical bronchospasm (potentially fatal)
Decongestants and other nasal preparations for topical
use in 12: Respiratory System for other information.
Pregnancy Category: B
R
ATC Code: R03BA02
OTC FLUTICASONE
Inhalation:
Nasal Aqueous Solution:
0.05%/dose (as propionate) x 120 doses
DPI:
50 micrograms/dose (as propionate) with appropriate
accompanying dispenser
250 micrograms/dose (as propionate) with appropriate
accompanying dispenser
MDI:
50 micrograms/dose (as propionate) x 60 doses and
120 doses
125 micrograms/dose (as propionate) x 60 doses and
120 doses
Respiratory solution for nebulization:
250 micrograms/mL (as propionate), 2 mL (unit dose)
A glucocorticoid with a fluorocarbothioate ester linkage at
the 17-carbon position. It has potent vasoconstrictive
and anti-inflammatory activity, but weak hypothalamic-
pituitary-adrenal (HPA) inhibitory effect when applied
topically.
Indication: Prophylaxis of asthma
564
RESPIRATORY SYSTEM
Dose:
Asthma prophylaxis, by aerosol inhalation, ADULT, 100–
200 micrograms 1–2 times daily in mild asthma; up to
500–1,000 micrograms twice daily in severe cases;
CHILD 4–16 years, 50–100 micrograms twice daily,
increased to 200 micrograms twice daily, if necessary.
Severe chronic asthma, by inhalation of nebulized solution,
ADULT, 500–2,000 micrograms twice daily CHILD 4–16
years, 1,000 micrograms twice daily.
Dose Adjustment: No information found
Precautions:
Patient with active or latent TB; Fungal, bacterial or systemic
viral infection; Cataracts and/or glaucoma; Untreated
localized infection of the nasal mucosa; Untreated
cutaneous infection, rosacea, acne vulgaris, perioral
dermatitis, perianal or genital pruritus, pruritus without
inflammation; Hepatic impairment; Avoid abrupt
withdrawal when switching from systemic to oral or orally
inhaled corticosteroid; Children; Pregnancy and
lactation.
Adverse Drug Reactions:
Common and Less Common: Eosinophilic conditions,
adrenal insufficiency, growth retardation, Cushing's
syndrome, decreased bone density, cataract, glaucoma,
Rare: Psychological effects
Drug Interactions:
Increases serum concentration of Fluticasone:
CYP3A4 Inhibitors e.g. Ritonavir
Administration: Administer twice daily every day by the orally
inhaled route only. After inhalation, rinse the mouth with
water and spit out the water without swallowing.
Pregnancy Category: C
ATC Code: R03BA05
Rx IPRATROPIUM
Inhalation:
MDI:
20 micrograms/dose (as bromide) x 200 doses
Respiratory solution for nebulization:
250 micrograms/mL (as bromide), 2 mL (unit dose)
A selective, anticholinergic bronchodilator that is a
quaternary ammonium compound chemically related to
atropine, and provides local, site-specific effect rather
than a systemic effect.
Indication: Chronic asthma
Dose:
Adjunct in acute bronchospasm, by inhalation of nebulized
solution, ADULT, 500 micrograms repeated as required;
CHILD 6–12 years, 250 micrograms (maximum, 1 mg
RESPIRATORY SYSTEM
daily); CHILD <6 years, 125–250 micrograms
(maximum, 1 mg daily).
Chronic asthma, by aerosol inhalation, ADULT, 20–40
micrograms, 3–4 times daily; CHILD 6–12 years, 20–40
micrograms 3 times daily; CHILD <6 years, 20
micrograms 3 times daily.
Dose Adjustment:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, use with caution.
For severe impairment, refer patient to a specialist.
Precautions:
Prostatic hypertrophy; glaucoma (care needed to protect the
patient's eyes from drug powder or nebulized drug);
myasthenia gravis; paradoxical bronchospasm (should
be distinguished from inadequate response); Medical
supervision is necessary for first dose of nebulized
solution; Elderly (they may find it difficult to use the MDI;
a spacer device may be useful to monitor urinary function
in elderly men with benign prostatic hypertrophy);
Pregnancy (inhaled ipratropium may be recommended
for use as additional therapy for severe asthma
exacerbations); breastfeeding (use with caution in
nursing women).
Adverse Drug Reactions:
Common: Back pain, bronchitis, COPD exacerbation, cough,
dry mouth, dyspepsia, dyspnea, headache, influenza-like
symptoms, nausea, sinusitis, taste disturbance, throat
irritation, urinary tract infections
Less Common: Blurred vision, dizziness
Rare: Acute closed-angle glaucoma, allergy (urticaria, rash,
angioedema, anaphylaxis), atrial fibrillation,
constipation, dental caries, dryness of skin, palpitations,
tachycardia, urinary retention
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Ipratropium:
Analgesics, Opioids (constipation; urinary retention),
Anticholinergic Drugs e.g. Atropine (central
anticholinergic delirium)
Other Drugs with Anticholinergic Effects (central
anticholinergic delirium)
Increases serum concentration of Thiazide Diuretics
e.g. Hydrochlorothiazide
Administration: Dilute solution for nebulization to 2–3 mL
with sodium chloride 0.9%.
NOTE: Do NOT reduce or stop inhaled corticosteroids even
if the patient feels better after starting this drug.
Do NOT let the mist from the nebulizer get into the eyes
(close eyes or wear eye protection).
Pregnancy Category: B
ATC Code: R03BB01
Rx TIOTROPIUM
Inhalation:
DPI:
18 micrograms/dose (as bromide) with appropriate
accompanying dispenser
A competitively acetylcholine inhibitor that reversibly
inhibits its action at type 3 muscarinic (M3) receptors in
bronchial smooth muscle causing bronchodilation.
Indications: Maintenance treatment of bronchospasm
associated with chronic obstructive pulmonary disease
(COPD), including chronic bronchitis and emphysema;
reduction of COPD exacerbations
Contraindications: Hypersensitivity to atropine or its
derivatives
Dose:
COPD, by aerosol inhalation, ADULT, 18 micrograms daily
via inhaler device at the same time each day.
NOTE: Must be used in combination with an inhaled
corticosteroid and a long-acting beta2-agonist.
Dose Adjustment:
Renal Impairment:
In patients with CrCl ≤50 mL/minute, use with caution.
Monitor patient closely.
R
Precautions:
Bronchospasm; CNS effects; Hypersensitivity reactions;
Glaucoma; Prostatic hyperplasia or bladder neck
obstruction; renal impairment (monitor closely for
anticholinergic events); Elderly (renal clearance is
decreased, and plasma concentrations are increased
due to decreased renal function; monitor urinary
function of men with benign prostatic hyperplasia);
Pregnancy and lactation.
SKILLED TASKS. May impair the ability to perform certain
tasks, e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Chest pain, edema, angina pectoris (including
exacerbation), palpitations, headache, depression,
insomnia, dizziness, paresthesia, voice disorder, skin
rash, pruritus, hypercholesterolemia, hyperglycemia,
xerostomia, abdominal pain, dyspepsia, constipation,
omitting, GERD, oropharyngeal candidiasis, stomatitis,
UTI, hypersensitivity reaction, infection, herpes zoster,
arthralgia, myalgia, arthritis, leg pain, skeletal pain,
cataract, upper respiratory tract infection, pharyngitis,
sinusitis, rhinitis, epistaxis, cough, flu-like symptoms,
laryngitis
Less Common: Anaphylaxis, angioedema, application site
irritation (including glossitis, oral mucosa ulcer,
pharyngolaryngeal pain), atrial fibrillation, blurred vision,
bronchospasm, dehydration, dermal ulcer, dysphagia,
dysuria, gingivitis, glaucoma, glossitis, hoarseness,
increased intraocular pressure, intestinal obstruction
(including paralytic ileus), joint swelling, paradoxical
bronchospasm, skin infection, mydriasis (contact with
565
 RESPIRATORY SYSTEM

eyes), supraventricular tachycardia, tachycardia, throat ADRENERGICS FOR SYSTEMIC USE

irritation, urinary retention, urticaria, xeroderma

Drug Interactions: Rx SALBUTAMOL

Monitor closely with:
Enhances therapeutic effect of Tiotropium:
Oral: 2 mg/5 mL syrup (as sulfate), 60 mL
Mianserin (anticholinergic effect)
A short-acting, beta2-adrenergic agonist used in the
Enhances anticholinergic effect of the following drugs:
treatment or prevention of bronchospasm.
Abobotulinumtoxin-A, Onabotulinumtoxin-A,
Rimabotulinumtoxin-B
Indications: Prophylaxis and treatment of asthma;
bronchospasm in patients with reversible obstructive
Increases risk of adverse or toxic effects of the following
airway disease; prevention of exercise-induced
drugs:
bronchospasm
Analgesics, Opioid (constipation; urinary retention)
Mirabegron
Contraindications: Severe pre-eclampsia and eclampsia;
Topiramate
intrauterine infection; intrauterine fetal death; ante-
Ramosetron (constipation)
partum hemorrhage, placenta previa; cord compression;
threatened miscarriage; cardiac disease;
Reduces therapeutic effect of Tiotropium:
Acetylcholinesterase Inhibitors e.g. Neostigmine
Dose:
Reduces therapeutic effect of the following drugs:
Chronic asthma, by mouth, ADULT, 2–4 mg 3–4 times daily
Gastrointestinal Agents, Prokinetic
(maximum, 8 mg 3–4 times daily); CHILD 6–12 years, 2
Itopride
mg 3–4 times daily; CHILD 2–6 years, 1–2 mg 3–4 times
daily; CHILD <2 years, 100 micrograms/kg 4 times daily.
Avoid concomitant use with:
Enhances anticholinergic effect of Tiotropium:
Administration: Multi-dose solution for nebulization may
Aclidinium, Ipratropium, Other Anticholinergic Agents,
need dilution with 0.9% sodium chloride to obtain final
Pramlintide, Umeclidinium
volume for the nebulizer.
Enhances anticholinergic effect of Cimetropium
See Salbutamol under Drugs for obstructive airway
diseases – Adrenergics, Inhalants in Chapter 12:
Increases risk of adverse or toxic effects of the following
Respiratory System for other information.
drugs:
R

Eluxadoline (constipation), Glucagon (GI adverse

effects), Loxapine, Potassium Chloride (ulcerogenic
effect)
Reduces therapeutic effect of the following drugs:
Levosulpiride, Secretin
Administration: Use only with appropriate accompanying
dispenser.
Prior to first use, insert cartridge into the inhaler and
prime the unit by actuating the inhaler toward the ground
until an aerosol cloud is visible. Repeat 3 more times.
The unit is then primed and ready for use.
If not used for more than 3 days, actuate the inhaler once
to prepare the inhaler for use.
If not used for more than 21 days, actuate the inhaler
until an aerosol cloud is visible and then repeat the
process 3 more times.
Pregnancy Category: C
ATC Code: R03BB04
Pregnancy Category: C
ATC Code: R03CC02
Rx TERBUTALINE
Oral: 5 mg and 1.5 mg/5 mL syrup (as sulfate), 60 mL
A direct acting sympathomimetic drug with beta-adrenergic
activity, selectively on beta2 receptors.
Indications: Bronchodilator in reversible airway obstruction
and bronchial asthma
Contraindications: Acute or chronic use in the prevention,
treatment, or management of preterm labor
Dose:
Asthma or bronchospasm, by mouth, ADULT and
ADOLESCENT >15 years, 5 mg per dose every 6 hours 3
times daily; if side effects occur, reduce dose to 2.5 mg
every 6 hours (maximum, 15 mg in 24 hours);
ADOLESCENT 12–15 years, 2.5 mg every 6 hours 3
times daily (maximum, 7.5 mg in 24 hours); CHILD <12
years, initially 0.05 mg/kg per dose 3 times daily,
increased gradually as required (maximum, 0.15 mg/kg
per dose 3–4 times daily or a total of 5 mg per 24 hours.

566
RESPIRATORY SYSTEM
Administration: Give drug around-the-clock to promote
decrease in variation in peak and trough serum levels.
See Terbutaline under Other Gynecologicals –
Sympathomimetics, Labor Repressants in Chapter 5:
Genito Urinary System and Sex Hormones for other
information.
Pregnancy Category: C
ATC Code: R03CC03
OTHER SYSTEMIC DRUGS FOR
OBSTRUCTIVE AIRWAY DISEASES
AMINOPHYLLINE (THEOPHYLLINE
Rx
ETHYLENEDIAMINE)
Inj.: 25 mg/mL, 10 mL ampule (IV)
A xanthine derivative that blocks phosphodiesterase-3 (PDE
III). It is a complex of theophylline and ethylenediamine
that promotes catecholamine stimulation of lipolysis,
glycogenolysis, and gluconeogenesis. It induces the
release of epinephrine from adrenal medulla cells, which
results in bronchodilation, diuresis, CNS and cardiac
stimulation, and gastric acid secretion.
Indications: Treatment of symptoms and reversible airway
obstruction due to asthma or other chronic lung diseases
(e.g., emphysema, chronic bronchitis)
Dose:
NOTE: Doses should be individualized based on peak serum
concentrations and should be based on ideal body
weight. Theophylline dose is 80% of aminophylline dose.
The treatment of asthma exacerbations with
aminophylline is not supported or recommended by
current clinical practice guidelines.
Acute symptoms, by IV injection, ADULT (not currently
receiving aminophylline or theophylline), 5.7 mg/kg
(equivalent to theophylline 4.6 mg/kg).
Acute symptoms, by IV injection, ADULT (currently receiving
aminophylline or theophylline), a loading dose is not
recommended without first obtaining a serum
theophylline concentration in patients who have received
aminophylline or theophylline within the past 24 hours;
calculate loading dose as follows:
Dose = (desired serum theophylline concentration ­
measured serum theophylline concentration) (Vd)
Acute symptoms, maintenance, by IV injection, ADULT 16–
60 years (otherwise healthy, nonsmokers), 0.51 mg/kg
per hour (equivalent to theophylline 0.4 mg/kg per hour),
(maximum daily dose, 1139 mg aminophylline
(equivalent to 900 mg theophylline) unless serum levels
indicate need for larger dose; ADULT >60 years, 0.38
mg/kg per hour (equivalent to theophylline 0.3 mg/kg
per hour), (maximum daily dose, 507 mg aminophylline
(equivalent to 400 mg theophylline) unless serum levels
indicate need for larger dose; ADOLESCENT 12–16 years
(nonsmokers), 0.63 mg/kg per hour (equivalent to
theophylline 0.5 mg/kg per hour), (maximum daily dose,
1139 mg aminophylline; equivalent to 900 mg
theophylline) unless serum levels indicate need for larger
dose; CHILD 12–16 years, (cigarette or marijuana
smokers), 0.89 mg/kg per hour (equivalent to
theophylline 0.7 mg/kg per hour); CHILD 9–12 years:
0.89 mg/kg per hour (equivalent to theophylline 0.7
mg/kg per hour); CHILD 1–9 years, 1.01 mg/kg per hour
(equivalent to theophylline 0.8 mg/kg per hour); INFANT
6–52 weeks, calculate dose as follows:
Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21]
divided by 0.79
Equivalent to theophylline:
Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21])
NOTE: To achieve a target theophylline concentration of 10
micrograms/mL unless otherwise noted. Lower initial
doses may be required in patients with reduced
theophylline clearance. Dosage should be adjusted
according to serum level measurements during the first
12- to 24-hour period.
Chronic conditions, by IV injection, ADULT 16–60 years
without risk factors for impaired theophylline clearance,
380 mg daily (equivalent to theophylline 300 mg daily) in
divided doses every 6–8 hours for 3 days, increase to
507 mg daily (equivalent to theophylline 400 mg daily) in
divided doses every 6–8 hours for 3 days (maintenance
dose, 760 mg daily; equivalent to theophylline 600 mg
daily) in divided doses every 6–8 hours.
R
NOTE: Increase dose only if tolerated. Consider lowering
dose or using a slower titration if caffeine-like adverse
events occur. Smaller doses given more frequently may
be used in patients with a more rapid metabolism to
prevent breakthrough symptoms, which could occur due
to low trough concentration prior to the next dose.
In patients with risk factors for impaired theophylline
clearance and patients in whom monitoring serum
theophylline levels is not feasible, do NOT exceed a dose
of aminophylline 507 mg daily (equivalent to
theophylline 400 mg daily).
Dose Adjustment:
Geriatric:
Do not exceed a dose of aminophylline 507 mg daily
(equivalent to theophylline 400 mg daily).
Renal Impairment:
In infants 1–3 months, consider dose reduction and
frequent monitoring of serum theophylline
concentrations.
Hepatic Impairment:
Initiate therapy at 0.25 mg/kg per hour (equivalent to
theophylline 0.2 mg/kg per hour). Maximum daily dose,
507 mg aminophylline daily (equivalent to 400 mg
theophylline day) unless serum concentrations indicate
need for larger dose.
Use with caution and monitor serum theophylline
concentrations frequently.
567

Cardiac Decompensation, cor pulmonale, hepatic
dysfunction, sepsis with multiorgan failure, shock:
0.25 mg/kg per hour (equivalent to theophylline 0.2 mg/kg
per hour), (maximum daily dose, 507 mg aminophylline
(equivalent to 400 mg theophylline) unless serum levels
indicate need for larger dose
After serum theophylline measurements:
Within normal limits, asthma: 5–15 micrograms/mL,
maintain dosage if tolerated. Recheck serum
theophylline concentration at 24-hour intervals. Finer
adjustments in dosage may be needed for some
patients. If levels ≥15 micrograms/mL, consider 10%
dose reduction to improve safety margin.
20–24.9 micrograms/mL, decrease dose by ~25%. [see
NOTE].
25–30 micrograms/mL, stop infusion for 12 hours
(children) or 24 hours (adults) and decrease subsequent
doses by ~25%. [see NOTE].
>30 micrograms/mL, stop dosing and treat overdose. If
resumed, decrease subsequent doses by 50%. [see
NOTE].
<9.9 micrograms/mL, if tolerated, but symptoms remain,
increase dose by ~25%. [see NOTE].
NOTE: Recheck serum theophylline levels after 12 hours
(children) or 24 hours (adults).
Precautions:
Extravasation (ensure proper catheter or needle position
prior to and during infusion; avoid extravasation);
Theophylline toxicity (if signs and symptoms develop,
e.g., persistent, repetitive vomiting, measure serum level
and withhold subsequent doses); Cardiovascular
disease, hyperthyroidism, peptic ulcer disease, and
R
seizure disorder; Elderly (use lower initial doses due to
slower hepatic clearance; monitor closely for response
and adverse reactions greater risk for toxicity due to
concomitant disease and drug use).
Adverse Drug Reactions: Flutter, tachycardia, behavior
alterations (children), headache, insomnia, irritability,
restlessness, seizures, allergic skin reactions, exfoliative
dermatitis, diarrhea, nausea, vomiting, tremor, diuresis
(transient)
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Aminophylline:
Atomoxetine (hypertensive and tachycardic effect),
Cannabinoid-containing Products (tachycardic effect),
Tedizolid (hypertensive and tachycardic effect)
Increases risk of adverse or toxic effects of the following
drugs:
Formoterol (hypokalemic effect), Indacaterol
(hypokalemic effect), Olodaterol (hypokalemic effect),
Other Sympathomimetics
Reduces therapeutic effect of Aminophylline:
Beta Blockers e.g. Propranolol (bronchodilator effect)
Avoid concomitant use with:
Decreases serum concentration of Aminophylline:
Carbamazepine, CYP1A2 Inducers (Strong), CYP3A4
Inducers (Strong)
Dabrafenib, Fosphenytoin, Mitotane
568
RESPIRATORY SYSTEM
Phenytoin
Decreases serum concentration of the following drugs:
Carbamazepine, Fosphenytoin, Phenytoin
Enhances therapeutic effect of Aminophylline:
Linezolid (hypertensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Doxofylline, Pancuronium, Quinolone Antibiotics e.g.,
Ciprofloxacin, Enoxacin [except Gemifloxacin,
Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic Acid,
Sparfloxacin] (augments seizure-producing potential),
Riociguat (hypotensive effect)
Increases serum concentration of Aminophylline:
Cimetidine, Conivaptan, CYP1A2 Inhibitors, CYP3A4
Inhibitors, Fluvoxamine, Fusidic Acid (Systemic),
Idelalisib
Macrolide Antibiotics [except Azithromycin, Fidaxomicin,
Spiramycin, Telithromycin]
Mexiletine, Mifepristone, Quinolone Antibiotics e.g.
Ciprofloxacin [except Gemifloxacin, Levofloxacin,
Lomefloxacin, Moxifloxacin, Nalidixic Acid, Sparfloxacin]
Stiripentol, Thiabendazole, Vemurafenib
Increases serum concentration of the following drugs:
Tizanidine [if concomitant use cannot be avoided, initiate
tizanidine at 2 mg and increase in 2–4 mg increments
based on patient response]
Reduces therapeutic effect of Aminophylline:
Nonselective Beta Blockers (bronchodilator effect)
Reduces therapeutic effect of the following drugs:
Adenosine
Benzodiazepines e.g. Diazepam, Iobenguane I 123
Pancuronium (neuromuscular-blocking effect)
Regadenoson (vasodilatory effect)
TEST INTERACTION. May increase plasma glucose, uric acid,
free fatty acids, total cholesterol, HDL, HDL/LDL ratio,
and urinary free cortisol excretion. May decrease
triiodothyronine.
Administration: For IV use only. IM use is NOT
recommended). Loading doses should be administered
over 30 minutes. Infusion rate should not exceed 21
mg/hour (equivalent to theophylline 17 mg/hour) in
patients with cor pulmonale, cardiac decompensation,
liver dysfunction, patients >60 years, or patients taking
medications which reduce theophylline clearance.
Vesicant. Ensure proper needle or catheter placement
prior to and during IV infusion. Avoid extravasation.
EXTRAVASATION MANAGEMENT: If extravasation occurs,
stop infusion immediately and disconnect. Leave needle
or cannula in place. gently aspirate extravasated
solution. Do NOT flush the line. Initiate hyaluronidase
antidote. Remove needle or cannula; apply dry cold
compresses and elevate extremity.
Pregnancy Category: C
RESPIRATORY SYSTEM
ATC Code: R03DA05
Rx EPINEPHRINE (ADRENALINE)
Inj.: 1 mg/mL (as hydrochloride), 1 mL ampule (IM, SC)
0.3 mg auto-injector (IM-preload), 0.3 mL preloaded
injection pen. [May be used in cases of serious and
fatal anaphylaxis]
A direct-acting, mixed alpha- and beta-adrenoceptor
agonist; a sympathomimetic catecholamine, which is a
potent cardiac stimulant vasoconstrictor and
bronchodilator.
NOTE: Vasodilator at low dose (beta2 receptors); but,
vasoconstrictor at high dose (alpha receptors).
Indications: For anaphylactic shock; may be used in cases
of serious and fatal anaphylaxis; severe angioedema
with laryngeal swelling or airway obstruction
Contraindications: Pheochromocytoma; use in local
anesthesia of fingers, toes, ears, nose or genitalia;
shock; organic heart disease or cardiac dilatation;
closed-angle glaucoma; labor
NOTE: There are no absolute contraindications to the use of
epinephrine in life-threatening allergic reactions.
Dose:
Anaphylaxis, by IM or SC injection of 1:1,000 epinephrine
injection, ADULT and ADOLESCENT, 500 micrograms
(0.5 mL); CHILD 6-12 years, 250 micrograms (0.25 mL);
CHILD 6 months-6 years, 120 micrograms (0.12 mL);
INFANT <6 months, 50 micrograms (0.05 mL); by SC
injection of 1:1,000 epinephrine injection, CHILD, 10
micrograms/kg (0.01 mL/kg) bodyweight, repeat if
necessary at intervals of 20 minutes to 4 hours
depending on the response of the patient and the
severity of the condition (maximum single dose, 500
micrograms).
Administration: Epinephrine is best administered as an SC
or IM injection into the anterolateral aspect of the middle
third of the thigh for anaphylaxis, and by IV injection for
cardiac arrest or emergency situations.
NOTE: Do NOT mix with alkaline solutions. Discard after 24
hours or if solution is discolored or contains precipitate.
See Epinephrine (Adrenaline) under Cardiac Therapy –
Cardiac Stimulants, excluding Cardiac Glycosides in
Chapter 3: Cardiovascular System for other information.
Pregnancy Category: C
ATC Code: C01CA24
Rx MONTELUKAST
Oral: 4 mg granules (as sodium salt), sachet
4 mg and 5 mg chewable tablet (as sodium salt)
10 mg tablet (as sodium salt)
A selective, leukotriene-receptor inhibitor, which
antagonizes airway smooth muscle contraction and
inflammation caused by leukotrienes.
Indications: Prophylaxis and treatment of asthma (as an
adjunctive therapy in combination with a corticosteroid);
symptomatic relief of seasonal allergic rhinitis in patients
with asthma
NOTE: There is a place for montelukast in children aged 2–
5 years with intermittent viral-induced asthma, where
leukotrienes play a minor role.
Dose:
Prophylaxis of asthma, by mouth, ADULT and CHILD >15
years, 10 mg once daily in the evening; CHILD 6–15
years, 5 mg chewable tablet once daily in the evening;
CHILD 2–6 years, 4 mg chewable tablet once daily in the
evening; INFANT 6–23 months, 1 packet (4 mg oral
granules).
Seasonal allergic rhinitis, by mouth, ADULT and CHILD >15
years, 10 mg daily in the evening.
Dose Adjustment:
Renal and Hepatic Impairment:
For severe impairment, refer patient to a specialist.
R
Precautions:
WARNING: Montelukast has no role in the treatment of
status asthmaticus. It cannot be substituted for
inhaled or oral corticosteroids especially for
persistent asthma. It should not be used as
monotherapy for exercise-induced bronchospasm
Eosinophilia and vasculitis; neuropsychiatric events;
phenylketonuria; Patients are instructed to have
appropriate rescue treatment available while on
montelukast; when this is being given with systemic
corticosteroids, appropriate tapering of corticosteroids is
needed under medical supervision; Children; Pregnancy
(may be administered at normal dose in women who
have shown a significant improvement in asthma, which
is not achievable with other drugs before becoming
pregnant); breastfeeding (avoid use unless essential).
NOTE: Rarely, the reduction of a systemic corticosteroid
while on another leukotriene receptor antagonist has
been reported to manifest with eosinophilia, vasculitic
rash, worsening pulmonary symptoms, cardiac
complications, or neuropathy, sometimes presenting as
Churg-Strauss syndrome.
Adverse Drug Reactions:
Common: Abdominal pain and discomfort, cough, diarrhea,
fatigue, fever, headache, hyperkinesia, otitis media,
pharyngitis, rash, sinusitis, thirst, upper respiratory
infection, weakness
Less Common: Abnormal dreams, arthralgia, bruising,
dizziness, dry mouth, dyspepsia, edema, epistaxis,
569

hypesthesia, malaise, myalgia, paresthesia, pruritus,
seizures, sleep disturbances, sleepwalking
Rare: Allergy (including urticaria, angioedema, anaphylaxis),
bleeding, Churg-Strauss syndrome, disorientation,
eosinophilia, erythema multiforme, erythema nodosum,
hallucinations, hepatic disorders, mood or behavioral
changes e.g., anxiety, depression and aggression;
neuropsychiatric effects e.g., nightmares and
hallucinations; palpitations, suicidal thoughts and
behavior, tremor
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Montelukast by decreasing
AUC:
CYP450 Inducers e.g., Phenobarbital, Rifampicin
Administration: Take the drug at only one dose daily in the
evening.
Administer the oral granules (sachet) within 15 minutes
after opening the packet (with or without mixing with
food).
NOTE: Do NOT use this drug to relieve symptoms of an
asthma attack. Use a short-acting reliever.
Pregnancy Category: B
ATC Code: R03DC03
Rx THEOPHYLLINE (ANHYDROUS)
R
Oral: 150 mg and 200 mg tablet
200 mg MR tablet
25 mg/5mL (26.7 mg/5 mL) syrup, 100 mL
A xanthine derivative that blocks phosphodiesterase-3 (PDE
III) promoting catecholamine stimulation of lipolysis,
glycogenolysis, and gluconeogenesis and induces
release of epinephrine from adrenal medulla cells. It
causes bronchodilation, diuresis, CNS and cardiac
stimulation, and gastric acid secretion.
Indications: Treatment of symptoms and reversible airway
obstruction due to chronic asthma, or other chronic lung
diseases
Contraindications: Allergy to corn-related products
Dose:
NOTE: For every 1 mg/kg theophylline given, blood levels will
rise 2 micrograms/mL.
Asthma exacerbation, by mouth, ADULT (no theophylline
received within the previous 24 hours), 5 mg/kg.
Asthma exacerbation, by mouth, ADULT (theophylline was
administered in the previous 24 hours), calculate loading
dose as follows:
Dose = (desired serum theophylline concentration ­
measured serum theophylline concentration) (Vd)
570
RESPIRATORY SYSTEM
Chronic conditions, treatment, by mouth, CHILD ≥1 year and
<45 kg, initially 10 – 14 mg/kg once daily (maximum,
300 mg daily); maintenance dose, up to 20 mg/kg daily
(maximum, 600 mg daily).
NOTE: Increase dose only if tolerated. Consider lowering
dose or using a slower titration if caffeine-like adverse
events occur. Smaller doses given more frequently may
be used in patients with a more rapid metabolism to
prevent breakthrough symptoms, which could occur due
to low trough concentration prior to the next dose.
In patients with risk factors for impaired theophylline
clearance and patients in whom monitoring serum
theophylline levels is not feasible, do NOT exceed a dose
of theophylline 400 mg daily.
Dose Adjustment:
Geriatric:
Use lower initial doses and monitor closely for response and
adverse reactions.
Renal Impairment:
In infants 1–3 months, consider dose reduction and
frequent monitoring of serum theophylline
concentrations.
Hepatic Impairment:
In patients with decreased hepatic function (e.g., cirrhosis,
acute hepatitis, cholestasis), dose reduction and
frequent monitoring of serum theophylline concentration
are required (maximum daily dose, 400 mg).
After serum theophylline measurements:
Within normal limits, asthma:
CHILD, 5–10 micrograms/mL, maintain dose if tolerated.
Recheck serum theophylline concentration at 6- to 12-
month intervals. Finer adjustments in dosage may be
needed for some patients. If levels ≥15 micrograms/mL,
consider 10% dose reduction to improve safety margin.
NOTE: Recheck serum theophylline levels after 3 days in
children.
Precautions:
CNS effects; Theophylline toxicity (if signs and symptoms
develop, e.g., persistent, repetitive vomiting, measure
serum level and withhold subsequent doses);
Cardiovascular disease, hyperthyroidism, peptic ulcer
disease, and seizure disorder; Elderly (use lower initial
doses due to slower hepatic clearance; monitor closely
for response and adverse reactions; greater risk for
toxicity due to concomitant disease and drug use).
Adverse Drug Reactions: Flutter, tachycardia, headache,
hyperactivity (children), insomnia, irritability,
restlessness, seizures, status epilepticus (non-
convulsive), hypercalcemia (with concomitant
hyperthyroid disease), nausea, reflux or ulcer
aggravation, vomiting, difficulty urinating (elderly males
with prostatism), tremor, diuresis (transient)
RESPIRATORY SYSTEM
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Theophylline:
Atomoxetine (hypertensive and tachycardic effect),
Cannabinoid-containing Products [except Cannabidiol]
(tachycardic effect)
Tedizolid (hypertensive and tachycardic effect)
Increases risk of adverse or toxic effects of Theophylline:
Other Sympathomimetics
Increases risk of adverse or toxic effects of the following
drugs:
Formoterol (hypokalemic effect)
Indacaterol (hypokalemic effect)
Olodaterol (hypokalemic effect)
Reduces therapeutic effect of Theophylline:
Beta Blockers (bronchodilator effect)
Avoid concomitant use with:
Decreases serum concentration of Theophylline:
Carbamazepine
CYP1A2 Inducers
CYP3A4 Inducers
Dabrafenib, Fosphenytoin, Mitotane, Phenytoin
Decreases serum concentration of the following drugs:
Carbamazepine, Fosphenytoin
Enhances therapeutic effect of Theophylline:
Linezolid (hypertensive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Doxofylline, Pancuronium, Quinolone Antibiotics e.g.,
Ciprofloxacin, Enoxacin [except Gemifloxacin,
Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic Acid,
Sparfloxacin] (augments seizure-producing potential),
Riociguat (hypotensive effect)
Increases serum concentration of Theophylline:
Cimetidine, Conivaptan
CYP1A2 Inhibitors
CYP3A4 Inhibitors
Fluvoxamine, Fusidic Acid (Systemic)
Idelalisib, Macrolide Antibiotics [except Azithromycin,
Fidaxomicin, Spiramycin, Telithromycin], Mexiletine,
Mifepristone
Quinolone Antibiotics e.g., Ciprofloxacin, Enoxacin
[except Gemifloxacin, Levofloxacin, Lomefloxacin,
Moxifloxacin, Nalidixic Acid, Sparfloxacin], Stiripentol
Thiabendazole, Vemurafenib, Zileuton [if concomitant
use cannot be avoided, reduce theophylline dose by 50%
upon initiation of zileuton]
Increases serum concentration of Tizanidine [if concomitant
use cannot be avoided, initiate tizanidine at 2 mg and
increase in 2–4 mg increments based on patient
response]
Reduces therapeutic effect of Theophylline:
Nonselective Beta-blockers e.g. Propranolol
(bronchodilator effect)
Reduces therapeutic effect of the following drugs:
Adenosine
Benzodiazepines, Iobenguane I 123, Regadenoson
(vasodilatory effect)
Pancuronium (neuromuscular-blocking effect)
TEST INTERACTION. May increase plasma glucose, uric acid,
free fatty acids, total cholesterol, HDL, HDL/LDL ratio,
and urinary free cortisol excretion. May decrease
triiodothyronine.
Administration: For IV use only. IM use is NOT
recommended). Loading doses should be administered
over 30 minutes. Infusion rate should not exceed 21
mg/hour (equivalent to theophylline 17 mg/hour) in
patients with cor pulmonale, cardiac decompensation,
liver dysfunction, patients >60 years, or patients taking
medications which reduce theophylline clearance.
Pregnancy Category: C
ATC Code: R03DA04
COUGH AND COLD PREPARATIONS
COUGH SUPPRESSANTS,
EXCLUDING COMBINATIONS
WITH EXPECTORANTS
OTC BUTAMIRATE
R
Oral: 50 mg MR tablet (as citrate)
7.5 mg/5 mL syrup (as citrate), 120 mL
A centrally-acting antitussive, which is neither chemically
nor pharmacologically related to the opioids, intended as
a cough suppressant.
Indications: Chronic, non-productive, irritative cough;
symptomatic treatment of cough of various origins
Dose:
Cough, by mouth, ADULT and CHILD >12 years, 10 to 20 mg
every 4 hours or 30 mg every 6–8 hours; INFANT and
CHILD 6–12 years, 1 mg/kg daily divide every 6–8 hours;
Alternatively, ADULT, 1 tablet 2–3 times daily; ADULT and
CHILD >9 years, 1–2 tablespoon 3 times daily; CHILD 1–
9 years, 1–2 teaspoon syrup 2–3 times daily.
Precautions:
Pregnancy (use in the first trimester is not recommended;
during the rest of pregnancy, use only if drug therapy is
essential).
SKILLED TASKS. May impair ability to drive or operate
machinery.
May cause somnolence. Take caution while driving or
performing other tasks which require alertness.
Adverse Drug Reactions:
Rare: Diarrhea, dizziness, GI discomfort, nausea, skin rash,
somnolence, urticaria
571

Drug Interactions:
Avoid concomitant use with:
Incompatible with the following products:
Penicillins, Phenobarbital, Salicylates, Tetracyclines
Increases risk of adverse or toxic effects of Butamirate:
Expectorants (bronchospasm; airways infection)
Administration: May be taken with or without food.
Pregnancy Category: C
ATC Code: R05DB13
OTC DEXTROMETHORPHAN
Oral: 10 mg tablet (as hydrobromide)
An N-methyl-D-aspartate receptor antagonist that
decreases the sensitivity of cough receptors and
interrupts cough impulse transmission by depressing the
medullary cough center through sigma receptor
stimulation.
Indication: Symptomatic relief of coughs caused by the
common cold or inhaled irritants
Contraindications: Known hypersensitivity to
dextromethorphan or any component of the formulation;
concurrent administration with or within 2 weeks of
discontinuing an MAO inhibitor
R
Dose:
Cough suppressant, by mouth, ADULT and CHILD >12 years,
10–20 mg every 4 hours or 30 mg every 6–8 hours
(maximum 120 mg daily); CHILD 6–12 years, 5–10 mg
every 4 hours or 15 mg every 6–8 hours (maximum 60
mg every 24 hours).
NOTE: NOT for use in children <4 years of age.
Dose Adjustment:
Hepatic Impairment:
Use with caution. Metabolized in the liver.
Precautions:
Serotonin syndrome (symptoms of agitation, confusion,
hallucinations, hyper­reflexia, myoclonus, shivering, and
tachycardia may occur with concomitant pro-
serotonergic drugs); Elderly (no specific information
found on use in elderly); children; debilitated patients
Adverse Drug Reactions: Confusion, excitement, irritability,
nervousness, serotonin syndrome
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Dextromethorphan:
Antiemetics, 5-HT3 Antagonists (serotonergic effect)
Enhances therapeutic effect of Antipsychotic Agents
(dopamine blockade; serotonergic effect)
572
RESPIRATORY SYSTEM
Increases risk of adverse or toxic effects of
Dextromethorphan:
Antiemetics, 5-HT3 Antagonists (serotonin syndrome)
Increases risk of adverse or toxic effects of the following
drugs:
Antipsychotic Agents (neuroleptic malignant syndrome;
serotonin syndrome)
Memantine, Metoclopramide (neuroleptic malignant
syndrome; serotonin syndrome), Parecoxib,
Peginterferon Alfa-2b
Avoid concomitant use with:
Enhances therapeutic effect of Dextromethorphan:
MAO Inhibitors e.g. Phenelzine (serotonergic effect),
Selective Serotonin Reuptake Inhibitors [except
Fluvoxamine] (serotonergic effect)
Increases risk of adverse or toxic effects of
Dextromethorphan:
Dapoxetine, MAO Inhibitors e.g. Phenelzine (serotonin
syndrome), Other Serotonin Modulators [except
Tedizolid] (serotonin syndrome)
Increases serum concentration of Dextromethorphan:
Abiraterone Acetate, CYP2D6 Inhibitors, Panobinostat,
Quinidine, Selective Serotonin Reuptake Inhibitors
[except Fluvoxamine]
TEST INTERACTIONS: False-positive phencyclidine, opioids
and heroin urine drug screen.
Administration: May be taken with or without food.
Pregnancy Category: C
ATC Code: R05DA09
ANTIHISTAMINES FOR
SYSTEMIC USE
OTC CETIRIZINE
Oral: 10 mg tablet (as dihydrochloride)
2.5 mg/mL syrup (oral drops) (as dihydrochloride), 10
mL
10 mg/mL drops (as dihydrochloride), 10 mL
1 mg/mL solution (as dihydrochloride), 30 mL and 60
mL
5 mg/5 mL syrup (as dihydrochloride), 30 mL
A piperazine-derived, long-acting, second-generation H1
receptor antagonist, which is often better tolerated than
sedating antihistamines due to less sedating and less
anticholinergic effects.
Indications: Perennial and seasonal allergic rhinitis; other
allergic symptoms such as hay fever, conjunctivitis, and
chronic idiopathic urticaria
Contraindications: Known hypersensitivity reactions to
cetirizine, levocetirizine, or hydroxyzine or any
component of the formulation; severe renal impairment
RESPIRATORY SYSTEM

Dose: ATC Code: R06AE07

Symptomatic relief of allergy, by mouth, ADULT, 10 mg once
daily or 5 mg twice daily, may be increased as necessary,
(maximum recommended daily dose 20 mg); CHILD >6 CHLORPHENAMINE
years, 10 mg daily or 5 mg twice daily; CHILD 2 to 6 years, OTC
(CHLORPHENIRAMINE)
5 mg once daily or 2.5 mg twice daily; CHILD 1–2 years,
0.25 mg/kg twice daily.
Oral: 4 mg tablet (as maleate)
2.5 mg/5 mL syrup (as maleate), 60 mL
Dose Adjustment:
Inj.: 10 mg/mL (as maleate), 1 mL ampule/vial (IM, IV)
Geriatric (≥77 years):
Use lower dose (5 mg daily).
An H1-receptor antagonist which competitively blocks H1-
Renal and Hepatic Impairment:
receptor sites on tissues.
For mild-to-moderate impairment, dose reduction is
warranted (5 mg daily).
Indications: For allergic conditions; an adjunct in
anaphylactic shock
Precautions:
WARNING: May cause CNS depression, which may Contraindication: Neonates
impair physical or mental abilities.
Dose:
CNS stimulation may occur with antihistamines, especially Allergic conditions, by mouth, ADULT, 4 mg every 4 to 6
in children (caution is advised in patients suffering from hours (maximum, 24 mg daily); CHILD 6–12 years, 2 mg
epilepsy); Children and elderly (risk of sedation and every 4–6 hours (maximum, 12 mg daily); CHILD 2–5
anticholinergic effects are increased; not recommended years, 1 mg every 4–6 hours (maximum, 6 mg daily);
for children <12 months); Renal impairment; hepatic CHILD 1–2 years, 1 mg twice daily (maximum, 6 mg
impairment; excess alcohol intake; avoid use of other daily).
sedative drugs; Lactation (excreted into breast milk). Adjunct in anaphylactic shock, by IV or IM injection, ADULT,
10–20 mg (maximum 40 mg daily).
SKILLED TASKS. May impair ability to perform certain tasks,
e.g., operating machinery or driving. Dose Adjustment: No information found

Adverse Drug Reactions: Precautions:

Common: Dizziness, drowsiness, dryness of mouth, fatigue, Pylori duodenal obstruction; angle-closure glaucoma;
headache, insomnia, malaise, nausea, pharyngitis, urinary retention; prostatic hyperplasia; epilepsy; renal

R
somnolence and hepatic impairment; BPH; bladder neck obstruction;
Less Common: Abdominal pain, anorexia, arthralgia, chest hypertension; Elderly.
pain, diarrhea, dyspepsia, dyspnea, epistaxis, fever,
flushing, increased appetite, myalgia, tachycardia, thirst, SKILLED TASKS. May impair ability to drive or operate
vomiting, weight gain machinery.
Rare: Dystonia, hemolytic anemia, hepatitis,
hypersensitivity (including anaphylaxis and Adverse Drug Reactions:
bronchospasm), hypotension, rash, thrombocytopenia Common and Less Common: CNS depression, sedation,
drowsiness, lassitude, dizziness, GI upsets, anorexia,
Drug Interactions: increased appetite, epigastric pain, blurring of vision,
Monitor closely with: dysuria, dryness of mouth, tightness in chest,
Enhances therapeutic effect of Cetirizine: hypotension, muscular weakness, tinnitus, euphoria,
Anticholinergics e.g., Ipratropium, Tiotropium headache, paradoxical CNS stimulation
(anticholinergic effect), CNS Depressants e.g., Alcohol, Potentially Fatal: CV collapse, respiratory failure
Sedatives (sedative effect)
Drug Interactions:
Increases risk of adverse or toxic effects of the following Monitor closely with:
drugs: Enhances therapeutic effect of Chlorphenamine:
Analgesics, Opioids (constipation; urinary retention), Psychotropic Drugs e.g., Barbiturates, Hypnotics, Opioid
CNS Depressants e.g., Alcohol, Sedatives, Warfarin Analgesics, Anxiolytics, Antipsychotics (sedative effect)
(increased INR; epistaxis)
Avoid concomitant use with:
Reduces therapeutic effect of Cetirizine: Increases risk of adverse or toxic effects of the following
Acetylcholinesterase Inhibitors (Central) drugs:
Alcohol, Ethyl (sedation or excitation), Clomipramine,
Avoid concomitant use with: Cyclobenzaprine
Increases risk of adverse or toxic effects of Cetirizine: Desipramine, Maprotiline, Melitracen
Doxylamine (CNS depression; psychomotor retardation) Nortriptyline, Opipramol, Protriptyline
Trimipramine
Administration: May be administered with or without food.
Administration: May be taken with or without food.
Pregnancy Category: B
Pregnancy Category: C

573

ATC Code: R06AB04
Rx (Inj.)
OTC (Oral)
DIPHENHYDRAMINE
Oral: 25 mg and 50 mg capsule (as hydrochloride)
12.5 mg/5 mL syrup (as hydrochloride), 30 and 60
mL
Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
A monoethanolamine-derived, first-generation H1-receptor
antagonist that exhibits antimuscarinic and pronounced
sedative property, with low incidence of GI side effects.
Indications: Relief of allergic symptoms caused by
histamine release, including rhinitis, cough,
conjunctivitis and allergic dermatoses; moderate to
severe angioedema and anaphylaxis (adjunct to
epinephrine)
Contraindications: Acute asthma; neonates or premature
infants; breastfeeding; use of the parenteral form as a
local anesthetic
Dose:
Allergic reactions, by mouth, ADULT, 25–50 mg every 6–8
hours, CHILD >12 years, 25–50 mg every 4–6 hours
(maximum, 300 mg daily); CHILD 6 to <12 years, 12.5–
25 mg every 4–6 hours (maximum, 10 mg daily); CHILD
2 to <6 years, 6.25 mg every 4–6 hours (maximum, 37.5
mg daily).
Allergic reactions, by IM or IV injection, ADULT, 10 to 50 mg
R
per dose, as a single dose, for up to 100 mg if needed
(maximum, 400 mg daily); CHILD, 5 mg/kg daily or 150
mg/m2 daily in divided doses every 6–8 hours (maximum
300 mg daily).
Dose Adjustment:
Geriatric:
For emergency allergic reactions only. Advanced age is
associated with reduced clearance of drug
If used, consider lower doses. Use only smallest effective
dose, 25 mg oral or IV every 8 to 12 hours.
Administration:
For oral administration, may be taken with or without
food.
For parenteral administration, for IV or IM administration
only. Visually inspect parenteral products for particulate
matter and discoloration prior to administration.
For IV administration, do NOT exceed a rate of 25
mg/minute.
IM administration must be deep. Local necrosis may
result with SC or intradermal use.
See Diphenhydramine under Anti-Parkinson Drugs in
Chapter 10: Nervous System for other information.
Pregnancy Category: B
ATC Code: R06AA02
574
RESPIRATORY SYSTEM
Rx HYDROXYZINE
Oral: 25 mg tablet (as dihydrochloride)
2 mg/mL syrup (as dihydrochloride or as
hydrochloride), 100 mL
A piperazine derivative, blocks histamine H1-receptors on
effector cells of the GI tract, blood vessels and
respiratory tract. It is a sedating antihistamine with
antimuscarinic and significant sedative properties.
Indications: Control of anxiety or agitation; adjunct to pre- or
post-operative sedation; short-term management of
anxiety; pruritus
Contraindications: Pregnancy; lactation
Dose:
Adjunct to pre- or post-operative sedation,
by mouth, ADULT, 50–100 mg; CHILD, 600
micrograms/kg.
Short-term management of anxiety, by mouth, ADULT, 50–
100 mg 4 times daily.
Pruritus in acute and chronic urticaria and dermatosis, by
mouth, ADULT, initially 25 mg at night, may be increased
if required up to 25 mg 3–4 times daily; CHILD >6 years,
initially 15–25 mg daily, may be increased up to 50–100
mg daily in divided doses; CHILD 6 months–6 years,
initially 5–15 mg daily, may be increased up to 50 mg
daily in divided doses.
Dose Adjustment:
Renal Impairment:
For moderate-to-severe impairment, reduce dose by 50%.
Hepatic Impairment:
For oral preparations, reduce total daily dose by 33%.
Precautions:
Porphyria; glaucoma; bladder outflow obstruction;
decreased GI motility; myasthenia gravis; dementia;
renal and hepatic impairment; Cardiovascular effects
(use with caution in patients with known predisposing
factor to cardiac arrhythmia, including electrolyte
imbalance, increased potential for convulsions, and pre-
existing heart disease).
SKILLED TASKS. May impair ability to perform certain tasks,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common and Less Common: Dizziness, ataxia, fatigue,
drowsiness, hallucination, seizure, dry mouth,
nervousness, xerostomia, involuntary movements,
slurred speech, headache, paresthesia, tremor, blurred
vision, respiratory depression, pruritus, rash, urticaria,
allergic reaction
Drug Interactions:
Enhances therapeutic effect of Hydroxyzine:
Analgesics (CNS depressant effects)
Anesthesia (CNS depressant effects)
Barbiturates (CNS depressant effects)
MAO Inhibitors (antimuscarinic effects)
Opiates (CNS depressant effects)
RESPIRATORY SYSTEM
Other Sedatives (CNS depressant effects)
Tricyclic Antidepressants (antimuscarinic effects)
Administration: May be taken with or without food.
NOTE: Do NOT administer by SC, IV, or intra-arterial
injection.
Pregnancy Category: C (in 2nd and 3rd trimester);
X (in first trimester)
ATC Code: Not available
OTC LORATADINE
Oral: 10 mg tablet / film coated tablet
5 mg/5 mL syrup, 30 mL
A piperidine-derived, non-sedating, second-generation H1-
receptor antagonist, which is extensively converted into
a metabolite having a longer half-life.
Indications: Relief of nasal and non-nasal symptoms of
seasonal allergic rhinitis; hay fever; chronic idiopathic
urticaria, and other allergic dermatological disorder
Contraindications: Children <2 years of age; pregnancy;
breastfeeding
Dose:
Chronic idiopathic urticaria and seasonal allergic rhinitis, by
mouth, ADULT, 10 mg once daily (not to exceed 10 mg
per day); CHILD >30 kg or >6 years, 10 mg once daily;
CHILD <30 kg or 2–5 years, 5 mg once daily.
NOTE: Safety and efficacy is not established for allergic
rhinitis in CHILD <2 years, and for urticaria in CHILD <6
years.
Dose Adjustment:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, the dose frequency is
reduced to alternate days.
For severe impairment, refer patient to a specialist.
Precautions:
Renal or hepatic impairment; prostatic hypertrophy; urinary
retention; susceptibility to angle-closure glaucoma and
pyloroduodenal obstruction; epilepsy; Elderly (may be
inappropriate in certain comorbidities, such as dementia
and delirium; increased risk of sedation and
anticholinergic effects); Lactation.
Adverse Drug Reactions:
Common: Abdominal pain, blurred vision, conjunctivitis,
drowsiness, dryness of mouth, dysphonia, earache,
epistaxis, fatigue, GI disturbances, headache,
hyperkinesia, impaired concentration, influenza-type
symptoms, laryngitis, malaise, nausea, nervousness,
psychomotor impairment, somnolence, stomatitis, upper
respiratory tract infection, urinary retention, viral
infection, wheezing
Less Common: Increased appetite, insomnia, weight gain
Rare: Abnormal hepatic function, agitation, alopecia,
amnesia, angle-closure glaucoma, blood disorders,
bronchitis, chest pain, confusion, convulsions,
depression, dermatitis, dizziness, erythema multiforme,
EPS, hemoptysis, hepatic necrosis, hepatitis,
hypotension, hypersensitivity reactions, including
anaphylaxis; hypertension, impotence, palpitation,
peripheral edema, purpura, seizures, sleep disturbance,
supraventricular tachyarrhythmias, syncope,
tachycardia, thrombocytopenia, urticaria, vertigo
Drug Interactions:
NOTE: Sedative interactions apply to a lesser extent to the
non-sedating antihistamines. Interactions do not
generally apply to antihistamines used for topical action,
as well as inhalation.
Monitor closely with:
Enhances therapeutic effect of Loratadine:
Alcohol (CNS depressant effect)
Enhances therapeutic effect of the following drugs:
Azithromycin, Conjugated Estrogens
Increases risk of adverse or toxic effects of SSRIs
(psychomotor impairment)
Administration: May be taken with or without food.
Pregnancy Category: B
ATC Code: R06AX13
R
OTHER RESPIRATORY SYSTEM
PRODUCTS
LUNG SURFACTANTS
PHOSPHOLIPID FRACTION FROM
Rx
BOVINE LUNG
Inj: 45 mg/mL (54 mg/1.2 mL) lyophilized powder for
suspension (intratracheal admistration)
A sterile, non-pyrogenic pulmonary surfactant intended for
intratracheal use only.
Indication: Treatment of respiratory distress syndrome in
premature neonates.
Dose:
Respiratory distress syndrome, by intratracheal injection,
NEONATE, 4 mL per kg birth weight. Four doses can be
administered in the first 48 hours of life. Doses should
be given no more frequently than every 6 hours.
Dose Adjustment:
No dosage adjustments provided in the manufacturer’s
labeling.
Precautions:
May cause transient rales and moist breath sounds after
administration;
575
 RESPIRATORY SYSTEM

Increased probability of post-treatment nosocomial sepsis;
Use in infant less than 600 g or more than 1750 g birth
weight has not been evaluated.
Adverse Drug Reactions:
Common: Bradycardia and oxygen desaturation.
Rare: Endotracheal tube reflux, pallor, vasoconstriction,
hypotension, endotracheal tube blockage, hypertension,
hypocarbia, hypercarba, and apnea.
Drug Interactions:
No information provided in the manufacturer’s labeling.
Administration: For intratracheal administration only.
Pregnancy Category: N/A
ATC Code: R07AA02
Rx BERACTANT
compliance that may require frequent adjustments to
oxygen delivery and ventilator settings).
Adverse Drug Reactions:
Common: Transient bradycardia, oxygen desaturation
Less Common: Apnea, endotracheal tube blockage,
hypercarbia, hypertension, hypocarbia, hypotension,
pallor, pulmonary air leaks, pulmonary interstitial
emphysema, increased probability of post-treatment
nosocomial sepsis, vasoconstriction
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Beractant:
Bretylium (AV blockade), Ruxolitinib (bradycardic effect)
Tofacitinib (bradycardic effect)
Other Bradycardia-causing Agents
Increases risk of adverse or toxic effects of the following
drugs:
Ivabradine (bradycardic effect), Lacosamide (AV-
blocking effect)

Avoid concomitant use with:

Inj.: 25 mg/mL suspension, 4 mL and 8 mL vial
Increases risk of adverse or toxic effects of Ceritinib
(intrathecal)
(bradycardic effect)
NOTE: Restricted to tertiary hospitals with adequately
Administration: For endotracheal administration only.
trained neonatologist and facilities for neonatal intensive
care
Administer endotracheally by instillation through a 5-
French end-hole catheter inserted into the infant's
A respiratory surfactant that replaces deficient or ineffective
endotracheal tube.
endogenous lung surfactant in neonates with respiratory
distress syndrome (RDS) or in neonates at risk of
Administer the dose in four 1 mL/kg aliquots. Each
R

developing RDS. Surfactants prevent the alveoli from

quarter-dose is instilled over 2–3 seconds followed by at
collapsing during expiration by lowering surface tension
least 30 seconds of manual ventilation or until stable.
between air and alveolar surfaces.
Each quarter-dose is administered with the infant in a
different position. Slightly downward inclination with
Indications: Prevention and treatment of respiratory
head turned to the right, then repeat with head turned to
distress syndrome (RDS) in premature infants
the left, then slightly upward inclination with head turned
to the right, then repeat with head turned to the left.
NOTE: Beractant is only indicated for use in premature
Following administration of 1 full dose, withhold
infants.
suctioning for 1 hour unless signs of significant airway
obstruction.
Dose:
Respiratory distress, prophylactic treatment, by
Suction infant prior to administration. Inspect solution to
endotracheal injection, PREMATURE INFANT, 4 mL/kg
verify complete mixing of the suspension. Mixture may be
(100 mg phospholipids/kg) as soon as possible; as many
swirled gently. Do NOT SHAKE. Do NOT filter dose and
as 4 doses may be administered during the first 48 hours
avoid shaking.
of life, no more frequently than 6 hours apart.
Rapidly affects oxygenation and lung compliance. Use is
NOTE: The need for additional doses is determined by
restricted to highly supervised clinical setting with
evidence of continuing respiratory distress; if the infant
immediately available clinicians experienced in
is still intubated and requiring at least 30% inspired
intubation and ventilatory management of premature
oxygen to maintain a PaO2 ≤80 torr.
infants.
Respiratory distress, rescue treatment, by endotracheal
Pregnancy Category: Not classified
injection, PREMATURE INFANT, 4 mL/kg (100 mg
phospholipids/kg) as soon as the diagnosis of RDS is
ATC Code: Not available
made, may repeat if needed, no more frequently than
every 6 hours to a maximum of 4 doses.

Precautions:
Transient adverse effects such as transient episodes of
bradycardia and decreased oxygen saturation occur
Acute changes in oxygenation and lung compliance
(produces rapid improvements in lung oxygenation and

576
RESPIRATORY SYSTEM

Weight Initial dose Repeat dose

Rx PORACTANT ALFA (grams) 2.5 mL/kg 1.25 mL/kg
1951 – 2000 5.00 2.50
Inj.: 80 mg/mL sterile suspension (intratracheal /
intrabronchial), 1.5 mL and 3 mL vial Dose Adjustment: No information found

A sterile, non-pyrogenic pulmonary surfactant intended for Precautions:

intratracheal use only. It is an extract of natural porcine
lung surfactant consisting of 99% polar lipids (mainly
phospholipids) and 1% hydrophobic low molecular
weight proteins (surfactant associated proteins SP-B and
SP-C).
It reduces surface tension at the air-liquid interface of the
alveoli during ventilation and stabilizes the alveoli
against collapse at resting transpulmonary pressures.
Indications: For the rescue treatment of respiratory distress
syndrome (RDS) in pre-term babies; prophylactic use in
premature infants at risk of RDS
Dose:
RDS, by intratracheal injection, PREMATURE INFANT,
initially 2.5 mL/kg of birth weight [see below],
administered as 1 or 2 aliquots depending on the
instillation procedure; up to 2 repeat doses of 1.25
mL/kg birth weight each may be administered at
approximately 12-hour intervals in infants who remain
intubated and in whom RDS is considered responsible
for their persisting or deteriorating respiratory status
(maximum total dose, 5 mL/kg).
Weight Initial dose Repeat dose
WARNING: Should only be administered by those
trained and experienced in the care, resuscitation,
and stabilization of pre-term infants.
Acute changes in oxygenation and lung compliance
(produces rapid improvements in lung oxygenation and
compliance that may require frequent adjustments to
oxygen delivery and ventilator settings); Transient
adverse effects; (associated with transient episodes of
bradycardia, hypotension, endotracheal tube blockade,
and oxygen desaturation).
Children (safety and efficacy in full term infants or older
pediatric patients with respiratory failure has not been
established).
Adverse Drug Reactions:
Common: Acquired pneumonia, acquired septicemia,
bronchopulmonary dysplasia, intracranial hemorrhage,
patent ductus arteriosus, pneumothorax, pulmonary
interstitial emphysema
Less Common: Pulmonary hemorrhage
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of the following drugs:
Paromomycin, Spectinomycin, Streptomycin

R
(grams) 2.5 mL/kg 1.25 mL/kg
Each dose (mL) Avoid concomitant use with:
600 – 650 1.60 0.80 Reduces therapeutic effect of the following drugs:
651 – 700 1.70 0.85 Amikacin, Amphotericin B, Gentamicin, Kanamycin,
701 – 750 1.80 0.90 Neomycin, Tobramycin, Vancomycin
751 – 800 2.00 1.00
801 – 850 2.10 1.05 Administration: For intratracheal administration only.
851 – 900 2.20 1.10
Slowly withdraw contents of the vial into a 3 or 5 mL
901 – 950 2.30 1.15
plastic syringe through a large-gauge needle (at least 20
951 – 1000 2.50 1.25 gauge). Each vial is single-use only. Attach the pre-cut 9-
1001 – 1050 2.60 1.30 cm 5-French end-hole catheter to the syringe. Fill the
1051 – 1100 2.70 1.35 catheter with the suspension. Discard excess
1101 – 1150 2.80 1.40 suspension through the catheter so that only the
1151 – 1200 3.00 1.50 required dose remains in the syringe. Administer in 2
1201 – 1250 3.10 1.55 divided aliquots:
1st dose: 1.25 mL/kg birth weight (BW)
1251 – 1300 3.20 1.60
Succeeding doses: 0.635 mL/kg BW
1301 – 1350 3.30 1.65
1351 – 1400 3.50 1.75 Should be administered by, or under the supervision of
1401 – 1450 3.60 1.80 clinicians experienced in intubation, ventilator
1451 – 1500 3.70 1.85 management, and general care of premature infants.
1501 – 1550 3.80 1.90
1551 – 1600 4.00 2.00 Prior to administration, ensure proper placement and
patency of the endotracheal tube. At the discretion of the
1601 – 1650 4.10 2.05
clinician, the endotracheal tube may be suctioned before
1651 – 1700 4.20 2.10 administration. Allow the infant to stabilize before
1701 – 1750 4.30 2.15 proceeding with dosing.
1751 – 1800 4.50 2.25
1801 – 1850 4.60 2.30 Administer either:
1851 – 1900 4.70 2.35 Intratracheally by instillation in 2 divided aliquots
1901 – 1950 4.80 2.40 through a 5-French end-hole catheter after briefly

577
 RESPIRATORY SYSTEM

disconnecting the endotracheal tube from the ventilator;

or
Intratracheally in a single aliquot through the secondary
lumen of a dual lumen endotracheal tube without
interrupting mechanical ventilation.

Pregnancy Category: Not classified

ATC Code: Not available

R

578
SENSORY ORGANS
SENSORY ORGANS
OPHTHALMOLOGICALS
ANTIINFECTIVES
Rx ACYCLOVIR (ACICLOVIR)
Ophth.: 3% eye ointment, 4.5 g tube
An acyclic purine nucleoside analogue which inhibits viral
DNA polymerase, thus preventing viral DNA synthesis.
Indication: Treatment of herpes simplex keratitis
Contraindication: Hypersensitivity to acyclovir, valacyclovir,
or any component of the formulation
Dose:
Herpes simplex keratitis, into the eye, ADULT, apply a small
amount (~1 cm ribbon) into the affected eye(s) 5 times
daily at approx. 4-hour intervals while awake, continue
treatment for at least 3 days after resolution of keratitis.
Dose Adjustment: Dose adjustment is unlikely due to low
systemic absorption
Precautions:
Ocular effects (e.g., transient stinging immediately following
application; blurred vision).
Adverse Drug Reactions:
Common: Foreign body sensation of the eye, epithelial
keratopathy, eye irritation, conjunctivitis, stinging of the
eye
Less Common: Blepharitis, eyelid edema, hypersensitivity
reaction
Drug Interactions: No known significant interactions
Administration: For ophthalmic application only.
Apply to the inside of the lower eyelid, then close the
eye(s) for 30 seconds following application.
Do NOT wear contact lenses during treatment. Avoid
touching the applicator to the eye or other surfaces.
Pregnancy Category: B
ATC Code: S01AD03
Rx ERYTHROMYCIN
Ophth.: 0.5% eye ointment, 3.5 g and 5 g tube
A macrolide antibiotic used for superficial ocular infections
caused by susceptible organisms. It inhibits protein
synthesis by irreversibly binding to the 50s ribosomal
subunit resulting in inhibition of cell growth.
Indications: Treatment of superficial ocular infections
involving the conjunctiva or cornea caused by organisms
susceptible to erythromycin; prophylaxis of ophthalmia
neonatorum from both N. gonorrhoeae and C.
trachomatis.
Contraindications: Minor ocular irritation
Dose:
Conjunctivitis, into the eye, ADULT, apply a half-inch (1.25
cm) on the affected eye(s) every 3–4 hours, 2–6 times a
day depending on the severity of the infection.
Prophylaxis of ophthalmia neonatorum, into the eye,
NEWBORN INFANT, apply 1 cm ribbon into each lower
conjunctival sac immediately after birth, then gently
massage the closed eyelids to spread the ointment.
NOTE: Prophylaxis should not be delayed by more than 1
hour after delivery since delayed application may reduce
efficacy. Ideally, a new tube or a single-use container of
ointment should be used for each neonate.
Dose Adjustment: No information found
Precautions:
S
Superinfection;
Pregnancy and breastfeeding.
Adverse Drug Reactions:
Common: Minor ocular reactions, redness
Rare: Hypersensitivity reactions
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Digoxin (digoxin toxicity), Vitamin K Antagonists e.g.,
Warfarin (bleeding)
Administration: For ophthalmic use only.
Apply ointment directly to the infected eye through the
pocket made by the lower lid and the eye. It is advisable
to apply the ointment at night.
Avoid contaminating the applicator tip with the material
from the eyes, fingers, or other sources.
Pregnancy Category: B
ATC Code: S01AA17
579
 SENSORY ORGANS

FUSIDATE SODIUM Rx GANCICLOVIR

Rx
(FUSIDIC ACID)
Ophth.: 1% eye drops suspension (as sulfate), 5 g tube Ophth.: 0.15% eye gel, 5 g tube

An aqueous sustained-release formulation of a narrow- An acyclic nucleoside analogue of 2’-deoxyguanosine that

spectrum antibiotic isolated from Fusidium coccineus.
Fusidic acid is active against staphylococci (including
methicillin-resistant strains) and streptococci.
Indications: Bacterial infections of the eye caused by
susceptible organisms in conjunctivitis, blepharitis, stye,
keratitis, dacryocystitis; prophylaxis in ophthalmic
surgery and in connection with removal of foreign bodies.
has antiviral effect against human cytomegalovirus and
other human herpes viruses. It is phosphorylated to a
substrate, which competitively inhibits the binding of
deoxyguanosine triphosphate to DNA polymerase
resulting in inhibition of viral DNA synthesis.
Indication: Treatment of acute herpetic keratitis (dendritic
ulcers)

Contraindications: Infections caused by non-susceptible Contraindication: Hypersensitivity to ganciclovir,

organisms.
Dose:
Ophthalmic infections, into the eye, ADULT, 1 drop in the
conjunctival sac every 4 hours for the 1st day of
treatment, then reduce dose to 1 drop every 12 hours;
continue treatment 2 days after the eye appears normal.
Surgical prophylaxis, into the eye, ADULT, 1 drop in the
conjunctival sac every 12 hours, 24–48 hours before
operation.
Dose Adjustment:
Hepatic Impairment:
Impaired biliary excretion may possibly increase risk of
hepatotoxicity. Avoid use or reduce dose. Monitor liver
function.
valganciclovir, other antivirals, or any component of the
formulation.
Dose:
Herpetic keratitis, into the eye, ADULT, instill 1 drop into the
inferior conjunctival sac of the affected eye 5 times daily
(approximately every 3 hours while awake) until the
corneal ulcer heals, then 1 drop 3 times daily for 7 days.
Dose Adjustment: Dose adjustment is unlikely due to low
systemic absorption.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.

Precautions: Ocular adverse effects (e.g., blurred vision and eye

Should not be used for more than 10 days (e.g., fungal irritation);
S

superinfection with prolonged use; discontinue Elderly (evaluate the patient’s or caregiver’s ability to safely
treatment if superinfection occurs; evaluate and treat and correctly administer the medication);
appropriately); Pregnancy and lactation (use with caution; safety has not
Avoid extended or recurrent use; been established).
Pregnancy;
Breastfeeding. Adverse Drug Reactions:
Common: Blurred vision, irritation, punctate keratitis,
Adverse Drug Reactions: conjunctival hyperemia
Common: Stinging (transient)
Drug Interactions: No known significant interactions
Drug Interactions:
Monitor closely with: Administration: For ophthalmic use only.
Reduces therapeutic effect of Penicillins
Do NOT use contact lenses during treatment. Avoid
Reduces therapeutic effect of Ciprofloxacin (antagonistic touching tip of applicator to eye or other surfaces.
effect)
Pregnancy Category: C
Avoid concomitant use with:
Increases risk of adverse or toxic effects of HMG-CoA ATC Code: S01AD09
Reductase Inhibitors (muscle toxicities, e.g.,
rhabdomyolysis)

Administration: For ophthalmic use only. Keep out of reach

of children.

Do NOT use contact lenses during treatment.

Pregnancy Category: C

ATC Code: S01AA13

580
SENSORY ORGANS

Rx LEVOFLOXACIN Rx MOXIFLOXACIN HYDROCHLORIDE

Eye Drops: 5 mg/mL (0.5% w/v) ophthalmic solution Eye Drops Solution: 5 mg/mL (0.5% w/v), 5 mL bottle

Levofloxacin inhibits DNA-gyrase and topoisomerase IV in Moxifloxacin is a DNA gyrase inhibitor, and also inhibits
susceptible organisms and thereby inhibits relaxation of topoisomerase IV. DNA gyrase is required for DNA
supercoiled DNA and promotes breakage of DNA replication and transcription, DNA repair, recombination,
strands. and transposition; inhibition is bactericidal.

Indications: Treatment of bacterial conjunctivitis secondary
to contact lens use.
Contraindications: Hypersensitivity to levofloxacin, other
quinolones, or to any component of the formulation.
Dose:
Bacterial conjunctivitis, ADULT and CHILD ≥6 years, days 1-
2: instill 1-2 drops into affected eye(s) every 2 hours
while awake, up to 8 times daily; days 3-7: instill 1-2
drops into affected eye(s) every 4 hours while awake, up
to 4 times daily.
Indications: Pre and postoperative sterilization.
Contraindications: Hypersensitivity to moxifloxacin, other
quinolones, or to any component of the formulation.
Dose:
Pre and postoperative sterilization, ADULT, instill 1 drop into
operative eye every 5-15 minutes for five doses within
the hour prior to the start of the procedure.
Dose Adjustment:
Renal and Hepatic impairment:
No dosage adjustments provided in the manufacturer’s
labeling.

Dose Adjustment: Precautions:

Renal and Hepatic impairment: May cause severe hypersensitivity reactions including
No dosage adjustments provided. anaphylaxis, angioedema, dermatologic reactions, and
superinfection.
Precautions:
Hypersensitivity: serious hypersensitivity reactions, Adverse Drug Reactions:
including anaphylaxis have been reported with system c Less Common: Eye irritation, conjunctivitis, decreased
quinolone therapy. Prolonged use may lead to visual acuity, eye discomfort, eye pain, eye pruritus,
overgrowth of non susceptible organisms including fungi. lacrimation, ocular hyperemia, subconjunctival
Superinfection. hemorrhage, and xerophthalmia.

S
Adverse Drug Reactions: Drg Interactions:
Less Common: Headache, burning sensation of eyes, eye None known.
pain, foreign body sensation of eye, photophobia, vision
loss, pharyngitis, and fever. Administration: For topical ophthalmic use only; not for
Rare: Dry eye syndrome, eyelid edema, eye pruritus, and injection. Avoid touching tip of applicator to eye or other
hypersensitivity reaction. surfaces.

Drug Interactions: Pregnancy Category: C

None known.
ATC Code: S01AE07
Administration: For ophthalmic use only; not for injection.
Avoid touching tip of applicator to eye or other surfaces.

Pregnancy Category: C Rx OFLOXACIN

ATC Code: S01AE05 Ophth.: 0.3% eye drops solution, 5 mL bottle

A DNA gyrase inhibitor that interferes with replication,

transcription, repair, recombination, and transposition of
bacterial DNA.

Indication: Treatment of superficial ocular infections

involving the conjunctiva or cornea due to strains of
susceptible organisms.

Contraindications: Hypersensitivity to ofloxacin or other

members of the quinolone group.

581
 SENSORY ORGANS

Dose:
Conjunctivitis, into the eye, ADULT and CHILD ≥1 year, instill Rx TOBRAMYCIN
1–2 drops into the affected eye(s) every 2–4 hours for
the first 2 days, then use 4 times daily for an additional Ophth.: 0.3% eye drops solution, 5 mL bottle
5 days. 0.3% eye ointment, 3.5 g tube
Corneal ulcer, into the eye, ADULT and CHILD ≥1 year, instill
1–2 drops every 30 minutes while awake and every 4–6 A topical ophthalmic antibiotic which binds to bacterial 30s
hours after retiring for the first 2 days; Beginning on day and 50s ribosomal subunits and interferes with bacterial
3, instill 1–2 drops every hour while awake for 4–6 protein synthesis.
additional days;
Thereafter, 1–2 drops 4 times daily until clinical cure. Indication: Treatment of external infections of the eye

Dose Adjustment: Dose adjustment is unlikely due to low
systemic absorption.
Precautions:
Hypersensitivity reactions (e.g., anaphylaxis);
Superinfection (e.g., fungal or bacterial superinfection with
prolonged use);
Tendon inflammation or rupture;
Elderly (evaluate the patient’s or caregiver’s ability to safely
and correctly administer the medication).
Pregnancy and lactation.
Adverse Drug Reactions:
Common and Less Common: Dizziness, nausea, blurred
vision, burning, chemical conjunctivitis or keratitis,
ocular discomfort, eye dryness, ocular edema, eye pain,
foreign body sensation in the eye, itching of the eye,
photophobia, redness of the eye, ocular stinging, tearing
of the eye.
Rare: Stevens-Johnson syndrome, toxic epidermal
necrolysis.
Drug Interactions:
S
Contraindication: Known hypersensitivity to tobramycin,
other aminoglycosides, or any component of the
formulation
Dose:
Ocular infection, mild-to-moderate, into the eye, ADULT and
CHILD ≥1 year,
as eye drops solution, instill 1 drop into the conjunctival
sac twice daily (morning and evening);
as eye ointment, apply ½ inch of ribbon into the affected
eye(s) 2–3 times daily.
Ocular infection, severe, into the eye, ADULT and CHILD ≥1
year,
as eye drops solution, instill 4 times on the affected
eye(s);
as eye ointment, apply ½ inch of ribbon into the affected
eye(s) every 3–4 hours.
Dose Adjustment: Dose adjustment is unlikely due to low
systemic absorption.
Precautions:
Hypersensitivity reactions (e.g., anaphylaxis);

Avoid concomitant use with: Superinfection (e.g., fungal or bacterial superinfection with
Decreases serum concentration of Ofloxacin: prolonged use);
Antacids containing Magnesium, Aluminum, or Calcium Tendon inflammation or rupture;
Elderly (evaluate the patient’s or caregiver’s ability to safely
Enhances therapeutic effect of Ofloxacin: and correctly administer the medication);
Aminoglycosides, e.g., Amikacin, Tobramycin (additive Children;
antibacterial activity) Pregnancy and lactation.

Increases risk of adverse or toxic effects of the following Adverse Drug Reactions:
drugs: Common: Hypersensitivity reactions, lid itching, lid swelling,
Class IA Antiarrhythmics, e.g., Quinidine, Procainamide conjunctival erythema
(QT interval prolongation), Class III Antiarrhythmics, e.g.,
Sotalol, Amiodarone (QT interval prolongation), Drug Interactions: No information found
Corticosteroids (severe tendon disorders), Theophylline
(theophylline-related adverse effects) Administration: For ophthalmic use only. Do NOT inject into
the eye.
Increases risk of adverse or toxic effects of Ofloxacin:
NSAIDs (seizures) Do NOT use contact lenses during treatment. Avoid
touching tip of applicator to eye or other surfaces.
Increases serum concentration of Theophylline
Pregnancy Category: B
Administration: For ophthalmic use only.
ATC Code: S01AA12
Avoid touching tip of applicator to eye or other surfaces.

WARNING: Do NOT use for longer than 2 weeks at a

time.

Pregnancy Category: C

ATC Code: S01AE01

582
SENSORY ORGANS
ANTIINFLAMMATORY AGENTS
Rx DEXAMETHASONE
Ophth.: 0.1% eye drops suspension, 5 mL bottle
A topical ophthalmic corticosteroid that decreases
inflammation by suppressing neutrophil migration,
decreasing production of inflammatory mediators, and
reversing of increased capillary permeability.
Indications: Management of steroid-responsive
inflammatory conditions such as allergic conjunctivitis,
iritis, or cyclitis; symptomatic treatment of corneal injury
from chemical, radiation, or thermal burns, or
penetration of foreign bodies.
Contraindications: Viral disease of the cornea and
conjunctiva (including epithelial herpes simplex keratitis,
vaccinia, varicella) ; mycobacterial or fungal infection of
the eye.
Dose:
Anti-inflammatory, into the eye, ADULT, instill 1–2 drops into
the conjunctival sac up to 4–6 times daily, may use
hourly for severe inflammation.
Dose Adjustment:
Geriatric:
Use with caution in the smallest possible dose.
Precautions:
Immunosuppression;
Ocular effects (e.g., ocular hypertension and/or glaucoma
with prolonged use, with damage to the optic nerve,
defects in visual acuity and fields of vision, and posterior
subcapsular cataract formation; perforations in diseases
which cause thinning of the cornea or sclera).
Elderly (evaluate the patient’s or caregiver’s ability to safely
and correctly administer the medication);
Lactation.
Adverse Drug Reactions:
Common and Less Common: Burning sensation of eyes,
cataract, decreased visual acuity, eye perforation,
filtering blebs, glaucoma (with optic nerve damage),
secondary ocular infection, stinging of eyes, visual field
defect.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs:
Ceritinib (hyperglycemic effect), Amphotericin B, Loop
diuretics e.g., Furosemide (hypokalemia),
Increases risk of adverse or toxic effects of Dexamethasone:
NSAID, Ophthalmic (delayed healing of ophthalmic tissue
with concomitant administration)
Administration: Shake well prior to use.
Do NOT touch tip of container to eye. Product may
contain benzalkonium chloride. Do NOT use contact
lenses during treatment.
NOTE: Taper dose prior to discontinuation.
Pregnancy Category: C
ATC Code: S01BA01
Rx NEPAFENAC
Ophth.: 1 mg/mL eye suspension, 5 mL bottle
A nonsteroidal anti-inflammatory and analgesic prodrug. It
penetrates the cornea and is converted to amfenac by
ocular tissue hydrolases. Amfenac inhibits the action of
prostaglandin H synthase resulting to inhibited
prostaglandin production.
Indication: Treatment of pain and inflammation associated
with cataract surgery.
Contraindication: Hypersensitivity to nepafenac, NSAIDs, or
any component of the formulation.
Dose:
Cataract surgery, into the eye, ADULT, instill 1 drop into the
affected eye(s) 3 times daily beginning 1 day prior to
cataract surgery, continued on the day of surgery and
through the first 2 weeks post-op.
Dose Adjustment: No information found
Precautions:
Cross-sensitivity;
S
Bleeding time;
Delayed healing;
Complicated ocular surgeries, corneal denervation, corneal
epithelial defects, diabetes mellitus, ocular surface
diseases, rheumatoid arthritis, or repeat ocular surgeries
within a short period of time (increases risk for corneal
adverse events, which may become sight threatening).
Adverse Drug Reactions:
Common: Capsular opacity, decreased visual acuity, foreign
body sensation, increased intraocular pressure, sticky
sensation, conjunctival edema, corneal edema, dry eye,
lid margin crusting, ocular discomfort, ocular hyperemia,
ocular pain, ocular pruritus, photophobia, tearing,
vitreous detachment, headache, hypertension, nausea,
vomiting, sinusitis.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Nepafenac:
Steroids, Topical (healing problems)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of drugs that
prolong bleeding time (hemorrhage)
Administration: Shake well prior to use.
If concomitant topical ophthalmic medication is being
used, administer medications at least 5 minutes apart.
583

Do NOT touch tip of container to eye. Do NOT use contact
lenses during treatment.
Pregnancy Category: C
ATC Code: S01BC10
Rx PREDNISOLONE
Ophth.: 0.5% and 1% eye drops suspension (as
acetate), 5 mL bottle
An adrenocortical steroid product prepared as sterile
ophthalmic suspension. It reduces inflammation by
inhibiting edema, leukocyte migration, fibrin deposition,
capillary proliferation and dilation, collagen deposition,
and scar formation.
Indications: Treatment of corneal injury from chemical,
thermal, or radiation burns, or from penetration of
foreign bodies; treatment of steroid-responsive
inflammatory conditions of the palpebral and bulbar
conjunctiva, cornea, and anterior segment of the globe
such as acne rosacea, allergic conjunctivitis, cyclitis,
herpes zoster keratitis, iritis, superficial punctate
keratitis, and selected infective conjunctivitis.
Contraindications: Acute untreated purulent ocular
infections; viral diseases of the cornea and conjunctiva;
mycobacterial or fungal infections of the eye;
hypersensitivity to other corticosteroids.
Dose:
S
Ophthalmic inflammatory conditions or corneal injury, into
the eye, ADULT, instill 1–2 drops in the affected eye(s)
2–4 times daily; during the initial 24–48 hours, dosing
frequency may be increased if necessary; if signs and
symptoms fail to improve after 2 days, re­evaluate.
Dose Adjustment: No dose adjustments provided in
manufacturer’s labeling.
Precautions:
Cataracts;
Corneal thinning;
Glaucoma;
Immunosuppression;
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common and Less Common: Conjunctival hyperemia,
conjunctivitis, corneal ulcers, delayed wound healing,
glaucoma, increased intraocular pressure, keratitis, loss
of accommodation, optic nerve damage, mydriasis,
posterior subcapsular cataract formation, ptosis,
secondary ocular infection.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Ceritinib
(hyperglycemic effect)
Increases risk of adverse or toxic effects of Prednisolone:
584
SENSORY ORGANS
NSAID, Ophthalmic (delayed healing of ophthalmic tissue
with concomitant administration)
Reduces therapeutic effect of the following drugs:
Insulin, Oral Hypoglycemics e.g., Gliclazide
Administration: For topical ophthalmic use only. Shake well
before use.
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for 1–2 minutes after instillation to
decrease risk of absorption and systemic effects.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
NOTE: Do NOT discontinue therapy prematurely. Withdraw
therapy with gradual tapering of dose in chronic
conditions.
Pregnancy Category: C
ATC Code: S01BA04
ANTIINFLAMMATORY AGENTS AND
ANTIINFECTIVES IN COMBINATION
Rx SULFACETAMIDE + PREDNISOLONE
Ophth.: 10% sulfacetamide + 0.25% prednisolone (as
acetate) eye drops suspension, 5 mL bottle
A sterile topical anti-inflammatory (prednisolone) and anti-
infective (sulfacetamide) product indicated for
ophthalmic use.
Indications: For steroid-responsive inflammatory ocular
conditions for which a corticosteroid is indicated and
where superficial bacterial ocular infection or a risk of
bacterial ocular infection exists.
Contraindications: Viral diseases of the cornea and
conjunctiva, including epithelial herpes simplex keratitis,
vaccinia, and varicella; mycobacterial infection of the
eye; fungal diseases of ocular structures.
Dose:
Uveitis, bacterial conjunctivitis, keratoconjuctivitis, or
keratitis, into the eye, ADULT, instill 2 drops into the
conjunctival sac every 4 hours during the day and at
bedtime; if signs and symptoms fail to improve after 2
days, re-evaluate.
Dose Adjustment: No information found
Precautions:
Cataracts;
Corneal thinning;
Glaucoma;
Immunosuppression;
Pregnancy;
Lactation.
SENSORY ORGANS
Adverse Drug Reactions:
Common and Less Common: Cataract, dizziness, eye
discharge, eyelid edema, eyelid erythema, eye irritation,
eye pain, eye pruritus, and hypersensitivity including
rash, skin pruritus, urticaria, ocular hyperemia, visual
disturbance (blurry vision), delayed wound healing,
elevation of intraocular pressure (IOP) with possible
development of glaucoma and infrequent optic nerve
damage, anterior uveitis or perforation of the globe,
mydriasis, loss of accommodation, ptosis, secondary
bacterial ocular infection.
Rare: SJS, toxic epidermal necrolysis, fulminant hepatic
necrosis, agranulocytosis, aplastic anemia and other
blood dyscrasias, systemic hypercorticoidism.
Drug Interactions:
Avoid concomitant use with:
Incompatible with the following products:
Silver-containing Preparations
Reduces therapeutic effect of Sulfacetamide:
Local Anesthetics related to p-aminobenzoic Acid
Administration: Shake well before use.
The initial prescription and renewal of the medication
order beyond 20 mL should be made by a physician only
after examination of the patient with the aid of
magnification, such as slit lamp biomicroscopy and,
where appropriate, fluorescein staining. If signs and
symptoms fail to improve after two days, the patient
should be re-evaluated.
Do NOT prescribe more than 20 mL initially. Do NOT refill
prescription without further evaluation.
Do NOT Inject into the eye.
NOTE: Do NOT discontinue therapy prematurely. Withdraw
therapy with gradual tapering of dose in chronic
conditions.
Pregnancy Category: C
ATC Code: S01CA02
Rx TOBRAMYCIN + DEXAMETHASONE
Ophth.: 0.3% tobramycin + 0.1% dexamethasone eye
drops suspension, 5 mL bottle
0.3% tobramycin + 0.1% dexamethasone eye
ointment, 3.5 g tube
A sterile topical anti-inflammatory (dexamethasone) and
anti-infective (tobramycin) product indicated for
ophthalmic use.
Indication: Steroid-responsive ocular inflammation with
suspected or confirmed bacterial infection
Contraindications: Viral infections of cornea and conjunctiva
(e.g., epithelial herpes simplex keratitis, vaccinia,
varicella); mycobacterial or fungal infection of the eye;
uncomplicated removal of a foreign body.
Dose:
Ocular inflammation with suspected or confirmed bacterial
infection, into the eye, ADULT,
as eye drops suspension, instill 1–2 drops into the
conjunctival sac(s) every 4–6 hours, may be increased to
every 2 hours during the initial 24–hour to 48–hour
period, decrease frequency gradually as improvement
seen;
as eye ointment, apply about ½ inch of ointment into the
conjunctival sac(s) up to 3–4 times daily.
Precautions:
Glaucoma (e.g., optic nerve damage);
Cataracts (e.g., posterior subcapsular cataract formation
with prolonged use);
Sensitivity;
Secondary infection;
Children;
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common: Hypersensitivity reactions, lid itching and
swelling, conjunctival erythema.
Less Common: Increased intraocular pressure, glaucoma,
optic nerve damage, posterior subcapsular cataract
formation, delayed wound healing, secondary infections
(prolonged use).
Administration: For external use only. NOT for injection.
Do NOT prescribe more than 20 mL or 8 g, initially. Do
NOT refill prescription without further evaluation.
See individual monographs for Tobramycin and
S
Dexamethasone under Ophthalmologicals in Chapter
13: Sensory Organs for other information.
Pregnancy Category: C
ATC Code: S01CA01
ANTIGLAUCOMA PREPARATIONS AND MIOTICS
Rx ACETAZOLAMIDE
Oral: 250 mg tablet
A reversible carbonic anhydrase inhibitor that causes
reduced hydrogen ion secretion and increased renal
excretion of sodium, potassium, bicarbonate, and water.
It decreases the production of aqueous humor and
inhibits carbonic anhydrase in CNS to retard abnormal
and excessive discharge from CNS neurons.
Indications: Adjunct in open-angle glaucoma; preoperative
management of angle-closure glaucoma.
Contraindications: Sodium and/or potassium depletion;
suprarenal gland failure; hyperchloremic acidosis;
hepatic cirrhosis; chronic non-congestive angle-closure
glaucoma; marked renal or hepatic impairment.
Dose:
585
 SENSORY ORGANS

Adjunct in open-angle glaucoma; preoperative management Pregnancy Category: C

of angle-closure glaucoma, by mouth, ADULT, 250–1000
mg daily, given in divided doses for amounts over 250 ATC Code: S01EC01
mg.

Precautions:
Diabetes mellitus; Rx BETAXOLOL
Respiratory acidosis;
Elderly; Ophth.: 0.25% eye drops suspension (as
Children; hydrochloride), 5 mL bottle
Pregnancy; 0.5% eye drops solution (as hydrochloride), 5
Lactation. mL and 10 mL bottle

Adverse Drug Reactions: A cardio-selective beta blocking agent in a sterile isotonic

Common and Less Common: Malaise, fatigue, depression,
excitement, headache, weight loss, GI disturbances,
drowsiness, paresthesia, diuresis, metabolic acidosis,
electrolyte imbalance, crystalluria, renal calculi, renal
colic, renal lesions, allergic skin reactions, fever, thirst,
dizziness, ataxia, irritability, confusion, reduced libido,
hematuria, glucosuria, renal failure, abnormal LFTs, loss
of appetite, taste alterations, transient myopia, tinnitus,
hearing disturbance.
Potentially fatal: Erythema multiforme, SJS, toxic
epidermal necrolysis, fulminant hepatic necrosis,
anaphylaxis.
Rare: Photosensitivity, cholestatic jaundice or hepatitis,
flaccid paralysis, convulsions, blood dyscrasias
(potentially fatal).
solution. When instilled into the eye, it reduces
intraocular pressure.
Indications: Treatment of ocular hypertension and chronic
open-angle glaucoma.
Contraindications: Sinus bradycardia greater than first-
degree atrioventricular block; cardiogenic shock; overt
cardiac failure.
Dose:
Ocular hypertension; open-angle glaucoma, into the eye,
ADULT, instill 2 drops into the affected eye(s) twice daily.
Dose Adjustment: No information found

Drug Interactions: Precautions:

Monitor closely with: WARNING: Has been shown to have a minor effect on
Decreases excretion of the following drugs: heart rate and blood pressure. Use with caution in
Amphetamines, Quinidine patients with a history of cardiac failure or heart block.
Discontinue at the first signs of cardiac failure.
S

Enhances therapeutic effect of Folic Acid Antagonists

Diabetes mellitus (use with caution; may mask signs and
Increases risk of adverse or toxic effects of Phenytoin
(osteomalacia) symptoms of acute hypoglycemia);
Thyrotoxicosis;
Avoid concomitant use with: Muscle weakness;
Increases excretion of Lithium Major surgery;
Pulmonary effects (e.g., asthmatic attacks);
Increases risk of adverse or toxic effects of Acetazolamide: Children;
Aspirin, High-Dose (anorexia, tachypnea, lethargy, Pregnancy;
metabolic acidosis, coma, death) Lactation.

Adverse Drug Reactions:

Increases risk of adverse or toxic effects of the following
drugs:
Sodium Bicarbonate (renal calculus formation)
Increases serum concentration of Cyclosporine
Reduces therapeutic effect of Methamine (urinary
antiseptic effect)
Administration: Should be taken with food.
Doses more than 1 g per 24 hours does NOT produce an
increased effect. Adjust doses carefully, paying attention
to symptoms and ocular tension. Continuous supervision
by a physician is advisable. A complementary effect has
been noted when acetazolamide has been used in
conjunction with miotics or mydriatics as the case
demanded.
Common: Eye discomfort (stinging and burning); occasional
tearing.
Less Common: Blurred vision, foreign body sensation,
dryness of eyes, inflammation, discharge, ocular pain,
decreased visual acuity, crusty lashes.
Rare: Decreased corneal sensitivity, erythema, itchy
sensation, corneal punctate staining, keratitis,
anisocoria, edema, photophobia, bradycardia, heart
block, congestive failure, pulmonary distress, insomnia,
dizziness, vertigo, headaches, depression, lethargy,
increased signs and symptoms of myasthenia gravis,
hives, toxic epidermal necrolysis, hair loss, glossitis.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Betaxolol by exerting
potential additive effects:

586
SENSORY ORGANS
Antiarrhythmics, Beta Blockers, Calcium Channel
Blockers, Catecholamine-depleting Drugs, e.g.,
Reserpine, Guanethidine, Parasympathomimetic Agents
Enhances therapeutic effect of Betaxolol:
Catecholamine-depleting Drugs, e.g., Reserpine (additive
effects)
Increases risk of adverse or toxic effects of Betaxolol:
Catecholamine-depleting Drugs, e.g., Reserpine
(hypotension and/or bradycardia), Digitalis
(bradycardia), Epinephrine (mydriasis)
Administration: For topical ophthalmic use only. Shake
suspension well before use.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
NOTE: Intraocular pressure may require a few weeks to
stabilize in some patients. If intraocular pressure is not
adequately controlled on this regimen, concomitant
therapy with pilocarpine and other miotics and/or
epinephrine and/or carbonic anhydrase inhibitors can be
instituted.
Pregnancy Category: C
ATC Code: S01ED02
Rx BRIMONIDINE
Ophth.: 0.15% ophthalmic solution (as tartrate), 5 mL
bottle
A relatively selective alpha2 adrenergic agonist for
ophthalmic use. It acts by reducing aqueous humor and
increasing uveoscleral outflow.
Indication: For the lowering of intraocular pressure in open-
angle glaucoma or ocular hypertension
Contraindication: Hypersensitivity to any component of the
formulation
Dose:
For lowering of intraocular pressure, into the eye, ADULT,
instill 1 drop into the affected eye(s) every 8 hours.
Dose Adjustment: No information found
Precautions:
Vascular insufficiency;
Children;
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common: Allergic conjunctivitis, conjunctival hyperemia,
eye pruritus, burning sensation, conjunctival folliculosis,
hypertension, ocular allergic reaction, oral dryness,
visual disturbance, allergic reaction, arthralgia, arthritis,
asthenia, blepharitis, blepharoconjunctivitis, blurred
vision, bronchitis, cataract, chest pain, conjunctival
edema, conjunctival hemorrhage, conjunctivitis, cough,
dizziness, diabetes mellitus, dyspepsia, dyspnea,
epiphora, eye discharge, eye dryness, eye irritation, eye
pain, eyelid edema, eyelid erythema, fatigue, flu
syndrome, follicular conjunctivitis, foreign body
sensation, gastrointestinal disorder, headache,
hypercholesterolemia, hypotension, infection, insomnia,
joint disorder, keratitis, lid disorder, osteoporosis,
pharyngitis, photophobia, rash, rhinitis, sinus infection,
sinusitis, somnolence, stinging, superficial punctate
keratopathy, tearing, visual field defect, vitreous
detachment, vitreous disorder, vitreous floaters,
worsened visual acuity.
Less Common: Corneal erosion, nasal dryness, taste
perversion.
Rare: Bradycardia, iritis, miosis, skin reactions, tachycardia,
apnea, hypothermia, hypotonia.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Brimonidine:
CNS Depressants e.g., Alcohol (additive or potentiation
effect)
Increases risk of adverse or toxic effects of Brimonidine:
MAO Inhibitors e.g., Sertraline (systemic side effects)
Avoid concomitant use with:
Enhances therapeutic effect of Alpha2 Agonists e.g.,
Methyldopa (reduced blood pressure)
Decreases metabolism of Brimonidine:
Tricyclic Antidepressants e.g., Amitriptyline (increased
uptake of circulating amines)
S
Administration: For ophthalmic use only.
NOTE: May be used concomitantly with other topical
ophthalmic drug products to lower intraocular pressure.
If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart.
Pregnancy Category: B
ATC Code: S01EA05
Rx BRINZOLAMIDE
Ophth.: 1% ophthalmic suspension, 5 mL bottle
A carbonic anhydrase inhibitor that inhibits the reversible
reaction involving carbon dioxide hydration. Inhibition of
carbonic anhydrase in the eye decreases aqueous
humor secretion, resulting in a reduction in intraocular
pressure (IOP).
Indication: Treatment of elevated intraocular pressure in
ocular hypertension or open-angle glaucoma
Contraindication: Hypersensitivity to any component of the
formulation
587
 SENSORY ORGANS

Dose: Dose:
Elevated intraocular pressure, into the eye, ADULT, 1 drop Miosis during surgery, reduction of postoperative rises in
into the affected eye(s) 3 times daily. intraocular pressure, by intraocular injection, ADULT,
instill up to 0.5 mL into the anterior chamber before or
Precautions: after securing sutures.
Cross-sensitivity;
Corneal endothelium; Dose Adjustment: No information found
Acute angle-closure glaucoma;
Renal impairment (not recommended in severe renal Precautions:
impairment); WARNING: The vial stopper contains natural rubber
Pregnancy; (latex), which may cause severe allergic reactions.
Lactation.
Children;
Adverse Drug Reactions: Pregnancy.
Common: Blurred vision, taste disturbance (bitter, sour, or
unusual), blepharitis, dermatitis, dry eye, foreign body Adverse Drug Reactions:
sensation, headache, hyperemia, ocular discharge, Common: Corneal clouding, persistent bullous keratopathy,
ocular discomfort, ocular keratitis, ocular pain, ocular retinal detachment, postoperative iritis following
pruritus, rhinitis. cataract extraction, eye irritation (transient), burning and
Less Common: Allergic reactions, alopecia, chest pain, stinging of the eye (transient), ciliary spasm, lacrimation,
conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, difficulty in dark adaptation, increased pupillary block,
dyspnea, dyspepsia, eye fatigue, hypertonia, vitreous hemorrhage, conjunctival vascular congestion,
keratoconjunctivits, keratopathy, kidney pain, lid margin lens changes, lid sensitization, conjunctiva.
crusting, sticky sensation, nausea, pharyngitis, tearing, Less Common: Corneal edema, prolonged miosis, eye
urticarial. inflammation, eye pain, increased intraocular pressure,
ocular hyperemia, blurred vision, visual impairment,
Drug Interactions: vomiting.
Monitor closely with: Rare: Nausea, vomiting, flushing, sweating, diarrhea,
Increases risk of adverse or toxic effects of Brinzolamide: headache, brow ache, abdominal pain, bronchial asthma
Salicylates e.g., Aspirin (acid-base and electrolyte and spasm, pulmonary edema, GI distress, salivation,
alterations) urinary frequency, cardiac arrhythmia, peripheral
vasodilation, tightness in urinary bladder.
Avoid concomitant use with:
Enhances systemic therapeutic effect of Brinzolamide: Drug Interactions:
Carbonic Anhydrase Inhibitors (Oral) e.g., Acetazolamide Monitor closely with:
S

Reduces therapeutic effect of Carbachol:

Administration: For topical ophthalmic use only. Cyclopentolate (Ophthalmic), NSAIDs (Ophthalmic)
Do NOT wear contact lenses during treatment. Avoid Avoid concomitant use with:
touching the applicator to the eye or other surfaces. Increases risk of adverse or toxic effects of Carbachol:
Acetylcholinesterase Inhibitors e.g., Neostigmine, Beta
NOTE: May be used concomitantly with other topical Blockers (cardiac conduction abnormalities;
ophthalmic drug products to lower intraocular pressure. bronchoconstriction)
If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart. Administration: For single-dose intraocular use only.
Pregnancy Category: C Use only if container is undamaged. Discard unused
portion.
ATC Code: S01EC04
Aseptically remove the sterile vial from the blister
package by peeling the backing paper and dropping the
Rx CARBACHOL vial onto a sterile tray. Withdraw the contents into a dry
sterile syringe and replace the needle with an atraumatic
cannula. Gently instill no more than ½ milliliter into the
Ophth.: 0.01% intraocular solution, 1.5 mL vial anterior chamber to produce satisfactory miosis. It may
be instilled before or after securing sutures. Miosis is
A sterile balanced salt solution of carbachol for intraocular usually maximal within 2–5 minutes.
injection. It is a potent cholinergic
(parasympathomimetic) agent, which produces Pregnancy Category: C
constriction of the iris and ciliary body resulting in
reduced intraocular pressure. ATC Code: S01EB02

Indications: For obtaining miosis during surgery; for

reduction of the intensity of intraocular pressure
elevation in the first 24 hours following cataract surgery.

588
SENSORY ORGANS
Rx DORZOLAMIDE
Ophth.: 2% eye drops solution (as hydrochloride), 5 mL
vial
A carbonic anhydrase inhibitor that inhibits the reversible
reaction involving carbon dioxide hydration. Dorzolamide
decreases aqueous humor secretion, resulting in a
reduction in intraocular pressure (IOP).
Indication: Treatment of elevated intraocular pressure in
ocular hypertension or open-angle glaucoma
Dose:
Elevated intraocular pressure, into the eye, ADULT, instill 1
drop in the affected eye(s) 3 times daily.
Precautions:
Cross-sensitivity;
Allergic reactions (local ocular adverse effects, i.e.,
conjunctivitis, lid reactions, have been reported with
chronic use);
Bacterial keratitis;
Corneal endothelium;
Acute angle-closure glaucoma;
Renal and hepatic impairment (use is not recommended);
Pregnancy (use with caution);
Lactation (use with caution).
Adverse Drug Reactions:
Common: Ocular burning or stinging, ocular discomfort,
bitter taste, superficial punctate keratitis, ocular allergic
reaction, conjunctivitis, lid reactions, blurred vision, eye
redness, eye tearing, eye dryness, photophobia.
Less Common: Headache, nausea, asthenia or fatigue.
Rare: Skin rashes, urolithiasis, iridocyclitis.
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Dorzolamide:
Alpha / Beta Agonists, Indirect Acting e.g., Methyldopa;
Salicylates, High-dose (acid-base and electrolyte
alterations)
Avoid concomitant use with:
Enhances systemic therapeutic effect of Dorzolamide:
Carbonic Anhydrase Inhibitors, Oral
Administration: For topical ophthalmic use only.
May be used concomitantly with other topical ophthalmic
drug products to lower intraocular pressure. If more than
one topical ophthalmic product is being used, administer
at least 5 minutes apart.
Pregnancy Category: C
ATC Code: S01EC03
Rx GLYCEROL (GLYCERIN)
Oral: USP grade
An osmotic dehydrating agent with hygroscopic and
lubricating properties. Glycerol increases plasma
osmolality, resulting in the movement of water from
extravascular spaces into the plasma through osmosis.
Indications: Management of glaucoma; reduction of
intraocular pressure prior to eye surgery
Dose:
Elevated intraocular pressure, by mouth, ADULT, 1–2 g/kg
taken as a single dose; additional doses of 500 mg/kg
every 6 hours may be taken if needed; CHILD, 1–1.5
g/kg taken as a single dose, may be repeated in 4–8
hours if needed.
Dose Adjustment: No information found
Administration: For use as an oral demulcent. Do NOT
swallow excessive amounts.
Mix it with a small amount of unsweetened lemon, lime,
or orange juice, pour over cracked ice, and sip through a
straw to mask its unpleasant taste. Lie down when taking
this medicine and for a short time after taking it to
prevent or relieve headaches.
NOTE: When used preoperatively, administer 60–90
minutes prior to surgery. Precautions should be taken to
avoid acute urinary retention.
S
See Glycerol (Glycerin) under Other Nervous System Drugs
in Chapter 10: Nervous System for other information.
Pregnancy Category: C
ATC Code: Not available
Rx LATANOPROST
Ophth.: 50 micrograms/mL eye drops solution, 2.5 mL
bottle
A prostaglandin F2α analogue that reduces intraocular
pressure by increasing the outflow of aqueous humor.
Indication: Reduction of elevated intraocular pressure (IOP)
in patients with open-angle glaucoma or ocular
hypertension.
Contraindication: Known hypersensitivity to latanoprost,
benzalkonium chloride, or any other ingredients in this
product.
Dose:
Elevated intraocular pressure, into the eye, ADULT, instill 1
drop into the affected eye(s) once daily in the evening.
Dose Adjustment: No information found
589

Precautions:
Pigmentation;
Macular edema (use with caution);
Intraocular inflammation (use with caution);
Eyelash changes (e.g., increased length, thickness,
pigmentation, number of lashes or hairs, and
misdirected growth of lashes);
Bacterial keratitis and herpetic keratitis;
Pregnancy (no adequate and well-controlled studies);
Lactation (not known if excreted in breast milk).
Adverse Drug Reactions:
Common: Iris pigmentation changes, eyelid skin darkening,
eyelash changes, intraocular inflammation, macular
edema, foreign body sensation, punctate keratitis,
stinging, conjunctival hyperemia, blurred vision, itching,
burning, excessive tearing, eyelid discomfort or pain, dry
eye, eye pain, eyelid margin crusting, erythema of the
eyelid, photophobia, eyelid edema, upper respiratory
tract infection, nasopharyngitis, myalgia, arthralgia, back
pain, allergic skin reaction.
Less Common: Dizziness, headache, toxic epidermal
necrolysis, asthma, dyspnea, pruritus, herpes keratitis,
angina, chest pain, trichiasis, iris cyst.
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Latanoprost:
Prostaglandins and Prostaglandin Analogs (paradoxical
elevations in IOP)
Administration: For topical ophthalmic use only. Do NOT
exceed once daily.
Contact lenses should be removed prior to
S
administration and may be reinserted 15 minutes after
administration.
NOTE: May be used concomitantly with other topical
ophthalmic drug products to lower IOP. If more than one
topical ophthalmic drug is being used, administer drugs
at least 5 minutes apart.
MISSED DOSE. In case of missed dose, continue with the
next dose as normal.
Pregnancy Category: C
ATC Code: S01EE01
Rx MANNITOL
Inj.: 20%, 250 mL and 500 mL bottle (IV)
A hexahydric alcohol related to mannose that acts as an
osmotic agent. When given parenterally, mannitol raises
the osmotic pressure of the plasma, thus drawing water
out of body tissues and producing osmotic diuresis.
Indication: Reduction of increased intraocular pressure
NOTE: NOT recommended to be used for the prevention of
acute renal failure and/or promotion of diuresis.
590
SENSORY ORGANS
Contraindications: Severe renal disease (anuria); severe
dehydration; active intracranial bleeding except during
craniotomy; progressive heart failure, pulmonary
congestion, or renal dysfunction after mannitol
administration; severe pulmonary edema or congestion.
Dose:
Reduction of intraocular pressure, by IV injection, ADULT,
0.25-2 g/kg administered over 30-60 minutes 1-1.5
hours prior to surgery; CHILD, 1-2 g/kg or 30-60 g/m2
administered over 30-60 minutes 1-1.5 hours prior to
surgery.
Reduction of intraocular pressure (traumatic hyphema), by
IV injection, ADULT, 1.5 g/kg administered over 45
minutes twice daily for IOP >35 mm Hg; may administer
every 8 hours; CHILD, 1.5 g/kg administered over 45
minutes twice daily for IOP >35 mm Hg; may administer
every 8 hours in patients with extremely high pressure.
Administration: For IV administration. Determine
concentration and rate of administration based on
indication or severity, or adjusted to urine flow.
Inspect for crystals prior to administration. If crystals are
present, re-dissolve by warming solution. Use filter type
administration set for infusion solutions containing
≥20% Mannitol.
Do NOT administer until adequacy of renal function and
urine flow is established. Use 1–2 test doses to assess
renal response.
NEVER add to whole blood for transfusion or administer
through the same set by which blood is being infused to
prevent crenation and agglutination of red blood cells.
See Mannitol under Blood Substitutes and Perfusion
Solutions – IV Solutions Producing Osmotic Diuresis in
Chapter 2: Blood and Blood Forming Organs for other
information.
Pregnancy Category: C
ATC Code: Not available
Rx PILOCARPINE
Ophth.:
1% eye drops solution (as hydrochloride), 10 mL and 15 mL
bottle
2% eye drops solution (as hydrochloride), 10 mL and 15 mL
bottle
A direct acting cholinergic parasympathomimetic agent that
acts through direct stimulation of muscarinic receptors
and smooth muscle, such as the iris and secretory
glands. It contracts the ciliary muscle, causing increased
tension on the scleral spur and opening of the trabecular
meshwork spaces. This reduces outflow resistance,
resulting in a decrease in intraocular pressure (IOP).
Pilocarpine also causes a contraction of the iris sphincter
muscle, producing miosis.
SENSORY ORGANS
Indications: Reduction of elevated IOP in open-angle
glaucoma or ocular hypertension; management of acute
angle-closure glaucoma; prevention of post-operative
elevated IOP associated with laser surgery; induction of
miosis.
Contraindication: Conditions where constriction is
undesirable (e.g., acute iritis).
Dose:
Reduction of elevated IOP in open-angle glaucoma or ocular
hypertension, into the eye, ADULT, 1 drop of 2% solution
in the affected eye(s) up to 4 times daily; CHILD <2 years,
1 drop of 2% solution in the affected eye(s) 3 times daily
[NOTE: The frequency of instillation and concentration of
pilocarpine are determined by the severity of the
elevated IOP and miotic response of the patient].
Management of acute angle-closure glaucoma, into the eye,
ADULT, initially 1 drop of 2% solution in the affected
eye(s) up to 3 times over a 30-minute period [NOTE:
Treatment with secretory suppressants and
hyperosmotic agents may be needed to lower IOP below
50 mmHg and relieve iris ischemia prior to
administration. If laser iridoplasty or iridotomy is used to
break the attack, instill 1 drop of 4% solution prior to the
procedure. Following laser iridoplasty, instill 1 drop of 2%
solution 4 times daily until an iridotomy can be
performed].
Prevention of post-operative elevated IOP associated with
laser surgery, into the eye, ADULT, instill 1 drop of 1% or
2% solution in the affected eye(s) 15–60 minutes prior
to surgery, or 2 drops 5 minutes apart.
Induction of miosis, into the eye, ADULT, instill 1 drop of 2%
solution in the affected eye(s) or 2 drops 5 minutes
apart; CHILD <2 years, 1 drop 2% solution in the affected
eye(s) 15 to 60 minutes prior to surgery.
Dose Adjustment: No information found
Precautions:
Poor illumination (e.g., accommodation spasm);
Pre-existing retinal disease (e.g., rare cases of retinal
detachment);
Iritis;
Primary congenital glaucoma (e.g., cases of paradoxical
increase in IOP);
Pregnancy (administer only if clearly needed);
Lactation (not known if excreted in breast milk).
SKILLED TASKS. May cause blurred vision. Avoid performing
tasks, which require mental alertness, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Common: Headache, brow ache, accommodative change,
blurred vision, eye irritation, visual impairment, eye pain,
ciliary spasm, conjunctival vascular congestion, induced
myopia, reduced visual acuity in poor illumination, lens
opacity (prolonged use).
Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of Pilocarpine:
Parasympathomimetics (additive effect)
Increases risk of adverse or toxic effects of the following
drugs:
Beta Blockers (conduction disturbances), Miotic drugs
(toxic reactions)
Reduces anticholinergic effects of Pilocarpine:
Atropine, Ipratropium (Inhalation)
Administration: For topical ophthalmic use only. NOT for
injection
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for 1–2 minutes after instillation to
decrease risk of absorption and systemic effects.
Contact lenses should be removed prior to the
administration and may be reinserted 10 minutes after
administration.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
NOTE: Pilocarpine-naïve patients should be started on 1%
concentration as higher concentrations are often not
tolerated initially.
May be used in combination with beta blockers, carbonic
anhydrase inhibitors, hyperosmotic agents, or
sympathomimetics. If more than one topical ophthalmic
product is being used, administer at least 5 minutes
apart.
Pregnancy Category: C
S
ATC Code: S01EB01
Rx TAFLUPROST
Eye Drops Solution: 15 mcg/mL, 0.3 mL bottle (single dose)
Tafluprost acid is a fluorinated prostaglandin F2-alpha
analog believed to reduce intraocular pressure by
increasing outflow of aqueous humor via the uveoscleral
pathway; exact mechanism by which it reduces
intraocular pressure is unknown.
Indications: Reduction of intraocular pressure in patients
with open-angle glaucoma or ocular hypertension.
Contraindications: None.
Dose:
Elevated intraocular pressure, ADULT, instill affected eye(s)
once daily in the evening.
Dose Adjustment:
Renal and Hepatic impairment:
No dosage adjustments provided in the manufacturer’s
labeling.
591

Precautions:
May cause changes to pigmented tissues and macular
edema;
Use in caution in patients with intraocular inflammation.
Adverse Drug Reactions:
Common: Conjunctival hyperemia.
Less Common: Headache, urinary tract infection, common
cold, eye irritation, stinging of eyes, conjunctivitis,
cataract, eye pain, xerophthalmia, blurred vision,
hyperpigmentation of eyelashes, increased eyelash
length, and cough.
Rare: Dyspnea, exacerbation of asthma, iris
hyperpigmentation, iritis, and uveitis.
Drug Interactions:
None known.
Administration: Instill into conjunctival sac of affected
eye(s). Do not exceed once daily dosing regimen. If other
ophthalmics are prescribed, each should be
administered 5 minutes apart. Use immediately after
opening preservative-free product.
Pregnancy Category: C
ATC Code: S01EE05
Rx TIMOLOL
Ophth.: 0.5% eye drops solution (as maleate), 5 mL
bottle
S
A non-selective beta blocking agent that reduces intraocular
pressure (IOP) whether accompanied by glaucoma or
not.
Indication: Treatment of elevated IOP in ocular hypertension
or open-angle glaucoma.
Contraindications: Bronchial asthma; severe chronic
obstructive pulmonary disease; sinus bradycardia;
second or third-degree atrioventricular block; overt
cardiac failure.
Dose:
Elevated IOP, into the eye, ADULT, 1 drop in the affected
eye(s) twice daily.
NOTE: Evaluate after approximately 4 weeks of treatment to
determine IOP.
If IOP is maintained at satisfactory levels, the dosage
schedule may be changed to 1 drop once daily in the
affected eye(s). Measure IOP at different times during
the day to best determine response to once-a-day dose
due to diurnal variations in intraocular pressure.
Dose Adjustment: No information found
Precautions:
WARNING: May exhibit the same adverse reactions as
with systemic beta blockers, including severe
respiratory reactions and cardiac reactions.
592
SENSORY ORGANS
If handled improperly, ophthalmic medications can
become contaminated by common bacteria known
to cause eye infections, which may cause serious
damage to the eye and subsequent loss of vision
Cardiac failure;
Obstructive pulmonary disease;
Major surgery (impairs response of heart to beta-
adrenergically mediated reflex stimuli; may augment risk
of general anesthesia in surgical procedures);
Muscle weakness;
Diabetes mellitus (may mask signs and symptoms of acute
hypoglycemia);
Thyrotoxicosis;
Bacterial keratitis (associated with use of multiple dose
containers of topical ophthalmic products);
Angle-closure glaucoma;
Children;
Pregnancy;
Lactation (detected in human milk).
Adverse Drug Reactions:
Common: Eye burning and stinging
Less Common: Headache, asthenia, fatigue, chest pain,
bradycardia, arrhythmia, hypotension, hypertension,
syncope, heart block, cerebral vascular accident,
cerebral ischemia, cardiac failure, worsening of angina
pectoris, palpitation, cardiac arrest, pulmonary edema,
edema, claudication, Raynaud's phenomenon, cold
hands and feet, nausea, diarrhea, dyspepsia, anorexia,
dry mouth, systemic lupus erythematosus, dizziness,
increase in signs and symptoms of myasthenia gravis,
paresthesia, somnolence, insomnia, nightmares,
behavioral changes, psychic disturbances, alopecia,
psoriasiform rash or exacerbation of psoriasis, signs and
symptoms of systemic allergic reactions, anaphylaxis,
bronchospasm, respiratory failure, dyspnea, nasal
congestion, cough, upper respiratory infections, ocular
irritation, ptosis, decreased corneal sensitivity, cystoid
macular edema, visual disturbances,
pseudopemphigoid, choroidal detachment following
filtration surgery, tinnitus, retinoperitoneal fibrosis,
decreased libido, impotence, Peyronie’s disease.
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of Timolol:
Catecholamine-depleting Drugs, e.g., Reserpine (additive
effects), Quinidine (potentiated systemic beta blockade)
Enhances therapeutic effect of the following drugs:
Clonidine (exacerbates rebound hypertension following
withdrawal of clonidine), Digitalis (prolonged
atrioventricular conduction time)
Increases risk of adverse or toxic effects of Timolol:
Catecholamine-depleting Drugs, e.g., Reserpine
(hypotension and/or marked bradycardia)
Avoid concomitant use with:
Enhances therapeutic effect of Timolol:
Beta Blockers
Increases risk of adverse or toxic effects of Timolol:
Calcium Antagonists (atrioventricular conduction
disturbances; left ventricular failure; hypotension)
SENSORY ORGANS
Reduces therapeutic effect of Epinephrine
(unresponsiveness to usual doses used in anaphylaxis)
Administration: For topical ophthalmic use only.
If using a bottle for the first time, make sure the safety seal
is unbroken.
Drop-tainer bottle: Wash hands before each use. Shake
once and remove the screw cap. Invert the bottle and
hold the bottle between your thumb and middle finger. (If
self-administered, instruct patient that the tips of the
fingers point towards them). Tilt head back and position
the bottle above the affected eye. With the opposite
hand, place a finger under the eye and gently pull down
until a “V” pocket is made between the eye and the lower
lid. With the hand holding the bottle, place the index
finger on the bottom of the bottle and push the bottom
of the bottle to dispense 1 drop. Do NOT squeeze the
sides of the bottle. Repeat with the other eye if needed.
Replace screw cap by turning until firmly touching the
bottle.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
The dispenser tip is designed to provide a pre-measured
drop. Do NOT enlarge the hole of the dispenser tip.
NOTE: Doses above 1 drop twice daily have not shown to
produce further reduction in IOP. If IOP is still not at a
satisfactory level on this regimen, concomitant therapy
with other agent(s) for lowering intraocular pressure can
be instituted. Concomitant use of 2 topical beta blockers
is not recommended.
If more than one topical ophthalmic product is being
used, administer at least 5 minutes apart.
Pregnancy Category: C
ATC Code: S01ED01
Rx TRAVOPROST
Ophth.: 0.004% ophthalmic solution, 2.5 mL bottle
A synthetic prostaglandin F analogue that reduces
intraocular pressure (IOP) by increasing uveoscleral
outflow.
Indication: For the reduction of elevated IOP in patients with
open-angle glaucoma or ocular hypertension
Contraindication: Hypersensitivity to any component of the
formulation.
Dose:
Elevated IOP, into the eye, ADULT, 1 drop in the affected
eye(s) once daily in the evening.
Precautions:
Pigmentation (e.g., increased pigmentation to the iris,
eyelid, and eyelashes);
Eyelash changes (e.g., increased length, thickness, and
number of lashes);
Intraocular inflammation;
Macular edema;
Angle-closure, inflammatory, or neovascular glaucoma;
Bacterial keratitis (associated with use of multiple-dose
containers)
Children (not recommended for patients <16 years due to
potential safety concerns related to increased
pigmentation following long-term chronic use).
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common: Ocular hyperemia, conjunctival hyperemia,
decreased visual acuity, eye discomfort, foreign body
sensation, eye pain, eye pruritus, abnormal vision,
blepharitis, blurred vision, cataract, conjunctivitis,
corneal staining, dry eye, iris discoloration, keratitis, lid
margin crusting, ocular inflammation, photophobia,
subconjunctival hemorrhage, tearing, allergy, angina
pectoris, anxiety, arthritis, back pain, bradycardia,
bronchitis, chest pain, cold or flu syndrome, depression,
dyspepsia, GI disorder, infection, headache,
hypercholesterolemia, hypertension, hypotension, pain,
prostate disorder, sinusitis, urinary incontinence, urinary
tract infections.
Less Common: Arrhythmia, vomiting, epistaxis, tachycardia,
insomnia.
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Travoprost:
NSAIDs
S
Administration: For topical ophthalmic use only.
Do NOT administer more than once daily since it has
been shown to decrease IOP lowering effect.
Contact lenses should be removed prior to the
administration and may be reinserted 15 minutes after
administration.
NOTE: May be used in combination with other topical
ophthalmic drugs to lower IOP. If more than one topical
ophthalmic product is being used, administer at least 5
minutes apart.
Pregnancy Category: C
ATC Code: S01EE04
593
 SENSORY ORGANS

MYDRIATICS AND CYCLOPLEGICS Drug Interactions:

Monitor closely with:
Enhances anticholinergic effects of Atropine by exhibiting
Rx ATROPINE additive effects:
Antidepressants, Antihistamines e.g., Diphenhydramine,
Quinidine
Ophth.: 1% eye drops solution (as sulfate), 5 mL and 10
mL bottle
Avoid concomitant use with:
Increases risk of adverse or toxic effects of MAO Inhibitors
An alkaloid from Atropa belladonna that acts as an
e.g., Selegeline (hypertensive crisis)
anticholinergic agent. Atropine blocks the responses of
the sphincter muscle of the iris and the accommodative
Administration: For topical ophthalmic use only. NOT for
muscle of the ciliary body of cholinergic stimulation,
injection. Keep out of reach of children.
producing pupillary dilation (mydriasis) and paralysis of
accommodation (cycloplegia).
Always wash hands before and after administration.
Indications: For mydriasis and/or cycloplegia; for cycloplegic
Drop-tainer bottle: Wash hands before each use. Shake
refraction; for pupillary dilation desired in inflammatory
once and remove the screw cap. Invert the bottle and
conditions of the iris and uveal tract.
hold the bottle between your thumb and middle finger. (If
self-administered, instruct patient that the tips of the
Contraindications: Primary glaucoma or tendency toward
fingers point towards them). Tilt head back and position
glaucoma.
the bottle above the affected eye. With the opposite
hand, place a finger under the eye and gently pull down
Dose:
until a “V” pocket is made between the eye and the lower
For eye refraction, into the eye, ADULT, instill 1 drop to the
lid. With the hand holding the bottle, place the index
eye(s) for 1–2 days before the procedure or on a single
finger on the bottom of the bottle and push the bottom
occasion 1 hour before refraction; CHILD, instill 1 drop
of the bottle to dispense 1 drop. Do NOT squeeze the
twice daily for 1–3 days before the procedure with an
sides of the bottle. Repeat with the other eye if needed.
additional dose 1 hour before the procedure.
Replace screw cap by turning until firmly touching the
For uveitis and inflammatory eye disorders, into the eye,
bottle.
ADULT, 1–2 drops of 1% solution to each eye up to 3–4
times daily; CHILD, instill 1 drop up to 3 times daily.
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for a few minutes after instillation to
Dose Adjustment: No information found
decrease risk of absorption and systemic effects.
Precautions:
S

Contact lenses should be removed prior to the

WARNING: Excessive use in children or certain administration and may be reinserted 10 minutes after
individuals with previous history of susceptibility to administration.
belladonna alkaloids may produce systemic
symptoms of atropine poisoning. Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
Photophobia and blurred vision (e.g., sensitivity to light; may Pregnancy Category: C
last up to 2 weeks);
Elevation of blood pressure; ATC Code: S01FA01
Children (use of 1% solution is not recommended in children
<3 months; limit use in children <3 years with Down
syndrome, spastic paralysis or brain damage to no more
than 1 drop per eye per day). Rx PHENYLEPHRINE
Pregnancy;
Lactation. Ophth.: 2.5% eye drops solution (as hydrochloride), 5
mL bottle
SKILLED TASKS. Causes dilation of pupils, which may impair
ability to perform tasks that require mental alertness, An alpha receptor sympathomimetic agent used in local
e.g., operating machinery or driving. ocular disorders because of its vasoconstrictor and
mydriatic action.
Adverse Drug Reactions:
Common: Photophobia, blurred vision, superficial keratitis, Indications: Vasoconstrictor, decongestant, and mydriatic in
decreased lacrimation, papillary conjunctivitis, contact a variety of ophthalmic conditions and procedures;
dermatitis, lid edema, decreased secretions from pupillary dilation in uveitis; for refraction without
mucous membranes, restlessness, irritability, delirium, cycloplegia; for funduscopy and other diagnostic
tachycardia, flushed skin of face and neck. procedures.
Less Common: Vascular congestion, exudate, eczematoid
dermatitis, hypotension with progressive respiratory Contraindications: Narrow angle glaucoma; low birth weight
depression, coma, death. infants; severe arteriosclerotic cardiovascular or
cerebrovascular disease; intraocular operative

594
SENSORY ORGANS
procedures where corneal epithelial barrier has been
disturbed.
Dose:
Vasoconstriction and pupil dilation, into the eye, ADULT, 1
drop on the upper limbus, may repeat after 1 hour if
needed.
Uveitis, into the eye, ADULT, 1 drop to the upper surface of
the cornea, may be repeated as necessary, not to exceed
3 times; treatment may be continued the following day if
necessary.
Mydriasis, into the eye, ADULT and CHILD ≥1 year, instill 1
drop, may repeat in 10–60 minutes as needed; CHILD
<1 year, instill 1 drop 15–30 minutes prior to procedure.
Ophthalmoscopic examination, into the eye, ADULT, 1 drop
in each eye; sufficient mydriasis to permit examination is
produced in 15–30 minutes; dilation lasts for 1–3 hours.
Blanching test, into the eye, ADULT, instill 1–2 drops to the
injected eye; examine for perilimbal blanching after 5
minutes [if blanching occurs, congestion is superficial].
NOTE: May instill a suitable topical anesthetic a few minutes
prior to phenylephrine to prevent stinging and
consequent dilution of the solution by lacrimation.
Dose Adjustment: No information found
Precautions:
WARNING: Prolonged exposure to air or strong light
may cause oxidation and discoloration. Do NOT use
if solution is brown or contains a precipitate.
Cardiac disease;
Significant hypertension;
Advanced arteriosclerosis;
Elderly (rebound miosis has been reported; may develop
transient pigment floaters in the aqueous humor 40–45
minutes following administration);
Children and infants (use with caution in children with
known cardiac anomalies).
Pregnancy (use only if clearly needed);
Lactation (use with caution).
Adverse Drug Reactions:
Common: Marked increase in blood pressure, syncope,
myocardial infarction, tachycardia, arrhythmia, fatal
subarachnoid hemorrhage.
Drug Interactions:
Monitor closely with:
Increases risk of systemic adverse effects of Beta Blockers
e.g., Propranolol
Enhances therapeutic effect of MAO inhibitors e.g.,
Selegeline (adrenergic effects)
Avoid concomitant use with:
Enhances systemic pressor effects of Phenylephrine,
including tachycardia:
Atropine, Tricyclic antidepressants e.g., Amitriptyline
Administration: For topical ophthalmic use only. NOT for
intraocular use.
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for 2–3 minutes after instillation to
decrease risk of absorption and systemic effects.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
Pregnancy Category: C
ATC Code: S01FB01
Rx TROPICAMIDE
Ophth.: 0.5% eye drops solution, 5 mL bottle
An anticholinergic agent that blocks the responses of the
sphincter muscle of the iris and the ciliary muscle to
cholinergic stimulation, producing mydriasis, with only
slight cycloplegia. It acts rapidly, and the duration of
activity is relatively short.
Indication: For mydriasis and cycloplegia for diagnostic
procedures.
Contraindications: Primary glaucoma
Dose:
Examination of fundus, into the eye, ADULT, instill 1 to 2
drops 15–20 minutes prior to examination.
NOTE: Patients with heavily pigmented irides may require
larger doses.
S
Mydriasis will reverse spontaneously with time, typically
4–8 hours. Some cases may take up to 24 hours.
Dose Adjustment: No information found
Precautions:
WARNING: May cause CNS disturbances, which may
be dangerous in pediatric patients.
Reproductive effects;
CNS effects (e.g., psychotic reaction and behavioral
disturbances);
Photophobia and blurred vision (e.g., sensitivity to light; may
last up to 2 weeks);
Elderly;
Children (psychotic reactions, behavioral disturbances, and
vasomotor or cardiorespiratory collapse have been
reported);
Pregnancy;
Lactation.
SKILLED TASKS. Causes dilation of pupils, which may impair
ability to perform tasks that require mental alertness,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Increased intraocular pressure, psychotic
reactions, behavioral disturbances, transient stinging,
cardiorespiratory collapse (children), dryness of mouth,
blurred vision, photophobia with or without corneal
595
 SENSORY ORGANS

staining, tachycardia, headache, parasympathetic Adverse Drug Reactions:

stimulation, allergic reaction. Clinically Significant: Shock, anaphylactoid reaction such as
erythema, rash, dyspnea, decreased blood pressure, and
Drug Interactions: eyelid edema, etc.
Monitor closely with: Incidence Unknown: Blepharitis, eyelid dermatitis, itching,
Reduces antihypertensive effect of the following drugs: conjunctivitis, corneal epithelium disorder, increased
Carbachol, Cholinesterase Inhibitors (Ophthalmic), intraocular pressure, dry mouth, facial flushing,
Pilocarpine tachycardia, and hypertension.

Administration: For topical ophthalmic use only. NOT for Drug Interactions:
injection. MAO inhibitors- rapid increase in blood pressure may occur.
Tricyclic/tetracyclic antidepressants e.g. Amitriptyline- rapid
Apply finger pressure to the lacrimal sac (inside corner of increase in blood pressure may occur.
the eye) during and for 2–3 minutes after instillation to
decrease risk of absorption and systemic effects. Administration: For ophthalmic use only. Apply into the
conjunctival sac after eyelid retraction, while the patient
Always wash hands before and after administration. is in a supine position. After application, the treated eye
should be closed for 1-5 minutes, while the lacrimal sac
Contact lenses should be removed prior to is compressed appropriately.
administration.
Pregnancy Category: C
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination. ATC Code: S01FA56

Pregnancy Category: C
DIAGNOSTIC AGENTS
ATC Code: S01FA06

Rx FLUORESCEIN
TROPICAMIDE + PHENYLEPHRINE
Rx
HYDROCHLORIDE) Inj.: 10% (100 mg/mL) (as sodium salt), 5 mL ampule (IV)

Eye Drops Solution: 5mg/5 mg per mL (fixed dose Ophth.: 1 mg and 9 mg strips (as sodium salt)
combination), 10 mL bottle
A precursor of eosins that temporarily stains any cell it
S

A clear colorless to pale yellow aqueous ophthalmic enters, marking damaged areas.
solution.
Indications: Angiography of the retina and iris vasculature;
Indications: Mydriasis and cyclopegia for the purpose of aid in the fitting of hard contact lenses; detection of
diagnosis or treatment. corneal lesions and foreign bodies; diagnostic
ophthalmic procedures; applanation tonometry.
Contraindications: Patients with glaucoma or predisposed
to ocular hypertension Dose:
Angiography of the retinal and iris vasculature, by
antecubital vein, ADULT, 500 mg over 5–10 seconds;
Dose: CHILD, 7.5 mg/kg.
Mydriasis, ADULT and CHILD, instill 1-2 drops once or 1 drop Aid in the fitting of hard contact lenses, detection of corneal
twice every 3-5 minutes. lesions and foreign bodies, and diagnostic ophthalmic
procedures, into the eye, ADULT, instill into the desired
Cyclopegia, ADULT and CHILD, 1 drop 2-3 times every 3-5 eye(s), may be given in combination with a local
minutes. anesthetic as 0.25% solution with oxybuprocaine HCl or
proxymetacaine HCl.
Dose Adjustment:
Use in Elderly: Dose Adjustment: No information found
Caution should be exercised when used in elderly.
Precautions:
Precautions: WARNING: An emergency tray should be available
Use in caution in children, hypertensive patients, patients prior to the injection of fluorescein.
with arteriosclerosis, heart disease, diabetes, and
hyperthyroidism;
May cause bradycardia, apnea when administered to Respiratory reaction;
premature infants; Severe local tissue damage (e.g., severe pain in the arm,
Activities requiring clear vision must be avoided; sloughing of the skin, superficial phlebitis, subcutaneous
Protection from direct sunlight or other powerful light should granuloma, and toxic neuritis along the median curve in
be exercised. the antecubital area);

596
SENSORY ORGANS
GI effects (e.g., nausea, vomiting, and GI distress commonly
occur within the first few minutes following injection);
Pregnancy (use only if clearly needed);
Lactation (excreted in breast milk for up to 4 days; following
fluorescein angiography, discontinue breastfeeding for
at least 4 days and the milk should be pumped off and
discarded during this period).
Adverse Drug Reactions:
Common: Nausea, vomiting, GI distress, strong taste,
extravasation, hypersensitivity reactions, transient
coloration of skin and urine, staining of the skin or
clothing, staining of soft contact lenses, headache,
thrombophlebitis.
Rare: Cardiac arrest, basilar artery ischemia, severe shock,
convulsions, syncope.
Drug Interactions: No information found
Administration:
For IV administration, inspect visually for particulate
matter and discoloration prior to administration. Do NOT
mix or dilute with other solutions or drugs. Attach a
syringe into a transparent tubing and a 23-gauge
butterfly needle for injection. Insert the needle and draw
the patient’s blood to the hub of the syringe so that a
small air bubble separates the patient’s blood in the
tubing from the fluorescein. With the room lights on,
slowly inject the blood back into the vein while watching
the skin over the needle tip. If the needle has
extravasated, blood will be seen to bulge the skin over
the needle tip. If this occurs, stop before any fluorescein
is injected. When assured that extravasation has not
occurred, the room light may be turned off and the
fluorescein injected rapidly (1 mL/second) into the
antecubital vein. Luminescence usually appears in the
retina and choroidal vessels in 7–14 seconds and can
be observed by standard viewing equipment. Flush IV
cannulas before and after drugs are injected to avoid
physical incompatibility reactions.
For sterile ophthalmic strips, hold the package in the
middle and tear down toward the sterile strip. Turn the
package over and tear down from the other side, taking
care not to tear the sterile strip. Grasp each end of the
package firmly and pull apart. Do NOT touch the sterile
strip. Moisten the strip with 1–2 drops of sterile irrigating
or saline solution prior to application to ensure full
fluorescence and patient comfort. Touch the conjunctiva
or fornix as required with the moistened tip. Instruct
patient to blink several times after application. Contents
may not be sterile if individual strips have been damaged
or previously opened.
Pregnancy Category: C
ATC Code: S01JA01
OTHER OPHTHALMOLOGICALS
FOR DRY EYES
OTC CARBOXYMETHYLCELLULOSE
Ophth.: 0.5% eye drops solution (as sodium),
0.4 mL and 15 mL bottle
A cellulose derivative prepared by the treatment of cellulose
with alkali and monochloroacetic acid or its sodium salt.
Indications: For the temporary relief of burning, irritation,
and discomfort due to dryness of the eye or from
irritation from wind or sun; for protection against further
irritation. It is commonly used in its salt form as a
viscosity enhancer and emulsifier in food products or as
a lubricant in eye drops.
Dose:
Eye irritation, into the eye, ADULT and CHILD, 1–2 drops in
the affected eye(s) as needed.
Dose Adjustment: No information found
Precautions:
Stop use and consult a doctor if eye pain, changes in vision,
or continued redness or irritation of the eye occurs and
persists for more than 72 hours.
Adverse Drug Reactions:
Rare: Allergic reaction, hives, itching, red, swollen, blistered,
or peeling skin with or without fever, wheezing, tightness
S
in the chest or throat, trouble breathing, swallowing, or
talking, unusual hoarseness, swelling of the mouth, face,
lips, tongue, or throat, change in eyesight, eye pain, or
very bad eye irritation.
Drug Interactions: No information found
Administration: For external use only. Always replace cap
after use.
Keep out of reach of children. If swallowed, get medical
help or contact a poison control center immediately.
Tilt head back and drop the product directly into the eye.
Apply finger pressure to the lacrimal sac (inside corner of
the eye) during and for 1–2 minutes after instillation to
decrease risk of absorption and systemic effects.
Do NOT use if solution is cloudy, leaking, has particles,
or changes color. Do NOT use if neck band is broken or
missing.
Do NOT wear contact lenses during treatment. Do NOT
touch dropper tip to eyelids or other surfaces when
placing drops in eyes to avoid contamination.
Pregnancy Category: Not classified
ATC Code: S01XA20
597

Rx CYCLOSPORINE (CICLOSPORIN)
Ophth.: 0.05% ophthalmic emulsion, 0.4 mL vial
An immunosuppressant prepared as a sterile ophthalmic
preparation. Cyclosporine increases tear production that
has been reduced due to inflammation in the eye(s).
Indication: To increase tear production when suppressed
tear production is presumed to be due to ocular
inflammation.
Dose:
Dry eyes, into the eye, ADULT, instill 1 drop once (0.1%) or
twice (0.05%) daily in each eye, approximately 12 hours
apart.
Dose Adjustment:
Renal and Hepatic Impairment:
Dose adjustment unlikely due to low systemic absorption.
Precautions:
Eye effects (e.g., burning sensation; vision changes, eye
pain, or severe eye irritation may occur);
Pregnancy (not recommended in women of childbearing
potential not using effective contraception);
Lactation (not known if excreted in breastmilk).
Adverse Drug Reactions:
Common: Burning sensation of eyes, foreign body sensation
in the eye, blurred vision, conjunctival hyperemia,
epiphora, eye discharge, eye pain, eye pruritus, stinging
of eyes, visual disturbance.
Less Common: Eye injury, hypersensitivity reaction (e.g.,
S
angioedema, dyspnea, facial swelling, pharyngeal
edema, swelling of eye, swollen tongue, urticaria).
Drug Interactions: No known significant interactions
Administration: For topical application to the eye only.
Invert bottle or vial several times to obtain a uniform
emulsion.
If using a multi-dose bottle for the first time, prime bottle
by squeezing 2 drops onto a tissue. Do NOT let bottle tip
touch tissue.
If using a single-dose bottle, administer immediately
after opening vial. Discard remaining contents after use.
Contact lenses should be removed prior to the
administration and may be reinserted 15 minutes after
administration.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
NOTE: May be used with lubricant eye drops. If more than
one topical ophthalmic product is being used, administer
at least 15 minutes apart.
Pregnancy Category: Not classified
ATC Code: S01XA18
598
SENSORY ORGANS
OTC HYPROMELLOSE
Ophth.: 5 mg/mL eye drop solution, and 10 mg/mL eye
drops solution,10 mL and 15 mL bottle
0.3% ophthalmic solution, 10 mL bottle
A methyl and hydroxypropyl mixed ether of cellulose that is
used as artificial tears to prevent conjunctival and
corneal damage due to impaired lacrimal secretions.
Indications: Protectant against further irritation or to relieve
dryness of the eye.
Dose:
Dry eyes, into the eye, ADULT, instill 1–2 drops into the
affected eye(s) as needed.
NOTE: Consult your doctor if symptoms worsen or persist for
more than 72 hours.
Dose Adjustment: No information found
Precautions:
Ocular effects (e.g., transient blurring of vision on
instillation);
Glaucoma;
Elderly and children (use with caution);
Pregnancy and lactation (use with caution).
SKILLED TASKS. May impair ability to perform tasks, which
require mental alertness, e.g., operating machinery or
driving.
Adverse Drug Reactions:
Common: Eye pain, changes in vision, blurred vision, mild
stinging of the eye, foreign body sensation, continued
redness, eye irritation, ocular hyperemia.
Drug Interactions: No information found
Administration: For external use only. Keep container tightly
closed if not in use.
Wash hands. Tilt the head back and pull the lower lid
away from the eye to form a pouch. Drop the medicine
into the pouch and gently close the eyes. Do not blink.
Keep the eyes closed for 1–2 minutes to allow
absorption of medicine.
If using a single-dose bottle, discard remaining contents
after use.
Do NOT use if solution is cloudy, leaking, has particles,
or changes color. Do NOT use if neck band is broken or
missing.
Do NOT touch dropper tip to eyelids or other surfaces
when placing drops in eyes to avoid contamination.
Pregnancy Category: C
ATC Code: S01KA02
SENSORY ORGANS
Rx SODIUM HYALURONATE
Ophth.: 0.1% (1 mg/mL) ophthalmic solution, 5 mL
and 15 mL bottle
A polysaccharide which functions as a tissue lubricant in
ophthalmic surgery because it forms a viscoelastic
solution in water. It is a suitable substitute for aqueous
and vitreous humor.
Indication: Surgical aid in the anterior segment during
cataract extraction and intraocular lens implantation.
Contraindications: Bleeding disorders; skin infection or skin
problem.
Dose:
Surgical aid in the anterior segment during cataract
extraction and intraocular lens implantation, into the
eye, ADULT, slowly administer a sufficient quantity into
the eye.
Dose Adjustment: No information found
Precautions:
Intraocular pressure (may cause a transient increase);
Pregnancy and lactation (use with caution).
Adverse Drug Reactions:
Common: Increased intraocular pressure (transient),
hypotensive crisis, change in eyesight, eye pain, very bad
eye irritation.
Rare: Allergic reaction, hives, itching, red, swollen, blistered,
or peeling skin with or without fever, wheezing, tightness
in the chest or throat, trouble breathing, swallowing, or
talking, unusual hoarseness, swelling of the mouth, face,
lips, tongue, or throat, post-operative inflammation,
corneal edema, corneal decompensation.
Drug Interactions: No known significant interactions
Administration: For external use only. Keep container tightly
closed if not in use.
Do NOT use if solution is cloudy, leaking, has particles,
or changes color. Do NOT use if neck band is broken or
missing.
Pregnancy Category: Not classified
ATC Code: Not available
LOCAL ANESTHETICS
Rx BUPIVACAINE
Inj.: 0.5% (as hydrochloride), 5 mL, 10 mL, and 20 mL vial
0.5% (as hydrochloride), 5 mL, 10 mL, 20 mL and 50
mL ampul/vial (local infiltration)
0.5% (as hydrochloride) 4 mL ampul (spinal) with 8%
dextrose
0.5% (as hydrochloride) (isobaric), 5 mL ampul
(spinal)
A local anesthetic that blocks the generation and
conduction of nerve impulses by increasing the threshold
for electrical excitation, by slowing the propagation of
nerve impulse, and by reducing the rate of rise of the
action potential.
Indication: To produce local or regional anesthesia in
ophthalmic surgery.
Contraindications: Obstetrical paracervical block
anesthesia.
Dose:
NOTE: Dose should be individualized and varies with
anesthetic procedure, area to be anesthetized, tissue
vasculature, number of neuronal segments to be
blocked, depth of anesthesia, degree of muscle
relaxation required, duration of anesthesia required,
individual tolerance, and the physical condition of the
patient.
Administer the smallest dose and concentration required
S
to produce the desired result.
Moderate to complete motor block of peripheral nerves, by
IV injection, ADULT, 5 mL (12.5 mg).
Dose Adjustment:
Geriatric, Acutely ill Patients, and Debilitated Patients:
Use with caution. Dose reduction may be required.
Hepatic Impairment and/or Cardiac Disease:
Reduce doses.
Administration: Do NOT use solutions containing
preservatives for epidural or caudal blocks. Avoid rapid
injection of large volume. Use fractional (incremental)
doses when feasible.
Use an infusion pump to slowly administer local
anesthetics to or around surgical wound sites and/or
near peripheral nerves for postoperative analgesia.
Avoid IV injections. Perform aspiration prior to
administration. Re-position the needle until no return of
blood can be elicited by aspiration. However, absence of
blood in the syringe does NOT guarantee that IV injection
has been avoided. Intravenous regional anesthesia (Bier
block) is not recommended;
Mixing or the prior or intercurrent use with other local
anesthetic is not recommended due to insufficient data
on the clinical use of such mixtures.
599

NOTE: Duration of anesthetic effect may be prolonged by the
addition of epinephrine.
See Bupivacaine under Anesthetics – Anesthetics, Local
(Amides) in Chapter 10: Nervous System for other
information.
Pregnancy Category: C
ATC Code: Not available
Rx LIDOCAINE
Inj.: 1% (as hydrochloride), 20 mL ampule
2% (as hydrochloride), 2 mL, 5 mL, 20 mL, and 50 mL
ampule/vial
2% (as hydrochloride), 5 mL and 50 mL vial (epidural,
local infiltration)
A moderately long-acting, local anesthetic, which blocks
initiation and transmission of nerve impulses at the site
of application by stabilizing neuronal membrane.
Indication: Surface anesthesia
Contraindications: Adjacent skin infection or inflamed skin
to the proposed site of injection; concomitant therapy
with anticoagulants or an abnormal bleeding tendency;
severe anemia or heart disease; spinal or epidural
anesthesia in dehydrated or hypovolemic patients.
Dose:
Surface anesthesia, into the eye, ADULT, apply 2 drops to
S
the ocular area where procedure will take place; may re-
apply to maintain effect.
Dose Adjustment:
Geriatric and/or Debilitated Patients:
Administer reduced doses commensurate with their age
and physical status.
Renal and Hepatic Impairment:
Reduce dose during prolonged infusion (>24 hours) or
repeated IV doses.
Administration: For parenteral administration, use an
infusion pump to slowly administer lidocaine to or around
surgical wound sites and/or near nerves for pre- or
postoperative regional anesthesia.
Visually inspect for particulate matter and discoloration
prior to administration whenever the solution and
container permit. Solutions that are discolored and/or
contain particulate matter should NOT be used. Unused
portion should be discarded.
See Lidocaine under Anesthetics – Anesthetics, Local
(Amides) in Chapter 10: Nervous System for other
information.
Pregnancy Category: B
ATC Code: S01HA07
600
SENSORY ORGANS
Rx PROXYMETACAINE (PROPARACAINE)
Ophth.: 0.5% eye drops solution (as hydrochloride), 5
mL and 15 mL bottle
A rapid acting topical anesthetic which induces anesthesia
that lasts approximately 10–20 minutes.
Indication: Surface anesthesia; for procedures where
corneal anesthesia of short duration is indicated, (e.g.
tonometry, gonioscopy, removal of corneal foreign
bodies, short corneal and conjunctival procedures).
Contraindication: Preterm neonates
Dose:
Removal of foreign bodies and sutures, and tonometry, into
the eye, ADULT, 1–2 drops as single instillation in each
eye before operation.
Tonometry, into the eye, ADULT and CHILD, 1–2 drops
immediately before measurement.
Short corneal and conjunctival procedures, into the eye,
ADULT, 1 drop in the eye every 5–10 minutes for 5–7
doses.
Dose Adjustment: No information found
Precautions:
WARNING: Permanent corneal opacification with
accompanying visual loss has been reported with
prolonged use.
Hyperallergic corneal reaction (a rare, severe, immediate-
type, apparently hyperallergic corneal reaction
characterized by acute, intense and diffuse epithelial
keratitis, a gray, ground glass appearance, sloughing of
large areas of necrotic epithelium, corneal filaments
and, sometimes, iritis with descemetitis has been
reported).
Prolonged use;
Known allergies;
Cardiac disease;
Hyperthyroidism;
Inflamed eye;
Pregnancy (not known if it causes fetal harm; administer
only if clearly needed);
Lactation (not known if excreted in breastmilk).
SKILLED TASKS. May cause transient blurring of vision.
Avoid performing tasks which require mental alertness,
e.g., operating machinery or driving.
Adverse Drug Reactions:
Common: Occasional temporary stinging, burning, and
conjunctival redness, allergic contact dermatitis
Rare: Hyperallergic corneal reaction
Drug Interactions: No information found
Administration: For topical ophthalmic use only. NOT for
injection.
SENSORY ORGANS

Proxymetacaine should be clear to straw-colored. If the Remove the outer overwrap. Clean and disinfect the
solution becomes darker, discard the solution. rubber stopper using a sterile alcohol wipe. Insert the
spike aseptically into the bag through the target area of
Pregnancy Category: C the rubber stopper. Allow the fluid to flow and remove air
from the tubing before irrigating.
ATC Code: S01HA04
For SINGLE patient use only. Unused content should be
discarded.
ADJUVANT TO SURGERY
Do NOT use unless outer overwrap and seal are intact,
product is clear, and bag is undamaged. Do NOT use if
INTRAOCULAR IRRIGATING product is discolored or contains a precipitate.
Rx SOLUTION (BALANCED SALT
SOLUTION) Pregnancy Category: C

Ophth.: 15 mL, 250 mL, and 500 mL bottle ATC Code: S01XA20

Composition:

Sodium chloride 0.64 % OTOLOGICALS

Potassium chloride 0.075 %
Calcium chloride 0.048 %
Magnesium chloride hexahydrate 0.03 % ANTIINFECTIVES
Sodium acetate 0.39 %

Sodium citrate 0.17 % Rx CLOTRIMAZOLE

Water for injection to make 100.00 %
A solution used as an intraocular irrigant during ocular
surgeries. The solution typically contains a combination
of sodium chloride, potassium chloride, calcium chloride,
and magnesium chloride. This solution mimics the
aqueous humor as closely as possible.
Indications: Irrigant during ocular surgery involving
Otic: 1% otic solution
A broad-spectrum imidazole that acts against fungi (both
dermatophytes and yeasts) and gram-positive cocci
(Staphylococcus and Streptococcus spp.).
Indication: Treatment of acute bacterial otitis externa
caused by organisms susceptible to the action of

S
perfusion of the eye with an expected maximum duration ciprofloxacin, such as Pseudomonas aeruginosa,
of less than 60 minutes. Staphylococcus aureus, and Enterobacteriaceae.

Dose: NOTE: NOT indicated for the treatment of otitis media

NOTE: Enhanced BSS solutions may be desirable for longer
ocular surgical procedures but are considerably costlier. Contraindications: Known or suspected perforated
tympanic membrane.
Irrigant during ocular surgery, into the eye, ADULT and
CHILD, consult specialized references for proper Dose:
administration technique during various ocular surgery Otitis externa, into the ear, CHILD ≥2 years, instill 3 drops
types. into the affected ear twice daily for 7 days or as directed
by the physician.
Dose Adjustment: No information found
Precautions:
Precautions: Hypersensitivity;
WARNING: Open under aseptic conditions only. Superinfection;
Pregnancy and lactation (use with caution; safety has not
been established in this population).
Diabetes mellitus (use with caution in diabetic patients
undergoing vitrectomy; intraoperative lens changes have Adverse Drug Reactions:
been observed). Less Common: Hypesthesia, paresthesia, pruritis, rash,
urticaria.
Adverse Drug Reactions: Corneal swelling, bullous Rare: Ear discomfort, hearing disorders, ear pain.
keratopathy, corneal edema, corneal decompensation.
Drug Interactions:
Drug Interactions: No known significant interactions Monitor closely with:
Reduces therapeutic effect of Clotrimazole:
Administration: For topical ophthalmic use only. NOT for Polyene Antibiotics e.g., Nystatin
injection or IV infusion.
Administration: Prior to first administration, remove the
closure and put the dropper assembly in place on the

601

bottle. Avoid contaminating the dropper with material
from the ear, fingers or other sources. Warm to room
temperature prior to administration.
Lie down with the affected ear upward. Instill the
medication. Remain in this position for at least 30
seconds to facilitate penetration of the drops into the
external ear canal. Repeat, if necessary, for the opposite
ear.
Discard unused portion after treatment is completed.
Pregnancy Category: C
ATC Code: S02AA15
Rx OFLOXACIN
Otic: 0.3% ear drops solution, 5 mL bottle
A DNA gyrase inhibitor that interferes with replication,
transcription, repair, recombination, and transposition of
bacterial DNA.
Indications: Otitis externa; chronic suppurative otitis media;
acute otitis media.
Contraindications: Hypersensitivity to ofloxacin or other
members of the quinolone group, such as oxolinic acid,
cinoxacin, norfloxacin, and ciprofloxacin.
Dose:
Otitis media or chronic suppurative with perforated
S
tympanic membranes, into the ear, ADULT and CHILD,
instill 10 drops into affected ear twice daily for 14 days.
Otitis externa, into the ear, ADULT, instill 10 drops into
affected ear(s) once daily for 7 days; CHILD 6 months –
13 years, instill 5 drops into affected ear(s) once daily for
7 days.
Acute otitis media with tympanotomy tubes, into the ear,
CHILD 1–12 years, instill 5 drops into affected ear twice
daily for 10 days.
Dose Adjustment: Dose adjustment unlikely due to low
systemic absorption.
Precautions:
Hypersensitivity reactions (e.g., severe hypersensitivity
reactions, including anaphylaxis, have occurred; itching,
urticaria, rash, or edema may occur after a single dose;
Stevens-Johnson, toxic epidermal necrolysis, vasculitis,
pneumonitis, nephritis, hepatic failure or necrosis,
anemia, or cytopenias may occur after multiple doses);
Superinfection;
Tendon inflammation or rupture;
Elderly (evaluate the patient's or caregiver's ability to safely
and correctly administer the medication);
Pregnancy and lactation (use with caution; safety has not
been established).
Adverse Drug Reactions:
Common: Application site reaction, dizziness, vertigo,
pruritus, taste perversion, paresthesia.
602
SENSORY ORGANS
Less Common: Diarrhea, fever, headache, hearing loss
(transient), hypertension, nausea, otorrhagia, tinnitus,
tremor, vomiting, xerostomia.
Drug Interactions: No known significant interactions
Administration: NOT for injection or for ophthalmic use.
Prior to use, warm solution by holding container in hands
for 1–2 minutes.
Lie down with the affected ear upward. Instill the
medication. Pump the tragus (cartilage flap over the
opening of the ear canal) 4 times to ensure penetration
of medication. Remain in this position for 5 minutes.
Pregnancy Category: C
ATC Code: S02AA16
CORTICOSTEROIDS AND ANTIINFECTIVES IN
COMBINATION
NEOMYCIN + POLYMYXIN B +
Rx
FLUOCINOLONE ACETONIDE
Otic: 3.5 mg neomycin (as sulfate) + 10,000 units
polymyxin B (as sulfate) + 0.025% fluocinolone
acetonide per mL ear drops solution, 5 mL bottle
A combination of a corticosteroid and anti-infectives
(aminoglycoside and basic peptides), which is used in
treating ear diseases.
Indications: Otitis externa, with or without associated otitis
media; adjunct therapy to acute or chronic dermatoses
of the external ear; chronic suppurative otitis media;
draining mastoidectomy cavities; otorrhea from
ventilation tubes.
Contraindications: Primary infection of the skin caused by
bacteria, fungi, acne rosacea, perioral dermatitis;
patients with herpes simplex, vaccinia, and varicella;
untreated fungal or viral infections; pregnancy (first
trimester).
Dose:
Ear infections, into the ear, ADULT and CHILD, instill 3–4
drops 2–4 times daily. [NOTE: Limit treatment to 5–7
days. Refer to ENT specialist if discharge continues].
Precautions:
Patients with perforated eardrum or long-standing chronic
otitis media; prolonged use.
Adverse Drug Reactions:
Common: Allergic dermatitis
Less Common: Acneiform eruptions, burning, decreased
hearing, dryness, ear pain, folliculitis, fungal overgrowth
inside ear canal, hypertrichosis, hypopigmentation,
irritation, itching, miliaria, perioral dermatitis, secondary
infections, tinnitus.
Rare: Inner ear damage
SENSORY ORGANS
Drug Interactions: No information found
Administration: Warm container in cup of warm water to
reduce viscosity. The ears should be clean and dry. Lie
down with the affected ear upward.
Gentle massage or pressure on the tragus (cartilage flap
over the opening of the ear canal) to aid penetration of
the drops.
Method of drug application based on degree of swelling
in ear canal:
For minimal swelling, instill drops directly into the ear
canal then remain in position for a few minutes.
For swelling that narrows the ear canal, saturate a
sponge wick or ribbon gauze with drops and insert into
the ear canal; review daily until swelling settles.
Pregnancy Category: C
ATC Code: Not available
EAR, NOSE, AND THROAT PREPARATIONS
BACITRACIN + NEOMYCIN +
OTC
POLYMYXIN B
Topical: 200 units bacitracin + 3 mg neomycin (as
sulfate) + 4,000 units polymyxin B (as sulfate)
per gram ointment, 10 g tube
A combination of a corticosteroid and anti-infectives
(aminoglycoside and basic peptides).
Indications: First aid for the prevention and treatment of
infection in minor cuts, scrapes, burns, abrasions, insect
bites, pimples, pustules and other skin breaks.
Contraindication:
Dose:
Treatment or prevention of infection, by topical
administration, ADULT and CHILD, apply 1 FTU on the
area 1–3 times daily.
See General Information on Corticosteroids under
Corticosteroids, Dermatological Preparations in Chapter
4: Dermatologicals for information on fingertip units
(FTU).
Dose Adjustment: No information found
Precautions:
In case of deep puncture wounds, animal bites or serious
burns, consult a physician.
Stop use and consult a physician if the condition persists or
gets worse, or if rash or other allergic reactions develop.
Adverse Drug Reactions: No information found
Drug Interactions: No information found
Administration: For external use only.
Clean the affected area prior to application. May be
covered with a sterile bandage. Not intended for use on
existing scars. Do NOT use for longer than 1 week unless
prescribed by a physician.
Do NOT use in or near the eyes. Do NOT use over large
areas of the body. Keep out of reach of children. If
swallowed, get medical help or contact a Poison Control
Center right away.
Pregnancy Category: Not classified
ATC Code: Not available
OTC FLUTICASONE
Topical: 0.05% nasal aqueous solution (as propionate)
per dose x 120 doses
A glucocorticoid with a fluorocarbothioate ester linkage at
the 17-carbon position. It has potent vasoconstrictive
and anti-inflammatory activities, but weak hypothalamic-
pituitary-adrenal (HPA) inhibitory effect when applied
topically.
Indication: For the temporary relief of symptoms of upper
respiratory allergies, including nasal congestion, runny
nose, sneezing, and itchy nose.
NOTE: NOT for the treatment of asthma
S
Contraindications: Injury or surgery to the nose that is not
fully healed.
Dose:
Symptomatic relief, by nasal administration,
ADULT and CHILD ≥12 years,
Week 1: 2 sprays in each nostril once daily;
Week 2–6 months: use 1–2 sprays in each nostril once
daily, as needed to treat symptoms;
CHILD 4–11 years, 1 spray in each nostril once daily.
Dose Adjustment: No information found
Precautions:
WARNING: Do NOT use in children under 4 years of
age.
Glaucoma;
Cataracts;
Growth effects;
Local site application reactions (e.g., stinging or sneezing
may occur a few seconds right after use);
Pregnancy and lactation (use with caution; consult a health
professional before use).
Adverse Drug Reactions:
Common: Stinging, sneezing.
Rare: Severe facial pain, thick nasal discharge, whistling
sound from the nose, visual changes, frequent
nosebleeds.
603
 SENSORY ORGANS

Drug Interactions: * Reduce dose during controlled ventilation

Avoid concomitant use with:
Increases serum concentration of Fluticasone:
CYP3A4 Inhibitors, e.g. Ritonavir, Ketoconazole
Administration: For nasal use only. Do NOT spray into the
eyes or mouth.
Local anesthetic for oral mucous membrane, by topical
administration, ADULT, apply to the affected area ≤4
times daily as needed (maximum dose, 3 mg/kg, not to
exceed 300 mg); CHILD and ADOLESCENT, dose varies
with age and weight (maximum dose, 3 mg/kg).

Keep out of reach of children. If swallowed, get medical Dose Adjustment:

help or contact a Poison Control Center right away. Geriatric:
Administer reduced doses commensurate with their age
Pregnancy Category: C and physical status.

ATC Code: Not available Administration: For external use only.

Apply a moderately thick layer to affected area (~1/8
inch thick), and allow time for numbness to develop,
approximately 20–60 minutes. Reapply if needed. It is
OTC LIDOCAINE unnecessary to dry the site prior to application.

Topical: 10% spray (as hydrochloride), 50 mL
A moderately long-acting, local anesthetic, which blocks
initiation and transmission of nerve impulses at the site
of application by stabilizing neuronal membrane.
Do NOT use in large quantities, particularly over raw
surfaces or blistered areas. Avoid contact with eyes, in
case of accidental contact with eyes, rinse immediately
with copious amounts of eyewash and seek treatment by
an eye care specialist.

Indication: Short duration local anesthesia (10 to 15 Keep out of reach of children. If swallowed, get medical
minutes) of the oral mucous membrane. help or contact a Poison Control Center right away.

Contraindications: Seizures; liver disease; pregnancy; See Lidocaine under Anesthetics – Anesthetics, Local
lactation. (Amides) in Chapter 10: Nervous System for other
information.
Dose:
Procedure-specific dose recommendations for adults: Pregnancy Category: B

ATC Code: S02DA01

Maximum Dose

Maximum Dose
Recommended
S

(mg) for Short

Procedures
Dose (mg)

Prolonged
(mg) for
Area

P d

Nasal procedures
(e.g., puncture of
20–60 500 600
the maxillary
sinus)
Oral and dental
20–
procedures (e.g., 500 600
200
prior to injection)
Procedures in the
oropharynx (e.g., 20–
500 600
gastrointestinal 200
endoscopy)
Procedures in the
50–
larynx, trachea, 200* 400
200
and bronchi
Procedures in the
respiratory tract
50–
(e.g., insertion of 400 600
400
instruments and
tubes)

NOTE: For short procedures, give drug for less than 1

minute.
For prolonged procedures, the duration of application is
>5 minutes.

604
VARIOUS
VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
GENERAL ANTIDOTES
Rx ACTIVATED CHARCOAL
Oral: USP grade powder, given as slurry
A fine, smooth, odorless, tasteless, black powder, prepared
from the carbonization of organic matter. Activated
charcoal reduces drug or poison absorption either by
binding to the drug in the GI tract or by interrupting its
entry into the enterohepatic recirculation.
Indications: Gastrointestinal decontamination for specific
drug or poison ingestion associated with significant risk
of toxicity; acute, oral poisoning
Contraindications: Bowel obstruction; poisoning by
hydrocarbons (e.g., petroleum distillates) with high
potential for harm if aspirated; poisoning by corrosive
substances; GI tract not anatomically intact; unprotected
airway
Dose:
Reduction of absorption, by mouth, ADULT and CHILD >12
years, 50–100 g in 100–150 mL distilled water as a
slurry given as a single dose, as soon as possible after
ingestion of poison; CHILD 1–12 years, 25 g as a single
dose (50 g in severe poisoning) in 50–100 mL distilled
water; INFANT, 1 g/kg as a single dose (maximum, 50 g)
[NOTE: May repeat lavage every 6 hours for 48–72
hours. To produce effective adsorption, a ratio of about
10-parts activated charcoal to 1-part poison is needed].
Active elimination, by mouth, ADULT, 50 g every 4 hours (in
case of intolerance, 25 g every 2 hours); CHILD >1 year,
25–50 g every 4–6 hours; INFANT, 1 g/kg every 4–6
hours.
Dose Adjustment:
Uremic Adult Patients:
Administer orally 20–50 g once daily.
Precautions:
WARNING: Electrolyte abnormalities (hypernatremia,
hypokalemia, hypermagnesemia) have been
reported to occur with the concomitant use of
cathartics, namely sorbitol.
NOT generally recommended in children <1 year.
Monitor for active bowel sounds before administering;
Drowsy, unconscious or comatose patient (ensure that
airway is protected);
Decreased peristalsis (administer within 1 hour of
ingestion);
Caution during multiple doses due to danger of intestinal
impaction (reduce initial dose to half to prevent
impaction;
Lavage should be followed by sodium sulfate cathartic).
Adverse Drug Reactions:
Common: Black stools, blackening of teeth and mouth,
colicky abdominal pain (discomfort, swelling),
constipation, nausea, vomiting
Less Common: Diarrhea, hypotension
Rare: Bowel obstruction, charcoal embolism, hypoglycemia,
hypothermia, pneumonitis (due to aspiration)
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of Laxatives, e.g.,
Mannitol, Sorbitol (volume depletion; electrolyte
abnormalities)
Avoid concomitant use with:
Reduces therapeutic effect of Activated Charcoal:
Food, e.g., Milk, Ice Cream, Sherbet (decreased
adsorptive capacity)
Reduces therapeutic effect of the following drugs due to
decreased absorption, reducing systemic circulation:
Anti-epileptics, Oral Contraceptives, Other Charcoal
Interactants, e.g., Digoxin, Paracetamol, Furosemide,
Salicylates, Sulfonylureas, Sulfones, Tetracyclines,
Theophylline, Tricyclic Antidepressants
Administration: In preparing lavage, ensure that the patient
is in trendelenburg (supine with feet higher than the
head) and left lateral decubitus position (lying on the
left).
Administer as a slurry (thick suspension) to increase
adsorptive capacity. Do NOT administer with food due to
decreased efficacy. Administer the smallest dose slowly
V
to avoid vomiting.
Adsorptive effectiveness is time-dependent. It is best
administered within 1 hour after poison ingestion.
NOT for use in poisoning with the following substances:
alcohols (e.g., ethanol, methanol), clofenotane (e.g.,
dicophane, DDT), corrosive substances, cyanides,
malathion, and metal salts, (e.g., iron, lithium).
NOTE: If the patient is conscious and cooperative, a slurry
form of the activated charcoal may be orally
administered. But in cases where NGT may be
obstructed, further dilution is allowed.
Pregnancy Category: B
ATC Code: A07BA01
605
 VARIOUS

Rx SODIUM SULFATE Pregnancy Category: C

Oral: USP grade powder ATC Code: A06AD13; A12CA02

A moderately water– and acid–soluble sodium source for

uses compatible with sulfates. It is a gastrointestinal
drug administered as a 0.5% solution as an osmotic
laxative to prompt bowel evacuation.
Indications: Gastrointestinal decontamination for specific
drug or poison ingestion
Dose:
Bowel cleansing, by mouth, ADULT, dilute with water to
approximately 450 mL and ingest as instructed.
Precautions:
WARNING: Direct ingestion of dry powder may
increase the risk of nausea, vomiting, dehydration,
and electrolyte disturbances.
Gout;
Elderly (use with caution);
Children;
Lactation (use with caution).
Adverse Drug Reactions:
Common: Overall discomfort, increased anion gap,
decreased bicarbonate, increased osmolality,
hyperkalemia increase potassium and hypernatremia
increased sodium, hyperuricemia, abdominal distension,
abdominal pain, nausea, vomiting, headache
Less Common: GI upset, bloating, stomach cramps
Rare: Allergic reactions, electrolyte abnormalities, irregular
heartbeat, dizziness, headache, rectal pain, rectal
bleeding, black, tarry, or bloody stools
Drug Interactions:
V
SPECIFIC ANTIDOTES
Rx ACETYLCYSTEINE
Oral: 600 mg effervescent tablet
100 mg and 200 mg sachet
100 mg/5 mL granules for suspension, 150 mL
Inj.: 200 mg/mL, 10 mL ampule and 25 mL bottle (IV
infusion)
A cysteine derivative with a free thiol (-SH) nucleophilic
group able to interact directly with electrophilic group of
oxidant radicals. It acts as a hepatoprotective agent that
restores hepatic glutathione. It serves as a glutathione
substitute and enhances the nontoxic sulfate
conjugation of acetaminophen.
Indications: Management of paracetamol, white or yellow
phosphorus "watusi," zinc phosphide, and carbon
tetrachloride (CCl4) poisoning; for cyclophosphamide-
induced hemorrhagic cystitis
Dose:
Poisoning, by mouth, ADULT, 72-hour regimen consisting of
18 doses (total dose, 1330 mg/kg), initially administer
140 mg/kg loading dose; then administer 70 mg/kg
every 4 hours as maintenance dose;
by IV infusion, ADULT, 21-hour regimen consisting of 3
doses (total dose, 300 mg/kg), initially administer 150
mg/kg in 200 mL D5W over 60 minutes as loading dose
(maximum, 15 g); followed by a second dose of 50 mg/kg
in 500 mL D5W over 4 hours; then administer a third

Monitor closely with: dose of 100 mg/kg in 1000 mL D5W over 16 hours
Increases risk of adverse or toxic effects of Sodium Sulfate, (maximum, 10 g).
particularly, affects renal function:
ACE Inhibitors, Angiotensin Receptor Blockers, Diuretics,
NSAIDs

Increases risk of adverse or toxic effects of the following

drugs:
QT-prolonging Drugs, e.g., Amiodarone, Clozapine,
Quinidine (ventricular arrhythmia, particularly torsade de
pointes)

Avoid concomitant use with:

Increases risk of adverse or toxic effects Sodium Sulfate:
Alcohol (seizures; arrhythmia; kidney problems),
Laxatives, Stool Softeners (electrolyte imbalance;
dehydration)

Administration: Mix with water and shake well prior to

ingestion. To be taken with additional water to improve
patient tolerance. Do NOT swallow the dry powder. Do
NOT take food or other drugs within 1 hour of
administration.

Drink lots of clear liquids before, during, and after

administration to prevent dehydration. Avoid purple or
red fluids.

606
VARIOUS

Dose Adjustment:
Patients weighing <40 kg: In patients who continue to experience symptoms of
Administer as follows: hepatotoxicity or elevated liver function tests after a 72-
hour oral or 21-hour IV regimen, extending the treatment

over 4 hours
course may be appropriate, specifically in patients with a
over 1 hour
150 mg/kg

100 mg/kg
Third Dose
50 mg/kg
Loading

over 16
Second
suspected massive overdose, concomitant ingestion of

hours
Dose

Dose
Body Weight (kg)

other substances, or patients with preexisting liver

disease.

NOTE: Consultation with a poison control center or clinical

toxicologist is highly recommended to determine optimal
IV drug

IV drug

IV drug
D5W

D5W

D5W
(mL)

(mL)

(mL)

(mL)

(mL)

(mL)
patient care.

Pregnancy Category: B
40 30 100 10 250 20 500
30 22.5 100 7.5 250 15 500 ATC Code: V03AB23
21 15.75 100 5.25 250 10.5 500
20 15 60 5 140 10 280
15 11.25 45 3.75 105 7.5 210 Rx ALCOHOL, ETHYL
10 7.5 30 2.5 70 5 140
5 3.75 15 1.25 35 2.5 70 Oral: 95%, USP grade
Inj.: absolute, 1 mL ampule (IV)
NOTE: Decreased volume of diluent may cause solution to Topical: 70% solution
remain hyperosmolar. Adjust osmolarity to
physiologically safe level prior to administration. A clear, aqueous solution of ethyl alcohol that is used in the
treatment of methanol toxicity due to its higher affinity to
Obesity: alcohol dehydrogenase, thus inhibiting the formation of
In patients >100 kg, administer a total dose of 30 g by IV toxic metabolites of methanol
infusion:
Loading dose: 15 g over 60 minutes Indication: Antidote for methyl alcohol (methanol) poisoning
Second dose: 5 g over 4 hours NOTE: Preferred antidote for methanol poisoning is
Third dose: 10 g over 16 hours fomepizole. Use only if fomepizole is unavailable.

Precautions: Dose:
Anaphylactoid reactions; NOTE: IV administration is the preferred route. Continue
Acute acetaminophen poisoning (treatment should begin therapy until methanol is no longer detected or at <20
within 8 hours of ingestion or as soon as possible after mg/dL AND the patient is asymptomatic and metabolic
ingestion); acidosis has been corrected.

Repeated supratherapeutic ingestion (RSTI) of
acetaminophen;
Lactation (use with caution).
Adverse Drug Reactions:
Common: Anaphylactoid reaction, flushing, tachycardia,
edema, tachycardia, urticaria, rash, pruritus, nausea,
vomiting, pharyngitis, rhinorrhea, rhonchi, throat
tightness
Less Common: Anaphylaxis, angioedema, bronchospasm,
chest tightness, cough, dizziness, dyspnea, headache,
hypotension, respiratory distress, stridor, wheezing
Drug Interactions: No known significant interactions
Administration:
For oral administration, administer as 5% solution within
1 hour of preparation. May be diluted with cola, orange
juice, or other soft drink. If patient vomits within 1 hour
of administration, re-administer dose.
For IV administration, use a slow infusion rate to avoid
hypersensitivity reactions. Dilute with D5W or physiologic
solution.
Undiluted acetylcysteine solution (IV) is hyperosmolar.
Adjust as instructed prior to administration.
V
Methanol poisoning, by IV injection, ADULT and CHILD,
initially 600–700 mg/kg (equivalent to 7.6 to 8.9 mL/kg
using a 10% solution);
maintenance dose for nondrinkers, 66 mg/kg per hour
maintenance dose (equivalent to 0.83 mL/kg per hour
using a 10% solution);
maintenance dose for chronic drinkers, 154 mg/kg per
hour maintenance dose (equivalent to 1.96 mL/kg per
hour using a 10% solution).
NOTE: Goal of therapy is to maintain serum alcohol levels
>100 mg/dL.
Methanol poisoning, by mouth, ADULT and CHILD, initially
600–700 mg/kg (equivalent to 0.09 mL/kg per hour
using a 98% solution); maintenance dose for
nondrinkers, 66 mg/kg per hour maintenance dose
(equivalent to 0.78 mL/kg per hour using a 98%
solution);
maintenance dose for chronic drinkers, 154 mg/kg per
hour maintenance dose (equivalent to 0.20 mL/kg per
hour using a 98% solution).
Dose Adjustment:
Hemodialysis:
Maintenance dose via IV administration:

607

For nondrinkers, 169 mg/kg per hour (equivalent to 0.22
mL/kg per hour using a 10% solution).
For chronic drinkers, 257 mg/kg per hour (equivalent to
3.26 mL/kg per hour using a 10% solution).
Maintenance dose via oral administration:
For nondrinkers, 169 mg/kg per hour (equivalent to 0.22
mL/kg per hour using a 98% solution).
For chronic drinkers, 257 mg/kg per hour (equivalent to
0.33 mL/kg per hour using a 98% solution).
Precautions:
Diabetes;
Hepatic impairment or shock (use with caution);
Children;
Pregnancy (crosses the placenta, enters fetal circulation,
and has teratogenic effects);
Lactation.
Adverse Drug Reactions:
Common: Flushing, hypotension, agitation, CNS depression,
coma, disorientation, drowsiness, encephalopathy,
headache, sedation, vertigo, hypoglycemia, gastric
irritation, nausea, vomiting, urinary retention, nerve and
tissue destruction, phlebitis, polyuria, intoxication
Rare: Seizure
Drug Interactions: No information found
NOTE: Ethanol may interact with other medications. See
specific drug monographs for details on interactions with
ethanol.
Administration:
For IV administration, administer via a central vein as a
10% solution in D5W. Administer the initial dose over 1
hour.
For oral administration, dilute solutions to ≤20%
V
concentration with water or juice and administer every
hour. May also be administered via nasogastric tube.
Alcoholic beverages may be substituted, but may contain
different percentages of ethanol:
Vodka ~40%
Wine ~12%
Beer ~5%
Out-of-hospital management is not recommended.
NOTE: Absolute ethyl alcohol [98% (196 proof) = 77.4 g
ethanol/dL]
Pregnancy Category: C
ATC Code: V03AB16
608
VARIOUS
Rx ASCORBIC ACID
Inj.: 250 mg/mL, 2 mL ampule (IV)
A water-soluble vitamin that acts as a free radical, an
antioxidant scavenger, and plays a major role in
oxidation-reduction reactions; Ascorbic acid is a cofactor
for enzymes involved in the biosynthesis of collagen,
carnitine, and neurotransmitters.
Indications: Treatment of methemoglobinemia; urinary
acidification
Contraindications: Anemia, breastfeeding, diabetes
mellitus, G6PD deficiency, hemochromatosis,
nephrolithiasis, pregnancy, sideroblastic anemia,
sodium restriction, thalassemia
Dose:
Idiopathic methemoglobinemia, by mouth, ADULT, 300–
600 mg daily in divided doses.
Urinary acidification, by mouth, ADULT, 4–12 mg daily in 3-
4 divided doses; CHILD, 500 mg every 6–8 hours.
Administration: Avoid rapid IV injection as this may cause
temporary faintness or dizziness.
See Ascorbic Acid (Vitamin C) under Vitamins in Chapter 1:
Alimentary Tract and Metabolism for other information.
Pregnancy Category: C
ATC Code: A11GA01
Rx ATROPINE
Oral: 600 micrograms (as sulfate) (equivalent to 500 mcg
atropine) tablet
Inj.: 500 micrograms/mL, 600 micrograms/mL and 1
mg/mL (as sulfate), 1 mL ampule (IM, IV, SC)
A naturally occurring tertiary amine anti-muscarinic alkaloid
from Atropa belladonna that competitively blocks
acetylcholine action in central and peripheral muscarinic
autonomic receptors.
Indications: For organophosphate and carbamate
poisoning; for anticholinesterase and muscarinic
symptoms
Contraindications: Angle-closure glaucoma; severe
inflammatory GI disease or GI obstruction; prostatic
hypertrophy; prostatism and urinary obstruction;
myasthenia gravis; thyrotoxicosis; organochlorine
poisoning; pyloric stenosis; poisoning caused by CNS
adrenergic stimulants; phenothiazines; tricyclic
antidepressants and other anticholinergics
Dose:
NOTE: Dose required varies considerably with the severity of
poisoning. Total amount of atropine used for carbamate
poisoning is usually less than with organophosphate
insecticide or nerve agent poisoning.
VARIOUS
Severely poisoned patients may exhibit significant
tolerance to atropine requiring ≥2 times the suggested
dose. Titrate to pulmonary status (decreased bronchial
secretions).
Consider administration of atropine via continuous IV
infusion in patients requiring large doses of atropine.
Once patient is stable, decrease the dose or dosing
frequency.
Organophosphate or carbamate insecticide or nerve agent
poisoning, by IV or IM injection, ADULT, initially 1–6 mg,
repeat every 3–5 minutes as needed; CHILD, initially
0.05–0.1 mg/kg, repeat every 5–10 minutes as needed
[NOTE: Double the dose if previous dose did not induce
atropinization. Maintain atropinization by administering
repeat doses as needed for ≥2 to 12 hours based on
recurrence of symptoms.]
by IV infusion, ADULT and CHILD, following
atropinization, administer 10–20% of the total loading
dose required to induce atropinization every hour, adjust
as needed to maintain adequate atropinization.
Mild symptoms of poisoning, by IM injection, ADULT, 2 mg
as soon as exposure is known or strongly suspected;
CHILD, administer weight-based dose [see below] as
soon as exposure is known or strongly suspected [NOTE:
If severe symptoms develop after the first dose,
administer 2 additional doses in rapid succession 10
minutes after the first dose. Do NOT administer more
than 3 doses].
Severe symptoms of poisoning, by IM injection, ADULT,
immediately administer three 2–mg doses in rapid
succession; CHILD, immediately administer three weight-
based doses in rapid succession.
WEIGHT-BASED DOSING:
>41 kg (90 lbs) 2 mg per dose
18–41 kg (40–90 lbs) 1 mg per dose
6.8–18 kg (15–40 lbs) 0.5 mg per dose
<6.8 kg (15 lbs) 0.25 mg per dose
Administration:
For oral administration, may be taken with or without
food.
For IV administration, administer undiluted by rapid IV
injection.
See Atropine under Drugs for Functional Gastrointestinal
Disorders in Chapter 1: Alimentary Tract and Metabolism
for other information.
Pregnancy Category: C
ATC Code: A03BA01
Rx BROMOCRIPTINE
Oral: 2.5 mg (as mesilate) tablet
A semisynthetic ergot alkaloid derivative and a dopamine
receptor agonist, which activates postsynaptic dopamine
receptors in the tuberoinfundibular and nigrostriatal
pathways, inhibiting prolactin secretion and enhancing
coordinated motor control.
Indication: Treatment of neuroleptic malignant syndrome
Contraindications: Syncopal migraine; uncontrolled
hypertension; postpartum women with a history of
coronary artery disease or other severe cardiovascular
conditions
Dose:
Neuroleptic malignant syndrome, by mouth, ADULT, 2.5 mg
every 8–12 hours, increased if needed (maximum 45 mg
daily).
Dose Adjustment:
Hepatic Impairment:
May require dose adjustment. Undergoes extensive hepatic
metabolism. Use with caution.
Administration: Administer with food to decrease GI
distress.
Do NOT discontinue abruptly to prevent acute
exacerbation. Discontinue gradually over a period of 1
week.
See Bromocriptine under Anti-Parkinson Drugs –
Dopaminergic Agents in Chapter 10: Nervous System for
other information.
Pregnancy Category: B
V
ATC Code: N04BC01
CALCIUM FOLINATE
Rx
(LEUCOVORIN CALCIUM)
Inj.: 10 mg/mL, 5 mL ampule/vial (IM, IV)
50 mg vial (IM, IV infusion)
A reduced form of folic acid that supplies the necessary
cofactor blocked by methotrexate. It actively competes
with methotrexate for transport sites, displaces
methotrexate from intracellular binding sites, and
restores active folate stores required for DNA/RNA
synthesis. It aids in the elimination of formic acid by
serving as a source of tetrahydrofolate.
Indications: Rescue agent after high-dose methotrexate
treatment; to diminish toxicity and counteract the effects
of impaired methotrexate elimination and of inadvertent
overdosage of folic acid antagonists; adjunct cofactor
therapy in methanol toxicity; antidote for formaldehyde
and methyl alcohol poisoning
609
 VARIOUS

Contraindication: Pernicious anemia and other 100 to 1000

megaloblastic anemias secondary to vitamin B12 ≥10
mg/m2 every 3 to
deficiency micromolar
6 hours
At 72 ~1 to 10 10 to 100 mg/m2
Dose: hours micromolar every 3 hours
High-dose methotrexate rescue, by IM or IV injection, ADULT
~0.1 to 1 10 mg/m2 every
and CHILD, 15 mg (~10 mg/m2) 24 hours after beginning
micromolar 3 to 6 hours
methotrexate infusion, continue every 6 hours for 10
doses until methotrexate level is <0.05 micromolar.
Adjust dose as follows:
NOTE: If serum creatinine is increased more than 50%
Methotrexate Serum
Dose above baseline, increase the standard leucovorin
elimination methotrexate
adjustment dose to 100 mg/m2 every 3 hours, then adjust
type level
according to methotrexate levels above.
~10 15 mg every Follow methotrexate levels daily, leucovorin may be
micromolar at 6 hours for discontinued when methotrexate level is <0.1
24 hours; 1 60 hours (10 micromolar.
micromolar at doses)
Normal
48 hours; beginning 24 Methotrexate overdose, inadvertent (begin as soon as
<0.2 hours after possible after overdose), by IM or IV injection, ADULT, 10
micromolar at the start of mg/m2 every 6 hours until the methotrexate level is <
72 hours infusion 0.01 micromolar [NOTE: If serum creatinine is increased
>0.2 15 mg every more than 50% above baseline 24 hours after
micromolar at 6 hours until methotrexate administration, if 24 hour methotrexate
72 hours; methotrexate level is >5 micromolar, or if 48 hour methotrexate level
Delayed late
>0.05 level is is >0.9 micromolar, increase leucovorin dose to 100
micromolar at <0.05 mg/m2 (IV) every 3 hours until the methotrexate level is
96 hours micromolar <0.01 micromolar].
150 mg Cofactor therapy in methanol toxicity, by IV injection, ADULT
every 3 and CHILD, 1 mg/kg over 30–60 minutes every 4–6
Delayed ≥50
hours until hours (maximum dose 50 mg); continue until methanol
early micromolar at
methotrexate and formic acid have been completely eliminated.
24 hours; ≥5
level is <1
micromolar at
micromolar, Administration: Administer by IV or IM route as a rescue
48 hours;
then 15 mg after folate antagonists. Administer by IM injection, IV
doubling of
every 3 push, or by IV infusion for 15 minutes to 2 hours. Do NOT
serum
Acute renal hours until administer at a rate >160 mg/minute due to calcium
creatinine
injury methotrexate content.
level at 24
level is
hours
<0.05
V

Do NOT administer intrathecally.

micromolar
Do NOT administer IV solutions at a rate >160
High-dose methotrexate overexposure, by IM or IV injection, mg/minute due to calcium content.
ADULT,
Serum NOTE: Do NOT administer concurrently with methotrexate. It
Duration methotrexate Dose adjustment is commonly initiated 24 hours after the start of
level methotrexate. Toxicity to normal tissues may be
Initially 1000 irreversible if leucovorin is not initiated by ~40 hours
≥100
mg/m2 every 6 after the start of methotrexate.
micromolar
hours
Initially 100 Fluorouracil is usually given after, or at the midpoint, of
At 24 ≥10 to <100
mg/m2 every 3 or leucovorin infusion by IV bolus injection or short IV
hours micromolar
6 hours infusion over 10–120 minutes. Other administration
Initially 10 schedules have been used; refer to individual protocols.
~1 to 10
mg/m2 every 3 or
micromolar See Calcium Folinate (Leucovorin Calcium) under
6 hours
≥100 1000 mg/m2 Antineoplastic Agents – Adjuncts to Antineoplastic
micromolar every 6 hours Chemotherapy in Chapter 8: Antineoplastic and
Immunomodulating Agents for other information.
≥10 to <100 100 mg/m2 every
micromolar 3 hours
At 48 Pregnancy Category: C
hours 100 mg/m2 every
6 hours ATC Code: V03AF03
~1 to 10
micromolar 10 to 100
mg/m2 every 3
hours

610
VARIOUS
Rx CALCIUM SALT
Oral: powder (as chloride), USP grade
Inj.: 10% solution (as gluconate), 10 mL ampule (IV)
The most abundant cation and is essential for the
maintenance of the nervous, muscular, and skeletal
systems, as well as for cell membrane and capillary
permeability.
Indications: Antidote for poisoning with white or yellow
phosphorus "watusi," organochlorines, and severe
jellyfish bites; verapamil toxicity; calcium antagonist
toxicity
Contraindications: Breastfeeding; cardiac arrhythmias;
dehydration; diarrhea; digitalis toxicity; extravasation;
hypercalcemia; hypercalciuria; hyperphosphatemia;
hypoparathyroidism; necrotizing enterocolitis;
pregnancy; sarcoidosis; ventricular fibrillation; vitamin D
toxicity
Dose:
Verapamil toxicity or calcium antagonist toxicity, by
intravenous injection, ADULT, 500-800 mg (maximum
dose, 3 g); CHILD and INFANT, 100 mg/kg (maximum
dose, 3 g).
Calcium channel blocking agent overdose, by IV infusion,
CHILD, as 10% calcium chloride, 0.272 mEq/kg (0.2
mL/kg) over 5–10 minutes.
Administration:
Acetate, carbonate, citrate, gluconate, lactate, and
phosphate salts are administered orally. Administer 1–
1.5 hours after meals or with a demulcent (e.g., milk).
Except calcium carbonate powder, which should be
mixed with food for administration.
Calcium chloride or gluconate may be administered
intravenously . Calcium gluconate usually is administered
as a 10% solution and calcium chloride as a 2–10%
solution. Administer calcium salts slowly through a small
needle into a large vein to avoid too rapid increase in
serum calcium and extravasation of calcium solution into
the surrounding tissue with resultant necrosis. Following
IV injections, the patient should remain recumbent for a
short time.
Closely monitor serum calcium concentrations during IV
administration of calcium. Replace IV calcium therapy
with oral calcium supplements or calcium-rich foods as
soon as possible.
NOTE: In patients with end-stage renal disease, administer
with meals (e.g., 10–15 minutes before or during).
See individual monographs under Mineral Supplements
– Calcium in Chapter 1: Alimentary Tract and
Metabolism for other information.
Pregnancy Category: C
ATC Code: Not available
Rx COBRA ANTIVENIN
Inj.: 800 IU/mL, 5 mL ampule (IV infusion)
800 MU/4.8 mL, 1 mL ampule (IV infusion)
The purified and concentrated serum of horses
hyperimmunized with the venom of the Philippine cobra
[TAG: Ulupong] (Naja-Naja philippinensis) and preserved
with 1:10,000 merthiolate.
Indications: Antidote for cobra bites
Dose: See Administration for dosing details
Dose Adjustment: No information found
Precautions:
WARNING: Usual preparation necessary for treatment
of anaphylactic reaction must be immediately
available prior to administration.
Adverse Drug Reactions:
Common and Less Common:
[Early (within a few hours)]: Urticaria, itching, dry cough,
fever, nausea, vomiting, abdominal colic, diarrhea,
tachycardia, chills, vasodilation
[Late (5 days or more)]: Nausea, vomiting, diarrhea,
itching, urticarial rash, pain in joints and muscles,
recurrent urticaria, fever, enlargement of lymph glands,
proteinuria
Rare:
[Late (5 days or more)]: Encephalitis
Drug Interactions: No information found
Administration: SC or IM administration is preferred.
Administer by IV only when symptoms of poisoning are
V
evident.
Most effective when injected immediately after the bite.
When possible, test for sensitivity to horse serum prior to
administration.
Kill and keep the snake responsible for the bite,
whenever possible, to identify the specific venom.
Apply a tourniquet immediately above the bite. It should
be tight enough to impede venous and lymph flow to and
from the bitten part but allows a finger to be inserted
under it. Loosen tourniquet every 15 minutes for 15–30
seconds to allow blood flow.
If done immediately or shortly after the bite, make short
deep incisions (¼ to ½ inch long and ½ inch deep) over
the site of the bite through the fang marks under aseptic
conditions. Avoid principal blood vessels.
Suction the blood with the mouth or with a mechanical
device to draw out the poison. If done using the mouth,
make sure there are no open lesions on the mucous
membrane. Rinse mouth with a mild solution of
potassium permanganate or water.
611

Inject part of the antivenin into the site of the bite and
around it if done soon after. Inject most of the antivenin
above the tourniquet, then slowly release the tourniquet.
Administer saline, plasma, or blood to combat shock.
Antibiotics and antitoxins may be needed for infections
commonly associated with snakebites. Antihistamines
may be necessary to control manifestations of allergy.
Patient should remain lying down. Do NOT allow to
patient to walk or run around, become overheated, or
take alcohol stimulants as thes hasten blood flow.
Black coffee or strong tea may be given to combat
weakness or giddiness.
Do NOT cauterize the wound with strong acid, potassium
permanganate or heat.
Pregnancy Category: Not classified
ATC Code: Not available
Rx DANTROLENE
Oral: 25 mg and 50 mg (as sodium salt) capsule
Inj.: 20 mg (as sodium salt) with 3 g mannitol per vial (for
reconstitution with 60 mL sterile water for injection)
(IV)
A skeletal muscle relaxant that acts directly on skeletal
muscle by interfering with release of calcium ion from the
sarcoplasmic reticulum. This prevents or reduces the
increase in myoplasmic calcium ion concentration that
activates the acute catabolic processes associated with
malignant hyperthermia.
V
Indications: Management of malignant hyperthermia (MH);
prevention of MH in susceptible individuals (preoperative
or postoperative administration); for neuroleptic
malignant syndrome
NOTE: Dantrolene prophylaxis is NOT recommended for
most MH-susceptible patients, provided non-triggering
anesthetics are used and an adequate supply of
dantrolene is available.
Contraindications: Active liver disease; should not be used
when spasticity is used to maintain posture/balance
during locomotion or to obtain or maintain increased
function
Dose:
NOTE: Dose should be titrated and individualized for
maximum effect. Use the lowest dose compatible with
optimal response. Some patients may not respond until
a higher daily dosage is achieved. Each dose level should
be maintained for 7 days to determine patient response.
If no further benefit observed with the higher dose level,
then decrease dosage to previous dose level.
Malignant hyperthermia, preoperative prophylaxis, by
mouth, ADULT, 4–8 mg/kg per day in 3–4 divided doses,
begin 1–2 days prior to surgery with last dose 3–4 hours
612
VARIOUS
prior to surgery; by IV injection, ADULT, 2.5 mg/kg ~1¼
hours prior to anesthesia and infused over at least 1
minute (Ryanodex) or 1 hour (Dantrium, Revonto) with
additional doses as needed and individualized.
Malignant hyperthermia, crisis, by IV injection, ADULT, 2.5
mg/kg; continuously repeat dose until symptoms
subside or a cumulative dose of 10 mg/kg is reached;
rarely, some patients may require up to 30 mg/kg for
initial treatment.
NOTE: Manufacturer's labeling suggests an initial minimum
dose of 1 mg/kg.
Malignant hyperthermia, post-crisis follow up, by continuous
IV infusion, ADULT, 0.25 mg/kg per hour for at least 24
hours; by mouth, ADULT, 4 to 8 mg/kg per day in 4
divided doses for 1–3 days
NOTE: IV dantrolene may be used to prevent or attenuate
recurrence of MH signs when oral therapy is not
practical.
Administration: For IV preparation, reconstitute with 60 mL
sterile water for injection.
Therapeutic or emergency dose can be administered by
rapid continuous IV push. Follow-up doses should be
administered over at least 1 minute (Ryanodex) or 1 hour
(Dantrium, Revonto).
EXTRAVASATION MANAGEMENT: Ensure proper needle or
catheter placement prior to and during infusion to avoid
extravasation. If extravasation occurs, stop infusion
immediately and disconnect (leave cannula or needle in
place), then gently aspirate extravasated solution (do
NOT flush the line). Remove needle or cannula and
elevate extremity.
See Dantrolene under Muscle Relaxants – Directly Acting
Agents in Chapter 9: Musculo-Skeletal System for other
information.
Pregnancy Category: C
ATC Code: M03CA01
Rx DIMERCAPROL
Inj.: 50 mg/mL in oil, 2 mL ampule (IM)
A specific antidote with a sulfhydryl group that combines
with ions of various heavy metals to form relatively
stable, nontoxic, soluble chelates excreted in the urine.
Indications: Antidote to gold, arsenic, or acute mercury
poisoning (excluding arsine and non-alkyl mercury) ;
adjunct to edetate calcium disodium in acute lead
poisoning
NOTE: NOT indicated for the treatment of iron, cadmium, or
selenium poisoning. May result in toxic dimercaprol-
metal complexes.
Contraindication: Hepatic insufficiency (unless due to
arsenic poisoning)
VARIOUS
Dose:
Arsenic or gold poisoning (acute, mild), by deep IM injection,
ADULT and CHILD, 2.5 mg/kg every 6 hours for 2 days,
then every 12 hours for 1 day, followed by once daily for
10 days.
Arsenic or gold poisoning (acute, severe), by deep IM
injection, ADULT and CHILD, 3 mg/kg every 4 hours for 2
days, then every 6 hours for 1 day, followed every 12
hours for 10 days.
Mercury poisoning (acute), by deep IM injection, ADULT and
CHILD, initially 5 mg/kg, followed by 2.5 mg/kg 1–2
times daily for 10 days.
Lead poisoning (blood lead levels ≥70 micrograms/dL,
symptomatic lead poisoning, or lead encephalopathy, in
conjunction with edetate calcium disodium), by deep IM
injection, ADULT and CHILD, 4 mg/kg every 4 hours for
2–7 days for at least 3 days. [NOTE: Begin treatment with
edetate calcium disodium with the second dimercaprol
dose. Administer drugs at separate sites.]
Precautions:
Nephrotoxicity (discontinue if acute renal insufficiency
develops during therapy; dimercaprol-metal chelate is
removed by hemodialysis);
Glucose 6­phosphate dehydrogenase deficiency;
Children;
Lactation.
Adverse Drug Reactions:
Common: Chest pain, hypertension (dose related),
tachycardia (dose related), anxiety, fever (children),
headache, nervousness, abscess, abdominal pain,
burning sensation (lips, mouth, throat), nausea,
salivation, throat irritation or pain, vomiting, burning
sensation (penis), leukopenia (polymorphonuclear),
injection site pain, paresthesia (hand), weakness,
blepharospasm, conjunctivitis, lacrimation, acute renal
insufficiency, rhinorrhea, throat constriction, diaphoresis
Drug Interactions:
Avoid concomitant use with:
Increases risk of adverse or toxic effects of the following
drugs:
Iron Salts (nephrotoxic effect)
Multivitamins / Minerals with Vitamins ADEK, Folate, Iron
(nephrotoxic effect)
TEST INTERACTION. May decrease iodine I131 thyroidal
uptake values.
Administration: Administer by deep IM injection. Rotate
injection sites. NOT for IV administration
Keep urine alkaline to protect renal function.
NOTE: Premedication with a histamine H1 antagonist (e.g.,
diphenhydramine) is recommended.
Pregnancy Category: C
ATC Code: V03AB09
DIMERCAPTOPROPANE SULFONATE
Rx
(DMPS)
Inj.: 100 mg/mL, 1 mL ampule and 10 mL vial (IM)
A sulfonic acid salt with free SH-groups that form complexes
with heavy metals, such as mercury, cadmium, arsenic,
lead, copper, silver, tin, etc.
Indication: Antidote to arsenic and methyl mercury
poisoning
Contraindications: Pregnancy; lactation
Dose:
Heavy metal poisoning, by slow IV injection, ADULT, 3 mg/kg
over 5 minutes.
Dose Adjustment: No information found
Precautions:
WARNING: Do NOT use in patients with silver
amalgam fillings as this may lead to acute toxicity
from heavy metal injury to the mucosa of the gut.
Patients will feel better within 3–4 weeks following
administration, then worsen due to manifestations of
heavy metals still present in the system.
Adverse Drug Reactions:
NOTE: May exhibit adverse effects associated with toxicity
of a specific heavy metal several days after
administration.
Common: Pain, burning, GI problems, injection site
reactions, feeling of emptiness in the head, difficulty
concentrating
Less Common: Temporary lowering of blood pressure,
V
allergic reactions, skin rash
Drug Interactions: No information found
Administration: Draw up drug into a 5 mL syringe and slowly
injected into the patient with a 25-gauge butterfly over 5
minutes (1 mL per minute).
Administer additional doses if any of the toxic metals are
elevated above normal or mercury excretion is more than
1 microgram in 24 hours. Six to eight treatments may be
needed to get the heavy metal burden down to normal.
Collect all urine for 24 hours and test for special mercury
and elements. Add nitric acid into the container as soon
as the first urine is collected. Do NOT administer mineral
supplements 24 hours before and 48 hours after the
test.
Pregnancy Category: Not classified
ATC Code: Not available
613

Rx DIPHENHYDRAMINE
Inj.: 50 mg/mL (as hydrochloride), 1 mL ampule (IM, IV)
A monoethanolamine-derived, first-generation H1-receptor
antagonist that exhibits antimuscarinic and pronounced
sedative property, with low incidence of GI side effects.
Indication: For phenothiazine extrapyramidal side effects
Contraindications: Acute asthma; neonates or premature
infants; breastfeeding; use of the parenteral form as a
local anesthetic
Dose:
NOTE: Dose should be individualized according to the needs
and response of the patient.
Drug-induced extrapyramidal effects, by IV infusion, ADULT,
10–50 mg at a rate not exceeding 25 mg/min (maximum
daily dose, 400 mg); CHILD, 5 mg/kg every 24 hours or
150 mg/m2 every 24 hours in 4 divided doses at a rate
not exceeding 25 mg/min (maximum daily dose, 300
mg);
by deep IM injection, ADULT, 100 mg (maximum daily
dose, 400 mg); CHILD, 5 mg/kg every 24 hours or 150
mg/m2 every 24 hours in 4 divided doses at a rate not
exceeding 25 mg/min (maximum daily dose, 300 mg).
Administration:
For IV administration, do NOT exceed a rate of 25
mg/minute.
IM administration must be deep. Local necrosis may
result with SC or ID use.
Inspect visually for particulate matter and discoloration
prior to administration.
V
See Diphenhydramine under Anti-Parkinson Drugs in
Chapter 10: Nervous System for other information.
Pregnancy Category: B
ATC Code: Not available
Rx GLUCAGON
Inj.: 1 mg lyophilized powder (as hydrochloride) + solvent
(IM, IV, SC)
A polypeptide that is produced by α cells of islets of
Langerhans in the pancreas. It promotes hepatic
glycogenolysis and gluconeogenesis, thus causing an
increase in blood glucose levels. Glucagon is synthesized
in a special non-pathogenic laboratory strain of
genetically altered Escherichia coli bacteria
Indications: Beta blocker-induced or calcium channel
blocker-induced myocardial depression (with or without
hypotension) unresponsive to standard measures
Contraindications: Pheochromocytoma
614
VARIOUS
Dose:
Beta blocker or calcium channel blocker toxicity, by IV
injection, ADULT, 3–10 mg (0.05–0.15 mg/kg) bolus,
followed by an infusion of 3–5 mg/hour (0.05–0.1
mg/kg per hour); titrate infusion rate to achieve
adequate clinical response.
Administration: Administer parenterally because glucagon is
destroyed in the GI tract.
Reconstitute as per manufacturer’s instructions. Use
reconstituted glucagon immediately. Discard any unused
portion.
Do NOT use at concentrations greater than 1 mg/mL (1
unit/mL).
NOTE: Patients with Type 1 diabetes may have less of an
increase in blood glucose levels compared with a stable
Type 2 patient. Administer supplementary carbohydrate
as soon as possible, especially to pediatric patients.
See Glucagon under Other Alimentary Tract and
Metabolism Products – Anti-Hypoglycemics in Chapter 1:
Alimentary Tract and Metabolism for other information.
Pregnancy Category: B
ATC Code: Not available
Rx FLUMAZENIL
Inj.: 100 micrograms/mL, 5 mL ampule (slow IV, IV
infusion)
Competitive inhibitor of the benzodiazepine receptor on the
GABA / benzodiazepine receptor complex. It does not
antagonize the CNS effect of drugs affecting GABA–ergic
neurons by means other than the benzodiazepine
receptor (ethanol, barbiturates, general anesthetics) and
does not reverse the effects of opioids.
Indication: For benzodiazepine, zolpidem, and zopiclone
poisoning
Contraindications: Patients given benzodiazepines for
control of potentially life-threatening conditions, e.g.,
control of intracranial pressure or status epilepticus;
patients who are showing signs of serious cyclic-
antidepressant overdose
Dose:
NOTE: Individualize doses and be prepared to manage
seizures.
Suspected benzodiazepine overdose, non-benzodiazepine
hypnotic overdose, by IV injection, ADULT, initially 0.2 mg
over 30 seconds; if the desired level of consciousness is
not obtained 30 seconds after the dose, administer 0.3
mg over 30 seconds; repeat doses, of 0.5 mg over 30
seconds may be repeated at 1–minute intervals
(maximum total cumulative dose, 3 mg; usual total dose,
1–3 mg);
VARIOUS

CHILD, initially 0.01 mg/kg (maximum dose, 0.2 mg) with Administration: Administer in freely-running IV into a large
repeated doses of 0.01 mg/kg (maximum dose, 0.2 mg) vein over 30 seconds.
every minute to maximum cumulative dose of 1 mg; or
by continuous infusion, 0.005–0.01 mg/kg per hour; Pregnancy Category: C
RE-SEDATION, repeat doses at 20-minute intervals
(maximum, 1 mg per dose) at 0.05 mg/minute and 3 ATC Code: V03AB25
mg/hour.

NOTE: If a patient has not responded 5 minutes after FOMEPIZOLE

cumulative dose of 5 mg, the major cause of sedation is
not likely due to benzodiazepines.
For re-sedation, repeat doses of 0.5 mg/minute may be
given at 20–minute intervals to a maximum of 1 mg total
dose and 3 mg in 1 hour.
Dose Adjustment:
Hepatic Impairment:
Reduce dose or frequency for repeat doses.
Precautions:
WARNING: Benzodiazepine reversal may result in
seizures. May occur more frequently in patients on
long-term benzodiazepine or following tricyclic
antidepressant overdose.
Rx
(4-METHYLPRAZOLE)
Inj.: 1 mg/mL, 1.5 mL vial (IV)
A competitive inhibitor of alcohol dehydrogenase. It
prevents the metabolism of ethylene glycol and
methanol to their toxic metabolites.
Indication: Antidote for methanol and ethylene glycol
poisoning
Dose:
Methanol or ethylene glycol poisoning, by slow IV infusion,
ADULT, 15 mg/kg loading dose, followed by 4 doses of
10 mg/kg every 12 hours, then 15 mg/kg every 12
hours.

Amnesia; Dose Adjustment:

CNS effects; Renal Impairment:
Re-sedation; In patients undergoing hemodialysis:
Seizures; If at the beginning of hemodialysis and ≥6 hours since
Respiratory depression; last fomepizole dose, administer next scheduled dose.
Head injury; During hemodialysis, administer dose every 4 hours.
Hepatic impairment; At completion of hemodialysis, administer next
Panic disorder; scheduled dose after 3 hours. If between 1–3 hours
Elderly; since end of hemodialysis, administer ½ of the next
Lactation. scheduled dose. If <1 hour since end of hemodialysis, do
NOT administer dose.
SKILLED TASKS. May impair ability to perform tasks which
Off hemodialysis, administer next scheduled dose 12

V
require mental alertness, such as operating machinery
or driving. hours from last dose as maintenance.

Precautions:
Adverse Drug Reactions: Local site irritation;
Common: Palpitation, flushing, vasodilation, ataxia, Allergic reactions;
dizziness, vertigo, agitation, anxiety, insomnia, Elderly and children;
nervousness, abnormal crying, depersonalization, Lactation.
depression, dysphoria, emotional lability, euphoria,
fatigue, headache, malaise, paranoia, hot flashes, Adverse Drug Reactions:
vomiting, xerostomia, nausea, pain at injection site, Common: Headache, nausea, dizziness, increased
injection site reaction, rash, skin abnormality, drowsiness, bad or metallic taste
thrombophlebitis, hypoesthesia, paresthesia, weakness, Less Common: Abdominal pain, fever, multi-organ system
tremor, blurred vision, abnormal vision, lacrimation, failure, pain or inflammation at injection site, lumbalgia
dyspnea, hyperventilation, diaphoresis or backache, hangover, bradycardia, phlebosclerosis,
Less Common: Abnormal hearing, altered blood pressure, tachycardia, phlebitis, shock, hypotension, vomiting,
arrhythmia, bradycardia, chest pain, confusion, coldness diarrhea, dyspepsia, heartburn, decreased appetite,
sensation, delirium, difficulty concentrating, dysphonia, transient transaminitis, hypereosinophilia or
generalized seizure, hiccups, hyperacusis, hypertension, eosinophilia, lymphangitis, disseminated intravascular
junctional tachycardia, rigors, seizure, shivering, coagulation, anemia, lightheadedness, seizure,
somnolence, stupor, tachycardia, thick tongue, tinnitus, agitation, feeling drunk, facial flush, vertigo, nystagmus,
transient hearing impairment anxiety, feeling of strangeness, decreased
environmental awareness, hiccups, pharyngitis,
Drug Interactions: application site reaction, rash, abnormal smell, speech
Monitor closely with: or visual disturbances, transient blurred vision, roar in
Reduces sedative effect of the following drugs: ear
Hypnotics, Non-Benzodiazepine [except Ramelteon,
Suvorexant,]

615

Drug Interactions:
Monitor closely with:
Decreases rate of elimination of Ethanol
Administration: Administer each dose as a slow IV infusion
over 30 minutes. Do NOT administer undiluted or by
bolus injection.
Using sterile technique, draw the appropriate dose from
the vial with a syringe and inject into at least 100 mL of
sterile 0.9% sodium chloride injection or dextrose 5%
injection. Mix well. Infuse the resulting solution over 30
minutes.
Visually inspect parenteral products for particulate
matter and discoloration prior to administration. Do NOT
use solutions showing haziness, particulate matter,
precipitate, discoloration, or leakage.
NOTE: Begin fomepizole treatment immediately upon
suspicion of ethylene glycol or methanol ingestion, or a
documented serum ethylene glycol or methanol
concentration greater than 20 mg/dL.
Discontinue treatment when ethylene glycol or methanol
concentrations are undetectable or have been reduced
below 20 mg/dL, and the patient is asymptomatic with
normal pH.
Consider hemodialysis to remove ethylene glycol or
methanol and the respective toxic metabolites of these
alcohols in patients with high ethylene glycol or methanol
concentrations (≥50 mg/dL), significant metabolic
acidosis, or renal failure. Dialyze to correct metabolic
abnormalities and to lower the ethylene glycol
concentrations below 50 mg/dL.
Fomepizole solidifies at temperatures <25°C (77°F). If
this occurs, liquefy the solution by running the vial under
V
warm water or by holding in the hand. Solidification does
not affect the efficacy, safety, or stability of fomepizole.
Fomepizole diluted as stated above remains stable and
sterile for at least 24 hours when stored in a refrigerator
or at room temperature. Do NOT use beyond 24 hours.
Fomepizole does NOT contain preservatives.
Pregnancy Category: C
ATC Code: V03AB34
Rx METHYLENE BLUE
Oral: 1% solution
Inj.: 10 mg/mL, 1 mL and 10 mL ampule / vial
A thiazine dye that hastens the conversion of
methemoglobin to hemoglobin.
Indication: Treatment of drug-induced methemoglobinemia
Contraindications: Pregnancy or intention to become
pregnant
616
VARIOUS
Dose:
Methemoglobinemia, by IV injection, ADULT and CHILD, 1–
2 mg/kg or 25–50 mg/m2 over 5–10 minutes, may be
repeated in 1 hour if necessary.
Precautions:
WARNING: Vesicant. Ensure proper needle or
catheter placement prior to and during infusion to
avoid extravasation.
Methemoglobinemia; renal impairment; G6PD deficiency
(use with caution); Pregnancy (hemolytic anemia,
methemoglobinemia, and phototoxicity in neonates
following in utero exposure).
Adverse Drug Reactions:
Common: Angina, arrhythmia, hypertension, precordial
pain, dizziness, headache, fever, mental confusion,
staining of skin, abdominal pain, diarrhea, discoloration
of urine and feces (blue-green), nausea, vomiting,
bladder irritation, anemia, paradoxical
methemoglobinemia (high doses), transient reduction in
oxygen saturation, dyspnea, diaphoresis
Less Common: Serotonin syndrome
Drug Interactions:
Monitor closely with:
Enhances therapeutic effect of the following drugs:
Abobotulinumtoxin-A, Onabotulinumtoxin-A,
Rimabotulinumtoxin-B, Clemastine, Doxylamine
(anticholinergic effect), Antihypertensives (hypotensive
effect), Blood Glucose Lowering Agents e.g., Insulin
(hypoglycemic effect), Doxapram, Epinephrine,
Norepinephrine (hypertensive effect)
Increases risk of adverse or toxic effects of Methylene Blue:
Antiemetics / 5HT3 Antagonists (serotonin syndrome),
Antipsychotic Agents (neuroleptic malignant syndrome),
Buprenorphine
Increases risk of adverse or toxic effects of the following
drugs:
Analgesics, Opioid e.g Morphine (constipation, urinary
retention), Anticholinergic Agents [except, Nasal],
Antihypertensives (orthostatic hypotension),
Antipsychotic Agents e.g., Risperidone (dopamine
blockade), Beta2 Agonists, e.g. Salbutamol Brimonidine,
Ophthalmic, Domperidone, Metoclopramide (serotonin
syndrome; neuroleptic malignant syndrome), Orthostatic
Hypotension Producing Agents, Ramosetron
(constipation), Topiramate
Reduces therapeutic effect of Methylene Blue:
Domperidone
Reduces therapeutic effect of the following drugs:
Acetylcholinesterase Inhibitors e.g., Neostigmine,
Domperidone, Gastrointestinal Agents, Prokinetic e.g.
Metoclopramide, Itopride
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:
Cimetropium, Cyproheptadine, Aclidinium, Ipratropium,
Pizotifen, Pramlintide (anticholinergic GI effects),
Tiotropium, Umeclidinium, Alpha / Beta Agonists,
Indirect-Acting, Alpha1 Agonists, Amphetamines,
VARIOUS
Atropine (Ophthalmic), Bupropion, Diethylpropion,
Mequitazine, Methylphenidate, Tetrahydrozoline, (Nasal)
(hypertensive effect)
Increases risk of adverse or toxic effects (e.g. serotonin
syndrome, hypertensive effect) Methylene Blue:
Anilidopiperidine Opioids e.g. Fentanyl [avoid
concomitant use within 14 days of either drug],
Buspirone, Carbamazepine [avoid concomitant use
within 14 days of either drug], COMT Inhibitors, Ethyl
Alcohol, Levodopa, MAO Inhibitors e.g. Mirtazapine,
Oxymorphone, Selective Serotonin Reuptake Inhibitors
e.g. Fluoxetine, Serotonin / Norepinephrine Reuptake
Inhibitors e.g. Venlafaxine, Tapentadol, Tramadol
(neuroexcitatory and/or seizure-potentiating effect),
Tricyclic Antidepressants, Tryptophan
Increases risk of adverse or toxic effects of the following
drugs:
Atomoxetine (neurotoxic / central effect), Dapoxetine,
Dextromethorphan (serotonin syndrome),
(constipation), Glucagon (GI adverse effects), , Linezolid,
Lithium, Meperidine (serotonin syndrome), Methadone,
Methyldopa, (neurotoxic effect), Moclobemide,
Morphine, Oxycodone [avoid concomitant use within 14
days of either drug], Potassium Chloride (ulcerogenic
effect), Reserpine (paradoxical effects of reserpine, e.g.,
excitation, hypertension), Serotonin Modulators [except
Tedizolid] (serotonin syndrome)
Increases serum concentration of Serotonin 5-HT1D
Receptor Agonists e.g Sumatriptan
Reduces serotonergic effect of Methylene Blue:
Cyproheptadine
Reduces therapeutic effect of the following drugs:
Levosulpiride, Secretin
Administration: Administer undiluted by direct IV injection
over 5–10 minutes. If administered by continuous IV
infusion, administer via central line to minimize the risk
of extravasation injury.
Do NOT administer by intraspinal or subcutaneous
injection.
Consider concomitant dextrose administration,
especially in patients who are hypoglycemic, to ensure
efficacy of methylene blue.
EXTRAVASATION MANAGEMENT. If extravasation occurs,
immediately stop infusion and disconnect, leaving the
cannula or needle in place. Gently aspirate extravasated
solution. Do NOT flush the line. Remove the cannula or
needle. Elevate extremity. Dry warm compresses may be
applied proximal to the injection site.
Pregnancy Category: X
ATC Code: Not available
Rx N-ACETYL PENICILLAMINE
Oral: crystals, 25 g/bottle
A chelating agent that chelates with lead, copper, mercury
and other heavy metals to form stable, soluble
complexes that are excreted in urine.
Indications: For copper, lead, and mercury poisoning
Contraindications: Patients with previous penicillamine-
related aplastic anemia or agranulocytosis;
breastfeeding
Dose:
NOTE: Consider dose reduction to 250 mg daily prior to
surgical procedures. May resume normal recommended
dosing post-operatively once healing is complete.
Lead poisoning, by mouth, ADULT, 900–1,500 mg daily in 3
divided doses for 1–2 weeks, then 750 mg daily in
divided doses until blood lead concentration is <60
micrograms/dL or urinary lead excretion is <500
micrograms/L for 2 consecutive months; CHILD, 30–40
mg/kg daily or 600–750 mg/m2 daily in 1–2 divided
doses (maximum dose, 750 mg daily). Treat until blood
lead concentration is <40 micrograms/dL for 2
consecutive months AND decrease in erythrocyte
protoporphyrin level to <3–5 times the average normal
level OR the excretion of coproporphyrin or delta–
aminolevulinic acid decrease to the upper limit of
normal.
Wilson’s disease, by mouth, ADULT, 750–1,500 mg daily in
divided doses (maximum dose, 2,000 mg daily); CHILD,
20 mg/kg daily in 2–3 divided doses, round off to the
nearest 250 mg dose [NOTE: Dose that results in an
initial 24–hour urinary copper excretion of >2 mg daily
should be continued for approximately 3 months.
V
Establish maintenance dose where serum copper levels
are controlled at <10 micrograms/dL].
Dose Adjustment:
Geriatric:
Initiate at low end of dosing range and “go slow” with dose
increase intervals. Do NOT exceed 750 mg daily.
Renal Impairment:
Avoid use in patients with CrCl<50 mL/minute.
In patients undergoing hemodialysis, administer 33% of
usual dose. Drug is dialyzable.
Pregnancy:
Limit daily dose to 750 mg daily.
If planned caesarian, limit dose to 250 mg daily during last
6 weeks of pregnancy and postoperatively until wound
healing is complete.
Precautions:
WARNING: Must be administered by physicians
familiar with its toxicity, special dosage
considerations, and therapeutic benefits. Closely
supervise patient during therapy.
617
 VARIOUS

Patients should be warned to report promptly any Antacids, Iron Salts, Oral [except Ferric Carboxymaltose,
symptoms suggesting toxicity (fever, sore throat, Ferric Gluconate, Ferric Pyrophosphate Citrate,
chills, bruising, or bleeding). Ferumoxytol, Iron Dextran Complex, Iron Sucrose]
(decreased absorption)
Allergic reactions;
Increases serum concentration of Penicillamine:
Dermatologic effects;
Multivitamins / Minerals with Vit ADEK, Folate, Iron [if
Bronchiolitis obliterans;
concomitant use cannot be avoided, separate doses by
Drug fever;
2 or more hours]
Goodpasture's syndrome;
Pemphigus;
Administration: Administer on an empty stomach, 1 hour
Myasthenia gravis;
before or 2 hours after meals, and at least 1 hour apart
Gastrointestinal effects (eg. taste alteration, oral
from other drugs, milk, antacids, and zinc or iron-
ulceration);
containing products. Penicillamine serum levels may be
Lupus erythematosus-like syndrome;
decreased if taken with food. Certain disease states
Hematologic toxicities (fatalities due to agranulocytosis,
require further diet adjustment.
aplastic anemia, and thrombocytopenia);
Hepatotoxicity (eg. intrahepatic cholestasis, toxic hepatitis);
Administer doses ≤500 mg as a single dose.
Proteinuria or hematuria;
Administer doses >500 mg in divided doses.
Renal impairment;
Cystinuria;
For patients who cannot swallow, contents of capsules
Elderly;
may be administered in 15–30 mL of chilled puréed fruit
Children (use only if asymptomatic with blood lead
or fruit juice.
concentrations of 50–80 micrograms/dL, erythrocyte
protoporphyrin level >400–500 micrograms/dL
Pyridoxine supplementation is recommended.
erythrocytes, excessive excretion of delta–aminolevulinic
acid and/or coproporphyrin);
NOTE: Patients with Wilson's disease should receive 25–50
Pregnancy (birth defects, including congenital cutix laxa and
mg daily of pyridoxine. A multivitamin (without copper)
associated defects, have been reported; discontinuation
may also be considered. Decrease copper in diet to <1–
has detrimental maternal and fetal effects);
2 mg daily and omit chocolate, nuts, shellfish,
Lactation.
mushrooms, liver, raisins, broccoli, copper-enriched
cereal, multivitamins with copper, and molasses. May
Adverse Drug Reactions:
consider short courses of iron supplementation if dietary
Common: Vasculitis, anxiety, agitation, fever, Guillain-Barré
modifications result in iron deficiency.
syndrome, hyperpyrexia, psychiatric disturbances,
worsening neurologic symptoms, alopecia, cheilosis,
For lead poisoning, decrease calcium in diet.
dermatomyositis, drug eruptions, exfoliative dermatitis,
lichen planus, pemphigus, pruritus, rash, increased skin
Pediatric patients and menstruating women may be
friability, toxic epidermal necrolysis, urticaria, excessive
particularly susceptible to iron deficiency. Allow 2 hours
wrinkling, yellow nail syndrome, hypoglycemia,
V

between administration of iron supplementation and

thyroiditis, diarrhea, taste alteration, anorexia, epigastric
penicillamine as iron may decrease drug absorption.
pain, gingivostomatitis, glossitis, nausea, oral
ulcerations, pancreatitis, peptic ulcer reactivation,
Pregnancy Category: D
vomiting, thrombocytopenia, leukopenia,
agranulocytosis, aplastic anemia, eosinophilia,
ATC Code: Not available
hemolytic anemia, leukocytosis, monocytosis, red cell
aplasia, sideroblastic anemia, thrombotic
thrombocytopenia purpura, thrombocytosis, increased
alkaline phosphatase, hepatic failure, intrahepatic Rx NALOXONE
cholestasis, toxic hepatitis, thrombophlebitis, white
papules at venipuncture and surgical sites, arthralgia,
dystonia, myasthenia gravis, muscle weakness, Inj.: 400 micrograms/mL (as hydrochloride), 1 mL ampule
neuropathies, polyarthralgia (migratory, often with (IM, IV, SC)
objective synovitis), polymyositis, diplopia, extraocular
muscle weakness, optic neuritis, ptosis, visual A pure opioid antagonist that competes and displaces
disturbances, tinnitus, proteinuria, Goodpasture's opioids at opioid receptor sites.
syndrome, hematuria, nephrotic syndrome, renal failure,
renal vasculitis, asthma, interstitial pneumonitis, Indication: For the complete or partial reversal of opioid
pulmonary fibrosis, obliterative bronchiolitis, allergic depression (including respiratory depression) induced by
alveolitis, anetoderma, elastosis perforans serpiginosa, natural and synthetic opioids (e.g., propoxyphene,
lupus-like syndrome, l, lymphadenopathy, mammary methadone, nalbuphine, butorphanol, pentazocine)
hyperplasia, positive ANA test
Dose:
Drug Interactions: Opioid overdose (with standard ACLS protocols), by IV, IM,
Avoid concomitant use with: or SQ injection, ADULT, initially 0.4–2 mg, may need to
Decreases serum concentration of Penicillamine: repeat doses every 2–3 minutes; ADOLESCENT, INFANT,
and CHILD ≥5 years or >20 kg, 2 mg; if no response,

618
VARIOUS

repeat every 2 to 3 minutes; ADOLESCENT, CHILD <5 Administration:

years or ≤20 kg, and INFANT, 0.1 mg/kg per dose
(maximum dose, 2 mg), repeat every 2–3 minutes if
needed. [NOTE: After reversal, re-administration of
dose(s) may be needed at a later interval (i.e., 20–60
minutes) depending on type or duration of opioid. If no
response is observed after 10 mg total, consider other
causes of respiratory depression].
Reversal of respiratory depression with therapeutic opioid
doses, by IV, IM, or SQ injection, ADULT, initially 0.04–
0.4 mg, may repeat until desired response achieved;
ADOLESCENT, CHILD, and INFANT, 0.001–0.015 mg/kg
per dose; may be repeated as needed. [NOTE: If desired
response is not observed after 0.8 mg total, consider
other causes of respiratory depression].
Reversal of respiratory depression in opioid-dependent
patients being treated for cancer pain, by slow IV push,
ADULT, 40–80 micrograms every 30 to 60 seconds until
improvement in symptoms. [NOTE: If no response is
observed after total naloxone dose 1 mg, consider other
causes of respiratory depression.]
Postoperative reversal, by IV injection, ADULT, 0.1–0.2 mg
every 2–3 minutes until desired response (adequate
ventilation and alertness without significant pain); repeat
doses may be needed within 1– to 2-hour intervals
depending on type, dose, and timing of the last dose of
opioid administered; ADOLESCENT, CHILD, and INFANT,
0.005–0.01 mg/kg, may repeat every 2–3 minutes as
needed based on response (adequate ventilation
without significant pain).
Precautions:
Acute opioid withdrawal (e.g. precipitate acute withdrawal,
unmask pain);
Cardiovascular disease (e.g. pulmonary edema,
cardiovascular instability, including ventricular
fibrillation);
Seizures (use with caution);
Pregnancy (use with caution in mild-to-moderate
hypertension during labor; severe hypertension may
IV administration is the preferred route. Administer via IV
push over 30 seconds as undiluted preparation or via
slow IV push as diluted preparation by diluting 0.4 mg (1
mL) ampule with 9 mL of normal saline for a total volume
of 10 mL to achieve a concentration of 0.04 mg/mL. May
also be administered via continuous IV infusion a diluted
preparation by diluting 2 mg in 500 mL of D5W or normal
saline to make 4 micrograms/mL.
May administer by IM or SQ route if unable to obtain IV
access.
Pregnancy Category: B / C (product-specific)
ATC Code: V03AB15
Rx NEOSTIGMINE
Inj.: 500 micrograms/mL, 10 mL vial
500 mcg/mL solution for injection (IM/IV/SC), 1 mL
ampule
A cholinesterase inhibitor competitively binds to
acetylcholinesterase binding sites, inhibiting the
hydrolysis of acetylcholine.
Indication: Reversal of neuromuscular blockade
Contraindications: Peritonitis; mechanical GI; urinary
obstruction
Dose:
NOTE: individualize doses based on weight. Determine time
of initiation of neostigmine and need for additional doses
using a peripheral nerve stimulator.

V
occur); Reversal of neuromuscular blockade, by IV injection, ADULT
Lactation (consider opioid concentrations in the milk of a and CHILD, 0.05–0.07 mg/kg over 60 seconds, as
breast­feeding mother and potential transfer of the required.
opioid to the infant).
Dose Adjustment:
Adverse Drug Reactions: Renal Impairment:
NOTE: Adverse reactions are related to reversing Dose adjustment may be required.
dependency and precipitating withdrawal. Withdrawal
symptoms are the result of sympathetic excess. Precautions:
WARNING: Should be administered by trained healthcare
Common: Cardiac arrest, fever, flushing, hypotension,
providers familiar with the use, actions, characteristics,
hypertension, tachycardia, ventricular fibrillation
and complications of neuromuscular blocking agents
ventricular tachycardia, agitation, hallucination, crying
(NMBA) and neuromuscular block reversal agents.
(excessive; neonates), encephalopathy, irritability,
nervousness, restlessness, seizure (neonates),
tremulousness, abdominal cramps, coma, diarrhea, Bradycardia;
nausea, vomiting, injection site reaction, ache, Cardiovascular disorders;
hyperreflexia (neonates), paresthesia, piloerection, Bronchial asthma;
tremor, weakness, dyspnea, hypoxia, pulmonary edema, Neuromuscular dysfunction;
respiratory depression, rhinorrhea, sneezing, Peptic ulcer disease;
diaphoresis, hot flashes, shivering, yawning Vagotonia;
Epilepsy;
Drug Interactions: Parkinsonism;
Avoid concomitant use with: Hyperthyroidism;
Increases risk of adverse or toxic effects of Naloxone: Recent intestinal or bladder surgery;
Methylnaltrexone (opioid withdrawal) Renal impairment;
Elderly (use with caution);

619
 VARIOUS

Children; PENICILLIN G CRYSTALLINE

Pregnancy; Rx
(BENZYLPENICILLIN)
Lactation.
Inj.: 1 MU and 5 MU (as sodium salt) (IM, IV)
Adverse Drug Reactions:
Common: Bradycardia, hypotension, tachycardia, dry
A beta lactamase-sensitive penicillin that protects against
mouth, nausea, vomiting, incision site complication,
lethal doses of amanitin by displacing amanitin from
pharyngolaryngeal pain, procedural complication,
plasma proteins, thus increasing renal excretion. It
procedural pain, dizziness, headache, postoperative
inhibits amanitin from entering hepatocytes by binding to
shivering, prolonged neuromuscular blockade, insomnia,
acid amanitin.
dyspnea, oxygen desaturation <90%, pruritus
Less Common: Hypersensitivity reactions, allergic reactions,
NOTE: Peak plasma concentrations are reached within 15–
convulsions, drowsiness, dysarthria, fasciculation, loss
30 minutes.
of consciousness, miosis, visual changes, cardiac arrest,
cardiac arrhythmias, non-specific EKG changes,
Indication: For amanita mushroom poisoning
syncope, bronchospasm, increased salivation,
Dose:
respiratory arrest, rash, urticaria, abdominal cramps,
Amanita mushroom poisoning, by IV injection, ADULT and
diarrhea, flatulence, increased peristalsis, urinary
CHILD, 250 mg/kg daily.
frequency, arthralgia, muscle cramps, spasms,
weakness, diaphoresis, flushing, neuromuscular
Dose Adjustment:
dysfunction (high doses), respiratory failure (potentially
Renal Impairment:
fatal)
For mild-to-moderate renal impairment, reduce dose.
For severe impairment, refer patient to a specialist.
Drug Interactions:
Do not exceed 6 g daily in renal failure.
Monitor closely with:
Reduces therapeutic effect of Neostigmine:
Precautions:
Chloroquine, Hydroxychloroquine, Lithium,
Penicillin allergy;
Procainamide, Propafenone, Quinidine, Quinine
Renal failure;
Neurotoxicity (eg. cerebral irritation, convulsions, or coma);
Avoid concomitant use with:
Sodium restriction, heart failure;
Increases risk of adverse or toxic effects of the following
Syphilis (eg. Jarisch-Herxheimer reaction);
drugs:
Lactation (safe in usual dosage; monitor infant).
Beta Blockers (prolonged bradycardia), Depolarizing
Muscle Relaxants, e.g., Suxamethonium (prolonged
Adverse Drug Reactions:
apnea due to potentiation of neuromuscular blockade)
Common: Pain and sterile inflammation at injection site,
phlebitis
Administration: For IV use only. Inject slowly over a period of
Less Common: Antibiotic-associated colitis, diarrhea,
at least 1 minute.
glossitis, nausea, stomatitis, vomiting
Rare: CNS toxicity, electrolyte disturbances, hemolytic
V

Prior to administration and until complete recovery of

anemia, hypersensitivity reactions including anaphylaxis;
normal ventilation, keep patient well-ventilated, and
interstitial nephritis, Jarisch-Herxheimer reaction,
maintain a patent airway.
neutropenia, non-allergic (embolic-toxic) reaction,
thrombocytopenia
Administer an anticholinergic agent, e.g., atropine
sulfate or glycopyrrolate prior to or concomitantly with
Drug Interactions:
neostigmine. Administer intravenously using a separate
Monitor closely with:
syringe. In the presence of bradycardia, administer the
Enhances therapeutic effect of Anticoagulants, e.g.,
anticholinergic agent prior to neostigmine.
Warfarin
NOTE: Judge satisfactory recovery based on adequacy of
Reduces therapeutic effect of Oral Contraceptives
skeletal muscle tone and respiratory measurements in
addition to response to peripheral nerve stimulation.
Avoid concomitant use with:
Increases serum concentration of Benzylpenicillin:
Pregnancy Category: C
Probenecid
ATC Code: N07AA01
Reduces therapeutic effect of Benzylpenicillin:
Tetracycline (antagonistic effect)

TEST INTERACTION. Produces a false positive urinary

glucose if tested for reducing substances.

Administration: Inspect reconstituted solutions visually. Use

only clear solutions, free of visible particles. Freshly-
prepared solutions for injection or infusion should be
used immediately.

620
VARIOUS

Avoid intrathecal route.

Drug Interactions:
NOTE: IV route is preferred for neonates and infants. Doses Monitor closely with:
over 1.2 g should be given by the IV route only. Enhances therapeutic effect of the following drugs:
Beta Blockers [except Levobunolol, Metipranolol]
See Penicillin G Crystalline (Benzylpenicillin) under (bradycardic effect)
Antibacterials for Systemic Use – Beta-Lactam
Antibacterials, Penicillins in Chapter 7: Antiinfectives for Increases risk of adverse or toxic effects of Physostigmine:
Systemic Use for other information. Corticosteroids, Systemic (increased muscular
weakness)
Pregnancy Category: B
Increases risk of adverse or toxic effects of Cholinergic
ATC Code: Not available Agonists

Reduces therapeutic effect of Physostigmine:

Rx PHYSOSTIGMINE
Inj.: 1 mg/mL (as salicylate), 2 mL ampule (IM, IV)
A carbamate that inhibits acetylcholinesterase and prolongs
the central and peripheral effects of acetylcholine.
Indications: Reversal of central nervous system
anticholinergic syndrome (i.e., atropine poisoning);
adjunct to cobra bite
NOTE: Consult with a clinical toxicologist or poison control
center.
Contraindications: Gastrointestinal or genitourinary
obstruction; asthma; gangrene; diabetes; cardiovascular
disease; vagotonic state; co-administration of choline
esters and depolarizing neuromuscular-blocking agents
(e.g. succinylcholine)
Dipyridamole
Reduces therapeutic effect of the following drugs:
Anticholinergic Agents, Neuromuscular-blocking Agents,
Nondepolarizing
Avoid concomitant use with:
Increases serum concentration Succinylcholine
Administration: If administered by IV injection, administer
no faster than 1 mg/minute in adults or 0.5 mg/minute
in children to prevent bradycardia, respiratory distress,
and seizures from too rapid administration.
May also be administered via IM route.
Pregnancy Category: C
ATC Code: V03AB19

Dose: PHYTOMENADIONE
Reversal of toxic anticholinergic effects, by IM or IV injection, Rx
(PHYTONADIONE, VITAMIN K1)
ADULT, 0.5–2 mg, may repeat every 10–30 minutes until

V
response occurs; CHILD, initially 0.02 mg/kg, may repeat Oral: 2 mg/0.2 mL (as mixed micelle) pediatric ampule
every 5–10 minutes until response occurs (maximum Inj.: 2 mg/0.2 mL (as mixed micelle) pediatric ampule (IM,
total dose, 2 mg). IV)
10 mg/mL (as mixed micelle), 1 mL ampule (IM, IV)
Precautions: 10 mg/mL (as aqueous colloidal solution with benzyl
WARNING: Should only be used to reverse toxic, life- alcohol), 1 mL ampule (IM, IV)
threatening delirium caused by pure
anticholinergic agents (i.e., atropine, A fat-soluble vitamin that is an essential cofactor in the
diphenhydramine, dimenhydrinate, deadly synthesis of blood coagulation factors: prothrombin (II),
nightshade [Atropa belladonna], or jimson weed VII, IX, X, and proteins C and S.
[Datura spp]).
Hazardous agent. Use appropriate precautions for Indications: For warfarin and white or yellow phosphorus
handling and disposal. “watusi” poisoning
Arrhythmia (use with caution);
Contraindications: Avoid IM if bleeding; pregnancy (3rd
Cholinergic effects (eg. excessive cholinergic activity);
trimester); it is not effective in hereditary
Hypersensitivity or overdose reactions;
hypoprothrombinemia and that caused by liver disease
Lactation.
Dose:
Adverse Drug Reactions:
Warfarin-induced hypoprothrombinemia, minor bleeding or
Common: Asystole, bradycardia, palpitation, hallucinations,
not bleeding, by slow IV injection, ADULT, 500
nervousness, restlessness, seizure, defecation,
micrograms.
diarrhea, nausea, salivation, stomach pain, vomiting,
Warfarin-induced hypoprothrombinemia, moderate
urinary frequency, twitching, lacrimation, miosis,
hemorrhage, by IM injection, ADULT, 10–20 mg.
bronchospasm, dyspnea, pulmonary edema, respiratory
Warfarin-induced hypoprothrombinemia, severe
distress, respiratory paralysis, diaphoresis,
hemorrhage, by slow IV injection, ADULT, 5–10 mg.
hypersensitivity

621

Administration: administer by slow IV injection over 30
seconds. Rapid infusion can cause dyspnea, chest and
back pain.
See Phytomenadione (Phytonadione, Vitamin K1) under
Vitamins in Chapter 1: Alimentary Tract and Metabolism
for other information.
Pregnancy Category: C; X in 3rd trimester or near term
ATC Code: Not available
PRALIDOXIME CHLORIDE
Rx
(2-PAM)
Inj.: 50 mg/mL, 20 mL vial (IV)
An antidote that reactivates cholinesterase that had been
inactivated by phosphorylation due to exposure to
organophosphate pesticides and cholinesterase-
inhibiting nerve agents.
Indication: Treatment of muscle weakness and/or
respiratory depression secondary to poisoning due to
organophosphate anticholinesterase pesticides and
chemicals (e.g., nerve agents)
Dose:
NOTE: Used in conjunction with atropine. Establish a
response to atropine before administering pralidoxime.
Organophosphate poisoning, by IV injection, ADULT and
ADOLESCENT >16 years, 1,000–2,000 mg loading dose,
followed by maintenance repeat bolus of 1,000–2,000
mg after 1 hour and repeated every 10–12 hours
thereafter, as needed; or 30 mg/kg loading dose
followed by a maintenance infusion of 8 mg/kg per hour;
ADOLESCENT ≤16 years and CHILD, 20–50 mg/kg
loading dose (maximum, 2,000 mg/dose), then
V
administer maintenance infusion of 10–20 mg/kg per
hour; or a repeat bolus of 20–50 mg/kg (maximum,
2000, mg/dose) may be administered after 1 hour and
repeated every 10–12 hours thereafter, as needed.
NOTE: For persistent symptoms, repeat the entire series
(severe symptoms) approximately 1 hour after
administration of the last injection.
Dose Adjustment:
Renal Impairment:
Dose reduction is recommended.
Precautions:
Myasthenia gravis;
Renal impairment;
Hepatic impairment;
Lactation.
Adverse Drug Reactions:
Common: Cardiac arrest, hypertension, tachycardia,
dizziness, drowsiness, headache, paralysis, seizure, skin
rash, nausea, fasciculations, laryngospasm, muscle
rigidity, weakness, accommodation disturbance, blurred
vision, diplopia, renal insufficiency, apnea,
hyperventilation
622
VARIOUS
Drug Interactions: No known significant interactions
Administration: Administer via IV infusion as 10–20 mg/mL
solution over 15–30 minutes. In the presence of
pulmonary edema and/or fluid restriction, administer as
a 50 mg/mL solution by slow IV injection over ≥5
minutes.
Administer continuous or intermittent IV infusion at a
rate not exceeding 200 mg/minute.
Discard any unused portions.
Consider IM or SQ administration when IV administration
is not feasible.
DILUTION. Dilute 1,000 mg with 20 mL SWFI to make 50
mg/mL for fluid-restricted patients or where a more rapid
administration is required. For all other patients, further
dilute with NS to a final concentration of 10–20 mg/mL.
Pregnancy Category: C
ATC Code: V03AB04
Rx PROTAMINE SULFATE
Inj.: 10 mg/mL, 5 mL and 25 mL ampule (IV)
Simple proteins of low molecular weight that are rich in
arginine and strongly basic. Forms a stable salt with
heparin (strongly acidic) to inhibit the anticoagulant
activity of both drugs.
Indication: Treatment of heparin overdose
Contraindication: Known drug intolerance
Dose:
NOTE: Individualize doses based on administered heparin,
its route of administration, time elapsed since heparin
administration, and blood coagulation studies. Each mg
of protamine, calculated on the dried basis, neutralizes
not less than 100 USP heparin units.
Dosing should be guided by blood coagulation studies.
Since heparin disappears rapidly from circulation,
protamine dose should also decrease with time elapsed
following heparin administration.
Heparin overdose (heparin administered via IV injection), by
IV injection, ADULT, administer at ≤5 mg/minute
(maximum, 50 mg/dose);
a few minutes after heparin administration, 1 mg for
every 100 U of heparin;
30–60 minutes after heparin administration, 0.5–0.75
mg for every 100 U of heparin;
≥2 hours after heparin administration, 0.25 to 0.375 mg
for every 100 U of heparin.
Heparin overdose (heparin administered via IV infusion), by
IV injection, ADULT, 25–50 mg after stopping heparin
administration.
Heparin overdose (heparin administered via SQ injection),
by IV injection, ADULT, 1–1.5 mg for every 100 U of
VARIOUS
heparin; or 25–50 mg loading dose via slow IV injection,
and the remaining dose via continuous IV infusion over
8–16 hours, or the expected duration of heparin
absorption.
Enoxaparin overdose, by IV infusion, ADULT, if ≤8 hours
since administration, 1 mg for every 1 mg of enoxaparin;
if >8 hours since administration, 0.5 mg for every 1 mg
of enoxaparin.
Dalteparin overdose, by IV infusion, ADULT, 1 mg for every
100 anti-Xa U of dalteparin; if aPTT remains prolonged
2–4 hours after first infusion, administer a second
infusion.
Precautions:
WARNING: Can cause severe hypotension,
cardiovascular collapse, noncardiogenic
pulmonary edema, catastrophic pulmonary
vasoconstriction, and pulmonary hypertension.
Vasopressors and resuscitation equipment should
be immediately available in case of a severe
reaction to protamine.
Should NOT be given when bleeding occurs without
prior heparin use.
Hyperheparinemia or bleeding has been reported
30 minutes – 18 hours after cardiac surgery. Keep
patient under close observation after cardiac
surgery.
Do NOT administer more than 50 mg over a short
period unless a larger dose is clearly needed.
Hypersensitivity;
Children;
Lactation.
Adverse Drug Reactions:
Common: Bradycardia, hypotension, flushing (transient),
feeling of warmth, dyspnea, nausea, vomiting, lassitude,
back pain, anaphylaxis or anaphylactoid reactions
Drug Interactions:
Avoid concomitant use with:
Incompatible with the following products:
Antibiotics, e.g., Cephalosporins, Penicillins
Administration: For IV use only.
Administer undiluted via very slow IV injection over a 10-
minute period in doses not exceeding 50 mg. If further
dilution is desired, dilute using D5W or NS. Do NOT store
diluted solutions.
Inspect visually for particulate matter and discoloration
prior to administration.
Pregnancy Category: C
ATC Code: V03AB14
OTC PYRIDOXINE (VITAMIN B6)
Oral: 100 mg tablet
A naturally occurring, water-soluble vitamin. It is converted
in erythrocytes to its active moiety, pyridoxal phosphate,
which acts as coenzymes in metabolic processes,
including metabolism of fat, protein, and carbohydrate.
Indications: Management of isoniazid, hydralazine,
hydrogen sulfide, gynomethrin mushroom, and
theophylline poisoning; to prevent development of
peripheral neuritis in patients receiving isoniazid or
hydralazine
Contraindications: Breastfeeding, pregnancy, premature
neonates, renal impairment
Dose:
NOTE: Dose is individualized and determined by the
physician.
For hydralazine toxicity related to pyridoxine deficiency, by
mouth, ADULT and ADOLESCENT, 100–300 mg daily;
CHILD, 10 to 50 mg daily.
Hydralazine toxicity prophylaxis, by mouth, ADULT, 100 mg
once daily; ADOLESCENT, 25–100 mg daily; CHILD, 1–2
mg/kg daily.
For isoniazid toxicity related to pyridoxine deficiency,
excluding seizures, by mouth, ADULT and ADOLESCENT,
25–100 mg daily; CHILD, 1–2 mg/kg daily.
Isoniazid toxicity prophylaxis, by mouth, ADULT, 10 to 75 mg
daily; or 25 mg daily; ADOLESCENT, 25–100 mg daily; or
25 mg daily; CHILD, 1–2 mg/kg daily. [NOTE: Guidelines
recommend prophylaxis only in patients at risk for
peripheral neuropathy, including those with nutritional
deficiency, diabetes, symptomatic HIV infection, renal
failure, or in patients who are breastfed.]
V
For the treatment of drug-induced seizures secondary to
acute isoniazid overdose, by mouth, ADOLESCENT,
CHILD, and INFANT,
Acute ingestion of known amount, pyridoxine dose equal
to amount of isoniazid ingested (maximum, 70 mg/kg
per dose, up to 5 g);
Acute ingestion of unknown amount, 70 mg/kg per dose
(maximum, 5 g per dose); administer until seizure stops
or maximum initial dose has been administered; if the
entire initial dose is not administered, give remaining
initial dose over the next 4–6 hours; may repeat dose
every 5–30 minutes as needed if seizures do not resolve
or consciousness is not regained;
Asymptomatic patients present within 2 hours of acute
ingestion, treat prophylactically with the initial ingestion
dose (e.g., 70 mg/kg per dose or 5 g) and monitor for 6
hours.
Seizures due to acute mushroom poisoning, by IV injection,
ADULT, 25 mg/kg over 15–30 minutes, may be repeated
as necessary to a total dose of 15–20 g daily;
ADOLESCENT, CHILD, and INFANT, 25 mg/kg over 15–
30 minutes (maximum initial dose, 5 g), repeat dose as
necessary up to 300 mg/kg daily (maximum daily dose,
15–20 g).
623

Administration: Administration: Administer whole. Do NOT
crush, break, or chew.
See Pyridoxine (Vitamin B6) under Vitamins in Chapter 1:
Alimentary Tract and Metabolism for other information.
Pregnancy Category: A
ATC Code: A11HA02
Rx SODIUM CALCIUM EDETATE
Inj.: 200 mg/mL, 5 mL ampule (IM)
The calcium chelate of edetate disodium. It chelates
divalent and trivalent metals, forming stable chelates
that displace calcium from the molecule, forming a
water-soluble complex excreted by the kidneys.
Indication: For the reduction of blood levels and depot
stores of lead in lead poisoning (acute and chronic) and
lead encephalopathy
Contraindications: Anuria; active renal disease; hepatitis
Dose:
Lead poisoning, asymptomatic with blood lead levels >70
micrograms/dL or symptomatic without encephalopathy,
by deep IM injection, ADULT, 167 mg/m2 every 4 hours
for 3–5 days, may treat with dimercaprol until blood lead
level is <50 micrograms/dL.
Lead poisoning, blood lead levels >70 micrograms/dL
and/or symptoms of encephalopathy, by deep IM
injection, ADULT, 250 mg/m2 every 4 hours for 5 days
with dimercaprol, administer first dose at least 4 hours
after first dose of dimercaprol, may be repeated after at
least 2 treatment-free days if needed [NOTE: Both drugs
may be given simultaneously at separate sites].
V
NOTE: Total daily dose (1000 mg/m2) should be divided into
equal doses spaced 8–12 hours apart.
Dose Adjustment:
Renal Impairment:
May require dose reduction.
Precautions:
WARNING: Do NOT confuse with sodium edetate.
Capable of producing toxic effects, which can be fatal.
Inform physician immediately if urine output stops for
a period of 12 hours. Stop therapy if anuria or
severe oliguria develops.
Renal damage (eg. proteinuria and microscopic hematuria;
dose-dependent);
Lactation.
Adverse Drug Reactions:
Common: Pain at injection site, fever, chills, malaise,
fatigue, myalgia, arthralgia, hypotension, cardiac rhythm
irregularities, acute necrosis of proximal tubules,
infrequent changes in distal tubules and glomeruli,
624
VARIOUS
glycosuria, proteinuria, microscopic hematuria, large
epithelial cells in urinary sediment, tremors, headache,
numbness, tingling, cheilosis, nausea, vomiting,
anorexia, excessive thirst, milk increases in SGOT and
SGPT, histamine-like reactions, rash, bone marrow
depression (transient), anemia, zinc deficiency,
hypercalcemia
Less Common: Nephrotoxicity (potentially fatal)
Drug Interactions:
Monitor closely with:
Incompatible with the following products:
Zinc Insulin Preparations (chelates with zinc)
Administration: For IM use only.
Administer IV fluid if possible prior to first dose to ensure
adequate diuresis and reduce incidence of treatment-
induced nephrotoxicity.
NOTE: Add lidocaine or procaine to minimize pain at
injection site. Final lidocaine or procaine concentration
should be 5 mg/mL (0.5%).
Pregnancy Category: B
ATC Code: V03AB03
Rx SODIUM NITRITE
Inj.: USP grade powder (IV)
A cyanide antidote that exerts its therapeutic effect by
reacting with hemoglobin to form methemoglobin, an
oxidized form of hemoglobin with high affinity to cyanide,
inhibiting the activity of cyanide on cytochrome oxidase.
Indication: For sequential use with sodium thiosulfate for
the treatment of cyanide poisoning that is judged to be
serious or life-threatening
Contraindications: None
Dose:
Cyanide poisoning, by slow IV injection, ADULT, 10 mL at
2.5–5 mL per minute; immediately followed by 50 mL
sodium thiosulfate;
CHILD, 0.2 mL/kg (6 mg/kg or 6–8 mL/m2 BSA) at 2.5–
5 mL per minute, not to exceed 10 mL; immediately
followed by 1 mL/kg (250 mg/kg or approximately 30–
40 mL/m2 BSA) sodium thiosulfate, not to exceed 50 mL
total dose.
NOTE: If signs of poisoning reappear, repeat treatment
using half of original dose of both sodium nitrite and
sodium thiosulfate.
Dose Adjustment:
Anemic patients:
Reduce dose in proportion to oxygen carrying capacity.
VARIOUS
Precautions:
WARNING: Causes life threatening hypotension and
methemoglobin formation, which diminishes
oxygen carrying capacity. Monitor patient closely to
ensure adequate perfusion and oxygenation.
Use with caution in patients where the diagnosis of
cyanide poisoning is uncertain.
Anemia (use with caution);
Smoke inhalation injury or carbon monoxide poisoning;
Renal impairment;
G6PD deficiency;
Elderly (select doses with care);
Children, neonates, and infants;
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common and Less Common: Hypotension, syncope,
tachycardia, methemoglobinemia, palpitations,
dysrhythmia, headache, dizziness, blurred vision,
seizures, confusion, coma, nausea, vomiting, abdominal
pain, tachypnea, dyspnea, anxiety, diaphoresis,
lightheadedness, injection site tingling, cyanosis,
acidosis, fatigue, weakness, urticaria, generalized
numbness and tingling
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of the following
drugs, specifically volume depletion:
Diuretics, PDE5 Inhibitors
Administration: For slow IV injection only.
Administer as early as possible after a diagnosis of acute
life-threatening cyanide poisoning has been established.
Administer sodium thiosulfate immediately after sodium
nitrite.
If to be used with other cyanide antidotes, do NOT
administer concurrently in the same IV line.
Pregnancy Category: C
ATC Code: V03AB08
Rx SODIUM THIOSULFATE
Inj.: 250 mg/mL, 50 mL ampule (IV)
An antidote in the treatment of cyanide poisoning. It acts as
a sulfur-donating substrate for rhodanese, speeding up
the conversion of cyanide to thiocyanide, a non-toxic
metabolite. It is also used as an antidote in the treatment
of cisplatin poisoning by rapid chemical inactivation of its
platinum component.
Indications: For sequential use with sodium nitrite in the
treatment of cyanide poisoning that is serious or life-
threatening; for cisplatin poisoning
Contraindication: None known
Dose:
Cyanide poisoning, by slow IV injection, ADULT, 50 mL
sodium thiosulfate administered immediately after 10
mL of sodium nitrite at 2.5–5 mL per minute;
CHILD, 1 mL/kg (250 mg/kg or approximately 30–40
mL/m2 BSA), not to exceed 50 mL total dose
administered immediately after 0.2 mL/kg (6 mg/kg or
6–8 mL/m2 BSA) of sodium nitrite at 2.5–5 mL per
minute, not to exceed 10 mL.
NOTE: If signs of poisoning reappear, repeat treatment
using ½ original dose of both sodium nitrite and sodium
thiosulfate.
Precautions:
Nausea and vomiting;
Renal impairment;
Elderly (select doses with care);
Children;
Lactation.
Adverse Drug Reactions:
Common and Less Common: Osmotic disturbances,
hypotension, headache, disorientation, nausea,
vomiting, prolonged bleeding time, salty taste in mouth,
warm sensation over body
Drug Interactions: No information found
Administration: May be used alone or in combination with
sodium nitrite.
If to be used with other cyanide antidotes, do NOT
administer concurrently in the same IV line.
Pregnancy Category: C
ATC Code: V03AB06
V
Rx SUGAMMADEX
Inj.: 100 mg/mL solution for injection, 2 mL vial (IV)
A modified gamma cyclodextrin that reverses
neuromuscular blockade induced by rocuronium and
vecuronium by complex formation, reducing the amount
of neuromuscular blocking agent available to bind to
nicotinic receptors in the neuromuscular junction.
Indication: For the reversal of neuromuscular blockade
induced by rocuronium and vecuronium in adults
undergoing surgery
Dose:
NOTE: Doses and timing of administration should be based
on monitoring for twitch responses and the extent of
spontaneous recovery that has occurred.
Neuromuscular blockade reversal, rocuronium and/or
vecuronium, by IV bolus injection, ADULT, 4 mg/kg if
spontaneous recovery of the twitch response has
reached 1 to 2 post-tetanic counts (PTC) and there are
no twitch responses to train-of-four (TOF) stimulation;
625
 VARIOUS

2 mg/kg if spontaneous recovery has reached the
reappearance of the second twitch (T2) in response to
TOF stimulation.
Neuromuscular blockade reversal, rocuronium only, by IV
bolus injection, ADULT, 16 mg/kg if there is a clinical
need to reverse neuromuscular blockade soon
(approximately 3 minutes) after administration of a
single dose of 1.2 mg/kg of rocuronium.
Dose Adjustment: No information found
Precautions:
WARNING: Should be administered by trained health care
providers familiar with the characteristics, actions, use,
and complications of neuromuscular blocking agents
and neuromuscular block reversal agents.
NOT for use in the reversal of neuromuscular blockade
for agents other than rocuronium or vecuronium.
Anaphylaxis and hypersensitivity (eg. anaphylaxis);
Marked bradycardia;
Severe renal impairment (not recommended);
Elderly;
Pregnancy;
Lactation.
Administration: For IV use only.
Administer as a single bolus injection over 10 seconds,
into an existing intravenous line of a running infusion
with either of the following:
0.9% sodium chloride
5% dextrose
0.45% sodium chloride and 2.5% dextrose
Isolyte P with 5% dextrose
Ringer’s lactate solution
Ringer’s solution
Ensure the infusion line is adequately flushed between
administration of sugammadex and other drugs.
Visually inspect for particulate matter and discoloration
prior to administration.
NOTE: Ventilatory support is mandatory until adequate
spontaneous respiration is restored and the ability to
maintain patent airway is assured.
Pregnancy Category: Not classified
ATC Code: V03AB35

RE-ADMINISTRATION. A minimum waiting time is necessary SUCCIMER

before administration of steroidal neuromuscular Rx (DIMERCAPTO SUCCINIC ACID,
blocking agent after sugammadex administration. DMSA)
Minimum Waiting Time Dose to be administered
5 minutes 1.2 mg/kg rocuronium Oral: 100 mg and 200 mg capsule
0.6 mg/kg rocuronium,
4 hours or An orally active, heavy metal chelating agent that forms
0.1 mg/kg vecuronium water-soluble chelates, and consequently, increases the
urinary excretion of heavy metals.
Adverse Drug Reactions:
Common: Incision site pain, procedural complication, airway Indication: For the treatment of lead, mercury, arsenic, and
V

complication of anesthesia, anesthetic complication, other heavy metal poisoning

wound hemorrhage, nausea, vomiting, abdominal pain,
flatulence, dry mouth, pain at administration site, NOTE: NOT to be used for prophylaxis of lead-poisoning in a
pyrexia, chills, headache, dizziness, hypoesthesia, lead-containing environment.
oropharyngeal pain, cough, pain in extremity, Dose:
musculoskeletal pain, myalgia, insomnia, anxiety, Heavy metal poisoning, by mouth, ADULT, 10 mg/kg (350
decreased RBC count, abnormal ECG QT-interval, mg/m2) every 8 hours for 5 days, then 10 mg/kg (350
hypertension, hypotension, pruritus, erythema, mg/m2) every 12 hours for an additional 2 weeks of
hypocalcemia, tachycardia, bradycardia therapy; CHILD, administer as follows every 8 hours for 5
Less Common: Recurrence of neuromuscular blockade, days, followed by dosing every 12 hours for 14 days:
restlessness, depression
Rare: Hysterectomy Pediatric weight
Dose (mg)
lbs kg
Drug Interactions:
18–35 8–15 100
Monitor closely with:
Enhances therapeutic effect of the following drugs, 36–55 16–23 200
specifically increased aPTT and prothrombin time: 56–75 24–34 300
Dabigatran, Rivaroxaban, Unfractionated Heparin 76–100 35–44 400
>100 >45 500
Reduces therapeutic effect of the following drugs due to
decreased serum concentration: NOTE: A course of treatment lasts 19 days. Repeated
Hormonal Contraceptives courses may be necessary if indicated by weekly
monitoring of blood lead concentration. A minimum of 2
Avoid concomitant use with: weeks between courses is recommended unless blood
Reduces therapeutic effect of Sugammadex: lead levels indicate the need for more prompt treatment.
Fusidic Acid (delayed reversal time), Toremifene (delayed Precautions:
recovery; high binding affinity for sugammadex)

626
VARIOUS
WARNING: Mild-to-moderate neutropenia has been
observed in some patients. Withhold or
discontinue therapy if absolute neutrophil count
(ANC) is below 1,200 per microliter.
Do NOT use for longer than 3 weeks. Safety of
uninterrupted dosing longer than 3 weeks has not
been established.
Rebound blood lead levels;
Children;
Pregnancy;
Lactation.
Adverse Drug Reactions:
Common: Nausea, vomiting, diarrhea, appetite loss,
hemorrhoidal symptoms, loose stools, metallic taste in
mouth, back pain, abdominal cramps, stomach pains,
head pain, rib pain, chills, flank pain, fever, flu-like
symptoms, heavy head/tired, head cold, headache,
moniliasis, elevated SGPT and SGOT (transient),
elevated alkaline phosphatase, elevated serum
cholesterol, drowsiness, dizziness, sleepiness,
sensorimotor neuropathy, paresthesia, popular rash,
herpetic rash, rash, mucocutaneous eruptions, pruritus,
cloudy film in eye, ears plugged, otitis media, watery
eyes, sore throat, rhinorrhea, nasal congestion, cough,
decreased urination, voiding difficulty, increased
proteinuria, kneecap pain, leg pain
Less Common: Arrhythmia, mild-to-moderate neutropenia,
intermittent eosinophilia
Drug Interactions: No known significant interactions
TEST INTERACTIONS. False-positive results for ketones in
urine using nitroprusside reagents; false decrease in
measurements of serum uric acid and CPK.
Administration: Keep out of reach of children.
NOTE: The treatment of lead poisoning should always be
accompanied by identification and removal of the source
of lead exposure.
Pregnancy Category: C
ATC Code: Not available
THIAMINE
Rx
(VITAMIN B1)
Inj.: 100 mg/mL, 1 mL ampule/vial (IV)
100 mg/mL (as hydrochloride), 10 mL vial (IM, IV)
A wat A water-soluble vitamin found in yeast, cereal grains,
legumes, peas, nuts, pork, and beef. It is used to prevent
peripheral neuritis associated with pellagra and
pregnancy. It combines with adenosine triphosphate
(ATP) to form thiamine pyrophosphate, an essential
coenzyme in carbohydrate metabolism.
Indication: For alcohol intoxication
Contraindications: Breast-feeding; encephalopathy;
pregnancy
Dose:
Alcohol intoxication, by IV or IM injection, ADULT, initially
100 mg by IV injection, followed by 50 to 100 mg daily
by IM or IV injection until a regular, balanced diet is
maintained.
Administration: Parenteral administration is reserved for
patients where oral thiamine is not feasible.
Inspect visually for particulate matter and discoloration
prior to administration.
For slow IV push, no dilution is necessary.
For continuous IV infusion, dilute thiamine in a
compatible infusion solution. Administer at a rate
prescribed by the physician.
For IM administration, inject deeply into a large muscle.
Aspirate prior to injection to avoid injection into a blood
vessel.
See Thiamine (Vitamin B1) under Vitamins in Chapter 1:
Alimentary Tract and Metabolism for other information.
Pregnancy Category: A
ATC Code: A11DA01
IRON CHELATING AGENTS
DEFEROXAMINE
Rx
(DESFERRIOXAMINE)
Inj.: 500 mg powder (as mesylate), vial (IM, IV infusion,
SC)
A chelating agent that complexes with ferric trivalent ions to
V
form ferrioxamine, which is removed by the kidneys. This
slows accumulation of hepatic iron and retards or
eliminated progression of hepatic fibrosis.
Indications: Adjunct in the treatment of acute iron
intoxication; treatment of chronic iron overload
secondary to multiple transfusions
Contraindications: Severe renal disease; anuria
Dose:
Acute iron toxicity, by IM injection, ADULT, initially 1,000 mg,
may be followed by 500 mg every 4 hours for 2 doses,
subsequent doses of 500 mg have been administered
every 4–12 hours based on clinical response (maximum
recommended dose, 6,000 mg daily); ADOLESCENT and
CHILD, 90 mg/kg per dose every 8 hours (maximum,
6,000 mg in 24 hours);
by IV infusion, ADULT, initially 1,000 mg at 15 mg/kg per
hour, subsequent doses may be given over 4–12 hours
at a rate not to exceed 125 mg/hour; ADOLESCENT and
CHILD, 15 mg/kg per hour (maximum, 6,000 mg in 24
hours).
Chronic iron overload, by IM injection, ADULT, 500 to 1,000
mg daily (maximum, 1,000 mg daily);
by IV infusion, ADULT, 40–50 mg/kg daily (maximum, 60
mg/kg daily) over 8–12 hours for 5–7 days per week;
627
 VARIOUS

ADOLESCENT and CHILD ≥3 years, 20–40 mg/kg daily
over 8–12 hours for 5–7 days per week, not to exceed
40 mg/kg daily until growth has ceased;
by SQ injection, ADULT, 1,000–2,000 mg daily or 20–40
mg/kg daily over 8–24 hours; ADOLESCENT and CHILD
≥3 years, 20–40 mg/kg daily over 8–12 hours
(maximum daily dose, 1,000–2,000 mg).
Dose Adjustment:
Geriatric:
Initiate at the lower end of the dosing range.
Increases risk of adverse or toxic effects of Prochlorperazine
(prolonged loss of consciousness)
TEST INTERATIONS. TIBC may be falsely elevated with high
serum iron concentrations or deferoxamine therapy.
Administration: Administer by IV injection when severe
toxicity is evidenced by cardiovascular collapse or
systemic symptoms (coma, shock, metabolic acidosis, or
GI bleeding) or potentially severe intoxications (peak
serum iron level >500 micrograms/dL).

Renal Impairment:
Deferoxamine is readily dialyzable.
In CrCl 10–50 mL/minute and CRRT, administer 25 to 50%
of normal dose.
In CrCl <10 mL/minute, hemodialysis, and peritoneal
dialysis, avoid use.
Precautions:
Acute respiratory distress syndrome, ARDS;
Auditory effects (eg. tinnitus, high frequency hearing loss);
Ocular effects (eg. blurred vision, cataracts, corneal
opacities, decreased visual acuity, impaired peripheral,
color, and night vision, optic neuritis, retinal pigment
abnormalities, scotoma, visual loss or defect);
Growth retardation;
Infection (increased susceptibility to infection with Yersinia
enterocolitica and Yersinia pseudotuberculosis);
Mucormycosis;
Renal effects (e.g., increases in serum creatinine, acute
renal failure and renal tubular disorders; monitor for
changes in renal function);
Urine discoloration;
Elderly (eg. hearing loss and ocular disorders);
Pregnancy;
Lactation.
Adverse Drug Reactions:
V
IM injection may be used for patients with acute iron
toxicity that do not exhibit severe symptoms, and in the
treatment of chronic iron toxicity.
NOTE: Limit vitamin C supplements in adults at 200 mg daily
in divided doses, in children ≥10 years at 100 mg daily,
and in children <10 years at 50 mg daily.
Pregnancy Category: C
ATC Code: V03AC01
Rx DEFERIPRONE
Oral: 500 mg tablet
An iron- chelating agent which binds to ferric iron and
removes it from the blood stream.
Indication: Management of transfusional iron overload if
current chelation therapy in patients with thalassemia is
not insufficient.
Contraindications: Neutropenia; agranulocytosis; pregnan-
cy; lactation

Common and Less Common: Flushing, hypotension, shock,

tachycardia, brain disease, dizziness, headache, Dose:
neuropathy, paresthesia, seizure, skin rash, urticaria, Iron overload, by mouth, ADULT, 25 mg/kg 3 times daily for
growth suppression (children), hyperparathyroidism a total of 75 mg/kg daily (maximum dose, 33 mg/kg 3
(aggravated), hypocalcemia, abdominal distress, times daily for a total of 99 mg/kg daily).
abdominal pain, diarrhea, nausea, vomiting, dysuria,
urine discoloration (reddish), dysplasia (metaphyseal; Tablet requirement to achieve 25 mg/kg (rounded to
children <3 years; dose related), leukopenia, the nearest half-tablet) for administration 3 times
thrombocytopenia, anaphylaxis, hepatic insufficiency, daily:
muscle spasm, angioedema, hypersensitivity, infection
Body weight (kg) Dose (mg) No. of tablets
(Yersinia, mucormycosis), injection site reaction,
arthralgia, myalgia, blurred vision, cataract, 20 500 1
chromatopsia, corneal opacity, decreased peripheral 30 750 1.5
vision, decreased visual acuity, nocturnal amblyopia, 40 1,000 2
optic neuritis, retinal pigment changes, scotoma, vision 50 1,250 2.5
loss, visual field defect, hearing loss, tinnitus, acute renal 60 1,500 3
failure, renal tubular disease, acute respiratory distress
70 1,750 3.5
(dyspnea, cyanosis, and/or interstitial infiltrates),
asthma, fever 80 2,000 4

Drug Interactions: Tablet requirement to achieve 33 mg/kg (rounded to

Avoid concomitant use with: the nearest half-tablet) for administration 3 times
Increases risk of adverse or toxic effects Deferoxamine: daily:
Ascorbic Acid (left ventricular dysfunction), Multivitamins Body weight (kg) Dose (mg) No. of tablets
/ Fluoride with ADE, Multivitamins / Minerals with ADEK, 20 660 1.5
Folate, Iron (left ventricular dysfunction), Multivitamins / 30 990 2
Minerals with AE, no Iron

628
VARIOUS

40 1,320 2.5 Pregnancy Category: D

50 1,650 3.5
60 1,980 4 ATC Code: V03AC02
70 2,310 4.5
80 2,640 5.5
Rx DEFERASIROX
Iron overload in patients with thalassemia, by mouth,
ADULT, 25 mg/kg 3 times daily, may be adjusted Oral: 125 mg and 250 mg dispersible tablet
according to response and therapeutic goals (maximum,
100 mg/kg daily). An orally active iron chelating agent that binds with ferric ion
and removes it from the blood stream
Precautions:
WARNING: Can cause agranulocytosis that can lead Indications: Management of chronic iron overload due to
to serious infections and death. repetitive blood transfusions in patients > 2 years.

Agranulocytosis or neutropenia (eg. fatal agranulocytosis); Contraindications: High-risk myelodysplastic syndromes;

Hepatic impairment;
Elderly and children;
Pregnancy (can cause fetal harm);
Lactation.
Adverse Drug Reactions:
Common: Neutropenia, agranulocytosis, nausea,
abdominal pain or discomfort, vomiting, diarrhea,
dyspepsia, decreased neutrophil, increased weight,
altered appetite, arthralgia, back pain, pain in extremity,
arthropathy, headache, chromaturia, decreased plasma
zinc concentration, urine discoloration (reddish-brown)
Less Common: Thrombocytosis, pancytopenia, atrial
fibrillation, cardiac failure, hypospadias, diplopia,
papilledema, retinal toxicity, enterocolitis, rectal
hemorrhage, gastric ulcer, pancreatitis, parotid gland
enlargement, chills, pyrexia, edema peripheral, multi-
organ failure, jaundice, hepatomegaly, anaphylactic
shock, hypersensitivity, cryptococcal cutaneous
infection, enteroviral encephalitis, pharyngitis,
pneumonia, sepsis, furuncle, infectious hepatitis, rash
pustular, subcutaneous abscess, metabolic acidosis,
advanced malignancies; platelet counts <50,000
cells/mm3; renal impairment (CrCl <60 mL/min); severe
hepatic impairment
Dose:
Chronic iron overload, transfusion-related, by mouth, ADULT
and CHILD >5 to 17 years, initially 20 mg/kg once daily,
adjust dose in increments or decrements of 5–10 mg/kg
every 3–6 months when needed (maximum, 40 mg/kg
daily); CHILD 2–5 years, initially 20 mg/kg once daily,
may require higher titration doses.
Dose Adjustment:
Renal Impairment:
In patients with CrCl of 40–60 mL/minute, reduce starting
dose by 50%.
Do not administer if CrCl <60 mL/minute.
Hepatic Impairment:
In patients with moderate impairment, considerably reduce
dose followed by progressive increase up to a limit of
50%.
Do not administer in patients with severe hepatic

V
dehydration, myositis, chondropathy, trismus, cerebellar impairment.
syndrome, cerebral hemorrhage, convulsion, gait
disturbance, increased intracranial pressure, impaired Precautions:
psychomotor skills, pyramidal tract syndrome, WARNING: May cause acute renal failure, hepatic
somnolence, bruxism, depression, OCD, glycosuria, failure, and death. GI hemorrhages may be fatal,
hemoglobinuria, acute respiratory distress syndrome, especially in the elderly.
epistaxis, hemoptysis, pulmonary embolism,
hyperhidrosis, periorbital edema, photosensitivity Bone marrow suppression (e.g. neutropenia,
reaction, pruritus, urticaria, rash, Henoch–Schönlein agranulocytosis, worsening anemia, and
purpura, hypotension, hypertension thrombocytopenia, including fatal events);
Hypersensitivity (e.g. anaphylaxis and angioedema within
Drug Interactions: the first month of treatment);
Monitor closely with: Skin reactions (e.g. severe cutaneous adverse reactions;
Incompatible with the following products: erythema multiforme);
Products containing Polyvalent Cations (may form Auditory abnormalities (e.g. high frequency hearing loss,
chelates) and decreased hearing);
Ocular abnormalities (e.g. lens opacities, cataracts,
Avoid concomitant use with: elevations in intraocular pressure, and retinal disorders);
Increases serum concentration of Deferiprone: Elderly;
UGT1A6 Inhibitors, e.g., Phenylbutazone Children;
Lactation.
Administration: May be taken with or without food.
Adverse Drug Reactions:
Foods, medications and supplements with polyvalent Common: Gastrointestinal disturbance, headache, fatigue,
cations (e.g., iron, zinc and aluminium) should be taken dizziness, rashes, skin pigmentation, erythema
within at least a 4- hour interval. multiforme, pyrexia, pruritus, anxiety, sleep disorders,

629
 VARIOUS

infections, pharyngolaryngeal pain, edema, Dose:

leucocytoclastic vasculitis, urticaria, alopecia, renal
tubulopathy, proteinuria, hearing loss, visual disorders
Less Common: Stevens-Johnson syndrome, hypersensitivity
reactions, urticaria, alopecia, toxic epidermal necrolysis,
acute renal failure, tubulointerstitial nephritis, hepatic
failure, GI perforation, worsening anemia
Potentially Fatal: Hepatitis, agranulocytosis,
neutropenia, thrombocytopenia, upper GI ulceration and
haemorrhage.
Drug Interactions:
Avoid concomitant use with:
Decreases serum concentration of Deferasirox:
Bile Acid Sequestrants, e.g., Cholestyramine, CYP3A4
Substrates, e.g., Cyclosporine, Hormonal Contraceptives,
Simvastatin, UGT Inducers, e.g., Rifampicin, Phenytoin,
Phenobarbital, Ritonavir
Incompatible with the following products:
Aluminum-containing Antacids (chelates with aluminum)
Increases serum concentration of Deferasirox:
CYP1A2 Substrates, e.g., Duloxetine, Theophylline,
CYP2C8 Substrates, e.g., Carbamazepine, Rifampicin,
Phenytoin
Reduces therapeutic effect of Deferasirox:
UGT Inducers, e.g., Rifampicin, Phenytoin,
Phenobarbital, Ritonavir
Administration: Should be taken on an empty stomach, at
least 30 minutes before meals, preferably at the same
time daily. Do NOT swallow the tablet whole.
Disperse tablet completely by stirring in 100–200 mL of
water, apple juice, or orange juice until a fine suspension
is obtained. Disperse <1 g in 105 mL and ≥1 g in 210 mL
of liquid. Consume contents completely. Rinse the glass
V
NOTE: Given as IV bolus injection in a dose equal to 20% of
the ifosfamide dose weight by weight (w/w) at the time
of ifosfamide administration, then at 4 and 8 hours after
each dose of ifosfamide. The total daily dose of mesna
injection is 60% of the ifosfamide dose.
Prophylaxis against ifosfamide-induced hemorrhagic
cystitis, by IV bolus injection, ADULT, recommended
dosing schedule:
0 hours 4 hours 8 hours
Ifosfamid 1.2
e g/m2
240 240 240
Mesna
mg/m2 mg/m2 mg/m2
Repeat on each day of ifosfamide administration.
Dose Adjustment:
Geriatric:
Select doses with caution, reflecting greater frequency of
decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drugs. The ratio of
ifosfamide to mesna should remain unchanged.
Precautions:
WARNING: Hazardous agent. Use appropriate
precautions for handling and disposal.
Hypersensitivity reactions (eg. anaphylaxis; may cause
fever, hypotension, tachycardia, acute renal impairment,
hypoxia, respiratory distress, urticaria, angioedema,
laboratory signs of disseminated intravascular
coagulation, hematological abnormalities, nausea,
vomiting, arthralgia, myalgia);
Dermatologic toxicity (eg. urticaria, rash, erythema, pruritus,
burning sensation, angioedema, periorbital edema,
flushing, and stomatitis reactions consistent with SJS or
TENhave);

with a little water or juice to resuspend any residue and Hematuria (monitor urine for hematuria; severe hematuria
drink the resulting suspension. despite utilization of mesna may require ifosfamide dose
reduction or discontinuation; examine morning urine
Do NOT disperse in fizzy drinks or milk. Do NOT chew, specimen for hematuria prior to ifosfamide or
break, or crush the tablet. cyclophosphamide treatment);
Ifosfamide or cyclophosphamide toxicities;
Pregnancy Category: C Elderly;
Children (avoid use in neonates, premature, and low-birth
ATC Code: V03AC03 weight infants);
Lactation.

DETOXIFYING AGENTS FOR Adverse Drug Reactions:

ANTINEOPLASTIC TREATMENT Common: Anorexia, arthralgia, conjunctivitis, back pain,
constipation, cough, diarrhea, dizziness, fever,
flatulence, flu-like syndrome, flushing, headache,
MESNA (SODIUM-2-MERCAPTO- hyperesthesia, rash, injection site reactions, nausea,
Rx
ETHANESULPHONATE) pharyngitis, rhinitis, rigors, somnolence, vomiting,
leukopenia, fatigue, thrombocytopenia, anemia,
Inj.: 100 mg/mL, 4 mL ampule (IV) granulocytopenia, asthenia, abdominal pain, alopecia,
dyspnea, chest pain, hypokalemia, pain, increased
A detoxifying agent that inhibits the hemorrhagic cystitis sweating, hematuria, edema, anxiety, confusion,
induced by ifosfamide by binding to the 4-hydroxy insomnia, dyspepsia, hypotension, pallor, dehydration,
ifosfamide forming a non-urotoxic 4- pneumonia
sulfoethylthioifosfamide. Less Common: Anaphylactic reaction, hypertension,
injection site erythema, injection site pain, limb pain,
Indication: Prophylactic agent in reducing incidence of malaise, myalgia, tachycardia, tachypnea
ifosfamide-induced hemorrhagic cystitis Rare: Dysgeusia, hepatitis, convulsion, hemoptysis

630
VARIOUS
Drug Interactions: No information found
TEST INTERACTIONS. False-positive results for urinary
ketones with nitroprusside-based urine tests, including
dipstick tests
Falsely low creatinine kinase levels by interfering with
enzymatic creatinine kinase activity tests, which use thiol
compounds
False-positive results for ascorbic acid with Tillman’s
reagent-based urine screening tests for ascorbic acid
Administration: May be given on a fractionated dosing
schedule of 3 bolus IV injections.
Maintain adequate hydration and urinary output during
ifosfamide treatment.
See Mesna (sodium-2-mercaptoethanesulphonate) under
Antineoplastic Agents – Adjuncts to Antineoplastic
Chemotherapy in Chapter 8: Antineoplastic and
Immunomodulating Agents for other information.
Pregnancy Category: B
ATC Code: V03AF01
MEDICAL GASES
Rx OXYGEN
Inhalational: Medicinal gas
A medicinal gas usually used for hyperbaric oxygen
treatment.
Indication: Anesthetic adjuvant
Contraindication: Untreated pneumothorax; chest surgery;
emphysema; middle ear surgery; uncontrolled high
fevers; upper respiratory infections; seizures; RBC
disorders
Dose: Individualize doses
Precautions:
WARNING: Oxidizer. May cause or intensify fire.
WARNING: For emergency use only.
To be administered by personnel properly trained
for oxygen deficiency and resuscitation.
Administration at concentrations less than 19.5%
oxygen may cause rapid suffocation.
Uninterrupted use of high concentrations over a
long duration, without monitoring its effect on
oxygen content of arterial blood, may be harmful.
Do NOT attempt to use on patients who have
stopped breathing unless used in conjunction with
resuscitative equipment.
Adverse Drug Reactions:
Common: Elevated blood pressure, increased ear pressure,
headache, numbness of fingers, temporary changes in
the eye lens, seizures
Drug Interactions: No information found
Administration: Do NOT handle until all safety precautions
have been read and understood.
Use and store in a well-ventilated place. Protect from
sunlight when ambient temperature exceeds 52°C
(125°F). Keep and store away from clothing and other
combustible materials. Keep valves and fittings free from
grease and oil.
Use a back-flow preventive device in the piping. Use only
with equipment cleaned for oxygen service. Open valve
slowly. Close valve after each use and when empty.
Pregnancy Category: Not classified
ATC Code: V03AN01
DIAGNOSTIC AGENTS
3% HYPERTONIC SALINE
Rx
SOLUTION
Neb.: 3% solution
A sterile nonpyrogenic hypertonic solution diagnostic agent
that stimulates cough reflex to help facilitate sputum
induction.
Indications: For diagnosis of pulmonary tuberculosis
V
Contraindications: Hyper-reactive airway disease; wheezing,
such as with asthma and COPD.
Dose:
Sputum induction, by nebulization, ADULT and CHILD, 20
mL.
EVALUATION. Evaluate sputum collected as follows:
Sputum samples from the tracheobronchial tree (VS
saliva) are typically more viscous, purulent and
malodorous, color tinged, and may have presence of
blood.
Samples that are from a patient with retained secretions
and allergic or infectious process are typically stringy,
mucoid, color tinged, and yellow or green in color.
631
 VARIOUS

Certain infections or disease states may produce sputum TST interpretation: Criteria for positive TST read at 48–72
characteristics: hours:
Characteristic Infectious Agent Induratio
Interpretation
n
Thick, green, musky Pseudomonas
HIV infection (or risk factors for HIV
odor aeruginosa
infection, but unknown status);
Three-layered Recent close contact to person with
sputum, foul Bronchiectasis ≥5 mm known active TB;
smelling Persons with chest x-ray consistent
Mucus plugs or with healed TB;
Asthma
casts Immunosuppressed individuals
Thick, sticky Cystic fibrosis Clinical conditions, which increase the
risk of TB infection;
Dose Adjustment: No information found Recent immigrants;
≥10 mm IV drug users;
Precautions: Residents and employees of high-risk
WARNING: Staff performing sputum collection must settings;
wear proper recommended TB respiratory Children <4 years of age
protection and disposable gloves Persons who do not meet any of the
≥15 mm above criteria (no risk factors for
Adverse Drug Reactions: No information found TB)

Drug Interactions: No information found NOTE: A two-step test is recommended if testing will be
performed at regular intervals (e.g., for healthcare
Administration: Instill 15 mL 3% saline into a small volume workers). If the first test is negative, a second TST
nebulizer medication cup. Instruct the patient to breathe should be administered 1–3 weeks after the first test
deeply, inhaling the aerosol. Instruct the patient to cough was read.
as needed and at 5-minute intervals. Collect expectorant
into the specimen cup. TST interpretation in a healthcare setting:
Interpretatio
Test Parameter Induration
NOTE: If bronchospasm occurs, administer a bronchodilator n
via small volume nebulizer. If adverse effects occur, Baseline ≥10 mm Positive
discontinue therapy and notify the physician. Serial testing
without known ≥10 mm Positive
If there are no results after 30 minutes of nebulizer exposure
treatment, discontinue therapy and notify the physician. Positive if
≥5 mm baseline is 0
Pregnancy Category: Not classified mm
V

Positive if
ATC Code: Not available negative
Known exposure
baseline or
≥10 mm previous
TUBERCULIN, PURIFIED screening
Rx result of ≥0
PROTEIN DERIVATIVE (PPD)
mm
Inj.: 2 TU/0.1 mL solution, 1 mL and 5 mL vial (ID) Read test at 48– 0 mm or Absence of
5 TU/0.1 mL, freeze-dried powder, vial + 2 mL diluent 72 hours less than infection
ampule (ID) following the defined with M.
placement cutoff point tuberculosis
Diagnostic agent containing culture extracts called
tuberculins which can indicate infection with a variety of NOTE: Test results should be documented in millimeters
non-tuberculosis mycobacteria or vaccination with the even if classified as negative. Erythema and redness
live attenuated mycobacterial strain of M. bovis vaccine, of skin are not indicative of a positive test result.
BCG, in addition to previous natural infection with M.
tuberculosis. Dose Adjustment:
Geriatric:
Indication: Skin test in diagnosis of tuberculosis Use a two-step procedure. Repeat test 2–4 weeks after
reading first test dose to elicit a “booster effect.”
Contraindications: Previous severe reaction to tuberculin
PPD skin test (TST) Precautions:
WARNING: Epinephrine (1:1000) should be available
Dose: to treat possible allergic reactions.
Diagnosis of tuberculosis, cell-mediated immuno-
deficiencies, by ID injection, ADULT and CHILD, 0.1 mL. Burns, eczema, tuberculosis (do not administer);
Viral infections (skin testing may be deferred);

632
VARIOUS

Vaccinations (skin testing may be deferred within 1 month);

Elderly (skin test response may be delayed or reduced in GENERAL NUTRIENTS
magnitude);
Children (infants <6 weeks may have an absent or delayed
FAT / CARBOHYDRATES / PROTEINS / MINERALS /
response);
VITAMINS, COMBINATIONS
Pregnancy (use with caution).
ENTERAL FEEDING
Adverse Drug Reactions: Rash, injection site reactions and
General Information
anaphylaxis
Enteral nutrition (EN) is the provision of nutrient via the GI
Drug Interactions:
tract through a feeding tube, catheter, or stoma. It is the
Avoid concomitant use with:
preferred route for the provision of nutrient for patients
Reduces diagnostic effect of Tuberculin:
who cannot meet their nutrition needs through voluntary
Vaccines, Live [do not administer TST within 4–6 weeks
oral intake and if GIT function is compromised.
of vaccination]
Every effort should be made to feed via the GIT Parenteral
nutrition is to be used only when the gut is non-
TEST INTERACTIONS.
functioning, inaccessible, or when complete bowel rest is
May produce false positive reactions may occur with BCG
required.
vaccination
May produce false positive reactions with previous
Indications: Prolonged anorexia, severe protein-energy
mycobacteria infection (non- TB)
undernutrition, coma or depressed sensorium, liver
May produce false negative reactions in patients with
failure, inability to take oral feedings due to head or neck
impaired cell- mediated immunity
trauma, critical illnesses causing metabolic stress (e.g.,
NOTE: BCG vaccination is not contraindicated in tuberculin
burns)
PPD
Contraindications: GI perforation; GI ischemia; complete
Administration: For ID administration only. Do NOT
mechanical or non-mechanical bowel obstruction; high
administer by IV, IM, or SQ.
output enterocutaneous fistula; inability to access GIT;
patient refusal of enteral feeding; severe pancreatitis
Administer to upper third of forearm (palm up) ≥2 inches
from elbow, wrist, or other injection site. If neither arm
Dose:
can be used, administer to back of shoulder. Administer
Enteral nutrition, by continuous infusion, ADULT, initiate full-
using ¼ to ½ inch 27-gauge needle or finer tuberculin
strength formula at 25–50 mL/hour, increase infusion
syringe. Should form wheal (6–10 mm in diameter) as
rate by 10–25 mL every 4–12 hours as tolerated until
liquid is injected which will remain for approximately 10
goal rate is reached; flush a minimum of 20 mL free
minutes. Avoid placing pressure or bandage at injection
water every 4–6 hours to maintain tube patency. [NOTE:
site.
If a patient has been tolerating continuous tube feeding
for several days and is felt to be stable, intermittent
NOTE: Document the date and time of injection, person

V
feeding may be initiated].
placing TST, location of injection site, and lot number of
Enteral nutrition, by intermittent infusion, ADULT, start with
solution.
125 mL full strength formula for the first 2 feedings,
increase each subsequent feeding by 125 mL as
Pregnancy Category: C
tolerated until goal rate is reached; flush the feeding
tube with minimum 20 mL of water before and after
ATC Code: V04CE01
administration to maintain patency. [NOTE: Determine
volume per feeding by dividing the total quantity of
formula needed for a 24-hour period by the desired
number of feedings (usually 3–6 feedings during the day,
each over 30–90 minutes)].

Dose Adjustment:
Fluid Restriction:
Concentrate formula to provide 1.5–2 kcal/mL.

Diabetes mellitus, hyperglycemia:

May require adjustment of antidiabetic therapy or addition
of insulin or other antidiabetic medications.

Precautions:
WARNING: Consult dietician for initial nutritional
assessment, recommendations regarding
appropriate enteral formula, administration, goal
rate, and ongoing monitoring of nutritional status.

633
 VARIOUS

Pressure necrosis; digestive or absorptive capabilities. Review actual

Aspiration pneumonitis; product label whenever exact nutrient content is
Cardiac insufficiency and respiratory difficulty; required.
Electrolyte abnormalities;
Dehydration; Select route of administration based on condition of GIT
Delayed gastric emptying (eg. retention, diarrhea and and anticipated duration of feeding.
vomiting);
Severe malnutrition (eg. severe cardiopulmonary and Duration
neurologic complications); Route GIT Condition of
Hepatic impairment; Feeding
Hyperlipidemia; Nasoenteric tube route
Phenylketonuria; Normal gastric
Renal impairment; function;
Elderly (at greater risk of developing nasogastric tube Nasogastric
Intact gag reflex; May
problems, eg. aspiration pneumonia; more likely to (pre-pyloric) <4 – 6
increase risk of
remove nasogastric tube); aspiration weeks
Children (may have milk sensitivity and metabolic disorders; Cannot tolerate gastric
children ≤1 year are known to have immature Nasoduodenal
feeding; High risk for
gastrointestinal, hepatic, and renal systems). or nasojejunal
gastroesophageal
(post-pyloric)
reflux and aspiration
Adverse Drug Reactions:
Enterostomy tube route
Common: Aspiration, constipation, dehydration, diarrhea,
hypermagnesemia, hyperglycemia, hyperkalemia, Normal gastric
hypernatremia, hypokalemia, hypophosphatemia, emptying;
Gastrostomy
hypomagnesemia, fluid overload, hyponatremia, Little risk of
tubes
hypercapnia, GI disturbances, low serum zinc, nausea, esophageal reflux and
vomiting, electrolyte retention problems (polymeric), aspiration
essential fatty acid (EFA) deficiency Upper GI disease with >4 – 6
Less Common: Hyperphosphatemia normal small bowel weeks
function; High risk of
Drug Interactions: esophageal reflux and
Jejunostomy
NOTE: Enteral formula that are administered continuously aspiration; Long-term
tubes
may reduce the rate and/or extent of absorption of enteral nutrition
medications that must be given on an empty stomach. support where gastric
Do NOT mix medications directly with the enteral feeding is
formula. contraindicated

Monitor closely with: If using nasal or oral feeding tubes, inspect the mouth,
Reduces absorption of the following drugs: nares, and pharynx daily for ulceration, skin irritation,
V

Phenytoin, Oral [withhold enteral feeding and flush pressure necrosis, and lesions. Clean nares daily with warm
nasogastric tube 2 hours before and 2 hours after water. Check the tape on the nose or mouth or the fixator
phenytoin administration] device and change every 3–5 days, or as needed.

Reduces therapeutic effect of Warfarin (causes warfarin
resistance)
Avoid concomitant use with:
Increases risk of adverse or toxic effects of Sucralfate
(bezoar formation due to protein-binding of sucralfate)
Reduces absorption of Ciprofloxacin
WARNING: Concomintant use with other medications; if
the medication is available as sold (especially EC
tablets, SR preparations and sorbitol-containing
medications only), reconsider crushing, as this may
alter the absorption characteristics of the medication
or plug the tube.
If using gastrostomy or jejunostomy , for the first 48–72
hours, place dressings over the feeding tube or stoma and
clean the skin with sterile normal saline and dry thoroughly.
After 48–72 hours, leave healed stoma open to air without
dressing, clean skin with soap and warm water, and dry
thoroughly. Clean under the discs, bumpers, or bolsters to
keep them dry. Do not place dressings under external
bolster to prevent application of pressure to the stomach
wall, which may force the tube out of the stomach and into
the peritoneum.

Administration: Patients should sit upright at 30–45

degrees during tube feeding and for 1–2 hours afterward
to minimize incidence of nosocomial aspiration
pneumonia and to allow gravity to help propel the food.

Select appropriate formula based on the individual

patient’s medical condition, nutritional status, and

634
VARIOUS

Determine the method of administration based on GI ADULT POLYMERIC ENTERAL

function, feeding site, patient tolerance. Rx
NUTRITION

Feeding Patient Oral:

GI function
site tolerance Composition:
Continuous Infusion Calories 100 – 475 kcal
Critically ill, Dilution 1:1 – 2:1
Small
Impaired GI function debilitated Carbohydrates 13.8 – 59 g
bowel
patients Protein 3.8 – 19.9 g
Intermittent Infusion Fat 3.4 – 21.5 g
Sodium 75 – 402 mg
Increased risk of Not for critically Potassium 370 – 580 mg
distention, Gastric ill patients; Calcium 80 – 500 mg
aspiration, and feeding Dependent on Magnesium 25 – 500 mg
other GI only functional ability Fiber 0 – 1.5 g
complications of the gut Phosphorus 47 – 307 mg
Bolus Infusion mOsm/ kg 270 – 730
GI intolerance and Into the Volume 100 mL – 1 L
Non-critical
increased risk for stomac
patients Contains intact protein from soy or casein, carbohydrate as
aspiration h only
disaccharides and polysaccharides, and variable
amounts of fat, fiber, and water. Requires normal or near
Continuous infusion is performed at 25–125 mL/hour
normal digestive and absorptive capacity and are
over 12–24 hours, usually by an enteral feeding pump.
nutritionally complete with all vitamin, minerals, and
trace elements at a specified volume.
Intermittent infusion is performed at 250–500 mL over
30 to 90 minutes several times a day, usually by gravity
Indications: Prolonged anorexia, severe protein-energy
flow or enteral feeding pump. Usually used for stable
undernutrition, coma or depressed sensorium, liver
patients requiring long-term feeding or when greater
failure, inability to take oral feedings due to head or neck
patient freedom and mobility are desired, like in a home
trauma, critical illnesses causing metabolic stress (e.g.,
setting.
burns)
Bolus infusion is performed at 200–500 mL over a short
See General Information on Enteral Feeding listed above
period of time (usually less than 15 minutes), several
for other information.
times a day by syringe. Usually used for home tube-
feeding patients or patients in rehabilitation, when
Pregnancy Category: Not classified
greater freedom and mobility are desired.
ATC Code: V06DB

V
NOTE: Use of enteral feeding pump is desirable to ensure a
constant infusion rate.

Water requirement should be based on patient’s fluid DISEASE SPECIFIC ENTERAL

Rx
status. Water requirement in a normal healthy adult is 1 NUTRITION
mL/kcal. Volume of water from all sources should be
calculated and measured against requirements, Oral:
including enteral feeding, flushes, intravenous, and oral. Composition:
Calories 100 – 1,000 kcal
Pregnancy Category: Not classified Dilution 1:1 – 2:1
Carbohydrates 10.4 – 156 g
ATC Code: V06DB Protein 5.5 – 88 g
Fat 3.3 – 108 g
Sodium 80 – 2,400 mg
Potassium 172 – 5,600 mg
Calcium 80 – 500 mg
Magnesium 25 – 500 mg
Phosphorus 50 – 1,789 mg
mOsm/kg 230 – 635
Volume 50 mL – 500 mL
50 g – 500 g

Specifically designed for patients with specific diseases or

medical conditions that may respond to nutrient
manipulation.

635
 VARIOUS

Indications: For correcting water electrolyte acid-base, and and are complete with respect to vitamin, minerals, and
caloric disturbances in major elective surgery, trauma, trace elements at a specified volume.
burns, head and neck cancer, ICU on mechanical
ventilation, and wound healing. Helps in improving Indications: Nutritional support in children to provide energy
immune cell function, modulates inflammation and and nutrients to support optimal growth, and neuromotor
reduces infection. development; inability to take enough food; maldigestion
and malabsorption; increased nutritional requirements
See General Information on Enteral Feeding listed above for (e.g., burns, trauma, cystic fibrosis, congenital heart
other information. disease); altered metabolism; primary disease
management (e.g., chronic diarrhea, Crohn’s disease)
Pregnancy Category: Not classified
NOTE: To be used on pediatric populations with growth
ATC Code: V06DB impairment but sufficiently preserved GI function:
Child <2 years with growth failure >1 month
Child >2 years with growth failure >3 months
FIBER CONTAINING ENTERAL Change on centile charts >2 growth channels
Rx Triceps skinfolds <5th percentile per age
NUTRITION
Dose:
Oral:
NOTE: Individualize dose based on age, clinical picture, and
Composition:
possibility of oral intake, absorptive and digestive
Calories 100 – 1,048 kcal
capacity, and dietary habits.
Dilution 1:1 – 2:1
Chosen approach should increase stepwise in respect to
Carbohydrates 13.8 – 148 g
underlying condition and impairment of nutritional status
Protein 3.8 – 40 g
Fat 3.4 – 34.7 g
See General Information on Enteral Feeding listed above for
mOsm/kg 270 – 375
other information.
Sodium 46.5 – 930 mg
Potassium 78.5 – 1,570 mg
Pregnancy Category: Not applicable
Phosphorus 63 – 720 mg
Fiber 2 – 10.6 g
ATC Code: V06DB
Volume 100 g – 400 g
500 mL

Serves as a source of fiber; beneficial for prevention or SEMI-ELEMENTAL ENTERAL

Rx
treatment of altered bowel function in enterally fed NUTRITION
patients.
Indications: Dietary management of diarrhea and Oral:
constipation Composition:
Calories 100 – 1,300 kcal
V

See General Information on Enteral Feeding listed above for Dilution 1:1 – 1.5:1
other information. Carbohydrates 13.8 – 177.2 g
Pregnancy Category: Not classified Protein 3 – 66.6 g
Fat 3.9 – 37.4 g
ATC Code: V06DB Sodium 66 – 1,040 mg
Potassium 135 – 1,730 mg
Phosphorus 22 – 867 mg
PEDIATRIC POLYMERIC ENTERAL mOsm/kg 375 – 575
Rx Volume 100 mL – 1 L
NUTRITION
76 g – 450 g
Oral:
Contains short chain carbohydrate or simple sugar and
Composition:
peptides or amino acid. The use of peptide-based
Calories 445 – 511 kcal
formula has been shown to be superior to free amino
Dilution 1:1
acids in promoting greater nitrogen absorption in both
Carbohydrates 14.9 – 62.2 g
healthy and disease gut.
Protein 13.4 – 54.3 g
Fat 16.2 – 26 g
Indications: Nutritional supplementation in conditions of
mOsm/kg 308 – 345
maldigestion or malabsorption
Sodium 120 – 250 mg
Potassium 400 – 750 mg
See General Information on Enteral Feeding listed above for
Phosphorus 150 – 760 mg
other information.
Volume 100 g
Pregnancy Category: Not classified
Contains protein, fat, and carbohydrates, which require
normal or near normal digestive and absorptive capacity
ATC Code: V06DB

636
VARIOUS

See Glucose (Dextrose) under Antihypoglycemics in Chapter

Rx MODULAR ENTERAL NUTRITION 01: Alimentary Tract and Metabolism for other
information.
Oral: Pregnancy Category: C
Composition:
Calories 9.5 – 380 kcal ATC Code: V06DC01
Dilution 0
Carbohydrates 0.67 – 94 g
Protein 5 – 23 g AMINO ACIDS / CARBOHYDRATES / MINERALS /
Fat 0.6 g VITAMINS, COMBINATIONS
Sodium 15 – 110 mg
Potassium 10 – 66 mg AMINO ACID SOLUTIONS
Phosphorus 5 – 30 mg
mOsm/kg 900
Volume 280 g – 400 g General Information

Provides protein, fat, or carbohydrate as single nutrients or
modular mixtures to allow adjustment of macronutrient
mix. They are not nutritionally complete; however, they
can be added to commercial formulas to alter the
nutrient content or caloric density.
See General Information on Enteral Feeding listed above for
other information.
Solution of amino acids intended to provide nutrition into
the body.
Indications: Parenteral nutrition
Contraindications Severe blood acid or electrolyte
problems; high blood ammonia levels; low blood volume;
amino acid metabolism problems

Pregnancy Category: Not classified Precautions:

Sulfite allergy; Elderly, children, and newborns (increased
ATC Code: V06DB sensitivity to side effects); Pregnancy and lactation (use
with caution).

CARBOHYDRATES Adverse Drug Reactions:

Common and Less Common: Severe allergic reactions
(rash, hives, tightness in the chest, swelling of the mouth,
Rx GLUCOSE / DEXTROSE face, lips, or tongue), shortness of breath, unexplained
weight gain, swelling of the hands, ankles, legs, or feet,
symptoms of fluid or electrolyte problems (e.g.,
Inj.: 50%, 10 mL and 20 mL ampule (IV) confusion, fainting, fast or irregular heartbeat, loss of
50%, 10 mL, 20 mL, and 50 mL (85 Kcal) vial (IV) appetite, mood changes, muscle pain, twitching, or
weakness, seizures, severe or persistent dizziness,

A sterile, hypertonic solution of glucose, which provides a
source of calories in a minimal volume of water and is
used in restoring blood glucose concentrations in the
treatment of hypoglycemia.
Indication: For parenteral nutrition during carbohydrate
depletion
Contraindications: Hyperglycemia; use of hyperosmotic
solutions in patients with anuria; diabetic coma; glucose-
galactose malabsorption syndrome; dehydrated patients
with delirium; intracranial or intraspinal hemorrhage;
should not be used after ischemic attacks.
Dose:
NOTE: Individualize dose based on patient requirements.
Carbohydrate depletion, by IV injection, ADULT, administer
as >5% solution via a peripheral vein.
V
unusual tiredness or weakness
Drug Interactions:
WARNING: Should NOT be mixed with other drugs due
to increased risk of microbial contaminations and
incompatibilities. Mixing with other drugs may alter
the chemical and physical properties of the
solution, giving rise to toxic reactions.
Administration: Administer by IV infusion. Keep out of reach
of children and pets, including syringes and needles.
Do NOT reuse needles, syringes, or other materials.
Dispose of properly after use.
Pregnancy Category: Not classified
ATC Code: V06DE

Administration: Administer via a large vein (e.g., into a

secure IV cannula in an antecubital vein).

Visually inspect parenteral products for particulate

matter and discoloration prior to administration.

637
 VARIOUS

AMINO ACID SOLUTIONS FOR AMINO ACID SOLUTIONS FOR

Rx
HEPATIC FAILURE Rx IMMUNONUTRITION /
IMMUNOENHANCEMENT
Inj.:
Composition: Inj.:
Volume 500 mL Composition:
Concentration 5–8% Volume 50 mL and 100 mL
5–10% Protein 20 g; L-alanyl-L-glutamate
Protein 35–50 g; rich in Calories 70–90
branched-chain amino acids Electrolytes none
Calories 50–200
Electrolytes variable Solution of amino acids intended to provide nutrition into
the body.
Management of hepatic failure in patients with acute and
chronic liver diseases. Helpful in patients under Indications: Parenteral nutrition
hypercatabolic state with negative nitrogen balance due
to increased skeletal muscle breakdown. Dose: Determine dose based on individual patient’s needs.

Indication: Management See General Information on Amino Acid Solutions listed

of hepatic encephalopathy in patients with acute and above for other information.
chronic liver diseases
Contraindications: Severe renal disorder; abnormal amino Pregnancy Category: Not classified
acid metabolism other than hepatic disorders
ATC Code: V06DE
Dose:
NOTE: Individualize dose based on patient’s needs. Adjust
dose based on a patient’s age, symptoms, and body AMINO ACID SOLUTIONS FOR
weight. Rx
INFANTS
Hepatic encephalopathy, by drip IV infusion, ADULT, 500 to
1,000 mL per dose at a rate of 500 mL over 180–300 Inj.:
minutes (about 25–40 drops/minute). Composition:
Volume 100 mL
Dose Adjustment: Concentration 5–10%
Pregnancy: Protein 5–10 g; including taurine
Adjust dose to achieve a reduction to less than 5,000 IU of Calories 20-40 kcal
vitamin A daily in pregnant women of gestational month Electrolytes none
of 3 months or earlier or women who have an intention
to become pregnant. A mixture of amino acids, carbohydrates, and fat emulsions
V

that may serve as total parenteral nutrition.

Precautions:
Severe acidosis; Congestive heart failure; Elderly and
children; Pregnancy (may cause cranial neural crest and
other malformations in newborns).
Adverse Drug Reactions:
Common: Acidosis, nausea, vomiting, chest discomfort,
palpitation, chills, fever, headache, vascular pain
Rare: Skin eruptions
Indication: For partial parenteral nutrition in premature
infants, babies, and small children
Contraindications: Disturbances in amino acid metabolism,
acidosis, hyperhydration, hypokalemia
Dose:
NOTE: Individualize dose based on patient’s needs.

Administration: Administer by slow IV infusion. 500–1,000 For parenteral nutrition, by IV infusion, INFANT, administer
mL is reconstitue with a dextrose solution and as required, not exceeding maximum dose, as follows:
administered over 24 hours via a central vein. Maximum daily dosage
1st year of living 1.5 – 2.5 g/kg
See General Information on Amino Acid Solutions listed 2nd–5th year of living 1.5 g/kg
above for other information. 6th–14th year of living 1 g/kg

Pregnancy Category: Not classified Dose Adjustment:

Renal and Hepatic Impairment:
ATC Code: V06DE Individualize doses.

Precautions:
Hyponatremia.

Administration: For IV infusion. Keep out of reach of

children.

638
VARIOUS
NOTE: Too rapid infusion may result in renal losses causing
amino acid imbalance.
See General Information on Amino Acid Solutions listed
above for other information.
Pregnancy Category: Not applicable
ATC Code: V06DE
AMINO ACID SOLUTIONS FOR
Rx
RENAL CONDITIONS
Inj.:
Composition:
Volume 250-500 mL
Concentration 3.5–7%
Protein 17.5–35 g; rich in essential
amino acids
Calories 50–200 kcal
Contains essential, semi- essential and non- essential
amino acids in optimum concentration for protein
synthesis.
Indications: Serves as a parenteral nutrition supplement for
renal failure following polytrauma, acute and chronic
renal insufficiency, and compensation of amino acid
losses in patients undergoing dialysis hemofiltration,
extensive surgery and sepsis.
Contraindications: Metabolic acidosis, renal and amino acid
disturbances, hypernatremia, hyperkalemia,
hyperhydration and congestive heart failure
Dose:
NOTE: Individualize dose based on patient’s needs. Adjust
doses according to amino acid requirements based on
age, body weight, and condition of patient
Acute and chronic renal insufficiency not treated by dialysis,
by IV infusion, ADULT, maximum dose, 0.5 g/kg daily.
Acute and chronic renal insufficiency treated by
hemofiltration, peritoneal dialysis, and hemodialysis, by
IV infusion, ADULT, maximum dose, 1 g/kg daily.
Precautions:
Intolerance and increased renal losses (may be
accompanied by amino acid imbalance if the solution is
infused too rapidly).
Adverse Drug Reactions:
Common: Nausea, vomiting, chill, fever
Less Common: Chest discomfort and palpitation
Administration: Administer through peripheral veins or by
central venous route using non-pyrogenic IV
administration set with aseptic technique.
Unsuitable for long-term parenteral use as it does not
contain adequate non-essential amino acids. Include fat
in the dietary regimen during long-term therapy to avoid
essential fatty acid deficiency.
See General Information on Amino Acid Solutions listed
above for other information.
Pregnancy Category: Not classified
ATC Code: V06DE
OTHER NUTRIENTS
Rx IODIZED OIL FLUID
Oral: 500 mg (equivalent to 200 mg elemental iodine) soft
gel capsule
NOTE: For DOH Program only.
A salt form of iodized oil intended to meet RDI for iodine for
pregnant and lactating women (200 micrograms daily) in
areas of moderate and severe iodine deficiency.
Indications: Prophylaxis of iodine-deficiency-related fetal
disorders, including endemic cretinism and neonatal
hypothyroidism for administration to pregnant women
and women of childbearing age
Dose:
NOTE: Select lowest dose and frequency that will ensure
protection throughout pregnancy, and during lactation
for at least first year postpartum.
Prophylaxis of iodine-deficiency-related fetal disorders, by
mouth, ADULT (pregnant women), 300–480 mg every 12
months; or 100–300 mg every 6 months; ADULT (non-
pregnant fertile women), 400–960 mg every 12 months;
or 200–480 mg every 6 months.
Dose Adjustment: No information found
V
Precautions:
Use only in pregnant women and women of childbearing age
where the prevalence of iodine deficiency disorder is
classified as moderate or severe, cretinism and neonatal
hypothyroidism are present, or universal salt iodization
programs will not reach women at reproductive age
within 1–2 years.
Identify optimal biological and process indicators to prevent
fetal brain damage as follows:
Biological indicators [NOTE: At least one should be
neonatal thyroid stimulating hormone (TSH) or maternal
urinary iodine]:
Infants
• Birth weight
• Perinatal mortality rate
• Neonatal serum TSH
Mothers
• Urinary iodine concentration
• Breastmilk iodine concentration
Adverse Drug Reactions: No information found
Drug Interactions: No information found
639
 VARIOUS

Administration: May be administered at any stage of the 300 mg/mL 350 mg/mL
pregnancy. Procedure
Preparation Preparation
(maximum
Pregnancy Category: Not classified
dose, 250 mL)
ATC Code: Not available

CHILD, 1–1.5
CONTRAST MEDIA CHILD, 1.5–2 mL/kg, usually
mL/kg, usually 1.25 mL/kg, of
1.75 mL/kg the 350
X-RAY CONTRAST MEDIA, IODINATED (maximum mg/mL
dose, 6 mL/kg (maximum
Rx IOHEXOL or 291 mL) dose, 5 mL/kg
or 250 mL)
CHILD, 1
Inj.: 300 mg iodine/mL, 50 mL and 100 mL vial Pulmonary
mL/kg as a
350 mg iodine/mL, 50 mL and 100 mL vial angiography
single injection
ADULT, 50–80 ADULT, 50–80
NOTE: For IV and other parenteral routes as appropriate. mL into the mL into the
aorta, may be aorta, may be
A nonionic, water-soluble radiographic contrast medium. It repeated if repeated if
will opacify blood vessels in the path of flow of the indicated indicated
contrast medium permitting radiographic visualization of (maximum (maximum
the internal structures until significant hemodilution total dose, 291 total dose, 250
occurs. mL) mL)
ADULT, 30–60 ADULT, 30–60
Indications: Angiocardiography (ventriculography, selective mL into major mL into major
coronary arteriography), aortography, including studies branches, branches,
of the aortic root, aortic arch, ascending aorta, including including
abdominal aorta and its branches; contrast celiac and celiac and
enhancement for computed tomographic head and body mesenteric mesenteric
imaging; intravenous digital subtraction angiography of arteries, may arteries, may
the head, neck, abdominal, renal and peripheral vessels; Aortography and be repeated if be repeated if
peripheral arteriography; excretory urography selective indicated indicated
visceral (maximum (maximum
Contraindications: Systemic or local infection arteriography total dose, 291 total dose, 250
mL) mL)
V

Dose: ADULT, 5–15 ADULT, 5–15

NOTE: Individualize dose based on size of the structure to mL into renal mL into renal
be visualized, anticipated degree of hemodilution, and arteries, may arteries, may
valvular competence, as well as the size, flow rate, and be repeated if be repeated if
disease state of the injected vessel. Consider weight in indicated indicated
infants and young children. (maximum (maximum
total dose, 291 total dose, 250
The volume to be administered is a more important mL) mL)
consideration than the total dose. CHILD, 1
mL/kg
By IV injection, (maximum
300 mg/mL 350 mg/mL total dose, 5
Procedure
Preparation Preparation mL/kg or 250
ADULT, 3–14 mL)
Selective
mL per ADULT, 6–12
coronary
injection, mL into the
arteriography
usually 5 mL carotid artery
ADULT, 20–75 ADULT, 8–10
Aortic root and
mL, usually 5 Cerebral mL into the
arch study,
mL as a single arteriography internal carotid
alone
injection artery
ADULT, 6–9
ADULT, 30–60 mL into the
mL, usually 40 vertebral artery
Ventriculography
mL, repeat as
necessary

640
VARIOUS

300 mg/mL 350 mg/mL By intrathecal injection,

Procedure
Preparation Preparation 300 mg/mL
Procedure
ADULT, 70– Preparation
ADULT, 80 mL
Contrast 150 mL (21– Thoracic myelography (via
(28 g)
enhanced 45 g) cervical or lumbar 6–10 mL (1.8–3 g)
computed CHILD, 1–2 injection)
tomography, mL/kg Cervical myelography (via
head imaging (maximum 6–10 mL (1.8–3 g)
lumbar injection)
dose, 35 g)
Cervical myelography (via
4–10 mL (1.2–3 g)
C1–2 injection)
Total columnar
300 mg/mL 350 mg/mL myelography (via lumbar 6–10 mL (1.8–3 g)
Procedure injection)
Preparation Preparation
Contrast
Dose Adjustment:
enhanced ADULT, 50– ADULT, 60– Pheochromocytoma:
computed 200 mL (15– 100 mL (21– Administer absolute minimum amount required.
tomography, 60 g) 35 g)
body imaging
Precautions:
ADULT, 30 –
WARNING: Procedures involving radiopaque
50 mL as a
diagnostic agents should only be done by
bolus at 7.5 –
qualified personnel with in- depth knowledge of
30 mL/second
using a the procedure to be done. Emergency treatment
Digital for severe reactions and appropriate facilities
pressure
subtraction needs to be readily available should there be
injector, may
angiography any complication in the procedure. Severe
require up to 3
delayed reactions may occur after
or more
injections, not administration; well- trained personnel and
emergency facilities should be readily available
to exceed 250
mL (87.5 g) within 30- 60 minutes after administration.
Peripheral
angiography, ADULT, 20–90 ADULT, 20–70 WARNING: Reports of serious and rarely fatal
aortofemoral mL mL thromboembolic events leading to myocardial
runoffs infarction and stroke have been documented.
Peripheral Exercise extra caution in intravascular
angiography, administration especially in angiographic
selective ADULT, 10–60 ADULT, 10–30 procedures (caution in guidewire and catheter

V
arteriograms mL mL manipulation, use of manifold systems and/or
(femoral or three-way stopcocks, frequent catheter flushing
iliac) with heparinized saline solutions and minimizing
Peripheral the length of the procedure should be
angiography, ADULT, 40– considered). Plastic syringes have decreased
venography 100 mL the possibility of in- vitro clotting.
(per leg) Potentially hazardous in patients with multiple
Excretory ADULT, 200– ADULT, 200– myeloma or other paraproteinemia, particularly
urography 350 mg/kg 350 mg/kg therapeutically resistant anuria.
CHILD, 0.5–3 May promote sickling in individuals who are
mL/kg, usually homozygous for sickle cell disease
1–1.5 mL/kg, Development of severe cutaneous adverse
not to exceed 3 reactions (SCAR) may develop after 1 hour to
mL/kg several weeks following IV administration,
including Stevens-Johnson syndrome and toxic
NOTE: When administered for multiple procedures, do NOT epidermal necrolysis (SJS/TEN), acute
exceed maximum dosage as follows: generalized exanthematous pustulosis (AGEP)
ADULT 250 mL of 350 mg/mL solution and drug reaction with eosinophilia and
CHILD 250 mL (5 mL/kg) of 350 mg/mL solution systemic symptoms (DRESS).
CHILD 291 mL (6 mL/kg) of 300 mg/mL solution
Severe liver and kidney functional disturbances, severe
thyrotoxicosis, or myelomatosis (use with extreme care);
Pheochromocytoma (measures for the treatment of
hypertensive crisis should be readily available);
Thyroid storm;
Renal impairment;

641
 VARIOUS

Hypotension; Maintaining the patient post-myelography in an upright

Slowed aortic circulation (increased likelihood for muscle position (via wheelchair or ambulation) may help
spasm); minimize adverse effects.
Epilepsy, severe cardiovascular disease, chronic
alcoholism, or multiple sclerosis (use with caution); Pregnancy Category: B
Elderly;
Children; ATC Code: V08AB02
Lactation.

Adverse Drug Reactions:

Common: Arrhythmias, angina, nausea, vomiting,
hypotension, photomas, headache, pain, dizziness
(transient), backache
Less Common: Asystole, cardiac failure, bradycardia,
tachycardia, vasovagal reaction, dyspnea, rhinitis,
coughing, laryngitis, urticaria, warm sensation
Rare: Diarrhea, dyspepsia, cramp, dry mouth, purpura,
abscess, pruritus, fever, hives, stomachache, visual
hallucination, neurological changes
Drug Interactions:
NOTE: Do NOT admix with other pharmaceuticals. Many
radiopaque contrast agents are incompatible in vitro with
many other drugs.
Avoid concomitant use with:
Increases risk of adverse or toxic effects Iohexol, specifically
seizures
[NOTE: Discontinue the following drugs at least 48 hours
prior to myelography]:
CNS Stimulants, MAO Inhibitors e.g., Phenothiazine
Derivatives
Tricyclic Antidepressants e.g. Amitriptyline
Major tranquilizers, Anti- psychotics
Administration: Always administer the lowest dose
necessary to obtain adequate visualization. Apply sterile
technique in the withdrawal from container and
administration of the product.
V
Rx IOPAMIDOL
Inj.: 612 mg/mL equivalent to 300 mg iodine, 50 mL and
100 mL vial
755 mg/mL equivalent to 370 mg iodine, 50 mL and
100 mL vial or bottle
A non-ionic radiopaque contrast that permits radiographic
visualization of the internal structures of the human body
by opacifying vessels in the path of flow of the contrast
medium.
Indications: For angiography throughout the cardiovascular
system, including cerebral and peripheral arteriography,
coronary arteriography and ventriculography, selective
visceral arteriography, and aortography; for peripheral
venography (phlebography); for angiocardiography; for
computed tomographic (CT) imaging of the head and
body.
Dose:
NOTE: Individualize dose and concentration based on age,
body size, size of the vessel and its blood flow rate,
anticipated pathology and degree and extent of
opacification required, structure(s) or area to be
examined, disease processes affecting the patient, and
equipment and technique to be employed. Use the
lowest dose necessary to obtain adequate visualization
to reduce the possibility of an adverse reaction.

Visually inspect for particulate matter and discoloration By rapid IV injection,

prior to administration. Slightly warm to body Procedure 300 mg Iodine
temperature immediately prior to injection.
Cerebral ADULT, 8–12 mL with total multiple
Patients should be well hydrated prior to and following Arteriography doses ranging to 90 mL
administration of any contrast medium. ADULT, 5–40 mL into the femoral or
Peripheral
subclavian artery; 25–50 mL into the
Arteriography
For intrathecal administration, always keep the head aorta
elevated above the highest level of the spine. Do not Cerebral ADULT, 8–12 mL with total multiple
lower head of table more than 15o in moving contrast Arteriography doses ranging to 90 mL
medium cranially. Inject slowly (over 1–2 minutes) to ADULT, 5–40 mL into the femoral or
Peripheral
avoid excessive mixing. To maintain as a bolus, move subclavian artery; 25–50 mL into the
Arteriography
medium to distal area very slowly. Use fluoroscopic aorta
monitoring.
By rapid IV injection,
Avoid intracranial entry of bolus. Avoid early and high Procedure 370 mg Iodine
cephalad dispersion of the medium. Avoid abrupt or
active patient movement to minimize excessive mixing of Selective ADULT, 50 mL into the aorta or
medium with CSF. Instruct patient to remain passive. Visceral celiac artery; 10 mL into the renal
Move patient slowly and only as necessary. Arteriography and arteries (maximum total dose,
Aortography 225 mL)
NOTE: In patients with excessive lordosis, consider lateral Pediatric CHILD 10–18 years, 20–50 mL
position for injection and movement of the medium Angiocardiography CHILD 2–9 years, 15–30 mL
cephalad. (single injection) CHILD <2 years, 10–15 mL

By rapid IV injection,

642
VARIOUS

Procedure 370 mg Iodine WARNING: Potentially hazardous in patients with

CHILD 10–18 years, 125 mL multiple myeloma or other paraproteinemia,
Pediatric particularly therapeutically resistant anuria.
Angiocardiography CHILD 5–9 years, 100 mL
(cumulative Development of severe cutaneous adverse
CHILD 2–4 years, 50 mL
injection) reactions (SCAR) may develop after 1 hour to
CHILD <2 years, 40 mL several weeks following IV administration,
ADULT, 2–10 mL for selective including Stevens-Johnson syndrome and toxic
coronary artery injections; 25–50 epidermal necrolysis (SJS/TEN), acute
Coronary
mL following injection at the generalized exanthematous pustulosis (AGEP)
Arteriography and
aortic root (maximum total dose and drug reaction with eosinophilia and
Ventriculography
for combined procedures, 200 systemic symptoms (DRESS).
mL)
Blood coagulation;
By rapid IV injection
Thrombosis, phlebitis, severe ischemic disease, local
370 mg infection, or total obstructed venous system (use with
Procedure 300 mg Iodine
Iodine special care when venography is performed);
ADULT, Renal and hepatic impairment;
ADULT, 50 mL Thyroid storm;
40 mL
Excretory Diabetes;
Urography CHILD, 1.2 to 3.6 mL/kg,
Children (at higher risk of experiencing adverse events, eg.,
not to exceed a total dose
asthma, cyanotic heart disease, and congestive heart
of 30 g Iodine
failure);
Lactation.
Dose Adjustment:
Pheochromocytoma: Adverse Drug Reactions:
Administer absolute minimum amount required. Common: Hot flashes, angina pectoris, flushing,
bradycardia, hypotension, hives, pain, burning
Precautions: sensation, nausea, warmth
WARNING: NOT for intrathecal use. Inadvertent Less Common: Tachycardia, hypertension, myocardial
intrathecal administration has resulted in death, ischemia, circulatory collapse, bigeminy, extrasystoles,
convulsions, cerebral hemorrhage, coma, ventricular fibrillation, angina pectoris, transient
paralysis, arachnoiditis, acute renal failure, ischemic attack, thrombophlebitis, vasovagal reaction,
cardiac arrest, seizures, rhabdomyolysis, tingling in arms, grimace, faintness, vomiting, anorexia,
hyperthermia, and brain edema. throat constriction, dyspnea, pulmonary edema, rash,
urticaria, pruritus, headache, fever, chills, excessive
WARNING: Procedures involving radiopaque sweating, back spasm, taste alterations, nasal
diagnostic agents should only be done by congestion, visual disturbances, urinary retention
qualified personnel with in- depth knowledge of

the procedure to be done. Emergency treatment
for severe reactions and appropriate facilities
needs to be readily available should there be
any complication in the procedure. Severe
delayed reactions may occur after
administration; well- trained personnel and
emergency facilities should be readily available
within 30- 60 minutes after administration.
Serious, rarely fatal, thromboembolic events
causing myocardial infarction and stroke have
been reported during angiographic procedures.
To minimize thromboembolic events, meticulous
IV administration techniques are recommended,
including close attention to guidewire and
catheter manipulation, use of manifold systems
and/or three-way stopcocks, frequent catheter
flushing with heparinized saline solutions, and
minimizing the length of the procedure. Use of
plastic syringes in place of glass syringes has
been reported to decrease but not eliminate the
likelihood of in vitro clotting.
May promote sickling in individuals who are
homozygous for sickle cell disease if injected
intravenously or intra-arterially.
V
Drug Interactions:
Monitor closely with:
Increases risk of adverse or toxic effects of
Cholecystographic Agents (renal toxicity)
TEST INTERACTION. May interfere with iodine uptake
studies, which depend on iodine estimations for up to 16
days following administration.
Administration: For IV and other parenteral routes as
appropriate.
Perform all preparation and administration processes in
a suitable work area, such as laminar flow hood, utilizing
aseptic technique. Warm solution to body temperature
shortly before administration to improve tolerability and
ease of injection. Do NOT admix with other drugs,
solutions, or total parenteral nutrition mixtures.
Draw product into the syringe and administer using
sterile technique. The container-closure system may be
penetrated only one time. Once punctured, do NOT
remove from aseptic work area during the entire period
of use. Fluid transfer should be completed no longer than
10 hours from withdrawal of contents.

643
 VARIOUS

Visually inspect parenteral products for particulate ADULT, 300 mg

matter and discoloration prior to administration. Discard Iodine per kg
products that show signs of crystallization or damage to (maximum total
the container-closure system, including the glass dose, 100 mL,
container, stopper and/or crimp. Excretory equivalent to 30 g
Urography Iodine)
Discard 10 hours after initial puncture. Discard unused CHILD, 1–2
portions. mL/kg, not to
exceed 3 mL/kg as
NOTE: Patients should be well hydrated prior to and total dose
following administration. ADULT, 50–200 ADULT, 41–162
mL mL
Pregnancy Category: B Contrast CHILD, 1–2
CT, head mL/kg, not to
ATC Code: V08AB04
exceed 3 mL/kg as
total dose
ADULT, 50–200 ADULT, 41–162
Rx IOPROMIDE mL by bolus mL by bolus
injection injection
(maximum total (maximum total
Inj.: 300 mg/mL equivalent to 623 mg iodine, 50 mL and dose, 200 mL, dose, 162 mL,
100 mL vial equivalent to 60 g equivalent to 60 g
370 mg/mL equivalent to 769 mg iodine, 50 mL and Iodine) Iodine)
100 mL vial ADULT, 100–200 ADULT, 81–162
Contrast mL by rapid mL by rapid
A non-ionic, water soluble x-ray contrast agent that permits CT, body infusion infusion
radiographic visualization of the internal structures of (maximum total (maximum total
the human body by opacifying vessels in the path of flow dose, 200 mL, dose, 162 mL,
of the contrast medium via intravascular administration. equivalent to 60 g equivalent to 60 g
Iodine) Iodine)
Indications: Radiocontrast media; for cerebral and
CHILD, 1–2
peripheral arteriography; for coronary arteriography and
mL/kg, not to
left ventriculography, visceral angiography, and
exceed 3 mL/kg as
aortography; for IV excretory urography; for contrast CT
total dose
imaging of head and body

Dose:
Dose Adjustment:
By intra-arterial injection,
Renal Impairment and Pheochromocytoma:
V

Procedure 300 mg/mL Administer absolute minimum amount required.

ADULT, 3–12 mL into the carotid
arteries; Precautions:
Cerebral
4–12 mL into the vertebral arteries; WARNING: NOT for intrathecal use. Inadvertent
Arteriography
20–50 mL into the aortic arch; intrathecal administration may cause death,
(maximum total dose, 150 mL) convulsions, cerebral hemorrhage, coma,
ADULT, 5–40 mL into the subclavian or paralysis, arachnoiditis, acute renal failure,
femoral artery; cardiac arrest, seizures, rhabdomyolysis,
Peripheral
25–50 mL into the aortic bifurcation hyperthermia, and brain edema.
Arteriography
(distal runoff)
(maximum total dose, 250 mL) WARNING: Procedures involving radiopaque
diagnostic agents should only be done by
By intra-arterial injection, qualified personnel with in- depth knowledge of
Procedure 370 mg/mL the procedure to be done. Emergency treatment
Coronary ADULT, 3–14 mL into the right or for severe reactions and appropriate facilities
Arteriography left coronary artery; needs to be readily available should there be
And Left 30–60 mL into the left ventricle any complication in the procedure. Severe
Ventriculography (maximum total dose, 225 mL) delayed reactions may occur after
Cardiac administration; well- trained personnel and
CHILD >2 years, 1–2 mL/kg; not to emergency facilities should be readily available
Chambers and
exceed 4 mL/kg as total dose within 30- 60 minutes after administration.
related arteries
Life-threatening or fatal, anaphylactoid
By IV injection, reactions, may occur during or after
administration.
Procedure 300 mg/mL 370 mg/mL

644
VARIOUS

Development of severe cutaneous adverse

reactions (SCAR) may develop after 1 hour to
several weeks following IV administration,
including Stevens-Johnson syndrome and toxic
epidermal necrolysis (SJS/TEN), acute
generalized exanthematous pustulosis (AGEP)
and drug reaction with eosinophilia and
systemic symptoms (DRESS).
Cardiovascular reactions;
Heart failure;
Thromboembolic complications (eg. local and distal organ
damage, ischemia, thromboembolism, and organ
failure, including stroke, brachial plexus palsy, chest
pain, myocardial infarction, sinus arrest, hepato-renal
function abnormalities);
Pheochromocytoma;
Thyroid storm;
Renal impairment;
Nervous system effects (may disrupt blood-brain barrier;
may accumulate in the brain);
Lactation.
Adverse Drug Reactions:
Common: Headache, dysgeusia, abnormal vision, chest
pain, vasodilation, nausea, vomiting, back pain, urinary
urgency, injection site and infusion site reactions, pain
Less Common: Atrioventricular block, bradycardia,
ventricular extrasystole, abdominal discomfort,
abdominal pain, abdominal pain upper, constipation,
diarrhea, dry mouth, dyspepsia, gastrointestinal
disorder, gastrointestinal pain, increased salivation,
stomach discomfort, rectal tenesmus, asthenia, chest
discomfort, chills, excessive thirst, extravasation, feeling
hot, hyperhidrosis, malaise, edema peripheral, pyrexia,
asthma, face edema, arthralgia, musculoskeletal pain,
myasthenia, neck pain, pain in extremity, agitation,
confusion, convulsion, dizziness, hypertonia,
hypesthesia, incoordination, neuropathy, somnolence,
Do NOT admix with other drugs, solutions, or total
parenteral nutrition mixtures.
For intra-arterial administration, administer at a flow rate
approximately equal to the flow rate in the vessel being
injected
NOTE: Patients should be well hydrated prior to and
following administration.
Pregnancy Category: B
ATC Code: V08AB05
Rx IOVERSOL
Inj.: 636 mg/mL equivalent to 300 mg/mL iodine, 50 mL
and 100 mL vial
741 mg/mL equivalent to 350 mg/mL iodine, 50 mL
and 100 mL vial
A non ionic radiographic contrast agent that opacifies
vessels in the path of the flow of ioversol resulting in
adiographic visualization of the internal structures.
Indications: Radiocontrast media for cerebral and
peripheral arteriography, coronary arteriography, and left
ventriculography; for angiocardiography; for CT imaging
of the head and body, venography, and IV excretory
urography; for IV digital subtraction angiography (IV-DSA)
Contraindications: Symptomatic hyperthyroidism
Dose:
NOTE: Use the lowest dose necessary to obtain adequate
visualization to reduce the possibility of an adverse

V
speech disorder, tremor, paresthesia, visual field defect, reaction. Individualize dose and concentration to be
anxiety, dysuria, renal pain, urinary retention, apnea, used, considering age, body size, size of the vessel and
increased cough, dyspnea, hypoxia, pharyngeal edema, its blood flow rate, anticipated pathology and degree and
pharyngitis, pleural effusion, pulmonary hypertension, extent of opacification required, structure(s) or area to
respiratory disorder, sore throat, coronary artery be examined, disease processes affecting the patient,
thrombosis, flushing, hypertension, hypotension, and equipment and technique to be employed.
peripheral vascular disorder, syncope, vascular anomaly
By intra-arterial injection
Drug Interactions: Procedure 300 mg/mL 350 mg/mL
Monitor closely with:
Cerebral
Increases risk of adverse or toxic effects of the following
Arteriography ADULT, 2–12
drugs:
(carotid or mL
Biguanides (lactic acidosis)
vertebral arteries)
Cholecystographic Agents (renal toxicity)
Cerebral
Beta- blockers
Arteriography ADULT, 20–50
(aortic arc, four mL
TEST INTERACTION. May interfere with iodine uptake vessel study)
studies, which depend on iodine estimations for up to 16
CHILD, 1.25
days following administration
mL/kg (1 – 1.5
May obscure lesions seen on non-contrast CT scans.
mL/kg), up to
a maximum
Administration: Warm solution to body temperature shortly Angiocardiography
total volume of
before administration to improve tolerability and ease of
250 mL
injection.
(maximum
cumulative
Visually inspect for particulate matter and discoloration
prior to administration.

645
 VARIOUS

dose, 5 ADULT, 30–50 mL at

mL/kg) 12–20 mL/second,
IV-DSA
may repeat as
(peripheral
necessary
injection)
(maximum dose,
250 mL)

Dose Adjustment:
Peripheral ADULT, 60 mL (20–90 mL);
Geriatric:
Arteriography maximum cumulative dose, 250
Start at the low end of dosing range, reflecting the greater
(aortic-iliac runoff) mL
frequency of decreased hepatic, renal or cardiac
Peripheral function, and of concomitant disease or other drug
ADULT, 40 mL (10–50 mL);
Arteriography therapy.
maximum cumulative dose, 250
(common iliac or
mL
femoral artery) Pheochromocytoma:
Peripheral Administer absolute minimum amount required.
ADULT, 20 mL (15–30 mL);
Arteriography
maximum cumulative dose, 250
(subclavian or
mL
brachial artery) Precautions:
Coronary ADULT, 8 mL WARNING: NOT for intrathecal use. Inadvertent
Arteriography (2–10 mL); intrathecal administration may cause death,
And Left maximum convulsions, cerebral hemorrhage, coma,
Ventriculography cumulative paralysis, arachnoiditis, acute renal failure, cardiac
(left coronary) dose, 250 mL arrest, seizures, rhabdomyolysis, hyperthermia,
Coronary ADULT, 6 mL and brain edema.
Arteriography (1–10 mL);
And Left maximum
Ventriculography cumulative WARNING: Procedures involving radiopaque
(right coronary) dose, 250 mL diagnostic agents should only be done by qualified
Coronary ADULT, 40 mL personnel with in- depth knowledge of the
Arteriography (30–50 mL); procedure to be done. Emergency treatment for
And Left maximum severe reactions and appropriate facilities needs
Ventriculography cumulative to be readily available should there be any
(left ventricle) dose, 250 mL complication in the procedure. Severe delayed
reactions may occur after administration; well-
trained personnel and emergency facilities should
By IV infusion
be readily available within 30- 60 minutes after
Procedure 300 mg/mL 350 mg/mL administration.
CT, head ADULT, 50–150 mL Procedures involving radiopaque diagnostic
V

agents should only be done by qualified personnel

CT, body ADULT, 50–150 mL with in- depth knowledge of the procedure to be
done. Emergency treatment for severe reactions
By IV bolus injection and appropriate facilities needs to be readily
Procedure 300 mg/mL 350 mg/mL available should there be any complication in the
procedure. Severe delayed reactions may occur
CT, body ADULT, 25–75 mL ADULT, 25–75 mL after administration; well- trained personnel and
emergency facilities should be readily available
By IV injection within 30- 60 minutes after administration.
Procedure 300 mg/mL 350 mg/mL Life-threatening or fatal cardiovascular reactions
have occurred, including cardiac arrest,
ADULT, 50–100 mL per extremity hypotensive collapse, and shock.
Venography
(maximum cumulative dose, 250 mL) Can cause life-threatening or fatal hypersensitivity
ADULT, 50– reactions, including anaphylaxis and anaphylactic
ADULT, 50–75 mL
IV 75 mL shock.
(maximum dose,
Urography (maximum May promote sickling in individuals who are
140 mL)
dose, 150 mL) homozygous for sickle cell disease
ADULT, 1.6
ADULT, 1.4 mL/kg Severe cutaneous adverse reactions (SCAR) may
High Dose mL/kg develop from 1 hour to several weeks following IV
(maximum dose,
Urography (maximum administration, including Stevens-Johnson
140 mL)
dose, 150 mL) syndrome and toxic epidermal necrolysis
ADULT, 30–50 mL at (SJS/TEN), acute generalized exanthematous
10–30 mL/second, pustulosis (AGEP) and drug reaction with
IV-DSA
may repeat as eosinophilia and systemic symptoms (DRESS).
(central
necessary
catheter) Renal impairment;
(maximum dose,
250 mL) Extravasation;

646
VARIOUS

Pheochromocytoma; X-RAY CONTRAST MEDIA, NON-IODINATED

Thyroid storm;
Children;
Pregnancy; Rx BARIUM SULFATE
Lactation.
Oral: USP grade powder suspended in water, 340 and 454
Adverse Drug Reactions:
g pouch, LDPE bag
Common: Nausea
Less Common: Cardiac arrest, myocardial infarction,
Powder for suspension that acts as a positive radio contrast
arrhythmia, atrioventricular block, nodal rhythm,
agent for radiographic studies. Barium sulfate is not
bradycardia, angina pectoris, palpitations, vertigo,
absorbed or metabolized and is eliminate from the GIT
tinnitus, blurred vision, periorbital edema, conjunctivitis,
unchanged
vomiting, abdominal pain, dysphagia, dry mouth, chest
pain, pain, injection site pain, injection site hematoma,
Indications: Radiographical contrast media for upper and
extravasation, pyrexia, swelling, asthenia, malaise,
lower gastrointestinal procedures by conventional x-ray
fatigue, chills, rhinitis, heat injury, vascular
or computed tomography
pseudoaneurysm, ST-segment depression, decreased
blood pressure, acidosis, muscular weakness, muscle
Contraindications: Proximal to a known obstruction of the
spasms, back pain, cerebral infarction, aphasia, tremor,
colon; known or suspected GI perforation.
dizziness, presyncope, headache, paresthesia,
dysgeusia, hallucination, disorientation, anxiety, urinary
Dose:
retention, renal pain, polyuria, laryngeal edema, hypoxia,
NOTE: Determine volume to be administered based on
pulmonary edema, dyspnea, hyperventilation, cough,
degree and extent of contrast required in the area(s)
sneezing, nasal congestion, urticaria, rash, pruritus,
under examination and on the technique employed.
swelling face, hyperhidrosis, erythema, hypertension,
hypotension, arterial spasm, vasospasm, vasodilation,
GI tract marking, by mouth, ADULT, 900–1,350 mL of
flushing
prepared suspension, 20–30 minutes prior to scheduled
procedure; for improved gastric marking, consume the
Drug Interactions:
final 200 mL immediately prior to the scan.
Monitor closely with:
Increases risk of adverse or toxic effects of the following
Dose Adjustment:
drugs:
Patients with history of food aspiration:
Cholecystographic Agents (renal toxicity), Metformin
Administer initially small amounts such as ½ teaspoon and
(lactic acidosis)
carefully observe swallowing under fluoroscopic control.
Avoid concomitant use with:
Obesity and patients with delayed transit:
Reduces therapeutic effect of Radioactive Iodine (interferes
Increase total volume up to 1,800 mL.
with thyroid uptake)
Precautions:

TEST INTERACTION. May interfere with iodine uptake
studies, which depend on iodine estimations for up to 16
days following administration.
Administration: For IV use only.
Use sterile technique for all handling and administration.
Warm and administer at body or room temperature.
Visually inspect for particulate matter or discoloration
before administration. Inspect glass and plastic
containers prior to use for breakage or other damage and
do not use damaged containers. Do NOT admix with
other drugs, solutions, or total parenteral nutrition
mixtures.
Avoid extravasation when injecting, especially in patients
with severe arterial or venous disease. Discard unused
portion after use.
NOTE: Patients should be well hydrated prior to and
following administration.
Pregnancy Category: B
ATC Code: V08AB07
V
WARNING: MRI Studies. Diagnostic procedures
involving the use of radiopaque contrast agents
should be carried out under the direction of
personnel with the requisite training and a
thorough knowledge of the particular procedure to
be performed.
Allergic Reactions. A history of bronchial asthma,
atopy, or a previous reaction to a contrast agent,
warrant special attention. Use with caution in
severely debilitated patients and in those with
marked hypertension or advanced cardiac disease.
History of food aspiration (barium swallow studies required);
Pregnancy (use radiographic procedures only if deemed
essential).
Adverse Drug Reactions:
Less Common: weakness, pallor, tinnitus, diaphoresis,
bradycardia
Rare: Aspiration pneumonitis, barium impaction, granuloma
formation, intravasation, embolization, peritonitis,
vasovagal episodes, syncopal episodes, fatalities,
generalized pruritus, erythema, urticaria, laryngeal
edema, bronchospasm, hypotension, peripheral
vasodilation, hypotension, reflex tachycardia, dyspnea,

647
 VARIOUS

agitation, confusion, cyanosis, unconsciousness, severe Dosing chart

stomach cramps (transient), diarrhea (transient) Body weight Total volume
Drug Interactions: No information found kg lb (mL)
TEST INTERACTION. May appear as a negative GI marker 10 22 2
with certain pulse sequences in MR studies. 20 44 4
30 66 6
Administration: Prepare solution to a concentration of 0.1%
40 88 8
w/v or 0.1% w/w. To be administered on an empty
50 110 10
stomach, free of fluids as much as possible. Patients
should be instructed to neither eat nor drink after the 60 132 12
evening meal on the night preceding the examination. 70 154 14
80 176 16
Rehydrate patient as quickly as possible following 90 198 18
barium study of the GI tract to prevent impaction of 100 220 20
barium. Cathartics may also be required. 110 242 22
120 264 24
NOTE: Saline cathartics are recommended on a routine 130 286 26
basis, especially in patients with a history of constipation,
unless clinically contraindicated. NOTE: Dosing in patients >286 lbs has not been studied
systematically.
If enema tips are used, use caution during insertion. Too
forceful or deep insertion may cause tearing or Precautions:
perforation of the rectum. WARNING: NOT for use in nephrogenic system fibrosis
(NSF). May result in fatal or debilitating fibrosis
If balloon retention tips are used, inflate under affecting the skin, muscle, and internal organs. Do
fluoroscopic control by qualified personnel. NOT administer in patients with chronic, severe
kidney disease (GFR <30 mL/min per 1.73 m2) or
NOTE: Use caution to avoid over-inflation. Overfilling or acute kidney injury. Do NOT exceed the
asymmetrical filling with tip displacement may occur, recommended dose and allow a sufficient period
which can lead to rectal perforation or barium for elimination prior to any re-administration.
granulomas.
Hypersensitivity reactions (eg. anaphylactoid and
Pregnancy Category: Not classified
anaphylactic reactions, with cardiovascular, respiratory
and/or cutaneous manifestations, resulting in death);
ATC Code: V08BA01; V08BA02
Injection site reactions (eg. skin and soft tissue necrosis,
thrombosis, fasciitis, and compartment syndrome
requiring surgical intervention);
MAGNETIC RESONANCE IMAGING CONTRAST
V

Renal failure (risk of renal failure may increase with

MEDIA
Rx DIMEGLUMINE GADOPENTETATE
Inj.: 469 mg/mL aqueous solution, 5 mL, 10 mL, and 20
mL vial
The N-methylglucamine salt of the gadolinium complex of
diethylenetriamine penta-acetic acid. It is an injectable
contrast medium for magnetic resonance imaging (MRI).
It is a paramagnetic agent that develops a magnetic
moment when placed in a magnetic field.
Indications: For use with MRI to visualize lesions with
abnormal vascularity in the brain (intracranial lesions),
spine and associated tissues, head and neck; for
visualization of intracranial lesions,; to
Contraindications: Chronic, severe kidney disease; acute
kidney injury.
increasing dose);
Children;
Lactation.
Adverse Drug Reactions:
Common: Headache, nausea, injection site coldness or
localized coldness, dizziness
Less Common: Injection site reactions, substernal chest
pain, back pain, pyrexia, asthenia, feeling cold,
generalized warmth, fatigue, chest tightness,
anaphylactoid reactions, hypotension, hypertension,
tachycardia, migraine, syncope, vasodilatation, pallor,
abdominal discomfort, teeth pain, increased salivation,
abdominal pain, vomiting, diarrhea, agitation, anxiety,
thirst, somnolence, diplopia, loss of consciousness,
convulsions, paresthesia, throat irritation, rhinitis,
sneezing, rash, sweating, pruritus, urticaria, facial
edema, conjunctivitis, taste abnormality, dry mouth,
lacrimation, eye irritation, eye pain, ear pain
Drug Interactions: No known significant interactions

Dose: TEST INTERACTION. May impair visualization of lesions seen

MRI visualization, by IV injection, ADULT, 0.2 mL/kg (0.1 on non-contrast MRI.
mmol/kg) at a rate not exceeding 10 mL per 15 seconds.
Administration: For IV administration. Administer at a rate
not to exceed 10 mL per 15 seconds. Follow with a 5-mL

648
VARIOUS

normal saline flush to ensure complete injection.
Complete imaging procedure within 1 hour of
administration.
Visually inspect parenteral products for particulate
matter and discoloration prior to administration.
Discard any unused portion. Discard IV tubing and
syringes used.
Preparation from bulk package:
Transfer from bulk package in an aseptic work area, such
as a laminar flow hood, using aseptic technique. Once
punctured, do NOT remove from aseptic work area
during the entire 24-hour period of use. Use contents
within 24 hours of initial puncture. Discard all unused
portions 24 hours after initial puncture.
Prior to initiating, determine blood pressure and weight
to evaluate patient's volume status and signs and
symptoms of pulmonary congestion or respiratory
distress.
NOTE: Obtain a basic metabolic panel of serum chemistries
on the morning of the procedure and on post-procedure
days 1 and 2 or until any increase of serum creatinine
resolves. Obtain urinary pH measurement after initial
bolus.
Make sure urine flow is at 150 mL/hour after procedure
to ensure adequate hydration.
Pregnancy Category: Category

Pregnancy Category: C ATC Code: Not available

ATC Code: Not available

MAGNETIC RESONANCE IMAGING CONTRAST
MEDIA
Rx GAS FORMING AGENT
PARAMAGNETIC CONTRAST MEDIA
Oral:
Components per tablet: Rx GADOBUTROL
Sodium bicarbonate 470 mg
Glutamic acid 70 mg
Tartaric acid 420 mg Inj: 1.0 mmol/mL solution for injection, 15 mL vial
Silicon resin 25 mg 1.0 mmol/mL solution for injection, 5 mL pre-filled
syringe
Indications: Radiocontrast media
Gadobutrol is a gadolinium-containing, nonionic
Contraindications: Volume overload. paramagnetic agent. Exposure to an external magnetic
field induces a large local magnetic field in exposed
Dose: tissues. The local magnetism disrupts water protons in
Condition, route, ADULT/CHILD, Dose. the vicinity, resulting in a change in proton density and
spin characteristics which can be detected by imaging
Dose Adjustment: device.

V
Renal Impairment:
If CrCl <15 mL/minute, refer patient to a specialist. Indications: Use in diagnostic magnetic resonance imaging
(MRI) in adults and children.
Precautions:
Electrolyte abnormalities (e.g., hypokalemia); Contraindications: Severe hypersensitivity reactions to
Volume overload, CHF, hypertension, and oliguric renal gadobutrol or any component of the formulation.
failure (use with caution due to high sodium content).
Dose:
Adverse Drug Reactions: None known Magnetic resonance imaging, by IV injection, ADULT and
CHILD, 0.1 mmol/kg (0.1 mL/kg).
Drug Interactions:
Avoid concomitant use with: Dose Adjustment:
Increases risk of adverse or toxic effects of Gas Forming
Renal impairment:
Dose adjustment is not recommended. However, risk for
Agent, specifically nephrotoxicity [withhold drug the day
NSF development increases as renal function decreases.
before and the day of the procedure]:
Acyclovir, Amphotericin B, Aminoglycosides, Gadobutrol is removed by hemodialysis.
Cyclosporine, Foscarnet, Loop Diuretics e.g. Furosemide,
NSAIDs Precautions:
May cause extravasation, gadolinium retention,
Increases risk of adverse or toxic effects of the following hypersensitivity reactions, nephrogenic systemic fibrosis;
Use in caution in patients with renal impairment and seizure
drugs:
disorder.
Metformin (lactic acidosis) [withhold drug prior to and for
48 hours after injection of gas forming agent]
Adverse Drug Reactions:
Administration: Do NOT administer using the same IV line as Less Common: Headache and nausea.
other IV medications.

649
 VARIOUS

Rare: Injection site reactions, dysgeusia, feeling hot, ATC Code: V08CA02
dizziness, vomiting, rash, pruritus, erythema, dyspnea,
paresthesia, cardiac arrest, nephrogenic systemic
fibrosis (NSF), and hypersensitivity/anaphylactoid DIAGNOSTIC RADIOPHARMACEUTICALS
reactions.

Drug Interactions: IOTHALAMATE

Rx
None known. (SODIUM IOTHALAMATE, 125I)
Administration: Do not administer other medications in the Inj.: 600 mg/mL, 30 mL, 50 mL, and 100 mL vial (usually
same IV line simultaneously. IV)

Pregnancy Category: C A sterile, nonpyrogenic aqueous injection containing

approximately 1 mg sodium iothalamate per mL. The
ATC Code: V08CA09 radioactive concentration of the material is
approximately 250–300 microCi/mL.

Indications: Contrast medium used orally in esophagograms

Rx GADOTERIC ACID and upper GI series

Inj: 0.5mmol/mL, 10 mL, 15 mL, and 20 mL vials Dose:

Gadolinium-based contrast agent for use in MRI of the brain,
spine, and associated tissues to detect and visualize
areas with disruption of the blood brain barrier and/or
vascularity.
Indications: Contrast medium for magnetic resonance
imaging (MRI) in central nervous system (CNS) and whole
body indications including angiography.
Contraindications: Hypersensitivity to gadoteric acid or any
component of the formulation.
Dose:
MRI imaging, by IV injection, ADULT and CHILD, 0.2 mL/kg
(0.1 mmol/kg).
Dose Adjustment:
V
Condition, route, ADULT/CHILD, Dose.
Dose Adjustment: No information found
Precautions:
WARNING: Take care to minimize radiation exposure
to patients and occupational workers.
Should be used by healthcare practitioners
qualified by training and experience in the safe use
and handling of radionuclides.
Children;
Pregnancy (administer only if clearly needed);
Lactation.
Adverse Drug Reactions: None reported

Renal impairment: Drug Interactions: No information found

Dose adjustment is not recommended. However, risk for
NSF development increases as renal function decreases. Administration: For intravenous administration. Do NOT
Gadoteric acid is removed by hemodialysis. administer by rapid or bolus-like injections.

Precautions: Do NOT administer via a central venous line.

May cause extravasation, gadolinium-retention,
hypersensitivity reactions, and nephrogenic systemic Inspect visually for particulate matter and discoloration
fibrosis; prior to administration.
Use in caution in patients with renal impairment.
Measure patient dose by suitable radioactivity
Adverse Drug Reactions: calibration system immediately prior to administration.
Less Common: Headache.
Rare: Nausea, injection site reactions, burning sensation, For continuous IV infusion, establish an adequate
feeling cold, rash, somnolence, fatigue, dizziness, diuresis by an oral water load of 1,500 mL 2 hours prior
vomiting, pruritus, asthenia, paraesthesia, dysgeusia, to the beginning of the clearance study. Insert a no. 14
pain in extremity, anxiety, hypertension, palpitations, and or 16 French Foley catheter aseptically into the bladder.
oropharyngeal discomfort. Start IV infusion lines of lactated Ringer’s solution in
each arm with two-way stopcocks (1 as injection site, 1
Drug Interactions: as blood withdrawal site). Divide dose equally into two (a
None known. priming dose to be injected as is and a sustaining dose
to be diluted in 30–60 mL of isotonic sodium chloride).
Administration: Infuse IV bolus at a rate of 1-2 mL per Inject priming dose into 1 arm, followed immediately by
second. To ensure complete injection, follow with saline the sustaining solution through the same site by IV
flush. infusion at 0.5 mL/minute. Discontinue the Lactated
Ringer’s solution during infusion. Wait 40–45 minutes to
Pregnancy Category: C achieve constant plasma concentration. Begin collecting

650
VARIOUS

urine samples every 15 minutes, 3 consecutive Dose equation corrected for 24-hour radioactive iodine
collection samples are sufficient for most clinical uptake:
studies. From the opposite arm, collect 5 mL blood Activity (mCi)
1
samples drawn 6 minutes prior to the midpoint of each ��gland wt in g × desired dose in mCi�g� �
24 hour uptake on %dose��
collection period, placed in heparinized tubes, mixed, =
1000
and centrifuged.
Thyroid cancer, by mouth, ADULT, 100–150 mCi (3,700 –
For single IV injection, administer Lugol’s solution, 3 5,550 megabecquerels).
drops orally, 3 times daily for 1–2 days prior to the test. Thyroid cancer, post-operative ablation of residual tissue, by
Begin oral water load 1 hour before the test. Start with mouth, ADULT, 50 mCi (1,850 megabecquerels).
20 mL/kg and force any clear liquid until the test is
complete. Empty the bladder and label sample as Urine Precautions:
control. Inject 10–30 mL and wait 30 to 60 minutes. WARNING: Adhere to radiation safety precautions
Collect the entire urine and label Urine discard. Draw 4– regarding radioactive iodine treatment. Use
5 mL of blood into a heparinized syringe and label appropriate precautions for handling and disposal.
Plasma #1. After another 30–60 minutes, collect the Wear waterproof gloves during preparation, handling,
entire urine and label Urine #1. Immediately draw and administration.
another blood specimen and label Plasma #2. After
another 30–60 minutes, collect the urine and label Urine
Hypersensitivity (eg. rash and hives);
#2. Immediately draw the last blood specimen and label Renal impairment;
Plasma #3. Infertility (eg. transient, dose-related testicular function
impairment);
Pregnancy Category: C
Radiation-induced thyroiditis (may occur with gland
enlargement and thyroid release);
ATC Code: V09CX03
Radiation toxicities (dose-dependent fatalities);
Thyroid enlargement (may occur with discontinuation; may
cause thyroid enlargement and obstructive
THERAPEUTIC RADIOPHARMACEUTICALS complications of the trachea, esophagus, or blood
vessels in the neck);
Elderly;
Patients <30 years (use is not recommended);
Rx SODIUM IODIDE 131 Children;
Pregnancy (may cause severe and irreversible
Oral: 0.8–100 mCi radioactivity range per capsule hypothyroidism in neonates);
1.0 to 250 mCi radioactivity range per capsule Lactation (excreted in breastmilk; discontinue
3.5–150 mCi radioactivity range solution per vial breastfeeding at least 4 weeks prior to therapy).

A radiopharmaceutical that is rapidly absorbed and Adverse Drug Reactions:

Common: Chest pain, tachycardia, metallic taste, alopecia,

distributed within the extracellular fluid of the body.
Iodide is concentrated in the thyroid via the
sodium/iodide symporter, and subsequently oxidized to
iodine. Beta emission of sodium iodide I131 destroys
thyroid tissue.
Indication: Treatment of hyperthyroidism and thyroid
carcinomas (if the lesions take up iodide) ; palliative
effects may be observed in patients with advanced
thyroid malignancy if the metastatic lesions take up
iodide
Contraindications: Preexisting vomiting and diarrhea
(treatment); concurrent antithyroid medication
(discontinue 3–4 days prior to administration) ; women
who are or may become pregnant; breastfeeding;
treatment of thyroid malignancies shown to have no
iodide uptake (including majority of medullary and
anaplastic carcinomas)
Dose:
NOTE: If dose or dose within range exceeds 1,000
microcuries, express dose as millicuries (mCi).
Hyperthyroidism, by mouth, ADULT, 4–10 mCi (148 to 370
megabecquerels).
V
pruritus, skin lesion (iododerma), skin rash, urticaria,
hypoparathyroidism, thyroid storm, hypothyroidism,
thyroiditis, gastritis, hyperthyroidism, nausea (high
dose), salivary gland disease, odynophagia, sialadenitis,
sore throat, unpleasant taste, vomiting, infertility
(transient; permanent in repeated or high dose), acute
leukemia, bone marrow depression (high dose),
hematologic abnormality, leukopenia, solid tumor,
thrombocytopenia, anaphylaxis, hypersensitivity
reaction, immunosuppression, neck discomfort
(tenderness or swelling), lacrimation, bronchospasm,
anemia, cough, chromosomal abnormality, local
swelling, radiation injury
Less Common: Conjunctivitis, epiphora, radiation
pneumonitis, xerophthalmia, xerostomia
Rare: Neoplasm
Drug Interactions:
Avoid concomitant use with:
Reduces therapeutic effect of Sodium Iodide I131:
Amiodarone
Antithyroid Agents [discontinue therapy 3 to 4 days prior
to sodium iodide I131 administration]
Thyroid Products
Administration: Ensure adequate hydration before and after
treatment.

651
 VARIOUS

Pregnancy Category: X

ATC Code: V10XA01

V

652
HERBAL PREPARATIONS
HERBAL PREPARATIONS
LAGUNDI
OTC [Vitex negundo L. (Fam.
Verbenaceae)]
Oral: 300 mg and 600 mg tablet
300 mg/5 mL syrup, 60 mL and 120 mL bottle
A natural medicinal preparation from the leaves of Vitex
negundo Linn. (Fam. Verbenaceae), which is used for the
relief of cough.
Indication: For the relief of mild to moderate cough due to
common colds and flu
Contraindications: Patients with severe allergy to Vitex
negundo or any of its components
Dose:
Cough, by mouth, ADULT, as 600 mg tablet, 1 tablet 3–4
times daily; as 300 mg/5 mL, 2 tsp 3-4 times per day;
CHILD 7–12 years, 1 tablet 3–4 times daily; as 300
mg/5 mL syrup, 10 mL (2 tsp) 3–4 times daily,; CHILD,
15 mg/kg per dose (0.25 mL/kg per dose for 300 mg/5
mL) administered 3 times daily; CHILD >40 kg body
weight, 2 tsp 3 times per day of 300 mg/5 mL; CHILD 6–
12 years (20–40 kg), 1½ to 2 tsp of 300 mg/5 mL 3
times per day; CHILD 4–6 years (15.5–20 kg), 1 tsp of
300 mg/5 mL 3 times daily; CHILD 2–4 years (10–15.5
kg), ½ to 1 tsp of 300mg/5mL syrup 3 times per day.
Dose Adjustment: All clinical trials were performed in
patients with normal renal and liver function tests; no
reports of adverse events in patients with renal and liver
dysfunction.
Precautions:
Patients with known allergy to lagundi plants.
Adverse Drug Reactions: Mild adverse effects have been
observed, such as itchiness, nausea, vomiting, and
diarrhea.
Drug Interactions: Possible interaction with ibuprofen,
potentiates anti-inflammatory activity
Administration: For syrup preparation, shake well before
use. May be taken with or without food.
Pregnancy Category: In vitro and animal studies have shown
Lagundi to be non-mutagenic and non clastogenic.
ATC Code: Not Available
SAMBONG
OTC [Blumea balsamifera (L.) DC (Fam.
Compositae)]
Oral: 500 mg tablet
A natural medicinal preparation from the leaves of Blumea
balsamifera Linn. DC (Fam. Asteraceae), which is utilized
in the treatment of urological disorders.
Indications: To increase urinary output in conditions
characterized by fluid retention or edema; for treatment
and prevention of kidney stones.
Contraindications: Patients with severe allergy to sambong
or any of its components.
Dose:
Anti-urolithiasis, by mouth, ADULT, for the 1st 2 weeks, give
40 mg/kg/day in 3 divided doses, then decrease to
20/mg/kg/day in 2-3 divided doses; CHILD 7–12 years,
1st 2 weeks give 40 mg/kg/day in 3 divided doses, then
decrease to 20/mg/kg/day in 2-3 divided doses.
Dose Adjustment: Clinical trials were performed in patients
with normal renal and liver function tests; no reports of
adverse effects in patients with renal and liver
dysfunction.
Precautions:
Patients with excretory urogram showing signs of renal
obstruction.
Pregnancy and lactation.
Adverse Drug Reactions: Epigastric pain, constipation.
Drug Interactions: None known
Administration: May be taken with or without food.
Pregnancy Category: In vitro and animal studies have shown
Sambong to be non-mutagenic and non clastogenic.
X
ATC Code: Not Available
TSAANG GUBAT
OTC [Carmona retusa (Vahl) Masam (Fam.
Boraginaceae)]
Oral: 250 mg tablet
A natural medicinal preparation from the leaves of Carmona
retusa (Vahl) Masam (Fam. Boraginaceae) used for the
treatment of biliary colic.
Indications: For the management of acute diarrhea, colic
from acute gastroenteritis and biliary colic; anti-motility;
antispasmodic.
Contraindications: Severe allergy to tsaang gubat or any of
its components.
Dose:
Acute diarrhea, colic from acute gastroenteritis, biliary colic,
by mouth, ADULT, 15 mg/kg/dose, may repeat after 6
653
 HERBAL PREPARATIONS

hrs up to 3times a day; CHILD 7–12 years, 15

mg/kg/dose, may repeat after 6 hrs up to 3 times per
day.

Dose Adjustment: Clinical trials were performed in patients

with normal renal and liver function tests; no reports of
adverse effects in patients with renal and liver
dysfunction.

Precautions:
When symptoms persist, or irritation occurs, stop and
consult your doctor.

Adverse Drug Reactions: Nausea

Drug Interactions: None known

Administration: May be taken with or without food.

Pregnancy Category: In vitro and animal studies have shown

Tsaang Gubat to be non-mutagenic and non clastogenic.

ATC Code: Not available

V

654
APPENDICES
 SUMMARY STATISTICS
No. of Sections of Therapeutics Categories = 15

No. of active ingredients = 631

No. of active ingredients added = 92 (see Appendix B)

No. of active ingredients deleted = 88 (see Appendix C)

No. of pharmaceutical products not registered with

the FDA but considered essential = 35 (see Appendix D)

No. of Dangerous Drug Preparations (A1) = 16 (see Appendix E)

No. of Controlled Chemicals (A2) = 2 (see Appendix F)

No. of essential medicines with narrow therapeutic

index/range = 10 (see Appendix G)

No. of reserve antimicrobials = 11 (see Appendix H)

No. of medicinal plant products registered with the

FDA and included in the PNF = 3 (see Appendix I)

A1
 LIST OF DRUG MOLECULES ADDED TO THE PHILIPPINE
NATIONAL FORMULARY (PNF) 8TH EDITION
(as of SEPTEMBER 2019)
1. Abacavir 34. 3% Hypertonic Saline Solution
2. Amino acid + carbohydrate + 35. Imiglucerase
multivitamins + electrolytes 36. Imiquimod
3. Amino acid + glucose + electrolytes + 37. Inactivated Poliomyelitis Vaccine (Type
vitamin B1 1, 2 and 3)
4. Anastrozole 38. Indacaterol + glycopyrronium
5. Aripiprazole 39. Iodixanol
6. Artesunate 40. Iron sucrose
7. Atorvastatin calcium 41. Isotonic electrolyte solution
8. Aztreonam 42. Lamivudine + Efavirenz + Tenofovir
9. Bedaquiline fumarate 43. Lamivudine + Tenofovir
10. Bicalutamide 44. Lamivudine + Zidovudine
11. Capreomycin 45. Lamivudine + Zidovudine + Nevirapine
12. Carbetocin 46. Lamotrigine
13. Carboprost 47. Latanoprost + timolol maleate
14. Clotrimazole 48. Levetiracetam
15. Colistin 49. Letrozole
16. Cycloserine 50. Linezolid
17. Daclatasvir 51. Lopinavir + Ritonavir
18. Deferasirox 52. Measles and Rubella vaccine (Live
19. Delamanid attenuated)
20. Diphtheria, Tetanus, Pertussis, 53. Memantine
Hepatitis B Recombinant and 54. Micafungin
Haemophilus Influenza Type B (Hib) 55. Micronutrient Powder
Combined Vaccine 56. Moxifloxacin
21. Donepezil 57. Nicotine
22. Efavirenz 58. Olodaterol
23. Entecavir 59. Oxcarbazepine
24. Eperisone hydrochloride 60. Oxycodone + naloxone
25. Etonogestrel 61. Paliperidone palmitate
26. Formoterol 62. Para-aminosalicylic acid
27. Fosfomycin 63. Phospholipid fraction from bovine lung
28. Fluticasone + Formoterol 64. Polymixin B sulfate
29. Gadobutrol 65. Poractant alfa
30. Gadoteric acid 66. Prothionamide
31. Human Papillomavirus vaccine types 67. Rabeprazole sodium
16 and 18 (Recombinant, AS04 68. Remifentanil
Adjuvanted) 69. Ribavirin
32. Human Recombinant Tissue Type 70. Rifaximin
Plasminogen Activator (Alteplase) 71. Rifapentine
33. Hypertonic Lactate Solution 72. Rilpivirine

A2
 73. Sacubitril + valsartan 83. Tenofovir disoproxil fumarate
74. Sevelamer carbonate 84. Terazosin hydrochloride
75. Sofosbuvir 85. Tolvaptan
76. Sofosbuvir + ledipasvir 86. Triclabendazole
77. Sofosbuvir + velpatasvir 87. Tropicamide + phenylephrine
78. Soya bean oil + Medium chain 88. Valganciclovir
triglycerides + Olive oil + Purified fish oil 89. Varenicline
79. Sugammadex 90. Voriconazole
80. Sumatriptan 91. 13-valent Pneumococcal Conjugate
81. Tafluprost Vaccine
82. Tenofovir alafenamide fumarate

NOTE: Please refer to the Philippine National Formulary (PNF) 8th Edition Essential Medicines List (EML) for the
updated summary list of medicines approved for inclusion. The medicines which were approved from October
2018 onwards are listed in the EML booklet, which may be downloaded from the website of the Pharmaceutical
Division, https://pharmadiv.doh.gov.ph.

A3
 LIST OF DRUG MOLECULES DELETED FROM THE
PNF 7TH EDITION

1. Acarbose 42. Interferon Alfa 2a (human)

2. Akapulko 43. Iodamide
3. Alpha-Tocopherol (vitamin E) 44. Ioxithalamic Acid
4. Aluminum Acetate 45. Iron Dextran
5. Amidotrizoate (Diatrizoate) 46. Isoniazid + Ethambutol
6. Beclomethasone 47. Isoniazid + Thiacetazone
7. Benzoic Acid + Salicylic Acid 48. Live Attenuated Trivalent Oral Polio
8. Calcium Dialysate, Low Vaccine
9. Candesartan 49. Lomustine
10. Carbimazole 50. Lorazepam
11. Carmustine 51. Meclozine (meclizine)
12. Cefadroxil 52. Minocycline
13. Chloral Hydrate 53. Molgramostim (Gm-CSF)
14. Coal Tar 54. Nadroparin
15. Colestyramine 55. Nelfinavir
16. Conjugated Equine Estrogen + 56. Netilmicin
Medroxyprogesterone Acetate 57. Nicotinamide (vitamin B3)
17. Daunorubicin 58. Norfloxacin
18. Dextran, Low Molecular Weight 59. Oxantel + Pyrantel
(Dextran 40) 60. Pirebedil
19. Didanosine 61. Polygeline
20. Dithranol 62. Potassium Free Dialysate Acetate-
21. Edrophonium Based Containing
22. Eprosartan 63. Potassium Free Dialysate Bicarbonate-
23. Ergocalciferol (calciferol, vitamin D2) Based Containing
24. Famciclovir 64. Potassium Permanganate
25. Fluoride 65. Procarbazine
26. Flurazepam 66. Raloxifene
27. Fosphenytoin 67. Riboflavin (vitamin B2)
28. Gadodiamide 68. Ritonavir
29. Galantamine 69. Rose Bengal
30. Glibenclamide 70. Rosiglitazone
31. Glipizide 71. Saquinavir
32. Glutaraldehyde (glutaral) 72. Silver Nitrate
33. Griseofulvin 73. Stavudine
34. Human Chorionic Gonadotrophin (HCG) 74. Sulfacetamide
35. Human Growth Hormone (biosynthetic) 75. Sulfadoxine + Pyrimethamine
36. Human Menopausal Gonadotrophin 76. Terizodone
(HMG, menotropin) 77. Tetracosactide (cosyntropin)
37. Hydroxocobalamin (vitamin B12) 78. Thiacetazone
38. Imipramine 79. Triamcinolone
39. Indinavir 80. Trichloracetic Acid
40. Indomethacin 81. Vasopressin
41. Insulin Zinc Suspension, Human 82. Vitamin B12 (see Hydroxocobalamin)

A4
83. Vitamin B2 (see Riboflavin) 87. Yerba Buena
84. Vitamin B3 (see Nicotinamide) 88. Zalcitabine
85. Vitamin D2 (see Ergocalciferol)
86. Vitamin E (see Alpha-Tocopherol)

A5
 LIST OF PHARMACEUTICAL PRODUCTS NOT REGISTERED
WITH THE FDA BUT CONSIDERED ESSENTIAL

1. Acetylcysteine
Inj.: 200 mg/mL, 10 mL ampul (IV infusion)

2. Activated charcoal x
Oral: powder, USP grade

3. Alcohol, ethyl
Inj.: absolute, 1 mL ampul (IV)

4. Antilymphocyte immunoglobulin (ALG) (equine)

Inj.: 100 mg/5mL vial (IV)

5. Antithymocyte immunoglobulin (ATG) (rabbit)

Inj.: 25 mg/5 mL vial (IV)

6. Clofazimine
Oral: 50 mg and 100 mg capsule (available under DOH program)

7. Codeine
Oral: 30 mg MR capsule (as phosphate)

8. Dantrolene
Oral: 25 mg and 50 mg capsule (as sodium salt)
Inj.: 20 mg (with 3 mg mannitol/vial)
For reconstitution with 60 mL sterile water for injection (IV) (as sodium salt)

9. Deferoxamine
Inj.: powder, 500 mg vial (IM, IV infusion, SC)

10. Desmopressin
Inj.: 15 micrograms/mL, 1 mL ampul (IM, SC) (as acetate)

11. Dimercaprol
Inj.: (in oil) 50 mg/mL, 2 mL ampul (IV)

12. Dimercaptopropane sulphonate (DMPS)

Inj.: 100 mg/mL, 1 mL ampul, 10 mL vial (IM)

13. Diphtheria antitoxin

Inj.: 10,000 IU and 20,000 IU, 5 mL and 10 mL (IV)

14. Factor IX Complex Concentrate (Coagulation Factors; II, VII, IX, X)

Inj.: 100 IU/mL, 5 mL and 10 mL vial (IV)

15. Fluorescein
Strips: 1 mg and 9 mg (as sodium salt)

16. Fomepizole
Inj.: 1 g/mL, 1.5 mL vial (IV)

A6
17. Gas forming agent
Oral: Components per tablet: Sodium bicarbonate
Glutamic acid
Tartaric acid
Silicon resin

18. Iodine
Oral: Aqueous iodine solution (Lugol's solution)
5% iodine, 10 % potassium iodide (total iodine ‐ 130 mg/mL), 30 mL

19. Methylene blue

Oral: 1% solution
Inj.: 10 mg/mL, 1 mL and 10 mL ampul/vial

20. Naltrexone
Oral: 50 mg tablet (as hydrochloride)
21. Physostigmine
Inj.: 1 mg/mL, 2 mL ampul (IM, IV)

22. Potassium chloride

Oral: 1 mmol/mL syrup, 30 mL and 60 mL

23. Potassium phosphate

Inj.: 224 mg monobasic potassium phosphate equiv. to 3 mmol phosphorus and
4.4 mEq K/236 mg dibasic‐potassium phosphate anhydrous per mL in 5 mL vial
(IV)

24. Protamine sulfate

Inj.: 10 mg/mL, 5 mL and 25 mL ampul (IV)

25. Prothionamide
Oral: 250 mg film coated tablet

26. Pyrimethamine
Oral: 25 mg and 75 mg tablet

27. Rifabutin
Oral: 150 mg capsule

28. Sodium calcium edetate

Inj.: 200 mg/mL, 5 mL ampul (IM)

29. Sodium iodide

Oral: capsule with radioactivity range of 0.8 to 100 mCi per capsule
capsule with radioactivity range of 1.0 to 250 mCi per capsule
solution with radioactivity range of 3.5 to 150 mCi per vial

30. Sodium nitrite

Inj.: powder, USP grade

31. Sodium thiosulfate

Inj.: 250 mg/mL, 50 mL ampul (IV)

A7
 32. Spectinomycin
Inj.: 2 g vial (IM)

33. Succimer (dimercapto succinic acid, DMSA)

Oral: 100 mg and 200 mg capsule

34. Thiamine
Inj.: 100 mg/mL, 1 mL ampul/vial (IV)

35. Varicella zoster immunoglobulin (VZIG)

Inj.: 125 units/1.25 mL vial (IM)

A8
 LIST OF DANGEROUS DRUG PREPARATIONS INCLUDED IN
THE PNF
Drugs requiring S-2 License using DDB Prescription Form:

1. Alprazolam
2. Bromazepam
3. Clonazepam
4. Codeine (as phosphate)
5. Diazepam
6. Fentanyl (as citrate)
7. Ketamine
8. Methylphenidate
9. Midazolam
10. Morphine (as sulfate)
11. Nalbuphine
12. Oxycodone
13. Phenobarbital
14. Pethidine (meperidine)
15. Remifentanil
16. Zolpidem

A9
 LIST OF CONTROLLED CHEMICALS INCLUDED IN THE PNF
Controlled precursors and essential chemicals listed in Table I of the 1988 UN Convention Against Illicit Traffic
in Narcotic Drugs and Psychotropic Substances 16th Edition, January 2018:

1. Ephedrine (as sulfate)

2. Ergotamine (as tartrate)

A10
 LIST OF ESSENTIAL MEDICINES WITH
NARROW THERAPEUTIC RANGE

1. Carbamazepine Tablets, Oral Suspension

2. Clindamycin Hydrochloride Capsules
3. Clonidine Hydrochloride Tablets
4. Ethinyl Estradiol/Progestin Oral Contraceptive Tablets
5. Lithium Carbonate Capsules, Tablets, ER Tablets
6. Phenytoin, Sodium Capsules (Prompt or Extended), Oral Suspension
7. Theophylline Capsules, ER Capsules, Tablets, ER Tablets
8. Valproic Acid Capsules, Syrup
9. Divalproex, Sodium DR Capsules, DR Tablets
10. Warfarin, Sodium Tablets

A11
 LIST OF RESERVE ANTIMICROBIALS
Medicines in the PNF which are to be used only in hospitals with DOH accredited Antimicrobial Resistance
Surveillance Program (ARSP):

MEDICINE DOSAGE FORMS / STRENGTHS

50 mg and 100 mg colloidal suspension (as cholesteryl
Amphotericin B
complex, lipid complex), vial (IV infusion)
50 mg lyophilized powder (as deoxycholate, non-lipid
complex), vial (IV infusion)

Aztreonam 1 g powder for injection

Cefepime 500 mg, 1 g, and 2 g (as hydrochloride), vial

Colistin 2,000,000 IU lyophilized powder for injection (IV infusion)

Ertapenem 1 g powder (as sodium), vial

600 mg tablet/film-coated tablet

Linezolid
2 mg/mL (600 mg/300 mL), solution for infusion (IV)

Meropenem 500 mg and 1 g powder (as trihydrate), vial

Micafungin 50 mg lyophilized powder for infusion (IV)

500,000 units powder for solutions for injection (as sulfate),

Polymixin B
5 mL vial (Intrathecal/IM/IV)

Vancomycin 500 mg and 1 g (as hydrochloride), vial

200 mg lyophilized powder for solution for IV infusion, 30 mL

Voriconazole
vial

A12
LIST OF MEDICINAL PLANT PRODUCTS REGISTERED WITH
THE FDA AND INCLUDED IN THE PNF

1. Lagundi [Vitex negundo L. (Fam. Verbenaceae)]

2. Sambong [Blumea balsamifera (L) DC (Fam. Compositae)]
3. Tsaang Gubat [Carmona retusa (Vahl) Masam (Fam. Boraginaceae]

A13
 DEFINITION OF DOSAGE FORMS
Ampule – A final container that is all glass in which the open end is sealed by heat (a.k.a. carpule)

Capsule – Solid dosage form in which the drug is enclosed within either a hard or soft soluble shell, usually
made of gelatin

Cream – Semisolid preparation containing one or more drug substance, dissolved or dispersed in a suitable
base

Drops – Solution, emulsion, or suspension that is administered in small volumes, by means of a suitable
device

Effervescent – Dosage form containing ingredients that rapidly release carbon dioxide when in contact with
water

Elixir – Clear, sweetened hydroalcoholic solution, intended for oral use, usually flavored to enhance
palatability

Emulsion – Two-phase system prepared by dispersing one liquid in another immiscible liquid in the form of
small droplets

Enema – Rectal injection or solution

Gargle – Aqueous solution used for treating the pharynx and nasopharynx by forcing air from the lungs
through the solution held in the throat

Gel – Semisolid system composed of either a suspension of small inorganic particles or large organic
molecules, interpenetrated by a liquid and rendered jelly-like by the addition of a gelling agent

Granule – Prepared dry agglomerates of powders that may contain one or more active ingredients with or
without other ingredients

Implant – Controlled drug delivery systems in which the active pharmaceutical ingredient is impregnated into
the material and is released slowly into the body tissue for local or systemic action

Inhalation – Solution or suspension of one or more drug substances administered by the nasal or oral
respiratory route for local or systemic effect

Injection – Preparation intended for parenteral administration or for constituting or diluting a parenteral
article prior to administration

Irrigation – Sterile solution intended to bathe or flush open wounds or body cavities

Jelly – Class of gel in which the structural coherent matrix contains a high portion of water

Lotion – Liquid suspension or emulsion for external application to the body

Mixture – Oral liquid containing one or more active pharmaceutical ingredients, which are dissolved,
suspended, or dispersed in a suitable liquid vehicle

A14
Mouthwash – Aqueous solutions used by swishing the liquid in the oral cavity, to cleanse the mouth or treat
diseases of the oral mucous membranes

Ointment – Semisolid dosage form applied externally on the skin or mucous membrane

Ophthalmic ointment – A sterile ointment intended for application to the eye

Ophthalmic solution – A sterile solution, essentially free from foreign particles, suitably prepared and
packaged for instillation into the eye

Ophthalmic suspension – A sterile liquid preparation containing solid particles dispersed in a liquid vehicle
intended for application to the eye

Ophthalmic strip – A sterile single-use container or sterile impregnated paper strip containing the drug to be
applied to the eye

Orally disintegrating – A solid oral dosage form that disintegrates rapidly in the mouth to facilitate release of
the active ingredient

Otic solution – A solution intended for instillation in the outer ear

Patch – A transdermal system containing a drug reservoir entrapped between backing and adhesive layers
and a drug diffusion-controlling membrane, which allow the passage of drugs from the skin (stratum
corneum) into systemic circulation

Powder – Intimate mixtures of dry, finely divided drugs and/or chemicals, which may be used internally or
externally

Rinse – A solution used to cleanse by flushing

Shampoo – A solution, emulsion, or suspension used to clean the hair and scalp

Solution – Liquid preparation containing one or more substances dissolved in a suitable solvent or a mixture
of mutually miscible solvents

Suppository – Solid mass intended to be inserted into a body cavity / orifice in which they will melt at body
temperature or dissolve in the aqueous secretions of the body cavity to release the active pharmaceutical
ingredient and produce local or systemic actions

Suspension – Liquid preparations that consist of solid particles (suspensoid) dispersed throughout a liquid
vehicle in which the particles are not soluble

Syrup – Concentrated or nearly saturated solutions of sucrose or other sugars in water or aqueous liquid

Tablet – Solid dosage forms that contains medicinal substance(s) with or without diluents and are prepared
by molding or compression

Tablet, Chewable – A tablet formulated so that it may be chewed, producing a pleasant-tasting residue that
is easily swallowed and does not leave a bitter or unpleasant aftertaste

A15
Tincture – Alcoholic or hydroalcoholic solutions prepared from soluble constituents of vegetable drugs or from
chemical substances

Vaginal tablet – Ovoid tablet formed by compression, which are inserted into the vagina using a plastic
inserter (a.k.a. vaginal insert)

MODIFIED RELEASE FORMS

Delayed-release – Drug release is other than the time of prompt administration

Extended-release – Provides a prompt desired effect followed by gradual release of the remaining amount

Targeted-release – Drug release is concentrated or isolated in a specific body region or tissue for absorption
and metabolism

A16
FDA ADVERSE DRUG REACTION (ADR) REPORTING FORM

A19
 DIRECTORY
DEPARTMENT OF HEALTH
Website: http://www.doh.gov.ph/
Phone Number: (02) 651 7800

DOH – Antimicrobial Resistance Surveillance Program (ARSP)

Antimicrobial Resistance Surveillance Reference Laboratory
DOH Compound, Filinvest Corporate City, Alabang, Muntinlupa
Website: www.ritm.gov.ph
Telefax: (02) 809 9763
E-mail Address: arsp_ph@yahoo.com

DOH – Pharmaceutical Division

Website: https://pharmadiv.doh.gov.ph
Phone Number: (02) 875 7734 local 253 or (02) 937 5314

PHILIPPINE FOOD AND DRUG ADMINISTRATION

Website: http://www.fda.gov.ph/
E-mail Address: info@fda.gov.ph

Center for Food Regulation and Research

Phone Number: (02) 857 1992; (02) 857 1993

Center for Cosmetic Regulation and Research

Phone Number: (02) 857 1940; (02) 857 1984

Center for Drugs Regulation and Research

Phone Number: (02) 857 1990

Center for Device Regulation, Radiation Health, and Research

Phone Number: (02) 749 9443; (02) 711 6824

NATIONAL DRUG INFORMATION CENTER

Website: http://www.druginfo.ph
Telefax: (02) 526 4384
E-mail Address: ndic@druginfo.ph

NATIONAL POISON MANAGEMENT AND CONTROL CENTER

LUZON
Philippine General Hospital
Phone Number: (02) 524 1078; (02) 554 8400 loc. 2311; (02) 404 0257; (02) 526 0062 (F)
Website: http://www.uppoisoncenter.org/network.html

East Avenue Medical Center

Phone Number: (02) 434 2511

Rizal Medical Center

Phone Number: (02) 570 6273; (02) 671 9615; (02) 6719740

Batangas Regional Hospital

A20
Phone Number: (043) 723 3578

VISAYAS
Eastern Visayas Regional Medical Center
Phone Number: (053) 321 3131; (053) 321 3129 (F)

Western Visayas Medical Center / Iloilo Doctors Hospital

Phone Number: (033) 337 7702

MINDANAO
Zamboanga Medical Center
Phone Number: (062) 991 2934; (062) 991 0537

PHILIPPINE HEALTH INSURANCE CORPORATION

Website: http://www.philhealth.gov.ph
Trunkline: (02) 441 7444
Call Center: (02) 441 7442
E-mail Address: actioncenter@philhelath.gov.ph

PHILIPPINE INSTITUTE OF TRADITIONAL AND ALTERNATIVE HEALTH CARE (PITAHC)

Phone Number: (02) 376 3068
Website: http://www.pitahc.piaem.org
E-mail Address: pitahc@gmail.com

A21
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BMJ Group and the Royal Pharmaceutical Society of Great Britain, September 2013 – March 2014, British
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BMJ Group and the Royal Pharmaceutical Society of Great Britain, March – September 2016, British National
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Canadian Diabetes Association (CDA), 2008.

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Carlos, C., et. al. Antimicrobial Resistance Surveillance Program 2015 Data Summary Report. Antimicrobial
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College of Psychiatric and Neurologic Pharmacists (CPNP), 2016, Psychiatric Pharmacotherapy Review,
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Council of Europe, 2005, European Pharmacopoeia, 5th edition, Strasbourg: Council of Europe.

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Family Health Office, 2014, Expanded Program on Immunization, Manila, Philippines: Department of Health.

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Gray, A.H., Wright, J., Goodey, V., et.al., 2011, Injectable Drugs Guide, London, UK: Pharmaceutical Press.

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International Diabetes Federation Global Guideline (IDF), 2005.

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 INDEX
A
Artesunate, 542-43
Abacavir, 269 Ascorbic Acid (Vitamin C), 30-31, 608
Acetated Ringer’s Solution, 75-76 Asparaginase, 360-62
Acetazolamide, 585-86 Aspirin, 50, 397
Acetylcysteine, 606-07 Atenolol, 128
Acyclovir / Aciclovir, 266, 579 Atorvastatin, 148
Activated Charcoal, 605 Atracurium, 406-07
Adenosine, 103-04 Atropine, 8-9, 104, 516-17, 594, 608-09
Adrenaline (Epinephrine), 107, 569 Azathioprine, 395-96, 420-22
Albendazole, 549-50 Azithromycin, 229-30
Albumin, Human, 66-67 Aztreonam, 226
Alcohol, Ethyl, 164, 607-08
Alendronate, 417-18 B
Alendronate + Cholecalciferol Bacitracin + Neomycin + Polymyxin B, 603
(Vitamin D3), 419-20 Baclofen, 412
Alfuzosin, 184-85 Balanced Multiple Maintenance Solution, 76-77
All-in-one Admixtures (“3 in 1 Solution” or “Dual Balanced Multiple Replacement Solution, 77
Energy Solution”), 69-70 Balanced Multiple Replacement Solution
Allopurinol, 415-16 with pH 7.4, 77-78
Alprazolam, 505-06 Barium Sulfate, 647-48
Alteplase (Human Recombinant Tissue Type Basiliximab, 389-90
Plasminogen Activator), 54 BCG Vaccine, 287
Aluminum Hydroxide + Magnesium Hydroxide, 1 Benzoyl Peroxide, 165-66
Amikacin, 233-35, 260 Benzyl Benzoate, 551
Amino Acid + carbohydrate + multivitamins Beractant, 576
+ electrolytes, 70 Betahistine, 533
Amino Acid + glucose + electrolytes Betamethasone, 160-61
+ vitamin B1, 70-71 Betaxolol, 586-87
Amino Acid Solutions for Hepatic Failure, 638 Bicalutamide, 371
Amino Acid Solutions for Biperiden, 481-82
Immunonutrition/Immunoenhancement, 638 Biphasic Isophane Human Insulin 70/30
Amino Acid Solutions for Infants, 638-39 (Recombinant DNA), 24
Amino Acid Solutions for Bisacodyl, 14
Renal Conditions, 639 Bisoprolol, 128-29
Amino Acids, Crystalline Standard, 71 Bleomycin, 347-48
Aminophylline (Theophylline Brimonidine, 587
Ethylenediamine), 567-69 Brinzolamide, 587-88
Amiodarone, 98-101 Bromazepam, 507
Amlodipine, 129-30 Bromocriptine, 482-83, 609
Amoxicillin, 7, 206-07 Budesonide, 553-54, 563-64
Amoxicillin + Potassium clavulanate Budesonide + Formoterol, 558-59
(Co-amoxiclav), 213-15 Bumetanide, 143-44
Amphotericin B (Lipid Complex), 250 Bupivacaine, 432-34
Amphotericin B (Non-Lipid Complex), 250 Butamirate, 571-72
Ampicillin, 207-08 Butorphanol, 447-48
Ampicillin + Sulbactam, 212-13
Antilymphocyte Immunoglobulin C
(ALG)(Equine), 381 Calamine, Plain, 156
Anti-Rabies Serum (Equine), 280-81 Calcipotriol, 156-57
Anti-Tetanus Serum (Equine), 281 Calcipotriol + Betamethasone, 157
Antithymocyte Immunoglobulin Calcitriol, 27-28
(ATG) (Rabbit), 382 Calcium Carbonate, 34-35
Aripiprazole, 487-89 Calcium Carbonate + Cholecalciferol
Artemether + Lumefantrin, 541-42 (Vitamin D3), 36-37

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Calcium Folinate Conjugated Equine Estrogen, 176-78, 420
(Leucovorin Calcium), 364-65, 609-10 Conjugated Estrogens, 420
Calcium Gluconate, 35, 84-85 Cotrimoxazole
Calcium Lactate, 35-36 (Sulfamethoxazole + Trimethoprim), 228-29
Calcium Salt, 611 Crotamiton, 551-52
Calcium Sennosides (Standardized Senna Cyclophosphamide, 313-15
Concentrate), 16-17 Cycloserine, 261
Capecitabine, 323-24 Cyproterone, 182-83, 371-73
Capreomycin, 260-61 Cytarabine, 325-27
Captopril, 115-16
Carbachol, 588 D
Carbamazepine, 459-60 Dacarbazine, 318-19
Carbetocin, 188 Daclatasvir, 276-77
Carboplatin, 349-50 Dactinomycin (Actinomycin D), 339-40
Carboprost, 168-69 Danazol, 183-84
Carboxymethylcellulose, 597 Dantrolene, 413-15, 612
Carvedilol, 124-26 Dapsone, 265
Castor Oil, 14-15 Deferasirox, 629-30
Cefalexin, 216-17 Deferiprone, 628-29
Cefazolin, 217-18 Deferoxamine (Desferrioxamine), 627-28
Cefepime, 225-26 Desflurane, 424-25
Cefixime, 220 Desmopressin, 187
Cefotaxime, 220-21 Dexamethasone, 189-91, 537, 583,
Cefoxitin, 218 Dextran, High Molecular Weight (Dextran 70), 67
Ceftazidime, 222-23 Dextromethorphan, 572
Ceftriaxone, 223-25 5% Dextrose in 0.3% Sodium Chloride, 73
Cefuroxime, 219 5% Dextrose in 0.45% Sodium Chloride, 73-74
Celecoxib, 405-06 5% Dextrose in 0.9% Sodium Chloride, 74
Cetirizine, 572-73 5% Dextrose in Lactated Ringer’s, 74-75
Chlorambucil, 312-13 5% Dextrose in Water, 82
Chloramphenicol, 205-06 10% Dextrose in Water, 83
Chlorhexidine, 162-63 Diazepam, 412-13, 474-75, 509-11
Chloroquine, 540, 543 Diclofenac, 398-99, 452
Chlorphenamine (Chlorpheniramine), 573 Dicycloverine (Dicyclomine), 9
Chlorpromazine, 489-91 Diethylcarbamazine, 550
Ciclosporin, 390-92, 598 Digoxin, 94-95
Cilostazol, 51-52 Diloxanide, 540-41
Cinnarizine, 533-34 Diltiazem, 137
Ciprofloxacin, 237-38 Dimeglumine Gadopentetate, 648-49
Cisplatin, 350-52 Dimercaprol, 612-13
Clarithromycin, 7, 230-31 Dimercaptopropanesulphonate (DMPS) 613
Clindamycin, 232-33 Diphenhydramine, 486-87, 574, 614
Clobetasol, 161 Diphtheria Antitoxin, 282
Clofazimine, 264-65 Diphtheria, Tetanus, Pertussis, Hepatitis B
Clomifene, 181 (Recombinant) and Hemophilus Influenza Type
Clonazepam, 470-71, 507-09 B (Hib) Combined Vaccine, 311
Clonidine, 139-40 Diphtheria-Tetanus Toxoid (Td), 288-89
Clopidogrel, 52-53 Diphtheria-Tetanus Toxoids (DT), 287-88
Clotrimazole, 152, 601-02 Diphtheria-Tetanus Toxoids and Acellular
Cloxacillin, 211 Pertussis Vaccines (DTaP), 300-01
Clozapine, 491-93 Diphtheria-Tetanus Toxoids and Pertussis Vaccine
Co-Amoxiclav (Amoxicillin + Potassium (DTP), 289-90
Clavulanate), 213-15 Dipyridamole, 53
Cobra Antivenin, 281-82, 611-12 Divalproex Sodium, 473-74, 518-19
Codeine, 440-41 Dobutamine, 105
Colchicine, 416-17 Docetaxel, 335-37
Colistin, 245-46 Domperidone, 10-11
Combined Glucose-Amino Acid Solutions, 71-72 Donepezil, 526-28

A94
Dopamine, 106 Finasteride, 186
Dorzolamide, 589 Fluconazole, 250-52
Doxorubicin, 341-42 Flucytosine (5-fluorocytosine), 254-55
Doxycycline, 203-04, 547-48 Flumazenil, 614-15
DTaP + Hemophilus Influenza Type B (Hib), 309 Flunarizine, 464-65
DTP + Hemophilus Influenza Type B (Hib), 309 Fluocinonide, 161-62
DTP + Hepatitis B Vaccine (Recombinant), 309-10 Fluorescein, 596-97
DTP + Inactivated Polio Vaccine (IPV), 310 Fluorouracil, 327-28
DTP + IPV + Hib, 310-11 Fluoxetine, 521-23
Dydrogesterone, 179-80 Flupentixol, 493-94
Fluphenazine, 494-96
E Flutamide, 373
Efavirenz, 271-72 Fluticasone, 564, 603-04
Enalapril, 116-17 Fluticasone + Formoterol, 559-60
Enalapril + Hydrochlorothiazide, 117-18 Fluticasone + Salmeterol, 560
Enoxaparin, 45-47 Folic Acid, 31, 62-63
Entecavir, 269-70 Fomepizole (4-methylprazole), 615-16
Enteral Nutrition Fondaparinux, 56-57
Adult Polymeric, 635 Formoterol, 556-57
Disease Specific, 635-36 Fosfomycin, 259-60
Fiber Containing, 636 Furosemide, 144-45
Modular, 637 Fusidate Sodium (Fusidic Acid), 158, 580
Pediatric Polymeric, 636
Semi-Elemental, 636 G
Eperisone Hydrochloride, 413 Gabapentin, 460-61, 475-76
Ephedrine, 534-35 Gadobutrol, 649-650
Epinephrine (Adrenaline), 107, 569 Gadoteric acid, 650-51
Epirubicin, 343-44 Ganciclovir, 267-68, 570
Epoetin Alfa Gas Forming Agent, 649
(Recombinant Human Erythropoietin), 63-64 Gemcitabine, 328-29
Epoetin Beta Gentamicin, 246-47
(Recombinant Erythropoietin), 64-66 Gliclazide, 25-26
Ergotamine, 461-62 Glucagon, 42, 614
Ertapenem, 226-27 Glucose (Dextrose), 41-42, 85, 637
Erythromycin, 231-33, 579 Glycerol (Glycerin), 15, 537-38, 589
Escitalopram, 520-21 Glyceryl Trinitrate (Nitroglycerin), 110-11, 113
Esmolol, 95-96, 535-36 Goserelin, 367-68
Ethambutol, 255-56
Ethinylestradiol + Desogestrel, 172 H
Ethinylestradiol + Levonorgestrel, 172-73 Haloperidol, 496-98
Ethinylestradiol + Norethisterone, 173 Halothane, 425
Ethinylestradiol + Norgestrel, 173 Hemodialysis Liquid Acid, 93
Etonogestrel, 173-75 Hemophilus Influenzae Type B Conjugate Vaccine
Etoposide, 333-35 (Hib), 291
Everolimus, 382-85 Heparin Sodium (Unfractionated), 47-48
Hepatitis A Vaccine (Inactivated), 297
F Hepatitis B Immunoglobulin (Human), 284-85
Factor IX Complex Concentrate (Coagulation Hepatits B Vaccine (Recombinant DNA), 297
Factors II, VII, IX, X), 58-60 Human Papillomavirus Quadrivalent Vaccine
Factor VIII Concentrate, 58 (Type 6, 11, 16, 18) (Recombinant), 299
Famotidine, 2-3 Human Papillomavirus Vaccine (Type 16, 18)
Felodipine, 130-31 (Recombinant, AS04 Adjuvanted), 299-300
Fenofibrate, 151 Human Recombinant Tissue Type Plasminogen
Fentanyl, 444-46 Activator (Alteplase), 54
Ferrous Salt, 38-39, 61 Hydralazine, 112-13
Ferrous Salt + Folic Acid, 39-40, 63 Hydrochlorothiazide, 140-41
Fiber Containing Enteral Nutrition, 636 Hydrocortisone, 162, 191-92
Filgrastim (G-CSF), 374-76 Hydrogen Peroxide, 164-65

A95
Hydroxychloroquine, 422 Ketoprofen, 402-03, 453-55
Hydroxyethyl Starch, 67-68 Ketorolac, 455-57
Hydroxyurea, 362
Hydroxyzine, 574-75 L
Hyoscine (Hyoscyamine), 9-10 Lactated Ringer’s Solution (Ringer’s Lactate), 650
3% Hypertonic Saline Solution, 631-32 Lactulose, 15-16
Hypromellose, 598 Lagundi, 653
Lamivudine, 270
I Lamivudine + Tenofovir, 273-74
Ibuprofen, 399-400, 452-53 Lamivudine + Tenofovir + Efavirenz, 274
Idarubicin, 344-45 Lamivudine + Zidovudine, 274-75
Ifosfamide, 315-16 Lamivudine + Zidovudine + Nevirapine, 275
Imatinib, 358-60 Lamotrigine, 476
Imiglucerase, 41 Lansoprazole, 4-5
Imiquimod, 159 Latanoprost, 589-90
Immunoglobulin Normal, Human (IGIM), 282-83 Letrozole, 373-74
Immunoglobulin Normal, Human (IGIV), 283-84 Leucovorin calcium (Calcium folinate), 364-65,
Indacaterol + glycopyrronium, 562-63 609-10
Indapamide, 141-43 Leuproreline, 368-69
Influenza Polyvalent Vaccine, 300-01 Levodopa + Carbidopa, 483-84
Influenza Polyvalent Vaccine (Split Virion, Levofloxacin, 239-41, 262, 581
Inactivated), 301 Levothyroxine, 197-99
Interferon Alfa-2b (Human), 376-79 Lidocaine, 95, 434-36, 600-01, 604
Intraocular Irrigating Solution (Balanced Salt Linezolid, 249-48
Solution), 80, 601 Lipids, 86
Iodine, 163, 200-01 Lithium Carbonate, 498-99
Iodized Oil Fluid, 639-40 Loperamide, 18-19
Iohexol, 640-42 Lopinavir + Ritonavir, 275-76
Iopamidol, 642-44 Loratadine, 575
Iopromide, 644-45 Losartan, 119-20
Iothalamate, 650-51 Losartan + Hydrochlorothiazide, 122
Ioversol, 645-47 Lynestrenol, 180-81
Ipratropium, 564-65
Ipratropium + Fenoterol, 560-61 M
Ipratropium + Salbutamol, 561-62 Magnesium Sulfate, 86-87, 104-05, 169-70, 479
Irbesartan, 119 Mannitol, 79-80, 147, 538-39, 590
Irbesartan + Hydrochlorothiazide, 121 Measles Vaccine (Live Attenuated), 302
Irinotecan, 363-64 Measles, Mumps, and Rubella (MMR) Vaccine
Iron Sucrose, 61-62 (Live Attenuated), 302-03
Isoflurane, 425-26 Measles and Rubella (MR) Vaccine (Live
Isoniazid, 256 Attenuated), 303
Isoniazid + Rifampicin, 259 Mebendazole, 550-51
Isoniazid + Rifampicin + Ethambutol, 259 Mebeverine, 10
Isoniazid + Rifampicin + Pyrazinamide, 259 Mecobalamin, 31-32, 62
Isoniazid + Rifampicin + Pyrazinamide + Medroxyprogesterone, 175, 179
Ethambutol, 259-60 Mefenamic Acid, 403-04
Isophane Insulin Human (Recombinant DNA), 24 Mefloquine, 543-44
Isosorbide Dinitrate, 109 Megestrol, 366-67
Isosorbide Mononitrate Melphalan, 317-18
(Isosorbide-5-Mononitrate), 110 Meningococcal Polysaccharide (Neisseria
Isotonic electrolyte solution for IV infusion, 78-79 meningitides) Vaccine, 291-92
Isoxsuprine, 169 Mercaptopurine, 322-23
Itraconazole, 252-53 Meropenem, 227-28
Mesalazine, 19-20
K Mesna (Sodium-2-Mercaptoethanesulphonate),
Kanamycin, 261-262 365-66, 630-31
Ketamine, 428-429 Metformin, 24-25
Ketoconazole, 152-53 Methimazole (Thiamazole), 199-200

A96
Methotrexate, 319-22 Oseltamivir, 276
Methyldopa, 140 Oxacillin, 211
Methylene Blue, 616-17 Oxcarbazepine, 472-73
Methylergometrine (Methylergonovine), 167-68 Oxiplatin (Oxaliplatin), 352-54
Methylphenidate, 525-26 Oxycodone, 443-44
Methylprednisolone, 193-94 Oxygen, 631
Metoclopramide, 12-13 Oxymetazoline, 554
Metoprolol, 96, 129 Oxytocin, 188-89
Metronidazole, 7, 246-47, 541
Micafungin, 254-55 P
Miconazole, 153 Paclitaxel, 337-39
Micronutrient Powder, 40-41 Paliperidone, 500-02
Midazolam, 477-78 Pancuronium, 407-08
Mitoxantrone, 346-47 Para-Aminosalicylic Acid, 262-63
Modified Fluid Gelatin, 68-69 Paracetamol, 457-59
Monobasic / Dibasic Sodium Phosphate, 16, 17 Peginterferon Alfa-2a, 379-81
Montelukast, 569-70 Penicillin G Benzathine (Benzathine
Morphine, 441-42 Benzylpenicillin), 208-09
Moxifloxacin, 241-43, 581 Penicillin G Crystalline (Benzylpenicillin), 209-10
Multivitamins, 26-27 Penicillin V (Phenoxymethylpenicillin), 210-11
Mumps Vaccine (Live Attenuated), 303-04 Peritoneal Dialysis Solution, 80-81
Mupirocin, 158 Permethrin, 552
Mycophenolate Mofetil, 385-87 Pethidine (Meperidine), 446-47
Mycophenolic Acid Petrolatum (Petroleum), 156
(as Mycophenolate Sodium), 387 Phenobarbital, 465-67
Phenylephrine, 594-95
N Phenytoin, 467-70
n-Acetyl Penicillamine, 617-18 Phospholipid fraction from bovine lung, 575-76
Nalbuphine, 448-49 Physostigmine, 621
Nalidixic Acid, 236-37 Phytomenadione
Naloxone, 618-19 (Phytonadione, Vitamin K1), 621-22
Naltrexone, 531-33 Pilocarpine, 590-91
Naproxen, 400-01 Piperacillin + Tazobactam, 215-16
Neomycin + Polymyxin B + Pneumococcal Conjugate
Fluocinolone Acetonide, 602-03 Vaccine (13-valent), 293-94
Neostigmine, 529-30, 619-20 Pneumococcal Polyvalent Vaccine, 294
Nepafenac, 583-84 Poliomyelitis Vaccine, Bivalent (Type 1, 2, 3)
Nevirapine, 272-73 (Inactivated), 304-05
Nicardipine, 131-33 Poractant Alfa, 577-78
Nifedipine, 133-35 Potassium Chloride, 37, 87-88
Nimodipine, 135-36 Potassium Citrate, 37
Nitrofurantoin, 247-48 Potassium Phosphate, 88-89
Nitroglycerin (Glyceryl Trinitrate), 110-11, 113 Povidone-Iodine, 163-64
Nitrous Oxide, 429-30 Pralidoxime Chloride, 622
Norepinephrine, 108-09 Praziquantel, 548-49
Norethisterone, 180-81 Prednisolone, 194-96, 584
Nystatin, 255 Prednisone, 196-97
Primaquine, 544-45
O Propofol, 430-31
Octreotide, 20-21 Propranolol, 97-98, 126, 201, 465
Ofloxacin, 238-39, 262, 581-82, 602 Propylthiouracil, 199
Olanzapine, 499-500 Protamine Sulfate, 622-23
Olodaterol, 557 Prothionamide, 263
Omeprazole, 5-6 Proxymetacaine (Proparacaine), 600-01
Ondansetron, 11-12 Pyrazinamide, 257
Oral Polio Vaccine, Bivalent (Type 1&3) (Live Pyridostigmine, 530-31
Attenuated), 304-05 Pyridoxine (Vitamin B6), 32-33, 623-24
Oral Rehydration Salts (ORS 75-replacement), 18 Pyrimethamine, 545-46

A97
 Sofosbuvir + Velpatasvir, 280
Q Somatostatin, 21-22
Quetiapine, 502-03 Soya bean oil + Medium chain triglycerides +
Quinine, 546-47 Olive oil + Purified fish oil, 72
Spectinomycin, 249
R Spironolactone, 146-47
Rabeprazole, 6-7 Standard Senna Concentrate, 16-17
Rabies Immunoglobulin (Human), 285 Sterile Water for Injection, 90-91
Rabies Vaccines – Chick Embryo Cell (Purified, Streptokinase, 54-55
Inactivated), 305-06 Streptomycin, 258
Rabies Vaccines – Vero Cell (Purified), 306 Succimer
Ranitidine, 3-4 (Dimercapto Succinic Acid, DMSA), 626-27
Regular, Insulin (Recombinant DNA, Human), 23- Sucralfate, 7
24 Sugammadex, 625-26
Retinol (Vitamin A), 28 Sulfacetamide + Prednisolone, 584-85
Ribavirin, 277-78 Sulfamethoxazole + trimethoprim (Cotrimoxazole),
Rifabutin, 263-64 228-229
Rifampicin, 257-58, 265 Sulfur, 552
Rifaximin, 17-18 Sumatriptan, 462-63
Rilpivirine, 273 Suxamethonium (Succinylcholine), 409-10
Risperidone, 503-05
Rituximab, 354-56 T
Rivastigmine, 528-29 Tacrolimus, 392-94
Rocuronium, 408-09 Tafluprost, 591-92
Ropivacaine, 436-38 Tamoxifen, 369-70
Rosuvastatin, 148-49 Tamsulosin, 185
Rubella vaccine (Live Attenuated), 306-07 Tegafur + Uracil, 329-30
Telmisartan, 120
S Telmisartan + Hydrochlorothiazide, 123
Sacubitril + Valsartan, 122-23 Tenofovir Alafenamide Fumarate, 270
Salbutamol, 555-56, 566 Tenofovir Disoproxil Fumarate, 271
Salicylic Acid, 153-54, 157 Terazosin, 185-86
Sambong, 653 Terbinafine, 154-55
Selegiline, 485-86 Terbutaline, 556-57, 566-67
Selenium Sulfide, 154 Testosterone, 175-76
Semi-Elemental Enteral Nutrition, 636 Tetanus Immunoglobulin (Human), 285-86
Sertraline, 523-25 Tetanus Toxoid, 295
Sevoflurane, 426-27 Tetracaine, 432
Silver Sulfadiazine, 159 Tetracycline, 204-05, 548
Simvastatin, 149-50 Theophylline (Anhydrous), 570-71
Sirolimus, 387-89 Thiamazole (Methimazole), 199-200
Sodium Bicarbonate, 1-2, 89-90 Thiamine (Vitamin B1), 29, 627
Sodium Bicarbonate for Hemodialysis, 89-90 Thiopental Sodium, 427-28, 479
Sodium Calcium Edetate, 624 Timolol, 592-93
Sodium Chloride, 90 Tinzaparin, 48-50
0.9% Sodium Chloride, 81-82 Tiotropium, 565-66
Sodium Dichloroisocyanurate, 165 Tobramycin, 582
Sodium Hyaluronate, 599 Tobramycin + Dexamethasone, 585
Sodium Hypochlorite, 165 Topiramate, 479-481
Sodium Iodide 1311, 651-52 Trace Elements, 91
Sodium Nitroprusside, 113-15 Tramadol, 450-51
Sodium Sulfate, 606 Tranexamic Acid, 57-58
Sodium Thiosulfate, 155, 625 Trastuzumab, 356-58
Sodium valproate, 473-74, 518-19 Travoprost, 593
Sodium valproate + valproic acid, 473-74, 518- Triclabendazole, 549
19 Trimetazidine, 111-12
Sofosbuvir, 278-79 Tropicamide, 595-96
Sofosbuvir + Ledipasvir, 279-80 Tropicamide + phenylephrine hydrochloride, 596

A98
Tsaang Gubat, 653-54 Vitamin B6 (Pyridoxine), 32-33, 623
Tuberculin, Purified Protein Derivative Vitamin C (Ascorbic Acid), 30-31, 608
(PPD), 632-33 Vitamins Intravenous (IV), Fat-Soluble, 91-92
Typhoid Vaccine, 295-96 Vitamins Intravenous (IV), Water-Soluble, 92
Vitamin K1 (Phytomenadione), 32, 621-22
U Voriconazole, 253
Ursodeoxycholic Acid, 13-14
W
V Warfarin, 42-44
Valaciclovir, 267
Valganciclovir, 268 Y
Valproic acid, 473-74, 518-19 Yellow Fever Vaccine, 308-09
Valsartan, 120-21
Valsartan + Hydrochlorothiazide, 123-24
Vancomycin, 243-45 Z
Varicella Vaccine (Live Attenuated), 307-08 Zidovudine, 271
Varicella Zoster Immunoglobulin (VZIG), 286 Zinc Gluconate, 38
Vecuronium, 410 Zinc Sulfate, 38
Verapamil, 101-03, 137-39 Zolmitriptan, 463-64
Vinblastine, 331-32 Zolpidem, 515-16
Vincristine, 332-33
Vitamin A (Retinol), 28
Vitamin B1 B6 B12 29-30

A99
Notes