Based on the Second Model List of Essential Medicines for Children 2009

2010

WHO Library Cataloguing-in-Publication Data: WHO model formulary for children 2010. Based on the second model list of essential medicines for children 2009. 1.Essential drugs. 2.Formularies. 3.Pharmaceutical preparations. 4.Child. 5.Drug utilization. I.World Health Organization. ISBN 978 92 4 159932 0 (NLM classification: QV 55)

© World Health Organization 2010
All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: permissions@who.int). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use.

Acknowledgements
(listed in alphabetical order)

Clinical Editors: Siobhan Andrews1, BPharm GradDipPharmPrac Noel Cranswick1, 3, MBBS BMedSc FRACP Suzanne Hill2, BMed (Hons) PhD GradDipEpi FAFPHM Brian Lilley1, BPharm GradDipHospPharm MBA Leith Lilley1, BPharm MClinPharm Kate Milner3, MBBS MPH Courtney Munro1, BPharm GradCertPharmPrac Christine Plover1, BPharm (Hons) MClinPharm David Tickell3, MBBS FRACP
1. The Royal Children’s Hospital, Melbourne 2. Department of Essential Medicines and Pharmaceutical Policies, World Health Organization, Geneva 3. Centre for International Child Health, Department of Paediatrics, The University of Melbourne

Reviewers: Jonathan Akikusa Chris Barnes Naor Bar-Zeev Robert Berkowitz Louise Bordun Penelope Bryant Thomas Connell Nigel Crawford Andrew Daley Andrew Davidson Trevor Duke James Elder Steve Graham Amy Gray Adam Jenney Joshua Kausman Julian Kelly Stuart Lewena Sarah McNab Rob McDougall Jodie McVernon Paul Monagle Anna Moon Anastasia Pellicano Rob Roseby Fiona Russell Helen Savoia Mike Starr Andrew Steer Garry Warne Keith Waters

WHO Reviewers: Pedro Albajar-Vinas Jorge Alvar Ezquerra Siobhan Crowley Denis Daumerie Margriet den Boer Tarun Dua Philippe Duclos Dirk Engels Olivier Fontaine Jose Ramon Franco Minguell M. Grzemska Jean Jannin Ivo Kocur Jose Martines Shanthi Mendis Lulu Muhe Peter Olumese Ana Padilla Marroquin Juan Pena-Rosas Pere Perez Simarro Cathy Roth Shekhar Saxena Joanna Tempowski Wilson Were

Special thanks to Monique Renevier for organizing the WHO reviews.
Publisher: MIMS Australia (UBM Medica Australia Pty Ltd) Editors: Matthew Bidgood, BPharm (Hons) PhD Elizabeth Donohoo, BSc GradCertHlthSc Niroshni Gunewardhane, MD Allyson Harvey, RN BA (Hons) DipBEP Valerie Hoa, MPharm (ClinPharm) Sue Hunter, BVSc (Hons) Sarah Keen, BPharm Olivia Wroth, BVSc DipBEP Production: Robert Johanson, BAppSc Karthick Mani, MCompSc Corrina Rivett Daniela Velcich Business: Margaret Gehrig,
Helen Gilmour,
BHealthSc (Mgt), AssocDipNursing (Mgt), RN BAppSc (Haem) GradDip (Mktg)

Special thanks to Julian Kelly for organizing the expert reviews.
WHO Model Formulary for Children 2010

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SELECTED WHO PUBLICATIONS OF RELATED INTEREST
The selection and use of essential medicines.
Report of the WHO Expert Committee (including the WHO Model List of Essential Medicines and the 2nd WHO Model List of Essential Medicines for Children) WHO Technical Report Series, No. 958, 2010 (in print)

Pocket book of hospital care for children.
2005 (378 pages)

The international pharmacopoeia, fourth edition.
Volume 1: general notices; monographs for pharmaceutical substances (A–O) Volume 2: monographs for pharmaceutical substances (P–Z); monographs for dosage forms and radiopharmaceutical preparations; methods of analysis; reagents. 2006 (1500 pages), also available in CD-ROM version

Basic tests for drugs: pharmaceutical substances, medicinal plant materials and dosage forms.
1998 (94 pages)

Quality assurance of pharmaceuticals: a compendium of guidelines and related materials.
Volume 1: 1997 (244 pages) Volume 2: Good manufacturing practices and inspection. 2nd updated edition, 2007 (in print)

WHO Expert Committee on Specifications for Pharmaceutical Preparations.
Forty-third report. WHO Technical Report Series, No. 953, 2009 (172 pages)

International nonproprietary names (INN) for pharmaceutical substances.
Cumulative List no. 13 2010 (available in CD-ROM format only) Further information on these and other WHO publications can be obtained from WHO Press, World Health Organization, 1211 Geneva 27, Switzerland (tel. +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int; order on line: http://www.who.int/bookorders) iv WHO Model Formulary for Children 2010

Contents
Selected WHO Publications of Interest ....................................................................................... iv Abbreviations ............................................................................................................................ vi Introduction ............................................................................................................................ vii Guidance for Prescribing in Paediatrics........................................................................................ viii How to Use the WMFC .............................................................................................................. xii Changes to the WHO Model List of Essential Medicines for Children........................................ xv Section 1: Anaesthetics ......................................................................................................... 2 Section 2: Analgesics, antipyretics, non-steroidal anti-inflammatory medicines (NSAIMs), medicines used to treat gout and disease modifying agents in rheumatoid disorders (DMARDs) ........................................................................................... 18 Section 3: Antiallergics and medicines used in anaphylaxis ................................................... 27 Section 4: Antidotes and other substances used in poisonings ............................................... 36 Section 5: Anticonvulsants/antiepileptics .............................................................................. 49 Section 6: Anti-infective medicines ....................................................................................... 64 Section 7: Antimigraine medicines........................................................................................ 240 Section 8: Antineoplastic, immunosuppressives and medicines used in palliative care ........... 246 Section 9: Antiparkinsonism medicines ................................................................................ 295 Section 10: Medicines affecting the blood ............................................................................... 297 Section 11: Blood products and plasma substitutes ................................................................. 308 Section 12: Cardiovascular medicines ..................................................................................... 313 Section 13: Dermatological medicines (topical) ...................................................................... 323 Section 14: Diagnostic agents ................................................................................................. 341 Section 15: Disinfectants and antiseptics ................................................................................ 345 Section 16: Diuretics .............................................................................................................. 352 Section 17: Gastrointestinal medicines ................................................................................... 359 Section 18: Hormones, other endocrine medicines and contraceptives ................................... 374 Section 19: Immunologicals.................................................................................................... 387 Section 20: Muscle relaxants (peripherally-acting) and cholinesterase inhibitors ..................... 431 Section 21: Ophthalmological preparations ............................................................................ 438 Section 22: Oxytocics and antioxytocics ................................................................................. 447 Section 23: Peritoneal dialysis solution ................................................................................... 449 Section 24: Psychotherapeutic medicines ................................................................................ 452 Section 25: Medicines acting on the respiratory tract .............................................................. 461 Section 26: Solutions correcting water, electrolyte and acid-base disturbances......................... 467 Section 27: Vitamins and minerals ......................................................................................... 478 Section 28: Ear, nose and throat conditions in children .......................................................... 488 Section 29: Specific medicines for neonatal care...................................................................... 493 Index ............................................................................................................................ 500 WHO Model Formulary for Children 2010 v

Abbreviations
ACE AIDS ALP APTT ART ATC AUC AV BCG BNFC BP BSA CNS CrCl CSF ECG EEG EMLc G6PD GFR GI GORD GVHD HIV Ht IM INR IV MB MDI MDR-TB MMR MRI MSSA MTCT NSAIM ORS PB PCP PDA PR PTB PVC SC SIADH spp. SSRI TB TSH USP WHO Wt angiotensin-converting enzyme acquired immunodeficiency syndrome alkaline phosphatase activated partial thromboplastin time antiretroviral anatomical therapeutic chemical area under the curve atrioventricular Bacillus Calmette–Guérin (vaccine) British National Formulary for Children British Pharmacopoeia body surface area central nervous system creatinine clearance cerebrospinal fluid electrocardiogram electroencephalogram Essential Medicines List for Children glucose 6-phosphate dehydrogenase glomerular filtration rate gastrointestinal gastro-oesophageal reflux disease graft-versus-host disease human immunodeficiency virus height intramuscular international normalized ratio intravenous multibacillary leprosy metered dose inhaler multidrug-resistant tuberculosis measles, mumps, rubella magnetic resonance imaging methicillin-sensitive Staphylococcus aureus mother-to-child transmission non-steroidal anti-inflammatory medicine oral rehydration solution paucibacillary leprosy Pneumocystis carinii (Pneumocystis jiroveci) pneumonia patent ductus arteriosus per rectum pulmonary tuberculosis polyvinyl chloride subcutaneous syndrome of inappropriate antidiuretic hormone secretion species selective serotonin reuptake inhibitor tuberculosis thyroid stimulating hormone United States Pharmacopeia World Health Organization weight

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Introduction
In 2007, the World Health Assembly passed a Resolution titled ‘Better Medicines for Children’. This resolution recognized the need for research and development into medicines for children, including better dosage forms, better evidence and better information about how to ensure that medicines for treating the common childhood diseases are given at the right dose for children of all ages. The World Health Organization has therefore developed a program of work on medicines for children, including the development of a Model List of Essential Medicines for children (EMLc). As an extra resource for health-care workers and national programmes that supply medicines for children, this new edition of the WHO Model Formulary has been prepared, based on the 2nd edition of the EMLc, to provide prescribers with the best information about how to use the medicines included on the List. In developing the WHO Model Formulary for Children, the editors have based decisions on treatment regimens on the best available evidence from clinical studies in children, that have been assessed and evaluated by the WHO Expert Committee on Selection and Use of Essential Medicines. However, as has been found by all authorities in relation to medicines for children, in many cases the recommendations on dose and duration of treatment in children have to be extrapolated from studies in adults and adjusted based on our understanding of the effect of age and development on the absorption, distribution and metabolism and excretion of different medicines in children of different ages. One of the aims of this publication is therefore not only to describe what is known about treatments, but to highlight where more research is needed. An electronic version of the WHO Formulary for Children is also available, intended as a starting point for developing institutional or national formularies. The text of the Formulary can be used by groups who wish to develop their own version, by adapting the text or by adding or deleting entries to align the formulary to their own list of essential medicines. This edition of the WHO Model Formulary is fully compatible with the 2nd List of Essential Medicines for Children, as recommended by the WHO Expert Committee on the Selection and Use of Essential Medicines in March 2009. Comments and suggestions are welcome and should be sent to: The Editor; WHO Model Formulary Medicines Access and Rational Use Department of Essential Medicines and Pharmaceutical Policies World Health Organization 20 Avenue Appia CH-1211 Geneva 27 Email : modelformulary@who.int

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Factors influencing paediatric drug therapy
Medicines in children
It was once said that the moral test of government is how that government treats those who are in the dawn of life, the children; those who are in the twilight of life, the elderly; and those who are in the shadows of life—the sick, the needy and the handicapped.1

Children are among the most vulnerable individuals in any society. Nowhere is this more true than in their access to appropriate health care. As part of the treatment of children, health-care workers need access to drug dosage information. This formulary aims to provide that information universally, to assist in the management of children. The use of medicines in infants and children presents a unique set of challenges to the prescriber. Physiological variances between children and adults, including the ontogeny of organ maturity and body composition, significantly influence the actions, effectiveness and safety of medicines. However, most pharmacokinetic and pharmacodynamic studies provide little, if any, information on drug action in infants and children, because they are usually conducted in adults. Paediatric pharmacology developed initially from the extrapolation of therapeutic practice and experience in adults and the use of “scaled down” adult doses. This practice is clinically successful for the majority of drugs which are relatively non-toxic and have a wide margin between therapeutic and toxic doses. Drugs with a narrow therapeutic margin, such as the aminoglycoside antibiotics and digoxin, require more sophisticated knowledge and individualized dosage regimens. Doses of such agents are scaled by weight or allometrically (wt¾), then modified according to the results of serum drug concentration measurements, if these are available. Over the last two decades, there has been an increased recognition of the necessity to perform studies specifically in children and adolescents. Major national and international approaches, such as those of the European Union and the United States, have resulted in some new information to improve the use of medicines in children. This formulary is the result of the establishment of the WHO Model List of Essential Medicines for Children (EMLc). The list can be accessed at http://www.who.int/selection_medicines/en/.

Absorption
Oral absorption
The gastrointestinal tract, particularly the stomach, undergoes significant changes from birth until around 3 years of age. Before then, the stomach has low levels of acid, and acid-labile drugs, such as the penicillins, show enhanced absorption. On the other hand, this depressed level of acidity may result in reduced absorption of weak acids such as phenobarbitone, phenytoin and rifampicin. The incomplete absorption experienced with these anticonvulsants may necessitate their continued parenteral administration. The delayed gastric emptying seen in neonates and young infants is probably not as important as previously believed. In the first few weeks of life this may be significant, but most sick neonates receive their drugs parenterally.

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Of considerable importance, particularly to the general public, is the question of drug administration and absorption relative to meals. Current evidence suggests that, with the exception of isoniazid, captopril, rifampicin, phenoxymethylpenicillin and tetracyclines (except doxycycline and minocycline), all medications should be administered with meals to avoid gastrointestinal irritation and to aid compliance.

Topical absorption
Topical absorption of drugs is enhanced in children and especially in infants. This is a direct result of the relative thinness of the stratum corneum. Absorption may be further enhanced in the presence of burnt or excoriated areas and with occlusive dressings. This has been well documented with the use of corticosteroid creams for eczema and nappy rash in infants, especially when the area treated has been occluded with plastic pants.

Rectal absorption
Rectal administration may be useful in patients who are vomiting and in infants and young children who are reluctant to take oral medication. The rectal route is not ideal for all drugs. Considerable individual variation in rectal venous drainage, and hence in the extent of drug absorption, can produce either sub-therapeutic or toxic drug levels. Drugs with narrow therapeutic margins should not be administered rectally. One drug which is recommended for rectal administration in children is diazepam for the treatment of seizures. Paracetamol may also be administered rectally; however, the absorption may be erratic and therapeutic levels cannot be guaranteed.

Distribution
Numerous factors, including body composition, plasma–protein binding and the blood–brain barrier influence drug distribution in the various paediatric age groups.

Body composition
Total body water and fat composition alter significantly during the transition from birth to adult life. Total body water as a percentage of body weight is approximately 80% at birth, 65% at 12 months and 60% for a young adult male. On the other hand, fat content as a percentage of body weight varies with age, being about 3% in premature infants, 12% in full-term neonates, 30% at 1 year of age and about 18% in the average adult. Therefore, larger mg/kg body weight doses of water-soluble drugs need to be given to neonates and infants to achieve plasma concentrations similar to those seen in adults. However, this has to be balanced against diminished hepatic function and renal elimination before arriving at a final dosage recommendation.

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Plasma protein binding
Drug–protein binding is diminished in neonates due to a lower concentration of plasma proteins, particularly albumin, and the lower drug-binding capacity of fetal albumin. This may lead to an increase in the fraction of unbound, pharmacologically active drug in the plasma. There may also be competition between endogenous substances, especially free fatty acids and bilirubin, and drugs for albumin-binding sites. However, when drugs administered to neonates are examined in detail, very few highly proteinbound drugs are used. From a practical point of view, highly protein-bound drugs such as phenytoin, sulfonamides, salicylates and diazepam should be given with caution in the presence of hyperbilirubinaemia. In older children, there are several disease states which may affect drug–protein binding, including hepatic disease, nephrotic syndrome, chronic renal failure, cardiac failure and malnutrition.

Blood–brain barrier
The blood–brain barrier is a permeability barrier between the circulation and the brain cells bathed in cerebrospinal fluid (CSF). The blood–brain barrier is functionally incomplete in the neonate, and certain substances show increased penetration into the brain. One of the most important factors which determine the rate of transport of drugs across the blood–brain barrier is their lipid solubility. This gives rise to increased brain uptake of barbiturates and morphine in infants. As meningitis is a relatively common problem in paediatric practice, the extent to which antimicrobial agents penetrate the CSF is an important consideration. Although some agents penetrate poorly under normal circumstances, in the presence of meningeal inflammation, penetration may be considerably enhanced, so that adequate CSF drug concentrations are attained. Drugs in this category include penicillins, cefalosporins, rifampicin and vancomycin. Drugs which penetrate well even in the absence of meningeal inflammation include chloramphenicol and the combination sulfamethoxazole and trimethoprim. Although the aminoglycosides continue to be used for meningitis caused by Gram-negative organisms, the CSF concentrations achieved are generally low and inconsistent. Higher concentrations can be obtained by direct intrathecal or intraventricular injections, but controversy exists over the efficacy of such routes of administration. The newer cefalosporins, such as cefotaxime, appear to be more appropriate agents in most cases.

Metabolism
The various metabolic reactions that occur in the mature liver are not fully developed at birth. Cardiac insufficiency and respiratory distress may also contribute to decreased metabolic activity. Lidocaine, phenobarbital, phenytoin and diazepam show decreased metabolism in the neonate, resulting in increased drug half-lives. During the first 15 days of life in premature and full-term babies, decreased metabolism is evident, but this is followed by a dramatic increase. Between 1 and 10 years of age, hepatic microsomal x WHO Model Formulary for Children 2010

the lower the gestational age of the infant. Hubert H. Most sick neonates receive antibiotics for suspected or proven infection. and should be used in conjunction with guidelines such as the WHO Pocket Book of Hospital Care for Children. so that half-lives similar to those seen in adults are usually achieved by the end of the first month. Speech at the dedication of the Hubert H Humphrey building. DC. however. Renal function is of particular importance to drug disposition in the neonatal period.oxidation is more rapid than in adults.shtml (accessed 30 March 2008). This more rapid metabolism is almost certainly due to the fact that. WHO Model Formulary for Children 2010 xi . Washington. during childhood. and most of these agents are water soluble. 4 November 1977. the liver is larger relative to body weight than in adult life. Therefore phenobarbital. Excretion Renal function is significantly less developed in premature and full-term neonates than it is in children and adults. Allometric scaling may give a better prediction of the metabolic activity of the liver.org/IcDQuotes/IcDQuoteA. phenytoin and theophylline have shorter half-lives in children than in adults. The WHO Model Formulary for Children The hope is that this Formulary improves therapies in children by offering the best dosing information for those medicines currently listed on the EMLc. Humphrey. a substitute for the appropriate use of treatment guidelines. while tubular function does not mature fully until after this. The rate of elimination increases rapidly during the ensuing weeks. In general.vernalproject. 1. http://www. The Formulary is not. Adult values for glomerular filtration rate are reached after about 3 to 6 months of age. the more prolonged the half-life will be in this period.

Standard treatment guidelines should be consulted for information on appropriate dosage forms. xii WHO Model Formulary for Children 2010 . most often in mg/kg. Omission of a particular medication does not necessarily indicate that it is not available or recommended in children. progressive dose adjustments may be required according to the patient’s response. Dose Forms The dose form is listed as per the WHO Model List of Essential Medicines for Children March 2009. Allowances must be made when using weight as a basis for dosing in oedematous or obese children. A single medication may appear multiple times on the list in different sections for differing indications. The Formulary is intended for use for children up to 12 years of age. merely that it is not considered an essential medicine for children by WHO. When a medicine is in solution or a mixture the concentration in the medication monograph is expressed as mg/ml to avoid confusion. New England Journal of Medicine. Some countries may have access to preparations which differ in terms of concentration or dose form. In such children the ideal weight for height and age should be used. In many cases. Medicines and dosage forms are listed in alphabetical order within each section and there is no implication of preference for one form over another. Definition of age ranges Neonate: 0–28 days Infant 1–12 months Child 1–12 years If a maximum dose is listed this provides an indication of the upper dose limit when dosing paediatrics per kilogram. Surface area is calculated by the following equation: Body surface area (m2) = Ht (cm) x Wt (kg) 3600 Mosteller RD. Drug Name The generic (non-proprietary) name. this may differ from the WHO Model List of Essential Medicines for Children March 2009. Explanatory notes for drug monographs: Section and section number This indicates the section and any subsection that the medicine is classified under as per the WHO Model List of Essential Medicines for Children March 2009. Doses based on surface area are quoted for some drugs. 1987. The WHO Model Formulary for Children classifies children by age and doses medicines accordingly. 317(17):1098 (letter). Simplified calculation of body surface area.How to use the WHO Model Formulary for Children Medication monographs are listed by section according to the WHO Model List of Essential Medicines for Children March 2009.

Route: Age dose and frequency. Renal impairment is usually divided into three grades: Mild: GFR 20–50 ml/minute or approximate serum creatinine 150–300 micromol/litre Moderate: GFR 10–20 ml/minute or serum creatinine 300–700 micromol/litre Severe: GFR < 10 ml/minute or serum creatinine > 700 micromol/litre Consult specialist texts for further information on use of drugs in renal impairment.000 people) WHO Model Formulary for Children 2010 xiii . Renal impairment Advice for use of this drug in these circumstances.1%–1% ( > 1 in 1. Contraindications Details of any contraindications to use of the drug.ATC Code The Anatomical Therapeutic Chemical (ATC) classification system code designated by WHO to classify drugs. Dose Indication.1% (< 1 in 1. Consult specialist texts for further information on use of drugs in hepatic impairment. Warnings Where there is a significant warning. Alternative route: Age dose and frequency. Adverse effects have been classified by incidence where possible: Common: > 1% (> 1 in 100 people) Uncommon: 0. notes if there is a WHO age/weight restriction or representative status. Special Notes Indicate if the medicine is also known by another name. different spelling or abbreviation. Also. Hepatic Impairment Advice for use of this drug in these circumstances. Precautions Details of any precautions or monitoring required. Indications Indications for use from the WHO Model List of Essential Medicines for Children March 2009. risk or adverse effect associated with using the medication. Adverse effects Details of adverse effects associated with this medication.000 people and < 1 in 100 people) Rare: < 0.

Interactions with no symbol do not usually have serious consequences. or only taken with caution and appropriate monitoring.int/medicines/areas/quality_assurance/en/index.Interactions with other medications Details any drug interactions. For recommendations and advice concerning all aspects of the quality assurance of medicines see the WHO Medicines web site http://www. Notes Includes ancillary information where applicable such as administration instructions. It is the responsibility of the relevant national or regional drug regulatory authority to ensure that each product is of appropriate pharmaceutical quality (including stability) and that when relevant.html xiv WHO Model Formulary for Children 2010 . Consult individual references for more information. The presence of an entry on the Essential Medicines List and/or WHO Children’s Formulary carries no assurance as to pharmaceutical quality. patient advice and storage instructions.who. References Includes a list of references used to compile this drug monograph. Potentially hazardous drug interactions are indicated by the symbol * meaning the combined administration of the drugs involved should be avoided. different products are interchangeable.

30 mg. 500 mg in vial. Sulfadiazine. injection: 50 mg/5 ml. solid oral dosage form: 100 mg. Carboplatin.5 mg/5 ml. 150 mg.2. tablet: 10 mg. Hyoscine hydrobromide. tablet (heat stable): 100 mg + 25 mg . 10 mg. parenteral formulation: 2 mg/ml in 1 ml ampoule. tablet (dispersible): 20 mg + 120 mg. Ibuprofen. xv Section 6. Lorazepam. Dexamethasone. Midazolam. 60 mg. Cefotaxime. Doxycycline. 25 mg. 100 mg.Changes to the WHO Model List of Essential Medicines for Children Changes made to the 1st List (October 2007) to produce the 2nd List (March 2009) are listed below. powder for injection: 250 mg per vial. Senna. Ciprofloxacin. injection: 4 mg/ml and tablet: 2 mg. Cyclizine. 400 mg and 600 mg. 5 mg. 4 mg/ml in 1 ml ampoule. powder for injection: 1 g (as pentahydrate) in vial. Artemether + lumefantrine. injection: 1 mg/ml and 5 mg/ml. tablet (heat stable): 25 mg. powder for reconstitution with water: 125 mg/5 ml. Amitriptyline. oral liquid: 250 mg/5 ml and solution for IV infusion: 2 mg/ml. oral liquid: 7.4.2 Section 6.4 Section 6. oral liquid: 100 mg/5 ml and tablet: 200 mg. granules (modified release) (to mix with water): 20 mg. injection: 50 mg/ml and tablet: 50 mg. Morphine.2 Section 8. 150 mg/15 ml. Diazepam. capsule: 100 mg and oral liquid: 50 mg/5 ml. 600 mg/60 ml. tablet: 30 mg + 60 mg. Ceftazidime.4 Section 8. 450 mg/45 ml. Atazanavir. injection: 400 micrograms/ml. 250 mg/5 ml and solid oral dosage form: 250 mg. Amikacin. Lopinavir + ritonavir (LPV/r). Lamivudine + nevirapine + stavudine.5 mg.1 Section 6. 200 mg + 50 mg. powder for injection: 100 mg. Ritonavir.3. 300 mg. 60 mg and tablet (immediate release): 10 mg.2 Section 5 Section 6.2. 100 mg. 600 micrograms/ml and transdermal patches: 1 mg/72 hours.5. 30 mg. Cefalexin. 10 mg and tablet: 5 mg. Changes to the List Additions Section 4.2.5.4 WHO Model Formulary for Children 2010 . Lamivudine + zidovudine. 60 mg + 100 mg + 12 mg. oral liquid: 10% and 20%.3 Section 6. injection: 5 mg/ml and oral liquid: 2 mg/5 ml and rectal solution: 2. tablet: 30 mg + 50 mg + 60 mg. tablet (dispersible): 30 mg + 50 mg + 6 mg. Docusate sodium. Lamivudine + nevirapine + zidovudine.2.1 Acetylcysteine. oral liquid: 25 mg/5 ml and 50 mg/5 ml. 200 mg and injection: 10 mg/ml and oral liquid: 10 mg/5 ml and tablet (controlled release): 10 mg. tablet: 500 mg.

Surfactant. age-appropriate formulations and doses including lipase. 10 mg/5 ml. Eq 8 mg base. Section 10. tablet: 2.1 mmol/ml). Dexamethasone.5 mg. WHO Model Formulary for Children 2010 Section 26. injection: 20 mg/ml (equivalent to 10 mg caffeine base/ml) and oral liquid: 20 mg/ml (equivalent to 10 mg caffeine base/ml). 4 mg.2 Enalapril. Ondansetron.05%. solution: 11. in alcohol.5 mg/5 ml.1 Section 17. solution for injection: 5 mg/ml. 20 mg.1 Section 17 Section 17. Budesonide. 2 ml and 4 ml tubes.2% in 20 ml ampoule changed to solution for dilution: 7. Section 18. 200 micrograms per dose. suspension for intratracheal instillation: 25 mg/ml or 80 mg/ml.Section 12. Spironolactone. solution: 20% (digluconate). nose and throat conditions in children (new section): Acetic acid. Chlorhexidine.2 xvi . Potassium chloride. Budesonide. nasal spray: 100 micrograms per dose.5% (equivalent to K+ 1 mmol/ml and Cl.5 mg. 10 mg. 2 mg/5 ml and solid oral dosage form: 0.3% drops. protease and amylase. injection: 4 mg/ml in 1 ml ampoule and oral liquid: 0. 5 mg. Fludrocortisone. 250 micrograms (dipropionate) per dose changed to inhalation (aerosol): 100 micrograms per dose. Ibuprofen. injection: 1000 IU/ml. 20 000 IU/ml in 1 ml ampoule changed to injection: 1000 IU/ml. Ear. Hydrocortisone. 5000 IU/ml. 40 mg.5 mg. Omeprazole. 1. topical: 2%.5 mg/ml in alcohol and Prostaglandin E2: 1 mg/ml. 0.3 Section 15. injection: 2 mg base/ml in 2 ml ampoule (as hydrochloride) and oral liquid: 4 mg base/5 ml and solid oral dosage form: Eq 4 mg base. Prostaglandin E.1 Section 28 Section 29 Amendments to dosage strength and form Section 5 Diazepam. 15% (equivalent to K+ 2 mmol/ml and Cl. 5000 IU/ml in 1 ml ampoule. Specific medicines for neonatal care (new section): Caffeine citrate.75 mg. tablet: 100 micrograms. Pancreatic enzymes.2 mmol/ml). nasal spray: 0. tablet: 5 mg. 40 mg sachets and solid oral dosage form: 10 mg. 50 micrograms per dose (dipropionate).5 ml. 25 mg/5 ml and tablet: 25 mg. Xylometazoline.1 Heparin sodium. solution for injection: Prostaglandin E: 0. powder for oral liquid: 20 mg. 20 mg.2 Section 16 Section 25. topical: 0. Ciprofloxacin. injection: 5 mg/ml in 2 ml ampoule (intravenous or rectal) changed to rectal solution or gel: 5 mg/ml in 0. oral liquid: 1 to 20 mg/ml and tablet: 25 mg changed to oral liquid: 5 mg/5 ml.

injection: 20 mg/ml (equivalent to 10 mg caffeine base/ml) and oral liquid: 20 mg/ml (equivalent to 10 mg caffeine base/ml).1% to 2. Rifampicin + isoniazid + pyrazinamide. injection: 250 mg (sodium salt) in 4 ml ampoule and tablet: 500 mg. 25 mg (hydrochloride). 50 mg in vial. solution: 11.Deletions Section 6. powder for injection: 50 mg in vial. Sulfadiazine. 60 mg + 60 mg (for intermittent use three times weekly). powder for injection: 10 mg.2 Amphotericin B. oral powder: 50 mg/g and tablet: 250 mg (as mesilate).3 Section 8. WHO Model Formulary for Children 2010 xvii .2.2. tablet: 60 mg + 30 mg + 150 mg. Intermediate-acting insulin. powder for injection: 500 mg (as lactobionate) in vial.5. Caffeine citrate. injection: 40 IU/ml in 10 ml vial (as compound insulin zinc suspension or isophane insulin).2 Section 18. injection: 40 IU/ml in 10 ml vial. 4% glucose. tablet: 60 mg + 30 mg. 0. ointment: 0. injection: 25 mg (hydrochloride)/ml in 2 ml ampoule and oral liquid: 5 mg (hydrochloride)/5 ml and tablet: 10 mg. As deoxycholate or liposomal. Rifampicin + isoniazid.2 Section 13.2 Section 26.2. Section 6. Cl.0%. Glucose with sodium chloride.2 Moved from complementary to core Section 6. Dithranol. Potassium chloride. Insulin injection (soluble).30 mmol/l). Nelfinavir (NFV).18% sodium chloride (equivalent to Na+ 30 mmol/l.2 Section 6.2% in 20 ml ampoule. Cisplatin.4 Erythromycin. Promethazine.5 Section 17.5 Section 25.4.

xviii WHO Model Formulary for Children 2010 .

........SECTION 1: Anaesthetics 1..................................1 1............................. 2 Local anaesthetics ...........................2 1..............................................................3 General anaesthetics and oxygen............ 8 Preoperative medication and sedation for short-term procedures.............. 13 WHO Model Formulary for Children 2010 1 ....

it is essential that facilities for intubation and mechanically assisted ventilation are available. Halothane Inhalation ATC code: N01AB01 Special Notes: This medicine is listed as a representative of its pharmacological class.e. opioid analgesics (section 2.3). cholinesterase inhibitors.1 Anaesthetics 1 1. Inhalation through specifically calibrated vaporizer: Infant or Child 0. Adverse effects: Common Bradycardia. Inhalation through specifically calibrated vaporizer: Infant or Child initially 0.1 Anaesthetics General anaesthetics and oxygen To produce a state of prolonged full surgical anaesthesia reliably and safely. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. Anaesthesia should be undertaken by non-specialist personnel only as a last resort. A range of other drugs including local anaesthetics (section 1. careful administration of a variety of drugs and close monitoring of the patient are required. Uncommon Arrhythmias. even when air is used as the carrier. Irrespective of the type of anaesthesia used (i. Maintenance of anaesthesia. Oxygen should be added routinely during anaesthesia with inhalation agents. Indications: Induction and maintenance of anaesthesia.2). hepatitis (may be fatal). section 20) may also be required.g. Dose: Induction of anaesthesia. respiratory depression. to protect against hypoxia. Hepatic impairment: Avoid if history of unexplained pyrexia or jaundice following previous exposure to halothane. Precautions: Anaesthetic history should be carefully taken to determine previous exposure and previous reactions to halothane (fulminant hepatic failure is a rare complication of re-exposure to halothane).1).5–2% in oxygen or nitrous oxide-oxygen. family history of malignant hyperthermia. raised cerebrospinal fluid pressure. The information in this monograph only applies to the medicine listed here.5% then gradually increase inspired gas concentration to 1. Anaesthesia may be induced and maintained with intravenous medications and/or inhalation of a volatile agent (section 1. preoperative medications (section 1. avoid use if adequate resuscitation facilities are not available. because anaesthetic drugs may be fatal if inappropriately used. 2 WHO Model Formulary for Children 2010 .5–2% in oxygen or nitrous oxide-oxygen. general or regional). Contraindications: History of unexplained jaundice or fever following previous exposure to halothane. porphyria.2). muscle relaxants and reversal agents (e.

int/medicines/publications/essentialmeds_committeereports/TRS_950. Vancomycin: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. administer an antisialogogue to prevent excessive salivation leading to respiratory difficulties. Stuart MC. for example riding a bike or operating machinery. Does not augment salivary or bronchial secretions. severe cardiac disease. British national formulary for children 2009. intracerebral mass or haemorrhage or other cause of raised intracranial pressure.1 Interactions with other medicines (* indicates severe): General anaesthetics and oxygen Amitriptyline: increased risk of arrhythmias and hypotension. hypertension. BMJ Group RBS Publishing. Paediatric Formulary Committee. 2008. during recovery. Enalapril: enhanced hypotensive effect.who. * Fluphenazine: enhanced hypotensive effect. * Levodopa: risk of arrhythmias. Suxamethonium: enhanced effects of suxamethonium. analgesia for painful procedures of short duration. eds. Kouimtzi M. London. porphyria. Precautions: Increased cerebrospinal fluid pressure. 950 (http://www. Spironolactone: enhanced hypotensive effect. Isoniazid: possible potentiation of isoniazid hepatotoxicity. WHO Technical Report Series. October 2007 (including the model list of essential medicines for children).pdf ). * Chlorpromazine: enhanced hypotensive effect. eye injury and increased intraocular pressure. predisposition to hallucinations or nightmares. Diazepam: enhanced sedative effect. WHO model formulary. Furosemide: enhanced hypotensive effect. psychiatric disorders. supplementary analgesia often required in surgical procedures involving visceral pain pathways (morphine may be used but addition of nitrous oxide will often suffice). The selection and use of essential medicines: report of the WHO expert committee. Geneva. patient must remain undisturbed but under observation. WHO expert committee on the selection and use of essential medicines.1. for 24 hours. cerebral trauma. Epinephrine (adrenaline): risk of arrhythmias. WHO Model Formulary for Children 2010 3 . * Haloperidol: enhanced hypotensive effect. history of cerebrovascular accident. Vecuronium: enhanced effects of vecuronium. References: Hill SR. World Health Organization. Contraindications: Thyrotoxicosis. Ketamine ATC code: N01AX03 Injection: 50 mg (as hydrochloride)/ml in 10 ml vial Indications: Induction and maintenance of anaesthesia. 2008. * Verapamil: enhanced hypotensive effect and AV delay. 2009. particularly hallucinations. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Notes: Preferred drug if intubation is likely to be difficult.

hypersalivation. Induction and maintenance of anaesthesia (longer procedures). * Fluphenazine: enhanced hypotensive effect. dressing of burns. Intravenous injection over at least 60 seconds: Neonate. Infant or Child 4–13 mg/kg (4 mg/kg sufficient for some diagnostic procedures). Diazepam: enhanced sedative effect. radiotherapeutic procedures. such as delirium. Adverse effects: Common Raised blood pressure and pulse rate. dilute to a concentration of no more than 50 mg/ml with glucose 5% or sodium chloride 0. Notes: For IV injection. Infant or Child 1–2 mg/kg produces 5–10 minutes of surgical anaesthesia. Enalapril: enhanced hypotensive effect. marrow sampling and minor orthopaedic procedures). Induction and maintenance of anaesthesia (short procedures). raised intracranial pressure. Interactions with other medicines (* indicates severe): Amitriptyline: increased risk of arrhythmias and hypotension. adjusted according to response. For continuous IV infusion. emergence reactions including hallucinations.g. * Chlorpromazine: enhanced hypotensive effect. Rare Arrhythmias. Anaesthesia persists for up to 15 minutes after a single intravenous injection and is characterized by profound analgesia. irrational behaviour. * Haloperidol: enhanced hypotensive effect. dilute to a concentration of 1 mg/ml with glucose 5% or sodium chloride 0. * Verapamil: enhanced hypotensive effect and AV delay.5–2 mg/kg followed by a continuous intravenous infusion of 500 micrograms/kg/hour adjusted according to response. Furosemide: enhanced hypotensive effect. use microdrip infusion for maintenance of anaesthesia. up to 2 mg/kg/hour may be used to produce deep anaesthesia. confusion. analgesia for short painful procedures. adjusted according to response. 10 mg/kg usually produces 12–25 minutes of surgical anaesthesia. Continuous intravenous infusion: Neonate initially 0.5–2 mg/kg followed by a continuous intravenous infusion of 0. increased muscle tone. Uncommon Hypotension.1 Anaesthetics Dose: Titrate dose to effect. Isoniazid: possible potentiation of isoniazid hepatotoxicity. bradycardia.9% or water for injection. Premedication with an anticholinergic to reduce secretions is recommended before its use in anaesthesia. Subanaesthetic doses may be used to provide analgesia and sedation for painful procedures of short duration (e.9%. Vancomycin: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. Recovery is relatively slow and associated with a high incidence of hallucinations and other emergence reactions. restlessness. 4 WHO Model Formulary for Children 2010 . Infant or Child initially 0.6–2. Spironolactone: enhanced hypotensive effect. raised intraocular pressure.7 mg/kg/hour adjusted according to response. Intramuscular injection: Neonate 4 mg/kg for 15 minutes of surgical anaesthesia (adjusted according to response).

Inhalation using suitable anaesthetic apparatus: Neonate. Uncommon Arrhythmias. Drugdex system. Greenwood Village. leukopenia. decompression sickness. pericardial or peritoneal space. during postoperative physiotherapy and for refractory pain in terminal illness. Paediatric Formulary Committee. 2010. 2009. Rare Malignant hyperthermia. Rossi S. Notes: Should not be used as a sole anaesthetic agent due to lack of potency. Contraindications: Demonstrable collection of air in pleural (pneumothorax). Australian medicines handbook. 2009. according to the child’s needs. ed. Diazepam: enhanced sedative effect.com. London. vitamin B12 deficiency. arterial air embolism. neuropathy and myeloneuropathy. Geneva. Inhalation using suitable anaesthetic apparatus: Neonate. British national formulary for children 2009. Paediatric Formulary Committee. * Methotrexate: increased antifolate effect (avoid concomitant use). Kouimtzi M. London. 2008. intestinal obstruction. Australian Medicines Handbook. Vancomycin: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. WHO model formulary. Furosemide: enhanced hypotensive effect. Spironolactone: enhanced hypotensive effect. occlusion of middle ear. Australian medicines handbook. after prolonged administration: megaloblastic anaemia. Dose: Maintenance of light anaesthesia. accessed 10 February 2010). Adelaide. Stuart MC. Hodding JH. Enalapril: enhanced hypotensive effect. * Chlorpromazine: enhanced hypotensive effect. * Haloperidol: enhanced hypotensive effect. * Fluphenazine: enhanced hypotensive effect. Interactions with other medicines (* indicates severe): Amitriptyline: increased risk of arrhythmias and hypotension. Taketomo CK. ed. Analgesia. WHO model formulary.1 References: General anaesthetics and oxygen Hill SR. BMJ Group RBS Publishing. 2008. Adelaide. Kouimtzi M. Kraus DM. analgesia for emergency management of injuries. ed. Adverse effects: Common Nausea and vomiting. Lexi-Comp.1. Isoniazid: possible potentiation of isoniazid hepatotoxicity. Stuart MC. Pediatric dosage handbook. Rossi S. 2009. 16th ed. * Verapamil: enhanced hypotensive effect and AV delay. Nitrous oxide ATC code: N01AX13 Inhalation Indications: Maintenance of anaesthesia in combination with other anaesthetic agents and muscle relaxants. agranulocytosis. World Health Organization. 2009. chronic obstructive airway disease. eds. emphysema. Infant or Child up to 50% in oxygen. British national formulary for children 2009. Geneva. World Health Organization. Infant or Child up to 66% in oxygen. Australian Medicines Handbook. References: Hill SR. Thomson Micromedex. WHO Model Formulary for Children 2010 5 .thomsonhc. (http://www. Klasco RK. eds. Precautions: Minimize exposure of staff. Hudson. 2009. BMJ Group RBS Publishing.

brain damage. Dose: Concentration of oxygen in inspired anaesthetic gases should never be less than 21%. eds. Thiopental ATC code: N01AF03 Powder for injection: 0. Short-term use of 100% is not associated with these toxic effects. Hepatic impairment: No dosage adjustment necessary. reducing valves on oxygen cylinders must not be greased (risk of explosion). Geneva. Interactions with other medicines (* indicates severe): * Bleomycin: serious pulmonary toxicity in patients exposed to conventional oxygen concentrations during anaesthesia. and especially in pre-term neonates can cause retinopathy with blindness and chronic lung disease. monitoring of the oxygen delivered is strongly recommended. Adverse effects: Long-term use of concentrations greater than 80% have a toxic effect on the lungs leading to pulmonary congestion. Notes: Monitoring of oxygen delivered is strongly recommended. Avoid use of cautery when oxygen is used with ether. porphyria. World Health Organization. Used during resuscitation and in the treatment of respiratory problems requiring supplemental oxygen. References: Hill SR. to protect against hypoxia. Indications: Maintain adequate tissue oxygenation in inhalational anaesthesia and other indications for use in neonates and children. Contraindications: Inability to maintain airway. if available. If available. severe cardiovascular disease. even when air is used as the carrier gas. 2008. The concentration required depends on the condition being treated. The concentration required depends on the condition being treated. anaesthesia of short duration. as inappropriate concentration may have serious or even lethal effects. Oxygen should be added routinely during anaesthesia with inhalational agents. dyspnoea or obstructive respiratory disease.5 g. Use of 100% oxygen should not be withheld in an emergency situation. 6 WHO Model Formulary for Children 2010 . use oxygen analyser to monitor inspired oxygen and pulse oximeter to monitor oxygen saturation. Risks include morbidity. 1 g (sodium salt) in ampoule Special Notes: Specialist skills required for administration and supportive management. and preferably 30% or above. hypersensitivity to barbiturates. Special Notes: Inhalation gas. Renal impairment: No dosage adjustment necessary. exudation and atelectasis. WHO model formulary. Kouimtzi M. Indications: Induction of anaesthesia prior to administration of inhalational anaesthetic.1 Anaesthetics Oxygen ATC code: V03AN01 Inhalation (medicinal gas) Fire hazard. Stuart MC.

Enalapril: enhanced hypotensive effect. hypotension. Silver sulfadiazine: enhanced effects of thiopental. give over at least 10–15 seconds. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.1.1 General anaesthetics and oxygen Precautions: Asthma. cough. administer slowly. dilute to a concentration of 25 mg/ml with water for injection. Repeated doses have a cumulative effect especially in neonates where recovery is slower. for 24 hours. Monitoring for hypotension and respiratory compromise is required. hepatic impairment. reconstituted solution is highly alkaline: extravasation can result in extensive tissue necrosis and sloughing. Sulfadoxine + pyrimethamine: enhanced effects of thiopental. Infant or Child initially up to 5 mg/kg. rash. Avoid rapid IV injection (may cause hypotension or decreased cardiac output). cardiorespiratory depression. * Haloperidol: enhanced hypotensive effect. Lower doses are needed in shock and low cardiac output states.5% (25 mg/ml) solution over 10–15 seconds: Neonate initially up to 2 mg/kg. Induction of anaesthesia. then 1 mg/kg repeated as necessary (maximum total dose 4 mg/kg). Renal impairment: May need to reduce dose in severe impairment. rapid administration may result in severe hypotension and hiccups. * Chlorpromazine: enhanced hypotensive effect. myotonic dystrophy. Furosemide: enhanced hypotensive effect. injection site reactions. WHO Model Formulary for Children 2010 7 . sneezing. Interactions with other medicines (* indicates severe): Amitriptyline: increased risk of arrhythmias and hypotension. myocardial depression. allergic reactions. anaesthesia of short duration (< 15–20 minutes). Isoniazid: possible potentiation of isoniazid hepatotoxicity. cardiovascular disease. intraarterial injection causes intense pain and may result in arteriospasm. Uncommon Laryngospasm. * Verapamil: enhanced hypotensive effect and AV delay. Thiopental does not have analgesic properties. haemolytic anaemia. prolonged somnolence and recovery. Induction is rapid and excitement does not usually occur. * Fluphenazine: enhanced hypotensive effect. Adverse effects: Common Hypotension. Hepatic impairment: Reduce dose for induction in severe liver disease. Rare Anaphylaxis. bronchospasm. cardiac arrhythmias. Sulfamethoxazole + trimethoprim: enhanced effects of thiopental. Dose: Titrate dose to effect. Spironolactone: enhanced hypotensive effect. Notes: For intravenous injection. Diazepam: enhanced sedative effect. Sulfadiazine: enhanced effects of thiopental. Vancomycin: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. then 1 mg/kg repeated as necessary (maximum total dose 7 mg/kg). transient erythema. renal impairment. Slow IV injection usually as a 2. for example riding a bike or operating machinery.

au/Search/Search. Indications: Infiltration anaesthesia. WHO expert committee on the selection and use of essential medicines. spinal or epidural anaesthesia (except in dehydrated or hypovolaemic patients). 2010. Precautions: Respiratory impairment.who. Local anaesthetics have variable properties and a range of uses. myasthenia gravis. Various drugs can serve as alternatives. post-operative analgesia.com. ed. Rossi S. MIMS Online.1 Anaesthetics References: Hodding JH. 1.pdf ). London.mimsonline. 2009.int/medicines/publications/essentialmeds_committeereports/TRS_950.5% (hydrochloride) in vial Injection for spinal anaesthesia: 0. WHO Technical Report Series. use in intravenous infusions. porphyria. 2008. 2009. epilepsy. Adelaide. septicaemia. Contraindications: Local inflammation or infection. BMJ Group RBS Publishing. epidural and spinal anaesthesia).com. Paediatric Formulary Committee. Therefore. nerve blocks and regional. The selection and use of essential medicines: report of the WHO expert committee. accessed 10 February 2010). 2009. local anaesthesia and more specialized anaesthetic procedures requiring higher level technical skills (e. Lexi-Comp. hepatic impairment. British national formulary for children 2009. Greenwood Village. Kraus DM. 8 WHO Model Formulary for Children 2010 . Bupivacaine ATC code: N01BB01 Injection: 0. UBM Medica.2 Local anaesthetics Drugs used for conduction anaesthesia (also termed local or regional anaesthesia) reversibly block conduction along nerve fibres. 16th ed. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. Thomson Micromedex. spinal or epidural anaesthesia in dehydrated or hypovolaemic patients. Pediatric dosage handbook.5% glucose solution Special Notes: Bupivacaine is a representative local anaesthetic. Facilities for resuscitation should be available at all times. great care should be taken to avoid accidental intravascular injection or unwanted systemic absorption. This medicine is listed as a representative of its pharmacological class. 0. Bier’s block). Sydney. peripheral and sympathetic nerve block.g.thomsonhc. ed. severe anaemia or heart disease. accessed 10 February 2010). (http://www. Klasco RK. The information in this monograph only applies to the medicine listed here.g. Local anaesthetic toxicity Local anaesthetic toxicity is usually due to excessively high plasma concentrations. Drugdex system. Australian medicines handbook. Hudson. 950 (http://www. Australian Medicines Handbook.5% (hydrochloride) in 4 ml ampoule to be mixed with 7. 2009 (http://www. Taketomo CK. These include topical (surface) anaesthesia. intravenous regional anaesthesia (e.25%.aspx. spinal or epidural anaesthesia in patients taking anticoagulant therapy or with coagulation disorders. October 2007 (including the model list of essential medicines for children). hypersensitivity to amide local anaesthetics.

WHO Model Formulary for Children 2010 9 .5 mg/kg). Australian medicines handbook.5 ml/kg of 0. tremors. epidural or caudal anaesthesia.3–2. 1–2. Quinidine: increased myocardial depression. Paediatric Formulary Committee. accessed 10 February 2010). cardiac arrest.5% solution (2. arrhythmias. * Propranolol: increased risk of bupivacaine toxicity.5 ml/kg of 0. Do not use solutions containing preservatives for spinal. References: Hodding JH. skin irritation. maximum dose 1 ml/kg of 0.com. dizziness. headache. 2009. BMJ Group RBS Publishing.5–2. 0. 0. Sydney. blurred vision. Hepatic impairment: Avoid (or reduce dose) in severe liver disease. ed. 0. vomiting.5% solution.1. Pediatric dosage handbook. epidural block in surgery. Common Hypotension. Greenwood Village. Rossi S.5 mg/kg as a 0. Renal impairment: No dosage adjustment necessary.5% preservative free solution. Uncommon Seizures. Drugdex system.25% or 0. UBM Medica. Adelaide. using 0. Rare Heart block. respiratory failure. Lexi-Comp.25% solution.5 mg/kg. 1–2.5 mg/kg as a 0.2 Dose: Local anaesthetics Dose needs to be adjusted according to child’s physical status and nature of procedure. 2009. petechiae. Adverse effects: Adverse effects generally occur only with excessive dosage or following intravascular injection. confusion.com. Kraus DM. oedema. maximum dose 1 ml/kg of 0. using 0.5% solution. ed. restlessness. 2009 (http://www.au/Search/Search. somnolence. 2009. London. 0. accessed 10 February 2010). (http://www.mimsonline. Interactions with other medicines (* indicates severe): Lidocaine: increased myocardial depression (interaction less likely when lidocaine used topically). Taketomo CK. Klasco RK.5% solution. Procainamide: increased myocardial depression. paraesthesia.5% preservative free solution. British national formulary for children 2009. Local infiltration. Caudal block in surgery. constipation. erythema at injection site. 2010. MIMS Online. hypersensitivity reactions.aspx. Peripheral nerve block.25% solution. Thomson Micromedex. or in epilepsy or acute illness. lightheadedness. nausea.thomsonhc. 16th ed. Hudson. Australian Medicines Handbook.25% or 0. NOTe Use lower doses for debilitated patients.5 mg/kg.

Child up to 3 mg/kg (0.3 ml/kg of 1% solution and 0. oedema. Various drugs can serve as alternatives. respiratory impairment. Common Hypotension. not repeated within 2 hours. Surface anaesthesia of urethra. epilepsy. tremors. Child up to 3 mg/kg (0. Rare Heart block. Indications: Local anaesthetic blocks. hypersensitivity to amide local anaesthetics. Local infiltration and peripheral nerve block. Surface anaesthesia of pharynx. cardiac arrest. Renal impairment: Severe: use with caution. Contraindications: Local inflammation or infection. petechiae. Do not use solutions containing preservatives for spinal. maximum dose 200 mg).5%). skin irritation. severe shock. Hepatic impairment: Avoid (or reduce dose) in severe liver disease. larynx. This medicine is listed as a representative of its pharmacological class. * Acetazolamide: hypokalaemia caused by acetazolamide antagonizes action of lidocaine. erythema at injection site. porphyria. spinal or epidural anaesthesia in dehydrated or hypovolaemic patients.075 ml/kg). not repeated within 2 hours. not repeated within 2 hours. Child up to 3 mg/kg (0. Uncommon Seizures. headache. epidural. using 1% or 2% solution. nausea. Child up to 3 mg/kg (0. dizziness. constipation. Adverse effects: Adverse effects generally occur only with excessive dosage or following intravascular injection.5% glucose solution Topical forms: 2% to 4% (hydrochloride) Special Notes: Lidocaine is a representative local anaesthetic. hepatic impairment. using 5% solution (with glucose 7. severe anaemia or heart disease.06 ml/kg). restlessness. The information in this monograph only applies to the medicine listed here. 2% (hydrochloride) in vial Injection for spinal anaesthesia: 5% (hydrochloride) in 2 ml ampoule to be mixed with 7. hypersensitivity reactions and respiratory failure. myasthenia gravis. 10 WHO Model Formulary for Children 2010 . Use the lowest effective dose and concentration. Precautions: Bradycardia. Dose: Dose needs to be adjusted according to child’s physical status and nature of procedure.15 ml/kg of 2% solution. trachea. caudal or intravenous regional anaesthesia. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. vomiting.075 ml/kg).1 Anaesthetics Lidocaine ATC code: N01BB02 Injection: 1%. arrhythmias. using 4% topical solution. impaired cardiac conduction. paraesthesia. somnolence. dental work and spinal anaesthesia. Instil using a jet spray or apply with a swab. not repeated within 2 hours. using 4% topical solution. renal impairment. septicaemia. lightheadedness. Spinal anaesthesia. blurred vision. Interactions with other medicines (* indicates severe): NOTe Interactions less likely when lidocaine is used topically. confusion. spinal or epidural anaesthesia in patients taking anticoagulant therapy or with coagulation disorders.

Australian Medicines Handbook. porphyria. 16th ed.1. MIMS Online. Lidocaine + Epinephrine (Adrenaline) ATC code: N01BB52 Dental cartridge: 2% (hydrochloride) + epinephrine 1:80 000 Injection: 1%. ears. septicaemia. ePINePHRINe Hypertension. Suxamethonium: neuromuscular blockade enhanced and prolonged. respiratory impairment. ed. 2009. * Furosemide: action of lidocaine antagonized by hypokalaemia caused by furosemide. cerebrovascular disease. Drugdex system. renal impairment. accessed 10 February 2010). hypersensitivity to amide local anaesthetics. 2009. Greenwood Village. Klasco RK. myasthenia gravis. Sydney. References: Hodding JH.au/Search/Search. * Procainamide: increased myocardial depression.com.com. Kraus DM. spinal or epidural anaesthesia in dehydrated or hypovolaemic patients. such as fingers. epilepsy. Lopinavir: possibly increased plasma concentration of lidocaine. Indications: Dental anaesthesia. Precautions: LIDOCAINe Bradycardia. * Propranolol: increased myocardial depression. Australian medicines handbook.2 Local anaesthetics * Atenolol: increased myocardial depression. severe shock. diabetes mellitus. heart disease. Do not repeat the dose within 2 hours. nose and penis. Taketomo CK. Rossi S. thyroid disease. British national formulary for children 2009. hepatic impairment. * Timolol: increased myocardial depression. avoid for ring block of digits or appendages (risk of ischaemic necrosis). ePINePHRINe Cerebral arteriosclerosis. Contraindications: LIDOCAINe Local inflammation or infection. peripheral nerve block. Hepatic impairment: LIDOCAINe Avoid (or reduce dose) in severe liver disease. arrhythmias.aspx. due to procedure. ed. 2010. Renal impairment: LIDOCAINe Severe: use with caution. Adelaide. severe anaemia or heart disease. infiltration anaesthesia. impaired cardiac conduction. Bupivacaine: increased myocardial depression. Dose: Child all ages dose needs to be adjusted according to child’s physical status and nature of Special Notes: Do not use in digits and appendages. WHO Model Formulary for Children 2010 11 . UBM Medica. Maximum dose of lidocaine with epinephrine is 7 mg/kg/dose. accessed 10 February 2010).thomsonhc. BMJ Group RBS Publishing. London. * Hydrochlorothiazide: action of lidocaine antagonized by hypokalaemia caused by hydrochlorothiazide. * Quinidine: increased myocardial depression. Use the lowest effective dose and concentration. Hudson.mimsonline. Pediatric dosage handbook. 2009 (http://www. toes. (http://www. Thomson Micromedex. 2009. * Verapamil: increased myocardial depression. spinal or epidural anaesthesia in patients taking anticoagulant therapy or with coagulation disorders. Paediatric Formulary Committee. Lexi-Comp. heart block. 2% (hydrochloride) + epinephrine 1:200 000 in vial risk of ischaemic necrosis. hypersensitivity to sympathomimetic amines. Mainly used for dental anaesthesia. increased risk of lidocaine toxicity.

* Timolol: increased myocardial depression. Use preservative free solutions for epidural or caudal use. lightheadedness. * Acetazolamide: hypokalaemia caused by acetazolamide antagonizes action of lidocaine.aspx. Kraus DM. British national formulary for children 2009.1 Anaesthetics injection. Suxamethonium: neuromuscular blockade enhanced and prolonged.thomsonhc. cardiac arrest.com. Sydney. hypersensitivity reactions. nausea. ed. (http://www. Uncommon Seizures. Lopinavir: possibly increased plasma concentration of lidocaine. Hudson. oedema. * Furosemide: action of lidocaine antagonized by hypokalaemia caused by furosemide. Paediatric Formulary Committee. accessed 10 February 2010). Drugdex system. 2009. Taketomo CK. bradycardia. * Verapamil: increased myocardial depression. Notes: Do not administer intravenously or intra-arterially. 2009. headache. * Procainamide: increased myocardial depression. 2010. constipation. paraesthesia. skin irritation. 16th ed. dizziness. ed. Bupivacaine: increased myocardial depression. Thomson Micromedex. Rare Heart block. * Quinidine: increased myocardial depression. Australian Medicines Handbook. 2009 (http://www. Adelaide. Pediatric dosage handbook.com. confusion. 12 WHO Model Formulary for Children 2010 . Before injecting for local anaesthesia. * Hydrochlorothiazide: action of lidocaine antagonized by hypokalaemia caused by hydrochlorothiazide. arrhythmias. restlessness.mimsonline. blurred vision. tremors. respiratory failure. accessed 10 February 2010). vomiting. Interactions with other medicines (* indicates severe): LIDOCAINe NOTe Interactions less likely when lidocaine is used topically. increased risk of lidocaine toxicity. somnolence. * Propranolol: increased myocardial depression. Adverse effects: Adverse effects generally occur only with excessive dosage or following intravascular Common Hypotension. Rossi S. 2009.au/Search/Search. Lexi-Comp. Klasco RK. erythema at injection site. * Atenolol: increased myocardial depression. References: Hodding JH. BMJ Group RBS Publishing. UBM Medica. MIMS Online. petechiae. withdraw syringe plunger to make sure that injection is not into a vein or artery. Australian medicines handbook. London. Greenwood Village.

delirium. Premedication may be used to help manage pain and anxiety and to improve the course of subsequent anaesthesia. severe gastrointestinal inflammatory disease. Large doses may cause paradoxical hyperexcitability. reversal of the muscarinic effects of cholinergic agents such as neostigmine and pyridostigmine. prostatic enlargement. Dose: Premedication. DOWN SyNDROMe Down syndrome children have both increased sensitivity to cardiac effects and mydriasis. Contraindications: Closed-angle glaucoma. Treatment of bradycardia secondary to cholinergic stimulation. WHO Model Formulary for Children 2010 13 . myasthenia gravis. treatment of bradycardia secondary to cholinergic stimulation. heart failure. A potent analgesic such as morphine (section 2. Atropine ATC code: A03BA01 Injection: 1 mg (as sulfate) in 1 ml ampoule Indications: Preoperative medication to inhibit salivation and secretions. maximum dose 600 micrograms) 30–60 minutes before induction of anaesthesia. Hepatic impairment: Use with caution. Renal impairment: Use with caution. Infant or Child 10–20 micrograms/kg (maximum dose 600 micrograms).3 Preoperative medication and sedation for shortterm procedures Appropriate premedication is an important consideration for procedures in children requiring conduction or general anaesthesia.3 Preoperative medication and sedation for short-term procedures 1. IV: Child all ages 20 micrograms/kg (max 600 micrograms) immediately before induction of anaesthesia. ulcerative colitis. constipation. diarrhoea.2) should be administered peri-operatively to patients in severe pain or for analgesia during and after surgery. Precautions: Down syndrome. IM: Infant or Child 20 micrograms/kg (minimum dose 100 micrograms. maximum dose 600 micrograms) 30–60 minutes before induction of anaesthesia. IV: Neonate 20 micrograms/kg. gastrointestinal obstruction. hypoxia. IV: Neonate 20 micrograms/kg.1. No dose adjustment necessary. CHILDReN Children are at increased risk for rapid rise in body temperature due to suppression of sweat gland activity. cardiac disorders. tachycardia. No dose adjustment necessary. hypertension. Children with Down syndrome also have more secretions and may require atropine more frequently. hyperthyroidism. Infant or Child 20 micrograms/kg (maximum dose 600 micrograms). gastrointestinal disorders. fever and in warm environments (monitor temperature and keep patients cool). SC: Neonate 10–15 micrograms/kg 30–60 minutes before induction of anaesthesia. children. Reversal of the muscarinic effects of cholinergic agents. Infant or Child 20 micrograms/kg (minimum dose 100 micrograms.

accessed 10 February 2010). Taketomo CK. 14 WHO Model Formulary for Children 2010 . Adelaide. confusion. Australian medicines handbook. shock. 2010. Klasco RK. marked neuromuscular respiratory weakness including unstable myasthenia gravis. Thomson Micromedex. slow injection may result in paradoxical bradycardia. porphyria.mimsonline. Notes: For IV administration. severe hepatic impairment. London. Uncommon Nausea. Diazepam Tablet: 5 mg ATC code: N05BA01 Injection: 5 mg/ml in 2 ml ampoule Special Notes: Drug subject to international control under the Convention on Psychotropic Substances (1971). BMJ Group RBS Publishing.1 Anaesthetics rash. for 24 hours. arrhythmias. MIMS Online. 2009. Kraus DM. Rare Closed-angle glaucoma. Greenwood Village. Drugdex system.thomsonhc. Neostigmine: antagonism of effects of neostigmine. seizures. palpitations. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Pyridostigmine: antagonism of effects of pyridostigmine. fever. Precautions: Respiratory disease. Late unopposed bradycardia may result. Interactions with other medicines (* indicates severe): NOTe Many drugs have antimuscarinic effects. acute pulmonary insufficiency. Indications: Premedication before major or minor surgery (for use in short-term procedures). Chlorphenamine: increased antimuscarinic adverse effects. Rossi S. blurred vision. muscle weakness and myasthenia gravis. concomitant use of two or more such drugs can increase adverse effects such as dry mouth. tachycardia. (http://www. respiratory depression. 2009. 2009. Metoclopramide: antagonism of effects of metoclopramide on gastrointestinal activity. flushing and dryness of skin. constipation. ed. British national formulary for children 2009. marked personality disorder.com. ed. hepatic impairment. This medicine is listed as a representative of its pharmacological class. Sydney. Hudson.com. Various drugs can serve as alternatives. sleep apnoea. close observation required until full recovery after sedation.aspx. vomiting. Contraindications: Central nervous system depression or coma. References: Hodding JH. Adverse effects: Common Dry mouth. Haloperidol: possibly reduced effects of haloperidol. photophobia.au/Search/Search. The information in this monograph only applies to the medicine listed here. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. urine retention and constipation. Chlorpromazine: increased antimuscarinic adverse effects (but reduced plasma chlorpromazine concentration). Pediatric dosage handbook. sedation with amnesia for endoscopic procedures and surgery under local anaesthetic. Intravenous diazepam can cause airway obstruction and hypoxia in exactly the same way as any other intravenous anaesthetic. accessed 10 February 2010). Diazepam is a representative benzodiazepine. Lexi-Comp. 2009 (http://www. for example riding a bike or operating machinery. difficulty in micturition. administer undiluted by rapid IV injection. Amitriptyline: increased antimuscarinic adverse effects. Paediatric Formulary Committee. UBM Medica. Australian Medicines Handbook. 16th ed. renal failure.

avoid concomitant use).aspx. Nitrous oxide: enhanced sedative effect. British national formulary for children 2009. References: Hodding JH. Rare Blood dyscrasias including neutropenia. Codeine: enhanced sedative effect. accessed 10 February 2010). Furosemide: enhanced hypotensive effect. Lexi-Comp.mimsonline. excitability. Haloperidol: enhanced sedative effect. Halothane: enhanced sedative effect. 16th ed. UBM Medica. muscle weakness. pain on intravenous injection.thomsonhc. Sydney.1. Rossi S. Low doses could be used but a shorter acting agent would be preferable. Thomson Micromedex. Rifampicin: metabolism of diazepam accelerated (reduced plasma concentration). Isoniazid: metabolism of diazepam inhibited. agranulocytosis. increased cerebral sensitivity. Reduce dose by half. route should only be used if oral or intravenous administration not possible. * Ritonavir: plasma concentration possibly increased by ritonavir (risk of extreme sedation and respiratory depression. Klasco RK. Spironolactone: enhanced hypotensive effect. slurred speech. Enalapril: enhanced hypotensive effect. hallucinations and aggression. 2009. London. Chlorphenamine: enhanced sedative effect. Taketomo CK. WHO Model Formulary for Children 2010 15 . Kraus DM. MIMS Online. hypotension. 2009 (http://www. Renal impairment: Severe: start with small doses. Thiopental: enhanced sedative effect. Uncommon Respiratory depression. Paediatric Formulary Committee. Adelaide. Slow intravenous injection into large vein reduces risk of thrombophlebitis. accessed 10 February 2010). Interactions with other medicines (* indicates severe): Amitriptyline: enhanced sedative effect. 2010. Hepatic impairment: Can precipitate coma. amnesia. Drugdex system. BMJ Group RBS Publishing. Chlorpromazine: enhanced sedative effect. Hudson. Australian medicines handbook. 2009. ataxia. ed. leukopenia and thrombocytopenia. Ketamine: enhanced sedative effect. Morphine: enhanced sedative effect. Phenytoin: plasma phenytoin concentrations possibly increased or decreased by diazepam.au/Search/Search. anaemia. Australian Medicines Handbook. 2009. paradoxical insomnia. confusion. Oral: Infant or Child 200–300 micrograms/kg (maximum 10 mg) 45–60 minutes prior to procedure. Slow IV (over 2–5 minutes): Infant or Child 100–200 micrograms/kg (maximum 5 mg) immediately before procedure.com. Greenwood Village. Pediatric dosage handbook. injection pain and thrombophlebitis. Resuscitation equipment must be available.com.3 Dose: Preoperative medication and sedation for short-term procedures Premedication and sedation for clinical procedures. sedation. ed. Notes: Do not use via intramuscular injection as absorption is slow and erratic. Adverse effects: Common Drowsiness. (http://www.

postural hypotension. dry mouth. Interactions with other medicines (* indicates severe): Amitriptyline: possibly increased sedation. prostatic hypertrophy. dysphoria. raised intracranial pressure or head injury (affects pupillary responses vital for neurological assessment). (http://www. Australian medicines handbook. Uncommon Respiratory depression (dose related). Rare Syndrome of inappropriate antidiuretic hormone secretion (SIADH). UBM Medica. British national formulary for children 2009. convulsive disorders. Haloperidol: enhanced sedative and hypotensive effect. Metoclopramide: antagonism of effect of metoclopramide on gastrointestinal activity. Hepatic impairment: Avoid or reduce dose. 2009. hepatic impairment. hypothyroidism. Risk of ten times overdose in small children. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Klasco RK. accessed 10 February 2010). constipation. spasm of urinary and biliary tract. miosis.1 mg/kg 5 minutes before the procedure. anaphylaxis. avoid injection in phaeochromocytoma. Pediatric dosage handbook. dizziness. pruritus. may precipitate coma. Notes: For intravenous administration. accessed 10 February 2010). Adelaide.thomsonhc. Dose: Special Notes: Risk of ten times overdose in small children. Diazepam: enhanced sedative effect. for example riding a bike or operating machinery. palpitations. IM: Infant or Child 0. Chlorpromazine: enhanced sedative and hypotensive effect. Precautions: Renal impairment. Paediatric Formulary Committee.com. risk of paralytic ileus. rash. vomiting. Contraindications: Respiratory depression. MIMS Online. Kraus DM. London.1 mg/kg 20 minutes before the procedure. bradycardia. Only use IM route for premedication if patient has no IV access and there is adequate respiratory monitoring available. 2009. decreased respiratory reserve and acute asthma. hypotension. Maximum dose 15 mg. Ciprofloxacin: avoid premedication with morphine (reduced plasma ciprofloxacin concentration) when ciprofloxacin used for surgical prophylaxis. Adverse effects: Common Nausea. tachycardia.mimsonline. ed. References: Hodding JH. dependence (severe withdrawal symptoms if withdrawn abruptly). increased and prolonged effect.aspx. 2009. sweating. Thomson Micromedex. extreme care required with dose Sedation and analgesia for procedures.05–0. ed. CNS depression. lightheadedness. 16 WHO Model Formulary for Children 2010 . BMJ Group RBS Publishing. Maximum dose 15 mg. 16th ed. Hudson.au/Search/Search.1 Anaesthetics Morphine ATC code: N02AA01 Injection: 10 mg (as sulfate or hydrochloride) in 1 ml ampoule calculation and preparation. Australian Medicines Handbook. 2009 (http://www. Sydney. * Ritonavir: possibly increases plasma concentration of morphine. for 24 hours. Lexi-Comp. anorexia. sedation. 2010. euphoria. Taketomo CK. Drugdex system. Rossi S. Renal impairment: Moderate to severe: reduce dose or avoid. increased cerebral sensitivity. administer slowly over 5 minutes. Indications: Preoperative sedative and analgesic. Drug subject to international control under the Single Convention on Narcotic Drugs (1961). Greenwood Village. overdosage.com. severe respiratory disease. IV: Infant or Child 0.

....2 Opioid analgesics ............................................................. antipyretics........................................ 25 WHO Model Formulary for Children 2010 17 ................. 22 2..........1 Non-opioids and non-steroidal anti-inflammatory medicines (NSAIMs).... 25 2.............................. non-steroidal anti-inflammatory medicines (NSAIMs)......SECTION 2: Analgesics.....3 Medicines used to treat gout .........4 Disease modifying agents used in rheumatoid disorders (DMARDs) ................................ medicines used to treat gout and disease modifying agents in rheumatoid disorders (DMARDs) 2.............................. 18 2......................

1). renal impairment. Non-drug strategies are also an important part of managing pain in children. active peptic ulceration or upper gastrointestinal bleeding. antipyretics. medicines used to treat gout and disease modifying agents in rheumatoid disorders (DMARDs) Pain management in children In general terms. previous peptic ulceration. NSAIMs. angioedema. hepatic failure or cardiac failure. non-steroidal anti-inflammatory medicines (NSAIMs). Ibuprofen ATC code: M01Ae01 Tablet: 200 mg. hepatic impairment. 400 mg Special Notes: WHO age/weight restriction: > 3 months. concomitant use of drugs that increase risk of bleeding. Contraindications: Hypersensitivity (including asthma.1 Non-opioids and non-steroidal anti-inflammatory medicines (NSAIMs) Non-opioid analgesics include paracetamol and NSAIMs (section 2. Combining a non-opioid with an opioid analgesic can provide more effective analgesia than either medication alone. Dose: Mild to moderate pain. such as in gastroenteritis or dehydration (increased risk of renal impairment). 18 WHO Model Formulary for Children 2010 . Precautions: Asthma. antipyretics. principles for drug management of pain in children follow the WHO Analgesic Ladder with the following recommendations for increasing pain: • mild pain: non-opioid with or without non-steroidal anti-inflammatory medicine (NSAIM) and adjuvant • moderate pain: mild opioid with non-opioid. medicines used to treat gout and DMARDs 2 Analgesics. NSAIM and adjuvant. volume depletion. 2. cardiac disease. coagulation defects. Indications: Mild to moderate pain. Oral: Infant or Child over 3 months 5–10 mg/kg three or four times daily with or after food. These are particularly suitable for musculoskeletal pain. urticaria or rhinitis) to acetylsalicylic acid or any other NSAIM. allergic disorders. NSAIM and adjuvant • severe pain: strong opioid with non-opioid. Maximum daily dose is 40 mg/kg/day.2 Analgesics. with or without specialist techniques. severe renal failure.

bronchospasm. World Health Organization. Ritonavir: plasma concentration possibly increased by ritonavir. reduced renal function and increased plasma digoxin concentration. London. colitis. British national formulary for children 2009. 2002. Kemp CA. McDowell JM. Pediatric dosage handbook. Notes: Give with or after food. * Fluoxetine: increased risk of bleeding. headache. Kouimtzi M. Dexamethasone: increased risk of gastrointestinal bleeding and ulceration. Heparin: possibly increased risk of bleeding. 2008. possibly increased risk of hyperkalaemia. WHO model formulary. Penicillamine: possible increased risk of nephrotoxicity.1 Non-opioids and non-steroidal anti-inflammatory medicines (NSAIMs) retention may occur as may deterioration in renal function possibly leading to renal failure. Lexi-Comp. Uncommon Rash. Prednisolone: increased risk of gastrointestinal bleeding and ulceration. Hydrocortisone: increased risk of gastrointestinal bleeding and ulceration. Propranolol: antagonism of hypotensive effect. Hodding JH. Kraus DM. BMJ Group RBS Publishing. Sydney.int/medicines/publications/essentialmeds_committeereports/TRS_950. dyspepsia. October 2007 (including the model list of essential medicines for children). * Phenytoin: effect of phenytoin possibly enhanced. urticaria. toxic epidermal necrolysis (Lyell syndrome). antagonism of diuretic effect. photosensitivity. 2009. * Ciclosporin: increased risk of nephrotoxicity. * Lithium: reduced excretion of lithium (increased risk of toxicity). pulmonary eosinophilia. dizziness. eds.aspx. 2008. * Warfarin: anticoagulant effect possibly enhanced. 2009. * Levofloxacin: possibly increased risk of convulsions. diarrhoea. Taketomo CK. avoid in severe liver disease. Zidovudine: increased risk of haematological toxicity. MIMS Online. 2009 (http://www. visual disturbances. Geneva. Interactions with other medicines (* indicates severe): Renal impairment: Mild: use lowest effective dose and monitor renal function. WHO Model Formulary for Children 2010 19 . Rare Angioedema. Stuart MC. gastrointestinal ulceration and bleeding. erythema multiforme (Stevens-Johnson syndrome). alveolitis. Moderate to severe: avoid. Hudson. UBM Medica. accessed 10 February 2010). Enalapril: antagonism of hypotensive effect.2. 13th ed. raised blood pressure. Digoxin: possibly exacerbation of heart failure. WHO expert committee on the selection and use of essential medicines. hepatic damage. Royal Children’s Hospital.com.mimsonline. 950 (http://www. Spironolactone: risk of nephrotoxicity of ibuprofen increased.who. References: Hill SR. Adverse effects: Common Nausea.au/Search/Search. Melbourne. fluid retention. renal impairment. The selection and use of essential medicines: report of the WHO expert committee. pancreatitis. WHO Technical Report Series. Hepatic impairment: Use with caution: increased risk of gastrointestinal bleeding and can cause fluid retention. * Methotrexate: excretion of methotrexate reduced (increased risk of toxicity). sodium and water * Acetylsalicylic acid: avoid concomitant use (increased adverse effects). increased risk of renal impairment. * Ofloxacin: possible increased risk of convulsions.pdf ). 16th ed. antagonism of diuretic effect. Furosemide: risk of nephrotoxicity of ibuprofen increased. aseptic meningitis. Paediatric pharmacopoeia. Paediatric Formulary Committee.

2009. 950 (http://www. WHO expert committee on the selection and use of essential medicines. 20 WHO Model Formulary for Children 2010 .2 Analgesics. Oral. 2009. Interactions with other medicines (* indicates severe): Metoclopramide: increased absorption of paracetamol.com. Australian medicines handbook. antipyretics. MIMS Online. in 24 hours. UBM Medica. Paediatric Formulary Committee. HePATOTOXICITy Hepatotoxicity (and less frequently renal damage) can occur after paracetamol overdosage. Refer to section 4. Hepatic impairment: Dose related toxicity. British national formulary for children 2009. fever. References: Hill SR. febrile illness.int/medicines/publications/essentialmeds_committeereports/TRS_950. Lexi-Comp. Indications: Mild to moderate pain. Stuart MC.2 for more information on paracetamol toxicity. a 5 mg/kg dose is suitable. Not recommended for anti-inflammatory use due to lack of proven benefit. avoid large doses. Pediatric dosage handbook. up to 1 g. Maximum 4 doses in 24 hours. obese. NOTe Infants under 3 months should not be given paracetamol unless advised by a doctor. Hudson.mimsonline. Precautions: Hepatic impairment.aspx. Sydney. Adelaide. Rossi S. 2009. medicines used to treat gout and DMARDs Paracetamol ATC code: N02Be01 Oral liquid: 25 mg/ml Suppository: 100 mg Tablet: 100 mg to 500 mg Special Notes: Also referred to as acetaminophen. or 4 g. WHO Technical Report Series. eds. fever. Warfarin: prolonged regular use of paracetamol possibly enhances anticoagulant effect. 2008. Geneva. October 2007 (including the model list of essential medicines for children).who. NSAIMs. every 4–6 hours as necessary. Hodding JH. renal impairment. rectal: Neonate 10 mg/kg every 6–8 hours as necessary.pdf ). thrombocytopenia. 2008. Taketomo CK. Notes: Shake suspension well before use. Infant or Child 15 mg/kg. hypersensitivity. 2009 (http://www. Kraus DM. Kouimtzi M. Maximum 4 doses. BMJ Group RBS Publishing. Dose: Mild to moderate pain. Australian Medicines Handbook. overdosage. London. accessed 10 February 2010). Children in the following situations may be at an increased risk of liver damage from paracetamol overdosage: malnourished. World Health Organization. not eaten for a few days or taking liver enzyme inducing drugs. prolonged course. pancytopenia. ed.au/Search/Search. The selection and use of essential medicines: report of the WHO expert committee. Adverse effects: Rare Rash. If neonate is jaundiced. 16th ed. neutropenia. WHO model formulary.

Reye syndrome with subsequent encephalopathy and severe hepatic injury. influenza. urticaria or rhinitis) to acetylsalicylic acid or any other NSAIM. oedema. uncontrolled hypertension. increased risk of gastrointestinal bleeding. myocarditis. If no evidence of coronary lesions after 8 weeks. gastrointestinal ulceration or bleeding. discontinue treatment or seek expert advice. increased bleeding time. G6PD deficiency. for simple analgesia and antipyrexia in children under 16 years (risk of Reye syndrome). Patients and carers should be instructed to contact the health-care provider if these symptoms develop. gastrointestinal bleeding. deterioration in renal function. previous peptic ulceration. increased risk of sodium and water retention. followed by 2–5 mg/kg once daily for 6–8 weeks. Dose: Administer with or after food. Precautions: Asthma. hepatic failure. WHO Model Formulary for Children 2010 21 . renal impairment. Oral: Infant or Child up to 130 mg/kg daily in 5–6 divided doses in acute conditions. rheumatic fever. changes in behaviour may be an early sign of Reye’s syndrome.5 mg/kg four times daily until afebrile. angioedema. bronchospasm and rash (including Stevens-Johnson syndrome). renal impairment. Infant or Child initially 7. oesophageal ulceration. Adverse effects: Common Nausea. Hepatic impairment: Avoid in severe hepatic impairment. Contraindications: Hypersensitivity (including asthma. Oral: Neonate initially 8 mg/kg four times daily until afebrile. blood dyscrasias. discontinue treatment or seek expert advice. vertigo. iron deficiency anaemia. Rare Major haemorrhage (including gastrointestinal. juvenile arthritis and Kawasaki disease. haemophilia and other bleeding disorders. If no evidence of coronary lesions after 8 weeks. Renal impairment: Increased risk of bleeding and acetylsalicylic acid induced renal impairment.5–12. dyspepsia. dexamethasone reduces plasma salicylate concentration. concomitant use of drugs that increase risk of bleeding. Interactions with other medicines (* indicates severe): Dexamethasone: increased risk of gastrointestinal bleeding and ulceration. Juvenile arthritis. Kawasaki disease. tinnitus. active peptic ulceration. dehydration.1 ATC code: N02BA01 Non-opioids and non-steroidal anti-inflammatory medicines (NSAIMs) Acetylsalicylic acid Suppository: 50 mg to 150 mg Tablet: 100 mg to 500 mg Do not use acetylsalicylic acid in children who have or who are recovering from chickenpox (varicella). Indications: Management of rheumatic fever. Severe: avoid. Special Notes: Also referred to as aspirin. 80–100 mg/kg daily in divided doses for maintenance. During treatment with acetylsalicylic acid. followed by 5 mg/kg once daily for 6–8 weeks. subconjunctival or other).2. confusion. hepatic impairment. Uncommon Hypersensitivity reactions including angioedema. acute febrile illness or flu symptoms due to the rare association with Reye’s syndrome.

com. * Ibuprofen: avoid concomitant use (increased adverse effects). Kraus DM. Geneva. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. ed. BMJ Group RBS Publishing. 2. antipyretics. Weaker opioids such as codeine are suitable for mild to moderate pain. Paediatric Formulary Committee. opioids can cause respiratory depression and coma with pinpoint pupils. 2009. WHO model formulary. 16th ed. October 2007 (including the model list of essential medicines for children). Australian Medicines Handbook. 22 WHO Model Formulary for Children 2010 . 2009 (http://www. hepatic impairment. UBM Medica. Morphine is effective in relieving moderate to severe pain.mimsonline. reduced respiratory reserve. overdosage (see section 4. 2009. medicines used to treat gout and DMARDs Enalapril: antagonism of hypotensive effect. Indications: Mild to moderate pain. MIMS Online. 2008. Metoclopramide: enhanced effect of acetylsalicylic acid (increased rate of absorption). for example riding a bike or operating machinery. Hydrocortisone: increased risk of gastrointestinal bleeding and ulceration. Opioid analgesic overdose In overdose. British national formulary for children 2009. accessed 10 February 2010). for 24 hours. The selection and use of essential medicines: report of the WHO expert committee. Spironolactone: antagonism of diuretic effect. Adelaide. eds. Hudson. * Methotrexate: reduced excretion of methotrexate (increased toxicity). Phenytoin: enhancement of effect of phenytoin. * Warfarin: risk of bleeding due to antiplatelet effect. prednisolone reduces plasma salicylate concentration.2 Analgesics. Codeine ATC code: R05DA04 Tablet: 15 mg (phosphate) Special Notes: Drug subject to international control under the Single Convention on Narcotic Drugs (1961). increased risk of renal impairment. particularly of visceral origin. 2008. hydrocortisone reduces plasma salicylate concentration. References: Hill SR. London. Pediatric dosage handbook. 2009. Naloxone (section 4.aspx. Sydney. risk of paralytic ileus. Stuart MC. antiplatelet effect of acetylsalicylic acid possibly reduced. WHO expert committee on the selection and use of essential medicines.2 Opioid analgesics Opioid analgesics act on the central nervous system. Notes: Give with or after food. Hodding JH. Precautions: Renal impairment.pdf ).who. respiratory depression. there is a large variation in patient response.2) is a specific antidote. Rossi S. Taketomo CK. WHO Technical Report Series.2). Australian medicines handbook.au/Search/Search.int/medicines/publications/essentialmeds_committeereports/TRS_950. NSAIMs. Fluoxetine: increased risk of bleeding. 950 (http://www. Kouimtzi M. Lexi-Comp. Prednisolone: increased risk of gastrointestinal bleeding and ulceration. Contraindications: Hypersensitivity to codeine or similar drugs. World Health Organization. * Heparin: enhanced anticoagulant effect of heparin. Valproic acid: enhancement of effect of valproic acid.

Adverse effects: Common Nausea. Stuart MC. ed. seizures. dry mouth.1 milligrams = 100 micrograms. headache. Indications: Postoperative pain. constipation (mainly with long-term use). UBM Medica. dependence (severe withdrawal symptoms if withdrawn abruptly). BMJ Group RBS Publishing. WHO Model Formulary for Children 2010 23 .2. London. for 24 hours. Paediatric Formulary Committee. There is a risk of misplacing the decimal point with morphine.mimsonline. Rare Syndrome of inappropriate antidiuretic hormone secretion (SIADH). pruritus. increased cerebral sensitivity. Contraindications: Respiratory depression. convulsive disorders.com. raised intracranial pressure or head injury (affects pupillary responses vital for neurological assessment). Geneva. Adelaide. severe acute and chronic pain. 2008. NOTe 0. 2009. anaphylaxis. sweating. World Health Organization. Renal impairment: Moderate to severe: reduce dose or avoid. 2009. Kouimtzi M. vomiting.au/Search/Search. eds. Hepatic impairment: Avoid or reduce dose. drowsiness. sedation. for example riding a bike or operating machinery. Australian medicines handbook. hypothyroidism. decreased respiratory reserve and acute asthma. severe respiratory disease. References: Hill SR. hypotension. hepatic impairment. British national formulary for children 2009.2 Dose: Opioid analgesics Mild to moderate pain. Sydney. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.5–1 mg/kg every 4–6 hours when needed. Notes: Increase fluid and fibre intake to avoid constipation. resulting in a 10 times overdose. Metoclopramide: antagonism of effect of metoclopramide on gastrointestinal activity. Uncommon Respiratory depression (dose related). risk of paralytic ileus. Drug subject to international control under the Single Convention on Narcotic Drugs (1961). Chlorpromazine: enhanced sedative and hypotensive effect. MIMS Online. Haloperidol: enhanced sedative and hypotensive effect. facial flushing. Infant or Child 0. Rossi S. Diazepam: enhanced sedative effect.aspx. CNS depression. avoid injection in phaeochromocytoma. euphoria. Oral: Neonate. accessed 10 February 2010). maximum 240 mg daily. 30 mg. Interactions with other medicines (* indicates severe): Amitriptyline: possibly increased sedation. increased and prolonged effect. urinary retention. Morphine ATC code: N02AA01 Injection: 10 mg (as hydrochloride or sulfate) in 1 ml ampoule Oral liquid: 2 mg (as hydrochloride or sulfate)/ml Tablet: 10 mg (as sulfate) Tablet (prolonged release): 10 mg. prostatic hypertrophy. 60 mg (as sulfate) Special Notes: extreme caution should be exercised in determining all drug doses in children. 2009 (http://www. overdosage. Precautions: Renal impairment. WHO model formulary. dependence. may precipitate coma. * Ritonavir: ritonavir possibly increases plasma concentration of codeine. Australian Medicines Handbook. dizziness.

Maximum dose is 15 mg. adjusted according to response. vomiting. adjusted according to response. Diazepam: enhanced sedative effect. Infant or Child 6 months–12 years initially 100 micrograms/kg every 4 hours. Renal impairment: Mild to moderate: reduce dose by 25%. tachycardia. Ciprofloxacin: manufacturer of ciprofloxacin advises avoid premedication with morphine (reduced plasma ciprofloxacin concentration) when ciprofloxacin used for surgical prophylaxis. increased cerebral sensitivity. 6 months–12 years initially by intravenous injection (over at least 5 minutes) 100–200 micrograms/kg then by continuous intravenous infusion 20–30 micrograms/kg/hour adjusted according to response. dizziness. may precipitate coma. adjusted according to response. adjusted according to response. adjusted according to response. palpitations. Oral (prolonged release): Child initially 200–800 micrograms/kg every 12 hours. lightheadedness. Chlorpromazine: enhanced sedative and hypotensive effect. Infant 1–6 months initially 100 micrograms/kg every 6 hours. sweating. adjusted according to response. euphoria. constipation. 2–12 years initially 200 micrograms/kg every 4 hours. anorexia. Continuous SC infusion: Child 1–3 months 10 micrograms/kg/hour. sedation. 3 months–18 years 20 micrograms/kg/hour. Oral: Child 1–12 months initially 80–200 micrograms/kg every 4 hours. Child 1– 6 months initially by intravenous injection (over at least 5 minutes) 100–200 micrograms/kg then by continuous infusion 10–30 micrograms/kg/hour adjusted to response. SC or IM: Neonate 100 micrograms/kg every 6 hours. bradycardia. Hepatic impairment: Avoid or reduce dose. dysphoria. anaphylaxis. Adverse effects: Common Nausea. adjusted according to response. 1–2 years initially 200–400 micrograms/kg every 4 hours. increased and prolonged effect. spasm of urinary and biliary tract. rash. IV injection over at least 5 minutes: Neonate initially 50 micrograms/kg every 6 hours. Rare Syndrome of inappropriate antidiuretic hormone secretion (SIADH). Severe: reduce dose by 50% or avoid. 2–12 years initially 200–500 micrograms/kg (maximum 20 mg) every 4 hours. miosis. Interactions with other medicines (* indicates severe): Amitriptyline: possibly increased sedation. dry mouth.2 Analgesics. postural hypotension. Infant or Child 6 months–2 years initially 100–200 micrograms/kg every 4 hours. sweating. Usual maximum dose is 15 mg. adjusted according to response. adjusted according to response. 24 WHO Model Formulary for Children 2010 . IV injection and infusion: Neonate initially by intravenous injection (over at least 5 minutes) 25–100 micrograms/kg then by continuous intravenous infusion 5–40 micrograms/kg/hour adjusted according to response. Uncommon Respiratory depression (dose related). medicines used to treat gout and DMARDs Dose: Pain. pruritus. Infant 1–6 months initially 100–200 micrograms/kg every 6 hours. adjusted according to response. NSAIMs. antipyretics. adjusted according to response.

dilute 2. Administer intravenous injection slowly over 5 minutes. London. Notes: Subcutaneous injection not suitable for oedematous patients. References: Hodding JH. UBM Medica.4 Disease modifying agents used in rheumatoid disorders (DMARDs) There are currently no medicines in this section of the 2nd WHO Model List of Essential Medicines for Children.2. 2. Australian Medicines Handbook. dilute with glucose 5% or 10% or sodium chloride 0. 2009 (http://www. 2009. Kraus DM. Prolonged release morphine preparations must not be crushed or chewed. Hudson. 16th ed. accessed 10 February 2010).5 mg/kg body weight to a final volume of 50 ml with infusion fluid.mimsonline. Australian medicines handbook. Pediatric dosage handbook. 2. Metoclopramide: antagonism of effect of metoclopramide on gastrointestinal activity.aspx. Paediatric Formulary Committee. 2009.4 Disease modifying agents used in rheumatoid disorders (DMARDs) Haloperidol: enhanced sedative and hypotensive effect. BMJ Group RBS Publishing. Adelaide.3 Medicines used to treat gout This section has been deleted from the 2nd WHO Model List of Essential Medicines for Children. Rossi S. British national formulary for children 2009. Child must be able to swallow the tablet whole. ed. For neonatal intensive care infusions. For continuous intravenous infusion.9%.com. MIMS Online. Sydney.au/Search/Search. * Ritonavir: ritonavir possibly increases plasma concentration of morphine. 2009. Taketomo CK. Doses should be adjusted according to response. Lexi-Comp. WHO Model Formulary for Children 2010 25 .

SECTION 3: Antiallergics and medicines used in anaphylaxis 26 WHO Model Formulary for Children 2010 .

Corticosteroids suppress or prevent almost all symptoms of inflammation associated with allergy. medications such as antihistamines and corticosteroids may be required. and thus relieve allergic symptoms. angioedema. urticaria. Intravenously as an adjunct in the emergency treatment of anaphylactic shock. Precautions: Asthma. allergic rhinitis (hayfever) and allergies to foods. for 24 hours. This medicine is listed as a representative of its pharmacological class.g. Steroids should be used for short-term suppression of inflammation.3 Antiallergics and medicines used in anaphylaxis 3 Antiallergics and medicines used in anaphylaxis Allergic disorders are a common problem in children. conjunctivitis and in pruritic skin disorders. stenosing peptic ulcer. rhinitis. bladder neck obstruction. but long-term use of steroids should be avoided. hepatic insufficiency. Contraindications: Hypersensitivity to chlorphenamine or dexchlorpheniramine. Allergic emergencies Severe allergic reactions such as anaphylaxis and angioedema are life-threatening emergencies. for example riding a bike or operating machinery. Indications: Allergic conditions including urticaria. First-line treatment for these conditions is epinephrine with appropriate resuscitation. symptomatic prostatic hypertrophy. due to the risk of significant side-effects. when symptoms are moderate or persistent. Chlorphenamine ATC code: R06AB04 Injection: 10 mg (hydrogen maleate) in 1 ml ampoule Oral liquid: 2 mg/5 ml Tablet: 4 mg (hydrogen maleate) Special Notes: Also referred to as chlorpheniramine maleate. WHO age/weight restriction: > 1 year. The information in this monograph only applies to the medicine listed here. pruritus. Allergic conditions include asthma. narrow angle glaucoma. pyloroduodenal obstruction. medicines and drugs. sedative effects. WHO Model Formulary for Children 2010 27 . SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Use of other medications in these conditions is secondary. However. eczema. urticaria and allergic rhinitis) may not require treatment. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. sneezing and nasal secretory responses that characterize allergy. Antihistamines inhibit the wheals. Allergic reactions which are mild and of limited duration (e.

28 WHO Model Formulary for Children 2010 . WHO expert committee on the selection and use of essential medicines. Thomson Micromedex. diarrhoea. Geneva. Chlorphenamine may cause excitability in children. 1–6 years 2. 6–12 years 2 mg every 4–6 hours (maximum 12 mg daily). somnolence. drowsiness. hypotension (more severe when used intravenously). Oral: 1–2 years 1 mg twice daily.who. confusion. epigastric distress. 2008. ed.org. Child under 1 year not recommended. Allergic reactions. Notes: Give intravenous injection over 1 minute.pdf ). constipation. drying effect throughout the respiratory tract and a thickening of bronchial mucus. headache.tg. Therapeutic Guidelines Limited. dry mouth. 2010. liver dysfunction. Lopinavir: possibly increased plasma concentration of chlorphenamine. Greenwood Village. 34th ed. eds.int/medicines/publications/essentialmeds_committeereports/TRS_950. 2008. Rare Disturbances in smell and taste. October 2007 (including the model list of essential medicines for children). blurred vision. anaphylaxis (adjunct). Pharmaceutical Press. Klasco RK. Renal impairment: Severe: dose reduction may be required. vomiting.5–5 mg. cardiac dysrhythmia. ed. depression. urinary retention. psychotic disorder. London. References: eTG complete. tremor. WHO model formulary. nausea.thomsonhc. 6–12 years 5–10 mg. London. World Health Organization. BMJ Group RBS Publishing. Hepatic impairment: Sedation caused by chlorphenamine inappropriate in severe liver disease. Atropine: increased antimuscarinic adverse effects.com. sleep disturbances.au/ip/. 950 (http://www. accessed 10 February 2010). Uncommon exfoliative dermatitis.3 Antiallergics and medicines used in anaphylaxis Dose: Allergy. Melbourne. paradoxical excitation. IM or IV: Child under 1 year not recommended. injection solution can be diluted with sodium chloride 0. Stuart MC. If necessary. accessed 10 February 2010). WHO Technical Report Series. eeG changes. pancytopenia and aplastic anaemia). (http://www.9% injection. 2005. The selection and use of essential medicines: report of the WHO expert committee. thrombocytopenia. Adverse effects: Common Anorexia. Martindale: the complete drug reference. blood dyscrasias (including agranulocytosis. weight gain. Diazepam: enhanced sedative effect. British national formulary for children 2009. Kouimtzi M. Sweetman SC. Hill SR. Drugdex system. Interactions with other medicines (* indicates severe): Amitriptyline: increased antimuscarinic and sedative effects. facial dyskinesias. SC. avoid. 2009. seizures. 2009 (http://etg. Paediatric Formulary Committee. 2–6 years 1 mg every 4–6 hours (maximum 6 mg daily).

Precautions: Increased susceptibility to and severity of infection. hypertension. burning or tingling in perineal area (after intravenous bolus). Short courses of high-dose systemic treatment cause fewer adverse effects than prolonged courses of lower doses. oral: oral contraceptives containing estrogens increase plasma concentration of dexamethasone. osteoporosis. activation or exacerbation of tuberculosis. Furosemide: antagonism of diuretic effect. increased appetite. hypertension. Enalapril: antagonism of hypotensive effect. myasthenia gravis. posterior subcapsular cataracts. increased susceptibility to infection. sleep and behaviour. increased risk of hypokalaemia. glaucoma. dexamethasone reduces plasma salicylate concentration. diabetes mellitus. amoebiasis. masking of signs of infection. Digoxin: increased risk of hypokalaemia. Erythromycin: erythromycin possibly inhibits metabolism of dexamethasone. cognition. Insulins: antagonism of hypoglycaemic effect. acne. IM or slow IV injection or infusion: Infant or Child 100–400 micrograms/kg in 1–2 divided doses (maximum 24 mg daily). increased risk of hypokalaemia. delayed wound healing. dyspepsia. Albendazole: plasma albendazole concentration possibly increased. strongyloidiasis. depression. Renal impairment: Dose reduction not necessary. Dose: Inflammatory and allergic disorders. * Carbamazepine: accelerated metabolism of dexamethasone (reduced effect). risk of severe chickenpox in non-immune patients (varicella zoster immunoglobulin required if exposed to chickenpox). sodium and water retention. WHO Model Formulary for Children 2010 29 . Hepatic impairment: Dose reduction not necessary. * Lopinavir: possibly reduced plasma lopinavir concentration. Adverse effects: Incidence of adverse effects is related to dose and duration of treatment. peptic ulcer. bruising. * Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions). hypersensitivity reactions including anaphylaxis. short-term suppression of inflammation in allergic disorders. psychiatric effects (see below). Hydrochlorothiazide: antagonism of diuretic effect. Common Nausea. Rare Peptic ulceration.3 Antiallergics and medicines used in anaphylaxis Dexamethasone ATC code: H02AB02 Injection: 4 mg dexamethasone phosphate (as disodium salt) in 1 ml ampoule Indications: Adjunct in the emergency treatment of anaphylaxis. Interactions with other medicines (* indicates severe): Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. Delirium or psychosis is less common. avoid exposure to measles (normal immunoglobulin possibly required if exposed). Contraindications: Not relevant to emergency use. PSyCHIATRIC eFFeCTS Include euphoria. hypomania. Contraceptives. hypokalaemia. disturbances of mood. oedema. INTRAVeNOUS Transient itching. hyperglycaemia. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. corneal perforation.

Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with dexamethasone. Praziquantel: plasma praziquantel concentration reduced.05 ml of 1 mg/ml solution). pulse and respiratory function. * Phenobarbital: metabolism of dexamethasone accelerated (reduced effect). References: Hill SR. Infant or Child 6 months–6 years 150 micrograms (0. Australian medicines handbook. BMJ Group RBS Publishing. * Phenytoin: metabolism of dexamethasone accelerated (reduced effect). Ritonavir: plasma concentration possibly increased by ritonavir. London. * Methotrexate: increased risk of haematological toxicity. hypertension.3 Antiallergics and medicines used in anaphylaxis Metformin: antagonism of hypoglycaemic effect. Propranolol: antagonism of hypotensive effect. Lexi-Comp. use during halothane or cyclopropane anaesthesia. World Health Organization. psychoneurosis. eds. WHO expert committee on the selection and use of essential medicines.int/medicines/publications/essentialmeds_committeereports/TRS_950. phaeochromocytoma. 2009.pdf ). diabetes mellitus. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose dexamethasone enhances anticoagulant effect). British national formulary for children 2009. 950 (http://www. IV (if circulation inadequate): Infant or Child 10 micrograms/kg (0. Dose: Anaphylaxis. Indications: Severe anaphylactic reaction. heart disease. 2009.15 ml of 1 mg/ml solution). Hodding JH. 2009. Paediatric Formulary Committee. Kraus DM. several times if necessary. Geneva. Special Notes: 1 mg/ml = 1:1000 or 0. IM: Infant under 6 months 50 micrograms (0.3 ml of 1 mg/ml solution). influenza: high doses of dexamethasone impair immune response. live: high doses of dexamethasone impair immune response.who. * Rifampicin: accelerated metabolism of dexamethasone (reduced effect). depending on blood pressure. Bethesda. The selection and use of essential medicines: report of the WHO expert committee. WHO model formulary. Kouimtzi M. Spironolactone: antagonism of diuretic effect. Contraindications: Closed-angle glaucoma. Adelaide. 30 WHO Model Formulary for Children 2010 . Mcevoy GK. AHFS drug information. Precautions: Hyperthyroidism. Australian Medicines Handbook. severe angioedema. Saquinavir: possibly reduced plasma saquinavir concentration. arrhythmias. 2008. Child 6–12 years 300 micrograms (0. 16th ed. 2008. Epinephrine (Adrenaline) ATC code: C01CA24 Injection: 1 mg (as hydrochloride or hydrogen tartrate) in 1 ml ampoule (1:1000) Intravenous epinephrine should be used with extreme care by specialists only. Rossi S. 2009. ed. These doses may be repeated at 5 minute intervals. susceptibility to closed-angle glaucoma. avoid use of live vaccines. October 2007 (including the model list of essential medicines for children). WHO Technical Report Series.1 ml/kg of the dilute 1 mg/10 ml solution) given over several minutes.1%. Stuart MC. * Vaccine. ed. Pediatric dosage handbook. Vaccine. cerebrovascular disease. Taketomo CK. Hudson. American Society of Health-System Pharmacists.

dizziness. eds. Kouimtzi M. Drugdex system. 2010. ed. Notes: 1 mg/ml = 1:1000 or 0. fear. WHO Technical Report Series. 950 (http://www. pallor. anxiety. tremor. Geneva. peripheral ischaemia and necrosis (at injection site). Contraindications: Not relevant to emergency use. Dose: Anaphylaxis. Hydrocortisone ATC code: H02AB09 Powder for injection: 100 mg (as sodium succinate) in vial Indications: Adjunct in the emergency treatment of anaphylaxis. October 2007 (including the model list of essential medicines for children). London.thomsonhc. Rossi S. WHO Model Formulary for Children 2010 31 . * Ergot derivatives: may precipitate hypertensive crisis Fluoxetine: increased effect or toxicity of epinephrine. ventricular arrhythmias. Greenwood Village. Adelaide. IM or IV: Infant under 6 months initially 25 mg up to four times daily adjusted according to response. Inject intramuscular epinephrine into anterolateral aspect of thigh. Infant or Child 6 months–6 years initially 50 mg up to four times daily adjusted according to response. 2008. do not inject into hands. The selection and use of essential medicines: report of the WHO expert committee. headache. nose. 2009. tachycardia. palpitations. * Halothane: may precipitate ventricular arrhythmias. Klasco RK. WHO model formulary. Antiallergics and medicines used in anaphylaxis Hepatic impairment: Dose reduction not necessary. severe hypertension. cerebral haemorrhage.1%. bradycardia. weakness. pulmonary oedema (on excessive dosage or extreme sensitivity).com. pulmonary oedema. sweating. Interactions with other medicines (* indicates severe): Amitriptyline: increased effect or toxicity of epinephrine. Child 6–12 years initially 100 mg up to four times daily adjusted according to response.who. Propranolol: hypertension. Precautions: Not relevant to emergency use. hyperglycaemia. genitals or buttocks. angina. (http://www. feet. References: Hill SR. Hepatic impairment: Dose reduction not necessary. Australian medicines handbook. dyspnoea. ed. Adverse effects: Common Nausea. WHO expert committee on the selection and use of essential medicines. Uncommon excessive increase in blood pressure.3 Renal impairment: Dose reduction not necessary. Thomson Micromedex. OVeRDOSe OR RAPID INTRAVeNOUS ADMINISTRATION Arrhythmias (ventricular and supraventricular). 2008. * Cyclopropane: may precipitate ventricular arrhythmias. cold extremities.int/medicines/publications/essentialmeds_committeereports/TRS_950. World Health Organization. ears. restlessness. BMJ Group RBS Publishing. Rare Allergic reaction (sodium metabisulfite in some products).pdf ). resistance to epinephrine effect. 2009. British national formulary for children 2009. accessed 10 February 2010). Australian Medicines Handbook. vomiting. Renal impairment: Dose reduction not necessary. Stuart MC. Paediatric Formulary Committee.

hyperglycaemia. Propranolol: antagonism of hypotensive effect. Erythromycin: erythromycin possibly inhibits metabolism of hydrocortisone. References: Hill SR. hypokalaemia. Paediatric Formulary Committee. 950 (http://www. Phenobarbital: metabolism of hydrocortisone accelerated (reduced effect). Common Nausea. avoid use of live vaccines. Insulins: antagonism of hypoglycaemic effect. Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose hydrocortisone enhances anticoagulant effect). Rifampicin: accelerated metabolism of hydrocortisone (reduced effect). Methotrexate: increased risk of haematological toxicity. cognition. Australian medicines handbook. increased appetite. Australian Medicines Handbook. eds. Hydrochlorothiazide: antagonism of diuretic effect. masking of signs of infection. psychiatric effects (including delirium or psychosis). Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions). Furosemide: antagonism of diuretic effect. increased risk of hypokalaemia. Rare Peptic ulceration. October 2007 (including the model list of essential medicines for children). 2008. oedema. posterior subcapsular cataracts. bruising.int/medicines/publications/essentialmeds_committeereports/TRS_950. Digoxin: increased risk of hypokalaemia. live: high doses of hydrocortisone impairs immune response. disturbances of mood. 32 WHO Model Formulary for Children 2010 . World Health Organization. Metformin: antagonism of hypoglycaemic effect. burning or tingling in perineal area (after intravenous bolus). delayed wound healing. 2009. sleep and behaviour). depression. Geneva. BMJ Group RBS Publishing. increased susceptibility to infection. hypersensitivity reactions including anaphylaxis. Spironolactone: antagonism of diuretic effect. Vaccine. dyspepsia. glaucoma. WHO model formulary. British national formulary for children 2009. psychiatric effects (including euphoria. Phenytoin: metabolism of hydrocortisone accelerated (reduced effect). 2009. Stuart MC. Interactions with other medicines (* indicates severe): * * * * * * * * Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration.pdf ). WHO expert committee on the selection and use of essential medicines. Adelaide. Enalapril: antagonism of hypotensive effect. Vaccine. acne.3 Antiallergics and medicines used in anaphylaxis Adverse effects: Incidence of adverse effects is related to dose and duration of treatment. influenza: high doses of hydrocortisone impairs immune response. Short courses of high-dose systemic treatment cause fewer adverse effects than prolonged courses of lower doses. increased risk of hypokalaemia.who. Kouimtzi M. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. Carbamazepine: accelerated metabolism of hydrocortisone (reduced effect). ed. WHO Technical Report Series. 2008. hydrocortisone reduces plasma salicylate concentration. London. hypertension. INTRAVeNOUS Transient itching. The selection and use of essential medicines: report of the WHO expert committee. Ritonavir: plasma concentration possibly increased by ritonavir. hypomania. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with hydrocortisone. sodium and water retention. Rossi S.

hypokalaemia. masking of signs of infection. glaucoma. acne. peptic ulcer. 25 mg Special Notes: Prednisone should be considered equivalent to prednisolone. history of steroid myopathy. osteoporosis. * Amphotericin B: increased risk of hypokalaemia. corneal perforation. Indications: Short-term suppression of inflammation. psychiatric effects (including euphoria. posterior subcapsular cataracts. psychiatric effects (including delirium and psychosis). cognition. increased susceptibility to infection. Enalapril: antagonism of hypotensive effect. Contraceptives. Rare Peptic ulceration. delayed wound healing. Hydrochlorothiazide: antagonism of diuretic effect. glaucoma. Furosemide: antagonism of diuretic effect. Increased severity of viral infections. * Carbamazepine: accelerated metabolism of prednisolone (reduced effect). dyspepsia. WHO Model Formulary for Children 2010 33 . prednisolone reduces plasma salicylate concentration. depression. increased risk of hypokalaemia. renal impairment. hypothyroidism. Precautions: Most precautions do not apply for emergency or short-term use. Interactions with other medicines (* indicates severe): Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. administration of live vaccines: usually not relevant to emergency treatment. increased risk of hypokalaemia. severe psychosis. Digoxin: increased risk of hypokalaemia. Ciclosporin: increased plasma concentration of prednisolone. Adverse effects: Incidence of adverse effects is related to dose and duration of treatment. disturbances of mood. sodium and water retention. hypomania. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. psoriasis. bruising. The information in this monograph only applies to the medicine listed here. oedema. Increased frequency may be required in certain clinical indications. hypertension. congestive heart failure. This medicine is listed as a representative of its pharmacological class. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. sleep and behaviour). oral: oral contraceptives containing estrogens increase plasma concentration of prednisolone. diabetes mellitus. Hepatic impairment: Adverse effects more common. epilepsy. hepatic impairment. Dose: Oral: Infant or Child 1–2 mg/kg once daily (usual maximum 60 mg). Erythromycin: erythromycin possibly inhibits metabolism of prednisolone. recent myocardial infarction. Short courses of high-dose systemic treatment cause fewer adverse effects than prolonged courses of lower doses. Contraindications: Untreated systemic infection. increased appetite.3 Antiallergics and medicines used in anaphylaxis Prednisolone ATC code: H02AB06 Oral liquid: 5 mg/ml Tablet: 5 mg. hypersensitivity reactions including anaphylaxis. Renal impairment: Dose reduction not necessary. Common Nausea. hyperglycaemia. reducing after a few days if appropriate.

pdf ). Kouimtzi M. eds. influenza: high doses of prednisolone impair immune response.who. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with prednisolone. * Rifampicin: accelerated metabolism of prednisolone (reduced effect). Geneva. 2010. Ritonavir: plasma concentration possibly increased by ritonavir. * Vaccine. ed. Vaccine. * Phenobarbital: metabolism of prednisolone accelerated (reduced effect). Greenwood Village. 34 WHO Model Formulary for Children 2010 . * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose prednisolone enhances anticoagulant effect). WHO model formulary. Notes: Take the tablets or oral liquid with food to help reduce stomach upset. Adelaide. References: Hill SR. ed. live: high doses of prednisolone impair immune response. WHO expert committee on the selection and use of essential medicines. 2009. accessed 10 February 2010). World Health Organization. Rossi S. Klasco RK. avoid use of live vaccines.3 Antiallergics and medicines used in anaphylaxis Insulins: antagonism of hypoglycaemic effect. October 2007 (including the model list of essential medicines for children).thomsonhc. * Phenytoin: metabolism of prednisolone accelerated (reduced effect).com. WHO Technical Report Series. The selection and use of essential medicines: report of the WHO expert committee. 2008. Spironolactone: antagonism of diuretic effect. Stuart MC. 2008. (http://www. Drugdex system. Australian medicines handbook. * Methotrexate: increased risk of haematological toxicity. 950 (http://www. Australian Medicines Handbook. Thomson Micromedex.int/medicines/publications/essentialmeds_committeereports/TRS_950. Propranolol: antagonism of hypotensive effect.

............................1 Non-specific.................... 36 4................................................................2 Specific .........................SECTION 4: Antidotes and other substances used in poisonings 4................. 38 WHO Model Formulary for Children 2010 35 ..................

removal from the source of poisoning. It is strongly recommended that poisons information centres or other local sources of expertise be consulted in cases of suspected poisoning. Symptoms and signs depend on the agent involved and therefore vary widely. Induction of emesis for treatment of poisoning is not recommended. paracetamol. poisoning by corrosive substances (may prevent visualization of lesions caused by poison). decontamination of the skin and eyes (with appropriate protection of staff and carers) should be undertaken. A diagnosis of poisoning is based on history.1 Non-specific Charcoal.4 Antidotes and other substances used in poisonings 4 Antidotes and other substances used in poisonings The following notes on treatment of poisoning are guidelines only. For inhaled poisons. and the results of investigations when appropriate. antidepressant drugs. or stridor (abnormal respiratory sounds suggesting laryngeal damage). the amount ingested. Precautions: Drowsy or unconscious child (risk of aspiration (intubate before administration via nasogastric or gastric tube)). Children who have ingested corrosives or petroleum products should not be sent home within 6 hours. and metal salts including iron and lithium. narcotics. administration of oxygen and further airway support may be required. pesticides. and most are treated symptomatically with supportive care and monitoring of vital signs. paraquat. Gastric lavage is rarely required. cyanides. due to ingestion of corrosives. unprotected airway. 36 WHO Model Formulary for Children 2010 . 4. Administration of activated charcoal to prevent further absorption is the treatment of choice for gastric decontamination. dichlorodiphenyltrichloroethane (DDT)). Supportive care Few patients require active removal of the poison. gastrointestinal tract not intact. bowel obstruction. active elimination of poisons. Check for burns in or around the mouth. the time of ingestion. aspirin. including details of the poisoning agent. activated ATC code: A07BA01 Powder Indications: Reduction of absorption of poisons. clofenotane (dicophane. Gastric decontamination Gastric decontamination (removal of poisons from the stomach) is most effective within 1 hour of ingestion. Contraindications: Poisoning by hydrocarbons with high potential for harm if aspirated. malathion. or who have taken modified-release or prolonged-release dose forms. lithium or warfarin. Admit all children who have ingested iron. Decontamination Depending on the substance involved and circumstances of poisoning. not effective for poisoning with alcohols. after this time it is usually of little benefit.

British national formulary for children 2009. Kraus DM.4. BMJ Group RBS Publishing. Administration after 1 hour is only of any potential benefit in selected poisonings. Renal impairment: Not absorbed. 16th ed. Rossi S. nausea. WHO Model Formulary for Children 2010 37 . Hudson. or cannot take. Adelaide. vomiting. Geneva. preferably within 1 hour for greatest effect. Child must drink slowly to reduce risk of vomiting. Adverse effects: Common Black stools. no dose adjustment necessary. Australian medicines handbook. Notes: Administer as soon as possible after ingestion if significant toxicity is anticipated. Infant or Child 1 g/kg (maximum 50 g) as a single dose as soon as possible after ingestion of poison. Taketomo CK. Refer to specialist texts for advice. fruit juice. Hepatic impairment: Not absorbed. Palatability is improved by chilling. Laxatives should not be used concurrently with repeat dose activated charcoal because of the risk of fluid and electrolyte disturbances. constipation or diarrhoea. Paediatric Formulary Committee. 37(6):731–751. no dose adjustment necessary. fruit syrup or chocolate syrup to mask the taste and form a drinkable solution. 2009. pneumonitis. Hill SR. Infant or Child 1 g/kg (maximum 50 g) every 4 hours. 2008. The powder should be mixed with fluid such as soft drinks. eds. Active elimination of poisons. Hodding JH. Activated charcoal can be administered via an orogastric or nasogastric tube after aspiration of stomach contents. european Association of Poisons Centres and Clinical Toxicologists. Stuart MC. Oral: Neonate. Rare Bowel obstruction. Lexi-Comp. 1999. colicky abdominal pain. This route may also be used in conscious patients who refuse. 2009. ed.1 Dose: Non-specific Reduction of absorption of poisons. London. References: American Academy of Clinical Toxicology. Drinking may be easier if mixture is covered or the child drinks with their eyes closed. Australian Medicines Handbook. 2009. World Health Organization. aspiration. oral charcoal. Do not mix with milk or ice cream. Unconscious patients in whom decontamination is indicated require intubation to protect their airway. Kouimtzi M. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. Clinical Toxicology. WHO model formulary. Oral: Neonate. Mix well immediately prior to ingestion. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Pediatric dosage handbook.

Uncommon Anaphylactoid reaction. Repeat oral dose if vomiting occurs within 1 hour of administration. Dose: Paracetamol overdosage. followed by 50 mg/kg in 250 ml glucose 5% and given over 4 hours. then 100 mg/kg in 500 ml glucose 5% and given over 16 hours. do not delay treatment). followed by 50 mg/kg in 7 ml/kg glucose 5% and given over 4 hours. 38 WHO Model Formulary for Children 2010 . followed by 70 mg/kg every 4 hours for 17 doses. continue the final infusion rate until hepatic transaminases are falling. but glucose 5% is preferable. emergency treatments such as antihistamines and H2-blockers should be readily available in case of adverse effects. urticaria. Precautions: Asthma (observe child carefully while slowly administering loading dose over 1–2 hours. NOTe Continued infusion beyond 20 hours may be required in late presentations or repeated supratherapeutic ingestions if there is evidence of liver toxicity. Rash may be managed with an antihistamine. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Renal impairment: No dosage adjustment recommended. Manufacturer also recommends other infusion fluids. Hypersensitivity-like reactions may be managed by reducing infusion rate or suspending infusion until reaction has settled. Hepatic impairment: No dosage adjustment recommended. Acute asthma may be managed with a short-acting beta2-agonist such as salbutamol. Contraindications: There are no contraindications to acetylcysteine when used for paracetamol toxicity. Adverse effects: Common Flushing. IV infusion: Neonate. starting 4 hours after loading dose. all doses should be given even if paracetamol plasma level has dropped below toxic range. then 100 mg/kg in 14 ml/kg glucose 5% and given over 16 hours. itch. Infant or Child initially 140 mg/kg. over 5 years or body weight over 20 kg initially 150 mg/kg in 100 ml glucose 5% and given over 15 minutes. Oral: Neonate. Notes: For oral therapy. Infant or Child up to 5 years and body weight under 20 kg initially 150 mg/kg in 3 ml/kg glucose 5% and given over 15 minutes. In such cases.2 Specific Acetylcysteine ATC code: V03AB23 Injection: 200 mg/ml in 10 ml ampoule Oral liquid: 10% and 20% Indications: Paracetamol overdosage. specialist advice may be needed. for example chlorphenamine.4 Antidotes and other substances used in poisonings 4.

CHILDReN Children are at increased risk for rapid rise in body temperature due to suppression of sweat gland activity. Taketomo CK. Interactions with other medicines (* indicates severe): NOTe Many drugs have antimuscarinic effects. BMJ Group RBS Publishing. fever. Unedited draft report of the 17th expert committee on the selection and use of essential medicines. 2009. Atropine ATC code: A03BA01 Injection: 1 mg (as sulfate) in 1 ml ampoule Indications: Treatment of cholinergic effects associated with organophosphate or carbamate poisoning. October 2007 (including the model list of essential medicines for children). Hepatic impairment: Use with caution. (http://www. Klasco RK. Hudson. ed. 2008. diarrhoea. Dose: Organophosphate or carbamate poisoning. WHO 17th expert committee on the selection and use of essential medicines. tachycardia. confusion. the pupils dilate and tachycardia develops.2 References: Specific Hill SR. 2008. myasthenia gravis. concomitant use of two or more such drugs can increase adverse effects such as dry mouth.4. Australian Medicines Handbook. Hodding JH. urine retention and constipation. children. Rare Closed-angle glaucoma. cardiac disorders. Contraindications: There are no contraindications to use of atropine for treatment of organophosphate or carbamate poisoning. Uncommon Nausea. 950 (http://www.who. Stuart MC. hypertension. heart failure.com. eds. hyperthyroidism.who. flushing and dryness of skin. Rossi S. Precautions: Down syndrome.pdf ). delirium. arrhythmias. 18 May 2009 (http://www. London. photophobia. Thomson Micromedex.int/selection_ medicines/committees/expert/17/WeBuneditedTRS_2009. Greenwood Village. The selection and use of essential medicines: report of the WHO expert committee. difficulty in micturition. Lexi-Comp. 2009. WHO expert committee on the selection and use of essential medicines. WHO Technical Report Series. ulcerative colitis. seizures. palpitations. DOWN SyNDROMe Down syndrome children have both increased sensitivity to cardiac effects and mydriasis. WHO Technical Report Series. World Health Organization. 2010. accessed 10 February 2010). Geneva. hypoxia. WHO Model Formulary for Children 2010 39 .thomsonhc. Please consider in the context of poisoning treatment whether interactions are clinically relevant. tachycardia. 16th ed. gastrointestinal disorders. ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. closed-angle glaucoma. Drugdex system. Adverse effects: Common Dry mouth. No dosage adjustment necessary. IM or IV: Infant or Child 20 micrograms/kg (maximum dose 2 mg) every 5–10 minutes (depending on the severity of poisoning) until the skin becomes flushed and dry. Dose may be repeated every 1–4 hours for at least 24 hours to maintain atropine effect. Kouimtzi M. Adelaide. Large doses may cause paradoxical hyperexcitability. Children with Down syndrome also have more secretions and may require atropine more frequently. 2009. rash. No dosage adjustment necessary. British national formulary for children 2009.pdf ). WHO model formulary. fever and in warm environments (monitor temperature and keep patients cool). Renal impairment: Use with caution. constipation. blurred vision. vomiting. constipation. Australian medicines handbook. Paediatric Formulary Committee. Pediatric dosage handbook. Kraus DM.

5 ml (250 mg) of injection solution in 100 ml of water soluble lubricant.4 Antidotes and other substances used in poisonings Amitriptyline: increased antimuscarinic adverse effects.5% calcium gluconate gel. consider intravenous infusion. Taketomo CK. Drugdex system. Maximum dose 200 mg (20 ml). Pediatric dosage handbook. 2009. Haloperidol: possibly reduced effects of haloperidol. 2008. such as K-y Jelly®. hyperkalaemia or hypermagnesaemia. Hodding JH. Continuous IV infusion: Neonate 200 mg/kg daily over 24 hours. 40 WHO Model Formulary for Children 2010 . Geneva. Contraindications: There are no contraindications to the use of calcium gluconate for treatment of toxicity or poisoning. 2009. Australian Medicines Handbook. IV: Neonate.com. combine 2. British national formulary for children 2009. Dose: Urgent correction of acute hypocalcaemia. Repeat dose after 10 minutes if necessary. accessed 10 February 2010). Kouimtzi M. Greenwood Village. eds. Topical: Child all ages apply 2. NOTe To extemporaneously prepare 2. Kraus DM.5% calcium gluconate gel to the affected area for at least 30 minutes. Thomson Micromedex. severe hyperkalaemia not due to digoxin toxicity. References: Hill SR. acute hypocalcaemia (including hypocalcaemia caused by ethylene glycol toxicity. renal impairment. Lexi-Comp. Maintenance correction of acute hypocalcaemia. Hydrofluoric acid burns. Late unopposed bradycardia may result. topical treatment of hydrofluoric acid burns. 2010. (http://www. Stuart MC. usually longer. World Health Organization. Neostigmine: antagonism of effects of neostigmine. digoxin therapy. adjusted to response. BMJ Group RBS Publishing. hyperkalaemia or hypermagnesaemia. Rossi S. London. Adelaide. ed. 2009. calcium channel blocker toxicity. calcium channel blocker toxicity. Pyridostigmine: antagonism of effects of pyridostigmine. maintenance treatment of calcium channel blocker toxicity. Australian medicines handbook. Hudson. Infant or Child under 2 years 500 mg/kg daily (usual maximum 4 g) over 24 hours. hydrofluoric acid ingestion and oxalate poisoning). Chlorphenamine: increased antimuscarinic adverse effects. Chlorpromazine: increased antimuscarinic adverse effects (but reduced plasma chlorpromazine concentration). Paediatric Formulary Committee. Notes: Administer undiluted via rapid intravenous injection as slow injection may result in paradoxical bradycardia. If effective. Calcium gluconate ATC code: A12AA03 Injection: 100 mg/ml in 10 ml ampoule Indications: Magnesium toxicity. WHO model formulary. Metoclopramide: antagonism of effects of metoclopramide on gastrointestinal activity. ed. Child over 2 years 4 g over 24 hours. 16th ed. Klasco RK. Precautions: Conditions associated with hypercalcaemia and hypercalciuria.thomsonhc. Infant or Child 50 mg/kg as a single dose.

4.2 calcium level. Risk of hypercalcaemia and renal calculi.

Specific

Renal impairment: Moderate to severe impairment: may require dosage adjustment depending on Hepatic impairment: No dosage adjustment necessary. Adverse effects: Common Gastrointestinal disturbances, constipation, injection site reactions, fall in

blood pressure.

Uncommon Bradycardia, arrhythmia, peripheral vasodilation. Rare Renal calculi, severe tissue damage with extravasation. Interactions with other medicines (* indicates severe):

Please consider in the context of poisoning treatment whether interactions are clinically relevant. Ciprofloxacin: reduced absorption of ciprofloxacin. Digoxin: large intravenous doses of calcium salts can precipitate arrhythmias. Hydrochlorothiazide: increased risk of hypercalcaemia. Levothyroxine: reduced absorption of levothyroxine. Ofloxacin: reduced absorption of ofloxacin. Notes: For intravenous infusion, dilute to 20 mg/ml with glucose 5% or sodium chloride 0.9%. Maximum administration rate is 20 mg/kg/hour (or 10 mg/kg/hour in neonates). For intravenous injection, administer via slow intravenous injection over 5–10 minutes. Avoid extravasation; should not be given by intramuscular or subcutaneous injection. Continuous eCG monitoring is recommended during intravenous calcium administration. Significant hydrofluoric acid poisoning (> 3% of body surface area) may result in marked systemic hypocalcaemia requiring intravenous therapy.
References:
Brent J et al. Critical care toxicology. Philadelphia, elsevier Mosby, 2005. Dart R, ed. Medical toxicology. 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2004. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Klasco RK, ed. Drugdex system. Greenwood Village, Thomson Micromedex, 2010. (http://www.thomsonhc.com, accessed 10 February 2010). Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009.

Deferoxamine
ATC code: V03AC01

Powder for injection: 500 mg (as mesilate) in vial Special Notes: Also referred to as desferrioxamine. Indications: Acute iron poisoning; chronic iron overload. Precautions: Renal impairment; eye and ear examinations before and at 3 month intervals during treatment are necessary to assess toxicity; aluminium encephalopathy (may exacerbate neurological dysfunction); for all children monitor body weight and height at 3 month intervals (risk of growth restriction with excessive doses).

WHO Model Formulary for Children 2010

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4

Antidotes and other substances used in poisonings
Dose:

Acute iron poisoning. Slow IV infusion: Neonate, Infant or Child initially 15 mg/kg/hour, reduced after 4–6 hours so that total dose does not exceed 80 mg/kg in 24 hours. Maximum dose 6 g/day. IM: 50 mg/kg/dose every 6 hours. Maximum dose 6 g/day. The preferred route of administration is IV.
NOTe It is uncommon to require more than 24 hours therapy for acute iron overdose. Therapeutic endpoints to cease infusion are poorly defined but may be indicated by clinically stable patient and serum iron < 60 micromol/l.

Chronic iron overload. SC or IV infusion: Infant or Child initially up to 30 mg/kg over 8–12 hours, on 3–7 days per week. For established iron overload the dose is usually between 20 and 50 mg/kg daily. The dose should reflect the degree of iron overload. Use the lowest effective dose. Diagnosis of iron overload. IM: Child 500 mg.
Renal impairment: Metal complexes excreted by kidneys (in severe renal impairment dialysis

increases rate of elimination).

Hepatic impairment: No dosage adjustment necessary. Adverse effects: Common Injection site reactions including redness, pain, swelling, rashes and itch, CHRONIC USe Growth retardation, bone deformities (both with high doses). Uncommon Renal failure, non-cardiogenic pulmonary oedema, disturbances of hearing and vision

hypotension (especially when given too rapidly by intravenous injection), fever, arthralgia, myalgia, rash, anaphylactoid reactions. (including lens opacity and retinopathy).

CHRONIC USe Neurosensory deafness. Rare Anaphylaxis, acute respiratory distress syndrome, neurological disturbances. CHRONIC USe Bone marrow depression, ocular toxicity, mucormycosis and other unusual infections. Interactions with other medicines (* indicates severe):

There are no known significant interactions where it is recommended to avoid concomitant use. Notes: For intravenous or subcutaneous infusion, reconstitute powder with water for injection to a concentration of 100 mg/ml. Dilute with glucose 5% or sodium chloride 0.9%. For intramuscular or subcutaneous administration, reconstitute powder with water for injection to a concentration of 100 mg/ml. No further dilution required. For all children, monitor body weight and height at 3 month intervals (risk of growth restriction with excessive doses). Iron excretion induced by deferoxamine is enhanced by ascorbic acid and ascorbic acid is sometimes prescribed for this purpose.
References:
Dart R, ed. Medical toxicology. 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2004. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Klasco RK, ed. Drugdex system. Greenwood Village, Thomson Micromedex, 2010. (http://www.thomsonhc.com, accessed 10 February 2010). Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009.

42

WHO Model Formulary for Children 2010

4.2

Specific

Dimercaprol

ATC code: V03AB09

Injection in oil: 50 mg/ml in 2 ml ampoule
Indications: Acute heavy metal poisoning by antimony, arsenic, bismuth, gold, mercury, possibly

thallium; adjunct (with sodium calcium edetate) in lead poisoning.

Contraindications: Not indicated for iron, selenium or cadmium poisoning; severe hepatic

impairment (unless due to arsenic poisoning).

Precautions: Hypertension; renal impairment; any abnormal reaction such as hyperpyrexia should be

assessed; peanut allergy (peanut oil in injection); G6PD deficiency.

Dose:

Heavy metal poisoning. IM: Infant or Child 2.5–3 mg/kg every 4 hours for 2 days, 2–4 times on the third day, then 1–2 times daily for 10 days or until recovery.
Renal impairment: Discontinue or use with extreme caution if impairment develops during

treatment. Haemodialysis may be required to remove the chelate in renal failure. Urinary alkalinization prior to commencing treatment may reduce nephrotoxicity caused by dissociation of dimercaprol-metal complexes in acid urine. Hepatic impairment: Severe: avoid use (unless arsenic poisoning). Adverse effects: Common Hypertension, fever, tachycardia, malaise, nausea, vomiting, abdominal pain, salivation, lacrimation, sweating, burning sensation in the mouth, throat and eyes, injection site pain, headache, muscle spasms, tingling of the extremities, feeling of constriction in throat and chest. Uncommon Abscess at injection site.
Interactions with other medicines (* indicates severe):

* Ferrous salts: avoid concomitant use. Notes: Administer undiluted via deep intramuscular injection.
References:
Dart R, ed. Medical toxicology. 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2004. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Klasco RK, ed. Drugdex system. Greenwood Village, Thomson Micromedex, 2010. (http://www.thomsonhc.com, accessed 10 February 2010). Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. WHO expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee, October 2007 (including the model list of essential medicines for children). WHO Technical Report Series, 2008, 950 (http://www.who.int/medicines/publications/essentialmeds_committeereports/TRS_950.pdf ).

Naloxone

ATC code: V03AB15

Injection: 400 micrograms/ml (hydrochloride) in 1 ml ampoule
Indications: Opioid overdosage. Contraindications: There are no contraindications to use of naloxone for treatment of opioid toxicity. Precautions: Physical dependence on opioids or other situations where acute withdrawal syndrome

may be precipitated; cardiovascular disease; postoperative patients (may reverse analgesia and increase blood pressure).

WHO Model Formulary for Children 2010

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4

Antidotes and other substances used in poisonings
Dose:

Opioid overdosage. IV: Neonate, Infant or Child 10 micrograms/kg; if no response give subsequent dose of 100 micrograms/kg. Review diagnosis if respiratory function does not improve. Further doses may be required if respiratory function deteriorates.
NOTe Naloxone hydrochloride may be administered in the same doses by intramuscular or subcutaneous injection, but only if the intravenous route is not feasible (slower onset of action).

Continuous IV infusion using an infusion pump: Neonate, Infant or Child 5–20 micrograms/kg/hour, adjusted according to response.
Renal impairment: excretion of some opioids and/or their active metabolites (codeine,

dextropropoxyphene, dihydrocodeine, morphine, pethidine, oxycodone) is delayed in impairment and they will accumulate; extended treatment with naloxone infusion may be required to reverse opioid effect. Hepatic impairment: No dose adjustment necessary. Adverse effects: Common Nausea, vomiting, sweating. Uncommon Tachycardia, ventricular arrhythmias. Rare Cardiac arrest.
Interactions with other medicines (* indicates severe):

There are no known interactions where it is advised to avoid concomitant use. Notes: For continuous intravenous infusion, dilute to a concentration of 4 micrograms/ml with glucose 5% or sodium chloride 0.9%. For intravenous bolus, administer over 30 seconds as undiluted preparation. Intravenous dose may be repeated every 2–3 minutes until response. After initial response, intravenous dose may need to be repeated every 20–60 minutes due to short duration of action. Do not give naloxone to neonates of mothers who have been taking methadone or heroin.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009.

Penicillamine
ATC code: M01CC01

Solid oral dosage form: 250 mg Penicillamine has been associated with fatalities due to agranulocytosis, aplastic anaemia, thrombocytopenia, Goodpasture syndrome and myasthenia gravis. Discontinue therapy if white blood cell count < 3.5 x 109/L. Temporarily discontinue treatment if the platelet count < 100 x 109/L. Patients and carers should be warned to promptly report any symptoms suggesting toxicity.
Special Notes: Also referred to as D-penicillamine.

Consider use of other metal chelators with better side-effect profile, including sodium calcium edetate and 2,3-dimercaptosuccinic acid if available. Indications: Heavy metal poisoning, particularly lead and copper. 44 WHO Model Formulary for Children 2010

4.2
Contraindications: Hypersensitivity; lupus erythematosus; pregnancy.

Specific

Precautions: Monitor blood counts and urine tests throughout treatment; concomitant nephrotoxic

drugs; renal impairment; avoid concurrent gold, chloroquine or immunosuppressive treatment; avoid oral iron within 2 hours of a dose; penicillin hypersensitivity (risk of cross-reactivity).

PATIeNT ADVICe Warn patient or carer to tell doctor immediately if sore throat, fever, infection, non-specific illness, unexplained bleeding and bruising, purpura, mouth ulcers or rash develop. Dose:

Heavy metal poisoning, particularly lead and copper. Oral: Child all ages 7.5 mg/kg 3–4 times daily. Duration of therapy depends on pretreatment blood levels and may vary from 4–12 weeks.
Renal impairment: Mild impairment: reduce dose and monitor renal function or avoid.

Moderate to severe impairment: avoid.
Hepatic impairment: No dosage adjustment necessary. Adverse effects: Common Rash, anorexia, nausea, vomiting, taste disturbance. Uncommon Mouth ulcers, fever, allergy, itching, urticaria, proteinuria. Rare Haematuria, thrombocytopenia, leukopenia, agranulocytosis, aplastic anaemia, haemolytic

anaemia, nephrotic syndrome, lupus erythematosus, Goodpasture syndrome, myasthenia gravis, polymyositis, breast enlargement, hepatic dysfunction, alopecia, pemphigus, dermatomyositis, Stevens-Johnson syndrome.

Interactions with other medicines (* indicates severe):

Antacids (aluminium hydroxide; magnesium hydroxide): reduced absorption of penicillamine. Digoxin: plasma concentration of digoxin possibly reduced. Ferrous salts: oral ferrous salts reduce absorption of penicillamine. Ibuprofen: possible increased risk of nephrotoxicity. Isoniazid: penicillamine potentiates isoniazid. Zinc sulfate: absorption of penicillamine and zinc sulfate reduced. Notes: Give on an empty stomach, at least 1 hour before meals or 2 hours after. Separate from milk, food or other drugs by at least 1 hour. For lead poisoning, continue treatment until urinary lead stabilized at less than 500 micrograms/day. Adverse effects may be minimized by starting with a small dose and gradually increasing while monitoring for adverse effects. Monitoring is strongly recommended. Measure urine and blood concentration of the intoxicating metal weekly. Perform complete blood count and urinalysis twice weekly for the first month, then every 2 weeks for 6 months and monthly thereafter. Monitor liver function every 6 months. Monitor patient’s skin, lymph nodes and body temperature.
References:
Dart R, ed. Medical toxicology. 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2004. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. MIMS Online. Sydney, UBM Medica, 2009 (http://www.mimsonline.com.au/Search/Search.aspx, accessed 10 February 2010). Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. WHO expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee, October 2007 (including the model list of essential medicines for children). WHO Technical Report Series, 2008, 950 (http://www.who.int/medicines/publications/essentialmeds_committeereports/TRS_950.pdf ).

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4

Antidotes and other substances used in poisonings

Sodium calcium edetate
ATC code: V03AB03

Injection: 200 mg/ml in 5 ml ampoule Patients with lead encephalopathy and cerebral oedema may experience a lethal increase in intracranial pressure following intravenous infusion; the intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. ethylenediaminetetraacetic acid, calcium disodium ethylenediaminetetraacetic acid, calcium disodium edathamil, calcium eDTA, calcium disodium eDTA and edetate calcium disodium. Usually given in conjunction with dimercaprol for lead poisoning. To avoid potentially serious errors, the abbreviation eDTA should never be used. Consider use of oral succimer (2,3-dimercaptosuccinic acid) if available in asymptomatic or minimally symptomatic patients due to better safety profile. Indications: Heavy metal poisoning, particularly lead; lead encephalopathy. Contraindications: Anuria; active renal disease; hepatitis. Precautions: Renal impairment; establish urine flow before treatment.
Dose: Special Notes: Also referred to as calcium disodium edetate, calcium disodium versenate,

Heavy metal poisoning, particularly lead, without encephalopathy. Continuous IV infusion: Child all ages 20–30 mg/kg per day for up to 5 days. OR Deep IM: Child all ages 20–30 mg/kg per day in 2–3 divided doses every 8–12 hours for up to 5 days.
NOTe Depending on blood lead level, additional courses may be necessary. A second course can be given with a 48 hour interval between the first and second courses, and a third course can be given with a 48 hour interval after the second course. Specialist texts should be consulted for further information on heavy metal poisoning other than lead.

Lead encephalopathy. Continuous IV infusion: Child all ages 30 mg/kg per day for 5 days. OR If evidence of cerebral oedema or increased intracranial pressure, intramuscular administration is recommended. Deep IM: Child all ages 30 mg/kg per day in 2–3 divided doses every 8–12 hours for 5 days.
NOTe Depending on blood lead level, additional courses may be necessary. A second course can be given with a 48 hour interval between the first and second courses, and a third course can be given with a 48 hour interval after the second course. Renal impairment: Reduce dose in all degrees of renal impairment. Use with extreme caution. Hepatic impairment: No dosage reduction necessary. Adverse effects: Common Sneezing, nasal congestion, numbness, tingling, nausea, diarrhoea,

abdominal cramps, fever, malaise, headache, myalgia, thirst, chills. too concentrated a solution), lacrimation, transient hypotension.

Uncommon Renal tubular necrosis, pain at injection site, thrombophlebitis (if given too rapidly or as Rare Mucocutaneous (mucous membrane) lesions.

46

WHO Model Formulary for Children 2010

4.2
Interactions with other medicines (* indicates severe):

Specific

Zinc insulin: interferes with zinc insulin by chelating zinc. Steroids: enhanced renal toxicity. Notes: For intravenous infusion, dilute to a concentration not more than 30 mg/ml with glucose 5% or sodium chloride 0.9%; give over at least 1 hour. Dimercaprol concomitant therapy recommended in symptomatic lead poisoning. Blood lead levels will determine if subsequent courses are required.
References:
Dart R, ed. Medical toxicology. 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2004. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. MIMS Online. Sydney, UBM Medica, 2009 (http://www.mimsonline.com.au/Search/Search.aspx, accessed 10 February 2010). Sweetman SC, ed. Martindale: the complete drug reference. 34th ed. London, Pharmaceutical Press, 2005.

WHO Model Formulary for Children 2010

47

SECTION 5: Anticonvulsants/antiepileptics

48

WHO Model Formulary for Children 2010

5

Anticonvulsants/antiepileptics

5

Anticonvulsants/antiepileptics

Guiding principles for drug treatment of epilepsy in children
The aim of drug treatment for epilepsy is to prevent the recurrence of seizures. Treatment of epilepsy in children should also include counselling of the patient and family, treatment of underlying causes where possible, avoidance of precipitating factors, and safety education. Guiding principles for drug treatment include the following: • Start with a low dose and increase gradually until seizures are controlled, the maximum dose is reached or there are significant side-effects. • Aim for single drug therapy (approximately 70% of children will achieve seizure control on a single drug). • Monitor plasma drug concentrations in some situations. • Use combination therapy when single drug therapy has failed to control seizures. • Avoid sudden cessation of medication, since this can precipitate uncontrolled seizures. If a drug fails to control seizures, it should be gradually substituted with another, and the first drug should be withdrawn only when the new regimen is mainly established.

Interactions
Anticonvulsant medication interactions are complex. It is important to check for potential interactions when making any changes to the medication schedule of a child on anticonvulsants.

Carbamazepine
ATC code: N03AF01

Oral liquid: 20 mg/ml Tablet (chewable): 100 mg; 200 mg Tablet (scored): 100 mg; 200 mg The US Food and Drug Administration (FDA) has issued a warning that all patients who are taking, or starting, any antiepileptic should be monitored for changes in behaviour that could indicate the emergence, or worsening, of suicidal thoughts or behaviour or depression. Rare but potentially fatal blood cell abnormalities (aplastic anaemia and agranulocytosis) have been reported in association with carbamazepine treatment. These mostly occur in the first 3–4 months of treatment. Stevens-Johnson syndrome and toxic epidermal necrolysis may occur. Patients and/or carers should be told how to recognize possible blood disorders and severe skin conditions, and to seek medical attention should they occur.
Special Notes: May be referred to as CBZ. Indications: Generalized tonic-clonic and partial seizures. Contraindications: Atrioventricular conduction abnormalities; history of bone marrow depression;

porphyria.

Precautions: Hepatic impairment; renal impairment; cardiac disease; skin reactions (see Adverse

effects); history of blood disorders (monitor blood counts before and during treatment); glaucoma; avoid sudden withdrawal. 49

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5

Anticonvulsants/antiepileptics
Dose:

Generalized tonic-clonic and partial seizures. Oral: Infant or Child initially 5 mg/kg at night or 2.5 mg/kg twice daily, increased by 2.5–5 mg/kg every 3–7 days if necessary; usual maintenance dose 5 mg/kg 2–3 times daily (up to 20 mg/kg daily may be needed).
Renal impairment: Use with caution.

Severe impairment: administer 75% of dose and monitor serum levels.
Hepatic impairment: Metabolism impaired in advanced liver disease. Adverse effects: Common Drowsiness, ataxia, dizziness, blurred vision, diplopia, headache (all dose

related), rash, dry mouth, abdominal pain, nausea, vomiting, anorexia, diarrhoea, constipation, asymptomatic hyponatraemia, leukopenia, thrombocytopenia, increased liver enzymes (usually not clinically significant). Rare Severe skin reactions (see below), systemic lupus erythematosus, agranulocytosis, aplastic anaemia, cholestatic jaundice, multi-organ hypersensitivity syndrome (including fever, lymphadenopathy, haematological abnormalities, hepatitis), psychosis, arrhythmia, orofacial dyskinesia, hepatitis, gynaecomastia, galactorrhoea, aggression, jaundice, osteomalacia, confusion, arthralgia.
SeVeRe SKIN ReACTIONS Include exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis; may also occur as part of multi-organ hypersensitivity syndrome. Serious reactions mostly occur within the first few months of treatment and are more common in those with the HLA-B*1502 allele, which occurs predominantly in people of Han Chinese or Thai ancestry. Interactions with other medicines (* indicates severe):

* Amitriptyline: antagonism of anticonvulsant effect (seizure threshold lowered); accelerated metabolism of amitriptyline (reduced plasma concentration; reduced antidepressant effect). Chloroquine: possibly increased risk of seizures. * Chlorpromazine: antagonism of anticonvulsant effect (seizure threshold lowered). Ciclosporin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). * Dexamethasone: accelerated metabolism of dexamethasone (reduced effect). Doxycycline: accelerated metabolism of doxycycline (reduced effect). * Erythromycin: increased plasma carbamazepine concentration. Ethosuximide: may be enhanced toxicity without corresponding increase in anticonvulsant effect; plasma concentration of ethosuximide possibly reduced. Fluoxetine: plasma concentration of carbamazepine increased. Furosemide: increased risk of hyponatraemia. * Haloperidol: antagonism of anticonvulsant effect (seizure threshold lowered); metabolism of haloperidol accelerated (reduced plasma concentration). Hydrochlorothiazide: increased risk of hyponatraemia. * Hydrocortisone: accelerated metabolism of hydrocortisone (reduced effect). * Isoniazid: increased plasma carbamazepine concentration (also isoniazid hepatotoxicity possibly increased). Levothyroxine: accelerated metabolism of levothyroxine (may increase levothyroxine requirements in hypothyroidism). * Lopinavir: possibly reduced plasma lopinavir concentration. Mebendazole: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infection). 50 WHO Model Formulary for Children 2010

Thomson Micromedex. emergency management of recurrent seizures. Spironolactone: increased risk of hyponatraemia. BMJ Group RBS Publishing. Plasma concentration for optimum response 4–12 mg/litre (17–50 micromol/litre). marked personality disorder. 2009 (http://etg. Notes: Therapeutic drug monitoring (TDM) is available for carbamazepine but routine monitoring is not required for the majority of patients. Praziquantel: plasma praziquantel concentration reduced. Kraus DM.5 Anticonvulsants/antiepileptics * Mefloquine: antagonism of anticonvulsant effect. Australian medicines handbook. (http://www. respiratory depression. Pediatric dosage handbook. Special Notes: Drug subject to international control under the Convention on Psychotropic Substances (1971). Melbourne. reduced plasma concentration of valproic acid. Stuart MC. Contraindications: CNS depression or coma. reduced plasma concentration of carbamazepine. neonates and infants. marked neuromuscular respiratory weakness including unstable myasthenia gravis. Hodding JH. Kouimtzi M. Saquinavir: possibly reduced plasma saquinavir concentration. plasma concentration of active metabolite of carbamazepine increased. 2008.org. accessed 10 February 2010). severe hepatic impairment. Geneva. References: eTG complete. hepatic impairment. Greenwood Village. Therapeutic Guidelines Limited. Miconazole: plasma concentration of carbamazepine possibly increased. British national formulary for children 2009. Precautions: Respiratory disease. 2010. close observation required until full recovery after sedation.5 ml. 2009. Diazepam ATC code: N05BA01 Rectal solution or gel: 5 mg/ml in 0. 2009. eds. * Warfarin: accelerated metabolism of warfarin (reduced anticoagulant effect). renal impairment.thomsonhc. muscle weakness and myasthenia gravis. for example riding a bike or operating machinery. Indications: Status epilepticus. 16th ed. Paediatric Formulary Committee.au/ip/. Rossi S. porphyria. Hill SR. plasma concentration of phenytoin often lowered but may be raised. 2009. Taketomo CK.com. Drugdex system. London. World Health Organization. acute pulmonary insufficiency. WHO model formulary. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. ed. 2 ml and 4 ml tubes. * Ritonavir: plasma concentration possibly increased by ritonavir. WHO Model Formulary for Children 2010 51 . ed. Phenobarbital: may be enhanced toxicity without corresponding increase in anticonvulsant effect. * Prednisolone: accelerated metabolism of prednisolone (reduced effect). Lexi-Comp. shock. plasma concentration of carbamazepine often lowered. Incidence of serious side-effects such as Stevens-Johnson syndrome may increase when used in combination. Incidence of serious side-effects such as StevensJohnson syndrome may increase when used in combination. Valproic acid: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Australian Medicines Handbook. * Phenytoin: may be enhanced toxicity without corresponding increase in anticonvulsant effect.tg. Klasco RK. accessed 10 February 2010). for 24 hours. Hudson. sleep apnoea. Vecuronium: antagonism of muscle relaxant effect (recovery from neuromuscular blockade accelerated). Adelaide.

Taketomo CK. World Health Organization. Enalapril: enhanced hypotensive effect. paradoxical insomnia. Isoniazid: metabolism of diazepam inhibited. amnesia. hypotension. Hill SR. Chlorphenamine: enhanced sedative effect.org. 2008. Adverse effects: Common Drowsiness. Severe impairment: avoid use. Rifampicin: metabolism of diazepam accelerated (reduced plasma concentration). aggression.au/ip/. sedation. injection pain. Melbourne. Stuart MC. Haloperidol: enhanced sedative effect. 16th ed. slurred speech. Pediatric dosage handbook. Geneva. increased cerebral sensitivity. emergency management of recurrent seizures. Rare Blood dyscrasias including neutropenia. confusion. excitability. Renal impairment: Severe impairment: consider dose reduction. References: eTG complete. Interactions with other medicines (* indicates severe): Amitriptyline: enhanced sedative effect. thrombophlebitis. Spironolactone: enhanced hypotensive effect. Therapeutic Guidelines Limited. NOTe Repeat doses should only be administered under medical supervision. Morphine: enhanced sedative effect. 52 WHO Model Formulary for Children 2010 . Chlorpromazine: enhanced sedative effect. Infant or Child less than 2 years 5 mg repeated once after 10 minutes if necessary. muscle weakness.tg. Kouimtzi M. leukopenia and thrombocytopenia.25–2. ataxia. * Ritonavir: plasma concentration possibly increased by ritonavir (risk of extreme sedation and respiratory depression. WHO model formulary. anaemia. avoid concomitant use). Furosemide: enhanced hypotensive effect. Codeine: enhanced sedative effect. Phenytoin: plasma phenytoin concentrations possibly increased or decreased by diazepam.5 mg repeated once after 10 minutes if necessary. Uncommon Respiratory depression especially with repeat doses. Nitrous oxide: enhanced sedative effect. agranulocytosis. Ketamine: enhanced sedative effect. 2009 (http://etg. London. Hodding JH. greater than 2 years 10 mg repeated once after 10 minutes if necessary. Lexi-Comp. eds. British national formulary for children 2009. BMJ Group RBS Publishing. Hudson. Rectal: Neonate 1. Thiopental: enhanced sedative effect. hallucinations. Kraus DM.5 Anticonvulsants/antiepileptics Dose: Status epilepticus. Hepatic impairment: Reduce dose as may precipitate coma. 2009. 2009. Halothane: enhanced sedative effect. accessed 10 February 2010). Paediatric Formulary Committee.

respiratory depression. vertigo. memory loss. oversedation. acute pulmonary insufficiency. light-headedness. Codeine: enhanced sedative effect. renal impairment.5 Anticonvulsants/antiepileptics Lorazepam ATC code: N05BA06 Parenteral formulation: 2 mg/ml in 1 ml ampoule. use a lower initial dose in severe impairment. In mild to moderate impairment. repeated once after 10 minutes if necessary. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. ataxia. paradoxical excitation. allergic reactions. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Contraindications: CNS depression or coma. Halothane: enhanced sedative effect. 4 mg/ml in 1 ml ampoule Special Notes: This medicine is listed as a representative of its pharmacological class. Chlorphenamine: enhanced sedative effect. anterograde amnesia. Amitriptyline: enhanced sedative effect. arrhythmias. Slow IV injection: Neonate. severe hepatic impairment. The information in this monograph only applies to the medicine listed here. for 24 hours. Precautions: Respiratory disease. respiratory depression. respiratory arrest. including leukopenia and leukocytosis. marked neuromuscular respiratory weakness including unstable myasthenia gravis. Chlorpromazine: enhanced sedative effect. shock. muscle weakness and myasthenia gravis. severe hypotension. Rare Blood disorders. use low doses of a short acting benzodiazepine to reduce risk of precipitating coma. Renal impairment: Increased sensitivity to CNS effects in renal impairment. Interactions with other medicines (* indicates severe): WHO Model Formulary for Children 2010 53 . neonates and infants. hypotension. sleep apnoea. hostility. Isoniazid: metabolism of lorazepam inhibited. jaundice. Ketamine: enhanced sedative effect. encephalopathy is present. Uncommon Headache. Dose: Status epilepticus. Morphine: enhanced sedative effect. euphoria. Haloperidol: enhanced sedative effect. anxiety. confusion. disorientation. Furosemide: enhanced hypotensive effect. hepatic impairment. for example riding a bike or operating machinery. Adverse effects: Common Drowsiness. slurred speech. Enalapril: enhanced hypotensive effect. including rash and anaphylaxis. marked personality disorder. Infant or Child 50–100 micrograms/kg (maximum 4 mg) as a single dose. porphyria. IV INJeCTION Pain and thrombophlebitis. aggression. hypersalivation. Indications: Status epilepticus. transient elevated liver Hepatic impairment: Contraindicated in severe hepatic impairment. particularly when hepatic function tests. close observation required until full recovery after sedation.

2009. Careful clinical monitoring and dosage adjustment are necessary in order to minimize the risk of adverse effects. Geneva. Australian Medicines Handbook. Generalized tonic-clonic seizures. avoid concomitant use). depression or suicidal tendencies. Hodding JH. Notes: Facilities for managing respiratory depression and hypoventilation such as mask. Taketomo CK. Oral: Infant or Child initially 1–1. generalized tonic-clonic seizures. absence seizures. Stuart MC. WHO model formulary. Kraus DM. dilute with an equal volume of sodium chloride 0. Spironolactone: enhanced hypotensive effect. Trough plasma concentration for optimum response 15–40 mg/litre (65–170 micromol/litre). Slow IV injection: Neonate. Rossi S. 54 WHO Model Formulary for Children 2010 . Hudson. ADMINISTRATION For intravenous injection. World Health Organization. Slow IV injection followed by oral: Neonate initial dose 20 mg/kg by slow IV injection followed by 2. Phenytoin: plasma phenytoin concentrations possibly increased or decreased by lorazepam. for example riding a bike or operating machinery. Adelaide.5–5 mg/kg orally once daily.5 mg/kg twice daily. Precautions: Renal impairment. debilitated. ed.5–5 mg/kg once or twice daily. Infant or Child initially 20 mg/kg followed by 2. hepatic impairment. for 24 hours. Dose: Status epilepticus. partial seizures. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Phenobarbital ATC code: N03AA02 Injection: 200 mg/ml (phenobarbital sodium) Oral liquid: 3 mg/ml (phenobarbital) Tablet: 15 mg to 100 mg (phenobarbital) Special Notes: Also known as phenobarbitone. Slow IV injection: Neonate 5–10 mg/kg every 20–30 minutes until control is achieved. Paediatric Formulary Committee. partial seizures. Pediatric dosage handbook. eds. respiratory depression. dilute injection solution to a concentration of 100 micrograms/ml).9% or water for injection (for neonates. References: Hill SR. Rifampicin: metabolism of lorazepam accelerated (reduced plasma concentration). British national formulary for children 2009. bag and/or mechanical ventilation should be at hand. 16th ed. Give slowly into a large vein at a rate not exceeding 50 micrograms/kg over 3–5 minutes. 2009. Australian medicines handbook. * Ritonavir: plasma concentration possibly increased by ritonavir (risk of extreme sedation and respiratory depression. Usual maintenance dose 2. avoid sudden withdrawal. BMJ Group RBS Publishing. Kouimtzi M. Indications: Status epilepticus. 2009. increased by 2 mg/kg daily as required. neonatal seizures. 2008. Drug subject to international control under the Convention on Psychotropic Substances (1971). may cause behavioural changes in children. Contraindications: Porphyria. THeRAPeUTIC DRUG MONITORING Therapeutic drug monitoring should be carried out. London. Neonatal seizures. Lexi-Comp.5–4 mg/kg once or twice daily.5 Anticonvulsants/antiepileptics Nitrous oxide: enhanced sedative effect.

Ethosuximide: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Etoposide: possibly reduced plasma concentration of etoposide. The incidence of serious side-effects such as Stevens-Johnson syndrome may be increased when used in combination. Avoid in severe impairment. Phenytoin: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Avoid large doses in severe impairment. Doxycycline: metabolism of doxycycline accelerated (reduced plasma concentration). hypotension. plasma concentration of carbamazepine reduced. haematological abnormalities. * Carbamazepine: may be enhanced toxicity without corresponding increase in anticonvulsant effect. toxic epidermal necrolysis and Stevens-Johnson syndrome (erythema multiforme). confusion. altered mood and behaviour. * Chloramphenicol: metabolism of chloramphenicol accelerated (reduced chloramphenicol concentration). * Haloperidol: antagonism of anticonvulsant effect (seizure threshold lowered). * Ciclosporin: metabolism of ciclosporin accelerated (reduced effect). * Amitriptyline: antagonism of anticonvulsant effect (seizure threshold lowered). * Dexamethasone: metabolism of dexamethasone accelerated (reduced effect). metabolism of amitriptyline possibly accelerated (reduced plasma concentration). restlessness. Folic acid and folinic acid: plasma concentration of phenobarbital possibly reduced. mental depression. paradoxical insomnia. hyperactivity in children. hepatitis). Griseofulvin: reduction in absorption of griseofulvin (reduced effect). lymphadenopathy. * Saquinavir: plasma concentration of saquinavir possibly reduced. * Lopinavir: plasma concentration of lopinavir possibly reduced. Mebendazole: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infection). Quinidine: metabolism of quinidine accelerated (reduced plasma concentration). Uncommon Ataxia. The incidence of serious side effects such as Stevens-Johnson syndrome may increase when used in combination. Metronidazole: metabolism of metronidazole accelerated (reduced plasma concentration). megaloblastic anaemia. Fluoxetine: antagonism of anticonvulsant effect (seizure threshold lowered).5 Anticonvulsants/antiepileptics Renal impairment: Use with caution. osteomalacia. Interactions with other medicines (* indicates severe): Abacavir: plasma concentration of abacavir possibly reduced. plasma concentration of ethosuximide possibly reduced. plasma concentration of phenobarbital often raised. WHO Model Formulary for Children 2010 55 . severe skin disease. * Chlorpromazine: antagonism of anticonvulsant effect (seizure threshold lowered). multi-organ hypersensitivity syndrome (including fever. * Prednisolone: metabolism of prednisolone accelerated (reduced effect). * Hydrocortisone: metabolism of hydrocortisone accelerated (reduced effect). Dupuytren contracture. Common Sedation. Adverse effects: Prolonged use may cause physical dependence. nystagmus. aggression. plasma concentration of phenytoin often lowered but may be raised. metabolism of haloperidol accelerated (reduced plasma concentration). Rare exfoliative dermatitis. Levothyroxine: metabolism of levothyroxine accelerated (may increase levothyroxine requirements in hypothyroidism). Hepatic impairment: May precipitate coma.

rash. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.5 mg/kg twice daily. 100 mg (sodium salt) Tablet (chewable): 50 mg *NOTe The possible availability of such similar strengths can cause confusion in prescribing and dispensing. * Warfarin: metabolism of warfarin accelerated (reduced anticoagulant effect). renal impairment. Hudson. 50 mg. partial seizures. Child 3 months–12 years: 10–20 mg/litre (40–80 micromol/litre). ADMINISTRATION For intravenous injection. 2009. extreme care must be taken when prescribing or dispensing this dose form. London. partial seizures. Notes: For therapeutic purposes phenobarbital and phenobarbital sodium may be considered equivalent in effect. give over 20 minutes (no faster than 1 mg/kg/minute). generalized tonic-clonic seizures. Dose: Status epilepticus. Infant or Child 18 mg/kg as a loading dose. Stuart MC. Generalized tonic-clonic seizures. heart block. monitor blood counts. Geneva.5–5 mg/kg twice daily. Kraus DM. Contraindications: Porphyria.5 mg/kg or 300 mg daily. 100 mg (sodium salt) Injection: 50 mg/ml in 5 ml vial (sodium salt) Oral liquid: 5 mg or 6 mg/ml* (base) Tablet: 25 mg. Therapeutic plasma phenytoin concentrations are reduced in the first 3 months of life because of reduced protein binding. Trough plasma concentration for optimum response: Neonate–3 months: 6–15 mg/litre (25–60 micromol/litre). Hodding JH. for example riding a bike or operating machinery.5–2.5 Anticonvulsants/antiepileptics Valproic acid: may be enhanced toxicity without corresponding increase in anticonvulsant effect. 2009. 16th ed. progressive or associated with clinical symptoms requires withdrawal (if necessary under cover of suitable alternative). WHO model formulary. THeRAPeUTIC DRUG MONITORING Therapeutic drug monitoring is required for optimum response and to avoid unnecessary toxicities. increased gradually according to clinical response and plasma phenytoin concentrations to 2. bruising or bleeding develop. World Health Organization. Leukopenia which is severe. IV: Neonate. Kouimtzi M. 2008. Pediatric dosage handbook. Usual maximum 7. 56 WHO Model Formulary for Children 2010 . injection solution alkaline (irritant to tissues). avoid sudden withdrawal. Taketomo CK. then 2.5–5 mg/kg twice daily. plasma concentration of valproic acid reduced. Hill SR. avoid intramuscular administration BLOOD OR SKIN DISORDeRS Patients or their carers should be told how to recognize signs of blood or skin disorders and advised to seek immediate medical attention if symptoms such as sore throat. for 24 hours. mouth ulcers. dilute to a concentration of 20 mg/ml with water for injections. 50 mg. eds. Paediatric Formulary Committee. BMJ Group RBS Publishing. Tablets may be crushed before administration. Oral: Infant or Child initially 1. phenobarbital concentration increased. Indications: Status epilepticus. References: Phenytoin ATC code: N03AB02 Capsule: 25 mg. Precautions: Hepatic impairment. sinus bradycardia. Lexi-Comp. British national formulary for children 2009.

rash (discontinue. partially explained by decreases in serum albumin. and alterations in respiratory function (including respiratory collapse). multi-organ hypersensitivity syndrome (including fever. systemic lupus erythematosus. vertigo. ataxia. serum phenytoin protein binding is altered in uraemia which can affect proper interpretation/evaluation of serum phenytoin concentrations. However. gingival hypertrophy. Adverse effects: Common Gastric intolerance. 57 WHO Model Formulary for Children 2010 . nystagmus. cerebellar/vestibular symptoms. impaired learning (dose related). neurological changes including peripheral neuropathy. toxic epidermal necrolysis. impaired cognition. Dactinomycin: possibly reduced absorption of phenytoin. Ciprofloxacin: plasma phenytoin concentration can be increased or decreased by ciprofloxacin. Chloramphenicol: plasma phenytoin concentration increased (increased risk of toxicity). hyperglycaemia. lymph node enlargement. Diazepam: plasma phenytoin concentration possibly increased or decreased by diazepam. severe skin disease. In these cases clinical outcomes should be considered before changing doses according to blood levels. Ciclosporin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). magnesium hydroxide): reduced absorption of phenytoin.5 Anticonvulsants/antiepileptics Renal impairment: No specific dose adjustment is necessary. haematological abnormalities. if mild. choreiform movements. Amitriptyline: antagonism of anticonvulsant effect (convulsive threshold lowered). cerebellar atrophy. agitation. Dacarbazine: possibly reduced absorption of phenytoin. sleeplessness. reintroduce cautiously but discontinue if recurrence). Bleomycin: possibly reduced absorption of phenytoin. acne. IV Cardiovascular and central nervous system depression (particularly if administered too rapidly) with arrhythmias. hirsutism. confusion. possibly reduced plasma amitriptyline concentration. Hepatic impairment: Reduce dose to avoid toxicity. coarse facies. behavioural disorders. increased seizure frequency. Daunorubicin: possibly reduced absorption of phenytoin. diplopia. may lead to soft tissue necrosis and limb ischaemia). plasma concentration of phenytoin often lowered but may be raised. The fraction of unbound phenytoin increases as renal function decreases. plasma concentration of carbamazepine often lowered. Cyclophosphamide: possibly reduced absorption of phenytoin. Dexamethasone: metabolism of dexamethasone accelerated (reduced effect). Rare Hallucinations. IV Thrombophlebitis. slurred speech. Carbamazepine: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Azathioprine: possibly reduced absorption of phenytoin. Stevens-Johnson syndrome. lymphadenopathy. hepatitis). discoloration and pain. Interactions with other medicines (* indicates severe): * * * * * * Abacavir: plasma concentration of abacavir possibly reduced. local skin necrosis. Incidence of serious side-effects such as Stevens-Johnson syndrome may be increased in combination therapy. ‘purple glove’ syndrome (progressive distal limb oedema. Acetylsalicylic acid: enhancement of effect of phenytoin. osteomalacia and rickets. Chlorpromazine: antagonism of anticonvulsant effect (convulsive threshold lowered). Antacids (aluminium hydroxide. Chloroquine: possible increased risk of seizures. sedation. blurred vision. Cytarabine: reduced absorption of phenytoin. hypotension and cardiovascular collapse. blood dyscrasias.

Procarbazine: reduced absorption of phenytoin. Hydrocortisone: metabolism of hydrocortisone accelerated (reduced effect). plasma concentration of phenobarbital often raised. Sulfadoxine + pyrimethamine: plasma phenytoin concentration possibly increased. Sulfamethoxazole + trimethoprim: antifolate effect and plasma phenytoin concentration increased. Fluconazole: plasma concentration of phenytoin increased (consider reducing dose of phenytoin). Doxycycline: increased metabolism of doxycycline (reduced plasma concentration). increased antifolate effect. Prednisolone: metabolism of prednisolone accelerated (reduced effect). Pyrimethamine: antagonism of anticonvulsant effect. Mefloquine: antagonism of anticonvulsant effect. Fluorouracil: metabolism of phenytoin possibly inhibited (increased risk of toxicity). WHO Model Formulary for Children 2010 * * * * * * * * * * * * * * * * 58 . Sulfadiazine: plasma phenytoin concentration possibly increased. Ethosuximide: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Levothyroxine: accelerated metabolism of levothyroxine (may increase levothyroxine requirements in hypothyroidism). Phenobarbital: may be enhanced toxicity without corresponding increase in anticonvulsant effect. Metronidazole: metabolism of phenytoin inhibited (increased plasma phenytoin concentration). Silver sulfadiazine: possibly increased plasma concentration of phenytoin. Lopinavir: plasma lopinavir concentration possibly reduced. Ibuprofen: effect of phenytoin possibly enhanced. Mercaptopurine: possibly reduced absorption of phenytoin. Incidence of serious side-effects such as Stevens-Johnson syndrome may be increased in combination therapy. antifolate effect of methotrexate increased. Doxorubicin: possibly reduced absorption of phenytoin.5 Anticonvulsants/antiepileptics Digoxin: plasma concentration of digoxin possibly reduced. Etoposide: possibly reduced absorption of phenytoin and possibly reduced plasma concentration of etoposide. plasma concentration of phenytoin possibly increased. increased antifolate effect. plasma concentration of phenytoin possibly increased. Folic acid and folinic acid: plasma phenytoin concentration possibly reduced. Fluoxetine: plasma concentration of phenytoin increased. Methotrexate: reduced absorption of phenytoin. Haloperidol: antagonism of anticonvulsant effect (convulsive threshold lowered). Levamisole: plasma phenytoin concentration possibly increased. Quinidine: accelerated metabolism of quinidine (reduced plasma quinidine concentration). Saquinavir: plasma saquinavir concentration possibly reduced. plasma concentration of ethosuximide possibly reduced. Mebendazole: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infections). Trimethoprim: antifolate effect and plasma phenytoin concentration increased. plasma concentration of phenytoin often lowered but may be raised. Praziquantel: plasma praziquantel concentration reduced. Rifampicin: accelerated metabolism of phenytoin (reduced plasma concentration). Isoniazid: metabolism of phenytoin inhibited (enhanced effect).

rash. but enhancement also reported). influenza: enhanced effect of phenytoin. Zidovudine: plasma phenytoin concentration increased or decreased by zidovudine. ADMINISTRATION For administration by mouth: interrupt enteral feeds for at least 1–2 hours before and after giving phenytoin. plasma concentration of valproic acid reduced. Preferably give phenytoin with or after food. hepatitis. Preferably take with or after food. family history of severe hepatic dysfunction. complete administration within 1 hour of preparation. 2009.5 micron) at a rate not exceeding 1 mg/kg/minute (maximum 50 mg/minute). 2010. 2009. Australian medicines handbook. Vincristine: possibly reduced absorption of phenytoin. porphyria. pancreatitis.5 Anticonvulsants/antiepileptics Vaccine. Hodding JH. 2008. London. * Warfarin: accelerated metabolism of warfarin (possibility of reduced anticoagulant effect. symptoms include fever. (http://www. give with water to enhance absorption.22–0. For intravenous injection: give at rate not exceeding 1 mg/kg/minute (maximum 50 mg/minute). ed. To ensure consistent absorption. haematological abnormalities. Thomson Micromedex. Geneva. Vinblastine: possibly reduced absorption of phenytoin. Adelaide. Notes: 100 mg phenytoin sodium contains approximately 92 mg phenytoin. plasma concentration of phenytoin increased or possibly reduced. administer at the same time in regard to meals. Contraindications: Active liver disease.9%. Klasco RK. Kouimtzi M. Indications: All forms of epilepsy and seizure disorders including infantile spasms. World Health Organization. BMJ Group RBS Publishing. Paediatric Formulary Committee. Valproic acid: may be enhanced toxicity without corresponding increase in anticonvulsant effect. References: Valproic acid (sodium valproate) ATC code: N03AG01 Oral liquid: 40 mg/ml Tablet (crushable): 100 mg Tablet (enteric coated): 200 mg. Hill SR. Lexi-Comp. previous history of Stevens-Johnson syndrome. Vecuronium: antagonism of muscle relaxant effect (accelerated recovery from neuromuscular blockade). For intravenous infusion: dilute to a concentration not exceeding 10 mg/ml with sodium chloride 0.thomsonhc. Hudson. 500 mg (sodium valproate) Hepatic failure resulting in death may occur. For intravenous administration: before and after administration flush intravenous line with sodium chloride 0. Taketomo CK. hepato-renal syndrome may occur. WHO Model Formulary for Children 2010 59 . Kraus DM. ed. British national formulary for children 2009. HyPeRSeNSITIVITy SyNDROMe Usually occurs in first 6 weeks and can be fatal. Greenwood Village. Pediatric dosage handbook. 16th ed. lymphadenopathy. eds. Monitoring of therapeutic concentrations in plasma can improve safety and efficacy. 2009. Cases of life-threatening pancreatitis (including fatalities) have been reported in children.com. Drugdex system. Stuart MC. WHO model formulary. Australian Medicines Handbook.9% and give through an inline filter (0. Rossi S. accessed 10 February 2010).

If dose exceeds 20 mg/kg twice daily.5 mg/kg twice daily. Renal impairment: Reduce dose and alter dosage according to free serum valproic acid concentration. lethargy. ensure no undue potential for bleeding before starting and before major surgery or anticoagulant therapy. false-positive urine tests for ketones. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. those with metabolic disorders. for example riding a bike or operating machinery. Adverse effects: Common Increased appetite and weight gain. sedation. Interactions with other medicines (* indicates severe): Acetylsalicylic acid: enhancement of effect of valproic acid. Renal impairment reduces protein binding. hyperammonaemia. Infant or Child initially 5–7. PANCReATITIS Patients or their carers should be told how to recognize signs of pancreatitis and advised to seek immediate medical attention if symptoms such as abdominal pain.5–15 mg/kg twice daily. tremor. hepatotoxicity and hepatic failure may occasionally occur (usually in first 6 months). monitor clinical chemistry and haematological parameters. fibrinogen reduction. Usual maintenance dose is 12. Fanconi syndrome). pancytopenia. toxic epidermal necrolysis. unless under medical supervision. Dose: All forms of epilepsy and seizure disorders including infantile spasms. lethargy. behavioural disturbances. Usual maintenance dose is 10 mg/kg twice daily. gynaecomastia. degenerative disorders. dementia. systemic lupus erythematosus. Hepatic impairment: Avoid if possible. Carbamazepine: may be enhanced toxicity without corresponding increase in anticonvulsant effect. especially in BLOOD OR HePATIC DISORDeRS Patients or their carers should be told how to recognize signs of blood or liver disorders. Oral: Neonate initially 20 mg/kg once daily. Rare Oedema. plasma concentration of active metabolite of carbamazepine increased. withdraw treatment immediately if malaise. or multiple antiepileptic therapy). Uncommon Transient hair loss (regrowth may be curly). impaired hepatic function. avoid sudden withdrawal. nausea. * Chloroquine: possible increased risk of seizures. organic brain disease or severe seizure disorders associated with mental retardation. fatal hepatic failure (see Precautions. inhibition of platelet aggregation. StevensJohnson syndrome (erythema multiforme). and advised to seek immediate medical attention if symptoms including loss of seizure control. abdominal pain. leukopenia. vomiting. weakness. measure plasma amylase if acute abdominal pain). ataxia. * Amitriptyline: antagonism of anticonvulsant effect (seizure threshold lowered). weakness. gastrointestinal irritation. * Chlorpromazine: antagonism of anticonvulsant effect (seizure threshold lowered). increased alertness. Up to 30 mg/kg twice daily in infantile spasms may be required. vasculitis. extrapyramidal symptoms. monitoring only total valproic acid serum concentrations may be misleading. irregular periods. abdominal pain. oedema. anorexia. hirsutism. 60 WHO Model Formulary for Children 2010 . drowsiness. malaise. discontinue sodium valproate if pancreatitis diagnosed.5 Anticonvulsants/antiepileptics patients at most risk (children under 3 years of age. jaundice. oedema. amenorrhoea. pancreatitis (see Precautions. acne. red cell hypoplasia. thrombocytopenia. renal impairment. nausea and vomiting develop. Precautions: Monitor liver function before and during first 6 months of therapy. anorexia. hearing loss. drowsiness or loss of seizure control). or spontaneous bruising or bleeding develop. plasma concentration of valproic acid reduced. vomiting. jaundice. hepatic impairment. blood disorders (see Precautions.

for 24 hours. British national formulary for children 2009. Drugdex system. not generally considered useful in assessing control.int/medicines/publications/essentialmeds_committeereports/TRS_950. Hodding JH. Notes: Plasma concentrations in therapeutic range of 40–100 mg/litre (280–700 micromol/litre). In patients with confirmed adherence. Australian Medicines Handbook. up to a maximum of 1 g twice daily may be needed). Kouimtzi M. WHO model formulary. Ethosuximide: may be enhanced toxicity without corresponding increase in anticonvulsant effect. bruising or bleeding and be advised to seek immediate medical attention if these symptoms occur.com. ed. Geneva. Klasco RK. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. ed. Ethosuximide ATC code: N03AD01 Capsule: 250 mg Oral liquid: 50 mg/ml Indications: Absence seizures. Oral: Infant or Child 1 month–6 years initially 5 mg/kg (maximum 125 mg) twice daily. Dose: Absence seizures. Hudson. for example riding a bike or operating machinery. * Haloperidol: antagonism of anticonvulsant effect (seizure threshold lowered).who. Rossi S. Adelaide. WHO expert committee on the selection and use of essential medicines. eds. The selection and use of essential medicines: report of the WHO expert committee. WHO Technical Report Series. but higher levels associated with increased incidence of adverse effects.pdf ). 2009. 2009. 6–12 years initially 250 mg twice daily. (http://www.5 Anticonvulsants/antiepileptics Erythromycin: metabolism of valproic acid possibly inhibited (increased plasma concentration).thomsonhc. BLOOD DISORDeRS Children or their carers should be told how to recognize signs of blood disorders such as fever. October 2007 (including the model list of essential medicines for children). Australian medicines handbook. Taketomo CK. 2010. mouth ulcers. World Health Organization. Kraus DM. Phenobarbital: may be enhanced toxicity without corresponding increase in anticonvulsant effect. increased by 250 mg at intervals of 4–7 days to a usual dose of 500–750 mg twice daily (occasionally. Phenytoin: may be enhanced toxicity without corresponding increase in anticonvulsant effect. plasma concentration of valproic acid reduced. phenobarbital concentration increased. Stuart MC. WHO Model Formulary for Children 2010 61 . Pediatric dosage handbook. Paediatric Formulary Committee. low or undetectable plasma levels are not necessarily an indicator of non-adherence. plasma concentration of phenytoin increased or possibly reduced. Thomson Micromedex. 950 (http://www. Greenwood Village. avoid sudden withdrawal. References: Hill SR. 2008. Warfarin: anticoagulant effect possibly enhanced. London. Precautions: Hepatic impairment. 2009. 16th ed. * Mefloquine: antagonism of anticonvulsant effect. accessed 10 February 2010). dose change or co-medication may be needed. sore throat. Lexi-Comp. increased gradually over 2–3 weeks to a maintenance dose of 10–20 mg/kg (maximum 500 mg) twice daily. plasma concentration of valproic acid reduced. plasma concentration of ethosuximide possibly increased. Zidovudine: plasma concentration of zidovudine possibly increased (risk of toxicity). porphyria. 2008. blood counts and hepatic and renal function tests recommended. renal impairment. BMJ Group RBS Publishing.

epigastric pain (particularly during initial treatment). ataxia. Chloroquine: possible increased risk of seizures. nausea and vomiting. thrombocytopenia and pancytopenia). vaginal bleeding. eds. Hepatic impairment: Use with caution.com. plasma concentration of phenytoin possibly increased. 2009. Interactions with other medicines (* indicates severe): * Amitriptyline: antagonism of anticonvulsant effect. * Haloperidol: antagonism of anticonvulsant effect (seizure threshold lowered). AHFS drug information. (http://www. Dose reduction not necessary. increased libido. Lexi-Comp. Hodding JH. agranulocytosis. WHO model formulary. Klasco RK. Pediatric dosage handbook. possibly reduced plasma concentration of ethosuximide. World Health Organization. The renal drug handbook. Oxford. Kraus DM. 2009. disturbances of liver and renal function. The selection and use of essential medicines: report of the WHO expert committee.5 Anticonvulsants/antiepileptics Renal impairment: Use with caution. increased mental state depression with overt suicidal ideation. dizziness. Valproic acid: may enhance toxicity of valproic acid without corresponding increase in anticonvulsant effect. myopia. 2008. Adelaide. Rossi S. drowsiness. October 2007 (including the model list of essential medicines for children). eds. plasma concentration of ethosuximide possibly reduced. 950 (http://www. Australian Medicines Handbook. Mcevoy GK.who. Carbamazepine: may enhance toxicity of carbamazepine without corresponding increase in anticonvulsant effect. 16th ed. gum hyperplasia. Bethesda. night terrors. psychosis.pdf.int/medicines/publications/essentialmeds_committeereports/TRS_950. Geneva. 2008. * Chlorpromazine: antagonism of anticonvulsant effect. WHO Technical Report Series. systemic lupus erythematosus. possibly increased plasma concentration of ethosuximide. Greenwood Village. References: Ashley C. 2009. Currie A. ed. Hill SR. euphoria. * Mefloquine: antagonism of anticonvulsant effect. * Isoniazid: metabolism of ethosuximide inhibited (increased plasma ethosuximide concentration and risk of toxicity). WHO expert committee on the selection and use of essential medicines. headache. Thomson Micromedex. Therapeutic drug monitoring (TDM) is available for ethosuximide but routine monitoring is not required for the majority of patients. 3rd ed. Australian medicines handbook. aplastic anaemia. hyperactivity. Notes: Administer with food or milk to reduce gastrointestinal upset. Uncommon Irritability. Radcliffe Publishing. American Society of Health-System Pharmacists. haematological disorders (including leukopenia. Taketomo CK. possibly reduced plasma concentration of ethosuximide. hiccups. Kouimtzi M. weight loss. Drugdex system. 2009. ed. Adverse effects: Common Gastrointestinal disturbances including anorexia. swelling of tongue. * Phenytoin: may enhance toxicity without corresponding increase in anticonvulsant effect. Plasma concentration for optimum response 40–100 mg/litre (300–700 micromol/litre). Stuart MC. Hudson. Rare Rash including Stevens-Johnson syndrome (erythema multiforme). 2010. aggressiveness. accessed 10 February 2010).thomsonhc. ed. sleep disturbances. depression. Phenobarbital: may enhance toxicity of phenobarbital without corresponding increase in anticonvulsant effect. Dose reduction not necessary. 62 WHO Model Formulary for Children 2010 .

.2......................................................................................................2 Antileishmaniasis medicines.. 64 6.........4.........................SECTION 6: Anti-infective medicines 6......... 230 6................................................... 148 6............................1 Anthelminthics ................... 148 6..........................3 Antischistosomals and antitrematode medicines.......................5...... 199 6........ 150 Fixed-dose combinations ....2 Non-nucleoside reverse transcriptase inhibitors ......1 For curative treatment .......4............3 Protease inhibitors........................ 122 6....5.2 Antifilarials ..........1 Intestinal anthelminthics ..............4..2............................................... 80 Other antibacterials ..... 72 6........2.............................................................. 64 6.....5........................... 208 6.1 Antiherpes medicines ......3...........................1...................................5......................4 Antifungal medicines ...........................1 6..................5 Antitrypanosomal medicines................3 6.................................. 75 6..........................1 African trypanosomiasis ..2 American trypanosomiasis.....1 Antiamoebic and antigiardiasis medicines .2 6..4......................... 220 6.............5.................................................................5.............4................................................................................2 Antibacterials ..................2........................3 Antimalarial medicines ... 187 6.......................5.............................2 Antiretrovirals ..................................1........ 197 6....4 Antipneumocystosis and antitoxoplasmosis medicines .................5.2 For prophylaxis ..................................2.................... 208 6..........................3 6.......................3 Other antivirals......... 201 6................ 163 6............................ 118 Antituberculosis medicines ........1.......................... 138 Antiviral medicines .....5...4........................5.....5 Antiprotozoal medicines ............. 225 6........................ 236 WHO Model Formulary for Children 2010 63 ...2....3............................................................. 199 6...........1 Nucleoside/nucleotide reverse transcriptase inhibitors ...........5........ 230 6.................4 Beta-lactam medicines ........................ 151 6....................................................... 180 6..............................2............................................................. 98 Antileprosy medicines . 79 6...............................

pinworms. 64 WHO Model Formulary for Children 2010 .6 Anti-infective medicines 6 6. Intestinal tapeworm infections are often asymptomatic. nausea and abdominal pain. retinal cysticercosis. Oral: Child 12 months–2 years 200 mg as a single dose. hookworms. There may be loss of appetite. ascariasis. then repeat for 2–3 cycles. trichostrongyliasis and trichuriasis. Treatment may be repeated in 3 weeks. pinworms.1. Dose: Hydatid disease (E. Precautions: Liver function tests and blood counts before treatment and every 2 weeks while on therapy. enterobiasis). visceral larva migrans and trichinosis. necatoriasis. which can include the pancreas. Oral: Child over 2 years 7. bile duct and appendix. whipworm. hairworm. diphyllobothriasis and echinococcosis (hydatid disease). tapeworm (taeniasis). Further symptoms may become apparent due to worm migration. Albendazole ATC code: P02CA03 Tablet (chewable): 400 mg Indications: Treatment of hydatid disease (Echinococcus granulosus. granulosus. roundworms. roundworms. dracunculiasis. strongyloidiasis. multilocularis) prior to or not amenable to surgery.1 Anti-infective medicines Anthelminthics Intestinal anthelminthics Cestode tapeworm infections Cestode infections include intestinal taeniasis and cysticercosis. trichinellosis and visceral larva migrans. neurocysticercosis (consider steroid and anticonvulsant therapy). filariasis. multilocularis). E. Intestinal nematode infections Intestinal nematode infections include ascariasis.1 6. pregnancy. Tissue nematode infections Tissue nematode infections include angiostrongyliasis. capillariasis. cutaneous larva migrans.5 mg/kg twice daily with food (maximum 400 mg twice daily) for 28 days. threadworms (ancylostomiasis. hymenolepiasis (dwarf tapeworm). greater than 2 years or < 10 kg 400 mg as a single dose before food. depending on the site affected. followed by 14 day break. anisakiasis. strongyloidiasis. threadworms. cutaneous larva migrans. E. Contraindications: Known hypersensitivity to benzimidazoles. Hookworms. hookworm infection. enterobiasis. neurocysticercosis.

nausea. diarrhoea. Oral: Child all ages 10 mg/kg daily (maximum 400 mg daily) for 5 days. greater than 10 kg 400 mg annually for 5 years. Treatment may be repeated in 3 weeks. urticaria). or in heavier infections. Whipworm (Trichuriasis). pancytopenia. dizziness. Notes: To aid administration. Oral or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of treatment. hepatitis. Oral: Child less than 10 kg 200 mg daily before food for 3 days. Rare Hypersensitivity (itch. increased liver function tests. cholestatic jaundice. Hepatic impairment: Patients with liver disease may be more susceptible to bone marrow suppression. alopecia. Blood counts should be monitored at the beginning of each 28 day cycle of therapy. Stevens-Johnson syndrome. Interactions with other medicines (* indicates severe): Dexamethasone: plasma albendazole concentration possibly increased. Oral: Child greater than 10 kg 400 mg as a single dose. convulsions and meningism in cerebral disease. fever. or crushed or chewed. Treatment may be repeated in 3 weeks.6. Visceral larva migrans (toxocariasis). tablets may be dispersed in water. Dosage adjustment in patients with impaired renal function does not appear necessary. Oral: Child greater than 10 kg 400 mg as a single dose. Oral: Child greater than 2 years 200–400 mg as a single dose. Oral: Child less than 10 kg 200 mg once annually for 5 years. abdominal pain. Adverse effects: Common or uncommon Headache.5 mg/kg (maximum dose 400 mg) twice daily after food for 7–30 days. Hairworm (Trichostrongyliasis). Oral: Child greater than 10 kg 400 mg daily for 8–14 days. Praziquantel: increased plasma concentration of active metabolite of albendazole. allergic shock if cyst leakage. Cutaneous larva migrans. strongyloidiasis. Trichinosis. and every 2 weeks while on therapy with albendazole in all patients. WHO Model Formulary for Children 2010 65 . Renal impairment: Renal elimination of albendazole is minimal.1 Anthelminthics Tapeworm (taeniasis). Neurocysticercosis. 400 mg daily for 3 days. greater than 10 kg 400 mg daily before food for 3 days. Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. bone marrow depression. Oral: Child under 60 kg 7. vomiting. Filariasis for community eradication programmes in combination with diethylcarbamazine or ivermectin. rash. or 400 mg daily for 3 days.

rash. Klasco RK. Precautions: epilepsy. ed. 2009. Geneva.com. seizures (especially at high doses). UBM Medica. Sydney. (http://www. Dose: Ascariasis (roundworm). London. Hookworm and mixed ascariasis with hookworm. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. accessed 10 February 2010). The information in this monograph only applies to the medicine listed here.aspx. elk Grove Village. ed. Thomson Micromedex. 2008. Red Book: 2009 report of the committee on infectious diseases. MIMS Online. Klasco RK. British national formulary for children 2009. Levamisole ATC code: P02Ce01 Tablet: 50 mg. blood disorders. hookworm and mixed ascariasis with hookworm infections. 2009 (http://www. 500 mg Special Notes: This medicine is listed as a representative of its pharmacological class. Mebendazole ATC code: P02CA01 Tablet (chewable): 100 mg.5–3 mg/kg (maximum dose 150 mg) as a single dose. 2009. Drugdex system. Oral: Infant and Child all ages 2. Adverse effects: Uncommon Abdominal pain.thomsonhc.6 Anti-infective medicines References: American Academy of Pediatrics. 66 WHO Model Formulary for Children 2010 . Drugdex system. Renal impairment: Dose reduction not necessary as only small amounts (approximately 3%) of a dose of levamisole are excreted unchanged in the urine. Notes: Leukocyte and platelet counts should be monitored regularly during levamisole therapy. References: American Academy of Pediatrics.mimsonline. British national formulary for children 2009. Interactions with other medicines (* indicates severe): Alcohol: possibility of disulfiram-like reaction. Phenytoin: plasma phenytoin concentration possibly increased. Oral: Infant and Child all ages 2. 2010. Thomson Micromedex. 28th ed. Paediatric Formulary Committee. American Academy of Pediatrics. American Academy of Pediatrics. * Warfarin: anticoagulant effect possibly enhanced. Paediatric Formulary Committee. WHO model formulary. vomiting. Hill SR. World Health Organization. Greenwood Village. 2009. BMJ Group RBS Publishing. Hepatic impairment: Use with caution. accessed 10 February 2010). BMJ Group RBS Publishing. juvenile idiopathic arthritis. 28th ed. Red Book: 2009 report of the committee on infectious diseases. elk Grove Village. dose adjustment may be necessary. accessed 10 February 2010).com. nausea. Kouimtzi M. 2010. vasculitis. dizziness and headache.5 mg/kg (maximum dose 150 mg) as a single dose repeated after 7 days if severe infection.thomsonhc. influenza-like syndrome. 150 mg (as hydrochloride) Indications: Treatment of ascariasis. 2009. myalgia. London. Sjogren syndrome. Stuart MC.au/Search/Search. insomnia. Greenwood Village.com. eds. Rare Taste disturbances (on prolonged treatment). arthralgia. (http://www.

Renal impairment: Dose reduction not necessary. greater than 10 kg or from 1 year 100 mg twice daily for 3 days. Trichinosis (gastrointestinal phase of illness only). dizziness. Toxocariasis: visceral larva migrans (mebendazole is second-line therapy. hookworms. raised liver enzymes. roundworms. Oral: Child all ages from 2 years 15mg/kg/dose three times daily. Oral: Child all ages from 2 years 5 mg/kg (maximum 200 mg) twice daily with food for 7 days. with high doses. multilocularis) before surgery or not amenable to surgery and also for toxocariasis. Notes: Doses should be taken between meals. Adverse effects: Rare Gastrointestinal disturbances. Contraindications: Known hypersensitivity to benzimidazoles. bone marrow depression. if reinfection occurs second dose may be needed after 2 weeks.1 Anthelminthics Indications: Treatment of pinworm. whipworm and hookworm infections. pinworms. Oral: Child all ages from 2 years 100–200 mg twice daily for 5 days although doses of up to 1 g/day have been used for 21 days. albendazole is preferred). Dose: Threadworms. children < 6 months old. allergic reactions.6. threadworm. Hepatic impairment: extensively metabolized in the liver. Severe disease may warrant corticosteroid use. late phase anthelminthic therapy not indicated. Phenobarbital: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infection). Precautions: Blood counts and liver function tests should be monitored (with high-dose regimens). alopecia. Interactions with other medicines (* indicates severe): Carbamazepine: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infection). Capillariasis. pregnancy. Oral: Child from 6 months up to 10 kg 50 mg twice daily for 3 days. Whipworms. if reinfection occurs second dose may be needed after 2 weeks. roundworm. severe infection may require concomitant corticosteroid use. WHO Model Formulary for Children 2010 67 . Hepatic insufficiency: lower dose to prevent toxic levels of mebendazole. Oral: Child from 6 months up to 10 kg 50 mg as a single dose. Also for the gastrointestinal phase of trichinosis (Trichinella spiralis) and for capillariasis (Capillaria philippinensis). greater than 10 kg or from 1 year 100 mg as a single dose. echinococcus (mebendazole is second-line therapy. albendazole is preferred). Phenytoin: reduced plasma mebendazole concentration (possibly increase mebendazole dose for tissue infection). As a second-line agent in the treatment of hydatid disease (Echinococcus granulosus and E. Oral: Child all ages from 2 years 200 mg twice daily for 20 days. headache.

Guerrant RL. Tropical infectious diseases: principles. 2009. Gilbert DN et al. 13th ed. T. Hepatic impairment: Dose reduction not necessary. Doses should be given after a light breakfast. (http://www. Johns Hopkins Point of Care Information Technology (POC-IT) Abx Guide.com. not effective against larval stage (cysticercosis) (i. 2010. ed. Oral: As for T. give antiemetic before treatment. Churchill Livingstone. 2006. McDowell JM. retching. Paediatric Formulary Committee. abdominal pain. 2004.e. solium. followed after 2 hours by a laxative. Adverse effects: Common Nausea. or 2 g daily for 7 days. Kemp CA. 2–6 years 1 g. 2–6 years 1 g on first day then 500 mg daily for 6 days. 46:1–12.e. 2nd ed. saginata. Weller PF. Notes: Niclosamide must be chewed thoroughly and then swallowed with a small amount of water. The Sanford guide to antimicrobial therapy. Drugdex system. pathogens. Repeated treatment may be necessary to cure intense infections or to eliminate the parasite within a family group or institution. solium but half the dose may be taken after breakfast and the remainder 1 hour later followed by a laxative after 2 hours. 2002. ed. 38th ed. London. Niclosamide ATC code: P02DA01 Tablet (chewable): 500 mg Special Notes: Niclosamide is listed for use only when praziquantel fails. (PDA reference. Sperryville. Uncommon Lightheadedness. Dipylidium caninum and Hymenolepis nana) infections. Indications: A second-line agent for the treatment of tapeworm (Taenia saginata. BMJ Group RBS Publishing. Royal Children’s Hospital. Walker DH. 28th ed. Thomson Micromedex. WHO Model Formulary for Children 2010 68 . Oral: Child under 2 years 500 mg on the first day then 250 mg daily for 6 days. elk Grove Village. Bartlett JG. 2008. & practice. intestinal stage in host). Rare Pruritus. British national formulary for children 2009. Philadelphia. autoinfection. The drug has a vanilla taste which is palatable for most children. American Academy of Pediatrics. Diphyllobothrium latum. Paediatric pharmacopoeia. The Medical Letter on Drugs and Therapeutics. tissue stage in host). only active against adult stage of tapeworm (i. Greenwood Village. Precautions: Chronic constipation (restore regular bowel movement before treatment). over 6 years 2 g as a single dose on first day then 1 g daily for 6 days. Melbourne.) 2003 (with updates 2004–2009). Antimicrobial Therapy. solium infection. Tablets may be crushed to a fine powder for administration to young children and mixed with a small amount of water to form a paste. over 6 years 2 g. Dipylidium caninum and Diphyllobothrium latum infection. Drugs for parasitic infection. Dose: T.thomsonhc. 2009. Red Book: 2009 report of the committee on infectious diseases. Oral: Child under 2 years 500 mg. Symptomatic persisting Hymenolepis nana infection.6 Anti-infective medicines References: American Academy of Pediatrics. Renal impairment: Dose reduction not necessary. accessed 10 February 2010). T. Klasco RK.

[PDA reference] 2009. Ocular or neurocysticercosis. Oral: Child over 4 years 15–25 mg/kg as a single dose. solium in tissues and CNS). Johns Hopkins Point of Care Information Technology (POC-IT) Abx Guide. Concomitant laxative use 2 hours after niclosamide. cardiac arrhythmias. Dose: Taenia saginata and T. Bartlett JG. and depends on activity status of disease. solium infections. for 24 hours. American Academy of Pediatrics. Symptomatic and persisting Hymenolepis nana infection. ed. Taenia saginata. Greenwood Village. although only specifically indicated for T. dermal cysticercosis.thomsonhc. Multidisciplinary expert consultation strongly advised (infectious diseases physician. 2009. Praziquantel ATC code: P02BA01 Tablet: 150 mg. 1995 (http://www. 2008. Diphyllobothrium latum infection. neurosurgeon (if cerebral or spinal). Hymenolepsis nana). solium infections. Diphyllobothrium latum.drugs. World Health Organization. Cysticercosis. BMJ Group RBS Publishing. Hepatic impairment: Consider reducing dose in moderate to severe impairment (increases concentration and half-life). Niclocide Product Information.1 Anthelminthics Niclosamide is effective but may cause disintegration of T. Oral: Child over 4 years 10–25 mg/kg as a single dose. Precautions: SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. accessed 10 February 2010). Thomson Micromedex. Oral: 17–33 mg/kg/dose three times daily for 14 days or for 30 days if giant cysts or subarachnoid cysts are present.com/mmx/niclocide. NOTe Praziquantel use in neurocysticercosis is controversial. Hill SR. Stuart MC. Bayer. Geneva.6. Drugdex system. 28th ed. (http://www. WHO model formulary. as the precise species of worm may not be confirmed. Active parenchymal neurocysticercosis.html. Renal impairment: Dose reduction not necessary. Oral: Child over 4 years 60 mg/kg daily in three divided doses for 6 days. ophthalmologist (if ocular)).com. Kouimtzi M. Klasco RK. elk Grove Village. Red Book: 2009 report of the committee on infectious diseases. 2009. solium segments and release viable eggs with subsequent cysticercosis (disease secondary to cysticercus encystment of larvae of T. Albendazole may be preferred over praziquantel. is widely recommended. 2010. eds. ed. WHO Model Formulary for Children 2010 69 . London. Repeated treatment may be necessary to cure intense infections or to eliminate the parasite within a family group or institution. Paediatric Formulary Committee. References: American Academy of Pediatrics. 600 mg Indications: Cestodiasis (tapeworm including Taenia solium. Oral: Child over 4 years 5–10 mg/kg as a single dose. British national formulary for children 2009. accessed 10 February 2010). for example riding a bike or operating machinery.

html. Stockley’s drug interactions. Stuart MC. Thomson Micromedex.treatment and prevention. Bartlett JG. vomiting. a bitter taste (which can promote gagging or vomiting) may be experienced. 70 WHO Model Formulary for Children 2010 . Klasco RK. 2009. rectal bleeding. Australian Medicines Handbook. Swallow whole (unchewed) and take with water during meals. arrhythmia. ed.thomsonhc. Many adverse effects result from Albendazole: increased plasma concentration of active metabolite of albendazole. 2009. 2010. 28th ed. pruritus. Interactions with other medicines (* indicates severe): Adverse effects: Usually mild and transitory with short courses. 46:1–12. Others such as skin reactions. Chloroquine: plasma praziquantel concentration possibly reduced. Drugs for parasitic infection. * Phenytoin: plasma praziquantel concentration reduced.com/pro/biltricide. Adelaide. * Rifampicin: increases metabolism of praziquantel and may reduce its concentration to ineffective levels. eosinophilia and fever are also thought to be responses to antigens released from dying parasites. Tablet may be cut into halves or quarters. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. 8th ed. retinal haemorrhages. Kouimtzi M. New England Journal of Medicine. nausea. WHO model formulary. Bayer Schering Pharma AG. Rare Hypersensitivity reactions including fever. Biltricide Product Information. ed. elk Grove Village. diarrhoea.) 2003 (with updates 2004–2009). 2004. ed. The Medical Letter on Drugs and Therapeutics. 2008. Garcia HH et al. Erythromycin: may increase praziquantel serum concentrations. (PDA reference. 2008. abdominal discomfort (dose dependent). 2010 (http://www.drugs. * Efavirenz: may significantly decrease praziquantel serum concentration. Tapeworms and seizures . malaise. Johns Hopkins Point of Care Information Technology (POC-IT) Abx Guide.6 Anti-infective medicines death of the parasite and are more severe with a high parasite burden. 2004. drowsiness. focal seizures and motor weakness may occur in people with neurocysticercosis (due to an intense inflammatory response to dying larvae in CNS). 2004. eds. eosinophilia (may be due to dead and dying parasites). headache. London. * Phenobarbital: may significantly decrease praziquantel serum concentration. BMJ Group RBS Publishing. New England Journal of Medicine. Greenwood Village. * Dexamethasone: plasma praziquantel concentration reduced. anorexia. London. Notes: If the tablets or parts of the tablets are kept in the mouth. American Academy of Pediatrics. Baxter K. Maguire JH. but do not chew. rash. 2009. Rossi S. accessed 10 February 2010). 350:215–217. Ritonavir: may increase praziquantel serum concentrations.com. Drugdex system. Red Book: 2009 report of the committee on infectious diseases. World Health Organization. * Carbamazepine: may significantly decrease praziquantel serum concentration. reversible rises in hepatic aminotransferases. Australian medicines handbook. Symptoms such as papilloedema. Hill SR. Common Dizziness (dose dependent). accessed 10 February 2010). 350:249–258. ed. Paediatric Formulary Committee. colic. Geneva. British national formulary for children 2009. (http://www. References: American Academy of Pediatrics. * Nevirapine: may significantly decrease praziquantel serum concentration. Pharmaceutical Press.

2008. hairworm (trichostrongyliasis). Klasco RK.thomsonhc. UBM Medica. Dose: Roundworm (ascariasis).com. Oral: Child all ages 10 mg/kg as a single dose with a second dose after 2–4 weeks.88 mg of pyrantel pamoate or embonate salt. Oral: Child all ages 10 mg/kg as a single dose. Sydney. Hookworm (Ancylostoma and Necator americanus) infections. Trichinosis. rash and elevated liver enzymes. ed.6. 1 mg of pyrantel base is equivalent to 2.1 Anthelminthics Pyrantel ATC code: P02CC01 Oral liquid: 50 mg (as embonate)/ml Tablet (chewable): 250 mg (as embonate) Special Notes: Also referred to as pyrantel embonate (eUR). insomnia. dose forms expressed as salt. References: American Academy of Pediatrics. 2009. pyrantel pamoate (US). pinworm. Hepatic impairment: Reduce dose in hepatic impairment. 28th ed. headache. 10 mg/kg daily for 4 days. Pinworm or threadworm (enterobiasis). (http://www. Primaquine: may decrease the effect and levels of pyrantel. Hill SR. Stuart MC. Greenwood Village. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concomitant use. drowsiness. in severe infections. World Health Organization.aspx. 2010. accessed 10 February 2010).au/Search/Search. Notes: Doses are expressed as base. Oral: Child all ages 10 mg/kg daily for 5 days.mimsonline. Kouimtzi M. elk Grove Village. Oral: Child all ages 10 mg/kg as a single dose. All family members should be treated. hookworm. threadworm and trichinosis. American Academy of Pediatrics. Adverse effects: Rare Mild gastrointestinal disturbances. 2009 (http://www. Thomson Micromedex. accessed 10 February 2010). eds. WHO model formulary. hairworm. Red Book: 2009 report of the committee on infectious diseases. Indications: Treatment of intestinal nematode infections such as roundworm. Drugdex system. Geneva. Precautions: Liver disease (reduce dose). WHO Model Formulary for Children 2010 71 . Renal impairment: Dose reduction not necessary.com. dizziness. MIMS Online.

Brugia malayi. Lymphatic filariasis Lymphatic filariasis is caused by infection with Wuchereria bancrofti (bancroftian filariasis). take with fatty food.6 Anti-infective medicines 6. Onchocerciasis Onchocerciasis (filariasis or river blindness) is caused by infection with the filarial nematode. Oral: Child over 5 years and over 15 kg 200 micrograms/kg once daily for 2 days. and may need to be repeated at monthly intervals or a longer course given.1.2 Loiasis Antifilarials Loiasis is an infection with the filarial nematode Loa loa. bancrofti infection. and is transmitted by the biting tabanid fly Chrysops. often a limb. Treatment is not always successful. Clinically it appears as an itchy papular rash progressing to skin thickening with loss of elasticity and subcutaneous nodules. 6 mg filariasis and strongyloidiasis. Precautions: Loiasis coinfection: may develop life-threatening encephalopathy. daily dosing may be required and expert advice should be sought. lymphatic Onchocerciasis and lymphatic filariasis. Onchocerca volvulus. Oral: Child over 5 years and over 15 kg 150 micrograms/kg as a single dose once a year or as necessary. The vector is the black fly which breeds near fast flowing rivers. Hyper-reactive onchodermatitis: more likely to have serious adverse reactions especially oedema. Uncomplicated disease. Most infections remain asymptomatic. or B. Immunocompromised patients. Strongyloidiasis. It is characterized by early fevers and lymphangitis. then progressive lymphatic obstruction of the affected area. In complicated or disseminated infection. Cutaneous larva migrans. Oral: Child over 5 years and over 15 kg an extended course of 200 micrograms/kg once daily on days 1. The eyes are often also involved. especially in immunosuppressed patients. Occult filariasis (tropical pulmonary eosinophilia) is a clinical variant of W. 15 and 16. Strongyloidiasis. transient worsening of onchodermatitis. timori (brugian filariasis). 2. Oral: Child over 5 years and over 15 kg 200 micrograms/kg daily for 1–2 days. complicated or disseminated infection. Dose: Indications: Suppressive treatment of onchocerciasis (also known as river blindness). 72 WHO Model Formulary for Children 2010 . Ivermectin ATC code: P02CF01 Tablet (scored): 3 mg. although the classical migration of the adult worm may be seen across the eye. Contraindications: Pregnancy (delay treatment until after delivery).

Interactions with other medicines (* indicates severe): Alcohol: may increase bioavailability of ivermectin. ONCHOCeRCIASIS Mazzotti reaction (see below). rash. lymphadenitis. Orange juice modestly reduces ivermectin absorption. other severe acute disease: delay diethylcarbamazine treatment until after recovery. Ghana). Australian Medicines Handbook.1 Renal impairment: Dose reduction not necessary. eds. Hepatic impairment: Dose reduction not necessary. fever. raised liver enzymes (ALT and AST). dizziness.au/ip/. 2008. Rossi S. risk of precipitating meningoencephalitis with heavy Loa loa microfilaraemia. 34th ed. Therapeutic Guidelines Limited. WHO Technical Report Series. tremor.5 to 8). pH 7. 950 (http://www.g. eosinophilia. weakness. see below). Sweetman SC.who. anaemia.6. 2009. accessed 10 February 2010). 8th ed. Kemp CA.tg. 2008. eTG complete. References: Baxter K. cough. Alkaline urine (e. rash. so you may need further treatment. 2008. October 2007 (including the model list of essential medicines for children). WHO expert committee on the selection and use of essential medicines. ed. Mcevoy GK. Onchocerciasis This treatment does not kill the adult worm. Geneva. ed. ONCHOCeRCIASIS Headache. toxic epidermal necrolysis. lymphadenopathy. nausea and vomiting. McDowell JM. tremor. Kouimtzi M.int/medicines/publications/essentialmeds_committeereports/TRS_950. abdominal pain. 2009 (http://etg.g. Stockley’s drug interactions. Diethylcarbamazine ATC code: P02CB02 Tablet: 50 mg. Adelaide. tachycardia. ed. itch. 13th ed. Stuart MC. nausea. Drug of choice for strongyloidiasis. 2009. 100 mg (dihydrogen citrate) Indications: Systemic lymphatic filariasis and occult filariasis. rash. Paediatric pharmacopoeia. sore throat. Anthelminthics Adverse effects: In onchocerciasis. cardiac disorders. WHO model formulary. Rare Postural hypotension. vomiting. STRONGyLOIDIASIS Diarrhoea. skin microfilariae levels are low for up to 9 months (ivermectin does not kill the adult worm). loiasis (Loa loa). Martindale: the complete drug reference. increased haemoglobin. Pharmaceutical Press. decreased leukocyte count. clinical significance of this is unknown but a dose reduction may be necessary. somnolence. adverse effects are more frequent and more severe due to allergic or inflammatory responses to death of the parasite (Mazzotti reaction. in certain regions (e. Uncommon Pruritus. Stevens-Johnson syndrome. Notes: PATIeNT ADVICe Absorption of ivermectin is enhanced when dosage is taken following ingestion of a fatty meal. After a single dose to treat onchocerciasis. vertigo. resulting from death of microfilariae. Bethesda. the diet is predominantly vegetarian. myalgia. WHO Model Formulary for Children 2010 73 . Australian medicines handbook. conjunctivitis. Contraindications: Pregnancy (delay treatment until after delivery). Melbourne.org. Common Urticaria. oedema. Hill SR. mild ocular irritation. Melbourne. AHFS drug information. ed. 2002. constipation. American Society of Health-System Pharmacists. which promotes alkaline urine. The selection and use of essential medicines: report of the WHO expert committee. World Health Organization. Strongyloidiasis you will need to have your stools checked to see if the treatment was effective. Pharmaceutical Press. STRONGyLOIDIASIS Fatigue. London.pdf ). arthralgia. MAZZOTTI ReACTION Occurs within 3 days of treatment. headache. diarrhoea. Precautions: Renal impairment. London. leukopenia. Royal Children’s Hospital. 2005.

drowsiness. induced by disintegrating microfilariae). headache. clinical importance of this is unknown. plasma half-life prolonged and urinary excretion IMMUNOLOGICAL ReACTIONS Usually occur within a few hours of the first dose. Loiasis (Loa Loa). Renal impairment: Moderate to severe: reduce dose. Uncommon or rare Headache. Dose reductions are indicated in patients with renal insufficiency. Oral: Adult and Child over 10 years 3–6 mg/kg in divided doses over 24 hours. once a year. including fever. Oral: Adult and Child over 10 years 1 mg/kg as a single dose on first day. under 10 years half the adult dose. Immunological reactions (see below). under 10 years half the adult dose. since many countries have developed specific treatment regimens. Lymphatic filariasis (bancroftian).g. Oral: Adult and Child over 10 years 1 mg/kg as a single dose on first day. transient lymphangitis and exacerbation of lymphoedema. nodules (palpable subcutaneously and along spermatic cord. increased gradually over 3 days to 6 mg/kg daily. anorexia.g. sodium bicarbonate): decreased loss of diethylcarbamazine. under 10 years half the adult dose. NOTe Corticosteroid and antihistamine cover should be considered for the first 2–3 days of therapy. Adverse effects: Usually mild and transitory with short courses.6 Anti-infective medicines Dose: Lymphatic filariasis (bancroftian). joint pain. formed by recently killed worms). asthma in asthmatics (similar to Mazzotti reaction. 6 times at weekly or monthly intervals. Lymphatic filariasis (brugian). dizziness. vomiting. for 12 days. transient haematuria. subsiding by the fifth day of treatment. Filariasis for community eradication programmes. Many adverse effects result from death of the parasite and are more severe and more common with a high parasite burden. Interactions with other medicines (* indicates severe): Urinary acidifiers: increased loss of diethylcarbamazine. under 10 years half the adult dose. Oral: Child all ages 6 mg/kg once annually. nausea and vomiting. increased gradually over 3 days to 3–6 mg/kg daily. for 6–12 days. Mass treatment control programmes. Lymphatic filariasis (brugian). Hepatic impairment: Dose reduction not necessary. preferably in divided doses after meals. Mass treatment control programmes. malaise. dizziness. clinical importance of this is unknown. considerably reduced. 74 WHO Model Formulary for Children 2010 . Oral: Adult and Child over 10 years 6 mg/kg in divided doses over 24 hours. preferably in divided doses after meals. The above dose regimens are intended only as a guide. Urinary alkalinisers (e. urticaria. Oral: Child all ages 6 mg/kg/day in three divided doses for 12 days. especially those with an alkaline urine (e. pH 8) yet specific dosing guidelines are not available.

ed. 8th ed. The selection and use of essential medicines: report of the WHO expert committee. In such cases treatment must be given under careful in-patient supervision and stopped at the first sign of cerebral involvement (and specialist advice sought). Oral: Child over 4 years 20 mg/kg/dose twice daily for 1 day. Pharmaceutical Press. 34th ed. mansoni. and Gastrodiscoides hominis. cardiac arrhythmias. Diethylcarbamazine should be administered after meals. intercalatum. Martindale: the complete drug reference. The lung flukes are of the genus Paragonimus. and in heavy Loa loa infection there is a small risk of encephalopathy. Schistosomiasis Schistosomiasis. Metagonimus yokogawai.3 Antischistosomals and antitrematode medicines Fluke infections The intestinal flukes include Fasciolopsis buski. is caused by several species of trematode worms (blood flukes). urinary schistosomiasis. Oral: Child over 4 years 20 mg/kg/dose three times daily for 1 day.int/medicines/publications/essentialmeds_committeereports/TRS_950. Or Schistosoma haematobium and S. Pharmaceutical Press. felineus and Fasciola hepatica. 2008.com.1 Praziquantel). for 24 hours. 950 (http://www. Echinostoma spp. The liver flukes include Clonorchis sinensis.1. Praziquantel ATC code: P02BA01 Tablet: 600 mg Indications: Intestinal schistosomiasis. London.6. Urinary schistosomiasis is caused by S. intestinal.who. References: Baxter K. 2005. WHO expert committee on the selection and use of essential medicines. mekongi and S.thomsonhc. October 2007 (including the model list of essential medicines for children). 6. Close medical supervision is necessary particularly in the early phase of treatment.pdf ). Schistosomiasis. Dose: Trematodiasis. Stuart MC. Contraindications: Ocular cysticercosis. Intestinal schistosomiasis is caused principally by Schistosoma mansoni as well as S. Greenwood Village. WHO model formulary. Klasco RK. Thomson Micromedex. London. a waterborne parasitic infection.1. ed. Hill SR. Precautions: SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. accessed 10 February 2010). japonicum. Opisthorchis viverrini. ed. Drugdex system. liver and lung fluke infections. Kouimtzi M. haematobium.1 Anthelminthics Notes: Should not be used first line for onchocerciasis. (http://www. WHO Technical Report Series. for example riding a bike or operating machinery. Heterophyes heterophyes. S. World Health Organization. Geneva. 2008. In heavy infections there may be a febrile reaction. Stockley’s drug interactions. O. 2008. 2010. Sweetman SC. WHO Model Formulary for Children 2010 75 . eds. Neurocysticercosis (see section 6.

* Phenobarbital: may significantly decrease praziquantel serum concentration. nausea. diarrhoea. * Phenytoin: plasma praziquantel concentration reduced. Chloroquine: plasma praziquantel concentration possibly reduced. drowsiness. WHO expert committee on the selection and use of essential medicines. * Nevirapine: may significantly decrease praziquantel serum concentration.int/medicines/publications/essentialmeds_committeereports/TRS_950. accessed 10 February 2010). Australian medicines handbook.tg. Oral: Child over 4 years 20 mg/kg/dose three times daily for 1 day. 2008. Notes: If the tablets or parts of the tablets are kept in the mouth. References: eTG complete. 76 WHO Model Formulary for Children 2010 . Swallow tablets whole (unchewed) and take with water during meals.com. 2010. Tablet may be cut into halves or quarters. Many adverse effects result from Albendazole: increased plasma concentration of active metabolite of albendazole. eds. Renal impairment: Dose reduction not necessary. japonicum and S. accessed 10 February 2010). ed. Interactions with other medicines (* indicates severe): Adverse effects: Usually mild and transitory with short courses. WHO model formulary. * Efavirenz: may significantly decrease praziquantel serum concentration. Oral: Child over 4 years 25 mg/kg/dose three times daily (at 5 hour intervals) for 1 day. Melbourne. mekongi. which are also thought to be responses to antigens released from dying parasites. headache. WHO Technical Report Series. ed. * Carbamazepine: may significantly decrease praziquantel serum concentration. Greenwood Village. arrhythmia. Therapeutic Guidelines Limited. * Dexamethasone: plasma praziquantel concentration reduced. malaise. October 2007 (including the model list of essential medicines for children).org. 2009. Rossi S. death of the parasite and are more severe with a high parasite burden. Kouimtzi M.pdf ). Rare Hypersensitivity reactions including fever. Australian Medicines Handbook. abdominal discomfort (dose-dependent).au/ip/. but do not chew. The selection and use of essential medicines: report of the WHO expert committee. 950 (http://www. 2008. Hill SR. 2009 (http://etg. colic.thomsonhc.who. Common Dizziness (dose-dependent). Adelaide. Stuart MC. rectal bleeding. Hepatic impairment: Consider reducing dose in moderate to severe impairment (increases concentration and half-life). Paragonimus westermani. vomiting. Thomson Micromedex. Oral: Child over 4 years 25 mg/kg dose three times daily for 2 days. (http://www. Klasco RK. eosinophilia and fever. Drugdex system. anorexia. Symptoms may include skin reactions. Geneva. Chlonorchiasis and opisthorchiasis. pruritus.6 Anti-infective medicines S. a bitter taste (which can promote gagging or vomiting) may be experienced. eosinophilia (may be due to dead and dying parasites). Ritonavir: may increase praziquantel serum concentration. * Rifampicin: increases metabolism of praziquantel and may reduce its concentration to ineffective levels. World Health Organization. Erythromycin: may increase praziquantel serum concentration. reversible rises in hepatic aminotransferases.

WHO Technical Report Series. Pharmaceutical Press.pdf ). WHO model formulary. Kouimtzi M. Oral: Child over 4 years 10 mg/kg as a single dose. (http://www. Precautions: Paragonimus infections: treatment in hospital as there may be central nervous system involvement. 2008. for 24 hours. for example riding a bike or operating machinery. Rare Leukopenia. Greenwood Village. Hill SR. fever. 34th ed. Paragonimiasis. Adverse effects: Common Abdominal pain (predominately right upper quadrant). ed. dizziness. ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. Ingestion of barley may reduce anthelminthic effectiveness. Notes: Take with food. Oxamniquine ATC code: P02BA02 Capsule: 250 mg Oral liquid: 50 mg/ml Special Notes: Oxamniquine is listed for use when praziquantel treatment fails. Klasco RK. eds. Drugdex system. Martindale: the complete drug reference. 15th ed. Hepatic impairment: Dose reduction not necessary. Contraindications: Pregnancy: delay treatment until after delivery unless immediate intervention necessary. elsevier. Meyler’s side effects of drugs. 2010. Sweetman SC. October 2007 (including the model list of essential medicines for children).1 Anthelminthics Triclabendazole ATC code: P02BX04 Tablet: 250 mg Indications: Fascioliasis. 2005. ed. The selection and use of essential medicines: report of the WHO expert committee.thomsonhc.6. 2006. Renal impairment: Dose reduction not necessary. accessed 10 February 2010). WHO expert committee on the selection and use of essential medicines. WHO Model Formulary for Children 2010 77 . 2008. 950 (http://www. London. Amsterdam.com. severe fascioliasis: biliary colic. Oral: Child over 4 years 10 mg/kg/dose twice daily for 1 day. epilepsy or a history of seizures. Precautions: SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Stuart MC. chills.who. paragonimiasis. World Health Organization. Thomson Micromedex. Indications: Intestinal schistosomiasis due to Schistosoma mansoni (acute stage and chronic hepatosplenic disease). Geneva. References: Aronson JK. Dose: Fascioliasis. due to obstruction by dying worms. headache.

Rare Changes in creatine kinase. Adverse effects: Common Dizziness. eds.6 Anti-infective medicines Dose: Intestinal schistosomiasis due to S. Intestinal schistosomiasis due to S. Martindale: the complete drug reference. Uncommon Urticaria. ed. 2005. hallucinations. mansoni (west Africa. scattered pulmonary infiltrates (Loeffler syndrome). World Health Organization. 2010. 30 kg and over 15 mg/kg as a single dose. Renal impairment: Dose reduction not necessary. mansoni (egypt and southern Africa). Amsterdam. administration after a meal or late in the daytime is recommended. drowsiness. diarrhoea. Meyler’s side effects of drugs. headache.int/medicines/publications/essentialmeds_committeereports/TRS_950. References: Aronson JK. 950 (http://www.who. excitement. fever. Caribbean islands). Thomson Micromedex. WHO expert committee on the selection and use of essential medicines. intense reddish discoloration of urine. WHO model formulary. elsevier. proteinuria. raised liver enzyme values. eeG abnormalities. October 2007 (including the model list of essential medicines for children). Greenwood Village. vomiting. 34th ed. mansoni (east and central Africa. Hepatic impairment: Dose reduction not necessary. Arabian peninsula). ed. but not by other Schistosoma spp. London. haematuria. epileptiform seizures. South America. 2008. The selection and use of essential medicines: report of the WHO expert committee. Used in the treatment of schistosomiasis caused by S.pdf ). pruritic skin rashes. Notes: To minimize gastrointestinal side effects. mansoni. 2008.com. accessed 10 February 2010). 78 WHO Model Formulary for Children 2010 . Pharmaceutical Press. Sweetman SC. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. WHO Technical Report Series. Intestinal schistosomiasis due to S. Drugdex system. Kouimtzi M. Stuart MC. Klasco RK. eosinophilia. Geneva. ed. (http://www. Oral: Child all ages 30 mg/kg in 2 divided doses. nausea. eCG abnormalities. 2006. 15th ed. Oral: Child under 30 kg 20 mg/kg in 2 divided doses.thomsonhc. myalgia. Oral: Child all ages 60 mg/kg in divided doses over 2–3 days (maximum single dose 20 mg/kg). Hill SR.

severity of illness.6. such as tuberculosis or chronic osteomyelitis. When possible. A policy may allow a range of drugs for general use. renal and hepatic function.g. • The dose of an antibacterial varies according to a number of factors including age. therefore it is important to prescribe a dose appropriate to the condition. Viral upper respiratory tract infections and uncomplicated diarrhoea do not require antibacterial medications. minimizes potential resistance and limits toxic effects to the patient. Courses should not be unduly prolonged because this encourages resistance. In such cases. However.2 Antibacterials 6. • Knowledge of prevalent organisms and their current sensitivity is of great help in choosing an antibacterial before bacteriological confirmation is available. The prescribing of the so-called “standard” dose in serious infections may result in failure of treatment. Life-threatening infections generally require intravenous therapy. ethnic origin and age). in certain infections. when possible. An inadequate dose may also increase the likelihood of antibacterial resistance. samples should be taken for culture and sensitivity testing. painful intramuscular injections should be avoided in children. WHO Model Formulary for Children 2010 79 . an aminoglycoside). Guidelines for the management of specific diseases should be consulted when selecting an antibacterial agent. “Blind” antibacterial prescribing for unexplained fever usually leads to further difficulty in establishing the diagnosis. immune status. and prolonged therapy may also lead to unwanted side-effects and unnecessary expense. those with severe acute malnutrition) when the infecting organism is either unknown or may be one many different species. the concentration of the drug in the plasma may need to be monitored. it is necessary to treat for prolonged periods.g. history of allergy. as well as consideration of various factors relating to the patient (e. However. • The choice of an antibiotic for a particular infection should be as specific as possible. Before starting therapy The following should be considered before starting antimicrobial therapy: • Viral infections should not be treated with antibacterials. hepatic function. Narrowing the spectrum. and permit use of other drugs only on the advice of a microbiologist or physician responsible for the control of infectious diseases. it is equally important to avoid an excessive dose. weight. • Duration of therapy depends on the nature of the infection and the response to treatment. antibacterials that are well absorbed can be given by mouth even for some serious infections. reserving broad-spectrum cover for very unwell patients (e. On the other hand.g.2 Antibacterials Choice of a suitable antibacterial drug The choice of an antibacterial drug is based on the identity of the likely pathogen and its antibacterial sensitivity. renal function and severity of infection. for an antibacterial with a narrow margin between its toxic and therapeutic doses (e. • The route of administration of an antibacterial often depends on the severity of the infection. and to reduce the development of resistant organisms. Antibacterial policy Local policies often limit the availability of antibacterials in order to achieve reasonable economy consistent with adequate antibacterial cover. • When possible.

6 Anti-infective medicines 6. a penicillin should not be withheld unnecessarily for a serious infection. which causes a rash. which can be fatal. About 10–15% of penicillinsensitive patients will be allergic to cefalosporins and other beta-lactams. doubled in severe infections. In these individuals. Individuals with a history of anaphylaxis. dental abscess and other oral infections. Allergic reactions to penicillins occur in 1–10% of exposed individuals. through a mechanism of action directed at the bacterial cell wall. 250 mg (anhydrous)/5 ml Solid oral dosage form: 250 mg. upper respiratory tract infections. Individuals with a history of a minor rash (a non-confluent rash restricted to a small area of the body) or a rash occurring more than 72 hours after penicillin administration are possibly not allergic to penicillin. maintain adequate hydration with high doses (risk of crystalluria). superinfection (including candidiasis). Dose: Infections due to sensitive organisms. rashes more common and risk of crystalluria. erythema.1 Beta-lactam medicines Beta-lactam antibiotics include penicillins. Renal impairment: Mild to moderate: risk of crystalluria with high doses. vomiting. endocarditis prophylaxis. Hypersensitivity The most important adverse effect of penicillins is hypersensitivity. urticaria. doubled in severe infections. cytomegalovirus infection. pneumonia. post-splenectomy prophylaxis. 500 mg (anhydrous) Indications: Urinary tract infections. Amoxicillin ATC code: J01CA04 Powder for oral liquid: 125 mg (anhydrous)/5 ml. otitis media. These share a common structure and are bactericidal. especially during prolonged treatment with broad-spectrum penicillins. Severe: reduce dose. associated disease. These individuals should not receive a penicillin. penicillin-associated jaundice or hepatic dysfunction. nausea. erythematous rashes common in glandular fever. bronchitis. gynaecological infections. Patients who are allergic to one penicillin will be allergic to them all because hypersensitivity is related to the basic penicillin structure. Clostridium difficile- 80 WHO Model Formulary for Children 2010 . over 10 years 250 mg every 8–12 hours. Contraindications: Hypersensitivity to penicillins (see section notes). exfoliative dermatitis. while anaphylactic reactions occur in fewer than 0. Uncommon Fever. Oral: 40 mg/kg daily in three divided doses (maximum 3 g daily). cefalosporin or any other beta-lactam antibiotic. allergy. angioedema. cefalosporins and carbapenems. Lyme disease. and occasionally anaphylaxis. gonorrhoea. Adverse effects: Common Diarrhoea. Precautions: History of allergy (see section notes).05%.2. Oral: Child up to 10 years 125 mg every 8–12 hours. rash. Otitis media. chronic lymphatic leukaemia and possibly HIV infection. renal impairment. urticaria or rash immediately after penicillin administration are at risk of immediate hypersensitivity with subsequent exposure to penicillins. osteomyelitis. anthrax. Hepatic impairment: Dose reduction not necessary.

hepatic impairment. Renal impairment: Risk of crystalluria with high doses (particularly during parenteral therapy). serum sickness-like syndrome. Taketomo CK. Kraus DM. eds. Lexi-Comp. erythematous rashes common in glandular fever. Paediatric Formulary Committee. genitourinary and abdominal infections. renal impairment.5 mg clavulanic acid/5 ml Tablet: 500 mg + 125 mg Indications: Infections due to beta-lactamase producing bacteria (where amoxicillin alone not appropriate) including respiratory tract infections. Hodding JH.g.pdf ). The selection and use of essential medicines: report of the WHO expert committee. 2009. 2009.who. BMJ Group RBS Publishing. bronchospasm. Kouimtzi M. Pediatric dosage handbook. Contraindications: Hypersensitivity to penicillins (see section notes). reduce dose if creatinine clearance less than 30 ml/minute. but common experience in anticoagulant clinics is that INR can be altered by a course of amoxicillin. This dose can be doubled in severe infections. electrolyte disturbances (due to their sodium or potassium content). Allopurinol: increased risk of rash. neurotoxicity (e. British national formulary for children 2009. cellulitis. animal bites. 2008. WHO Technical Report Series. October 2007 (including the model list of essential medicines for children). Contraceptives. cytomegalovirus infection. maintain adequate hydration with high doses (risk of crystalluria).25 mg clavulanic acid/5 ml. tooth discoloration. otitis media. 2008. Dose: Infections due to susceptible beta-lactamase producing organisms. Amoxicillin + Clavulanic acid ATC code: J01CR02 Oral liquid: 125 mg amoxicillin + 31. over 12 years 250 mg every 8 hours. Hudson. toxic epidermal necrolysis. London. seizures with high doses or impaired renal function). World Health Organization. interstitial nephritis. Haemophilus influenzae. severe dental infections. Interactions with other medicines (* indicates severe): References: Hill SR. 1–6 years 125 mg every 8 hours. Stuart MC. WHO model formulary. blood dyscrasias (e. Warfarin: studies have failed to demonstrate an interaction. haemolytic anaemia. chronic lymphatic leukaemia and possibly HIV infection. nephropathy (with parenteral use). oral: contraceptive effect of estrogens possibly reduced (risk probably small). coagulation disorders. thrombocytopenia).6. Geneva. osteomyelitis and surgical prophylaxis. 950 (http://www.2 Antibacterials Rare Anaphylaxis. Precautions: History of allergy (see section notes). Stevens-Johnson syndrome. neutropenia (related to dose and duration of treatment). WHO expert committee on the selection and use of essential medicines. Oral (expressed in terms of amoxicillin): Child under 1 year 20 mg/kg daily in three divided doses. history of penicillin or amoxicillin with clavulanic acid-associated jaundice or hepatic dysfunction.g. WHO Model Formulary for Children 2010 81 . Methotrexate: reduced excretion of methotrexate (increased risk of toxicity).int/medicines/publications/essentialmeds_committeereports/TRS_950. 6–12 years 250 mg every 8 hours. 250 mg amoxicillin + 62. 16th ed.

interstitial nephritis. Lexi-Comp. toxic epidermal necrolysis. 2008. Uncommon Dizziness. cholestatic hepatitis (generally less severe than flucloxacillin hepatitis and is usually reversible. Drugdex system. 1 g (as sodium salt) in vial Not to be given by intrathecal injection as can cause encephalopathy which may be fatal. 2008. References: Hill SR.6 Anti-infective medicines Hepatic impairment: Monitor liver function in liver disease. renal impairment. coagulation disorders.int/medicines/publications/essentialmeds_committeereports/TRS_950. Pediatric dosage handbook. bronchospasm. World Health Organization. blood dyscrasias (e. cholecystitis. The selection and use of essential medicines: report of the WHO expert committee. jaundice. 2009. Symptoms may appear during. October 2007 (including the model list of essential medicines for children). nephropathy (with parenteral use). Contraceptives. more common in patients over the age of 65 years and in males. 16th ed. electrolyte disturbances (due to their sodium or potassium content). Warfarin: studies have failed to demonstrate an interaction. urticaria. serum sickness-like syndrome. Clostridium difficile-associated disease. Precautions: History of allergy (see section notes). oral: contraceptive effect of estrogens possibly reduced (risk probably small). BMJ Group RBS Publishing. duration of treatment should not usually exceed 14 days. exfoliative dermatitis. Greenwood Village. WHO Technical Report Series. erythema. The risk increases with age (> 55 years). vomiting. British national formulary for children 2009. endocarditis. Kraus DM. tooth discoloration. Indications: Mastoiditis. headache. meningitis. ed. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). treatment and may persist for 5–6 weeks. Geneva. but common experience in anticoagulant clinics is that INR can be altered by a course of amoxicillin. neurotoxicity (e. transient increases in liver enzymes and bilirubin. WHO model formulary. 2010. seizures with high doses or impaired renal function). haemolytic anaemia. neutropenia (related to dose and duration of treatment).g.com. nausea.pdf ). Interactions with other medicines (* indicates severe): Allopurinol: increased risk of rash. peritonitis. Notes: The risk of acute liver toxicity has been estimated to be about six times higher with amoxicillin + clavulanic acid than amoxicillin. Hodding JH. WHO expert committee on the selection and use of essential medicines. 2009. erythematous rashes common in glandular fever. Ampicillin ATC code: J01CA01 Powder for injection: 500 mg. Hudson. thrombocytopenia). angioedema. (http://www. rash. eds. Paediatric Formulary Committee. Taketomo CK. Kouimtzi M. septicaemia. gynaecological infections. acute generalised exanthematous pustulosis. Cholestatic jaundice reported either during or shortly after treatment. male sex and length of treatment). Rare Anaphylaxis. accessed 10 February 2010). London. 82 WHO Model Formulary for Children 2010 . Stevens-Johnson syndrome. allergy. acute or chronic lymphocytic leukaemia and cytomegalovirus infection.g. hepatitis. Klasco RK. or several weeks after.who. 950 (http://www. superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins. Stuart MC. Thomson Micromedex. Adverse effects: Common Diarrhoea. Contraindications: Hypersensitivity to penicillins (see section notes). fever.thomsonhc. osteomyelitis.

Warfarin: studies have failed to demonstrate an interaction. 2009. Uncommon Fever. 2010. blood dyscrasias (e. Neonate 7–21 days 50–100 mg/kg every 8 hours. including convulsions. but common experience in anticoagulant clinics is that INR can be altered by a course of amoxicillin. Kraus DM. WHO expert committee on the selection and use of essential medicines.int/medicines/publications/essentialmeds_committeereports/TRS_950. urticaria. neutropenia (related to dose and duration of treatment). pain and inflammation at injection site. Pediatric dosage handbook.com. Hodding JH. Avoid rapid IV administration of large doses as it may result in seizures. vomiting. Lexi-Comp. Australian medicines handbook. Aminoglycosides: separate in terms of IV administration by 1 hour. due to inactivation of the aminoglycoside by the penicillin. Taketomo CK. neurotoxicity (e. Renal impairment: Severe: reduce dose or frequency. nausea. BMJ Group RBS Publishing. October 2007 (including the model list of essential medicines for children). Australian Medicines Handbook. convulsions with high doses or impaired renal function). Interactions with other medicines (* indicates severe): Allopurinol: increased risk of rash. rash. interstitial nephritis. ed. WHO model formulary. serum sickness-like syndrome. exfoliative dermatitis. bronchospasm. Hepatic impairment: Dose reduction not necessary. Clostridium difficileassociated disease. haemolytic anaemia. WHO Model Formulary for Children 2010 83 . Adverse effects: Common Diarrhoea. toxic epidermal necrolysis. 2009.2 Dose: Antibacterials Severe infections due to sensitive organisms (e. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). Stevens-Johnson syndrome. 2008. 2008. IV or IM: Neonate under 7 days 50–100 mg/kg every 12 hours. World Health Organization. Thomson Micromedex. Neonate 21– 28 days 50–100 mg/kg every 6 hours. ADMINISTRATION IV administration is preferred. superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins.thomsonhc. 2009. Klasco RK. Notes: IV penicillins are physically incompatible with many substances (including aminoglycosides). preferably. British national formulary for children 2009. Rare Anaphylaxis. angioedema. WHO Technical Report Series. Adelaide. eds. London. allergy. If IM injection is required. Geneva. coagulation disorders. IV: give over 30 minutes when using doses greater than 50 mg/kg to avoid CNS toxicity.g.6.g. Stuart MC. oral: contraceptive effect of estrogens possibly reduced (risk probably small).who. Rossi S. erythema. Paediatric Formulary Committee. (http://www. Kouimtzi M. ed. give separately. Hudson. The selection and use of essential medicines: report of the WHO expert committee. lidocaine can be used to reconstitute the injection to reduce local pain. References: Hill SR. Contraceptives. nephropathy (with parenteral use).g. Child 1 month–12 years 50 mg/kg every 4–6 hours (maximum 2 g every 4 hours). electrolyte disturbances (due to their sodium or potassium content).pdf ). Drugdex system. meningitis). Greenwood Village. 16th ed. thrombocytopenia). accessed 10 February 2010). 950 (http://www.

yaws. renal failure. Indications: Streptococcal pharyngitis. Adverse effects: Common Diarrhoea. e.4 million IU) in 5 ml vial Do not give by intravenous injection. toxic epidermal necrolysis. serum sickness-like syndrome. 84 WHO Model Formulary for Children 2010 . exfoliative dermatitis. intravascular injection. can be dangerous in cardiovascular syphilis or where there is serious risk of local damage. hypotension and flare-up of lesions (due to release of pyrogens from the organisms and endotoxins) during treatment for syphilis and other spirochaete infections. symptoms can be alleviated by acetylsalicylic acid (aspirin) or prednisolone. Jarisch-Herxheimer reaction. rheumatic fever prophylaxis. pain and inflammation at injection site. joint pain. Streptococcal pharyngitis. Deep IM: Child under 30 kg 450 mg (600 000 IU) once every 3–4 weeks. primary prophylaxis of rheumatic fever. electrolyte disturbances (due to their sodium or potassium content). superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins. blood dyscrasias (e. Lasts for 12–24 hours. Hepatic impairment: Dose reduction not necessary. Secondary prophylaxis of rheumatic fever. 30 kg and over 900 mg (1.2 million IU) in 5 ml vial. Renal impairment: Severe: neurotoxicity. Contraindications: Penicillin hypersensitivity (see section notes). pinta and bejel. neurotoxicity (e.2 million IU) once every 3–4 weeks. 1. diphtheria. interstitial nephritis. chills. vomiting. Deep IM: Child up to 2 years 37. neurosyphilis. Rare Anaphylaxis.8 g benzathine benzylpenicillin (= 2. angioedema. nausea.5 mg/kg (50 000 IU/kg) as a single dose. neutropenia (related to dose and duration of treatment).g. 30 kg and over 900 mg (1. high doses may cause convulsions. coagulation disorders. Stevens-Johnson syndrome. seizures with high doses or impaired renal function). Clostridium difficileassociated disease. Dose: Do not give by intravenous injection. rash. bronchospasm. headache. erythema. Precautions: History of allergy (see section notes). Deep IM: Child 450 mg (600 000 IU) as a single dose.g.2 million IU) as a single dose. urticaria. This consists of fever. Deep IM: Child under 30 kg 450–675 mg (600 000–900 000 IU) as a single dose.6 Anti-infective medicines Benzathine benzylpenicillin ATC code: J01Ce08 Powder for injection: 900 mg benzathine benzylpenicillin (= 1. pinta. bejel). allergy. tooth discoloration. syphilis and other treponemal infections (yaws. thrombocytopenia).g. haemolytic anaemia. Congenital syphilis (where no evidence of CSF involvement). optic atrophy. nephropathy (with parenteral use). Uncommon Fever.

accessed 10 February 2010). Contraindications: Penicillin hypersensitivity (see section notes). Geneva. eds. Klasco RK. meningococcal disease. 2009. actinomycosis. fear of death and hallucinations (usually resolving in 15–30 minutes. London. 950 (http://www. IV or IM: Neonate under 1 week 50 mg/kg daily in two divided doses. IV or IM: Premature infant and Neonate under 1 week 100 mg/kg daily in two divided doses. 2008. agitation. Adelaide.2 million IU. 2009. Australian medicines handbook. otitis media. ed. throat infections. leptospirosis. necrotizing fasciitis. osteomyelitis. Greenwood Village.thomsonhc. brain abscess. Interactions with other medicines (* indicates severe): Contraceptives. Benzylpenicillin ATC code: J01Ce01 Powder for injection: 600 mg (= 1 million IU). gas gangrene. low concentrations of benzylpenicillin are appropriate and adequate. anthrax. Child 1 month–12 years 100 mg/kg daily in four divided doses. ed. BMJ Group RBS Publishing. Australian Medicines Handbook. Precautions: History of allergy (see section notes). 2008. 3 g (= 5 million IU) (sodium or potassium salt) in vial Special Notes: Also known as penicillin G. Dose: Mild to moderate infections due to sensitive organisms. Give doses > 900 mg (1.pdf ). Kouimtzi M. (http://www. relapsing fever.int/medicines/publications/essentialmeds_committeereports/TRS_950. part syringe dosing is not accurate but is used. avoid intrathecal route (see section notes). Benzathine benzylpenicillin 900 mg = 720 mg benzylpenicillin = 1. Notes: Give by deep IM injection only. neurosyphilis. necrotizing enterocolitis. Child 1 month–2 years 180–300 mg/kg daily in 4–6 divided doses. References: Hill SR. WHO Model Formulary for Children 2010 85 . Neonate 1–4 weeks 150 mg/kg daily in three divided doses.2 Antibacterials ACCIDeNTAL INTRAVASCULAR ADMINISTRATION May result in severe neurovascular damage. renal failure. British national formulary for children 2009. Neonate 1–4 weeks 75 mg/kg daily in three divided doses. but rarely lasting for up to 24 hours) may also occur. In adults duration of effect of 900 mg (1.2 million IU) dose is 2–4 weeks. Meningococcal disease. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). It may require that the dose to be divided into two sites if there is reduced muscle bulk. heart failure. The selection and use of essential medicines: report of the WHO expert committee. including anxiety. Drugdex system. WHO model formulary.com.who. Thomson Micromedex. Higher doses are used in severe infections (see also below). CNS effects.2 million IU) as two injections at separate sites.6. use when prolonged. Rossi S. World Health Organization. oral: contraceptive effect of estrogens possibly reduced (risk probably small). WHO Technical Report Series. Syringes are not graduated. Paediatric Formulary Committee. WHO expert committee on the selection and use of essential medicines. cellulitis. Indications: Pneumonia. Stuart MC. October 2007 (including the model list of essential medicines for children). 2010. Lyme disease. Absorbed slowly into circulation and hydrolysed to benzylpenicillin. streptococcal endocarditis.

optic atrophy. Stevens-Johnson syndrome. London. angioedema. 2009.who. vomiting. allergy. WHO model formulary. 2008. World Health Organization. 10 years and over 1. Uncommon Fever.2 g. References: Hill SR. Interactions with other medicines (* indicates severe): Contraceptives. blood dyscrasias (e. superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins. headache. WHO Technical Report Series. thrombocytopenia). bronchospasm. Greenwood Village. seizures with high doses or impaired renal function).4 mmol (78 mg) sodium per 1.g. pain and inflammation at injection site. Jarisch-Herxheimer reaction. Australian Medicines Handbook. Klasco RK. nephropathy (with parenteral use). Adelaide. IV or IM: Infant under 1 year 300 mg.int/medicines/publications/essentialmeds_committeereports/TRS_950. Renal impairment: Severe: maximum 6 g daily. (http://www. Rossi S.44 g) daily in 4–6 divided doses for 10–14 days. Drugdex system. Thomson Micromedex. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). Australian medicines handbook. chills.2 g by intravenous route only.g. neutropenia (related to dose and duration of treatment). hypotension and flare-up of lesions (due to release of pyrogens from the organisms and endotoxins) during treatment for syphilis and other spirochaete infections. neurotoxicity (high doses may cause convulsions). exfoliative dermatitis. Contains 3.thomsonhc. Congenital syphilis. nausea. 2008. October 2007 (including the model list of essential medicines for children). neurotoxicity (e.g. Lasts for 12–24 hours. joint pains. coagulation disorders. Notes: Intravenous route preferred for neonates and infants. ed. toxic epidermal necrolysis. BMJ Group RBS Publishing. The selection and use of essential medicines: report of the WHO expert committee.com.6 Anti-infective medicines Suspected meningococcal disease (before transfer to hospital). haemolytic anaemia. British national formulary for children 2009. 950 (http://www. urticaria. IV or IM: Child 2 years and over 120–180 mg/kg (to a maximum of 1.pdf ). Rare Anaphylaxis. tooth discoloration. interstitial nephritis. can be dangerous in cardiovascular syphilis or where there is serious risk of local damage. 2009. serum sickness-like syndrome. Hepatic impairment: Dose reduction not necessary. give separately. then 30 mg/kg three times daily for 3 days. Longer administration time is particularly important when using doses of ≥ 50 mg/kg to avoid CNS toxicity. accessed 10 February 2010). oral: contraceptive effect of estrogens possibly reduced (risk probably small). Paediatric Formulary Committee. 2010.2 g injection. Avoid rapid IV administration of large doses as it may result in convulsions. e. Stuart MC. Clostridium difficileassociated disease. This consists of fever. ed. IV: Infant and Child up to 2 years 30 mg/kg twice daily for the first 7 days of life. 86 WHO Model Formulary for Children 2010 . IV penicillins are physically incompatible with many substances (including aminoglycosides). eds. doses over 1. Adverse effects: Common Diarrhoea. Geneva. Kouimtzi M. electrolyte disturbances (due to their sodium or potassium content). rash. Child 1–9 years 600 mg. erythema. WHO expert committee on the selection and use of essential medicines. symptoms can be alleviated by acetylsalicylic acid (aspirin) or prednisolone.

however this is not recommended if > 500 mg per dose is required. WHO Model Formulary for Children 2010 87 . References: Hill SR. live: a decreased immunological response to the typhoid vaccine. arthritis. skin and soft tissue infections. Klasco RK. toxic epidermal necrolysis. Kouimtzi M.thomsonhc.g. World Health Organization.5 mg/kg/dose every 6 hours. 2010. Rossi S. ed. 2009. thrombocytopenia). 50 mg/ml Solid oral dosage form: 250 mg Special Notes: Also referred to as cephalexin. oral and vaginal candidiasis. Paediatric Formulary Committee.25–12. eosinophilia. Up to maximum of 25 mg/kg/dose every associated disease.int/medicines/publications/essentialmeds_committeereports/TRS_950. eds. Uncommon Vomiting. serum sickness-like syndrome. WHO expert committee on the selection and use of essential medicines. Renal impairment: Reduce dose in moderate impairment.pdf ). bleeding.5% of penicillin sensitive patients. Dose: Oral: 6 hours may be used in severe infections. headache). cholestatic hepatitis. The same daily dose may be given twice daily for uncomplicated urinary tract infections. Rare Anaphylactic shock. Stuart MC. bronchial obstruction.5–6.com. London. diarrhoea. low vitamin K stores (chronic disease and malnutrition) as increased risk of bleeding. ed. mild cellulitis. vomiting. 2008.2 Antibacterials Cefalexin ATC code: J01DB01 Powder for reconstitution with water: 25 mg/ml. dizziness. Australian Medicines Handbook. Precautions: Renal impairment. administration with other drugs which also have this effect may increase risk of nephrotoxicity. urinary tract infections. allergy to cefalosporins. a severe or immediate allergic reaction (including urticaria.who. Greenwood Village. electrolyte disturbances. blood dyscrasias (e. 950 (http://www. WHO model formulary.6. streptococcal pharyngitis and tonsillitis. British national formulary for children 2009. accessed 10 February 2010). neutropenia (related to dose and treatment duration). Stevens-Johnson syndrome. Indications: Infection due to sensitive organisms. Australian medicines handbook. Notes: Hypersensitivity to cefalosporins occurs in about 0. (http://www. headache. renal impairment. Thomson Micromedex. 2008. Contraindications: Cefalosporin hypersensitivity. Clostridium difficile- Infant and Child 6. angioedema. Drugdex system. Interactions with other medicines (* indicates severe): Cefalosporins can cause renal impairment. BMJ Group RBS Publishing. urticaria. October 2007 (including the model list of essential medicines for children). anaphylaxis or interstitial nephritis) to a penicillin. WHO Technical Report Series. The selection and use of essential medicines: report of the WHO expert committee. Metformin: increase in metformin plasma levels and may increase risk of metformin side-effects (nausea. rash. asthenia. Geneva. Hepatic impairment: Dose reduction not necessary. impaired vitamin K synthesis. haemolytic anaemia. nausea. neurotoxicity (including seizures). drug fever. Typhoid vaccine. superinfection. 2009. Adelaide. Adverse effects: Common Diarrhoea. interstitial nephritis.

Contraindications: Cefalosporin hypersensitivity (see section 6. 2009. Hepatic impairment: Dose reduction not necessary. The selection and use of essential medicines: report of the WHO expert committee. Melbourne. Australian medicines handbook. Pharmacy Department. arthritis. eosinophilia. Royal Children’s Hospital. 88 WHO Model Formulary for Children 2010 . Precautions: Sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction. Further doses may be given every 6–8 hours postoperatively for 24 hours if necessary.int/medicines/publications/essentialmeds_committeereports/TRS_950. nausea. Lexi-Comp. administration with other drugs which also have this effect may increase risk of nephrotoxicity. eosinophilia.1).com. electrolyte disturbances. * Warfarin: possibly enhanced anticoagulant effect. WHO model formulary. 16th ed. leukopenia. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. avoid mixing with other drugs. ed. McDowell JM. Renal impairment: Moderate: reduce dose. 2008. anaphylaxis. headache. renal impairment including interstitial nephritis. Kraus DM. 3rd ed. Kemp CA. live: a decreased immunological response to the typhoid vaccine. Hudson. Stuart MC. Intramuscular administration may be painful and should be avoided where possible. 2008. 2010. urticaria. ed. Kouimtzi M. Stevens-Johnson syndrome. Dose: Surgical prophylaxis. thrombocytopenia. If IM injection is required/necessary cefazolin can be reconstituted with lidocaine 0. superinfection. Thomson Micromedex. Adelaide. WHO expert committee on the selection and use of essential medicines. Pediatric dosage handbook. oral and vaginal candidiasis.5%. Melbourne. thrombocythaemia and bleeding. October 2007 (including the model list of essential medicines for children). serum sickness-like syndrome. see section 6. false-positive urinary glucose (if tested for reducing substances) and false-positive Coombs’ test. Greenwood Village.who. The information in this monograph only applies to the medicine listed here.pdf ). Adverse effects: Common Diarrhoea. repeated if necessary if surgery lasts over 3 hours. dizziness. Typhoid vaccine.2. or for up to 5 days in continued risk of infection. accessed 10 February 2010). blood dyscrasias including neutropenia. 2002. Hodding JH. Geneva. moderate renal impairment. Rossi S. bronchial obstruction. rash. Deep IM or IV: Infant over 1 month 25 mg/kg (maximum 1 g dose) as a single dose at induction of anaesthesia. seizure disorders. References: Hill SR. Klasco RK.1). Paediatric pharmacopoeia. Clostridium difficile- associated disease. neurotoxicity (including seizures). toxic epidermal necrolysis. pain and inflammation at injection site. haemolytic anaemia. treatment of MSSA in non-anaphylactic penicillin allergy. 2006. This medicine is listed as a representative of its pharmacological class. Interactions with other medicines (* indicates severe): Cefalosporins can cause renal impairment. angioedema. 950 (http://www. Rare Confusion (after large doses in renal failure). The Royal Children’s Hospital. World Health Organization.6 Anti-infective medicines Cefazolin ATC code: J01DB04 Powder for injection: 1 g (as sodium salt) in vial Special Notes: WHO age/weight restriction: > 1 month. drug fever. 13th ed. Uncommon Vomiting. WHO Technical Report Series. Paediatric Injectable Guidelines. Indications: Prophylaxis of infection in surgery. Notes: IV products are physically incompatible with many substances. The Royal Children’s Hospital. Australian Medicines Handbook. (http://www. abnormal liver function tests.2. eds. 2009.thomsonhc. Taketomo CK. Drugdex system.

see also section 6. acidosis or impaired bilirubin binding.1). concomitant treatment with calcium (ceftriaxone should not be used in neonates less than 28 days of age if they are receiving (or are expected to receive) calcium-containing intravenous products. Deep IM or IV: Neonate 7 days or under 50 mg/kg daily (maximum dose 1 g). Precautions: Sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction. Administer by intravenous injection (over at least 3 minutes) or by intravenous infusion (over 30 minutes). Prophylaxis of secondary case of meningococcal meningitis. Intramuscular doses over 1 g divided between more than one site. Special Notes: WHO age/weight restriction: > 41 weeks corrected gestational age. dehydration or concomitant total parenteral nutrition (risk of ceftriaxone precipitation in gallbladder). also monitor plasma concentration if both severe renal impairment and hepatic impairment. In patients > 28 days of age. renal failure.1). hypoalbuminaemia. Indications: Serious infections due to sensitive bacteria.2. septic arthritis. treatment longer than 14 days. prophylaxis of meningococcal meningitis. gonococcal conjunctivitis. false-positive urinary glucose (if tested for reducing substances) and false-positive Coombs’ test. including septicaemia. osteomyelitis. ceftriaxone and calcium-containing products may be administered sequentially. higher dose reserved for severe infections. premature neonates (may displace bilirubin from serum albumin). pneumonia and meningitis. Dose: Infections due to susceptible organisms. Hepatic impairment: Reduce dose and monitor plasma concentration if both hepatic and severe renal impairment. Haemophilus influenzae epiglottitis.2 Antibacterials Ceftriaxone ATC code: J01DD04 Powder for injection: 250 mg. ADMINISTRATION Doses of 50 mg/kg and over should be given by intravenous infusion only.6. Infant and Child under 50 kg 50–100 mg/kg daily (maximum dose 1 g). shigellosis. Contraindications: Cefalosporin hypersensitivity (see section 6. Lyme disease. gonorrhoea. pelvic inflammatory disease. IM: Neonate 50 mg/kg as a single dose (maximum 125 mg). provided the infusion lines are thoroughly flushed between infusions with a compatible fluid). Neonatal gonococcal conjunctivitis. neonates with jaundice. 1 g (as sodium salt) in vial Use with calcium (see Contraindications) and avoid in infants with hyperbilirubinaemia. endocarditis. For IM injection: ceftriaxone may be mixed with lidocaine 1% to 450 mg/ml to reduce pain at intramuscular site. porphyria. surgical prophylaxis. Neonate over 7 days 75 mg/kg daily (maximum dose 1 g). Intravenous infusions for neonates should be over 60 minutes (see also Contraindications). Renal impairment: Severe: maximum 50 mg/kg daily (maximum 2 g daily). severe renal impairment. WHO Model Formulary for Children 2010 89 . invasive salmonellosis.2. 12–18 years 250 mg as a single dose. IM: Child 1 month–12 years 125 mg as a single dose. hepatic impairment if accompanied by renal impairment.

Kouimtzi M. ceftriaxone and calcium-containing products may be administered sequentially. Interactions with other medicines (* indicates severe): Calcium salts. anaemia. 2009. 2009. 2008. leukopenia. neutropenia. single dose ceftriaxone is used to treat neonatal gonococcal conjunctivitis. 2008. 950 (http://www. Ringer’s solution: formation of ceftriaxone-calcium precipitates and is contraindicated. thrombocytosis. nausea. increased bilirubin. Paediatric Injectable Guidelines. Lactated Ringer’s solution: formation of ceftriaxone-calcium precipitates and is contraindicated. Typhoid vaccine. Stuart MC. 16th ed. Kraus DM. However. urticaria. Australian Medicines Handbook. live: decreased immunological response to the typhoid vaccine. haemolytic anaemia. The Royal Children’s Hospital. Australian medicines handbook. References: Hill SR. Contraceptives. (http://www. ed. provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. usually reversible). ed. 2010. sometimes requiring treatment. pain and inflammation at injection site. rash. has been mistaken for gallstones on ultrasound scans and usually resolves after stopping treatment). Ciclosporin: increased risk of ciclosporin toxicity (renal dysfunction. Ceftriaxone should not be used in neonates (< 28 days of age) if they are receiving (or are expected to receive) calcium-containing intravenous products. Taketomo CK. asymptomatic and reversible biliary sludge formation due to calcium-ceftriaxone complex. Greenwood Village. paraesthesia).com. The selection and use of essential medicines: report of the WHO expert committee. electrolyte disturbances. Clostridium difficile- associated disease. StevensJohnson syndrome. abnormalities in liver Uncommon Vomiting. accessed 10 February 2010). Rare Anaphylaxis. oral: contraceptive effect of estrogens possibly reduced (risk probably small). Melbourne. superinfection. blood dyscrasias (including thrombocytopenia. The Royal Children’s Hospital. Pharmacy Department. * Warfarin: possibly enhanced anticoagulant effect.thomsonhc. Geneva. serum sickness-like syndrome.6 Anti-infective medicines function enzymes. eosinophilia. interstitial nephritis. Thomson Micromedex. 2006. October 2007 (including the model list of essential medicines for children). eds. haemolysis). jaundice. 90 WHO Model Formulary for Children 2010 . Klasco RK. bronchial obstruction. WHO model formulary. cholestasis. Hodding JH. arthritis. renal impairment. WHO Technical Report Series. Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in neonates (< 28 days of age). neurotoxicity (including seizures). Rossi S.int/medicines/publications/essentialmeds_committeereports/TRS_950. pancreatitis. WHO expert committee on the selection and use of essential medicines. toxic epidermal necrolysis. nephrolithiasis (formation of calcium-ceftriaxone renal stones. Ceftriaxone must not be administered simultaneously with intravenous calciumcontaining solutions via a y-site in any age group. World Health Organization.who. haemolytic anaemia. Lexi-Comp. In patients > 28 days of age. Drugdex system. prolongation of prothrombin time. Pediatric dosage handbook. headache. 3rd ed. dizziness. Notes: Cefotaxime is preferred to ceftriaxone for Gram-negative septicaemia in neonates as ceftriaxone displaces bilirubin from albumin and may increase risk of bilirubin encephalopathy. oral and vaginal candidiasis. Adelaide. angioedema. Adverse effects: Common Diarrhoea. Hudson. drug fever.pdf ). pseudolithiasis (dose-dependent.

nail damage. Typhoid vaccine. Stevens-Johnson syndrome. jaundice. renal and hepatic impairment. electrolyte disturbances (due to their sodium or potassium content). pneumonia. rash. heart failure. The information in this monograph only applies to the medicine listed here. Cholestatic jaundice may occur up to several weeks after treatment has been stopped. Clostridium difficile-associated disease. nephrotoxicity. 1 g (sodium salt) Powder for injection: 500 mg (as sodium salt) in vial Powder for oral liquid: 125 mg (as sodium salt)/5 ml Special Notes: This medicine is listed as a representative of its pharmacological class. septicaemia. Warfarin: increased risk of bleeding. Oral: Child all ages 12.5–50 mg/kg/dose four times daily. depending upon severity of infection. Notes: Take on an empty stomach 30 minutes before meals as the presence of food in the stomach decreases absorption. superinfection (including candidiasis). live: decreased immunological response to the typhoid vaccine. WHO Model Formulary for Children 2010 91 . Contraceptives. coagulation disorders. hepatotoxicity. staphylococcal endocarditis. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price.6. pain and inflammation at injection site.2 Antibacterials Cloxacillin ATC code: J01CF02 Capsule: 500 mg. Parenteral therapy would be preferred. Precautions: History of allergy (see section notes). Oral cloxacillin is not optimal for the treatment of severe infections. serum sickness-like syndrome. administration for more than 2 weeks and increasing age are risk factors. transient increases in liver enzymes and bilirubin. septic arthritis and osteomyelitis. depending upon severity of infection. Indications: Infections due to beta-lactamase-producing staphylococci including impetigo. Uncommon Fever. agranulocytosis.5–50 mg/kg/dose four times daily. nausea. Rare Contact dermatitis. observe for worsening hepatic function. Contraindications: Hypersensitivity to penicillins (see sections notes). Suggestion: allow 24 hours or more to elapse between the last dose of antibiotic and the administration of oral live typhoid vaccine. Preferable to separate administration by 1 hour. Interactions with other medicines (* indicates severe): Aminoglycosides: concomitant penicillin and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. Renal impairment: Severe: reduce dose. Dose: Infections due to susceptible beta-lactamase-producing staphylococci. toxic epidermal necrolysis. cholestatic hepatitis. IM or IV: Child all ages 12. vomiting. Adverse effects: Common Diarrhoea. immune hypersensitivity reaction. Hepatic impairment: Dose reduction not necessary. cellulitis and other soft-tissue infections. urticaria. interstitial nephritis. pyomyositis. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). oral: contraceptive effect of estrogens possibly reduced (risk probably small). otitis externa. phlebitis or thrombophlebitis at injection sites.

erythema. Notes: Relatively acid-stable. Interactions with other medicines (* indicates severe): Aminoglycosides: concomitant penicillin and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. PATIeNT ADVICe Phenoxymethylpenicillin should be taken at least 30 minutes before or 2 hours after food. interstitial nephritis. so it can be given orally. mouth infections. Pharmaceutical Press.int/medicines/publications/essentialmeds_committeereports/TRS_950. oral: contraceptive effect of estrogens possibly reduced (risk probably small). Greenwood Village. Stuart MC. 2008. cellulitis. Dose: Infections due to sensitive organisms. Chloramphenicol: decreased antibacterial effectiveness. 34th ed. Geneva. ed. Precautions: History of allergy (see section notes). Typhoid vaccine. neutropenia (related to dose and duration of treatment). London. infectious mononucleosis (high incidence of rash). accessed 10 February 2010). 2010. Kouimtzi M. nausea. Adverse effects: Common Diarrhoea. Oral: Child all ages 10–12. associated disease. Oral: Child all ages 10–12. StevensJohnson syndrome.thomsonhc. Klasco RK. 2008. tooth discoloration. superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins. Contraceptives. (http://www. joint pains. vomiting. World Health Organization. serious infections (see section notes). neurotoxicity (e. live: decreased immunological response to the typhoid vaccine. blood dyscrasias (e. Martindale: the complete drug reference. Contraindications: Hypersensitivity to penicillins (see section notes). WHO Technical Report Series. toxic epidermal necrolysis. otitis media. Hepatic impairment: Dosage adjustment may be necessary in patients with impaired liver function when they also have renal failure. thrombocytopenia). October 2007 (including the model list of essential medicines for children). angioedema. secondary prophylaxis of rheumatic fever. Secondary prophylaxis of rheumatic fever.who.pdf ).6 Anti-infective medicines References: Hill SR.g.5 mg/kg/dose (maximum 500 mg) twice daily. Drugdex system. Phenoxymethylpenicillin ATC code: J01Ce02 Powder for oral liquid: 250 mg (as potassium salt)/5 ml Tablet: 250 mg (as potassium salt) Special Notes: Also referred to as penicillin V. coagulation disorders. allergy. 950 (http://www. Renal impairment: Dosage adjustment not necessary. bronchospasm. 2005. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). serum sickness-like syndrome. Sweetman SC. nephropathy (with parenteral use). Thomson Micromedex. seizures with high doses or impaired renal function). haemolytic anaemia. rash.g. Clostridium difficileRare Anaphylaxis. eds. Dose may be doubled in severe infections.5 mg/kg/dose (maximum 500 mg) every 6 hours. The selection and use of essential medicines: report of the WHO expert committee. exfoliative dermatitis. WHO model formulary. urticaria. ed.com. Uncommon Fever. WHO expert committee on the selection and use of essential medicines. Indications: Streptococcal pharyngitis. Preferable to separate administration by 1 hour. post-splenectomy prophylaxis. 92 WHO Model Formulary for Children 2010 .

WHO expert committee on the selection and use of essential medicines. serum sickness-like syndrome. 3 g (= 3 million IU) in vial Accidental intravascular administration may result in severe neurovascular damage. symptoms can be alleviated by acetylsalicylic acid (aspirin) or prednisolone. anthrax. 2008. WHO Model Formulary for Children 2010 93 . Special Notes: Also referred to as penicillin G procaine. angioedema. 950 (http://www. 2008. pneumonia. Never administer intravenously.6. heart failure (some Dose: parenteral penicillins have high sodium content). The selection and use of essential medicines: report of the WHO expert committee. Kemp CA. but rarely lasting for up to 24 hours) may also occur.2 References: Antibacterials Hill SR. toxic epidermal necrolysis. Klasco RK. Adverse effects: Common Diarrhoea. Australian Medicines Handbook. October 2007 (including the model list of essential medicines for children). haemolytic anaemia. Kouimtzi M. superinfection (including candidiasis) especially during prolonged treatment with broad-spectrum penicillins. Contraindications: Hypersensitivity to penicillins (see section notes). Deep IM: Child all ages 50 mg/kg (maximum 1. muscular contractures in neonates and infants. neutropenia (related to dose and duration of treatment)). CNS effects including anxiety. Melbourne. Adelaide.int/medicines/publications/essentialmeds_committeereports/TRS_950. Renal impairment: Severe: neurotoxicity. electrolyte disturbances (due to sodium or potassium content). Jarisch-Herxheimer reaction (fever.pdf ). allergy. neurological reactions). fear of death and hallucinations (usually resolving in 15–30 minutes. coagulation disorders. eds. erythema. Stevens-Johnson syndrome. WHO model formulary. Congenital syphilis. accessed 10 February 2010). intravascular injection. 2010. headache. Royal Children’s Hospital.2 g) daily for 10 days. 2009. interstitial nephritis. can be dangerous in cardiovascular syphilis or where there is serious risk of local damage. Paediatric pharmacopoeia. bronchospasm. bites. Deep IM: Child up to 2 years 50 mg/kg daily for 10 days. blood dyscrasias (e. agitation.com.who. Drugdex system. World Health Organization. Greenwood Village. Clostridium difficileassociated disease. mouth infections. Uncommon Fever. urticaria. Hoigné syndrome (bizzare behaviour.g. Stuart MC. ed. nausea. diphtheria. (http://www. hypotension and flare-up of lesions (due to release of pyrogens from the organisms and endotoxins) during treatment for syphilis and other spirochaete infections. pain and inflammation at injection site (less common with benzylpenicillin). neurotoxicity. infectious mononucleosis (high incidence of rash). cellulitis. e. 13th ed. WHO Technical Report Series. Rare Anaphylaxis. Australian medicines handbook. chills. McDowell JM. optic atrophy). 2002.thomsonhc. vomiting. Procaine benzylpenicillin ATC code: J01Ce09 Powder for injection: 1 g (= 1 million IU). renal failure. Lasts for 12–24 hours. ed. rash. nephropathy (with parenteral use). Indications: Syphilis. Thomson Micromedex. sodium restriction. Geneva. Precautions: History of allergy (see section notes). Pneumonia. exfoliative dermatitis. Hepatic impairment: Dose reduction not necessary. Rossi S.g. high doses may cause convulsions.

Rossi S.com. Lyme disease. 2010. shigellosis. Adelaide. surgical prophylaxis. ed. haemophilus epiglottitis and meningitis. Thomson Micromedex. sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction: see section 6. McDowell JM. 2009. Kouimtzi M. Renal impairment: Reduce dose in moderate renal impairment. Hodding JH. Neonate 21–28 days 25 mg/kg every 6–8 hours. Australian Medicines Handbook. IV or IM: Child 1 month–18 years 500 mg as a single dose. Precautions: Renal impairment. The selection and use of essential medicines: report of the WHO expert committee. including septicaemia. accessed 10 February 2010). Greenwood Village. oral: contraceptive effect of estrogens possibly reduced (risk probably small). invasive salmonellosis. AHFS drug information. WHO Technical Report Series. Child 1 month–18 years 50 mg/kg every 8–12 hours. Gonorrhoea. Procaine benzylpenicillin is not recommended as first-line treatment for neonatal sepsis except in settings with high neonatal mortality.thomsonhc. gonorrhoea. Neonate 7–21 days 25 mg/kg every 8 hours. ed. Methotrexate: reduced excretion of methotrexate (increased risk of toxicity). Melbourne.int/medicines/publications/essentialmeds_committeereports/TRS_950. 2008. when given by trained health workers in cases where hospital care is not achievable. References: Hill SR. Notes: Inject at a slow. surgical prophylaxis. American Society of Health-System Pharmacists. Hudson. If IM injection is required cefotaxime may be reconstituted with lidocaine 0. Lexi-Comp. Taketomo CK.who. Haemophilus influenzae epiglottis. prophylaxis of meningococcal meningitis. Paediatric pharmacopoeia. 2009.pdf ). October 2007 (including the model list of essential medicines for children).1). ADMINISTRATION IV administration is preferred. Mcevoy GK. Bethesda. increase to every 6 hours in severe infection and meningitis (maximum 12 g daily). endocarditis. gonococcal conjunctivitis. impaired vitamin K synthesis. Klasco RK. WHO expert committee on the selection and use of essential medicines. IV or IM: Neonate under 7 days 25 mg/kg every 12 hours.6 Anti-infective medicines Interactions with other medicines (* indicates severe): Contraceptives. septic arthritis. Australian medicines handbook. Pediatric dosage handbook. Kraus DM. 2008. osteomyelitis. (http://www. 950 (http://www. ed. steady rate to avoid blockage of the needle. Hepatic impairment: Dose reduction not necessary. Dose equivalence: 1 g = 1 million units. Contraindications: Cefalosporin hypersensitivity. Kemp CA. eds. Cefotaxime ATC code: J01DA10 Powder for injection: 250 mg per vial Indications: Serious infections due to sensitive bacteria. Geneva. Royal Children’s Hospital. 2009. 2002. World Health Organization. 94 WHO Model Formulary for Children 2010 . Stuart MC. 16th ed. low vitamin K stores (chronic disease and malnutrition) as increased risk of bleeding. WHO model formulary. pelvic inflammatory disease. Inject IV over 3–5 minutes to avoid arrhythmias.2.5% to 300 mg/ml. Neonatal doses may be doubled in severe infection and meningitis. pneumonia and meningitis. 13th ed. Dose: Infections due to sensitive Gram-positive and Gram-negative bacteria. Drugdex system.

aztreonam allergy: person may cross-react to ceftazidime. thrombocytopenia). WHO Technical Report Series. oral and vaginal candidiasis. blood dyscrasias (e.1). Neonate 7–21 days 25–50 mg/kg every 12 hours. 950 (http://www.tg. accessed 10 February 2010). Aminoglycosides: concomitant cefalosporins and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. Greenwood Village. bleeding. Adelaide. false-positive urinary glucose (if tested for reducing substances) and false-positive Coombs’ test. superinfection. Child 1 month–18 years 25-50 mg/kg every 8 hours (maximum 6 g daily). October 2007 (including the model list of essential medicines for children).who. dizziness. McDowell JM. renal impairment. 2009. WHO Model Formulary for Children 2010 95 . Currie A. WHO model formulary. especially those due to Pseudomonas spp. see section 6. Australian medicines handbook. eosinophilia.6. Drugdex system. 13th ed. Melbourne. live: decreased immunological response to the typhoid vaccine. and including those resistant to aminoglycosides. WHO expert committee on the selection and use of essential medicines. eTG complete. toxic epidermal necrolysis. accessed 10 February 2010). (http://www. bronchial obstruction. Interactions with other medicines (* indicates severe): Cefalosporins can cause renal impairment. Therapeutic Guidelines Limited. neutropenia (related to dose and treatment duration). Melbourne. Kemp CA. Royal Children’s Hospital. Deep IM or IV: Neonate under 7 days 25–50 mg/kg every 24 hours. renal impairment. 2010. haemolytic anaemia. interstitial nephritis. References: Ashley C. Precautions: Sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction. Ceftazidime ATC code: J01DD02 Powder for injection: 250 mg or 1 g (as pentahydrate) in vial Indications: Infections due to sensitive bacteria. Use instead of ceftriaxone for Gram-negative septicaemia in neonates. Stevens-Johnson syndrome. Suggestion: allow 24 hours or more to elapse between the last dose of antibiotic and the administration of oral live typhoid vaccine.2.com. eds. drug fever. AHFS drug information. nausea. Contraindications: Cefalosporin hypersensitivity (see section 6.int/medicines/publications/essentialmeds_committeereports/TRS_950. Neonate 21–28 days 25–50 mg/kg every 8 hours.2. urticaria. Hill SR. Preferable to separate administration by one hour.1). Notes: Rapid IV administration of large doses may result in seizures. especially if inappropriately high doses are used in renal impairment. administration with other drugs which also have this effect may increase risk of nephrotoxicity. neurotoxicity (including seizures). Mcevoy GK. Kouimtzi M. Stuart MC.g. 2009 (http://etg. arthritis. The renal drug handbook.thomsonhc. eds. 2009. 2008. pain and inflammation Uncommon Vomiting. serum sickness-like syndrome. 3rd ed. Clostridium difficile- associated disease. World Health Organization.au/ip/. 2009. Radcliffe Publishing. electrolyte disturbances. Rossi S. American Society of Health-System Pharmacists.2 at injection site. 2008. Oxford.pdf ). Australian Medicines Handbook. Rare Life-threatening arrhythmias with rapid IV administration. Thomson Micromedex. Bethesda. porphyria. ed. ed. ed. Dose: Infections due to sensitive Gram-positive and Gram-negative bacteria. anaphylactic shock.org. headache. Klasco RK. rash. Typhoid vaccine. Paediatric pharmacopoeia. The selection and use of essential medicines: report of the WHO expert committee. Geneva. Antibacterials Adverse effects: Common Diarrhoea. 2002. angioedema.

who. Aminoglycosides: concomitant cefalosporins and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. Thomson Micromedex. Adverse effects: Common Diarrhoea. 13th ed. Australian Medicines Handbook. drug fever. 2010. Contraindications: Meningitis. pain and inflammation at injection site. Oxford. Hudson.thomsonhc.pdf ). 2009. References: Aronson JK. 16th ed. nausea. The renal drug handbook. WHO model formulary. StevensJohnson syndrome. Notes: IV products are physically incompatible with many substances. ed. BMJ Group RBS Publishing. elsevier. live: decreased immunological response to the typhoid vaccine. Preferable to separate administration by 1 hour. oral: contraceptive effect of estrogens possibly reduced (risk probably small). London. elevations in liver enzymes.6 Anti-infective medicines Renal impairment: Reduce dose in mild renal impairment. avoid mixing with other drugs. Hansten PD. Melbourne. eds. administration with other drugs which also have this effect may increase risk of nephrotoxicity. Clostridium difficileassociated disease. Drugdex system. 2002. toxic epidermal necrolysis. 2006. oral and vaginal candidiasis. British national formulary for children 2009. WHO expert committee on the selection and use of essential medicines. Ashley C. ed. interstitial nephritis. 2009. 3rd ed. including infections caused by resistant Pseudomonas and Acinetobacter spp. 96 WHO Model Formulary for Children 2010 . a gas relief needle may be needed to relieve positive pressure. The selection and use of essential medicines: report of the WHO expert committee. electrolyte disturbances. leukopenia and drug-induced eosinophilia).com. Hill SR. blood dyscrasias (including thrombocytosis. arthritis. headache. Currie A. Wolters Kluwer Health. neurotoxicity (including seizures). Meyler’s side effects of drugs. McDowell JM. serum sickness-like syndrome. renal impairment. haemolytic anaemia. Radcliffe Publishing. eds. prothrombin time elevations. Imipenem + Cilastatin ATC code: J01DH51 Powder for injection: 250 mg (as monohydrate) + 250 mg (as sodium salt). Royal Children’s Hospital. urticaria.int/medicines/publications/essentialmeds_committeereports/TRS_950. Indications: Severe aerobic and anaerobic Gram-positive and Gram-negative infections in hospital (not indicated for CNS infections). Contraceptives. 2009. Amsterdam. WHO Technical Report Series. St Louis. Hodding JH. October 2007 (including the model list of essential medicines for children). Rare Anaphylaxis. Horn JH. World Health Organization. Pediatric dosage handbook. 2009. accessed 10 February 2010). Interactions with other medicines (* indicates severe): Cefalosporins can cause renal impairment. Hepatic impairment: Dose reduction not necessary. bronchial obstruction. Drug interactions analysis and management. Carbon dioxide is released during reconstitution. superinfection. Kemp CA. Greenwood Village. Kouimtzi M. Typhoid vaccine. 2008. Lexi-Comp. Suggestion: allow 24 hours or more to elapse between the last dose of antibiotic and the administration of oral live typhoid vaccine. 2008. Australian medicines handbook. blood dyscrasias (including thrombocytopenia and haemolytic anemia). Rossi S. Paediatric Formulary Committee. Kraus DM. Paediatric pharmacopoeia. Stuart MC. Taketomo CK. 15th ed. Klasco RK. Uncommon Vomiting. 500 mg (as monohydrate) + 500 mg (as sodium salt) in vial Special Notes: Only listed for the treatment of life-threatening hospital-based infection due to suspected or proven multi-resistant infection. rash. angioedema. Adelaide. 2009. (http://www. 950 (http://www. Geneva. ed. dizziness.

500 mg or less: over 20–30 minutes. oral: contraceptive effect of estrogens possibly reduced (risk probably small). Kemp CA.2. Renal impairment: Reduce dose in mild renal impairment. blood dyscrasias. neutropenia: drug-related nausea and vomiting is more likely to occur. headache.6.g. e. CNS disorders. Dose: Infections due to aerobic and anaerobic Gram-positive and Gram-negative organisms. ADMINISTRATION Follow manufacturers instructions dependent on product. Pediatric dosage handbook. phlebitis. Further dilute to 5 mg/ml with a compatible fluid to give a clear solution. positive Coombs’ test. WHO model formulary. Hodding JH. Caution: complex administration. Uncommon Rash. IV (expressed in terms of imipenem): Neonate under 7 days 20 mg/kg every 12 hours. vomiting. accessed 10 February 2010). 2008. 3 months–18 years and over 40 kg 250–500 mg every 6 hours. Stuart MC. increases in liver function tests and bilirubin. Royal Children’s Hospital. hepatitis. 13th ed. dizziness. Interactions with other medicines (* indicates severe): Contraceptives. Greenwood Village. renal impairment. WHO Model Formulary for Children 2010 97 . McDowell JM. raised urea and creatinine. paraesthesia. psychiatric disturbances. Typhoid vaccine.thomsonhc. Do not administer this suspension without further dilution. 2010. itch. Lexi-Comp. Suggestion: allow 24 hours or more to elapse between the last dose of antibiotic and the administration of oral live typhoid vaccine. somnolence. anaphylaxis. pruritus. Geneva. taste alteration. renal toxicity. Dose may be doubled for less susceptible organisms. see also section 6. Neonate 7–21 days 20 mg/kg every 8 hours. Imipenem is thought to have similar epileptogenic potential to highdose benzylpenicillin). Kraus DM. rash. Drugdex system. 2002. eds. (http://www. local injection site reactions. diarrhoea. Hudson. Check product and instructions carefully. hypotension. ed. 2009. Rare Red discoloration of the urine in children. Clostridium difficile-associated disease. Infant 1–3 months 20 mg/kg every 6 hours. live: decreased immunological response to the typhoid vaccine. urticaria. References: Hill SR.com. World Health Organization. Stevens-Johnson syndrome. tachycardia. convulsions (risk of convulsions is higher in people with pre-existing CNS disorders or renal impairment (especially when excessive doses are used). Notes: Suitability of this preparation for intravenous or intramuscular administration varies dependent on product. such as epilepsy. More than 500 mg: over 40–60 minutes. tremor. 16th ed. Thomson Micromedex. Melbourne. Adverse effects: Common Nausea.9% to form a cloudy suspension. The intramuscular preparation must not be administered intravenously and the infusion preparation must not be administered intramuscularly. Child 3 months–18 years and under 40 kg 15 mg/kg (maximum 500 mg) every 6 hours. fever. Neonate 21–28 days 20 mg/kg every 6 hours. angioedema. Kouimtzi M. Paediatric pharmacopoeia. Valproic acid: decreased valproic acid plasma concentrations and loss of anticonvulsant effect.2 Antibacterials Precautions: Sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction. hospital acquired septicaemia.1). encephalopathy. Taketomo CK. confusion. Hepatic impairment: Dose reduction not necessary. Reconstitute with 10 ml NaCl 0. Klasco RK.

despite its hepatic metabolism. interstitial nephritis. jaundice reported. British national formulary for children 2009. The selection and use of essential medicines: report of the WHO expert committee. Hepatic impairment: Mild or moderate hepatic impairment: no modification of dosage is necessary. dyspnoea. 2005. renal impairment. hearing loss. Dose: Trachoma. hepatotoxicity. Precautions: Prolongation of QT interval. cough. magnesium hydroxide): reduced absorption of azithromycin. 2009. abdominal pain and cramps). Azithromycin ATC code: J01FA10 Capsule: 250 mg.who. Clostridium difficile-associated disease. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide. Australian medicines handbook. rash. BMJ Group RBS Publishing. hepatic impairment. Rossi S. Oral: Child all ages 20 mg/kg (maximum 1 g) as a single dose.pdf ). taste disturbances. headache. American Society of Health-System Pharmacists. diarrhoea.6 Anti-infective medicines Mcevoy GK. acute respiratory distress.2 Other antibacterials This section contains a number of antibiotics from different classes which do not fit within other categories but should be available to treat serious infections. 98 WHO Model Formulary for Children 2010 . psychiatric disturbances. October 2007 (including the model list of essential medicines for children). 500 mg Oral liquid: 40 mg/ml Indications: Trachoma. torsades de pointes. and particularly in those with intensive care facilities. Bethesda. * Ciclosporin: possible inhibition of metabolism of ciclosporin (increased plasma concentration). 6. cholestatic jaundice. pyloric stenosis. 2008. WHO expert committee on the selection and use of essential medicines. ed. Rare Prolonged QT interval. London. thrombocytopenia. myasthenia gravis. candida infections. wheeze. 34th ed. Paediatric Formulary Committee. 2009. Adelaide. seizures. * Artemether with lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. ed. Australian Medicines Handbook. leukopenia. pancreatitis. Sweetman SC.2. WHO Technical Report Series. Stevens-Johnson syndrome. vomiting. agitation. Adverse effects: Common Gastrointestinal intolerance (nausea. Contraindications: Severe hepatic impairment. Severe impairment: avoid. 2009. London. Uncommon Dizziness. AHFS drug information. The use of some of these agents may be restricted by local policy to ensure their cost effective and efficacious use. 950 (http://www. Renal impairment: Use with caution in patients with severe renal impairment. fixed drug eruptions. anaphylaxis. Pharmaceutical Press. ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. Martindale: the complete drug reference. They should all be available in centres providing secondary or tertiary level hospital care.

Irreversible bone marrow suppression may occur weeks or months after therapy. 2010. Adelaide. Taketomo CK. G6PD deficiency. 2008. UBM Medica. Thomson Micromedex. hepatic impairment. Lexi-Comp. Paediatric Formulary Committee. In children under 2 years. 950 (http://www. World Health Organization. ed.thomsonhc. Pediatric dosage handbook.5 g (as sodium succinate)/ml in 2 ml ampoule Oral liquid: 30 mg (as palmitate)/ml Powder for injection: 1 g (sodium succinate) in vial Serious and fatal blood dyscrasias (aplastic anaemia. Hudson. breastfeeding. azithromycin causes the least inhibition of cytochrome P450 3A4. WHO model formulary. 2009 (http://etg. Paediatric pharmacopoeia. Indications: Severe life-threatening infections. Ritonavir: plasma concentration of azithromycin possibly increased. Warn patient or carer to report pale skin. accessed 10 February 2010). Therapeutic Guidelines Limited. Australian Medicines Handbook. 2008. 2009. Drugdex system. porphyria. Some strains of Haemophilus influenzae type b and Salmonella typhi are resistant to chloramphenicol. or unusual bleeding or bruising in the months after stopping this medicine.int/medicines/publications/essentialmeds_committeereports/TRS_950.au/Search/Search. 13th ed. Should be reserved for the treatment of life-threatening infections. Royal Children’s Hospital.com. treatment of epidemic meningitis in children older than 2 years. The selection and use of essential medicines: report of the WHO expert committee. MIMS Online. Avoid repeated courses of treatment. British national formulary for children 2009. Geneva. presumptive treatment of bacterial meningitis in meningococcal epidemic in children older than 2 years. fever. Chloramphenicol ATC code: J01BA01 Capsule: 250 mg Oily suspension for injection*: 0. 2009 (http://www. monitor plasma concentrations in neonates (see Warnings). (http://www. WHO Model Formulary for Children 2010 99 Special Notes: *Oily suspension for injection is included on the list only for the presumptive . Australian medicines handbook. Hill SR. Melbourne. tiredness or weakness. Digoxin: increased plasma concentration of digoxin (increased risk of toxicity).aspx. Sydney. Klasco RK.6. hypoplastic anaemia. eds.tg. Precautions: Avoid repeated courses and prolonged use. use ceftriaxone which is approved for use from > 41 weeks corrected gestational age. WHO Technical Report Series. 2009.who. ed. McDowell JM. 2002. London. Notes: Capsules should be taken at least 1 hour before or 2 hours after food. BMJ Group RBS Publishing.au/ip/. References: eTG complete. Of all the macrolide antibiotics. 2009. October 2007 (including the model list of essential medicines for children). WHO expert committee on the selection and use of essential medicines. discontinue if evidence of myelosuppression. accessed 10 February 2010). Kouimtzi M. 16th ed. blood counts required before and during treatment. Kraus DM. Monitor full blood count with platelets frequently in all patients.pdf ). Stuart MC. Contraindications: Pregnancy. Grey baby syndrome may follow excessive doses in neonates with immature hepatic metabolism.mimsonline. accessed 10 February 2010).org. Kemp CA. * Warfarin: possibly enhanced anticoagulant effect of warfarin. renal impairment. Rossi S. monitoring of plasma concentrations is required. Greenwood Village. thrombocytopenia and granulocytopenia) have occurred after both short-term and prolonged therapy. Hodding JH.2 Antibacterials Contraceptives. oral: contraceptive effect of estrogens possibly reduced (risk probably small). Melbourne. sore throat.com. Mixture should be taken on an empty stomach.

Iron: systemic chloramphenicol increases serum iron concentration due to chloramphenicolinduced bone marrow toxicity. Up to 25 mg/kg every 6 hours may be required in severe infections provided plasma concentrations are measured and high doses reduced as soon as possible. reversible bone marrow suppression. Rare Peripheral neuropathy. Maximum daily dose 4 g. Uncommon Diarrhoea. Protease inhibitors: may increase chloramphenicol serum concentration. urticaria. Lopinavir + ritonavir: may increase chloramphenicol serum concentration. Monitor carefully for bone marrow suppression. bronchospasm. Pre-dose trough concentration should not exceed 15 mg/litre. onycholysis. THeRAPeUTIC DRUG MONITORING Plasma concentration monitoring required in neonates and high doses. Monitor carefully for bone marrow suppression. Maximum dose 3 g. Interactions with other medicines (* indicates severe): Atazanavir: may increase chloramphenicol serum concentration. hypothermia. * Phenobarbital: metabolism of chloramphenicol accelerated (reduced chloramphenicol concentration).5 mg/kg every 6 hours. contact dermatitis. consider stopping chloramphenicol. grey baby syndrome (see below). IM injection (using oily injection): Child over 2 years 100 mg/kg as a single dose. glossitis. Clostridium difficile infection. enterocolitis. metabolic acidosis. Hepatic impairment: Avoid if possible. may follow excessive doses in neonates with immature hepatic metabolism. 100 WHO Model Formulary for Children 2010 . if myelosuppression occurs. irreversible bone marrow suppression (aplastic anaemia. anaphylaxis. irregular respiration. delirium. IV injection or infusion: Infant or Child 12. leukopenia.6 Anti-infective medicines Dose: Severe life-threatening infections. dose-related depression of haematopoiesis. also reported in infants born to mothers treated in late pregnancy. abdominal distension.5 mg/kg every 6 hours. ototoxicity.5 mg/kg every 12 hours. or 2 hours after oral administration): 15–25 mg/litre. monitor iron stores and decrease iron dose as needed. peripheral neuritis. Oral. pallid cyanosis. hepatotoxicity. Hydroxocobalamin: response to hydroxocobalamin reduced. optic neuritis. * Ciclosporin (+ calcineurin inhibitors): plasma concentration of ciclosporin possibly increased. mild depression. Adverse effects: Common Nausea. IV injection or infusion: Neonate under 2 weeks 12. vomiting. circulatory collapse. thrombocytopenia. headache. preferred in those under 4 years of age and in hepatic impairment. Presumptive treatment of bacterial meningitis in meningococcal epidemic. Renal impairment: Severe: avoid unless no alternative. seek specialist advice. angioedema. haemolytic anaemia and leukaemia). Jarisch-Herxheimer reaction. greenish diarrhoea. Recommended peak plasma chloramphenicol concentration (approximately 1 hour after intravenous injection or infusion. dry mouth. confusion. Monitor carefully for bone marrow suppression. stomatitis. GRey BABy SyNDROMe Vomiting. * Phenytoin: plasma phenytoin concentration increased (increased risk of toxicity). increased risk of bone marrow depression. optic atrophy. reduce dose and monitor plasma chloramphenicol concentration. Neonate over 2 weeks 12.

Hey e. 2007. Geneva. Thomson Micromedex. Whipple disease. 950 (http://www. ReCONSTITUTION AND ADMINISTRATION Reconstitute according to manufacturer’s directions. 2007 (http://www. October 2007 (including the model list of essential medicines for children). Oxford. dilute reconstituted solution further in glucose 5% or sodium chloride 0. consider stopping treatment if haematological changes occur.int/medicines/publications/essentialmeds_committeereports/TRS_950. Ciprofloxacin ATC code: J01MA02 Oral liquid: 50 mg/ml Solution for IV infusion: 2 mg/ml Tablet: 250 mg (as hydrochloride) Achilles tendinitis and tendon rupture have been reported with fluoroquinolones in patients of all ages. WHO model formulary. Hodding JH. ed. epiglottitis.com. Contraindications: History of tendon disorders related to quinolone use. Indications: Treatment of infections due to susceptible organisms including Pseudomonas. cholera. Mcevoy GK. reduce it as soon as possible.9%. ed. 34th ed. Q fever and psittacosis. WHO Model Formulary for Children 2010 101 . Australian Medicines Handbook. accessed 10 May 2010). 2005. 2008. Stop treatment if peripheral neuropathy or optic neuritis occur.2 Antibacterials Rifampicin: accelerated metabolism of chloramphenicol (reduced plasma chloramphenicol concentration). World Health Organization. Hudson. 2009. Kraus DM. Meyler’s side effects of drugs. World Health Organization. Monitor carefully for bone marrow suppression.who. avoid repeated courses and prolonged treatment. cerebral abscess. Blackwell Publishing. AHFS drug information.int/csr/resources/publications/meningitis/WHO_CDS_ePR_2007_3. Australian medicines handbook. ed. meningitis. London. Lexi-Comp. Notes: Chloramphenicol should be reserved for life-threatening infections including (but not limited to) typhoid fever. pregnancy. Ritonavir: may increase chloramphenicol serum concentration. Bethesda. 2006. if using a high dose. Pharmaceutical Press. Paediatric Formulary Committee. Martindale: the complete drug reference. 2009. The oily injection is for intramuscular use only (see notes above). 2009. Geneva.pdf. Hill SR. Greenwood Village. Obtain complete blood picture before and during treatment (this will not warn of aplastic anaemia). Pediatric dosage handbook. * Warfarin: enhanced anticoagulant effect. American Society of Health-System Pharmacists. 2010. accessed 10 February 2010). Monitor carefully for bone marrow suppression. Standardized treatment of bacterial meningitis in Africa in epidemic and non-epidemic situations. Local resistance patterns need to taken into account. breastfeeding. References: Aronson JK.who. ed. (http://www. ed. Stuart MC. WHO expert committee on the selection and use of essential medicines.thomsonhc. 2009. rickettsia. Amsterdam.pdf ). WHO Technical Report Series. 2008. BMJ Group RBS Publishing. 4th ed. mastoiditis. Taketomo CK.6. 16th ed. listeriosis. 2005. typhoid and gonorrhoea. British national formulary for children 2009. Sweetman SC. London. The selection and use of essential medicines: report of the WHO expert committee. Neonatal formulary. elsevier. For intermittent intravenous infusion. Systemic use is limited by its toxicity. Pocket book of hospital care for children: guidelines for the management of common illnesses with limited resources. Geneva. World Health Organization. Klasco RK. Saquinavir: may increase chloramphenicol serum concentration. Drugdex system. Adelaide. eds. 15th ed. Campylobacter. Kouimtzi M. Rossi S. pneumonia. shigellosis. septicaemia.

G6PD deficiency. Oral: Neonate 7.5 mg/kg twice daily. for 24 hours. including severe rash.5 mg/kg twice daily. Other antibiotics may be used if and when sensitivities are known. Tendon rupture may occur within 48 hours of starting treatment. Maximum 500 mg twice daily. Infant 4 mg/kg every 12 hours. 102 WHO Model Formulary for Children 2010 . Oral: Infant 15 mg/kg twice daily. Child 6 mg/kg every 8 hours. Dose: Precautions: History of epilepsy. Infant 5–7.5 mg/kg twice daily. conditions that predispose to seizures. avoid excessive alkalinity of urine and ensure adequate fluid intake as risk of crystalluria. Dose may be doubled in severe infections. gastrointestinal infections. IV infusion: Neonate 5 mg/kg every 12 hours. for example riding a bike or operating machinery. Maximum 400 mg per dose. Child 10 mg/kg every 8 hours. Maximum dose 750 mg twice daily. the quinolone should be discontinued immediately. Dose may be doubled in severe infections. Dose may be doubled in severe infection. Maximum dose 750 mg twice daily. avoid exposure to excessive sunlight (discontinue if photosensitivity occurs). neurological or hypersensitivity reactions. tendon damage. TeNDON DAMAGe Tendon damage (including rupture) has been reported rarely in patients receiving quinolones.6 Anti-infective medicines myasthenia gravis. Maximum dose 400 mg every 8 hours. Oral: Neonate 7. Dose may be doubled in severe infections. NOTe Cutaneous anthrax should be treated for 7 days. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Oral: Infant or Child 15 mg/kg twice daily. IV infusion: Neonate 5 mg/kg every 12 hours. Pseudomonal lower respiratory tract infection in cystic fibrosis. Child 10 mg/kg twice daily. Infant 5–7. Maximum dose 750 mg twice daily. The drug should be discontinued if psychiatric. inhalational or gastrointestinal should be treated for 60 days. IV: Infant or Child 10 mg/kg every 12 hours. occur. Post-exposure prophylaxis should be administered for 60 days. increased to 10 mg/kg every 8 hours in severe infections. if tendinitis is suspected. Maximum dose 400 mg every 8 hours. Health-care workers should be aware that the risk of tendon rupture is increased by the concomitant use of corticosteroids. renal impairment. Infant 4 mg/kg every 12 hours. Child 20 mg/kg twice daily. Treatment and post-exposure prophylaxis of anthrax. Dose may be doubled in severe infections. Severe respiratory tract infections. IV: Infant 4–8 mg/kg every 12 hours. Complicated urinary tract infection. Maximum dose 400 mg every 8 hours. Child 10 mg/kg every 8 hours.5 mg/kg twice daily. Child 20 mg/kg twice daily.

blood dyscrasias (including agranulocytosis. separate drug administration times during a long ciprofloxacin course. photosensitivity. Separate doses from iron. disturbances in vision. Uncommon Headache.6. magnesium hydroxide): reduced absorption of ciprofloxacin. Final concentration for administration should not exceed 2 mg/ml. depression. leukopenia. * Ibuprofen: possibly increased risk of seizures. psychotic reactions. Calcium salts: reduced absorption of ciprofloxacin. ADMINISTRATION For intravenous administration. arthritis. myalgia. antacids and milk by 2 hours. orofacial dyskinesia. resulting in hypothyroidism. transient hearing impairment. Notes: Best taken on an empty stomach. anaphylaxis. cholestatic jaundice. dyspepsia. Dairy products: reduced absorption of ciprofloxacin. abdominal pain). monitor methotrexate concentration carefully as increased rescue treatment with calcium folinate may be needed. Use sunscreen. peripheral oedema. tremors. administer by slow intravenous infusion over 60 minutes. angioedema. restlessness. gastrointestinal intolerance (nausea. toxic epidermal necrolysis. seizures. insomnia. Stevens-Johnson syndrome. Jarisch-Herxheimer reaction. itch. peripheral neuropathy. Phenytoin: plasma phenytoin concentration can be increased or decreased by ciprofloxacin. hyperglycaemia. pain or thrombophlebitis at intravenous infusion site. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. Important to maintain an adequate fluid intake. Thyroid hormones: ciprofloxacin may interfere with absorption of thyroxine. raised liver enzymes. renal failure. WHO Model Formulary for Children 2010 103 . vomiting. vasculitis. tendinitis. Morphine: manufacturer of ciprofloxacin advises to avoid premedication with morphine (reduced plasma ciprofloxacin concentration) when ciprofloxacin used for surgical prophylaxis. Theophylline: may result in increased plasma levels of theophylline and significant adverse effects. Contraceptives. Consider the necessity for intravenous administration as adequate levels can be achieved using oral formulations due to high bioavailability. * Warfarin: enhanced anticoagulant effect. oral: contraceptive effect of estrogens possibly reduced (risk probably small). blood coagulation disorder. hepatitis. arthralgia. and monitor thyroid function. Clostridium difficile infection.2 Renal impairment: Reduce dose if CrCl < 30 ml/minute. metallic taste. Zinc sulfate: reduced absorption of ciprofloxacin. haemolytic anaemia. fixed drug eruption. aplastic anaemia. movement disorders. pancytopenia and thrombocytopenia). Rare Interstitial nephritis. wear protective clothing and a hat. diarrhoea. erythema. tendon inflammation and rupture. pancreatitis. erythema multiforme. Can cause photosensitivity. Ferrous salts: absorption of ciprofloxacin reduced by oral ferrous salts. methaemoglobinaemia. Antibacterials Adverse effects: Common Rash. crystalluria. dizziness. * Ciclosporin: increased risk of nephrotoxicity. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide. Methotrexate: increased methotrexate concentration and risk of toxicity when high-dose methotrexate is given.

2009. Taketomo CK. 13th ed. 2008. concomitant hepatotoxic drugs.who. 2009. The selection and use of essential medicines: report of the WHO expert committee.thomsonhc. bulging fontanelles in infants. World Health Organization. Adverse effects: Common Gastrointestinal intolerance (nausea. 2008. toxic epidermal necrolysis. 104 WHO Model Formulary for Children 2010 . 100 mg (hydrochloride) Special Notes: WHO age/weight restriction: > 8 years (except for serious infections.com. Paediatric Formulary Committee. Geneva. British national formulary for children 2009. ed. London. magnesium hydroxide): reduced absorption of doxycycline. renal impairment. Rare Photo-onycholysis and nail discoloration. porphyria. pancreatitis. Adelaide. Klasco RK. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide. Maximum daily dose 200 mg. bone deformity. Royal Children’s Hospital. oral: contraceptive effect of estrogens possibly reduced (risk probably small). oesophageal ulcers (due to partly swallowed tablets or capsules). hepatic impairment. diarrhoea. hepatitis. avoid excessive doses. systemic lupus erythematosus. stomatitis. tooth discoloration (permanent in children aged < 8 years). BMJ Group RBS Publishing. Dose: Bacterial infections.pdf ). JarischHerxheimer reaction when treating spirochetal infections. Ferrous salts: absorption of oral ferrous salts reduced by doxycycline. hepatotoxicity. Uncommon Rash. epigastric burning). vomiting. Kraus DM. photosensitivity (depends on dose and degree of sun exposure). Carbamazepine: accelerated metabolism of doxycycline (reduced effect).g. WHO Technical Report Series. allergic reactions including anaphylaxis (less common than with penicillins). Australian medicines handbook. Hudson. Thomson Micromedex. (http://www. worsening of systemic lupus erythematosus. Renal impairment: Use with caution. Contraindications: Pregnancy. 10 mg/ml Solid oral dosage form: 50 mg. serum sickness-like reactions. Stuart MC. breastfeeding. accessed 10 February 2010). headache and visual disturbances may indicate benign intracranial hypertension. then 2 mg/kg (maximum 100 mg) daily. myasthenia gravis. Contraceptives.6 Anti-infective medicines References: Hill SR. e. Paediatric pharmacopoeia. WHO model formulary. October 2007 (including the model list of essential medicines for children). Precautions: Children under 8 years (avoid unless life-threatening infection when no other alternative exists). cholera). 2010. fatty liver degeneration (with high doses. fungal overgrowth. 950 (http://www. Hodding JH. 2002. 16th ed. Indications: Bacterial infections. Melbourne. Drugdex system. WHO expert committee on the selection and use of essential medicines. antibiotic-associated colitis (Clostridium difficile-associated disease). or twice daily in severe infections such as rickettsia. Hepatic impairment: Avoid (or use with caution). Lexi-Comp. eds. Oral: Child over 8 years 2 mg/kg (maximum 100 mg) twice daily on day 1. avoid exposure to sunlight or sunlamps (photosensitivity reported).int/medicines/publications/essentialmeds_committeereports/TRS_950. enamel dysplasia. 2009. Kouimtzi M. Pediatric dosage handbook. Australian Medicines Handbook. McDowell JM. * Ciclosporin: possibly increased plasma ciclosporin concentration. especially in pregnancy). Rossi S. Kemp CA. reduced bone growth (in children < 8 years). Greenwood Village. absorption of doxycycline reduced by oral ferrous salts. Doxycycline ATC code: J01AA02 Oral liquid: 5 mg/ml. ed.

2 Antibacterials Methotrexate: increased risk of methotrexate toxicity.who. (http://www. oral infections. respiratory tract infections (including pneumonia. Swallow whole with plenty of water and remain upright (do not lie down) for an hour after taking doxycycline to prevent oesophageal irritation.au/ip/. Prevention of secondary case of diphtheria in non-immune patient. 2002. Rifampicin: plasma doxycycline concentration possibly reduced. Hill SR.6. WHO Model Formulary for Children 2010 105 . Melbourne. Oral: Infant or Child under 2 years 125 mg every 6 hours for 7 days. Klasco RK. Infant or Child under 2 years 125 mg every 6 hours. Notes: Separate dose from antacids and iron supplements by 2 hours. Thomson Micromedex. McDowell JM. severe hepatic impairment. Oral: Neonate 12.thomsonhc. 2008. doubled in severe infections. World Health Organization. porphyria. Treat for a further 10 days if nasopharyngeal swabs are positive after first 7 days of treatment. Oral: Infant or Child under 2 years 125 mg every 6 hours for 7 days. October 2007 (including the model list of essential medicines for children). 2008. Phenobarbital: metabolism of doxycycline accelerated (reduced plasma concentration).pdf ).org. The selection and use of essential medicines: report of the WHO expert committee. Kemp CA. prevention of secondary case of diphtheria and pertussis in nonimmune patients. cholera. doubled in severe infections. Phenytoin: increased metabolism of doxycycline (reduced plasma concentration). renal impairment. * Warfarin: anticoagulant effect possibly enhanced. Contraindications: Hypersensitivity to erythromycin or other macrolides.int/medicines/publications/essentialmeds_committeereports/TRS_950. treatment with cisapride. ed. 2–8 years 250 mg every 6 hours for 7 days. legionnaires’ disease. Kouimtzi M. Erythromycin ATC code: J01FA01 Powder for oral liquid: 25 mg/ml (as stearate or ethyl succinate) Solid oral dosage form: 250 mg (as stearate or ethyl succinate) Indications: Treatment of susceptible infections as an alternative to penicillin in hypersensitive patients. Greenwood Village. WHO expert committee on the selection and use of essential medicines. over 8 years 500 mg every 6 hours for 7 days. Dose: Treatment of susceptible infections. accessed 10 February 2010). doubled in severe infections. Melbourne. WHO Technical Report Series. Prevention of secondary case of pertussis in non-immune patient. Royal Children’s Hospital. Paediatric pharmacopoeia. Drugdex system. 2–8 years 250 mg every 6 hours. neonates under 2 weeks. References: eTG complete. predisposition to QT interval prolongation. Single daily doses are best taken in the morning rather than at night. Adelaide. Geneva.5 mg/kg every 6 hours. WHO model formulary. accessed 10 February 2010). over 8 years 250–500 mg every 6 hours. Precautions: Hepatic impairment. 2010. 950 (http://www. eds. Australian Medicines Handbook. 2009. treatment of susceptible infections such as Campylobacter enteritis.tg. ed. 2009 (http://etg. streptococcal pharyngitis) and diphtheria. 2–8 years 250 mg every 6 hours for 7 days. over 8 years 500 mg every 6 hours for 7 days. Stuart MC. Therapeutic Guidelines Limited. 13th ed. porphyria. Rossi S. Australian medicines handbook.com.

Adverse effects: Common Gastrointestinal intolerance (nausea. Digoxin: increased plasma concentration of digoxin (increased risk of toxicity). urticaria. cough. hearing loss. The ethyl succinate (eeS) salt is given without regard to food. * Carbamazepine: increased plasma carbamazepine concentration. Notes: Total oral daily dose may be halved and given every 12 hours. phlebitis. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. vomiting. Valproic acid: metabolism of valproic acid possibly inhibited (increased plasma concentration). diarrhoea). Interactions with other medicines (* indicates severe): erythromycin has multiple drug-drug interactions as it is a potent inhibitor of cytochrome P450 3A4 and 1A2. Rare Myasthenia-like syndrome. * Quinidine: increased risk of ventricular arrhythmias with parenteral erythromycin. anaphylaxis. abdominal discomfort. cholestatic jaundice. Ritonavir: plasma concentration possibly increased by ritonavir. headache. * Theophylline: may increase theophylline concentration and toxicity. Stevens-Johnson syndrome. * Ciclosporin: increased plasma ciclosporin concentration (inhibition of metabolism of ciclosporin). * Vinblastine: increased toxicity of vinblastine (avoid concomitant use). Stop erythromycin if severe hepatic dysfunction develops. candidal infections. 106 WHO Model Formulary for Children 2010 . Uncommon Rash. Risk of ototoxicity. however diarrhoea is a common side effect. The base and stearate salt are given on an empty stomach 1 hour before or 2 hours after meals. * Warfarin: enhanced anticoagulant effect. prolonged QT interval. INFANTILe HyPeRTROPHIC PyLORIC STeNOSIS Has occurred in about 5% of a cohort of infants receiving erythromycin for pertussis prophylaxis. erythema multiforme. Hepatic impairment: May cause idiosyncratic hepatotoxicity. Clostridium difficile infection. reversible hearing loss after large doses. possibly affecting its efficacy. Parents of neonates: tell your doctor if your baby develops vomiting or is irritable when feeding while taking erythromycin. * Verapamil: increased risk of cardiotoxicity and serious prolongation of QT interval. Prednisolone: erythromycin possibly inhibits metabolism of prednisolone. toxic epidermal necrolysis. erythromycin levels may concurrently decrease.6 Anti-infective medicines Renal impairment: Severe impairment: reduce dose. psychiatric disturbances. Hydrocortisone: erythromycin possibly inhibits metabolism of hydrocortisone. dyspnoea. hepatic impairment may worsen. pancreatitis. Severe impairment: avoid use. torsades de pointes. Dexamethasone: erythromycin possibly inhibits metabolism of dexamethasone. acute respiratory distress. Warn patients or carers that erythromycin interacts with many drugs and even herbal products so inform doctor or pharmacist before taking additional medication. fixed drug eruptions. Mild to moderate impairment: use with caution. seizures. infantile hypertrophic pyloric stenosis (see below). no increased risk in infants receiving erythromycin after 2 weeks of age. risk increased with increasing length of treatment.

WHO Technical Report Series. auditory and vestibular function. WHO expert committee on the selection and use of essential medicines. avoid prolonged use. pneumonia. Thomson Micromedex. obesity (use ideal body weight to calculate dose and monitor serum gentamicin concentration closely). Paediatric Formulary Committee. Renal impairment: Reduce dose frequency. Risk of ototoxicity increases with use of potent diuretics. BMJ Group RBS Publishing. Indications: Treatment of infections with susceptible organisms taking local resistance factors into account. Pediatric dosage handbook. Lexi-Comp. neonates and infants (use with caution and monitor renal. Greenwood Village.6. Klasco RK. Australian Medicines Handbook. neuromuscular blockade (see below). 2008. vestibular and permanent bilateral auditory ototoxicity can occur. Taketomo CK. as necessary. 2009. Kraus DM. Hepatic impairment: Dose reduction not necessary. Pre-dose (“trough”) concentration should be less than 1 mg/litre.who. Risk of nephrotoxicity increases when used concurrently with other potentially nephrotoxic drugs. 950 (http://www. accessed 10 February 2010). THeRAPeUTIC DRUG MONITORING Monitor serum gentamicin concentration and reduce doses or increase dosing intervals. 2010. Adelaide.com. October 2007 (including the model list of essential medicines for children). Precautions: Renal impairment. (http://www. Special Notes: This medicine is listed as a representative of its pharmacological class. Infant or Child under 10 years 7. Geneva. bronchospasm. or both. IV or IM: Term neonate 3.2 References: Antibacterials Hill SR. World Health Organization. hypocalcaemia. eds. British national formulary for children 2009. 16th ed. Dose: Treatment of infections with susceptible organisms. Drugdex system. antibiotic-associated colitis. WHO model formulary.int/medicines/publications/essentialmeds_committeereports/TRS_950. Hudson. 40 mg (as sulfate)/ml in 2 ml vial Aminoglycosides are associated with significant nephrotoxicity. 2009. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. 2008. Monitor renal. ed. ed. conditions characterized by muscular weakness.5 mg/kg once daily.5–5 mg/kg once daily. peripheral neuropathy.thomsonhc. oliguria. Contraindications: Myasthenia gravis. The selection and use of essential medicines: report of the WHO expert committee. Rossi S. Stuart MC.pdf ). high-dose therapy or prolonged therapy. over 10 years 6 mg/kg once daily (maximum dose 240–360 mg). renal damage is usually reversible. Rare Hypomagnesaemia. The information in this monograph only applies to the medicine listed here. ototoxicity (see below). Gentamicin ATC code: J01GB03 Injection: 10 mg. Hodding JH. Adverse effects: Common Nephrotoxicity (see below). Australian medicines handbook. Kouimtzi M. 2009. anaphylaxis (probably due to sulfites in some formulations). Monitor serum gentamicin concentration. WHO Model Formulary for Children 2010 107 . auditory and vestibular function. acute pyelonephritis and meningitis. tinnitus or vertigo are indications of vestibular injury and impending bilateral irreversible deafness. hypokalaemia. and serum gentamicin concentrations). Risk of nephrotoxicity and ototoxicity is increased in patients with impaired renal function. London. including septicaemia.

eds. Hodding JH. Kraus DM. can usually be reversed with prompt administration of IV calcium gluconate. Preferable to separate administration by 1 hour. may lead to respiratory insufficiency. * Vecuronium: enhanced muscle relaxant effect. Notes: In obese or severely oedematous children use the ideal weight for height to calculate dose.thomsonhc. ed. WHO model formulary. 2008. 2002. usually presents as gradually worsening non-oliguric renal failure with increasing serum creatinine and proteinuria. McDowell JM. Australian medicines handbook.who.pdf ). it may appear to begin after stopping treatment. permanent deafness may occur. Vancomycin: increased risk of nephrotoxicity and ototoxicity. 108 WHO Model Formulary for Children 2010 . such as cefalosporins and penicillins. monitor respiratory function. Magnesium sulfate: additive neuromuscular blocking effect with aminoglycosides and parenteral magnesium sulfate.com. Drugdex system. Paediatric Formulary Committee. tinnitus. Klasco RK. feeling of fullness in ear) have been associated with gentamicin use. Ototoxicity caused by gentamicin can be irreversible. British national formulary for children 2009. use combinations cautiously. (http://www. ed. Hudson. Taketomo CK. Target serum concentrations may vary depending on indication and institution. WHO Technical Report Series. 2010. Adelaide. Thomson Micromedex. Paediatric pharmacopoeia. dilute in glucose 5% or sodium chloride 0. 13th ed. Administer other antibiotics. * Suxamethonium: enhanced muscle relaxant effect. October 2007 (including the model list of essential medicines for children). 950 (http://www. World Health Organization. Penicillins: concomitant penicillin and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. Capreomycin: increased risk of nephrotoxicity and ototoxicity. vertigo. 16th ed. Digoxin: possibly increased plasma concentration of digoxin. WHO expert committee on the selection and use of essential medicines. infuse over 30–60 minutes. Geneva. References: Hill SR. at least 1 hour before or after gentamicin. Kouimtzi M. nystagmus. accessed 10 February 2010). Rossi S. OTOTOXICITy Clinically evident vestibular ototoxicity (nausea. Stuart MC. The selection and use of essential medicines: report of the WHO expert committee. 2008. Interactions with other medicines (* indicates severe): Amphotericin B: increased risk of nephrotoxicity. Nondepolasing neuromuscular blockers: aminoglycosides prolong effect of nondepolarising neuromuscular blockers. difficulties with gait) and cochlear ototoxicity (noticeable hearing loss. Royal Children’s Hospital. 2009. As the patient is unaware of the first symptoms of cochlear toxicity. 2009. Greenwood Village.int/medicines/publications/essentialmeds_committeereports/TRS_950.9%. 2009. * Ciclosporin: increased risk of nephrotoxicity. Pediatric dosage handbook. Kemp CA. Australian Medicines Handbook. Lexi-Comp. BMJ Group RBS Publishing. Final concentration of intravenous administration should not exceed 10 mg/ml. * Neostigmine: antagonism of effect of neostigmine. but may present as acute tubular necrosis.6 Anti-infective medicines NePHROTOXICITy Usually reversible and can be anticipated if treatment lasts > 7–10 days. NeUROMUSCULAR BLOCKADe May result in respiratory depression. ADMINISTRATION For intravenous infusion. the effect of neostigmine is variable. Melbourne. Other nephrotoxic agents: co-administration with other drugs which are ototoxic or nephrotoxic may increase risk of these adverse effects. * Furosemide: increased risk of ototoxicity. vomiting. London. * Pyridostigmine: antagonism of effect of pyridostigmine.

5 mg/kg may be given every 8 hours for high-risk procedures. Surgical prophylaxis. anorexia. metallic taste. Maximum dose 400 mg. Fluorouracil: metabolism of fluorouracil inhibited (increased toxicity). Use with caution in hepatic encephalopathy. anaphylaxis. Hepatic impairment: Severe impairment: reduce total daily dose to one third and give once daily. Uncommon Furry tongue. peripheral neuropathy.6. disulfiram-like reaction with alcohol. HIGH-DOSe AND/OR PROLONGeD TReATMeNT Leukopenia is reversible and usually only occurs after prolonged treatment. abnormal liver function tests. for example riding a bike or operating machinery. flushing. oral: contraceptive effect of estrogens possibly reduced (risk probably small). Clostridium difficile infection should be treated orally. Oral or IV infusion: Infant or Child 7. Dose adjustment is not usually necessary. for 24 hours. hepatitis. NOTe Acute ulcerative gingivitis is usually successfully treated in 3 days. Clostridium difficile-associated disease. Infant or Child 7. Precautions: Hepatic impairment.2 Antibacterials Metronidazole ATC code: J01XD01 Injection: 500 mg in 100 ml vial Oral liquid: 40 mg (as benzoate)/ml Tablet: 200 mg to 500 mg Indications: Anaerobic bacterial infections including ulcerative gingivitis. rash. Rare Pancreatitis. Maximum dose 500 mg. CNS effects (e. tetanus. vomiting. peripheral neuropathy (usually reversible) and/or CNS toxicity (including seizures) may occur. glossitis. IV infusion: Neonate 15 mg/kg as a single loading dose. skin and soft tissue infections. thrombophlebitis (IV). Dose: Anaerobic bacterial infections. itch. diarrhoea).g. darkening of the urine. dizziness. Stevens-Johnson syndrome. thrombocytopenia.5 mg/kg every 8 hours. Renal impairment: Metabolites may accumulate in severe impairment possibly causing adverse effects. leukopenia. stomatitis. angioedema. abdominal pain. Infant or Child 7.5 mg/kg every 8 hours. followed by 7. Interactions with other medicines (* indicates severe): Alcohol: disulfiram-like reaction. paraesthesia. seizures. WHO Model Formulary for Children 2010 109 . optic neuritis. headache). acute oral infections. surgical prophylaxis. Contraceptives.5 mg/kg every 12 hours.5 mg/kg every 12 hours starting 24 hours after loading dose. while other anaerobic and oral anaerobic conditions usually treated for only 7 days. Up to 3 further doses of 7. clinical and laboratory monitoring in courses lasting longer than 10 days. jaundice.g. and Clostridium difficile infection (oral therapy). Adverse effects: Common Gastrointestinal intolerance (nausea. and is usually treated for 7–10 days. erythema multiforme.5 mg/kg 2 hours before surgery. fever). hypersensitivity reactions (e. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Oral: Neonate initially 15 mg/kg then 7. Maximum dose 500 mg.

prophylaxis of urinary tract infection.6 Anti-infective medicines Lithium: increased lithium toxicity reported. Lopinavir liquid: disulfuram-like reaction. World Health Organization. Australian medicines handbook. Hepatic impairment: Cholestatic jaundice and chronic active hepatitis reported. Drugdex system. Royal Children’s Hospital. 2002. WHO expert committee on the selection and use of essential medicines. susceptibility to peripheral nephritis. Melbourne. infuse over 20–30 minutes.who. Precautions: Pulmonary disease. Hudson. for example riding a bike or operating machinery. Phenobarbital: metabolism of metronidazole accelerated (reduced plasma concentration). Adelaide. hepatic impairment. Geneva. * Warfarin: enhanced anticoagulant effect. ed. BMJ Group RBS Publishing. Paediatric Formulary Committee. Maximum dose 100 mg.com. Prophylaxis of urinary tract infection. electrolyte imbalance. diabetes mellitus. anaemia. Contraindications: Renal impairment. for 24 hours. Kouimtzi M. accessed 10 February 2010). * Phenytoin: metabolism of phenytoin inhibited (increased plasma phenytoin concentration). British national formulary for children 2009. Renal impairment: Avoid in all degrees of renal impairment. during or after food. porphyria. 950 (http://www. 13th ed. ed. October 2007 (including the model list of essential medicines for children). 110 WHO Model Formulary for Children 2010 . Pediatric dosage handbook. 2010. Treatment may be ineffective because of inadequate urine concentrations. 16th ed. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. vitamin B and folate deficiency. infants less than 3 months.thomsonhc.pdf ). (http://www. Stuart MC. Nitrofurantoin ATC code: J01Xe01 Oral liquid: 5 mg/ml Tablet: 100 mg Indications: Treatment of acute uncomplicated urinary tract infection. 2009. Hodding JH. Maximum dose 100 mg. monitor lung and liver function on long- term therapy (discontinue if lung function deteriorates). McDowell JM. The selection and use of essential medicines: report of the WHO expert committee. 2008. 2009. Lexi-Comp. WHO model formulary.int/medicines/publications/essentialmeds_committeereports/TRS_950. Australian Medicines Handbook. 2008. false-positive urinary glucose (if testing for reducing substances). Kraus DM. Patients should be advised to swallow tablets whole with water. Kemp CA. Klasco RK. ADMINISTRATION For intravenous infusion. London. 2009. Dose: Treatment of acute uncomplicated urinary tract infection. Thomson Micromedex. suspension is best taken 1 hour before food (or on an empty stomach). Rossi S. at term. urine may be coloured yellow or brown. G6PD deficiency. Paediatric pharmacopoeia. Oral: Infant or Child over 3 months 750 micrograms/kg four times daily for 3–7 days. eds. pregnancy. Notes: Well absorbed orally and the intravenous route is normally reserved for severe infections. References: Hill SR. Oral: Infant or Child over 3 months 1 mg/kg at night. Taketomo CK. Oral absorption from the suspension is lower than from the tablets. Risk of peripheral neuropathy. WHO Technical Report Series. Greenwood Village.

The main predisposing factor appears to be renal impairment. accessed 10 February 2010). Rare Peripheral polyneuropathy (see below). 111 WHO Model Formulary for Children 2010 . anorexia. Klasco RK. Rossi S. Hill SR. eosinophilia. anaphylaxis. drug fever. PeRIPHeRAL POLyNeUROPATHy Begins with peripheral paraesthesia and sensory loss (usually in lower limbs). McDowell JM. HePATOTOXICITy Acute hepatocellular or cholestatic reactions generally occur in the first 6 weeks of treatment. Royal Children’s Hospital. 2009. WHO expert committee on the selection and use of essential medicines. Folic acid: concurrent use may result in decreased folic acid serum levels. WHO Technical Report Series. Lexi-Comp. 13th ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. cholestatic jaundice. Adelaide. 16th ed. Hodding JH. Pediatric dosage handbook. Stuart MC. Uncommon Drowsiness. PULMONARy TOXICITy Pulmonary fibrosis has been reported. hepatitis. 2008. eds. 2009. diarrhoea and abdominal pain). as onset of hepatotoxicity may be insidious. World Health Organization. dizziness. ed. sometimes with fever. may be associated with pulmonary toxicity (see below). PATIeNT ADVICe Patients and their carers should be advised to tell their doctor immediately if they have difficulty breathing. 2010. arthralgia. Melbourne. BMJ Group RBS Publishing. (http://www. sialadenitis. Norfloxacin: may result in antagonism of the antibacterial effect of norfloxacin. 2008. 950 (http://www. hypersensitivity reactions (including urticaria. Notes: Give with food or milk to reduce nausea and to improve absorption. angioedema). rash. London.2 Antibacterials Adverse effects: Common Dose related gastrointestinal disorders (including nausea and vomiting. benign intracranial hypertension. Kouimtzi M. ed. MONITORING During long-term treatment monitor the following: pulmonary function. Australian Medicines Handbook. Both types can be fatal. Possible association with lupus erythematosus-like syndrome.thomsonhc. Local antimicrobial patterns need to be taken into account. Indications: Treatment of infections with susceptible organisms including urinary tract infections. British national formulary for children 2009.com. usually after about 6 months treatment. Paediatric pharmacopoeia. exfoliative dermatitis. hepatotoxicity (see below). 80 mg + 16 mg/ml in 10 ml ampoule Oral liquid: 40 mg + 8 mg/ml Tablet: 100 mg + 20 mg. blood disorders including eosinophilia. References: Sulfamethoxazole + Trimethoprim ATC code: J01ee01 Injection: 80 mg + 16 mg/ml in 5 ml ampoule. 400 mg + 80 mg Special Notes: Also referred to as co-trimoxazole. Drugdex system. pancreatitis. Australian medicines handbook. lupus-like syndrome. Chronic active hepatitis (sometimes reversible) mostly occurs in women. Stevens-Johnson syndrome. Thomson Micromedex. Greenwood Village. liver function every month for 3 months.6. then every 3 months. develop a cough or get any numbness or tingling. 2009. vertigo. but it may be incomplete. skin reactions including erythema multiforme. Paediatric Formulary Committee. acute and chronic pulmonary reactions (see below). renal function as peripheral polyneuropathy is more likely to occur if this is impaired. Hudson. WHO model formulary. Taketomo CK. Kraus DM. 2002. October 2007 (including the model list of essential medicines for children). The selection and use of essential medicines: report of the WHO expert committee. Kemp CA. respiratory tract infection. for development of paraesthesia as stopping treatment early can prevent severe neuropathy.who. rash and are usually reversible. pruritus. Interactions with other medicines (* indicates severe): Fluconazole: concurrent use may result in increased risk of hepatic and pulmonary toxicity. Geneva. can progress to motor loss and muscle atrophy. Improvement usually occurs after stopping treatment.pdf ). headache. typhoid fever and otitis media.

6 Anti-infective medicines anaemia. eosinophilia. thrombocytopenia. neutropenia. Dose: Doses are expressed in terms of the trimethoprim component. maintain adequate fluid intake (to avoid crystalluria). severe renal impairment. antibiotic-associated colitis. dyspnoea. jaundice. nausea. aseptic meningitis. tremor. Hepatic impairment: Severe impairment: avoid use. hepatitis. thrombocytopenia. 112 WHO Model Formulary for Children 2010 . drowsiness. lupuslike syndrome. the most serious effects include anaphylaxis. interstitial nephritis. serum sickness-like syndrome. e. ataxia (after IV use in HIV patients). rash. rash (discontinue immediately). photosensitivity. raised hepatic aminotransferases) is substantially higher in patients with AIDS. cough. Maximum 160 mg twice daily. Digoxin: plasma concentration of digoxin possibly increased. avoid in infants under 6 weeks. systemic vasculitis and pancytopenia. Lamivudine: competes for renal excretion. Maximum 160 mg twice daily. * Azathioprine: increased risk of haematological toxicity. anorexia.g. eosinophilia. pneumonitis. Moderate impairment: use half normal dose. pyrimethamine. plasma ciclosporin concentration possibly reduced by intravenous trimethoprim. hepatitis. hyponatraemia. severe hepatic impairment. Stevens-Johnson syndrome. Contraindications: Hypersensitivity to sulfonamides or trimethoprim. avoid in blood disorders (unless under specialist supervision). Uncommon Headache. crystalluria. porphyria. Trimethoprim can cause hyperkalaemia. monitor blood counts on prolonged treatment. Trimethoprim with sulfamethoxazole can cause nephrotoxicity. hepatic necrosis. * Ciclosporin: increased risk of nephrotoxicity. G6PD deficiency. hyperkalaemia. Treatment of infections with susceptible organisms. diarrhoea. hypoglycaemia. vomiting. urinary obstruction with anuria/oliguria. Incidence of some adverse effects (rash. predisposition to folate deficiency. hyperkalaemia. Renal impairment: Severe impairment: avoid use. pancreatitis. Clostridium difficile-associated disease. depression. megaloblastic Precautions: Mild to moderate renal impairment. rash. itch. Plasma monitoring may be required with high doses in renal impairment. vasculitis. IV infusion: Infant or Child over 6 weeks 3 mg/kg every 12 hours. seek expert advice. Interactions with other medicines (* indicates severe): Trimethoprim is a folate antagonist and will add to the effects on bone marrow of other folate antagonists. leukopenia. methaemoglobinaemia). giving with other nephrotoxic drugs may cause additional renal adverse effects. nephrotoxicity. nausea. megaloblastic anaemia. Adverse effects: Some adverse effects may be hypersensitivity reactions (see below). asthma. fever. Rare erythema. * Mercaptopurine: increased risk of haematological toxicity. Dapsone: plasma concentration of both dapsone and trimethoprim may increase with concomitant use. increasing lamivudine concentration and risk of toxicity. Oral: Infant or Child over 6 weeks 4 mg/kg/dose twice daily. discontinue immediately if blood disorder develops. lowered mental acuity. toxic epidermal necrolysis. stomatitis. blood disorders (including neutropenia. HyPeRSeNSITIVITy May present with fever. thrombocytopenia. Common Fever. administration with potassium supplements or other drugs which also cause potassium retention can further increase potassium concentration.

ed. ed. If fluid restriction necessary. 2008. dilute each 5 ml of injection solution to 125 ml. sore throat. patients and their carers should be told how to recognize signs of blood disorders and advised to seek immediate medical attention if symptoms such as fever. predisposition to folate deficiency. Check container for haze or precipitant during administration. 13th ed.6. WHO Model Formulary for Children 2010 113 . Precautions: Mild to moderate renal impairment. Attention should be paid to the folate status of the patient should treatment be prolonged or high dose. Warfarin: possibly enhanced anticoagulant effect. Infuse over 60–90 minutes (but may be adjusted according to fluid requirements). Paediatric pharmacopoeia. British national formulary for children 2009. References: Hill SR. Royal Children’s Hospital.pdf ). Stuart MC. 16th ed. 2009. London. Indications: Treatment of urinary tract infection and respiratory tract infection. rash. Kraus DM. Drugdex system.int/medicines/publications/essentialmeds_committeereports/TRS_950. Kemp CA. * Phenytoin: antifolate effect and plasma phenytoin concentration increased. Paediatric Formulary Committee. Klasco RK. accessed 10 February 2010). Oral: Infant or Child over 6 months 4 mg/kg twice daily. 200 mg Special Notes: WHO age/weight restriction: > 6 months. Geneva. decreasing its efficacy. Hudson. Adelaide. WHO model formulary. Thomson Micromedex. DILUTION AND ADMINISTRATION For intermittent intravenous infusion may be further diluted in glucose 5% and 10% or sodium chloride 0. porphyria. 2002. Lexi-Comp.9% or Ringer’s intravenous solution. bruising or bleeding develop. Maximum 200 mg twice daily.who. Melbourne. WHO expert committee on the selection and use of essential medicines. 2009. Kouimtzi M.com. * Pyrimethamine: increased antifolate effect.thomsonhc. Trimethoprim ATC code: J01eA01 Oral liquid: 10 mg/ml Tablet: 100 mg. 5 ml may be diluted with 75 ml of glucose 5% and the required dose infused over a maximum of 60 minutes. World Health Organization. 2009. Rifampicin: decreases concentrations of trimethoprim and sulfamethoxazole when used for prophylaxis in HIV-positive patients. Australian medicines handbook. The selection and use of essential medicines: report of the WHO expert committee. 2008. Notes: Oral dose is best given with or after food. 2010. prophylaxis of urinary tract infection. Australian Medicines Handbook. mouth ulcers. Dose: Treatment of urinary tract infection and respiratory tract infection. BMJ Group RBS Publishing. In severe fluid restriction may be given undiluted via a central venous line. Must be further diluted. October 2007 (including the model list of essential medicines for children). blood counts on long-term therapy. Contraindications: Blood disorders including megaloblastic anaemia due to folate deficiency. Rossi S. neonates and infants < 6 months. severe renal impairment. purpura. Prophylaxis of urinary tract infection. Taketomo CK. Greenwood Village. Pediatric dosage handbook. McDowell JM. Hodding JH. BLOOD DISORDeRS On long-term treatment. 950 (http://www. (http://www. * Sulfadoxine + pyrimethamine: increased antifolate effect.2 Antibacterials * Methotrexate: antifolate effect of methotrexate increased (avoid concomitant use). WHO Technical Report Series. eds. hepatic impairment. Oral: Infant or Child over 6 months 2 mg/kg (maximum 100 mg) at night.

glossitis. superinfection (Candida species). (http://www. British national formulary for children 2009. Geneva. October 2007 (including the model list of essential medicines for children). toxic epidermal necrolysis. 950 (http://www.com.who. * Sulfadoxine + pyrimethamine: increased antifolate effect. pruritus. erythema multiforme (StevensJohnson syndrome). Drugdex system. aseptic meningitis.g. is taking drugs which can cause hyperkalaemia or is taking a high dose. Klasco RK. e. WHO model formulary. WHO Technical Report Series. Stuart MC. The selection and use of essential medicines: report of the WHO expert committee. accessed 10 February 2010). renal impairment and use of other potassium-retaining drugs (see Interactions). allergy including anaphylaxis.thomsonhc. nausea. Thomson Micromedex. Interactions with other medicines (* indicates severe): Trimethoprim is a folate antagonist and will add to the effects on bone marrow of other folate antagonists. * Mercaptopurine: increased risk of haematological toxicity. Kouimtzi M. 114 WHO Model Formulary for Children 2010 . * Pyrimethamine: increased antifolate effect. Hepatic impairment: Use with caution. Risk factors are high doses. * Azathioprine: increased risk of haematological toxicity. Notes: Monitor complete blood picture and folate status during prolonged or high-dose treatment. Adelaide. Adverse effects: Common Fever. hyperkalaemia (see below). Rossi S.6 Anti-infective medicines Renal impairment: Mild to moderate impairment: use half normal dose if CrCl 15–30 ml/minute. Enalapril: increased risk of hyperkalaemia. Australian Medicines Handbook. 2008. London. * Ciclosporin: increased risk of nephrotoxicity. 2010. beginning on day 3. Moderate to severe impairment: avoid use if CrCl less than 15 ml/minute. World Health Organization. rash. Greenwood Village. Average onset is 4–5 days. ed. HyPeRKALAeMIA Trimethoprim causes potassium retention. Digoxin: plasma concentration of digoxin possibly increased. Hyperkalaemia can occur with usual doses but is more likely to be clinically significant as dose increases. BMJ Group RBS Publishing. if the patient has renal impairment. Monitor serum potassium. thrombocytopenia. 2009. ed. WHO expert committee on the selection and use of essential medicines. increasing lamivudine concentration and risk of toxicity. References: Hill SR. pyrimethamine. increase in serum creatinine. Lamivudine: competes for renal excretion. Warfarin: possibly enhanced anticoagulant effect.int/medicines/publications/essentialmeds_committeereports/TRS_950. Dose reduction not required. Give at night to maximize urinary concentration for urinary tract infection prophylaxis.pdf ). * Methotrexate: antifolate effect of methotrexate increased (avoid concomitant use). Rare Leukopenia. eds. 2009. vomiting. 2008. Uncommon Sore mouth. methaemoglobinaemia (especially with high doses or prolonged treatment). Paediatric Formulary Committee. plasma ciclosporin concentration possibly reduced by intravenous trimethoprim. Australian medicines handbook. megaloblastic anaemia. Dapsone: plasma concentration of both dapsone and trimethoprim may increase with concomitant use. * Phenytoin: antifolate effect and plasma phenytoin concentration increased.

Special Notes: Clindamycin is a complementary drug when penicillin is not appropriate. Maximum dose 450 mg four times daily. IM Pain.5 mg three times daily). Contraindications: Diarrhoeal states. anaphylaxis (often related to the tartrazine in the capsule preparation). avoid rapid intravenous administration. Hepatic impairment: Severe impairment: reduce dose. Dose: Treatment of infections with susceptible organisms where allergy to penicillin and resistance to first-line drugs. agranulocytosis and thrombocytopenia). minimum dose 37. IV Hypotension. toxic epidermal necrolysis (“slow” red man syndrome). hepatotoxicity (with high doses). IV infusion or deep IM injection: Infant or Child 3. exfoliative and vesiculobullous dermatitis. sterile abscess. Pyridostigmine: antagonism of effects of pyridostigmine. Adverse effects: Common Diarrhoea (mild to severe: discontinue treatment). Rare Taste disturbance. polyarthritis. Neonate 14–28 days 3–6 mg/kg four times daily.75–6. nausea. urticaria. Renal impairment: Severe impairment: reduce dose. rash. vomiting. renal impairment. eosinophilia. up to 1. Infant or Child 3–6 mg/kg four times daily (body weight under 10 kg. including staphylococcal bone and joint infections.25 mg/kg four times daily.2 g four times daily may be used. oesophagitis. thrombophlebitis. monitor liver and renal function on prolonged therapy and in neonates and infants.6. increased up to 10 mg/kg four times daily in severe infections. blood dyscrasias (neutropenia. Oral: Neonate under 14 days 3–6 mg/kg three times daily. pruritus. Interactions with other medicines (* indicates severe): Neostigmine: antagonism of effects of neostigmine. discontinue treatment immediately if diarrhoea develops. WHO Model Formulary for Children 2010 115 . Precautions: Discontinue immediately if diarrhoea or colitis develop. avoid taking with antidiarrhoeal medication. cardiac arrest (rapid injection). avoid injections containing benzyl alcohol in neonates. StevensJohnson syndrome. Single doses over 600 mg must be given by intravenous infusion. In lifethreatening infection. peritonitis and pneumonia. Uncommon Antibiotic-associated colitis (Clostridium difficile infection). Total daily dose may alternatively be given in three divided doses. porphyria. abdominal discomfort. induration. Indications: Treatment of infections with susceptible organisms where allergy to penicillin and resistance to first-line drugs.2 Antibacterials Clindamycin ATC code: J01FF01 Capsule: 150 mg Injection: 150 mg (as phosphate)/ml Oral liquid: 15 mg/ml Antibiotic-associated colitis (Clostridium difficile infection) may be fatal. hepatic impairment. jaundice and altered liver function tests. females.

(http://www. monitor plasma vancomycin concentration (after three or four doses in normal renal function. 16th ed.6 Anti-infective medicines * Suxamethonium: enhanced effects of suxamethonium. WHO Technical Report Series. see Adverse effects). rotate infusion sites. renal impairment. IV infusion: Neonate. Antibiotic-associated colitis. Hodding JH. Geneva. Oral (using the injection solution): Infant or Child under 5 years 5 mg/kg four times daily for 7–10 days. ed. Adelaide. World Health Organization. Paediatric Formulary Committee. References: Hill SR. BMJ Group RBS Publishing.thomsonhc. Greenwood Village. eds. 5–12 years 62. Dose: Treatment of infections with susceptible organisms. Maximum daily dose 2 g. Australian medicines handbook. Infant or Child 15 mg/kg every 8 hours. THeRAPeUTIC DRUG MONITORING Plasma concentration monitoring required. adjusted according to plasma concentration. blood counts. 2009. Vancomycin ATC code: J01XA01 Powder for injection: 250 mg (as hydrochloride) in vial Special Notes: Vancomycin is a complementary antibacterial drug for use only when there is significant resistance to other drugs on the WHO Model List of essential Medicines for Children. Kouimtzi M. monitor auditory function and plasma vancomycin concentrations in renal impairment. urine analysis and renal function tests: use only in hospital setting. 2008. pre-dose (trough) concentration should be 10–15 mg/litre (15–20 mg/litre for less sensitive strains of methicillin-resistant Staphylococcus aureus). 116 WHO Model Formulary for Children 2010 . ed. Drugdex system. cardiac arrest). Kraus DM. dilute in glucose 5% or sodium chloride 0. Local antimicrobial patterns need to be taken into account. 2009. British national formulary for children 2009.5 mg four times daily for 7–10 days. 2008.who. Lexi-Comp. Indications: Treatment of infections with susceptible organisms including methicillin-resistant staphylococcal pneumonia. London.9% to concentration not > 12 mg/ml and infuse slowly IV over 30–40 minutes to reduce risk of adverse cardiac effects (hypotension. 2010. ADMINISTRATION ADVICe For intravenous infusion. Hudson. earlier if renal impairment). WHO expert committee on the selection and use of essential medicines. Stuart MC. * Vecuronium: enhanced muscle relaxant effect. Thomson Micromedex. Notes: Consider the necessity for IV administration as adequate levels can be achieved using oral formulations due to high bioavailability. Australian Medicines Handbook. Precautions: Avoid rapid infusion (risk of anaphylactoid reactions. Contraindications: History of deafness.pdf ). Taketomo CK. 2009. October 2007 (including the model list of essential medicines for children). accessed 10 February 2010). capsules should be swallowed with a glass of water. The selection and use of essential medicines: report of the WHO expert committee. endocarditis treatment and prophylaxis. Pediatric dosage handbook. PATIeNT ADVICe Patients should discontinue immediately and contact doctor if diarrhoea develops. 950 (http://www. Rossi S. Klasco RK.com. staphylococcal meningitis.int/medicines/publications/essentialmeds_committeereports/TRS_950. WHO model formulary. antibiotic-associated colitis.

severe hypotension (with shock. interstitial nephritis. Interactions with other medicines (* indicates severe): Amikacin: increased risk of nephrotoxicity and ototoxicity. Amphotericin B: possibly increased risk of nephrotoxicity. Gentamicin: increased risk of nephrotoxicity and ototoxicity. exfoliative dermatitis. NePHROTOXICITy Although reports of frequency are conflicting. chills. facial and upper torso rash. vomiting. diarrhoea and chills. vasculitis. Vancomycin alone rarely causes ototoxicity. it is more common when used with aminoglycosides and in renal impairment. Rare Ototoxicity (discontinue if tinnitus occurs). leukopenia. Streptomycin: increased risk of nephrotoxicity and ototoxicity. Oral: usually only causes gastrointestinal adverse effects if significant serum concentrations occur.g. Do not mix with other drugs in parenteral solutions.g. * Furosemide: increased risk of ototoxicity.2 Monitor plasma vancomycin concentration and renal function regularly. * Suxamethonium: enhanced effects of suxamethonium. Nitrous oxide: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. cardiac arrest). WHO Model Formulary for Children 2010 117 . Uncommon Nephrotoxicity including renal failure (see below). in renal impairment. they include fever. Paromomycin: increased risk of otoxicity.g. Thiopental: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. drug rash with eosinophilia and systemic symptoms (DReSS)). flushing of the upper body (“red man” syndrome (see below)). toxic epidermal necrolysis. anaphylaxis. Nausea. May be treated with antihistamines (e. Capreomycin: increased risk of nephrotoxicity and ototoxicity. successful administration is usually possible by increasing the infusion time (e. never give IM. in renal impairment and when given with other ototoxic drugs. risk is higher with prolonged use. Adverse effects: Common IV: local pain (may be severe). avoid extravasation. erythema. * Ciclosporin: increased risk of nephrotoxicity. OTOTOXICITy Dizziness. e. thrombophlebitis. to 120 minutes). Notes: Injection may be given orally for Clostridium difficile infection (see Dose). or both. in renal impairment. deafness may be permanent.g. linear IgA bullous disease. Blood disorders including thrombocytopenia (may be immune-mediated). superinfection. It appears to be related to vancomycin serum concentration. Halothane: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. serious skin reactions (e. ReD MAN SyNDROMe Usually due to infusion being given too quickly. flavouring syrups may be added to the solution at the time of administration. promethazine). It is not an allergic reaction although symptoms are partly due to histamine release. ADMINISTRATION Give over at least 60 minutes (rate not to exceed 10 mg/minute for doses > 500 mg) via central venous catheter if possible. Ketamine: hypersensitivity-like reactions can occur with concomitant intravenous vancomycin. Clostridium difficile-associated disease. neutropenia (more likely after at least 1 week and total dose > 25 g). which may be followed by hypotension.6. aminoglycosides. agranulocytosis. e. angioedema and itch. erythema multiforme (Stevens-Johnson syndrome). Antibacterials Renal impairment: Increase dose interval or reduce dose. vertigo and tinnitus can occur.g.

16th ed. treatment of type 2 lepra reactions (erythema nodosum leprosum). BMJ Group RBS Publishing. the nasal and other mucosa and the eyes. Thomson Micromedex. World Health Organization. eds. but facilities are not always available to process them and their reliability is often doubtful. Hodding JH. PB leprosy: one to five skin lesions. Australian medicines handbook. Drugdex system. 6. for example riding a bike or operating machinery. increase dose interval or discontinue if symptoms develop during treatment). The two forms may be distinguished by skin smears.3 Antileprosy medicines Leprosy is a chronic mycobacterial infection due to Mycobacterium leprae. Hudson. i. more than five skin lesions. Leprosy multidrug therapy should continue without interruption during a lepra reaction. characterized by fever and multiple red tender nodules. October 2007 (including the model list of essential medicines for children). 2002.int/medicines/publications/essentialmeds_committeereports/TRS_950. This reduces the frequency and severity of lepra reactions. it affects people of all ages and both sexes. Geneva. 2008. ed.thomsonhc. Combination therapy is essential to prevent the emergence of drug resistance. 2009. The incubation period between infection and appearance of leprosy is normally between 2 and 10 years. accessed 10 February 2010). which is a slow-growing intracellular bacillus that infiltrates the skin.pdf ). Rossi S. Kemp CA. Indications: Treatment of multibacillary (MB) leprosy (and where classification between MB and paucibacillary leprosy cannot be made) as part of combination therapy. patients may be classified as having either paucibacillary (PB) or multibacillary (MB) leprosy. (http://www. Adelaide. most leprosy programmes classify patients and choose a regimen based on the number of skin lesions.2. Royal Children’s Hospital. Kraus DM. London. 2010. The selection and use of essential medicines: report of the WHO expert committee. In practice. It is transmitted from person to person when bacilli are shed from the nose. The type 2 lepra reaction (erythema nodosum leprosum [eNL]). 2009. peripheral nerves. 2008. WHO expert committee on the selection and use of essential medicines. McDowell JM. Pediatric dosage handbook. Kouimtzi M. 100 mg Special Notes: Medicines used in the treatment of leprosy should never be used except in combination. 950 (http://www. this is essential to prevent the emergence of resistance. Australian Medicines Handbook.e. liver and renal impairment. Lexi-Comp. For treatment purposes. Rifampicin. Paediatric pharmacopoeia. Type 1 lepra reactions (reversal reactions) are delayed hypersensitivity reactions. 13th ed. may discolour soft contact lenses. 2009.who. MB leprosy. Reactions must always be treated promptly to prevent permanent nerve damage and disability. and are often accompanied by neuritis. ed. WHO Technical Report Series. Paediatric Formulary Committee. Greenwood Village. but may be up to 20 years. Melbourne. Lepra reactions are episodes of sudden increase in the activity of leprosy. is an antibody response to dead leprosy bacteria and occurs only in MB leprosy.com. This may occur in either PB or MB leprosy. Clofazimine ATC code: J04BA01 Capsule: 50 mg. 118 WHO Model Formulary for Children 2010 . Precautions: Pre-existing gastrointestinal symptoms (reduce dose. clofazimine and dapsone are used in the treatment of leprosy and should always be used as combination therapy. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. for about 24 hours. British national formulary for children 2009.6 Anti-infective medicines References: Hill SR. characterized by redness and swelling of pre-existing skin lesions and possible increased motor/sensory loss before ulceration of the lesion. WHO model formulary. Klasco RK. Taketomo CK. Stuart MC.

2009 (http://emedicine. Adverse effects: Uncommon Reversible discoloration of skin. Rare Headache. decreased sweat production. Type 2 lepra reaction (erythema nodosum leprosum). rash. WHO-recommended multi-drug therapy (MDT) regimens. for 24 hours. tears. 50 mg. nausea. sweat. eMedicine. 10–12 years 150 mg once a month and 50 mg on alternate days. Indications: Treatment of leprosy as part of combination therapy (paucibacillary and multibacillary). patients and their carers should be told how to recognize blood disorders and advised to seek immediate medical attention if symptoms such as fever. photosensitivity.com/article/965605-overview. Continue treatment for 12 months. for example riding a bike or operating machinery. diarrhoea. purpura. BLOOD DISORDeRS On long-term treatment. susceptibility to haemolysis including G6PD deficiency (including breastfeeding affected infants).6. WHO Model Formulary for Children 2010 119 . 100 mg Special Notes: Medicines used in the treatment of leprosy should never be used except in combination. The drug causes brownish black discoloration and dryness of skin. vomiting. Oral: Child under 10 years 100 mg once a month and 50 mg twice a week. References: estrada B. severe mucosal and submucosal oedema. gastrointestinal pain. hair. Interactions with other medicines (* indicates severe): * Phenytoin: reduced phenytoin serum concentrations and loss of phenytoin efficacy. rashes. weight loss. Oral: Child all ages 100 mg two or three times daily. mouth ulcers. gastrointestinal bleeding. pruritus. Continue treatment for 3 months. severe anaemia. Geneva. elevation of blood glucose concentration. accessed 10 February 2010). sore throat. taste disorders. conjunctiva. Continue treatment for 12 months. accessed 10 February 2010).2 Dose: Antibacterials Multibacillary leprosy (in combination with dapsone and rifampicin). New york. cornea.medscape. dizziness. Contraindications: Hypersensitivity to sulfones. Dapsone ATC code: J04BA02 Tablet: 25 mg. Combination therapy is essential to prevent the emergence of drug resistance. sputum. dry eyes. Leprosy. However. 4–6 weeks treatment may be required before effect is seen. WebMD. World Health Organization. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. This should be explained to patients starting a MDT regimen for MB leprosy. bruising or bleeding develop. Precautions: Anaemia (treat severe anaemia before therapy.int/lep/ mdt/regimens/en/. 2010 (http://www. drowsiness. this disappears within a few months after stopping treatment. and monitor blood counts during treatment). Notes: The drug is well tolerated and virtually non-toxic in the dosage used for multidrug therapy (MDT). faeces and urine. porphyria.who. dry skin. acne-like eruptions.

hepatitis. MIMS Online. Do not split the tablet. 300 mg Special Notes: Medicines used in the treatment of leprosy should never be used except in combination. jaundice. Renal impairment: Increased levels can occur in renal impairment. nervousness. Continue treatment for 12 months. Taketomo CK.thomsonhc. 2009 (http://www. Adverse effects: Common Gastrointestinal irritation.com. fever. (http://www. paraesthesia.mimsonline. reversible peripheral neuropathy. monitor liver function tests and blood counts in patients with liver disorders or on prolonged therapy. Sulfamethoxazole + trimethoprim: plasma concentration of both dapsone and trimethoprim may increase with concomitant use. Pediatric dosage handbook. Combination therapy is essential to prevent the emergence of drug resistance. 10–12 years 50 mg once daily. Oral: Child under 10 years 25 mg once daily. insomnia. jaundice and eosinophilia). Kemp CA. May be taken with food to reduce stomach upset. psychoses. Oral: Child under 10 years 25 mg once daily. Kouimtzi M. accessed 10 February 2010). 10–12 years 50 mg once daily. discolours soft contact lenses. Stuart MC. Royal Children’s Hospital. 2009. Multibacillary leprosy (in combination with rifampicin and clofazimine). “dapsone syndrome” resembling mononucleosis (rare hypersensitivity reaction with symptoms including rash. UBM Medica. Rare Haemolysis. 2002. Paediatric pharmacopoeia. 2008. ed. Trimethoprim: plasma concentration of both dapsone and trimethoprim may increase with concomitant use. Drugdex system. headache. Precautions: Hepatic impairment. tachycardia.6 Anti-infective medicines Dose: Paucibacillary leprosy (in combination with rifampicin). Continue treatment for 6 months. Kraus DM. Lexi-Comp. photosensitivity. WHO model formulary. Klasco RK. Patients with high acetylation rates or who are receiving treatment that affects acetylation may require a dosage adjustment. References: Hill SR. Continue treatment for 12 months. Indications: Treatment of leprosy as part of combination therapy (paucibacillary and multibacillary). Notes: May cause photosensitivity. 16th ed. accessed 10 February 2010). McDowell JM. Geneva. allergic dermatitis (rarely including toxic epidermal necrolysis and Stevens-Johnson syndrome). WHO Model Formulary for Children 2010 120 . Continue treatment for 6 months. Hodding JH. 2010. Rifampicin ATC code: J04AB02 Solid oral dosage form: 150 mg. eds. Greenwood Village. Interactions with other medicines (* indicates severe): Rifampicin: reduced plasma dapsone concentration.com.au/Search/Search. Sydney. methaemoglobinaemia.aspx. World Health Organization. porphyria. Thomson Micromedex. blurred vision. Hudson. agranulocytosis. 13th ed. renal impairment (if dose above 600 mg daily). Tablets should be taken whole and small doses should be made up from 25 mg tablets. Contraindications: Hypersensitivity to rifamycins. Melbourne.

Dose: Paucibacillary leprosy (in combination with dapsone). Continue treatment for 12 months. influenza-like syndrome. magnesium hydroxide): reduced absorption of rifampicin. acute renal failure. oedema. Ciclosporin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration).2 IMPORTANT Advise patients on hormonal contraceptives to use additional means. saliva and sputum coloured orange-red. Diazepam: metabolism of diazepam accelerated (reduced plasma concentration). Amitriptyline: plasma concentration of amitriptyline possibly reduced. headache. leukopenia. Continue treatment for 6 months. fever. monitor liver function. tears. myopathy. diarrhoea. Digoxin: plasma concentration of digoxin possibly reduced. collapse. avoid or do not exceed 8 mg/kg daily. 121 WHO Model Formulary for Children 2010 . Hydrocortisone: accelerated metabolism of hydrocortisone (reduced effect). Dapsone: reduced plasma dapsone concentration. vomiting. exfoliative dermatitis. Continue treatment for 12 months. PATIeNT ADVICe Take dose at least 30 minutes before a meal. Chloramphenicol: accelerated metabolism of chloramphenicol (reduced plasma chloramphenicol concentration). Continue treatment for 6 months. rashes. since absorption is reduced by food. Oral: Child under 10 years 300 mg once a month. 10–12 years 450 mg once a month. Contraceptives. menstrual disturbances. respiratory symptoms. vomiting. malaise or jaundice develop. Rare Alterations of liver function. Antacids (aluminium hydroxide. haemolysis or thrombocytopenia. potentially fatal hepatitis (dose related. Adverse effects: Common Urine. toxic epidermal necrolysis. pemphigoid reactions. Oral: Child under 10 years 300 mg once a month. anorexia. Interactions with other medicines (* indicates severe): * * * * * * * Abacavir: plasma concentration of abacavir possibly reduced. haemolytic anaemia. Haloperidol: accelerated metabolism of haloperidol (reduced plasma haloperidol concentration). drowsiness. muscular weakness. 10–12 years 450 mg once a month. oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect). Doxycycline: plasma doxycycline concentration possibly reduced. jaundice. antibiotic-associated colitis. Fluconazole: accelerated metabolism of fluconazole (reduced plasma concentration). resulting in renal impairment. Glibenclamide: possibly accelerated metabolism (reduced effect) of glibenclamide. do not exceed maximum dose of 600 mg daily). Dexamethasone: accelerated metabolism of dexamethasone (reduced effect). eosinophilia. Hepatic impairment: Impaired elimination. Antibacterials NOTe Resumption of rifampicin treatment after a long interval may cause serious immunological reactions.6. discontinue permanently if serious adverse effects occur. shock. Multibacillary leprosy (in combination with dapsone and clofazimine). Efavirenz: reduced plasma concentration of efavirenz (increase efavirenz dose). thrombocytopenic purpura. nausea. LIVeR DISORDeRS Patients or their carers 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.

(http://www. prevent the development of drug resistance (by using a combination of drugs) 5. Propranolol: metabolism of propranolol accelerated (significantly reduced plasma concentration).2. Klasco RK. * Nifedipine: accelerated metabolism of nifedipine (plasma concentration significantly reduced). * Nevirapine: reduced plasma concentration of nevirapine (avoid concomitant use). British national formulary for children 2009. 6. Paediatric Formulary Committee. Avoid contact during dosing/preparation due to risk of contact sensitization. Notes: Capsules should be swallowed whole. Treatment outcomes in children are generally good. * Nelfinavir: plasma concentration of nelfinavir significantly reduced (avoid concomitant use).com. even in young and immunocompromised children.thomsonhc. * Saquinavir: plasma concentration of saquinavir significantly reduced. London. References: Hill SR. 122 WHO Model Formulary for Children 2010 . accessed 10 February 2010). TB meningitis and miliary TB) occurs more frequently in young children (less than 3 years old). Both the bacillary load and the type of disease may influence the effectiveness of treatment regimens. They also develop extrapulmonary TB more often than adults. eds. Stuart MC. Zidovudine: avoidance of rifampicin advised by manufacturer of zidovudine.6 Anti-infective medicines * Indinavir: metabolism accelerated by rifampicin (plasma indinavir concentration reduced. cure the patient of tuberculosis (TB) (by rapidly eliminating most of the bacilli) 2. Studies demonstrate that very few of the drug adverse events more commonly reported in adults occur as commonly in children. Levothyroxine: accelerated metabolism of levothyroxine (may increase levothyroxine requirements in hypothyroidism). Kouimtzi M. 2010. when used in doses suggested in WHO treatment regimens. * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). * Verapamil: accelerated metabolism of verapamil (plasma concentration significantly reduced). avoid concomitant use. 2009. * Phenytoin: accelerated metabolism of phenytoin (reduced plasma concentration). * Quinidine: accelerated metabolism of quinidine (reduced plasma quinidine concentration). * Lopinavir: reduced plasma concentration of lopinavir (avoid concomitant use). * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). Geneva. World Health Organization. * Warfarin: accelerated metabolism of warfarin (reduced anticoagulant effect). avoid concomitant use). prevent death from active TB or its late effects 3. Thomson Micromedex. * Prednisolone: accelerated metabolism of prednisolone (reduced effect). WHO model formulary.4 Antituberculosis medicines Antituberculosis treatment in children The main objectives of antituberculosis treatment are to: 1. BMJ Group RBS Publishing. 2008. provided treatment is started promptly. Children with TB usually have paucibacillary (low organism numbers) pulmonary disease. Severe and disseminated TB (e. ed. prevent relapse of TB (by eliminating the dormant bacilli) 4. decrease TB transmission to others.g. Greenwood Village. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). Drugdex system.

severe renal impairment. in combination with other drugs. There is limited experience with the safety of many of these drugs in children. Recommended dosages Note that dose recommendations for several first-line anti-TB medications have recently been revised. because current evidence suggests that serum drug levels may be lower in children than in adults. Fewer drugs are generally used in this phase because the risk of acquiring drug resistance is low. Second-line drugs are required to manage these infections. Three times weekly therapy is not recommended in settings where there is high HIV-prevalence. Ethambutol ATC code: J04AK02 Oral liquid: 25 mg/ml Tablet: 100 mg. Precautions: Visual disturbances. every effort should be made to find the most likely cause for the failure or relapse. Recommended doses for several medications have been increased. Contraindications: Optic neuritis. The purpose of the intensive phase is to rapidly eliminate the majority of organisms and to prevent the emergence of drug resistance.2 Antibacterials Treatment regimens Anti-TB treatment is divided into two phases: an intensive phase and a continuation phase. Two or more new drugs should be added to any re-treatment regimen in cases of genuine failure of treatment. No drug is absolutely contraindicated in children. Daily treatment is preferred for therapy. as most of the organisms have already been eliminated. WHO Model Formulary for Children 2010 123 . or for HIV-positive individuals. but treatment can be given three times weekly provided the treatment is directly observed. Children with TB who are co-infected with HIV HIV-infected children are at greater risk for TB infection and TB disease than children not infected with HIV. Management of relapse and drug-resistant TB in children In childhood TB cases when anti-TB treatment fails or a relapse occurs. 400 mg (hydrochloride) Indications: Treatment of tuberculosis. Mycobacterial culture and drug susceptibility testing should be performed for all re-treatment cases. This phase uses a greater number of drugs than the continuation phase. The purpose of the continuation phase is to eradicate the dormant organisms. benefits have to be carefully weighed against risks. HIV-infected children also have a poorer response to TB treatment and higher rates of mortality associated with TB disease. Children with TB must be followed up regularly and have dosages adjusted for weight gained. however.6. These drugs are indicated for the treatment of multidrug-resistant TB in children and should only be used in specialized centres. renal impairment. VISUAL DISTURBANCeS Patients should report visual disturbances immediately and discontinue treatment. Drug-resistant TB is a public health problem in many countries. The majority of deaths in HIV-infected children being treated for TB occur in the first 2 months of TB treatment during the intensive phase.

1997(1):12–15. 2010.who. Renal impairment: Mild/moderate: reduce dose. 2009 (http://www. Red Book: 2009 report of the committee on infectious diseases. Geneva. Thomson Micromedex. accessed 10 February 2010). weakness. 1998. Patients or their carers must be advised to report any prodromal symptoms of hepatitis. Hodding JH.cdc. American Thoracic Society. 2009. Should ethambutol be recommended for routine treatment of tuberculosis in children? A review of the literature. 124 WHO Model Formulary for Children 2010 . gout. Kraus DM. prompt withdrawal may prevent blindness)). World Health Organization. 4th ed. accessed 10 February 2010). elk Grove Village. 28th ed. Contraindications: Drug-induced hepatic disease. BMJ Group RBS Publishing. 2009. history of psychosis.6 Anti-infective medicines Dose: Treatment of tuberculosis. Graham SM et al. diabetes mellitus or HIV infection. CDC. slow acetylator status. prophylaxis of tuberculosis. Hudson. Adverse effects: Uncommon Optic neuritis (reduced visual acuity and red/green colour blindness (early changes usually reversible.htm. usually occurs within the first 3 months of treatment. 79:274–278.stoptb. 2006 (http://www. thrombocytopenia. 2009. (http://www. World Health Organization. NOTe Serum ethambutol concentrations should be monitored. accessed 10 February 2010). World Health Organization. Pediatric dosage handbook. Treatment of tuberculosis. malaise. accessed 10 February 2010). and Infectious Diseases Society of America. Dosing instructions for the use of currently available fixed-dose combination TB medicines for children. porphyria. Severe: avoid. The doses in this monograph are based on the 2009 WHO “Dosing instructions for the use of currently available fixed-dose combination TB medicines for children”. Oral: Infant or Child 20 mg/kg (range 15–25 mg/kg) once daily. Treatment of tuberculosis guidelines.who. Geneva. accessed 10 February 2010). in combination with other drugs. immediately. London. nausea or vomiting. Greenwood Village. Lexi-Comp. Paediatric Formulary Committee. urticaria. epilepsy. Taketomo CK. such as fatigue.pdf. Rare Rash. they may differ from other paediatric TB treatment guidelines. anorexia. Special Notes: Also referred to as INH. References: American Academy of Pediatrics. ed.int/tb/publications/2006/en/index. Geneva. gov/mmwr/preview/mmwrhtml/rr5211a1. risk of peripheral neuritis (prophylactic pyridoxine recommended) in patients with malnutrition. Indications: Treatment of tuberculosis. Precautions: Hepatic impairment. peripheral neuritis (especially in legs). pdf.thomsonhc. Therefore. American Academy of Pediatrics. monitor plasma ethambutol concentration. Klasco RK. Trebucq A. pruritus. 2003 (http://www. renal impairment. International Journal of Tuberculosis and Lung Disease. chronic renal failure. 2010 (http://whqlibdoc.int/ publications/2010/9789241547833_eng.org/gdf/assets/documents/Interim Paediatric FDCs detailed dosing instructions_Sept09. 300 mg Tablet (scored): 50 mg Severe and sometimes fatal hepatitis may occur. Drugdex system. 16th ed. British national formulary for children 2009. Ethambutol efficacy and toxicity: literature review and recommendations for daily and intermittent dosage in children.com. ethambutol in tuberculosis: time to reconsider? Archives of Disease in Childhood. in combination with other drugs.html. if creatinine clearance less than 30 ml/minute Isoniazid ATC code: J04AC01 Oral liquid: 10 mg/ml Tablet: 100 mg.

malaise or jaundice develop. A literature review of the pharmacokinetics of rifampicin. Therefore. constipation. hypersensitivity reactions (including fever. mouth. Red Book: 2009 report of the committee on infectious diseases. Notes: PATIeNT ADVICe Isoniazid should be taken on an empty stomach. if taken with food to reduce gastrointestinal irritation. elk Grove Village. difficulty with micturition. The doses in this monograph are based on the 2009 WHO “Dosing instructions for the use of currently available fixed-dose combination TB medicines for children”. hyper-reflexia. erythema multiforme and purpura). seizures. Unpublished 2007. Diazepam: metabolism of diazepam inhibited. pellagra. isoniazid and pyrazinamide and a recommendation for the dosages to be used in children. dry Rare Hepatotoxicity (withdraw treatment). they may differ from other paediatric TB treatment guidelines. * Phenytoin: metabolism of phenytoin inhibited (enhanced effect). Geneva. American Academy of Pediatrics. gynaecomastia. Halothane: possible potentiation of isoniazid hepatotoxicity.6. Antacids (aluminium hydroxide. 2009. Donald PR. optic neuritis.2 Antibacterials LIVeR DISORDeRS Patients or their carers should be told how to recognize signs of liver disease and be advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea. * Ethosuximide: metabolism of ethosuximide inhibited (increased plasma ethosuximide concentration and risk of toxicity). rashes. References: American Academy of Pediatrics. blood disorders (including agranulocytosis. World Health Organization. gastrointestinal pain. risk of peripheral neuropathy. Hepatic impairment: Use with caution. Thiopental: possible potentiation of isoniazid hepatotoxicity. hyperglycaemia. Oral: Infant or Child greater than 3 months 10 mg/kg (range 10–15 mg/kg) once daily (maximum 300 mg daily). haemolytic anaemia. vomiting. p-Aminosalicylic acid: increased plasma concentration of isoniazid. Nitrous oxide: possible potentiation of isoniazid hepatotoxicity. 2 months. World Health Organization. Hepatotoxicity of antituberculosis agents in children: a literature review. aplastic anaemia). Geneva. Renal impairment: Severe: reduce dose to maximum 4 mg/kg daily or 200 mg daily. Donald PR. Cycloserine: increased risk of CNS toxicity. diarrhoea. toxic psychoses. 28th ed. Unpublished 2009. WHO Model Formulary for Children 2010 125 . peripheral neuropathy. * Carbamazepine: increased plasma carbamazepine concentration (also isoniazid hepatotoxicity possibly increased). joint pain. Interactions with other medicines (* indicates severe): Amitriptyline: increased plasma concentration of isoniazid. magnesium hydroxide): reduced absorption of isoniazid. systemic lupus erythematosus-like syndrome. prophylaxis of tuberculosis. Ketamine: possible potentiation of isoniazid hepatotoxicity. monitor liver function regularly and frequently in the first Adverse effects: Uncommon Nausea. vomiting. oral absorption and bioavailability may be impaired. Dose: Treatment of tuberculosis (in combination with other drugs).

2010. and Infectious Diseases Society of America. The doses in this monograph are based on the 2009 WHO “Dosing instructions for the use of currently available fixed-dose combination TB medicines for children”. Pediatric dosage handbook. vomiting. dysuria. idiosyncratic hepatotoxicity more common. liver failure). may change suddenly). Tropical Medicine and International Health. 2009. World Health Organization. Zidovudine: decreased serum concentration and efficacy of pyrazinamide. porphyria. Taketomo CK. pdf. vomiting. Thomson Micromedex. 14(11):1329–1337.cdc. accessed 10 February 2010). Geneva. Dose: Treatment of tuberculosis. Pyrazinamide ATC code: J04AK01 Oral liquid: 30 mg/ml Tablet: 400 mg Tablet (dispersible): 150 mg Tablet (scored): 150 mg Special Notes: Also referred to as PZA. Hodding JH. accessed 10 February 2010). World Health Organization. gout. Lexi-Comp. Severe hepatic impairment: avoid use. gout.thomsonhc. Contraindications: Severe hepatic impairment. 126 WHO Model Formulary for Children 2010 .com. hepatotoxicity (including fever. Renal impairment: Severe impairment: reduce dose. Oral: Infant or Child 35 mg/kg (range 30–40 mg/kg) once daily. photosensitivity. accessed 10 February 2010). Maximum 2 g daily. 16th ed. Rifampicin: risk of severe hepatic injury.stoptb. Rare Flushing. Kraus DM. Hepatic impairment: Monitor hepatic function. Indications: Treatment of tuberculosis. Greenwood Village. Frydenberg AR. British national formulary for children 2009. LIVeR DISORDeRS Patients or their carers should be told how to recognize signs of liver disease and be advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea.who. Toxicity of first-line drugs for treatment of tuberculosis in children: review. renal impairment. they may differ from other paediatric TB treatment guidelines. 4th ed. accessed 10 February 2010). splenomegaly. Precautions: Hepatic impairment. anorexia. Klasco RK. gov/mmwr/preview/mmwrhtml/rr5211a1.6 Anti-infective medicines Dosing instructions for the use of currently available fixed-dose combination TB medicines for children. sideroblastic anaemia. malaise or jaundice develop. 2009. Treatment of tuberculosis. Graham SM. (http://www. Treatment of tuberculosis guidelines. 2003 (http://www. diabetes mellitus (monitor blood glucose. arthralgia. in combination with other medicines. Therefore. Interactions with other medicines (* indicates severe): * Ciclosporin: reduced ciclosporin serum concentrations and potentially reduced immunosuppressive efficacy.org/gdf/assets/documents/Interim Paediatric FDCs detailed dosing instructions_Sept09. 2009 (http://www. Hudson. Uncommon Rash. Paediatric Formulary Committee. in combination with other medicines. Adverse effects: Common Nausea. 2009. concurrent medications associated with liver injury (particulary rifampicin). ed.htm. 2010 (http://whqlibdoc.pdf. CDC. jaundice. American Thoracic Society. BMJ Group RBS Publishing.int/ publications/2010/9789241547833_eng. London. Drugdex system. Geneva. hepatomegaly.

WHO Model Formulary for Children 2010 127 . 16th ed. ed. 2009. jaundice. Lexi-Comp.who. fever. CDC. Contraindications: Hypersensitivity to rifamycins. Greenwood Village.cdc. tears. eosinophilia. London. Kraus DM. menstrual disturbances. leukopenia. Oxford. 300 mg Special Notes: Also referred to as rifampin. discolours soft contact lenses. NOTe Resumption of rifampicin treatment after a long interval may cause serious immunological reactions. porphyria. they may differ from other paediatric TB treatment guidelines. 3rd ed. gov/mmwr/preview/mmwrhtml/rr5211a1. Hepatic impairment: Impaired elimination. 2006 (http:// whqlibdoc. saliva and sputum coloured orange-red. accessed 10 February 2010). respiratory symptoms. Red Book: 2009 report of the committee on infectious diseases. elk Grove Village.com. World Health Organization.pdf. World Health Organization. Radcliffe Publishing.int/publications/2006/9241546956_eng. muscular weakness. shock. The renal drug handbook. accessed 10 February 2010). accessed 10 February 2010). jaundice. 4th ed. Maximum 600 mg daily. Guidelines for the programmatic management of drug-resistant tuberculosis. drowsiness. malaise or jaundice develop.2 References: Antibacterials American Academy of Pediatrics. Indications: Treatment of tuberculosis. collapse. American Thoracic Society. rashes. Renal impairment: Dose reduction not necessary. discontinue permanently if serious adverse effects occur. Adverse effects: Common Urine.htm. 2009. Pediatric dosage handbook. Treatment of tuberculosis guidelines. haemolytic anaemia. 2010. 2009 (http://www. 2010 (http://whqlibdoc. pemphigoid reactions. pdf. Paediatric Formulary Committee.pdf. Drugdex system.stoptb. Klasco RK. LIVeR DISORDeRS Patients or their carers should be told how to recognize signs of liver disease and be advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea. Oral: Infant or Child 15 mg/kg (range 10–20 mg) once daily. resulting in renal impairment. vomiting. 28th ed. Currie A. Taketomo CK.who. liver function tests and blood counts required in liver disorders and on prolonged therapy. The doses in this monograph are based on the 2009 WHO “Dosing instructions for the use of currently available fixed-dose combination TB medicines for children”. 2009. thrombocytopenic purpura. 2009. Rifampicin ATC code: J04AB02 Oral liquid: 20 mg/ml Solid oral dosage form: 150 mg. Therefore. potentially fatal hepatitis. in combination with other drugs. Hodding JH. Treatment of tuberculosis. acute renal failure. diarrhoea. haemolysis or thrombocytopenia. exfoliative dermatitis. IMPORTANT Advise patients on hormonal contraceptives to use additional means. accessed 10 February 2010). 2003 (http://www. BMJ Group RBS Publishing. vomiting.6. influenza-like syndrome. British national formulary for children 2009.org/gdf/assets/documents/Interim Paediatric FDCs detailed dosing instructions_Sept09.thomsonhc. monitor liver function. accessed 10 February 2010). Rare Alterations of liver function. (http://www. Geneva. eds. Precautions: Hepatic impairment. Geneva. avoid or do not exceed 8 mg/kg daily. myopathy.int/ publications/2010/9789241547833_eng. anorexia. Ashley C. Thomson Micromedex. American Academy of Pediatrics. Dose: Treatment of tuberculosis. headache. nausea. in combination with other drugs. toxic epidermal necrolysis. Geneva. Hudson. and Infectious Diseases Society of America. Dosing instructions for the use of currently available fixed-dose combination TB medicines for children. World Health Organization. oedema.

Diazepam: metabolism of diazepam accelerated (reduced plasma concentration). Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). Lopinavir: reduced plasma concentration of lopinavir (avoid concomitant use). Warfarin: accelerated metabolism of warfarin (reduced anticoagulant effect). Phenytoin: accelerated metabolism of phenytoin (reduced plasma concentration). Verapamil: accelerated metabolism of verapamil (plasma concentration significantly reduced). as absorption is reduced when taken with food. avoid concomitant use). Digoxin: plasma concentration of digoxin possibly reduced. Zidovudine: avoidance of rifampicin advised by manufacturer of zidovudine. Levothyroxine: accelerated metabolism of levothyroxine (may increase levothyroxine requirements in hypothyroidism). Prednisolone: accelerated metabolism of prednisolone (reduced effect). Nifedipine: accelerated metabolism of nifedipine (plasma concentration significantly reduced). Haloperidol: accelerated metabolism of haloperidol (reduced plasma haloperidol concentration). Glibenclamide: possibly accelerated metabolism (reduced effect) of glibenclamide. Fluconazole: accelerated metabolism of fluconazole (reduced plasma concentration). Quinidine: accelerated metabolism of quinidine (reduced plasma quinidine concentration). Amitriptyline: plasma concentration of amitriptyline possibly reduced. Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). Capsules should be swallowed whole. Efavirenz: reduced plasma concentration of efavirenz (increase efavirenz dose). Indinavir: metabolism accelerated by rifampicin (plasma indinavir concentration reduced. Nevirapine: reduced plasma concentration of nevirapine (avoid concomitant use). Saquinavir: plasma concentration of saquinavir significantly reduced. Hydrocortisone: accelerated metabolism of hydrocortisone (reduced effect). 128 WHO Model Formulary for Children 2010 . Ciclosporin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect). Avoid contact during dosing/preparation due to risk of contact sensitization. magnesium hydroxide): reduced absorption of rifampicin. Propranolol: metabolism of propranolol accelerated (significantly reduced plasma concentration). Chloramphenicol: accelerated metabolism of chloramphenicol (reduced plasma chloramphenicol concentration). Nelfinavir: plasma concentration of nelfinavir significantly reduced (avoid concomitant use). avoid concomitant use. Dexamethasone: accelerated metabolism of dexamethasone (reduced effect).6 Anti-infective medicines Abacavir: plasma concentration of abacavir possibly reduced. Doxycycline: plasma doxycycline concentration possibly reduced. Contraceptives. Antacids (aluminium hydroxide. Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). Dapsone: reduced plasma dapsone concentration. Interactions with other medicines (* indicates severe): * * * * * * * * * * * * * * * * * * * * * Notes: PATIeNT ADVICe Take dose at least 30 minutes before a meal.

* Furosemide: increased risk of ototoxicity. Red Book: 2009 report of the committee on infectious diseases. thrombocytopenia. * Ciclosporin: increased risk of nephrotoxicity. Dose: Treatment of tuberculosis. Monitor plasma concentrations. Contraindications: Hearing disorders. accessed 10 February 2010). Dosing instructions for the use of currently available fixed-dose combination TB medicines for children. vomiting.htm.who. avoid use if possible). Treatment of tuberculosis guidelines. 2010. infants (monitor renal. Klasco RK. paraesthesia of mouth. Severe: avoid use. haemolytic anaemia. (http://www. 28th ed. BMJ Group RBS Publishing. 2003 (http://www. Hodding JH. * Cisplatin: increased risk of nephrotoxicity and possibly of ototoxicity. Renal impairment: Mild to moderate: extend dosing frequency. 16th ed. American Thoracic Society. and Infectious Diseases Society of America. and plasma streptomycin concentrations). pdf. Interactions with other medicines (* indicates severe): * Alcuronium: enhanced muscle relaxant effect. Treatment of tuberculosis. myasthenia gravis. Deep IM injection: Infant or Child 20–40 mg/kg once daily. Hudson. accessed 10 February 2010). 4th ed. CDC. World Health Organization. Adverse effects: Common Pain and abscess at injection site. Kraus DM. gov/mmwr/preview/mmwrhtml/rr5211a1. Amphotericin B: increased risk of nephrotoxicity. British national formulary for children 2009. agranulocytosis. Indications: Treatment of tuberculosis. hypersensitivity to aminoglycoside antibiotics. ed.com. auditory and vestibular function. Geneva. pre-dose (trough) concentration should be less than 5 mg/litre (less than 1 mg/litre in renal impairment).int/ publications/2010/9789241547833_eng. Precautions: Children (painful injection.cdc. World Health Organization. 2009. WHO Model Formulary for Children 2010 129 . hearing loss. Greenwood Village. * Pyridostigmine: antagonism of effect of pyridostigmine. aplastic anaemia. neuromuscular disorders. Uncommon Vestibular and auditory damage. renal impairment. Taketomo CK. Drugdex system. nephrotoxicity. * Neostigmine: antagonism of effect of neostigmine. 2009 (http://www. in combination with other drugs. Streptomycin ATC code: J01GA01 Powder for injection: 1 g (as sulfate) in vial Special Notes: Intramuscular injection of streptomycin is very painful. Maximum 1 g daily. rash.org/gdf/assets/documents/Interim Paediatric FDCs detailed dosing instructions_Sept09. hypomagnesaemia on prolonged therapy. elk Grove Village. 2009. nausea. London. vertigo. American Academy of Pediatrics. NOTe 1 hour (peak) concentration should be 15–40 mg/litre. accessed 10 February 2010). in combination with other drugs.stoptb. 2010 (http://whqlibdoc. Thomson Micromedex. Geneva.thomsonhc. tinnitus. Rare Antibiotic-associated colitis. Lexi-Comp. hypersensitivity reactions (withdraw treatment). accessed 10 February 2010).2 References: Antibacterials American Academy of Pediatrics.6. Paediatric Formulary Committee. Pediatric dosage handbook. 2009.pdf.

pre-existing vestibular or auditory impairment. 500 mg. Dose: Treatment of multidrug-resistant tuberculosis. Adverse effects: Common Ototoxicity. Interactions with other medicines (* indicates severe): * Alcuronium: enhanced effects of alcuronium. accessed 10 February 2010). (http://www. Amphotericin B: increased risk of nephrotoxicity. American Thoracic Society. Geneva. NOTe Pre-dose (trough) concentration should be less than 5 mg/litre for once daily dosing. Red Book: 2009 report of the committee on infectious diseases. subsequent doses and/or dosing intervals should be adjusted. World Health Organization. Geneva. Greenwood Village. Target amikacin serum levels for once daily dosing: pre-dose (trough) concentration should be < 5 mg/litre. in combination with other drugs. Renal impairment: Dosage adjustment is required in patients with renal impairment. 4th ed. and Infectious Diseases Society of America. Notes: ReCONSTITUTION AND ADMINISTRATION Reconstitute following manufacturer’s instructions. in combination with other drugs. Vancomycin: increased risk of nephrotoxicity and ototoxicity. Drugdex system. Uncommon Rash. References: American Academy of Pediatrics. concomitant neurotoxic. dehydration. 16th ed. Taketomo CK. Precautions: Renal impairment.htm.pdf. urticaria and alopecia. 2003 (http://www. Treatment of tuberculosis guidelines. American Academy of Pediatrics. gov/mmwr/preview/mmwrhtml/rr5211a1. inject deep intramuscularly into a large muscle mass.thomsonhc.pdf. 130 WHO Model Formulary for Children 2010 . * Vecuronium: enhanced muscle relaxant effect. neonates and infants. CDC. IV or IM: Infant or Child 15–30 mg/kg once daily (maximum 1 g). accessed 10 February 2010). myasthenia gravis. 1 g in vial Special Notes: Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. For IM injection. 2010.int/ publications/2010/9789241547833_eng. Rare exfoliative dermatitis. accessed 10 February 2010). Amikacin ATC code: J01GB06 Powder for injection: 100 mg. Rotate injection sites. Treatment of tuberculosis. Administer at a concentration not to exceed 500 mg/mL.who. Kraus DM. ototoxic or nephrotoxic drugs. accessed 10 February 2010). purpura. Hepatic impairment: Dose reduction not necessary. elk Grove Village. Adjustment may be based on amikacin serum levels.com. 2010 (http://whqlibdoc. 2006 (http:// whqlibdoc. Guidelines for the programmatic management of drug-resistant tuberculosis.int/publications/2006/9241546956_eng. myasthenia gravis. 2009. concomitant anaesthesia or neuromuscular blockers.6 Anti-infective medicines * Suxamethonium: enhanced muscle relaxant effect. World Health Organization. conditions characterized by muscle weakness. Patients should receive the usual loading dose. Contraindications: Hypersensitivity to amikacin or aminoglycoside antibiotics. 28th ed.who. ed. Lexi-Comp.cdc. Hodding JH. 2009. however. Indications: Treatment of multidrug-resistant tuberculosis. nephrotoxicity. Thomson Micromedex. Hudson. Pediatric dosage handbook. Klasco RK.

2 Antibacterials * Benzylpenicillin: concomitant penicillin and aminoglycoside therapy has been reported to result in inactivation of the aminoglycoside. Drugdex system. simultaneous administration of these agents with capreomycin is not recommended. Kraus DM. 4th ed. amikacin. Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. 2010. gentamicin.pdf. Paediatric Formulary Committee. Special Notes: Monitor body weight monthly and adjust dose accordingly. tobramycin. American Academy of Pediatrics.com.9% or compound sodium lactate. * Suxamethonium: enhanced effects of suxamethonium. 2009. accessed 10 February 2010). and Infectious Diseases Society of America. Red Book: 2009 report of the committee on infectious diseases. Preferable to separate administration by 1 hour. * Neostigmine: antagonism of effects of neostigmine. British national formulary for children 2009. renal impairment. WHO Model Formulary for Children 2010 131 . Taketomo CK. Contraindications: Hypersensitivity to aminoglycoside antibiotics. 2010 (http://whqlibdoc. renal injury. dilute with glucose 5% or sodium chloride 0. Pediatric dosage handbook. For intravenous infusion. * Pyridostigmine: antagonism of effects of pyridostigmine. CDC. American Academy of Pediatrics. concomitant use with streptomycin or viomycin. vancomycin. American Thoracic Society. 2009. in combination with other drugs. Greenwood Village.int/ publications/2010/9789241547833_eng. World Health Organization. colistin sulfate. accessed 10 February 2010). 28th ed. viomycin) also have similar and sometimes irreversible toxic effects. Use with non-antituberculosis drugs (polymyxin A sulfate.who. Since other parenteral antituberculosis agents (streptomycin. particularly on cranial nerve VIII and renal function. Treatment of tuberculosis. * Ciclosporin: increased risk of nephrotoxicity. London. Risk of additional cranial nerve VIII impairment or renal injury. 2009. ed. should be undertaken only with great caution. Treatment of tuberculosis guidelines. myasthenia gravis. * Vecuronium: enhanced effects of vecuronium. 16th ed.cdc. gov/mmwr/preview/mmwrhtml/rr5211a1. Geneva. Precautions: Auditory impairment. Lexi-Comp. kanamycin and neomycin) having ototoxic or nephrotoxic potential. elk Grove Village. accessed 10 February 2010). 2003 (http://www. Thomson Micromedex.6. References: Capreomycin ATC code: J04AB30 Powder for injection: 1 g in vial The use of capreomycin in patients with renal insufficiency or pre-existing auditory impairment must be undertaken with great caution. Hudson.thomsonhc. Klasco RK. Notes: ADMINISTRATION Administer by intramuscular injection or slow intermittent intravenous infusion over 30 minutes at a final concentration not to exceed 10 mg/ml. Indications: Treatment of multidrug-resistant tuberculosis. Hodding JH.htm. Vancomycin: increased risk of nephrotoxicity and ototoxicity. * Furosemide: increased risk of ototoxicity. BMJ Group RBS Publishing. (http://www. * Cisplatin: increased risk of nephrotoxicity and possibly of ototoxicity.

accessed 10 February 2010). 2009. nephrotoxicity). elk Grove Village. In all degrees of impairment.9% sodium chloride or water for injection. hypomagnesaemia. nephrotoxicity). * Fazadinium: enhanced or prolonged neuromuscular blockade. electrolyte disturbances (including hypokalaemia. 28th ed. Capastat Product Information. * Rapacuronium: enhanced or prolonged neuromuscular blockade. * Vecuronium: enhanced or prolonged neuromuscular blockade.nlm. nephrotoxicity. Uncommon Urticaria and rash.6 Anti-infective medicines Dose: Treatment of multidrug-resistant tuberculosis. IV or IM: Child 15–30 mg/kg (maximum 1 g) once daily. nephrotoxicity). * Gallamine: enhanced or prolonged neuromuscular blockade. Renal impairment: Use with caution. * Rocuronium: enhanced or prolonged neuromuscular blockade. nephrotoxicity). Red Book: 2009 report of the committee on infectious diseases. * Cisatracurium: enhanced or prolonged neuromuscular blockade. Aspen. 132 WHO Model Formulary for Children 2010 . Netilmicin: netilmicin toxicity (ototoxicity. Administer by deep intramuscular injection into a large muscle or dilute further with 0. * Metocurine: enhanced or prolonged neuromuscular blockade. * Suxamethonium: enhanced or prolonged neuromuscular blockade. Streptomycin: streptomycin toxicity (ototoxicity. * Doxacurium: enhanced or prolonged neuromuscular blockade.cfm?id=16185. hypocalcaemia. leukopenia.nih. * Hexafluorenium: enhanced or prolonged neuromuscular blockade. * Tubocurarine: enhanced or prolonged neuromuscular blockade. dosing frequency should be reduced to 2–3 times weekly. American Academy of Pediatrics. Tobramycin: tobramycin toxicity (ototoxicity. nephrotoxicity). Kanamycin: kanamycin toxicity (ototoxicity. * Pancuronium: enhanced or prolonged neuromuscular blockade. in combination with other drugs. Amikacin: amikacin toxicity (ototoxicity. nephrotoxicity). hyponatraemia and hypochloraemia). eosinophilia.9% sodium chloride and infuse over 60 minutes. References: American Academy of Pediatrics. Notes: ADMINISTRATION Reconstitute with 0. Gentamicin: gentamicin toxicity (ototoxicity. neuromuscular blockade. Rare Thrombocytopenia. 2010 (http://dailymed. Adverse effects: Common Injection site pain.gov/dailymed/drugInfo. * Mivacurium: enhanced or prolonged neuromuscular blockade. * Pipecuronium: enhanced or prolonged neuromuscular blockade. * Atracurium: enhanced or prolonged neuromuscular blockade. ototoxicity. changes in liver function tests. Interactions with other medicines (* indicates severe): * Alcuronium: enhanced or prolonged neuromuscular blockade. Hepatic impairment: Dose reduction not necessary.

Measure 3–4 hours after dose. Pediatric dosage handbook. Treatment of tuberculosis guidelines. vertigo. psychosis.thomsonhc. Klasco RK. Klasco RK. in combination with other drugs. changes in liver function tests. 2009. Indications: Treatment of multidrug-resistant tuberculosis.2 Antibacterials Guidelines for the programmatic management of drug-resistant tuberculosis.int/publications/2006/9241546956_eng. Paediatric Formulary Committee. elk Grove Village. World Health Organization. depression. Lexi-Comp. CDC. drowsiness. CDC.cdc. Adverse effects: Common Neurological (headache. in combination with other drugs. 2003 (http://www. Treatment of tuberculosis. and Infectious Diseases Society of America. Geneva. Taketomo CK. seizures. dizziness.com. (http://www. Precautions: Neuropsychiatric status assessed at least monthly. accessed 10 February 2010). Notes: Penetrates the cerebrospinal fluid. Hudson. Geneva. NOTe Serum concentration measurements aiming for a peak concentration of 20–35 mg/ml are often useful in determining the optimum dose for a given patient. accessed 10 February 2010). 2006 (http:// whqlibdoc. Maximum 1 g daily. gov/mmwr/preview/mmwrhtml/rr5211a1.cdc. American Thoracic Society. American Thoracic Society. American Academy of Pediatrics. confusion. accessed 10 February 2010).com. 2010 (http://whqlibdoc.int/publications/2006/9241546956_eng. accessed 10 February 2010).who. 4th ed. Treatment of tuberculosis. porphyria.pdf. Renal impairment: Avoid use in all degrees of renal impairment. 2010. 2009. accessed 10 February 2010). tremor. severe anxiety. depression). World Health Organization. severe renal impairment. Uncommon Rash. heart failure. Guidelines for the programmatic management of drug-resistant tuberculosis. gov/mmwr/preview/mmwrhtml/rr5211a1.htm.pdf. Geneva.who. Drugdex system. Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. 2010.int/ publications/2010/9789241547833_eng. 4th ed.who. accessed 10 February 2010). and Infectious Diseases Society of America. Geneva.thomsonhc. Treatment of tuberculosis guidelines. 2009. ed. 2010 (http://whqlibdoc. References: American Academy of Pediatrics. Red Book: 2009 report of the committee on infectious diseases. London. BMJ Group RBS Publishing. Greenwood Village. 16th ed. (http://www. Thomson Micromedex. Contraindications: epilepsy. Hodding JH.who. 2003 (http://www. Kraus DM. World Health Organization. British national formulary for children 2009. Isoniazid: increased risk of CNS toxicity. Dose: Treatment of multidrug-resistant tuberculosis. Thomson Micromedex. accessed 10 February 2010). ed.int/ publications/2010/9789241547833_eng. Cycloserine ATC code: J04AB01 Solid oral dosage form: 250 mg Special Notes: Safety and effectiveness in paediatrics have not been established. accessed 10 February 2010). WHO Model Formulary for Children 2010 133 .pdf. 2006 (http:// whqlibdoc. 28th ed. Rare Megaloblastic anaemia. Drugdex system.6. Oral: Child 5–10 mg/kg twice daily (initially 5 mg/kg/dose and adjust according to blood concentration and response). Interactions with other medicines (* indicates severe): * Alcohol: increased risk of seizures. World Health Organization. psychosis. renal impairment. Greenwood Village.pdf. more frequently if symptoms develop.htm.

visual disturbances. is common with therapeutic doses. Pyrazinamide: hepatotoxicity. hepatic impairment. Abdominal discomfort. neuropathy. hypothyroidism. 134 WHO Model Formulary for Children 2010 . Renal impairment: Severe: reduce to 50% of dose. bilirubin and alkaline phosphatase should be obtained and regularly monitored (e. Adverse effects: Common Gastrointestinal disturbance (see below). 250 mg Special Notes: Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. and are less common in children. hepatotoxicity and encephalopathy. vomiting and diarrhoea. thrombocytopenia. headache. In general. Ethambutol: excessive adverse effect (GI distress. GASTROINTeSTINAL ADVeRSe eFFeCTS Gastrointestinal irritation is the major limiting factor in the therapeutic use of ethionamide. Anorexia. Oral: Child 15–20 mg/kg once daily if tolerated. Administration of an antiemetic agent 30 minutes prior to ethionamide and administration of ethionamide at bedtime have been suggested in patients experiencing gastrointestinal adverse effects. seizures. Precautions: AIDS infection (drug malabsorption may be a problem). neuritis and hepatotoxicity). half of the patient population is unable to tolerate 1 g of ethionamide as a single dose. confusion. described as epigastric pain or burning. ototoxicity.g. including seizures. every 2–4 weeks) during ethionamide therapy. divided doses if necessary. renal impairment. Contraindications: Severe hepatic impairment.6 Anti-infective medicines Ethionamide ATC code: J04AD03 Tablet: 125 mg. Uncommon Hepatotoxicity. encephalopathy. Maximum 1 g/day. Rifampicin: hepatotoxicity. rash. Indications: Treatment of multidrug-resistant tuberculosis and tuberculosis meningitis. Baseline liver function tests including serum transaminases. hypoglycaemia. Gastrointestinal effects are more common in females than males. Severe impairment: avoid use. Cycloserine: neurological adverse effects. peripheral neuritis. photosensitivity. gynaecomastia. Hepatic impairment: Mild and moderate impairment: use with caution. diabetes mellitus. Notes: Concurrent administration of pyridoxine may reduce peripheral neuropathy. Interactions with other medicines (* indicates severe): Aminosalicylic acid: excessive adverse effects (GI distress and hepatotoxicity). Persons of Asian or African descent reportedly tolerate this drug better than those of european descent. Isoniazid: increased isoniazid levels. stomatitis and a metallic taste in the mouth occur less frequently. These effects appear to be dose related. Dose: Treatment of multidrug-resistant tuberculosis and tuberculosis meningitis. The most frequent adverse effects of ethionamide are nausea. excessive salivation. fever. Rare Hypotension.

in combination with other drugs. Maintain optimal peak serum levels of 15–30 micrograms/ml. 4th ed.thomsonhc. birth weight of 2 kg or less and aged greater than 7 days 10 mg/kg every 12 hours.2 References: Antibacterials American Academy of Pediatrics. American Academy of Pediatrics. World Health Organization. Mild impairment: 60–90% of the normal dose every 8–12 hours. impaired neuromuscular transmission. World Health Organization. hepatic impairment. vestibular impairment. 16th ed. 2009. * Neuromuscular blocking drugs: enhanced and/or prolonged neuromuscular blockade which may lead to respiratory depression and paralysis. Renal impairment: The dosage of kanamycin must be reduced in patients with impaired renal function.int/publications/2006/9241546956_eng.pdf. Severe impairment: 20–30% of the dose every 24–48 hours. concomitant administration with rapid acting diuretic agents. Treatment of tuberculosis. Hudson. (http://www. Kraus DM.6. CDC.com. parkinsonism. Hodding JH. Treatment of tuberculosis guidelines. 2003 (http://www. Red Book: 2009 report of the committee on infectious diseases. accessed 10 February 2010). Drugdex system. Suitable times to collect blood for kanamycin assays are 1 hour after an IM dose or 30 minutes after an IV dose (peak) then just prior to the next dose (trough). Guidelines for the programmatic management of drug-resistant tuberculosis. Contraindications: Intestinal obstruction. 2009. infant botulism. NOTe Whenever possible. gov/mmwr/preview/mmwrhtml/rr5211a1. 2010. Thomson Micromedex. birth weight of more than 2 kg and aged greater than 7 days 10 mg/kg every 8 hours. Rare Skin rash. 2006 (http:// whqlibdoc. local irritation or pain after IM injection.htm.int/ publications/2010/9789241547833_eng. Lexi-Comp. Taketomo CK. ototoxicity. Geneva. Klasco RK. cross-allergenicity among other aminoglycosides (see Notes). in combination with other drugs. Pediatric dosage handbook. Indications: Treatment of multidrug-resistant tuberculosis.who. Dose: Treatment of multidrug-resistant tuberculosis. Uncommon Neuromuscular blockade. IM or IV: Neonate with birth weight of less than 2 kg and aged 7 days or less 7. 28th ed. Kanamycin ATC code: J01GB04 Powder for injection: 1 g vial Special Notes: Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control.who. paraesthesia. accessed 10 February 2010). Geneva. Adverse effects: Common Nephrotoxicity. 2010 (http://whqlibdoc.5 mg/kg every 12 hours. dosage should be guided by kanamycin serum concentrations. American Thoracic Society. Precautions: Concomitant administration with nephrotoxic or ototoxic antibiotics. Interactions with other medicines (* indicates severe): * Penicillins: loss of kanamycin activity. and Infectious Diseases Society of America. vomiting and diarrhoea. Hepatic impairment: Dose reduction not necessary. accessed 10 February 2010). Greenwood Village. WHO Model Formulary for Children 2010 135 . Infant or Child 15–30 mg/kg once daily (maximum 1 g daily).pdf.cdc. ed. Moderate impairment: 30–70% of the dose every 12 hours. headache. elk Grove Village. birth weight of more than 2 kg and aged 7 days or less 10 mg/kg every 12 hours. renal impairment. myasthenia gravis. drug fever. nausea. accessed 10 February 2010).

Ciclosporin: renal dysfunction or nephrotoxicity. 2010 (http://whqlibdoc.who. 2009. 2010.int/ publications/2010/9789241547833_eng.cdc. Hudson. elk Grove Village. gov/mmwr/preview/mmwrhtml/rr5211a1.6 Anti-infective medicines Loop diuretics: an increased risk of ototoxicity (tinnitus. sotalol) antiarrhythmic agents should be avoided. Amikacin and kanamycin are very similar and have almost 100% cross-resistance.pdf. Carboplatin: increased ototoxicity.rxlist. Lexi-Comp. 16th ed. Greenwood Village. 2003 (http://www. Typhoid vaccine. 400 mg tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. and Infectious Diseases Society of America. ed.5–10 mg/kg twice daily. Direct intravenous push is not recommended. Bristol-Myers Squibb. breastfeeding.htm. Dose: Special Notes: Second-line medicines should be reserved for the treatment of multidrug-resistant Treatment of multidrug-resistant tuberculosis. diabetic patients. Kantrex Product Information.com. in combination with other drugs. 2009. CDC. Tacrolimus: additive or synergistic renal function impairment. but this does not indicate a loss of potency. Hepatic impairment: elimination may be reduced. seek specialist advice. in combination with other drugs. some vials may darken during the shelf-life of the product. Treatment of tuberculosis guidelines. References: American Academy of Pediatrics. Renal impairment: All degrees of renal impairment: increased risk of seizure. excessive sunlight (risk for phototoxic reactions).com/kantrex-drug.htm. Red Book: 2009 report of the committee on infectious diseases. 136 WHO Model Formulary for Children 2010 .thomsonhc. quinidine) or class III (e.g. Precautions: Tendinitis and tendon rupture. reduce dose in severe liver disease. dosage adjustment recommended.5–5 mg/ml administered over 30–60 minutes. 2008 (http://www. Thomson Micromedex. ADMINISTRATION INSTRUCTIONS The minimum dilution of kanamycin is 2. dizziness. transient or permanent hearing loss. Cidofovir: nephrotoxicity. Occasionally. 28th ed. (http://www. central nervous system disorders (may predispose patient to seizures or lower seizure threshold).g. Taketomo CK. Indications: Treatment of multidrug-resistant tuberculosis. Levofloxacin may be an alternative based on availability and programme considerations. Notes: 62. 4th ed. Treatment of tuberculosis. procainamide. vertigo). accessed 10 February 2010). Hodding JH. live: decreased immunological response to the typhoid vaccine. accessed 10 February 2010). Maximum 800 mg/day. Klasco RK. renal impairment.2% of patients allergic to kanamycin demonstrated cross-sensitivity to gentamicin. World Health Organization. American Thoracic Society. Geneva. co-administration with class IA (e. amiodarone. Kraus DM. Oral: Child 7. Ofloxacin ATC code: J01MA01 Tablet: 200 mg. Contraindications: Pregnancy. Pediatric dosage handbook. American Academy of Pediatrics. hepatic impairment. accessed 10 February 2010). accessed 10 February 2010). Drugdex system. especially patients receiving oral hypoglycemic agents or insulin (may cause hyperglycaemia or hypoglycaemia).

American Academy of Pediatrics.htm. cardiac arrest). Drugdex system. 2010 (http://whqlibdoc. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. diarrhoea. Contraceptives. Ferrous salts: absorption of ofloxacin reduced by oral ferrous salts. headache. Pediatric dosage handbook. elk Grove Village. Rare Arrhythmias including QT prolongation. Treatment of tuberculosis. Geneva. Uncommon Seizures. arthralgia. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide.pdf. cardiac arrest). * Ciclosporin: increased risk of nephrotoxicity. in combination with other drugs.2 taste disturbance. cardiac arrest). 2009. live: a decreased immunological response to the typhoid vaccine. CDC. arthropathy. gov/mmwr/preview/mmwrhtml/rr5211a1. 4th ed. Guidelines for the programmatic management of drug-resistant tuberculosis. 28th ed. and Infectious Diseases Society of America. Taketomo CK. Antibacterials Adverse effects: Common Rash. Greenwood Village. torsades de pointes. Lexi-Comp. * Warfarin: enhanced anticoagulant effect. photosensitivity. WHO Model Formulary for Children 2010 137 . accessed 10 February 2010).cdc. p-Aminosalicylic acid ATC code: J04AA01 Granules: 4 g in sachet Tablet: 500 mg Special Notes: Also referred to as PAS and as 4-aminosalicylic acid (4-ASA). Zinc sulfate: reduced absorption of ofloxacin. torsades de pointes.pdf. 16th ed. 2009. accessed 10 February 2010). * Amiodarone: an increased risk of cardiotoxicity (QT prolongation. Second-line medicines should be reserved for the treatment of multidrug-resistant tuberculosis (MDR-TB) and should be used in specialized centres adhering to WHO standards for TB control. World Health Organization. World Health Organization. American Thoracic Society. 2010. Thomson Micromedex.who. insomnia. 2003 (http://www. vomiting. dizziness. ed. Indications: Treatment of multidrug-resistant tuberculosis. Hudson. nausea. oral: contraceptive effect of estrogens possibly reduced (risk probably small). torsades de pointes.thomsonhc. tendon rupture. * Sotalol: an increased risk of cardiotoxicity (QT prolongation. Contraindications: Hypersensitivity to aminosalicylic acid products. Red Book: 2009 report of the committee on infectious diseases.6. magnesium hydroxide): reduced absorption of ofloxacin. hepatic impairment/failure. accessed 10 February 2010). cardiac arrest).int/publications/2006/9241546956_eng. 2006 (http:// whqlibdoc. * Quinidine: an increased risk of cardiotoxicity (QT prolongation. Typhoid vaccine.int/ publications/2010/9789241547833_eng. Treatment of tuberculosis guidelines. torsades de pointes.who. Kraus DM. * Flecainide: an increased risk of cardiotoxicity (QT prolongation. References: American Academy of Pediatrics. Theophylline: an increased risk of elevated theophylline concentrations. hypoglycaemia or hyperglycaemia. arthritis. Geneva.com. * Ibuprofen: possible increased risk of convulsions. end-stage renal disease. Klasco RK. myopathy. blood dyscrasias. Hodding JH. nephrotoxicity. (http://www. accessed 10 February 2010).

haemolysis. Dose reduction not considered necessary. (http://www. blood dyscrasias.6 Anti-infective medicines impairment. Notes: PATIeNT ADVICe Should be taken with acidic food or drink (yoghurt. 2009. Isoniazid: reduction in the acetylation of isoniazid (increased isoniazid levels). Greenwood Village. hair. In some infections.cdc. Duration of therapy depends on the initial severity of the infection and the clinical response of the patient. apple or fruit juice containing drinks. Jacobus. Do not use granules if packet is swollen or the granules have lost their tan colour and have turned dark brown or purple. in combination with other drugs. hepatic Dose: Treatment of multidrug-resistant tuberculosis. References: American Academy of Pediatrics.int/ publications/2010/9789241547833_eng. Vitamin B12: reduced absorption of vitamin B12. rash. renal impairment. Adverse effects: Common Nausea. orange. Systemic fungal infections may occur as opportunistic infections in patients who are immunocompromised. systemic fungal infections affect the body as a whole. Sprinkle granules on apple sauce or yogurt or suspend in tomato. vomiting. Increase laboratory and clinical monitoring. Treatment of tuberculosis. abdominal pain. Interactions with other medicines (* indicates severe): * Digoxin: reduced digoxin serum concentrations. 2003 (http://www. World Health Organization. Superficial infections affect the skin. Granules should be stored in the refrigerator.com. Rare Hepatotoxicity. Treatment of tuberculosis guidelines. and are associated with high mortality rates. Drugdex system. peptic ulcer disease.com/paser-drug. American Academy of Pediatrics. elk Grove Village. 2010.htm.pdf. Maximum 10 g daily. Patients should be advised that the skeleton of the granules may be seen in the stool. Can be stored at room temperature for short periods of time. CDC. accessed 10 February 2010). crystalluria. Hepatic impairment: Use with caution.3 Antifungal medicines Fungal infections are increasing in prevalence globally. patients on therapy of more than 1 month should be considered for maintenance vitamin B12. congestive heart failure. Paser Product Information. grapefruit. Oral: Child 200–300 mg/kg per day in 2–4 divided doses. Ethionamide: excessive adverse effects (GI distress and hepatotoxicity). nails or mucous membranes. accessed 10 February 2010). ed. 6. Geneva. 138 WHO Model Formulary for Children 2010 . 2004 (http://www. Thomson Micromedex. gov/mmwr/preview/mmwrhtml/rr5211a1. 28th ed.rxlist. accessed 10 February 2010). Precautions: Glucose-6-phosphate dehydrogenase (G6PD) deficiency (risk of haemolysis).who.thomsonhc. a satisfactory response is only obtained after several months or more of continuous treatment. cranberry. accessed 10 February 2010).html. 4th ed. Red Book: 2009 report of the committee on infectious diseases. hypoglycaemia. encephalopathy. and can be classified as superficial or systemic. American Thoracic Society. fever. and Infectious Diseases Society of America. apple sauce or fruit juice). grape. Klasco RK. 2010 (http://whqlibdoc. diarrhoea. Renal impairment: Not recommended to be used in patients with severe renal impairment.

2–4 weeks 6–12 mg/kg every 48 hours. Cryptococcal meningitis following amphotericin B induction therapy or systemic candidiasis (in patients unable to tolerate amphotericin B). Dose: Systemic mycoses. candiduria and noninvasive bronchopulmonary infections. Mucosal candidiasis (except genital). paracoccidioidomycosis and blastomycosis. oesophageal and oropharyngeal candidiasis. Oral or IV: Infant or Child 6 mg/kg (maximum 200 mg) daily. have been reported. Vaginal candidiasis. concomitant hepatotoxic drugs.6. susceptibility to QT interval prolongation. Contraindications: Acute porphyria. Infant or Child 6–12 mg/kg (maximum 800 mg) daily. then 3 mg/kg daily (maximum 100 mg) for 7–14 days. patients with proarrhythmic conditions. Oral or IV: Neonate under 2 weeks 3–6 mg/kg on first day then 3 mg/kg every 72 hours. Indications: Systemic mycoses including histoplasmosis. treatment and. Precautions: Renal impairment. Infant or Child 3–6 mg/kg on the first day. in HIV and other immunosuppressed patients. Oral or IV: Neonate under 2 weeks 6–12 mg/kg every 72 hours. WHO Model Formulary for Children 2010 139 . prevention of fungal infections in immunocompromised patients. Oral or IV: Child over 2 years 3–6 mg/kg (maximum 200 mg) daily for at least 6 months. non-meningeal coccidioidomycosis.3 Antifungal medicines Fluconazole Capsule: 50 mg ATC code: J02AC01 Injection: 2 mg/ml in vial Oral liquid: 10 mg/ml Rare cases of fluconazole-associated hepatotoxicity. Treat for 14–30 days for other mucosal infections such as oesophagitis. monitor liver function: discontinue if signs or symptoms of hepatic disease (risk of hepatic necrosis). including fatalities. prophylaxis of cryptococcal meningitis. 2–4 weeks 3–6 mg/kg on first day then 3 mg/kg every 48 hours. Oral: Child post-puberty 150 mg as a single dose. vaginal candidiasis and systemic candidiasis. Prevention of relapse of cryptococcal meningitis in AIDS patients after completion of primary therapy. Treatment should continue according to response and should be for at least 8 weeks for cryptococcal meningitis.

Diazepam: fluconazole may inhibit diazepam’s metabolism. Oral or IV: Neonate under 2 weeks 3–12 mg/kg every 72 hours according to duration and extent of neutropenia. Infant or Child 3–12 mg/kg (maximum 400 mg) daily according to duration and extent of neutropenia. abdominal pain. Ritonavir: plasma concentration of fluconazole increased by ritonavir. paraesthesia. Adverse effects: Common Rash. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. Amphotericin B: possible antagonism of effect of amphotericin. give over 60 minutes at a maximum rate of 200 mg/hour. vomiting. * Rifampicin: accelerated metabolism of fluconazole (reduced plasma concentration). diarrhoea. Notes: For intravenous infusion. Hepatic impairment: Use with caution. Higher doses are best infused over 2 hours. oral: anecdotal reports of failure of estrogen containing contraceptives. * Ciclosporin: metabolism of ciclosporin inhibited (increased plasma concentration). Stevens-Johnson syndrome. fatigue. Interactions with other medicines (* indicates severe): Fluconazole can cause prolonged QT interval and torsades de pointes. increasing the risk of adverse effects. seizures. constipation. angioedema. Ibuprofen: fluconazole may inhibit ibuprofen’s metabolism. Fluconazole oral liquid may contain sodium benzoate and should be used with caution in neonates. nausea. * Phenytoin: plasma concentration of phenytoin increased (consider reducing dose of phenytoin). Commence treatment before anticipated onset of neutropenia and continue for 7 days after neutrophil count in desirable range. monitor carbamazepine concentration and for adverse effects. * Nevirapine: increased plasma concentration of nevirapine. headache. prolonged QT interval. Food decreases the rate but not the extent of absorption. other blood dyscrasias. Saquinavir: plasma concentration of saquinavir possibly increased. * Warfarin: enhanced anticoagulant effect. increasing its concentration and may increase risk of adverse effects. serious hepatotoxicity including hepatic failure. anaphylactic/anaphylactoid reactions. avoid concomitant use of other cardiotoxic or arrhythmogenic drugs. 2–4 weeks 3–12 mg/kg every 48 hours according to duration and extent of neutropenia. thrombocytopenia. Carbamazepine: fluconazole may inhibit metabolism of carbamazepine and may increase concentration and risk of adverse effects. toxic epidermal necrolysis (severe skin reactions more common in patients with AIDS). Renal impairment: Reduce dose in mild to severe impairment by 50%. Bioavailability is excellent at > 90%. * Zidovudine: increased plasma concentration of zidovudine (increased risk of toxicity). alopecia. torsades de pointes. Rare Oliguria. dizziness. Uncommon Anorexia. elevated liver enzymes. hypokalaemia. Contraceptives.6 Anti-infective medicines Prevention of fungal infections in immunocompromised patients. 140 WHO Model Formulary for Children 2010 .

pdf ). confusion. WHO model formulary. Drugdex system. Rare Precipitation/exacerbation of systemic lupus erythematosus. Greenwood Village. dizziness. taste disturbance. hypersensitivity. diarrhoea. Adverse effects: Common Headache.3 References: Antifungal medicines Ashley C. Up to 25 mg/kg/day for 6–8 weeks may be required for the treatment of tinea capitis. World Health Organization. Hodding JH. Rossi S. Australian medicines handbook. Contraindications: Severe liver disease. Hill SR. Interactions with other medicines (* indicates severe): WHO Model Formulary for Children 2010 141 . for 24 hours. WHO expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee. Kouimtzi M. London. 16th ed. hepatotoxicity. Oxford. toxic epidermal necrolysis. (http://www. systemic lupus erythematosus (risk of exacerbation).thomsonhc. Griseofulvin ATC code: D01BA01 Oral liquid: 25 mg/ml Solid oral dosage form: 125 mg. ed. Stevens-Johnson syndrome. Paediatric Formulary Committee. fatigue. Duration of treatment depends on the infection and thickness of keratin at site of infection. at least 6 weeks for scalp ringworm and in severe hair. Kraus DM. Adelaide. Oral: Infant or Child 10–20 mg/kg (maximum 1 g) once daily or in divided doses. As a guide: at least 4 weeks for skin and hair. up to 3 months. Radcliffe Publishing. Indications: Fungal infections of the skin. 3rd ed.g. 2010. Ciclosporin: plasma ciclosporin concentration possibly reduced.int/medicines/publications/essentialmeds_committeereports/TRS_950. nausea. Hudson. eds. vomiting. Stuart MC. severe diarrhoea. serum sickness-like reaction. Currie A. 2008. 2009. Taketomo CK. for example riding a bike or operating machinery. 2009. leukopenia. men should not father children within 6 months of treatment). Uncommon Photosensitivity. 2008. Geneva. menstrual irregularities.who. Dose: Fungal infections of the skin. blood disorders (monitor blood count weekly during first month of treatment). blurred vision. penicillin hypersensitivity (cross-reactivity with griseofulvin is possible). eds. Klasco RK. The renal drug handbook. e. Thomson Micromedex. WHO Technical Report Series. 2009. Precautions: Avoid exposure to intense sunlight to prevent photosensitivity reactions. 950 (http://www. anorexia.com. scalp or hair where topical treatment has failed or is inappropriate. 2009. Pediatric dosage handbook. rash. accessed 10 February 2010). Australian Medicines Handbook. Hepatic impairment: Contraindicated in severe liver disease. pre-existing hepatic insufficiency (closely monitor hepatic function throughout treatment). SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.6. urticaria. pregnancy (avoid pregnancy and use additional nonhormonal contraception during and for 1 month after treatment. Renal impairment: Dose reduction not necessary. scalp or hair where topical treatment has failed or is inappropriate. BMJ Group RBS Publishing. skin and scalp infections. British national formulary for children 2009. porphyria. 250 mg Special Notes: The formulations and doses in this formulary refer to microsize (fine particle) griseofulvin and these are not equivalent to ultramicrosize (ultra microfine crystal) formulations. Lexi-Comp. ed. October 2007 (including the model list of essential medicines for children).

g. Rossi S. PATIeNT ADVICe Avoid consumption of alcoholic beverages during treatment with griseofulvin. wear protective clothing and use sunscreen as griseofulvin may make you more sensitive to sunlight. vomiting. you should use additional contraception. 2010. Treatment of intestinal and oesophageal candidiasis. 2009. Phenobarbital: reduction in absorption of griseofulvin (reduced effect). * Ethanol: disulfiram-like reaction (nausea. Paediatric Formulary Committee. accessed 10 February 2010). October 2007 (including the model list of essential medicines for children). Hodding JH. Kraus DM. Klasco RK. oesophageal and intestinal candidiasis. Thomson Micromedex. 500 000 IU Special Notes: Nystatin should not be used for the treatment of systemic mycoses. ed. Oral: Child all ages 100 000 units four times daily after feeds. 2008. The contraceptive pill will not be as effective while you are taking griseofulvin. Renal impairment: Dose reduction not necessary. * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect).pdf ). oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect). Kouimtzi M. Taketomo CK. (http://www. Australian Medicines Handbook. 2008. during treatment and for 4 weeks afterwards.who.int/medicines/publications/essentialmeds_committeereports/TRS_950. 16th ed. Stuart MC. WHO Technical Report Series. Drugdex system. WHO expert committee on the selection and use of essential medicines. 950 (http://www.6 Anti-infective medicines * Contraceptives. Pediatric dosage handbook. World Health Organization. Hepatic impairment: Dose reduction not necessary. * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). 100 000 IU/ml Tablet: 100 000 IU.com. Administer with a fatty meal or with food or milk to improve absorption and to avoid gastrointestinal upset. WHO model formulary. Immunocompromised children may require 500 000 units four times daily. BMJ Group RBS Publishing. Hudson. Greenwood Village. Adelaide. Oral: Child all ages 100 000 units four times daily after feeds. Geneva. diarrhoea. eds. Avoid sun exposure. References: Hill SR. * Warfarin: reduced anticoagulant effect. Australian medicines handbook. The selection and use of essential medicines: report of the WHO expert committee. 2009. Notes: Fatty meals will increase griseofulvin absorption. tachycardia. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). London. Indications: Oral. Nystatin ATC code: A07AA02 Lozenge: 100 000 IU Oral liquid: 10 mg/ml. e. Treatment is usually given for 7 days and continued for 2 days after lesions have healed. Lexi-Comp. flushing. condoms. Dose: Treatment of oral candidiasis. ed.thomsonhc. 2009. British national formulary for children 2009. hypotension). 142 WHO Model Formulary for Children 2010 .

Australian Medicines Handbook. Hodding JH. WHO expert committee on the selection and use of essential medicines. avoid rapid infusion (risk of arrhythmias). 950 (http://www. Paediatric Formulary Committee. Amphotericin B is available as the conventional deoxycholate complex and liposomal forms. Rossi S. October 2007 (including the model list of essential medicines for children). 16th ed.5 mg/kg. Stuart MC.thomsonhc. 2009. diarrhoea (more severe with doses > 5 million units Rare Oral irritation and sensitization. Taketomo CK. 2009. Amphotericin B ATC code: J02AA01 Powder for injection: 50 mg in vial As deoxycholate or liposomal Amphotericin B is available as deoxycholate. Mcevoy GK. Hudson. Special Notes: Also known as amphotericin. cryptococcosis. 2008. AHFS drug information. Bethesda. lipid complex and liposomal. Intravenous amphotericin B is used primarily for the treatment of patients with progressive fungal infections. References: Hill SR. 2009. Contraindications: Known hypersensitivity. Care with product formulation. WHO Technical Report Series.6. PATIeNT ADVICe Oral liquid: shake well before use.3 daily). blastomycosis. BMJ Group RBS Publishing. The selection and use of essential medicines: report of the WHO expert committee. aspergillosis. 2010. Kouimtzi M. Indications: Life-threatening fungal infections including histoplasmosis. 2009. below). coccidioidomycosis. It is best to use the oral liquid after (rather than before) a meal or drink. (http://www. Single daily doses of conventional amphotericin B formulation never exceed 1. London. mucormycosis. Klasco RK. facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. vomiting. blood counts and plasma electrolyte (including potassium and magnesium concentration) monitoring. sporotrichosis and candidiasis. Thomson Micromedex. 2008. Drugdex system. accessed 10 February 2010). Australian medicines handbook. renal impairment. hepatic and renal function tests. British national formulary for children 2009.pdf ). Kraus DM.com. Geneva. ed. Adelaide. not to be used for non-invasive forms of fungal disease. WHO model formulary.who. Lexi-Comp. Anaphylaxis has been reported with amphotericin B containing drugs. Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid based or liposomal products. Notes: each mg of nystatin contains not less than 4400 units of activity. World Health Organization. Continue to use for 2 days after your symptoms/lesions disappear. ed. It is also available in a lipid complex form (not included in the 2nd WHO Model list of essential medicines for children).int/medicines/publications/essentialmeds_committeereports/TRS_950. WHO Model Formulary for Children 2010 143 . Pediatric dosage handbook. paracoccidioidomycosis. American Society of Health-System Pharmacists. Antifungal medicines Adverse effects: Common Nausea. eds. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concomitant use. rash and erythema multiforme (Stevens-Johnson syndrome). Should be swished around mouth and retained for as long as possible then swallowed. ed. Greenwood Village. Precautions: Close medical supervision throughout treatment and initial test dose required (see Anaphylaxis. these should not be considered interchangeable.

Rare Anaphylactoid reactions. anorexia. chills. then 250 micrograms/kg daily. increased in steps of 1 mg/kg daily up to 3 mg/kg once daily. With liposomal amphotericin B one or more acute infusion reactions (chest pain. a higher dose (maximum 1. recommence at 250 micrograms/kg daily and increase gradually. blurred vision. Nephrotoxicity may be associated with sodium depletion. seizures. Dose: Conventional amphotericin B (as deoxycholate) Systemic fungal infections. Infant or Child initial test dose 100 micrograms/kg (maximum 1 mg) then 1 mg/kg once daily. Renal impairment: Mild to severe: use only if no alternative. INFUSION ReACTIONS Include fever. The patient should be observed for at least 30 minutes after the test dose. anorexia. No dosage reduction is necessary. diarrhoea. If treatment is interrupted for longer than 7 days. ANAPHyLAXIS Anaphylaxis occurs rarely with intravenous amphotericin B and a test dose is advisable before the first infusion. confusion. Liposomal amphotericin B is less nephrotoxic than conventional (deoxycholate) amphotericin B. gradually increased up to 1 mg/kg daily or in severe infection. For prolonged treatment. changes are dose related and generally reversible (except with cumulative doses > 3–5 g). Prolonged treatment is usually necessary. the rates depend on the formulation used. arrhythmias (rapid infusion of conventional amphotericin B). hypotension. these may be related to the liposomal component. headache. headache. hyperkalaemia (especially in renal impairment). flank or leg pain. Risk is greater in those with renal impairment or when used with other nephrotoxic drugs. eCG changes). severe abdominal. gastrointestinal bleeding. hepatotoxicity. hypertension. epigastric pain. up to maximum of 1. but further impairment is likely with conventional (as deoxycholate) amphotericin B. frequency is very variable. hearing loss. muscle and joint pain. flushing and urticaria) may occur. IV: Neonate. cardiovascular toxicity (including arrhythmias. Nephrotoxicity may be reduced with use of liposomal formulations. hypokalaemia and hypomagnesaemia. IV: Neonate. infusion reactions (see below). NePHROTOXICITy Conventional (as deoxycholate) amphotericin B affects renal function in all patients. rash. muscle and joint pain. hypomagnesaemia. anaemia. usually lessen with continued treatment. maximum 5 mg/kg once daily if necessary for severe infection.5 mg/kg) may be given on alternate days. Liposomal amphotericin B Systemic fungal infections. Hepatic impairment: Dose reduction not necessary. nausea. Distal tubular damage may lead to loss of concentrating ability. Infant or Child initial test dose of 100 micrograms/kg (maximum 1 mg) included as part of first dose. malaise. elevated liver enzymes. Adverse effects: Adverse effects are similar for all amphotericin B formulations.6 Anti-infective medicines LIPOSOMAL Diabetes as each 50 mg vial of liposomal amphotericin B contains 900 mg of sucrose. neurological effects (e. thrombophlebitis. vomiting. hypokalaemia. Prophylactic antipyretics or hydrocortisone should only be used in patients who have previously experienced acute adverse reactions (in whom continued treatment with amphotericin B is essential). cardiac arrest.5 mg/kg daily. blood dyscrasias. Continuous infusion of conventional (as deoxycholate) amphotericin B reduces infusion reactions. dyspnoea. nephrocalcinosis. Uncommon Hypotension. Common Fever. tinnitus). nephrotoxicity (see below). Anuria or oliguria may occur. hypoxia. 144 WHO Model Formulary for Children 2010 . liposomal formulations are generally better tolerated. nausea and vomiting.g. renal tubular acidosis.

which may allow a shorter infusion. potentially reduced antifungal efficacy. ADMINISTRATION ADVICe (both formulations).1 mg/ml (in fluid restricted children up to 0. administration with other drugs with this effect may worsen hypokalaemia. It may also reduce potassium concentration. Miconazole: possible antagonism of effects of amphotericin B. Furosemide: increased risk of hypokalaemia. Hydrochlorothiazide: increased risk of hypokalaemia. supplements may be needed. infuse the initial treatment dose slowly over 4–6 hours. administration with other nephrotoxic drugs or cytotoxic drugs may cause additional renal impairment. WHO Model Formulary for Children 2010 145 . Reconstitute as per product instructions including further dilution with glucose 5% to produce a final concentration of 0. Then infuse subsequent doses over 30–60 minutes. however. Paromomycin: possible increased risk of nephrotoxicity. Fluconazole: possible antagonism of effect of amphotericin B. Liposomal amphotericin B Reconstitute as per product instructions including filtering through a 5 micron filter and further dilute with glucose 5% to produce a final concentration of 0. Streptomycin: increased risk of nephrotoxicity. * Digoxin: hypokalaemia caused by amphotericin B increases cardiac toxicity of digoxin. do not give over < 2 hours. Pentamidine: possible increased risk of nephrotoxicity. After initial reconstitution. paracetamol and/or hydrocortisone in patients who have previously experienced acute adverse reactions to prevent or treat infusion reactions. Conventional amphotericin B (as deoxycholate) Reduce risk of thrombophlebitis by using large peripheral veins or a central venous catheter. Liposomal formulations of amphotericin B are less nephrotoxic than conventional amphotericin B. Gentamicin: increased risk of nephrotoxicity. Flucytosine: renal excretion of flucytosine decreased and cellular uptake increased (flucytosine toxicity possibly increased). * Ciclosporin: increased risk of nephrotoxicity. Monitor potassium concentration. do not administer without further dilution. tolerance to infusion reactions increases with subsequent doses. Conventional (as deoxycholate): use an antihistamine.2–2 mg/ml.3 Interactions with other medicines (* indicates severe): Antifungal medicines Amphotericin B is nephrotoxic. Vancomycin: possible increased risk of nephrotoxicity. * Hydrocortisone: increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions). Initial test dose should be given over 10 minutes. * Prednisolone: increased risk of hypokalaemia (avoid concomitant use unless prednisolone needed to control reactions). fluconazole): possible antagonistic effect. monitor renal function and electrolytes (especially potassium.4 mg/ml if given via a central line). Initial test dose should be given over 20–30 minutes.g. To minimize infusion related reactions. changing venous access sites frequently and infusing over longer periods. Notes: Check renal function before starting treatment. Incompatible with sodium chloride solutions. the few comparative clinical trials between conventional and liposomal formulations appear to show similar efficacy. Do not mix with any other drugs. magnesium and sodium) at least three times a week and complete blood picture and hepatic function twice a week during treatment and until stable after treatment stops.6. * Dexamethasone: increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions). Amikacin: increased risk of nephrotoxicity. flush existing line with glucose 5% or use a separate line. Azoles (e.

rashes. Precautions: Renal impairment. hepatic necrosis. Infant or Child 50 mg/kg every 6 hours. adjunct to amphotericin B in systemic candidiasis. vertigo. Hodding JH.com. 16th ed. Kraus DM. WHO expert committee on the selection and use of essential medicines. Interactions with other medicines (* indicates severe): Flucytosine depresses the bone marrow. photosensitivity. leukopenia and aplastic anaemia. Treatment does not usually extend beyond 7 days. Pediatric dosage handbook. Severe renal impairment: usual dose every 24–48 hours. Adelaide.6 Anti-infective medicines References: Hill SR. ed. Greenwood Village. London. diarrhoea. 2010. Stuart MC. 2009.int/medicines/publications/essentialmeds_committeereports/TRS_950. Paediatric Formulary Committee. hallucinations. eds. thrombocytopenia. World Health Organization. Australian Medicines Handbook. Rossi S. adjunct to amphotericin B in systemic candidiasis. Geneva. hepatic impairment. British national formulary for children 2009. Adverse effects: Common Nausea. Flucytosine ATC code: J02AX01 Capsule: 250 mg Infusion: 10 mg/ml in 250 ml Keep flucytosine injection at 15–25 °C (forms fluorouracil above 25 °C and can precipitate below 15 °C). Klasco RK. Drugdex system. 950 (http://www. 2009. Continue for at least 4 months in cryptococcal meningitis. myelosuppressive drugs. 2008. ed. Indications: Adjunct to amphotericin B (or fluconazole) in cryptococcal meningitis. (http://www. 146 WHO Model Formulary for Children 2010 . Uncommon Cardiotoxicity. The selection and use of essential medicines: report of the WHO expert committee. Thomson Micromedex. WHO Technical Report Series. vomiting. WHO model formulary. Moderate renal impairment: usual dose every 24 hours. Hepatic impairment: Dose reduction not necessary. Mild renal impairment: usual dose every 12 hours. renal and hepatic status of all patients is essential. Oral or IV: Neonate 50 mg/kg every 12 hours. blood disorders including thrombocytopenia. Kouimtzi M. use with amphotericin B (both nephrotoxic). toxic epidermal necrolysis. Dose: Adjunct to amphotericin B (or fluconazole) in cryptococcal meningitis.pdf ). Close monitoring of haematological. confusion.thomsonhc. Taketomo CK. seizures. sedation. monotherapy due to emergent resistance. Use with extreme caution in patients with impaired renal function. administration with other drugs which also have this effect may increase the risk of myelosuppression. accessed 10 February 2010). patients with AIDS have an increased risk of blood dyscrasias. 2008. In infections due to extremely sensitive organisms. Rare Anaphylaxis. Lexi-Comp.5 mg/kg every 6 hours may be sufficient. peripheral neuropathy. Renal impairment: Reduce dose and monitor plasma flucytosine concentration. Hudson. October 2007 (including the model list of essential medicines for children). gastrointestinal haemorrhage. psychosis. bone marrow depression. radiation treatment. headache. Australian medicines handbook. alterations in liver function tests including hepatitis. BMJ Group RBS Publishing. Special Notes: Also known as 5-FC. 25–37. 2009.who. liver and kidney function tests and blood counts required (weekly in renal impairment or in blood disorders).

2009. Radcliffe Publishing. 2009. acute bronchitis or active tuberculosis. Rossi S. Amphotericin B: renal excretion of flucytosine decreased and cellular uptake increased (flucytosine toxicity possibly increased). Mcevoy GK. Bethesda. London. BMJ Group RBS Publishing.3 Antifungal medicines If it is given with nephrotoxic drugs. or Lugol’s solution). Hudson. 3rd ed. October 2007 (including the model list of essential medicines for children). Current Opinion in Infectious Diseases. myotonia congenita. Pediatric dosage handbook. NOTe If signs of iodism occur. References: Potassium iodide ATC code: D01BA Saturated solution Special Notes: Also referred to as saturated solution of potassium iodide or SSKI®. Greenwood Village. Hill SR. Geneva.g. whichever is lowest. increasing as tolerated. 2008. subcutaneous phycomycosis. Notes: Monitoring is essential in renal impairment. Adelaide. 2009. increasing the risk of toxicity. Oral: Child all ages initiate at 1 drop three times daily. Treatment should be continued for at least 4 weeks after resolution or stabilization of lesions. Plasma concentration for optimum response 25–50 mg/l (200–400 micromol/l) and should not exceed 80 mg/l (620 micromol/l). Contraindications: Hypersensitivity to iodides. Cytarabine: plasma flucytosine concentration possibly reduced. in patients with AIDS. Therapeutic Guidelines Limited. Jarvis JN et al. Hodding JH. These doses assume a solution of 1 g/ml. Zidovudine: concomitant administration may increase the risk of haematological toxicity. Oxford. 2008. Klasco RK. Resistance to flucytosine can develop during therapy and sensitivity testing is essential before and during treatment. Red Book: 2009 report of the committee on infectious diseases. WHO expert committee on the selection and use of essential medicines. Ashley C. PLASMA CONCeNTRATION MONITORING For plasma concentration monitoring. 16th ed. elk Grove Village. Kouimtzi M. World Health Organization. Melbourne. Kraus DM. accessed 10 February 2010). ed. 2009. 2008. renal impairment. when using with amphotericin B. easily confused with potassium iodide and iodine (strong iodide solution. eTG complete. Indications: Sporotrichosis. Thomson Micromedex. eds. 2009. Caution if used together. up to a maximum of 1 drop per kg of body weight or 40–50 drops three times daily.au/ip/. hyperthyroidism. 2010. Lexi-Comp. Australian medicines handbook.org. Currie A. The renal drug handbook. Take the capsules with food to reduce stomach upset. cardiac disease.pdf ). British national formulary for children 2009. blood should be taken shortly before starting the next infusion (or before next dose by mouth). 950 (http://www.int/medicines/publications/essentialmeds_committeereports/TRS_950. 2009 (http://etg. its renal excretion may be reduced. Paediatric Formulary Committee. 21(6):596–603.tg. WHO Model Formulary for Children 2010 147 .who. or if there is an increased risk of bone marrow suppression. American Society of Health-System Pharmacists. The selection and use of essential medicines: report of the WHO expert committee. Addison disease. WHO model formulary. Taketomo CK. 2009. suspend treatment temporarily and restart after a few days at lower dosage. WHO Technical Report Series. AHFS drug information. Dose: Sporotrichosis and subcutaneous phycomycosis. eds. Managing cryptococcosis in the immunocompromised host. American Academy of Pediatrics. ed. American Academy of Pediatrics.com. Australian Medicines Handbook. (http://www.thomsonhc. 28th ed. Drugdex system. e. accessed 10 February 2010). Precautions: Not for long-term use. ed.6. Stuart MC.

Thyroid blockade with iodine prior to MIBG scan (nuclear medicine procedure) . eczema herpeticum. Jod-Basedow phenomenon (iodine-induced thyrotoxicosis). Unpublished 2008. hyperthyroidism. genital herpes. 2006. Hepatic impairment: Dose reduction not necessary. October 2007 (including the model list of essential medicines for children). metallic taste. skin reactions including acneiform. Geneva. herpetic whitlow and eye involvement. WHO Technical Report Series. 2008. HSV encephalitis is a serious. ed. Uncommon Pulmonary oedema. Adelaide. Notes: ADMINISTRATION Give after meals with food or milk. Pharmaceutical Press. Bethesda. Australian medicines handbook. Hill SR. Treatment should be reserved for debilitating disease and when there is a high risk of serious complications.int/medicines/publications/essentialmeds_committeereports/TRS_950. Hynes.4 6. American Society of Health-System Pharmacists. BMJ Group RBS Publishing. goitre. Royal Children’s Hospital. Rare Pain or inflammation of salivary glands. eds. WHO expert committee on the selection and use of essential medicines. Pharmacy Department. 15th ed. Rossi S. ed. Amsterdam. Interactions with other medicines (* indicates severe): Potassium iodide contains potassium and can cause hyperkalaemia. World Health Organization. 34th ed.who. Kay. Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America. bronchitis. conjunctivitis. * Spironolactone: risk of hyperkalaemia. HSV infections can be primary or reactivation infections. 2009. * Enalapril: increased risk of severe hyperkalaemia. ed. depression. British national formulary for children 2009. 950 (http://www. increased salivation. those with severe cardiovascular or respiratory disease or a chronic skin disorder). laryngitis. headache. Otherwise.g. elsevier. The selection and use of essential medicines: report of the WHO expert committee.6 Anti-infective medicines Renal impairment: Use with caution. 2009. 2008.4. such as in advanced HIV disease. ed. gastrointestinal disturbances. London. and include superficial infections. lacrimation. diarrhoea. AHFS drug information. hypersensitivity reactions. some will suffer repeated episodes. Meyler’s side effects of drugs. Stuart MC. WHO model formulary. While most HIV-positive patients with herpes zoster (shingles) experience only one self-limiting disease course. 2005. 148 WHO Model Formulary for Children 2010 . insomnia. coryza-like symptoms and irritation and swelling of the eyes. Clinical Infectious Diseases. It is indicated in children for herpes simplex virus (HSV) infections but is only effective if started early in the course of infection. Australian Medicines Handbook. Kauffman C et al.1 Antiviral medicines Antiherpes medicines Herpes simplex infections Aciclovir is active against herpes viruses but does not eradicate them. References: 6.pdf ). Kouimtzi M. treatable condition that should not be missed. * Ciclosporin: increased risk of hyperkalaemia. Mcevoy GK. Paediatric Formulary Committee. Melbourne. Aronson JK.Lugol’s iodine dosage protocol. 2009. Sweetman SC. Varicella-zoster infection (chickenpox) Chickenpox in neonates should be treated with parenteral aciclovir to reduce the risk of severe disease. London. Martindale: the complete drug reference. Potassium salts and medicines which may increase serum potassium concentrations should be used with caution. Adverse effects: Common Hypothyroidism. antiviral treatment is generally not required except for immunocompromised patients and those at special risk (e. 45(10):1255–1265 (Medline accessed 16 December 2009). Invasive and disseminated infection can occur in immunocompromised patients. 2007.

Hepatic impairment: Dose reduction not necessary. over 5 years 800 mg four times daily. Child 3 months–12 years 250 mg/m2 every 8 hours usually for 5 days. 2 years and over 200 mg five times daily. IV: Neonate to Infant under 3 months 20 mg/kg every 8 hours for 10–14 days (21 days if CNS involvement). 2 years and over 200–400 mg four times daily. 2–12 years 400 mg five times daily for 7–14 days. Dose: Herpes simplex (non-encephalitis) treatment including genital herpes. Immunocompetent patients. Chickenpox treatment (usually only prescribed if immunocompromised). Immunocompetent patients. renal impairment. Child 3 months–12 years 250 mg/m2 every 8 hours.4 Antiviral medicines Aciclovir ATC code: J05AB01 Oral liquid: 40 mg/ml Powder for injection: 250 mg (as sodium salt) in vial Tablet: 200 mg Special Notes: Also referred to as acyclovir. Oral: Child less than 2 years 200 mg four times daily. zoster infections. Indications: Treatment and prophylaxis of herpes simplex infections. 2–5 years 400 mg four times daily. WHO Model Formulary for Children 2010 149 . longer if new lesions appear during treatment or if healing incomplete. Oral: Child 1 month–2 years 200 mg five times daily for 7–14 days. IV: Neonate to Infant under 3 months 10–20 mg/kg every 8 hours for at least 7 days. IV: Child 3 months–12 years 500 mg/m2 every 8 hours usually for 14–21 days. Oral: Child less than 2 years 100 mg five times daily. Treatment usually for 5 days. Immunocompromised patients. usually for 5 days. Herpes simplex prophylaxis in immunocompromised patients. Oral: Child less than 2 years 100–200 mg four times daily. Herpes simplex encephalitis treatment. Disseminated herpes simplex treatment. Immunocompromised patients. Varicella zoster treatment. Renal impairment: Intravenous dose reduction required in mild to severe impairment. IV: Neonate to Infant under 3 months 20 mg/kg every 8 hours for at least 7 days.6. Child 3 months–12 years 500 mg/m2 every 8 hours usually for 5 days. Precautions: Maintain adequate hydration. Oral dose reduction required in moderate to severe impairment.

Paediatric Formulary Committee. 2008. Kraus DM.g. 2010. hallucinations (high dose). Greenwood Village.g. eds.g. WHO Technical Report Series. October 2007 (including the model list of essential medicines for children). ed. crystalluria. BMJ Group RBS Publishing. leading to uncertain dosing regimens for some medications 150 WHO Model Formulary for Children 2010 . you can disperse tablets in water. Interactions with other medicines (* indicates severe): Ciclosporin: increased risk of nephrotoxicity. Australian medicines handbook. leukopenia. 6. lopinavir] and short shelf-life [e. diarrhoea. abdominal pain. WHO expert committee on the selection and use of essential medicines. fatigue. anorexia. If you wish. 2009. 2009. 2009. in order to improve immune function. confusion. vertigo. Pediatric dosage handbook. hepatitis. constipation.com. London. Oxford. prevention of mother-to-child transmission (MTCT) and post-exposure prophylaxis.g. Body surface area (m2) = References: height (cm) x weight (kg) 3600 Ashley C. arthralgia. Currie A. Adelaide. 950 (http://www. 16th ed. anaemia. drug therapy should be designed to minimize the risk of toxicity and development of resistance. Studies of ART in children demonstrate that similar improvements to those obtained in adults are seen in morbidity. ed. dizziness. efavirenz is not approved for children less than 3 years of age) • limitations of formulations for paediatric patients (e. thrombocytopenia. Klasco RK.g. vomiting. large volumes required [e.6 Anti-infective medicines encephalopathy (reported in 1% patients with IV use). ritonavir]. seizures. mortality and surrogate markers with many different potent ART regimens. Rare Coma. In all populations. the need for refrigeration [e. neutropenia. Stuart MC. Australian Medicines Handbook. Hill SR. Unique considerations for the use of ART in children include the following: • fewer drug choices than for adults (e. reduce risk of opportunistic infections and other complications of human immunodeficiency virus (HIV) infection (e. The renal drug handbook.g. Thomson Micromedex. encephalopathy and malignancy) and facilitate improved growth.thomsonhc.2 Antiretrovirals Antiretroviral therapy in children Antiretroviral (ART) medicines are essential for the treatment and prevention of HIV infection in children. World Health Organization. didanosine]) • limitations of currently available pharmacokinetic data for children. 2008. injection site reactions. rash. Taketomo CK. Hudson. Uncommon Agitation. development and quality of life. The selection and use of essential medicines: report of the WHO expert committee. toxic epidermal necrolysis. British national formulary for children 2009.4. eds. Drugdex system. Radcliffe Publishing.g. Hodding JH. 3rd ed.int/medicines/publications/essentialmeds_committeereports/TRS_950.who. Zidovudine: neurotoxicity. renal impairment. 2009. Rossi S. poor palatability [e. ART in children is aimed at reducing the plasma viral load as much as possible for as long as possible. weakness. anaphylaxis. sore throat. Kouimtzi M. Geneva. headache. stavudine liquid]. Lexi-Comp. Notes: Make sure that you drink plenty of fluids. Adverse effects: Common Nausea. oedema.pdf ). (http://www. and maximize long-term compliance. WHO model formulary. Stevens-Johnson syndrome. accessed 10 February 2010).

Recommendations for a public health approach). Detailed recommendations for prevention of MTCT of HIV.4 Antiviral medicines • the need for dose adjustment as children grow (to avoid under-dosing and drug resistance) • less data regarding toxicity for children and non-specific clinical manifestations of toxicity in infants • longer potential cumulative treatment duration. avoiding dosing errors and potentially improving adherence.who. Prevention of mother-to-child transmission To prevent the transmission of HIV from mother to baby. Current WHO guidelines on post-exposure prophylaxis to prevent HIV infection are accessible at the following website: http://www. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. now available in many regions. including the role of ART. care and support to mothers living with HIV and to their children and families. more tolerable for children than multiple tablets. They have the advantages of being relatively more affordable. these guidelines were under review. allow for easier administration of antiretroviral medications based on age or weight bands.int/hiv/topics/mtct/en/index. Lamivudine + Nevirapine + Stavudine ATC code: J05AR07 Tablet: 150 mg + 200 mg + 30 mg Tablet (dispersible): 30 mg + 50 mg + 6 mg.html Post-exposure prophylaxis Treatment with antiretroviral drugs may be appropriate following exposure to HIV-contaminated materials and sexual assault. At the time of printing.6. WHO Model Formulary for Children 2010 151 .who. 60 mg + 100 mg + 12 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection infants and children: towards universal access. which includes the following four components: • primary prevention of HIV infection among women of childbearing age • preventing unintended pregnancies among women living with HIV • preventing HIV transmission from a woman living with HIV to her infant • providing appropriate treatment. WHO promotes a comprehensive approach. can be accessed at the following website: http://www.int/hiv/topics/prophylaxis/en/ Fixed-dose drug combinations • Fixed-dose drug combinations.

discontinue permanently if liver abnormalities accompanied by hypersensitivity reaction (rash. oral lesions. monitor closely for skin reactions during first 18 weeks. incidence reduced if introduced at low dose and dose increased gradually. close monitoring required during first 18 weeks. is most common side-effect. chronic hepatitis B or C. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. discontinue permanently if significant liver function abnormalities recur. renal impairment. use with extreme caution in children with advanced HIV infection. general malaise or hypersensitivity reactions. usually in first 6 weeks. Pancreatitis If no suitable alternative exists. arthralgia. hepatitis (especially hepatitis C treated with interferon alfa and ribavirin). renal impairment. Rash Rash. the antiretroviral drug formulation choices. exacerbation of hepatitis in patients with chronic hepatitis B may occur on discontinuation of lamivudine. symptomatic hyperlactataemia. severe skin reaction or hypersensitivity reactions develop. caution in children with hepatomegaly. PATIeNT ADVICe Patients and/or caregivers should be told how to recognize hypersensitivity reactions and advised to discontinue treatment and seek immediate medical attention if symptoms of hepatitis. renal impairment. chronic hepatitis B or C. monitor patient closely if mild to moderate liver abnormalities with no hypersensitivity reaction. Special Notes: Also referred to as 3TC+NVP+d4T. conjunctivitis. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. fever. granulocytopenia). Hepatic disease Potentially life-threatening hepatotoxicity including fatal fulminant hepatitis reported usually in the first 6 weeks. if rash mild or moderate. high CD4 cell count. progressive hepatomegaly or lactic acidosis.6 Anti-infective medicines The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. post-exposure prophylaxis. pancreatitis (see below). Precautions: LAMIVUDINe Pancreatitis (see below). discontinue if rapid deterioration in liver function tests. The target doses for each drug are included in the tables. and were directed towards what could be considered the “optimal” dose for a particular weight band. hepatic disease (see below). liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. Situations that are frequently encountered in resource-limited settings. suspend if severe liver abnormalities but no hypersensitivity reaction. and expert paediatric pharmacology consultation. may continue without interruption but dose should not be increased until rash resolves. or in combination with other antiretroviral drugs). Indications: HIV infection (alone as a complete regimen. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. myalgia. NeVIRAPINe Hepatic impairment. discontinue permanently if severe rash or if rash accompanied by blistering. previous history of pancreatitis or risk factors for pancreatitis. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. facial oedema. hepatic disease (see below). 152 WHO Model Formulary for Children 2010 . Decisions about dosing were based upon manufacturer’s information. chronic hepatitis B or C. hepatitis. lymphadenopathy. eosinophilia. STAVUDINe Peripheral neuropathy (see below). available data from clinical studies. Contraindications: NeVIRAPINe Moderate or severe hepatic impairment.

4 Antiviral medicines Peripheral neuropathy Suspend if peripheral neuropathy develops (characterized by persistent numbness.9 a.9 10. Lamivudine + Nevirapine + Stavudine: recommended dosing based on weight bands Weight range (kg) Target doses Lamivudine 4 mg/kg twice daily Nevirapine 160–200 mg/m2 twice daily after 2 week induction dose Stavudine 1 mg/kg twice daily Formulation Lamivudine/ nevirapine/ stavudine tablets 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 30 mg/50 mg/6 mg 150 mg/200 mg/30 mg 150 mg/200 mg/30 mg Dose (tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3. Wait no longer than 28 days for the rash to resolve then seek an alternative regimen.9 29. Caution in patients with hepatomegaly.6. Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. Since significant elevations of triglycerides cause pancreatitis. resume treatment at half previous dose.m.9 11. on return to normal values. Whenever possible. tingling or pain in feet or hands).m. Pancreatitis Avoid use or use extreme caution in patients with history of pancreatitis. discontinue if rapid deterioration in liver function tests. If symptoms of pancreatitis develop or if serum amylase or lipase is raised (even if asymptomatic). is used for 2 weeks to decrease the likelihood of rash incidence. If the child experiences a rash in the lead-in period. re-initiate treatment only if essential (using low dose increased gradually if appropriate). suspend treatment until diagnosis of pancreatitis excluded.9 6. Dose: HIV infection (alone as a complete regimen.9 7. symptomatic hyperlactataemia.9 34. monitor closely if elevated. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p. intravenous pentamidine isetionate).9 9.9 13. half of the normal daily dosage. SPeCIAL CONSIDeRATIONS FOR DOSING A lead-in dose of nevirapine. For children < 30 kg. use individual components during induction period.9 5. liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. monitor closely if concomitant therapy unavoidable.9 24. hepatitis.9 4. then remain on the half dosage until the rash resolves.9 16. Contains a fixed dose of nevirapine. therefore cannot be used for nevirapine induction as nevirapine dose escalation is required.9 19. avoid concomitant treatment with other drugs known to cause pancreatic toxicity (for example. use of 14 day lead-in decreases the incidence of rash. if symptoms resolve satisfactorily on withdrawal and if stavudine needs to be continued. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 WHO Model Formulary for Children 2010 153 . or in combination with other antiretroviral drugs). See individual drug monographs for dose recommendations. progressive hepatomegaly or lactic acidosis.9 8.

severe hepatomegaly with steatosis. skin rash. fat redistribution (see Lipodystrophy. fatigue. nausea. use with caution in patients with liver disease. STAVUDINe Mild: reduce dose to 50%. Uncommon Peripheral neuropathy. skin rashes. life threatening and possibly fatal). Rare Increased liver enzymes. NeVIRAPINe Mild and moderate: no dosage adjustment required. See notes in Precautions. myalgia. NeVIRAPINe * Contraceptives. fat redistribution (see Lipodystrophy. anaemia and granulocytopenia. * Rifampicin: reduced plasma concentration of nevirapine (avoid concomitant use). NeVIRAPINe Avoid in moderate or severe hepatic impairment. See notes in Precautions. 154 WHO Model Formulary for Children 2010 . up to 14%). vomiting. Severe: use with caution. Efavirenz: plasma efavirenz concentration reduced. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). Indinavir: nevirapine reduces plasma concentration of indinavir. nausea. Interactions with other medicines (* indicates severe): LAMIVUDINe * Emtricitabine: no information available. angioedema. Lopinavir: plasma concentration of lopinavir possibly reduced. diarrhoea. gastrointestinal disturbances. * Ribavirin: increased risk of hepatic toxicity. sleep disorders. manufacturer advises avoid concomitant use. Moderate: reduce dose to 25%. fatigue. severe hepatomegaly with steatosis. fever.6 Anti-infective medicines Renal impairment: LAMIVUDINe Moderate to severe: reduce dose. NeVIRAPINe Common Rash. increased liver enzymes. abdominal pain. Rare Toxic epidermal necrolysis. anorexia. decreased neutrophil count. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. Use with caution in mild and moderate impairment. pancreatitis (more commonly reported in children. Hepatic impairment: LAMIVUDINe Dosage adjustment not required. Adverse effects: LAMIVUDINe Common Headache. STAVUDINe Common Headache. Saquinavir: plasma concentration of saquinavir reduced. abdominal pain. Stevens-Johnson syndrome. Uncommon Hepatotoxicity (can be severe. * Interferon alfa: increased risk of hepatic toxicity. but a direct causal relationship has not been established. Uncommon Peripheral neuropathy. * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). * Fluconazole: increased plasma concentration of nevirapine. Sulfamethoxazole + trimethoprim: plasma concentration of lamivudine increased (avoid concomitant use of high-dose sulfamethoxazole + trimethoprim). use with caution in patients with decompensated liver disease. STAVUDINe Dosage adjustment not required. lactic acidosis. hypersensitivity reactions. headache. anaemia. diarrhoea. oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect). below). lactic acidosis. pancreatitis. below). See notes in Precautions. rapidly progressive ascending neuromuscular weakness. * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). arthralgia.

Hill SR. Geneva. Guidelines for the use of antiretroviral agents in pediatric HIV infection. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.6.nih. accessed 10 February 2010). HIV Medicine. accessed 10 February 2010). also increased risk of fatal and non-fatal lactic acidosis. WHO 17th expert committee on the selection and use of essential medicines.pdf ). WHO Model Formulary for Children 2010 155 . At the time of printing. October 2007 (including the model list of essential medicines for children). * Voriconazole: increased plasma concentration of nevirapine and reduced concentration of voriconazole. 150 mg + 200 mg + 300 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. 23 February 2009:1–139 (http://aidsinfo. * Ribavirin: may decrease stavudine levels. WHO Technical Report Series. Geneva.who. Forthcoming 2010. World Health Organization. Tablets should preferably not be split unless scored. 2009. accessed 10 February 2010). eds. Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Twice daily fixed dose tablet can be started if no rash or liver function test abnormalities present. References: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access: Recommendations for a public health approach. 2006 (http://www. World Health Organization. therefore cannot be used for nevirapine induction as dose escalation required. During induction period. British national formulary for children 2009. 18 May 2009 (http://www.int/hiv/paediatric/external_report_dosing_paediatric_ARVs. World Health Organization. The selection and use of essential medicines: report of the WHO expert committee. 2008.pdf. Paediatric Formulary Committee. 2008. Geneva. Notes: Can be given without regard to food.who. BMJ Group RBS Publishing. Stuart MC. * Zidovudine: may antagonize effect of stavudine (concomitant use contraindicated). Kouimtzi M. Unedited draft report of the 17th expert committee on the selection and use of essential medicines. 2009. STAVUDINe * Didanosine: increased risk of adverse effects. Recommendations for a public health approach). Contains a fixed dose of nevirapine.int/medicines/publications/essentialmeds_committeereports/TRS_950. Working group on antiretroviral therapy and medical management of HIV-infected children.pdf. 10(10):591–613. WHO Technical Report Series. * Warfarin: enhanced or reduced anticoagulant effect. PeNTA Steering Committee. London. Lamivudine + Nevirapine + Zidovudine ATC code: J05AR05 Tablet: 30 mg + 50 mg + 60 mg. WHO expert committee on the selection and use of essential medicines.pdf ). Geneva. Paediatric antiretroviral drugs: dosing: A report prepared for the WHO working group on paediatric ARV medicines.int/hiv/pub/guidelines/paediatric020907. give individual drugs separately. 950 (http://www. these guidelines were under review. World Health Organization.pdf.gov/contentfiles/pediatricguidelines.int/selection_ medicines/committees/expert/17/WeBuneditedTRS_2009. 2007 (http://www.who. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. WHO model formulary.who.4 Antiviral medicines * St John’s wort (Hypericum): reduced plasma concentration of nevirapine (avoid concomitant use).

and were directed towards what could be considered the “optimal” dose for a particular weight band. conjunctivitis. Contraindications: NeVIRAPINe Severe hepatic impairment. symptomatic hyperlactataemia. granulocytopenia). chronic hepatitis B or C. exacerbation of hepatitis in patients with chronic hepatitis B may occur on discontinuation of lamivudine. Situations that are frequently encountered in resource-limited settings. hepatitis. monitor patient closely if mild to moderate liver abnormalities with no hypersensitivity reaction.6 Anti-infective medicines The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. general malaise or hypersensitivity reactions. NeVIRAPINe Hepatic impairment. suspend if severe liver abnormalities but no hypersensitivity reaction. discontinue permanently if significant liver function abnormalities recur. Pancreatitis If no suitable alternative exists. monitor closely for skin reactions during first 18 weeks. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. progressive hepatomegaly or lactic acidosis. hepatitis (especially hepatitis C treated with interferon alfa and ribavirin). caution in children with hepatomegaly. lymphadenopathy. renal impairment. discontinue permanently if severe rash or if rash accompanied by blistering. myalgia. fever. ZIDOVUDINe Abnormally low neutrophil counts or haemoglobin. arthralgia. usually in first 6 weeks. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. is most common side-effect. Zidovudine also referred to as AZT. incidence reduced if introduced at low dose and dose increased gradually. hepatic disease (see below). may continue without interruption but dose should not be increased until rash resolves. eosinophilia. available data from clinical studies. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. discontinue permanently if liver abnormalities accompanied by hypersensitivity reaction (rash. PATIeNT ADVICe Patients and caregivers should be told how to recognize hypersensitivity reactions and advised to discontinue treatment and seek immediate medical attention if symptoms of hepatitis. use with extreme caution in children with advanced HIV infection and previous history of pancreatitis or risk factors for pancreatitis. neonates either with hyperbilirubinaemia requiring treatment other than phototherapy or with raised transaminase. oral lesions. the antiretroviral drug formulation choices. acute porphyria. facial oedema. chronic hepatitis B or C. Precautions: LAMIVUDINe Pancreatitis (see below). if rash mild or moderate. The target doses for each drug are included in the tables. Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. high CD4 cell count. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Decisions about dosing were based upon manufacturer’s information. and expert paediatric pharmacology consultation. post-exposure prophylaxis. liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. renal impairment. Hepatic disease Potentially life-threatening hepatotoxicity including fatal fulminant hepatitis reported usually in the first 6 weeks. Indications: HIV infection. Special Notes: Also referred to as 3TC+NVP+ZDV. close monitoring required during first 18 weeks. Rash Rash. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. severe skin reaction or hypersensitivity reactions develop. discontinue if rapid deterioration in liver function tests. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. 156 WHO Model Formulary for Children 2010 .

m. If the child experiences a rash in the lead-in period. Dose: HIV infection (alone as a complete regimen.9 24. For children < 30 kg.9 10.9 9. ZIDOVUDINe Severe: reduce dose. See individual drug monographs for dose recommendations.6. Wait no longer than 28 days for the rash to resolve then seek an alternative regimen. chronic hepatitis B or C. discontinue if there is any rapid deterioration in liver function tests.9 6. use with caution in patients with decompensated liver disease. SPeCIAL CONSIDeRATIONS FOR DOSING A lead-in dose of nevirapine. liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. Severe: use with caution.9 a. anaemia and myelosuppression. hepatic disease (see below). use of 14 day lead-in decreases the incidence of rash.9 19.9 16. See notes in Precautions. renal impairment. NeVIRAPINe Mild and moderate: no dosage adjustment required. progressive hepatomegaly or lactic acidosis. half of the normal daily dosage.4 Antiviral medicines ZIDOVUDINe Haematological toxicity. use individual components during induction period. WHO Model Formulary for Children 2010 157 . hepatitis.9 34. Lamivudine + Nevirapine + Zidovudine: recommended dosing based on weight bands Weight range (kg) Target doses Lamivudine 4 mg/kg twice daily Nevirapine 160–200 mg/m2 twice daily after 2 week induction dose Zidovudine 180–240 mg/m2 twice daily Formulation Lamivudine/ nevirapine/ zidovudine tablets 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 30 mg/50 mg/60 mg 150 mg/200 mg/300 mg 150 mg/200 mg/300 mg Dose (tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.m. Contains a fixed dose of nevirapine. then remain on the half dosage until the rash resolves. or in combination with other antiretroviral drugs).9 11.9 29.9 7.9 5. is used for 2 weeks to decrease the likelihood of rash incidence. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 Renal impairment: LAMIVUDINe Reduce dose in moderate and severe impairment. exercise caution in patients with hepatomegaly. symptomatic hyperlactataemia.9 13. Hepatic impairment: LAMIVUDINe Dosage adjustment not required. Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p. therefore cannot be used for nevirapine induction as nevirapine dose escalation required.9 8. including vitamin B12 deficiency.9 4.

life threatening and possibly fatal). increased liver enzymes. abdominal pain. including Stevens-Johnson syndrome. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. severe headache. Sulfamethoxazole + trimethoprim: plasma concentration of lamivudine increased (avoid concomitant use of high-dose sulfamethoxazole + trimethoprim). monitor for haematological toxicities frequently. anaemia. Uncommon Peripheral neuropathy. See notes in Precautions. NeVIRAPINe Common Rash. oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect). nausea. * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). diarrhoea. abdominal pain. arthralgia. Efavirenz: plasma efavirenz concentration reduced. Use with caution. myalgia. myositis. nausea. malaise. hypersensitivity reactions. anaemia and granulocytopenia. accumulation may occur. nausea. ZIDOVUDINe Dosage adjustment may be required. fatigue. Uncommon Myopathy (associated with prolonged use). * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). severe hepatomegaly with steatosis. lactic acidosis. Rare Toxic epidermal necrolysis. 158 WHO Model Formulary for Children 2010 . * Fluconazole: increased plasma concentration of nevirapine. Indinavir: nevirapine reduces plasma concentration of indinavir. Uncommon Hepatotoxicity (can be severe. Adverse effects: LAMIVUDINe Common Headache. up to 14%). but a direct causal relationship has not been established. ZIDOVUDINe Common Haematological toxicity including neutropenia. severe hepatomegaly with steatosis. anorexia. Lopinavir: plasma concentration of lopinavir possibly reduced. leukopenia and anaemia. lactic acidosis. Use with caution in mild impairment. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). pancreatitis (more commonly reported in children. skin rash. vomiting. * Rifampicin: reduced plasma concentration of nevirapine (avoid concomitant use). diarrhoea. Saquinavir: plasma concentration of saquinavir reduced. skin and nail pigmentation. fat redistribution (see Lipodystrophy. angioedema. decreased neutrophil count. headache. liver toxicity. * Interferon alfa: increased risk of hepatic toxicity. fatigue. NeVIRAPINe * Contraceptives. anorexia. below). * Ribavirin: increased risk of hepatic toxicity. vomiting.6 Anti-infective medicines NeVIRAPINe Avoid in moderate and severe hepatic impairment. Interactions with other medicines (* indicates severe): LAMIVUDINe * Emtricitabine: no information available. fat redistribution (see Lipodystrophy. neuropathy. fever. manufacturer advises avoid concomitant use. below).

Kouimtzi M. Geneva. London. World Health Organization.int/medicines/publications/essentialmeds_committeereports/TRS_950. Unedited draft report of the 17th expert committee on the selection and use of essential medicines. WHO 17th expert committee on the selection and use of essential medicines.who. 2008. Paediatric Formulary Committee. Kraus DM. During induction period.nih. Contains a fixed dose of nevirapine. HIV Medicine. Pyrimethamine: increased antifolate effect. Taketomo CK. BMJ Group RBS Publishing. * Warfarin: enhanced or reduced anticoagulant effect.pdf ). accessed 10 February 2010). give individual drugs separately. Guidelines for the use of antiretroviral agents in pediatric HIV infection.who.gov/contentfiles/pediatricguidelines. Hodding JH. Hudson.int/hiv/pub/guidelines/paediatric020907. Stavudine: may antagonize effect of stavudine (concomitant use contraindicated).int/hiv/paediatric/external_report_dosing_paediatric_ARVs. 23 February 2009:1–139 (http://aidsinfo. The selection and use of essential medicines: report of the WHO expert committee. British national formulary for children 2009. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. Twice daily fixed dose tablet can be started if no rash or liver function test abnormalities present.pdf ). Phenytoin: plasma phenytoin concentration increased or decreased by zidovudine. WHO model formulary. WHO expert committee on the selection and use of essential medicines. WHO Technical Report Series. Geneva. 2007 (http://www. Stuart MC. 2008. Working group on antiretroviral therapy and medical management of HIV-infected children. 10(10):591–613. Geneva. Lexi-Comp. WHO Technical Report Series. Pediatric dosage handbook. they may be crushed and mixed with a small amount of food or water and taken immediately. World Health Organization.who. eds. * Voriconazole: increased plasma concentration of nevirapine and reduced concentration of voriconazole. 2009. * Ribavirin: increased risk of hepatic and haematological toxicity. PeNTA Steering Committee. 2009. ZIDOVUDINe NOTe Increased risk of toxicity with nephrotoxic and myelosuppressive drugs.6. Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach.who. Tablets should preferably not be split unless scored (to ensure accurate dosing). * Interferon alfa: increased risk of hepatic and haematological toxicity.int/selection_ medicines/committees/expert/17/WeBuneditedTRS_2009.pdf.pdf. Fluconazole: increased plasma concentration of zidovudine (increased risk of toxicity). Ganciclovir: increased risk of haematological toxicity.4 Antiviral medicines * St John’s wort (Hypericum): reduced plasma concentration of nevirapine (avoid concomitant use). Forthcoming 2010. Paediatric antiretroviral drugs: dosing: A report prepared for the WHO working group on paediatric ARV medicines. World Health Organization.pdf. 18 May 2009 (http://www. 2009. 2006 (http://www. 950 (http://www. WHO Model Formulary for Children 2010 159 . Notes: Can be given without regard to food. Rifampicin: avoidance of rifampicin advised by manufacturer of zidovudine. World Health Organization. accessed 10 February 2010). accessed 10 February 2010). October 2007 (including the model list of essential medicines for children). References: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access: Recommendations for a public health approach. therefore cannot be used for nevirapine induction as dose escalation required. Hill SR. 16th ed. Geneva. Valproic acid: plasma concentration of zidovudine possibly increased (risk of toxicity).

hepatic disease (see below). Zidovudine also referred to as AZT. 150 mg + 300 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. ZIDOVUDINe Haematological toxicity including vitamin B12 deficiency. hepatitis (especially hepatitis C treated with interferon alfa and ribavirin). neonates either with hyperbilirubinaemia requiring treatment other than phototherapy or with raised transaminase. At the time of printing. discontinue if rapid deterioration in liver function tests. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. exacerbation of hepatitis in patients with chronic hepatitis B may occur on discontinuation of lamivudine. the antiretroviral drug formulation choices. Decisions about dosing were based upon manufacturer’s information. these guidelines were under review. and expert paediatric pharmacology consultation. progressive hepatomegaly or lactic acidosis. symptomatic hyperlactataemia. caution in children with hepatomegaly. available data from clinical studies. chronic hepatitis B or C. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. chronic hepatitis B or C. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose.6 Anti-infective medicines Lamivudine + Zidovudine ATC code: J05AR01 Tablet: 30 mg + 60 mg. 160 WHO Model Formulary for Children 2010 . Pancreatitis If no suitable alternative exists. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. Special Notes: Also referred to as 3TC + ZDV. Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. Recommendations for a public health approach). Hepatic disease Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. and were directed towards what could be considered the “optimal” dose for a particular weight band. The target doses for each drug are included in the tables. hepatic disease (see below). including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. renal impairment. exercise caution in patients with hepatomegaly. acute porphyria. renal impairment. Precautions: LAMIVUDINe Pancreatitis (see below). Contraindications: ZIDOVUDINe Abnormally low neutrophil counts or haemoglobin. symptomatic hyperlactataemia. discontinue if there is any rapid deterioration in liver function tests. progressive hepatomegaly or lactic acidosis. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. use with extreme caution in children with advanced HIV infection and a previous history of pancreatitis or risk factors for pancreatitis. Indications: HIV infection (in combination with other antiretroviral drugs). hepatitis. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. anaemia and myelosuppression. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Situations that are frequently encountered in resource-limited settings. liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis.

malaise. skin rash.9 a.6. vomiting. Interactions with other medicines (* indicates severe): LAMIVUDINe * Emtricitabine: no information available.m. liver toxicity. increased liver enzymes. fatigue.9 19. anorexia.m. fat redistribution (see Lipodystrophy below). WHO Model Formulary for Children 2010 161 . severe hepatomegaly with steatosis.9 5. lactic acidosis.4 Dose: Antiviral medicines HIV infection (alone as a complete regimen. diarrhoea.9 7. skin and nail pigmentation. severe hepatomegaly with steatosis. but a direct causal relationship has not been established. manufacturer advises to avoid concomitant use. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 Renal impairment: LAMIVUDINe Moderate or severe: reduce dose. neuropathy. * Interferon alfa: increased risk of hepatic toxicity. leukopenia and anaemia. ZIDOVUDINe Severe: reduce dose.9 16.9 13. nausea. use with caution in patients with decompensated liver disease. lactic acidosis. up to 14%). abdominal pain.9 8. severe headache.9 11. Use with caution. decreased neutrophil count. ZIDOVUDINe Dosage adjustment may be required.9 29. nausea. Uncommon Peripheral neuropathy. pancreatitis (more commonly reported in children. fat redistribution (see Lipodystrophy below). myositis. ZIDOVUDINe Common Haematological toxicity including neutropenia.9 24. Lamivudine + Zidovudine: recommended dosing based on weight bands Weight range (kg) Target doses Lamivudine 4 mg/kg twice daily Zidovudine 180–240 mg/m2 twice daily Formulation Lamivudine/zidovudine tablets 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 30 mg/60 mg 150 mg/300 mg 150 mg/300 mg Dose (tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 6. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. anorexia. accumulation may occur. or in combination with other antiretroviral drugs). Uncommon Myopathy (associated with prolonged use). Adverse effects: LAMIVUDINe Common Headache. Hepatic impairment: LAMIVUDINe Dosage adjustment not required.9 34. anaemia.9 10. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p.9 4. See notes in Precautions.9 9. monitor for haematological toxicities frequently.

950 (http://www. Ganciclovir: increased risk of haematological toxicity. Stuart MC. * Interferon alfa: increased risk of hepatic and haematological toxicity. WHO Technical Report Series. 2008. Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Geneva. * Ribavirin: increased risk of hepatic and haematological toxicity.gov/contentfiles/pediatricguidelines. London.who. Fluconazole: increased plasma concentration of zidovudine (increased risk of toxicity). Sulfamethoxazole + trimethoprim: plasma concentration of lamivudine increased (avoid concomitant use of high dose sulfamethoxazole + trimethoprim). 23 February 2009:1–139 (http://aidsinfo. Forthcoming 2010. 18 May 2009 (http://www. Valproic acid: plasma concentration of zidovudine possibly increased (risk of toxicity). Tablets can be crushed and mixed with a small amount of water or food and taken immediately. Unedited draft report of the 17th expert committee on the selection and use of essential medicines. Phenytoin: plasma phenytoin concentration increased or decreased by zidovudine. ZIDOVUDINe NOTe Increased risk of toxicity with nephrotoxic and myelosuppressive drugs. accessed 10 February 2010). Paediatric Formulary Committee. Rifampicin: avoidance of rifampicin advised by manufacturer of zidovudine. 2009.nih.int/hiv/paediatric/external_report_dosing_paediatric_ARVs. World Health Organization. 2007 (http://www. World Health Organization. accessed 10 February 2010). eds. British national formulary for children 2009. Working group on antiretroviral therapy and medical management of HIV-infected children.int/medicines/publications/essentialmeds_committeereports/TRS_950. WHO 17th expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee. 2006 (http://www. HIV Medicine. World Health Organization. WHO expert committee on the selection and use of essential medicines. BMJ Group RBS Publishing. Pyrimethamine: increased antifolate effect.who.pdf. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. Geneva. Geneva. Stavudine: may inhibit effect of stavudine (avoid concomitant use). Notes: No food restrictions apply. Paediatric antiretroviral drugs: dosing: A report prepared for the WHO working group on paediatric ARV medicines. References: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access: Recommendations for a public health approach.who. Tablets should not be split unless they are scored. 162 WHO Model Formulary for Children 2010 .pdf. Kouimtzi M. WHO Technical Report Series. Geneva. WHO model formulary. PeNTA Steering Committee. World Health Organization.pdf ). 2009. 10(10):591–613.who. Hill SR.int/hiv/pub/guidelines/paediatric020907.6 Anti-infective medicines * Ribavirin: increased risk of hepatic toxicity.int/selection_ medicines/committees/expert/17/WeBuneditedTRS_2009.pdf ).pdf. 2008. Guidelines for the use of antiretroviral agents in pediatric HIV infection. accessed 10 February 2010). October 2007 (including the model list of essential medicines for children).

malaise. abdominal pain. oedema. dyspnoea. and expert paediatric pharmacology consultation. but may occur at any time. Laboratory abnormalities may include raised liver enzymes (see below) and creatine kinase. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. monitor patients for symptoms every 2 weeks for 2 months. arthralgia. vomiting. influenza-like illness. Precautions: Chronic hepatitis B or C.2. the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose.1 Nucleoside/nucleotide reverse transcriptase inhibitors Abacavir ATC code: J05AF06 Oral liquid: 20 mg (as sulfate)/ml Tablet: 300 mg (as sulfate) Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir: approximately 5% of adults and children (rate varies by race/ethnicity) receiving abacavir develop a potentially fatal hypersensitivity reaction. paraesthesia. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. lethargy. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. The target doses for each drug are included in the tables. renal failure and anaphylaxis (hypersensitivity reactions presenting as sore throat. severe hepatic impairment. conjunctivitis. discontinue immediately if any symptom of hypersensitivity develops and WHO Model Formulary for Children 2010 163 . Special Notes: Also referred to as ABC. available data from clinical studies. less frequently by mouth ulceration. the antiretroviral drug formulation choices. ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. these guidelines were under review. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. lymphocytopenia. sore throat. Indications: HIV infection. and were directed towards what could be considered the “optimal” dose for a particular weight band. previous hypersensitivity reaction to abacavir. however in many cases.6. Contraindications: Severe renal impairment. At the time of printing. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. lymphadenopathy.4 Antiviral medicines 6. adult respiratory distress syndrome. cough and breathlessness identified). Decisions about dosing were based upon manufacturer’s information. cough. HyPeRSeNSITIVITy ReACTIONS Life-threatening hypersensitivity reactions characterized by fever or rash and possibly nausea. Recommendations for a public health approach). diarrhoea. headache and myalgia. Situations that are frequently encountered in resource-limited settings. Symptoms usually appear in the first 6 weeks.4. and rarely by myolysis. renal impairment. hepatic impairment. in combination with other antiretroviral drugs. hypotension.

9 13. Studies have shown an association between abacavir hypersensitivity and a specific HLA genotype (HLA-B*5701). even when other diagnoses possible (if rechallenge necessary. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p. Simplified dosing tables based on weight bands are designed around 60 mg tablets (not on the 2nd WHO Model List of essential Medicines for Children).5 kg: 300 mg/dose given twice daily Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 6.9 10. The incidence of abacavir hypersensitivity reaction is lower in the non-Caucasian population.9 19. HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis have been reported. care needed with concomitant use of drugs which cause skin toxicity.5 kg: 8 mg/kg/dose given twice daily Maximum dose > 16 years or ≥ 37.6 Anti-infective medicines do not rechallenge (risk of more severe hypersensitivity reaction). and advised to seek immediate medical attention if symptoms develop or before restarting treatment.9 34. exclude hypersensitivity reaction as the cause.m. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 Dose (tablets) 164 WHO Model Formulary for Children 2010 . it must be carried out in hospital setting).9 11. and rechallenge only if medical assistance is readily available.9 16. discontinue if hypersensitivity cannot be ruled out.9 9.9 4. symptomatic hyperlactataemia.9 7. liver enzyme abnormalities. Abacavir: recommended dosing based on weight bands using 60 mg and 300 mg tablets Weight range (kg) Target dose < 16 years or < 37. hepatitis.9 8. in combination with other antiretroviral drugs. progressive hepatomegaly or lactic acidosis.9 Formulation 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 300 mg tablet 300 mg tablet a. how to recognize signs of hypersensitivity. Oral: Infant or Child 8 mg/kg/dose given twice daily.9 24.m. Caution in patients with hepatomegaly. maximum 300 mg twice daily. discontinue if rapid deterioration in liver function tests. This genetic screening for HLA-B*5701 is recommended prior to initiation of abacavir based therapy.9 5. If abacavir is stopped for any reason other than hypersensitivity.9 29. Dose: HIV infection. or risk factors for liver disease and hepatic steatosis (including alcohol abuse). PATIeNT ADVICe Patients and caregivers should be told the importance of regular dosing (intermittent therapy may increase sensitization).

rash. Phenobarbital: plasma concentration of abacavir possibly reduced. pancreatitis.9 16. Rare Increased liver enzymes.9 5. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents.9 8.9 10. Uncommon Lactic acidosis. elevated triglycerides.4 Antiviral medicines Abacavir: recommended dosing based on weight bands using oral liquid and 300 mg tablets Weight range (kg) Target dose < 16 years or < 37.9 19.9 24. fatigue.5 0.5 1 1 1 p.m. hypersensitivity.5 0.9 6.6. Severe: avoid. elevated blood glucose.9 9.9 11. Abacavir should be stopped permanently if hypersensitivity reaction occurs. Notes: Parents and carers must be warned about potential hypersensitivity reaction.5 0. Interactions with other medicines (* indicates severe): Methadone: plasma concentration of methadone possibly reduced. Tablets may be crushed with a small amount of water or food and administered immediately. Adverse effects: Common Nausea. but a direct causal relationship has not been established. anorexia. possible increased risk of myocardial infarction. Can be given without regard to food.9 13. WHO Model Formulary for Children 2010 165 .9 34. lipodystrophy (see below). Store oral solution at room temperature (20–25 ºC). 3 ml 3 ml 3 ml 4 ml 4 ml 4 ml 4 ml 6 ml 6 ml 6 ml 0. may be refrigerated.m. headache.5 kg: 300 mg/dose given twice daily Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.5 kg: 8 mg/kg/dose given twice daily Maximum dose > 16 years or ≥ 37. Rifampicin: plasma concentration of abacavir possibly reduced.9 Formulation 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 20 mg/ml syrup 300 mg tablet 300 mg tablet 300 mg tablet 300 mg tablet 300 mg tablet a. vomiting. diarrhoea. fever. 3 ml 3 ml 3 ml 4 ml 4 ml 4 ml 4 ml 6 ml 6 ml 6 ml 0. Hepatic impairment: Moderate: avoid unless essential. Phenytoin: plasma concentration of abacavir possibly reduced.9 7. severe hepatomegaly with steatosis.5 1 1 Dose (ml or tablets) Renal impairment: Severe: avoid.9 4.9 29.

Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. available data from clinical studies. and were directed towards what could be considered the “optimal” dose for a particular weight band. Situations that are frequently encountered in resource-limited settings. dispersible): 25 mg.int/hiv/pub/guidelines/paediatric020907. Geneva. 166 WHO Model Formulary for Children 2010 .int/hiv/paediatric/external_report_dosing_paediatric_ARVs. 100 mg. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally.who. 2006 (http://www. Hudson. London.pdf. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. The target doses for each drug are included in the tables. World Health Organization. Australian Medicines Handbook.pdf. 10(10):591–613. 16th ed. HIV Medicine. 250 mg packets Capsule (unbuffered enteric coated): 125 mg. ed. Lexi-Comp. Adelaide. 2009. World Health Organization. 2009. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. British national formulary for children 2009. 23 February 2009:1–139 (http://aidsinfo. At the time of printing. Australian medicines handbook. Hodding JH. Rossi S. Paediatric antiretroviral drugs: dosing: A report prepared for the WHO working group on paediatric ARV medicines. 167 mg. Decisions about dosing were based upon manufacturer’s information. ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. these guidelines were under review. 2009. the antiretroviral drug formulation choices. and expert paediatric pharmacology consultation. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. 50 mg. Taketomo CK. accessed 10 February 2010). accessed 10 February 2010). PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. PeNTA Steering Committee. 200 mg. 2009. Working group on antiretroviral therapy and medical management of HIV-infected children. Kraus DM. 250 mg. Pediatric dosage handbook. 200 mg Fatal and non-fatal pancreatitis have been reported during therapy. 400 mg Tablet (buffered chewable. accessed 10 February 2010). Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. Didanosine ATC code: J05AF02 Buffered powder for oral liquid: 100 mg. 2007 (http://www.gov/contentfiles/pediatricguidelines. 150 mg. Paediatric Formulary Committee.who. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Geneva.nih. BMJ Group RBS Publishing.6 Anti-infective medicines References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach.pdf. Recommendations for a public health approach).

Asymptomatic peripheral retinal depigmentation in < 5% of children can also occur. WHO Model Formulary for Children 2010 167 .4 Special Notes: Also referred to as ddI. retinal or optic nerve changes. a reduced dose may be tolerated when symptoms resolve. PANCReATITIS Avoid use or use extreme caution in patients with history of pancreatitis. on return to normal values. hyperuricaemia. symptomatic hyperlactataemia. If symptoms of pancreatitis develop or if serum amylase or lipase is raised (even if asymptomatic). liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis. Not associated with vision loss and reverses when treatment is stopped. Antiviral medicines Didanosine is usually reserved for second-line regimens. Please note that giving a lower dose may result in suboptimal therapy and an increased risk of treatment failure and the development of resistant mutations. see interactions. it may be advisable to change to another drug at full dose. PeRIPHeRAL NeUROPATHy Dose related. Oral: Infant under 3 months 50 mg/m2/dose twice daily. peripheral neuropathy. Indications: HIV infection. in combination with at least two other antiretroviral drugs. Infant over 3 months or Child 90–120 mg/m2/dose twice daily (maximum 200 mg/dose twice daily or 400 mg once daily). hepatic impairment. discontinue if rapid deterioration in liver function tests. renal impairment. avoid concomitant treatment with other drugs known to cause pancreatic toxicity (for example intravenous pentamidine isetionate. or if visual changes occur. Whenever possible. Since significant elevations of triglycerides cause pancreatitis. monitor closely if elevated. chronic hepatitis B or C. Suspend treatment. in combination with at least two other antiretroviral drugs. progressive hepatomegaly or lactic acidosis. NOTe Antacids in formulation may affect absorption of other drugs. exercise caution in patients with hepatomegaly. re-initiate treatment only if essential (using low dose increased gradually if appropriate).6. hepatitis. ReTINAL OR OPTIC NeRVe CHANGeS Dilated retinal examinations recommended (especially in children) every 6 months. HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. Dose: HIV infection. suspend treatment until diagnosis of pancreatitis excluded. monitor closely if concomitant therapy unavoidable. HyPeRURICAeMIA Suspend treatment if significant elevation occurs. especially in advanced HIV infection. Simplified dosing tables based on weight bands are designed around the 25 mg tablets. stavudine and hydroxyurea). Precautions: Pancreatitis. lactic acidosis or severe hepatomegaly with steatosis.

9 11.m. NR NR 2 3 3 3 3 3 3 3 4 4 4 5 5 p.9 5.9 29. NR NR 2 2 2 2 2 3 3 3 3 3 4 5 5 Didanosine: recommended dosing based on weight bands using oral suspension and 25 mg tablets Weight range (kg) Target dose < 3 months: 50 mg/m2/dose twice daily 3 months to < 13 years: 90–120 mg/m2/dose twice daily Maximum dose (≥ 13 years or > 60 kg): 200 mg/dose twice daily or 400 mg once daily Formulation 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 10 mg/ml suspension 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet Dose (ml or tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 11.9 13.9 6.m.9 34.9 13.9 34.9 a.9 16.9 24.9 9.9 4.9 6.9 4.9 5.9 a.9 10.9 9.9 7.9 24.m.9 10.6 Anti-infective medicines Didanosine: recommended dosing based on weight bands using 25 mg tablets Weight range (kg) Target dose < 3 months: 50 mg/m2/dose twice daily 3 months to < 13 years: 90–120 mg/m2/dose twice daily Maximum dose (≥ 13 years or > 60 kg): 200 mg/dose twice daily or 400 mg once daily Formulation 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet 25 mg tablet Dose (tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 8. 3 ml 3 ml 3 ml 5 ml 5 ml 5 ml 5 ml 6 ml 6 ml 6 ml 4 4 4 5 5 p.9 19.9 29.9 16.9 19. 3 ml 3 ml 3 ml 5 ml 5 ml 5 ml 5 ml 6 ml 6 ml 6 ml 3 3 4 5 5 168 WHO Model Formulary for Children 2010 .9 8.m.9 7.

6.4 individual preparations for further specific dosing information. patients with hepatic impairment; monitor for toxicity.

Antiviral medicines

Renal impairment: Reduce dose in all degrees of impairment; consult product information for Hepatic impairment: No dose adjustment recommended. Possible increased risk of toxicity in Adverse effects: Common Diarrhoea (sometimes severe, may be related to the antacid present in the

preparation), abdominal pain, nausea, vomiting.

Uncommon Peripheral neuropathy, electrolyte abnormalities, hyperuricaemia, lactic acidosis, severe

hepatomegaly with steatosis, pancreatitis, increased liver enzymes, retinal depigmentation, retinal changes, optic neuritis, hepatic toxicity, hepatic failure, lipodystrophy (see below).

LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents, but a direct causal relationship has not been established. Interactions with other medicines (* indicates severe):

* Allopurinol: possibly increased plasma concentration of didanosine. * Hydroxyurea: increased risk of adverse effects. Avoid concurrent use if possible. * Ribavirin: increased risk of toxicity, hepatic reactions, peripheral neuropathy and pancreatitis. * Ritonavir: simultaneous administration can inactivate both drugs. Give didanosine 1 hour before or 2 hours after ritonavir. * Stavudine: increased risk of adverse effects. Avoid concurrent use if possible. * Tenofovir: plasma concentration of didanosine increased (increased risk of toxicity; avoid concomitant use).
Notes: Best given on an empty stomach 30 minutes before or at least 2 hours after a meal.

Didanosine is degraded rapidly unless given as an enteric formulation or combined with buffering agents or antacids. In children, this degradation effect may be less marked and didanosine may not have to be administered on an empty stomach.
ORAL SUSPeNSION Is not easy to use and should be avoided if possible; should be kept refrigerated; stable for 30 days; must be well shaken. TABLeTS At least two tablets of appropriate strength must be used at any one time for adequate buffering (e.g. if the child’s dose is 50 mg, administer two 25 mg tablets instead of one 50 mg tablet); didanosine tablets should be chewed, crushed or dispersed in water or clear juice before they are taken; tablets should not be swallowed whole. eNTeRIC-COATeD BeADLeTS IN CAPSULeS Can be opened and sprinkled on a small amount of food, but this may decrease the area under the curve; do not crush or chew beadlets.
Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access: Recommendations for a public health approach. Geneva, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/WHOpaediatric. pdf, accessed 10 February 2010). Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. PeNTA Steering Committee. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Medicine, 2009, 10(10):591–613. WHO expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee, October 2007 (including the model list of essential medicines for children). WHO Technical Report Series, 2008, 950 (http://www.who.int/medicines/publications/essentialmeds_committeereports/TRS_950.pdf ). Working group on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 23 February 2009:1–139 (http://aidsinfo.nih.gov/contentfiles/pediatricguidelines.pdf, accessed 10 February 2010).

References:

WHO Model Formulary for Children 2010

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6

Anti-infective medicines

Emtricitabine
ATC code: J05AF09

Capsule: 200 mg Oral liquid: 10 mg/ml ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. Recommendations for a public health approach). At the time of printing, these guidelines were under review. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available.
Special Notes: Also referred to as FTC.

emtricitabine is an acceptable alternative to lamivudine, based on knowledge of the pharmacology, the resistance patterns and clinical trials of antiretrovirals. WHO age/weight restriction: > 3 months.
Indications: HIV infection, in combination with at least two other antiretroviral drugs. Contraindications: Avoid concomitant use with lamivudine. Precautions: Renal impairment; hepatic disease. HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. exercise caution in patients with hepatomegaly, hepatitis (especially hepatitis C treated with interferon alfa and ribavirin), liver enzyme abnormalities or risk factors for liver disease and hepatic steatosis; discontinue if rapid deterioration in liver function tests, symptomatic hyperlactataemia, progressive hepatomegaly or lactic acidosis. exacerbation of hepatitis in patients with chronic hepatitis B may occur on discontinuation of emtricitabine; monitoring required. Dose: NOTe Oral liquid and capsules are not bioequivalent. 240 mg oral solution ≡ 200 mg capsule; where appropriate, capsules may be used instead of oral solution; oral solution contains propylene glycol as an excipient.

HIV infection, in combination with other antiretroviral drugs. Oral: Child over 3 months 6 mg/kg (maximum 200 mg) daily.
Renal impairment: Mild or worse impairment: reduce dose or increase dosing interval. Consult

product literature.

Hepatic impairment: Dosage adjustment not required; use with caution in patients with liver disease.

See notes in Precautions.

Adverse effects: Common Diarrhoea, nausea, rash (may be higher in African Americans; up to 32%

incidence reported), hyperpigmentation of palms and/or soles (more common in children, females and non-Caucasian people). below).

Uncommon Neutropenia, lactic acidosis, severe hepatomegaly with steatosis, lipodystrophy (see LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents, but a direct causal relationship has not been established.

170

WHO Model Formulary for Children 2010

6.4
Interactions with other medicines (* indicates severe):

Antiviral medicines

* Ganciclovir: possible increased toxicity of emtricitabine. Lamivudine: avoid concomitant use. * Ribavirin: possible increased toxicity of emtricitabine. * Valganciclovir: possible increased toxicity of emtricitabine. Notes: Can be given without regard to food. Oral solution should be refrigerated. Can be kept at room temperature up to 25 °C if used within 3 months.
References:
Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Geneva, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf, accessed 10 February 2010). Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. PeNTA Steering Committee. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Medicine, 2009, 10(10):591–613. Working group on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 23 February 2009:1–139 (http://aidsinfo.nih.gov/contentfiles/pediatricguidelines.pdf, accessed 10 February 2010).

Lamivudine
Tablet: 150 mg

ATC code: J05AF05

Oral liquid: 10 mg/ml

ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. Recommendations for a public health approach). At the time of printing, these guidelines were under review. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables, as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. The target doses for each drug are included in the tables; however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. Decisions about dosing were based upon manufacturer’s information, the antiretroviral drug formulation choices, available data from clinical studies, and expert paediatric pharmacology consultation, and were directed towards what could be considered the “optimal” dose for a particular weight band, given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. Situations that are frequently encountered in resource-limited settings, including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. WHO Model Formulary for Children 2010 171

6

Anti-infective medicines

Special Notes: Also referred to as 3TC. Indications: HIV infection, in combination with at least two other antiretroviral drugs. Precautions: Pancreatitis (see below); renal impairment; chronic hepatitis B or C; hepatic disease (see

below).

PANCReATITIS If no suitable alternative exists, use with extreme caution in children with advanced HIV infection, previous history of pancreatitis or risk factors for pancreatitis. HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported; caution in children with hepatomegaly, hepatitis (especially hepatitis C treated with interferon alfa and ribavirin), liver enzyme abnormalities, or risk factors for liver disease and hepatic steatosis; discontinue if rapid deterioration in liver function tests, symptomatic hyperlactataemia, progressive hepatomegaly or lactic acidosis. exacerbation of hepatitis in patients with chronic hepatitis B may occur on discontinuation of lamivudine. Dose:

HIV infection, in combination with other antiretroviral drugs. Oral: Neonate 2 mg/kg/dose given twice daily. Infant or Child 4 mg/kg/dose given twice daily, maximum 150 mg twice daily. Simplified dosing tables based on weight bands are designed around 30 mg tablets (not on the 2nd WHO Model List of essential Medicines for Children). Lamivudine: recommended dosing based on weight bands using 30 mg and 150 mg tablets
Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 4.9 5.9 6.9 7.9 8.9 9.9 10.9 11.9 13.9 16.9 19.9 24.9 29.9 34.9 Target dose Infant or Child: 4 mg/kg twice daily to a maximum of 150 mg twice daily Formulation 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 30 mg tablet 150 mg tablet 150 mg tablet Dose (tablets) a.m. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p.m. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1

172

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6.4

Antiviral medicines

Lamivudine: recommended dosing based on weight bands using the oral liquid and 150 mg tablets
Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 4.9 5.9 6.9 7.9 8.9 9.9 10.9 11.9 13.9 16.9 19.9 24.9 29.9 34.9 Target dose Infant or Child: 4 mg/kg twice daily to a maximum of 150 mg twice daily Formulation 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 10 mg/ml solution 150 mg tablet 150 mg tablet 150 mg tablet 150 mg tablet 150 mg tablet Dose (ml or tablets) a.m. 3 ml 3 ml 3 ml 4 ml 4 ml 4 ml 4 ml 6 ml 6 ml 6 ml 0.5 0.5 1 1 1 p.m. 3 ml 3 ml 3 ml 4 ml 4 ml 4 ml 4 ml 6 ml 6 ml 6 ml 0.5 0.5 0.5 1 1

Renal impairment: Moderate to severe: reduce dose. Hepatic impairment: Dosage adjustment not required; use with caution in patients with

decompensated liver disease. See notes in Precautions.

Adverse effects: Common Headache, fatigue, nausea, anorexia, diarrhoea, skin rash, abdominal pain,

pancreatitis (more commonly reported in children; up to 14%).

Uncommon Peripheral neuropathy, anaemia, decreased neutrophil count, increased liver enzymes, fat

redistribution (see Lipodystrophy below), lactic acidosis, severe hepatomegaly with steatosis.

LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents, but a direct causal relationship has not been established. Interactions with other medicines (* indicates severe):

* Emtricitabine: no information available; manufacturer advises to avoid concomitant use. * Interferon alfa: increased risk of hepatic toxicity. * Ribavirin: increased risk of hepatic toxicity. Sulfamethoxazole + trimethoprim: plasma concentration of lamivudine increased (avoid concomitant use of high dose sulfamethoxazole + trimethoprim).
Notes: Well tolerated.

Can be given without regard to food. Store oral solution at room temperature. Use within 1 month of opening. Tablets may be crushed with a small amount of water or food and administered immediately. Also active against hepatitis B. Patients co-infected with HIV and hepatitis B should receive the HIV doses of lamivudine as above. WHO Model Formulary for Children 2010 173

6

Anti-infective medicines

References:

Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Geneva, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf, accessed 10 February 2010). Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. MIMS Online. Sydney, UBM Medica, 2009 (http://www.mimsonline.com.au/Search/Search.aspx, accessed 10 February 2010). PeNTA Steering Committee. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Medicine, 2009, 10(10):591–613. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Working group on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 23 February 2009:1–139 (http://aidsinfo.nih.gov/contentfiles/pediatricguidelines.pdf, accessed 10 February 2010).

Stavudine

ATC code: J05AF04

Capsule: 15 mg; 20 mg; 30 mg Powder for oral liquid: 1 mg/ml ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. Recommendations for a public health approach). At the time of printing, these guidelines were under review. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables, as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. The target doses for each drug are included in the tables; however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. Decisions about dosing were based upon manufacturer’s information, the antiretroviral drug formulation choices, available data from clinical studies, and expert paediatric pharmacology consultation, and were directed towards what could be considered the “optimal” dose for a particular weight band, given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. Situations that are frequently encountered in resource-limited settings, including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally.
Special Notes: Also referred to as d4T.

Higher incidence of lactic acidosis and hepatic steatosis than with other NRTIs. Indications: HIV infection, in combination with at least two other antiretroviral drugs. Precautions: Peripheral neuropathy (see below); pancreatitis (see below); chronic hepatitis B or C; hepatic disease (see below); renal impairment. 174 WHO Model Formulary for Children 2010

6.4

Antiviral medicines

PeRIPHeRAL NeUROPATHy Suspend if peripheral neuropathy develops (characterized by persistent numbness, tingling or pain in feet or hands); if symptoms resolve satisfactorily on withdrawal, and if stavudine needs to be continued, resume treatment at half previous dose. Please note that giving a lower dose may result in suboptimal therapy and an increased risk of treatment failure and the development of resistance mutations; it may be advisable to change to another drug at full dose. PANCReATITIS Avoid use or use extreme caution in patients with history of pancreatitis. If symptoms of pancreatitis develop or if serum amylase or lipase is raised (even if asymptomatic), suspend treatment until diagnosis of pancreatitis excluded; on return to normal values, re-initiate treatment only if essential (using low dose increased gradually if appropriate). Whenever possible, avoid concomitant treatment with other drugs known to cause pancreatic toxicity (for example intravenous pentamidine isetionate); monitor closely if concomitant therapy unavoidable. Since significant elevations of triglycerides cause pancreatitis, monitor closely if elevated. HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. Caution in patients with hepatomegaly, hepatitis, liver enzyme abnormalities, or risk factors for liver disease and hepatic steatosis; discontinue if rapid deterioration in liver function tests, symptomatic hyperlactataemia, progressive hepatomegaly or lactic acidosis occurs. Dose:

HIV infection, in combination with other antiretroviral drugs. Oral: Infant or Child 1 mg/kg twice daily up to 30 mg twice daily. Simplified dosing tables based on weight bands are designed around 6 mg capsules (not on the 2nd WHO Model List of essential Medicines for Children). Stavudine: recommended dosing based on weight bands using 6 mg and 30 mg capsules
Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 4.9 5.9 6.9 7.9 8.9 9.9 10.9 11.9 13.9 16.9 19.9 24.9 29.9 34.9 Target dose 1 mg/kg twice daily up to 30 mg/kg twice daily Formulation 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 6 mg capsule 30 mg capsule 30 mg capsule a.m. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p.m. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 Dose (capsules)

WHO Model Formulary for Children 2010

175

6

Anti-infective medicines Stavudine: recommended dosing based on weight bands using oral liquid and 15 mg, 20 mg and 30 mg capsules
Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 4.9 5.9 6.9 7.9 8.9 9.9 10.9 11.9 13.9 16.9 19.9 24.9 29.9 34.9 Target dose 1 mg/kg twice daily up to 30 mg twice daily Formulation 1 mg/ml syrup 1 mg/ml syrup 1 mg/ml syrup 1 mg/ml syrup 1 mg/ml syrup 1 mg/ml syrup 1 mg/ml syrup 15 mg capsule 15 mg capsule 15 mg capsule 20 mg capsule 20 mg capsule 20 mg capsule 30 mg capsule 30 mg capsule Dose (ml or capsules) a.m. 6 ml 6 ml 6 ml 9 ml 9 ml 9 ml 9 ml 1 1 1 1 1 1 1 1 p.m. 6 ml 6 ml 6 ml 9 ml 9 ml 9 ml 9 ml 1 1 1 1 1 1 1 1

Renal impairment: Mild: reduce dose to 50%.

Moderate to severe: reduce dose to 25%. Hepatic impairment: Dosage adjustment not required; use with caution in patients with liver disease. See notes in Precautions. Adverse effects: Common Headache, gastrointestinal disturbances, skin rashes and lipoatrophy. Uncommon Peripheral neuropathy, pancreatitis, fat redistribution (see Lipodystrophy below), lactic acidosis, severe hepatomegaly with steatosis, sleep disorders. Rare Increased liver enzymes, rapidly progressive ascending neuromuscular weakness.
LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents, but a direct causal relationship has not been established. Interactions with other medicines (* indicates severe):

* Didanosine: increased risk of adverse effects, i.e. increased risk of fatal and non-fatal lactic acidosis or pancreatitis. * Ribavirin: may decrease stavudine levels, also increased risk of fatal and non-fatal lactic acidosis. * Zidovudine: may inhibit effect of stavudine (avoid concomitant use). Notes: Well tolerated. Do not use stavudine with zidovudine (AZT) due to an antagonistic effect. Can be given without regard to food. Oral solution is well tolerated and palatable. Powder for oral solution should be protected from excessive moisture in tightly closed containers at 25 °C. Reconstituted solution requires refrigeration; discard any unused portion after 30 days. Shake oral solution well prior to each use. Capsules can be opened and mixed with a small amount of food or water. 176 WHO Model Formulary for Children 2010

6.4
References:

Antiviral medicines

Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Geneva, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf, accessed 10 February 2010). Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. WHO expert committee on the selection and use of essential medicines. The selection and use of essential medicines: report of the WHO expert committee, October 2007 (including the model list of essential medicines for children). WHO Technical Report Series, 2008, 950 (http://www.who.int/medicines/publications/essentialmeds_committeereports/TRS_950.pdf ). Working group on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 23 February 2009:1–139 (http://aidsinfo.nih.gov/contentfiles/pediatricguidelines.pdf, accessed 10 February 2010).

Zidovudine

ATC code: J05AF01

Capsule: 100 mg; 250 mg Oral liquid: 10 mg/ml Solution for IV infusion injection: 10 mg/ml in 20 ml vial Tablet: 300 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection infants and children: towards universal access. Recommendations for a public health approach). At the time of printing, these guidelines were under review. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables, as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. The target doses for each drug are included in the tables; however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. Decisions about dosing were based upon manufacturer’s information, the antiretroviral drug formulation choices, available data from clinical studies, and expert paediatric pharmacology consultation, and were directed towards what could be considered the “optimal” dose for a particular weight band, given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. Situations that are frequently encountered in resource-limited settings, including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally.
Special Notes: Also referred to as ZDV, AZT and azidothymidine. NOTe The abbreviation AZT which has sometimes been used for zidovudine has also been used for azathioprine and aztreonam. exercise extreme caution with abbreviations. Indications: Treatment of HIV infection in combination with other antiretroviral drugs; prevention

of mother-to-child HIV transmission.

WHO Model Formulary for Children 2010

177

6

Anti-infective medicines hyperbilirubinaemia requiring treatment other than phototherapy or with raised transaminase; acute porphyria.

Contraindications: Abnormally low neutrophil counts or haemoglobin; neonates either with

Precautions: Haematological toxicity, including vitamin B12 deficiency, anaemia and

myelosuppression; renal impairment; chronic hepatitis B or C; hepatic disease (see below).

HePATIC DISeASe Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported. exercise caution in patients with hepatomegaly, hepatitis, liver enzyme abnormalities, or risk factors for liver disease and hepatic steatosis; discontinue if there is any rapid deterioration in liver function tests, symptomatic hyperlactataemia, progressive hepatomegaly or lactic acidosis. Dose:

Prevention of mother-to-child transmission of HIV. Oral: Neonate or Infant 4 mg/kg every 12 hours starting within 12 hours after birth and continuing up to 1–6 weeks of age, depending on national recommendations. IV: Neonate or Infant 1.5 mg/kg infused over 30 minutes, every 6 hours until oral dosing is possible. HIV infection, in combination with other antiretroviral drugs. Oral: Infant over 6 weeks old 180–240 mg/m2 twice daily, maximum 300 mg twice daily. Simplified dosing tables based on weight bands are designed around 60 mg tablets (not on the 2nd WHO Model List of essential Medicines for Children). Zidovudine: recommended dosing based on weight bands using 60 mg and 300 mg tablets
Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 4.9 5.9 6.9 7.9 8.9 9.9 10.9 11.9 13.9 16.9 19.9 24.9 29.9 34.9 Target dose 180–240 mg/m2 twice daily Formulation 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 60 mg tablet 300 mg tablet 300 mg tablet Dose (tablets) a.m. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p.m. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1

178

WHO Model Formulary for Children 2010

Hepatic impairment: Dosage adjustment may be required.5 1 1 Renal impairment: Severe: reduce dose.9 13. leukopenia and anaemia. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. Stavudine: may inhibit effect of stavudine (avoid concomitant use). liver toxicity. anorexia. * Interferon alfa: increased risk of hepatic and haematological toxicity. WHO Model Formulary for Children 2010 179 . Valproic acid: plasma concentration of zidovudine possibly increased (risk of toxicity). 6 ml 6 ml 6 ml 9 ml 9 ml 9 ml 9 ml 12 ml 12 ml 12 ml 0.9 Target dose Infants > 6 weeks old: 180–240 mg/m2 twice daily Maximum dose 300 mg twice daily Formulation 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 300 mg tablet 300 mg tablet 300 mg tablet 300 mg tablet 300 mg tablet Dose (ml or tablets) a.9 10.5 0. neuropathy.9 19. Adverse effects: Common Haematological toxicity. Notes: Do not use stavudine with zidovudine due to an antagonistic effect. Pyrimethamine: increased antifolate effect. Use with caution. Interactions with other medicines (* indicates severe): NOTe Increased risk of toxicity with nephrotoxic and myelosuppressive drugs. severe headache. lactic acidosis.9 7.9 29.9 16. vomiting. monitor for haematological toxicities frequently. but a direct causal relationship has not been established. fat redistribution (see Lipodystrophy. myositis. Ganciclovir: increased risk of haematological toxicity.9 6. 6 ml 6 ml 6 ml 9 ml 9 ml 9 ml 9 ml 12 ml 12 ml 12 ml 0.m. severe hepatomegaly with steatosis.9 9.9 4. Phenytoin: plasma phenytoin concentration increased or decreased by zidovudine.5 0. accumulation may occur. below).9 5. nausea. Fluconazole: increased plasma concentration of zidovudine (increased risk of toxicity). * Ribavirin: increased risk of hepatic and haematological toxicity.9 11. including neutropenia.6. Rifampicin: avoidance of rifampicin advised by manufacturer of zidovudine.5 1 1 1 p.m.9 24.5 0. malaise. Uncommon Myopathy (associated with prolonged use).9 8. skin and nail pigmentation.9 34.4 Antiviral medicines Zidovudine: recommended dosing based on weight bands using oral liquid and 300 mg tablets Weight range (kg) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.

MIMS Online. Recommendations for a public health approach). BMJ Group RBS Publishing. Lexi-Comp.pdf. accessed 10 February 2010). as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. accessed 10 February 2010).who.2. Administer immediately. Working group on antiretroviral therapy and medical management of HIV-infected children. dilute to concentration 2 mg/ml or 4 mg/ml with glucose 5% and give over 1 hour. 2009 (http://www. UBM Medica. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose.2 Non-nucleoside reverse transcriptase inhibitors Efavirenz ATC code: J05AG03 Capsule: 50 mg. Do not administer by intramuscular injection. 23 February 2009:1–139 (http://aidsinfo. 2009. 2009. Kraus DM. Guidelines for the use of antiretroviral agents in pediatric HIV infection. intravenous push or rapid infusion.4. 100 mg. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. 16th ed. At the time of printing. The target doses for each drug are included in the tables. 200 mg Oral liquid: 30 mg/ml Tablet: 600 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection infants and children: towards universal access. the antiretroviral drug formulation choices.6 Anti-infective medicines Can be given without regard to food. 2006 (http://www. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. Paediatric Formulary Committee. 10(10):591–613. or 30 minutes in neonates. Situations that are frequently encountered in resource-limited settings. Geneva. Hudson. PeNTA Steering Committee. Pediatric dosage handbook.com.aspx.int/hiv/pub/guidelines/paediatric020907. Sydney. 6. Taketomo CK. available data from clinical studies. Hodding JH.mimsonline. Store oral liquid at room temperature and protect from light. and expert paediatric pharmacology consultation. References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. 180 WHO Model Formulary for Children 2010 . World Health Organization.pdf. British national formulary for children 2009. For intermittent intravenous infusion. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. these guidelines were under review. 2009. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. London. HIV Medicine. Tablets may be crushed and combined with a small amount of food and administered immediately. accessed 10 February 2010).au/Search/Search. Capsules can be opened and dissolved in water.gov/contentfiles/pediatricguidelines. and were directed towards what could be considered the “optimal” dose for a particular weight band.nih. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. Decisions about dosing were based upon manufacturer’s information.

Oral: Infants over 3 months or 10 kg or Child 19.9 16.9 29. RASH Rash.5 2. Simplified dosing tables based on weight bands are designed around 100 mg capsules. Barrier methods in combination with other (hormonal) methods of contraception should be used.4 Antiviral medicines Special Notes: Also referred to as eFV or eFZ. Contraindications: Pregnancy (substitute nevirapine for efavirenz in pregnant women or women for whom effective contraception cannot be assured). Antihistamines may be useful for treatment and prophylaxis. Dose: NOTe The bioavailability of efavirenz oral solution is lower than that of the capsules and tablets. HIV infection in combination with other antiretroviral drugs. history of mental illness or seizures. mucosal involvement or fever. Indications: HIV infection in combination with other antiretroviral drugs. if rash is mild or moderate.9 11.9 13. Dosing with capsules or tablets is preferred due to better bioavailability. Oral: Infants over 3 months or 10 kg or Child 15 mg/kg once daily. discontinue if severe rash with blistering. PSyCHIATRIC DISORDeRS Patients should be advised to seek medical attention if severe depression. HIV infection in combination with other antiretroviral drugs.5 mg/kg once daily.) Precautions: Chronic hepatitis B or C.5 4 (may be substituted with 2 capsules of 200 mg) WHO Model Formulary for Children 2010 181 .9 24. the oral solution is not interchangeable with either capsules or tablets on a milligram for milligram basis. is the most common adverse effect.9 34. usually occurring in the first 2 weeks. 50 mg capsules should be substituted.9 19. experienced by up to 40% of patients.6. desquamation. WHO age/weight restriction: > 3 years or > 10 kg weight. as efavirenz may decrease the effectiveness of the oral contraceptive pill. where available. PATIeNT ADVICe Women of childbearing potential should undergo pregnancy testing as well as counselling about the risk to the fetus and the need to avoid pregnancy before initiating efavirenz therapy and for 12 weeks after stopping therapy. Rash is the principal side-effect seen in children. (See Interactions.5 3 3. hepatic impairment. psychosis or suicidal ideation occurs. severe renal impairment.9 Once daily 2 2 2 2. using tablets or capsules. may continue without interruption (rash usually resolves within 1 month). NOTe Where half capsules are called for. Efavirenz: recommended maintenance dosing based on weight bands Weight range (kg) Target dose 15 mg/kg once daily (capsule) Weight > 40 kg: 600 mg once daily Formulation (capsule) 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg 100 mg Dose (capsules) Bottom 10 11 12 14 17 20 25 30 Top 10. using oral liquid.

Nevirapine: plasma efavirenz concentration reduced. particularly during the first 2–4 weeks of therapy. Hepatic impairment: Mild to moderate: monitor for dose-related adverse effects (for example central NeUROLOGICAL SIDe-eFFeCTS Include somnolence. 2009. diarrhoea.gov/contentfiles/pediatricguidelines. Working group on antiretroviral therapy and medical management of HIV-infected children.pdf. Possible congenital abnormalities in infants exposed in utero during the first trimester. pancreatitis. Hodding JH. London. increased transaminase levels. neurological side-effects occur more commonly in adults than in children. Indinavir: efavirenz reduces plasma concentration of indinavir. abnormal thinking. abnormal dreams. impaired concentration. to improve tolerability of central nervous system side-effects. accessed 10 February 2010). Paediatric Formulary Committee. Notes: Take on an empty stomach. confusion. accessed 10 February 2010). abdominal pain. Capsules may be opened and added to liquids or small amounts of food to disguise their peppery taste.nih. see note in Precautions). Hudson. Rare Depression. Bedtime dosing is recommended. Rifampicin: reduced plasma concentration of efavirenz (increase efavirenz dose). Grapefruit juice: plasma concentration of efavirenz possibly increased. * Ergometrine: increased risk of ergotism (avoid concomitant use). 23 February 2009:1–139 (http://aidsinfo. BMJ Group RBS Publishing. Adverse effects: Common Rash (up to 40%. British national formulary for children 2009.6 Anti-infective medicines Renal impairment: Severe: avoid use. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2006 (http://www. suicidal ideation. World Health Organization. Food. amnesia.pdf. 16th ed. seizures. Lexi-Comp. Taketomo CK. mania. Ritonavir: increased risk of toxicity (monitor liver function tests). nervous system effects) and monitor liver function. Geneva. * St John’s wort (Hypericum): decreased efavirenz concentration and treatment failure. References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Lopinavir: plasma concentration of lopinavir reduced. Interactions with other medicines (* indicates severe): Contraceptives. 2009. oral: efficacy of estrogen containing oral contraceptives possibly reduced. Pediatric dosage handbook. agitation. * Voriconazole: decreased voriconazole levels and increased efavirenz levels. depersonalization. insomnia. * Midazolam: increased midazolam toxicity (avoid concomitant use). hallucinations.int/hiv/pub/guidelines/paediatric020907. nausea. preferably at bedtime. Saquinavir: efavirenz significantly reduces plasma concentration of saquinavir. 182 WHO Model Formulary for Children 2010 . Therapeutic drug monitoring is possible and may assist in dosing hepatically impaired patients. Safety of increased levels not assessed. Uncommon Hepatitis. Kraus DM. increases absorption by 50%. Severe: avoid use. psychosis. particularly high fat food.who. neurological side effects (see below). euphoria. consult specialist texts for management advice if this combination is necessary.

general malaise or hypersensitivity reactions. assess liver function before treatment then every 2 weeks for 2 months. including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. renal impairment. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. discontinue permanently if significant liver function abnormalities recur. Recommendations for a public health approach).4 Antiviral medicines Nevirapine ATC code: J05AG01 Oral liquid: 10 mg/ml Tablet: 200 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection in infants and children: towards universal access. and expert paediatric pharmacology consultation. eosinophilia. and were directed towards what could be considered the “optimal” dose for a particular weight band. severe skin reaction or hypersensitivity reactions develop. The target doses for each drug are included in the tables. close monitoring required during first 18 weeks. Indications: Progressive or advanced HIV infection. HePATIC DISeASe Potentially life-threatening hepatotoxicity including fatal fulminant hepatitis reported usually in the first 6 weeks. suspend if severe liver abnormalities but no hypersensitivity reaction. monitor patient closely if mild to moderate liver abnormalities with no hypersensitivity reaction. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. facial oedema. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. At the time of printing. chronic hepatitis B or C. prevention of mother-to-child transmission. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Contraindications: Moderate or severe hepatic impairment. WHO Model Formulary for Children 2010 183 . post-exposure prophylaxis. hepatitis. discontinue permanently if liver abnormalities accompanied by hypersensitivity reaction (rash. rash (see below). is most common side-effect. Decisions about dosing were based upon manufacturer’s information. Precautions: Hepatic impairment (see below). myalgia. fever. Situations that are frequently encountered in resource-limited settings. the antiretroviral drug formulation choices. may continue without interruption but dose should not be increased until rash resolves. oral lesions. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. lymphadenopathy. monitor closely for skin reactions during first 18 weeks. usually in first 6 weeks. discontinue permanently if severe rash or if rash accompanied by blistering. Special Notes: Also referred to as NVP. if rash mild or moderate. these guidelines were under review. PATIeNT ADVICe Patients and/or caregivers should be told how to recognize hypersensitivity reactions and advised to discontinue treatment and seek immediate medical attention if symptoms of hepatitis. then after 1 month and then regularly. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. available data from clinical studies. high CD4 cell count (preferably avoid in women with CD4 cell count greater then 250 cells/mm3 or in men with CD4 cell count greater than 400 cells/mm3). incidence reduced if introduced at low dose and dose increased gradually. granulocytopenia). conjunctivitis. RASH Rash.6. in combination with at least two other antiretroviral drugs. arthralgia.

9 34.9 19.9 7. Oral: Neonate.9 10. Nevirapine: recommended maintenance dosing based on weight bands using 50 mg and 200 mg tablets Weight range (kg) Target dose Maintenance dose after 2 week induction: 160–200 mg/m2 to maximum 200 mg twice daily Formulation 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 50 mg tablet 200 mg tablet 200 mg tablet Dose (tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3. c) If a mild rash occurs during the first 14 days of induction dosing. it is generally half the daily maintenance dose given once daily except where the maintenance dose is divided unequally between a. NOTe If treatment interrupted for more than 7 days.9 13. Simplified dosing tables based on weight bands are designed around 50 mg tablets (not on the 2nd WHO Model List of essential Medicines for Children).9 16.m. SPeCIAL CONSIDeRATIONS ON DOSING a) Induction dose: once daily for first 14 days. 1 1 1 1 1 1 1 2 2 2 2 2 3 1 1 184 WHO Model Formulary for Children 2010 .6 Anti-infective medicines Dose: Progressive or advanced HIV infection. b) Maintenance dose: target dose is 160–200 mg/m2 given twice daily and adjusted for more aggressive dosing in the younger age group.9 9.9 8.m.9 6. in combination with other antiretroviral drugs. If a severe rash occurs (especially if accompanied by fever.9 11.9 4. continue once daily dosing and only escalate dose once the rash has subsided and the dose is well tolerated. below). reintroduce with lowest dose and increase dose cautiously. Infant or Child initially 160–200 mg/m2 (maximum 200 mg) once daily for the first 14 days. increasing to twice daily after 14 days in the absence of nevirapine-induced rash (see Special considerations on dosing. 1 1 1 2 2 2 2 2 2 2 3 3 3 1 1 p.m. discontinue drug.m.9 29.9 5. and p.9 24. blistering or mucosal ulcerations).9 a.

Moderate to severe: avoid. diarrhoea.9 16.9 11. Hepatic impairment: See note in Precautions. Oral: Neonate or Infant birth to 6 weeks.9 4. oral: accelerated metabolism of estrogens and progestogens (reduced contraceptive effect).4 Antiviral medicines Nevirapine: recommended maintenance dosing based on weight bands using 10 mg/ml syrup and 200 mg tablets Weight range (kg) Target dose Maintenance dose after 2 week induction: 160–200 mg/m2 to maximum 200 mg twice daily Formulation 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 10 mg/ml syrup 200 mg tablet 200 mg tablet 200 mg tablet 200 mg tablet 200 mg tablet Dose (ml or tablets) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3.9 a. fever. Interactions with other medicines (* indicates severe): * Contraceptives. 5 ml 5 ml 5 ml 8 ml 8 ml 8 ml 8 ml 10 ml 10 ml 10 ml 0. Severe: use with caution. fatigue. Rare Toxic epidermal necrolysis. abdominal pain.9 34.9 10. myalgia. Adverse effects: Common Rash (including Stevens-Johnson syndrome which occurs in 0.6. under 2500 g 10 mg daily.5 0. If the infant weight is not available.9 13. over 2500 g 15 mg daily. abnormal hepatic transaminases.9 7. 5 ml 5 ml 5 ml 8 ml 8 ml 8 ml 8 ml 10 ml 10 ml 10 ml 1 1 1 1 1 p.9 24. 6 months–9 months 30 mg daily. administer 1 ml of 10 mg/ml oral suspension and thereafter follow national MTCT dosing recommendations. nausea. hypersensitivity reactions. Infant 6 weeks–6 months 20 mg daily. anaemia and granulocytopenia.9 8.9 6. headache.9 29.9 19. Mild: use with caution. arthralgia. Renal impairment: Mild and moderate: no dosage adjustment required.5 0.m. life threatening and possibly fatal). vomiting. NOTe Give first dose as early as possible after delivery.9 9.9 5.m. angioedema.5 1 1 Prevention of mother-to-child transmission (MTCT) of HIV infection. WHO Model Formulary for Children 2010 185 . 9 months to end of breastfeeding 40 mg daily. preferably within the first 6 hours.3% of patients). Uncommon Hepatotoxicity (can be severe.

23 February 2009:1–139 (http://aidsinfo.pdf. References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. * Rifampicin: reduced plasma concentration of nevirapine (avoid concomitant use). Tablets can be crushed and combined with a small amount of water or food and immediately administered. Working group on antiretroviral therapy and medical management of HIV-infected children. * Warfarin: enhanced or reduced anticoagulant effect. * Voriconazole: increased plasma concentration of nevirapine and reduced concentration of voriconazole. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. BMJ Group RBS Publishing. Hudson. Kouimtzi M. do not increase the dose until the rash has resolved. 186 WHO Model Formulary for Children 2010 . store at room temperature. HIV Medicine. * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). * St John’s wort (Hypericum): reduced plasma concentration of nevirapine (avoid concomitant use). Guidelines for the use of antiretroviral agents in pediatric HIV infection: Supplement I: pediatric antiretroviral drug information. A two week half dose lead-in is required to reduce the risk of serious rash. Stuart MC. Hodding JH. Tablets are scored and can be divided into two equal parts to give a 100 mg dose. Lexi-Comp.nih.6 Anti-infective medicines Efavirenz: plasma efavirenz concentration reduced. Working group on antiretroviral therapy and medical management of HIV-infected children. London. World Health Organization. 2009. Lopinavir: plasma concentration of lopinavir possibly reduced.pdf. WHO model formulary. Taketomo CK.gov/contentfiles/pediatricguidelines. 2008.int/hiv/pub/guidelines/paediatric020907. Paediatric Formulary Committee. World Health Organization. Saquinavir: plasma concentration of saquinavir reduced. British national formulary for children 2009. Notes: Can be given without regard to food. life-threatening rash during the 14 day lead-in period. Geneva. nih. accessed 10 February 2010). Monitor liver function prior to commencing nevirapine and then at frequent intervals (see note in Precautions). Nevirapine is preferred NNRTI for children under 3 years. Oral suspension must be shaken well. 10(10):591–613. Geneva. * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). Hill SR. accessed 10 February 2010). eds. Discard 6 months after opening. * Fluconazole: increased plasma concentration of nevirapine. 2009. 16th ed. 2006 (http://www.pdf.who. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Kraus DM. 2009. accessed 10 February 2010). PeNTA Steering Committee. fulminant hepatitis and Stevens-Johnson syndrome. Warn parents and carers about a potential severe. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). 23 February 2009:1–139 (http://aidsinfo.gov/contentfiles/pediatricguidelines. If a rash occurs during lead-in. Indinavir: nevirapine reduces plasma concentration of indinavir. Permanently cease nevirapine in children who experience severe rash. Pediatric dosage handbook.

in combination with other antiretroviral drugs and usually with low dose ritonavir booster. decreased gastric acidity. diarrhoea. lactic acidosis.4 Antiviral medicines 6. in combination with other antiretroviral drugs. HIV infection. porphyria. Continue treatment if rash is mild to moderate (usually resolves in 1–2 weeks). Hepatic impairment: Avoid use. WHO age/weight restriction: > 25 kg weight. Indications: HIV infection. fever. Recommendations for a public health approach). prolonged QT interval. Renal impairment: No dosage adjustment required. fat redistribution and lipid abnormalities (see Lipodystrophy. Oral: Target dose Child over 6 years 15 kg up to 25 kg 150 mg atazanavir and 80 mg ritonavir once daily. nausea. 25–30 kg 200 mg atazanavir and 100 mg ritonavir once daily. current recommendations differ. nephrolithiasis. treatment with rifampicin or St John’s wort. Dose: NOTe The 2nd WHO Model List of essential Medicines for Children (2009) has a weight restriction of > 25 kg for atazanavir. 300 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection infants and children: towards universal access. RASH Rash is common and median onset is 7 weeks. WHO Model Formulary for Children 2010 187 . Uncommon Asymptomatic first-degree heart block. diabetes mellitus. below). Contraindications: Hepatic impairment. risk factors for QT prolongation. vomiting. However. prolongation of the PR interval. arthralgia.4. jaundice. NOTe To be used in combination with ritonavir (as above) and other antiretrovirals. headache. Special Notes: Also referred to as ATV. Rare Second-degree heart block. dizziness. haemophilia.3 Protease inhibitors Fixed-dose combinations Atazanavir ATC code: J05Ae08 Solid oral dosage form: 100 mg. Stevens-Johnson syndrome. elevated total bilirubin (asymptomatic unconjugated hyperbilirubinaemia associated with scleral icterus or visible jaundice). depression. discontinue therapy in the case of a severe rash. Adverse effects: Common Rash (see below). Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. Recommended for patients from 6 years of age. paraesthesias. hepatitis. 30 kg and over 300 mg atazanavir and 100 mg ritonavir once daily (maximum dose). where other antiretroviral therapy has failed. 150 mg.2. Precautions: Cardiac conduction abnormalities.6. Currently insufficient data for patients less than 6 years of age. these guidelines were under review. At the time of printing. insomnia.

Ritonavir: plasma concentration possibly increased by ritonavir. Avoid combination. Dose adjustment required.pdf. oral: increased concentration and possible toxicity. Use with ritonavir booster and give with food. Swallow capsules whole. Advantage of once daily dosing over other protease inhibitors. St John’s wort: substantially reduced atazanavir concentration. Consider non-hormonal contraceptive methods. accessed 10 February 2010). PeNTA Steering Committee. Use with ritonavir. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Notes: Give with food to enhance absorption. * Ranitidine: reduced absorption. Avoid combination. 2009. Pediatric dosage handbook. The Liverpool Pharmacology Group. Dose adjustment may be required. Australian Medicines Handbook. Rossi S. References: Hodding JH. UBM Medica.gov/contentfiles/pediatricguidelines. Consult product literature. do not open. 2009. care with toxicity. Avoid combination. * Ergot derivatives: increased risk of ergot toxicity. MIMS Online. ©1999–2010 (http://www. Use with caution in patients taking other medications which affect AV conduction.6 Anti-infective medicines LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. * Rifampicin: decreased atazanavir concentrations. Increased tenofovir concentration. Administer atazanavir 2 hours before or 1 hour after didanosine. but a direct causal relationship has not been established.mimsonline. Tenofovir: reduced atazanavir concentration. * Midazolam: increased plasma levels of midazolam. * Omeprazole: decreased atazanavir concentration and therapeutic effect. Atazanavir may prolong the PR interval. When used in combination with ritonavir. Antacids: reduced absorption. 16th ed.com. 188 WHO Model Formulary for Children 2010 . 2009. Adelaide. 2009 (http://www. 23 February 2009:1–139 (http://aidsinfo. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. Sydney. Taketomo CK. Efavirenz: reduced atazanavir concentration. Hudson. If used with ritonavir. Nevirapine: reduced atazanavir concentration.aspx. Drug interaction charts. Lexi-Comp. Administer atazanavir 2 hours before or 1 hour after antacids. Kraus DM. Interactions with other medicines (* indicates severe): NOTe Atazanavir is extensively metabolized by hepatic CyP450 and is a potent CyP3A4 inhibitor and therefore interacts with numerous drugs.nih. Working group on antiretroviral therapy and medical management of HIV-infected children. Should be used in combination with ritonavir to optimize drug levels. The University of Liverpool. ed. accessed 10 February 2010). consult product literature. accessed 10 February 2010).hivdruginteractions. * Contraceptives.org. 10(10):591–613. This interaction is beneficial and ritonavir is used at low doses to increase the serum concentration of other protease inhibitors. Consult specialist texts for details and advice on management.au/Search/Search. Australian medicines handbook. efficacy of estrogen containing oral contraceptives possibly reduced. * Didanosine: buffered formulations of didanosine reduce atazanavir absorption. Avoid combination. see also ritonavir drug interactions. Dose adjustment or careful dose scheduling required. HIV Medicine.

pancreatitis (see below).3 mg Oral liquid: 80 mg + 20 mg/ml Tablet (heat stable): 100 mg + 25 mg. Situations that are frequently encountered in resource-limited settings. diabetes mellitus. Indications: HIV infection. and were directed towards what could be considered the “optimal” dose for a particular weight band. Precautions: Chronic hepatitis B or C (increased risk of hepatotoxicity). The target doses for each drug are included in the tables. and expert paediatric pharmacology consultation. Decisions about dosing were based upon manufacturer’s information. 200 mg + 50 mg ANTIReTROVIRAL DOSING The doses of antiretroviral drugs included in this formulary are based on the WHO guidelines for treatment of paediatric HIV (Antiretroviral therapy of HIV infection infants and children: towards universal access.3 mg + 33. Some of the formulations used to create these simplified dosing guidelines are not included on the 2nd WHO Model List of essential Medicines for Children but may be available locally. Special Notes: Also referred to as LPV/r or LPV/RTV. NOTe Ritonavir increases effect of lopinavir. haemophilia. as the calculation and administration of exact doses based on body surface area may be impractical in resource-limited settings. concomitant use with drugs that prolong QT interval. severe renal impairment. oral solution excipients include propylene glycol and alcohol 42%. the antiretroviral drug formulation choices. discontinue if pancreatitis diagnosed. At the time of printing. available data from clinical studies. however in many cases the dose achieved for a particular patient weight may be significantly higher or slightly lower than the target dose.6. cardiac conduction disorders.4 Antiviral medicines Lopinavir + Ritonavir ATC code: J05Ae03. Contraindications: Severe hepatic impairment. The dosing guidance for antiretroviral drugs provided in this formulary has been simplified and includes weight-based tables. Prescribers are encouraged to consult the latest guidelines as they are continually updated as further data or newer formulations become available. in combination with other antiretroviral drugs. these guidelines were under review. Prescribers are urged to consider if the dosing guidelines are appropriate for adoption given the antiretroviral drugs and formulations available locally. WHO Model Formulary for Children 2010 189 . capsules may be used instead of oral solution. where appropriate. renal impairment. NOTe 5 ml oral solution is equivalent to 3 capsules. Recommendations for a public health approach). including the possible lack of refrigeration and the lack of syrup or liquid forms for small children are taken into consideration. given the limitations imposed by currently available drug formulations and the public health advantages of simplified dosing tables. structural heart disease. oral solution contains propylene glycol: increased susceptibility to propylene glycol toxicity in slow metabolizers. PANCReATITIS Signs and symptoms suggestive of pancreatitis (including raised serum amylase and lipase) should be evaluated. hepatic impairment. the low doses of ritonavir used for this purpose do not have intrinsic antiviral activity. J05Ae06 Capsule: 133. porphyria.

5 1.9 a.m.9 kg: 12 mg/kg twice daily 14−39.5 1.5 2.9 kg: 16 mg/kg twice daily 8−9.5 1.5 2 2 2 2.9 29.9 5.9 13. 1 1 1 1.5 1.9 8.9 16.m.9 11.9 10.5 2. 1 1 1 1.5 1.9 9.9 34.6 Anti-infective medicines Dose: HIV infection.9 19.9 7.9 kg: 10 mg/kg twice daily Ritonavir target doses: 7−15 kg: 3 mg/kg twice daily 15−40 kg: 2.9 4.5 1.5 4 p.9 kg: 14 mg/kg twice daily 10−13.5 mg/kg twice daily Maximum dose: 400 mg lopinavir + 100 mg ritonavir twice daily Formulation (per ml solution) 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir 80 mg lopinavir/ 20 mg ritonavir Dose (ml) Bottom 3 4 5 6 7 8 9 10 11 12 14 17 20 25 30 Top 3. Lopinavir + Ritonavir: recommended dosing based on weight bands for oral liquid Weight range (kg) Target dose Lopinavir target doses: 5−7.5 3 4 4 or 190 WHO Model Formulary for Children 2010 . in combination with other antiretroviral drugs.9 6.9 24.5 3 3.5 2 2 2 2.

prolonged PR interval. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. Hepatic impairment: Mild to moderate: avoid use of oral solution due to propylene glycol content.9 16.9 24. headache. fat redistribution (lipoatrophy of peripheral fat and accumulation of central fat. Adverse effects: Common Diarrhoea. lipid abnormalities. * Efavirenz: plasma concentration of lopinavir reduced. spontaneous bleeding in haemophiliacs. raised hepatic enzymes. nausea. Uncommon Pancreatitis. WHO Model Formulary for Children 2010 191 . * Carbamazepine: possibly reduced plasma lopinavir concentration. Consult specialist texts for details and advice on management.6. 1 1 1 2 2 2 3 3 Renal impairment: Use with caution. 2 2 2 2 2 3 3 3 p.9 11.4 Antiviral medicines Lopinavir + Ritonavir: recommended dosing based on weight bands for tablets Weight range (kg) Target dose Lopinavir target doses: 5−7. Severe: avoid use. Rare Hepatitis. insomnia. below).9 kg: 14 mg/kg twice daily 10−13. Use tablets with caution in severe impairment. rash. Stevens-Johnson syndrome. hyperglycaemia.9 13.9 kg: 10 mg/kg twice daily Ritonavir target doses: 7−15 kg: 3 mg/kg twice daily 15−40 kg: 2. depression. Use tablets and capsules with caution.9 19. haemolytic anaemia. * Ergot derivatives: increased risk of ergot toxicity. asthenia. new onset diabetes mellitus. In combination with ritonavir.9 34. Avoid oral solution (contains propylene glycol) in severe impairment. amenorrhoea. Interactions with other medicines (* indicates severe): NOTe Lopinavir and ritonavir are extensively metabolized by hepatic CyP450 and are potent CyP3A inhibitors and therefore interact with numerous drugs. exacerbation of existing diabetes mellitus. Tablets have less gastrointestinal side-effects than capsules.5 mg/kg twice daily Maximum dose: 400 mg lopinavir + 100 mg ritonavir twice daily Formulation (tablet) 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir 100 mg lopinavir/ 25 mg ritonavir Dose (tablets) Bottom 10 11 12 14 17 20 25 30 Top 10.m. see also Ritonavir. vomiting. * Dexamethasone: possibly reduced plasma lopinavir concentration. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use.9 kg: 16 mg/kg twice daily 8−9.9 a.9 kg: 12 mg/kg twice daily 14−39. but a direct causal relationship has not been established. see Lipodystrophy. hypertension.m.9 29.

Lidocaine: possibly increased plasma concentration of lidocaine.hivdruginteractions. give didanosine 1 hour before or 2 hours after lopinavir + ritonavir. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Drug interaction charts. 2009. Pediatric dosage handbook. Hill SR. 23 February 2009:1–139 (http://aidsinfo. Rossi S. Working group on antiretroviral therapy and medical management of HIV-infected children. Australian Medicines Handbook. HIV Medicine. 10(10):591–613. PeNTA Steering Committee. Stuart MC. Notes: Tablets can be given without regard to food. Nelfinavir: plasma concentration of lopinavir reduced. 2009.who. Indications: HIV infection. World Health Organization.gov/contentfiles/pediatricguidelines. Geneva. The University of Liverpool.pdf. Nevirapine: plasma concentration of lopinavir possibly reduced. * Rifampicin: reduced plasma concentration of lopinavir (avoid concomitant use). 2008. accessed 10 February 2010). accessed 10 February 2010). plasma concentration of active metabolite of nelfinavir increased. References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Taketomo CK. 2009. Phenytoin: plasma lopinavir concentration possibly reduced. Ritonavir is recommended for use in combination as a pharmacological booster.6 Anti-infective medicines * Garlic: concurrent use of garlic and protease inhibitors can lead to reduced plasma levels and treatment failure. Oral solution and capsules should be given with food to increase absorption. Geneva. 192 WHO Model Formulary for Children 2010 . accessed 10 February 2010). 2006 (http://www. Ritonavir ATC code: J05Ae03 Oral liquid: 80 mg/ml Solid oral dosage form: 100 mg Tablet (heat stable): 25 mg. Kouimtzi M. * Simvastatin: increased risk of myopathy. 16th ed. ©1999–2010 (http://www. in combination with other antiretroviral drugs. as a pharmacological booster to increase other protease inhibitors. World Health Organization. WHO model formulary. British national formulary for children 2009. and not as an antiretroviral in its own right. Must be swallowed whole. Hudson. ed. Liquid has a low volume for each dose but a very bitter taste. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. Hodding JH. If co-administered with didanosine. Heat stable tablets cannot be broken or crushed as bioavailability is lost. Adelaide. Kraus DM. Australian medicines handbook.org. Lexi-Comp. The Liverpool Pharmacology Group. Saquinavir: increased plasma concentration of saquinavir. * Tenofovir: plasma concentration of tenofovir increased. Capsules and liquid should be refrigerated or stored at up to 25 °C with reduced 2 month expiry.int/hiv/pub/guidelines/paediatric020907. 100 mg Special Notes: Also referred to as r or RTV. Paediatric Formulary Committee. BMJ Group RBS Publishing. 2009.nih. eds. London. * Phenobarbital: plasma concentration of lopinavir possibly reduced. Once daily dosing is currently not recommended. Capsules should not be crushed or opened.pdf.

in combination with other antiretroviral drugs. exacerbation of liver disease. dizziness.6. * Codeine: ritonavir possibly increases plasma concentration of codeine. seizures. PANCReATITIS Signs and symptoms suggestive of pancreatitis (including raised serum amylase and lipase) should be evaluated. * Carbamazepine: plasma concentration possibly increased by ritonavir. * Contraceptives. anorexia. LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents. fat Rare Hyperglycaemia. renal insufficiency. 15–40 kg 2. pancreatitis (see below).5 mg/kg twice daily (maximum 100 mg twice daily). * Ciclosporin: plasma concentration possibly increased by ritonavir. Consult specialist texts for details and advice on management. diarrhoea (may impair absorption. Dexamethasone: plasma concentration possibly increased by ritonavir. * Amiodarone: increased risk of cardiac toxicity and arrhythmias. lipid abnormalities. below). hepatic impairment. dehydration. WHO Model Formulary for Children 2010 193 . discontinue if pancreatitis diagnosed. Antiviral medicines Precautions: Chronic hepatitis B or C (increased risk of hepatotoxicity). vomiting. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoidance of concomitant use. exacerbation of existing diabetes mellitus. Avoid combination. prolongation of PR interval. hyperglycaemia. structural heart disease. as a pharmacological booster to increase other protease inhibitors. Dose: HIV infection. * Amitriptyline: plasma concentration possibly increased by ritonavir. syncope. taste disturbances. Renal impairment: No dosage adjustment necessary (renal clearance is negligible). hypotension. new onset diabetes mellitus. diabetes mellitus. dyspepsia. but a direct causal relationship has not been established. * Clomipramine: plasma concentration possibly increased by ritonavir. if no alternative. Uncommon Vasodilatation. Adverse effects: Common Nausea.9 kg 3 mg/kg twice daily. Oral: Child 7–14. headache. * Amlodipine: possibly increased plasma concentration of amlodipine. spontaneous bleeding in haemophiliacs. abdominal pain. Azithromycin: plasma concentration of azithromycin possibly increased. atrioventricular block. circumoral and peripheral paraesthesia. * Chlorpromazine: plasma concentration possibly increased by ritonavir. menorrhagia. pancreatitis. oral: accelerated metabolism of estrogens (reduced contraceptive effect). cardiac conduction abnormalities. hepatitis. close monitoring required).4 Contraindications: Severe hepatic impairment. Severe: avoid in severe hepatic impairment. haemophilia. porphyria. Interactions with other medicines (* indicates severe): NOTe Ritonavir is extensively metabolized by hepatic CyP450 and is a potent CyP3A inhibitor and therefore interacts with numerous drugs. use with extreme caution. Hepatic impairment: Mild to moderate: no dosage adjustment recommended. redistribution (see Lipodystrophy.

Erythromycin: plasma concentration possibly increased by ritonavir. chocolate pudding or ice cream. * Warfarin: plasma concentration possibly increased by ritonavir. Patient can store in fridge or store at room temperature (use within 30 days). This interaction is beneficial and ritonavir is used at low doses to increase the serum concentration of other protease inhibitors. Efavirenz: increased risk of toxicity (monitor liver function tests). * Morphine: ritonavir possibly increases plasma concentration of morphine. Notes: Unpleasant/foul taste may require special techniques to increase tolerance in children. * Haloperidol: plasma concentration possibly increased by ritonavir. Shake well before use. * Simvastatin: increased risk of myopathy. 194 WHO Model Formulary for Children 2010 . * St John’s wort (Hypericum): reduced ritonavir concentration and possible loss of efficacy. avoid concomitant use). Give didanosine 1 hour before or 2 hours after ritonavir. Hydrocortisone: plasma concentration possibly increased by ritonavir. Ibuprofen: plasma concentration possibly increased by ritonavir. * Garlic: concurrent use of garlic and protease inhibitors can lead to reduced plasma levels and treatment failure. Fluconazole: plasma concentration increased by ritonavir. Administer strong flavoured foods. * Didanosine: simultaneous administration can inactivate both drugs. such as maple syrup. * Medroxyprogesterone: accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception). Do not refrigerate. * Fluoxetine: plasma concentration of fluoxetine possibly increased. Store soft gelatin capsules in fridge until dispensed. separate drugs by 2 hours. * Levonorgestrel: accelerated metabolism of levonorgestrel (reduced contraceptive effect). Give with food to increase absorption and reduce gastrointestinal adverse effects. * Voriconazole: reduced voriconazole concentration and possible treatment failure. Oral solution should be stored at room temperature. * Verapamil: plasma concentration possibly increased by ritonavir.6 Anti-infective medicines * Diazepam: plasma concentration possibly increased by ritonavir (risk of extreme sedation and respiratory depression. avoid concomitant use). Do not mix with other liquids or water. * Ergot derivatives: increased risk of ergot toxicity. * Rifampicin: plasma concentration possibly increased by ritonavir. Prednisolone: plasma concentration possibly increased by ritonavir. * Nifedipine: plasma concentration possibly increased by ritonavir. * Norethisterone: accelerated metabolism of norethisterone (reduced contraceptive effect). If prescribed with didanosine. Capsules and liquid formulations contain alcohol as a major excipient. Should be taken with food. Oral solution can be mixed with milk. Saquinavir: ritonavir increases plasma concentration of saquinavir. cheese or jam. * Fluphenazine: plasma concentration possibly increased by ritonavir. * Quinidine: increased plasma quinidine concentration (increased risk of ventricular arrhythmias. immediately after dose.

avoid in severe impairment.4 References: Antiviral medicines Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Dose: haemophilia. WHO Model Formulary for Children 2010 195 . pancreatitis. WHO age/weight restriction: > 25 kg weight. in combination with at least two other antiretroviral drugs and usually with low-dose ritonavir booster. hepatic impairment. buccal and mucosal ulceration. accessed 10 February 2010). LIPODySTROPHy Lipodystrophy has been observed in patients taking antiretroviral agents.6. rash. 16th ed. Oral: Child over 25 kg some studies reported using 33 mg/kg three times daily.com. 2006 (http://www. Adverse effects: Common Diarrhoea. 2009 (http://www. exacerbation of diabetes mellitus. Geneva. Contraindications: Severe hepatic impairment. BMJ Group RBS Publishing. eds. Should not be taken as the sole protease inhibitor. accessed 10 February 2010). Rossi S. 23 February 2009:1–139 (http://aidsinfo. hypersensitivity reactions. UBM Medica. elevation in serum transaminases. London. 2009. Stuart MC. in combination with other antiretroviral drugs and usually with low-dose ritonavir booster. but a direct causal relationship has not been established. liver damage. nausea. 2009. There is limited information available on the appropriate dose of saquinavir in children. fat redistribution (see Lipodystrophy. acne. HIV infection. Pediatric dosage handbook. headache.aspx. nephrolithiasis. British national formulary for children 2009. pancreatitis.au/Search/Search.int/hiv/pub/guidelines/paediatric020907. paraesthesia. pruritus. HIV Medicine. Precautions: Chronic hepatitis B or C. ketoacidosis. thrombocytopenia. diabetes mellitus.pdf. abdominal discomfort. Hodding JH. Kraus DM.who. Rare New onset diabetes mellitus. Working group on antiretroviral therapy and medical management of HIV-infected children. porphyria. 2008.mimsonline. photosensitivity. below). Hill SR.gov/contentfiles/pediatricguidelines. Geneva. MIMS Online. renal impairment. hypoglycaemia. Australian Medicines Handbook. spontaneous bleeding in haemophiliacs.nih. ed. Stevens-Johnson syndrome. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Lexi-Comp. World Health Organization. Hudson. Hepatic impairment: Manufacturer advises caution in moderate hepatic impairment. concomitant use of garlic (reduces plasma saquinavir concentration). Paediatric Formulary Committee. Taketomo CK. Adelaide. Renal impairment: Severe: dose adjustment possibly required in severe impairment. accessed 10 February 2010). lipid abnormalities. Indications: HIV infection. Sydney. hyperglycaemia. PeNTA Steering Committee. Uncommon exacerbation of chronic liver disease. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. World Health Organization. Kouimtzi M. 2009. Australian medicines handbook. WHO model formulary.pdf. 2009. vomiting. 10(10):591–613. fever. Saquinavir ATC code: J05Ae01 Solid oral dosage form: 200 mg Special Notes: Also referred to as SQV.

Avoid combination. Lopinavir: increased plasma concentration of saquinavir. * Simvastatin: increased risk of myopathy. * Amiodarone: increased risk of cardiac toxicity and arrhythmias. Adelaide. PeNTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. * Ciclosporin: plasma concentration of both ciclosporin and saquinavir increased.pdf. Australian medicines handbook. 196 WHO Model Formulary for Children 2010 .mimsonline.who. Stuart MC. Sun exposure may cause photosensitivity. Efavirenz: efavirenz significantly reduces plasma concentration of saquinavir. PeNTA Steering Committee.aspx. 2009 (http://www.int/hiv/pub/guidelines/paediatric020907. avoid combination. 2008. Pediatric dosage handbook. * Ergot derivatives: increased risk of ergot toxicity. * Phenobarbital: plasma concentration of saquinavir possibly reduced. 2009. avoid combination. BMJ Group RBS Publishing. British national formulary for children 2009. accessed 10 February 2010). Kraus DM. * Rifampicin: plasma concentration of saquinavir significantly reduced. Indinavir: indinavir increases plasma concentration of saquinavir.nih. Notes: Give with or after food. Safety and effectiveness not well established in children less than 16 years. Fluconazole: plasma concentration of saquinavir possibly increased. 2009. 2009. * Midazolam: increased midazolam toxicity.gov/contentfiles/pediatricguidelines. Dexamethasone: possibly reduced plasma saquinavir concentration. 16th ed.6 Anti-infective medicines Interactions with other medicines (* indicates severe): NOTe Saquinavir is extensively metabolized by hepatic CyP450 and is a potent CyP3A inhibitor and therefore interacts with numerous drugs. Working group on antiretroviral therapy and medical management of HIV-infected children.com. possibly due to enzyme inhibition. Rossi S. * Garlic: concurrent use of garlic and protease inhibitors can lead to reduced plasma levels and treatment failure. accessed 10 February 2010). * Ritonavir: ritonavir increases plasma concentration of saquinavir. Should be taken within 2 hours after food to increase absorption. London. Taketomo CK. This interaction is beneficial and ritonavir is used at low doses to increase the serum concentration of other protease inhibitors. Warfarin: possibly enhanced anticoagulant effect. ed. UBM Medica. Geneva. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 10(10):591–613. Sydney. 23 February 2009:1–139 (http://aidsinfo. Consult specialist texts for details and advice on management. Australian Medicines Handbook. Nevirapine: plasma concentration of saquinavir reduced. Kouimtzi M. avoid concomitant use. Hudson. accessed 10 February 2010). MIMS Online. * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. References: Antiretroviral therapy of HIV infection in infants and children: towards universal access: Recommendations for a public health approach. Hodding JH. WHO model formulary. Hill SR. sunscreen and protective clothing recommended. eds. Phenytoin: plasma saquinavir concentration possibly reduced. Lexi-Comp. Nelfinavir: combination may lead to increased plasma concentration of either drug (or both). World Health Organization. Paediatric Formulary Committee. Carbamazepine: possibly reduced plasma saquinavir concentration. Geneva.au/Search/Search. 2009. World Health Organization. Must be taken with ritonavir (never unboosted). 2006 (http://www. HIV Medicine.pdf.

Slow IV infusion: No paediatric dose. PReGNANCy Teratogenic risk. condoms must be used if the partner of the male patient is pregnant (as ribavirin is excreted in semen). maternal benefit should be considered. then 7 mg/kg (maximum 500 mg) every 6 hours for 6 days. with maternal death or fetal loss occurring in more than 80% of cases during the third trimester. tumour promoting and gonadotoxic. then 8 mg/kg (maximum 500 mg) every 8 hours for 6 days. renal impairment. Both males and females should avoid pregnancy during treatment and for at least 6 months after treatment has ceased. then 7 mg/kg every 8 hours for 6 days. then 16 mg/kg (maximum 1 g) every 6 hours for 4 days. monitor blood counts at least weekly. Argentine haemorrhagic fever and Crimean-Congo haemorrhagic fever. Lassa fever is especially severe late in pregnancy.4. haemoglobin levels less than 8 g/dl. pregnant health-care workers should not administer ribavirin. severe cardiac disease. including unstable or uncontrolled cardiac disease in previous 6 months. In particular it is indicated for treatment of Lassa fever. Dose: Haemorrhagic fevers. Oral: Child all ages initially 30 mg/kg (maximum 2 g) then 15 mg/kg (maximum 1 g) every 6 hours for 4 days. May cause birth defects and/or death of the exposed fetus. Special Notes: Also referred to as tribavirin. Adult initially 33 mg/kg (maximum 1 g) as a single dose. Argentine haemorrhagic fever. 600 mg Ribavirin is potentially mutagenic. severe hepatic dysfunction or decompensated cirrhosis of the liver. autoimmune disease (including autoimmune hepatitis). WHO Model Formulary for Children 2010 197 . Indications: Treatment of haemorrhagic fever. including Lassa fever. risk of serious fetal abnormalities exists when ribavirin is used during pregnancy. Ribavirin ATC code: J05AB04 Injection for intravenous administration: 800 mg/10 ml and 1 g/10 ml phosphate buffer solution Solid oral dosage form: 200 mg. 400 mg.3 Other antivirals Ribavirin is listed as an essential medication in children for treatment of viral haemorrhagic fevers only.4 Antiviral medicines 6.6. breastfeeding. Precautions: For both males and females: contraception essential during and for at least 6 months after treatment has ceased. but because of the high risk of mortality from haemorrhagic fevers for both pregnant women and the fetus. haemoglobinopathies (including thalassemia or sickle-cell anaemia). Contraindications: Pregnancy (see below). Haemorrhagic fever with renal syndrome. severe debilitating medical conditions. haemorrhagic fever with renal syndrome (Hantavirus). Crimean–Congo haemorrhagic fever and haemorrhagic fever with renal syndrome (HFRS). Slow IV infusion: Child all ages 17 mg/kg every 6 hours for 4 days.

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): ribavirin may inhibit activation of NRTIs (lamivudine. 198 WHO Model Formulary for Children 2010 . British national formulary for children 2009. increase in uric acid concentration. Paediatric Formulary Committee. Interactions with other medicines (* indicates severe): Ribavirin causes anaemia.pdf ). haemolytic anemia Uncommon Dizziness. particularly AST and ALT. Drug interactions with ribavirin may occur for up to 2 months after stopping ribavirin due to its long half-life. Kouimtzi M. Adelaide.thomsonhc. Hodding JH. retinal haemorrhage. pancreatitis. avoid combinations or monitor closely. anorexia. 2008. Didanosine: ribavirin with didanosine has resulted in didanosine toxicity. lactic acidosis. accessed 10 February 2010). arthralgia. Monitor closely for NRTI toxicity. Adverse effects: Common Rash. anxiety. hyperthyroidism. Klasco RK. monitor HIV RNA level closely and review NRTI treatment if this increases.who. October 2007 (including the model list of essential medicines for children). Rossi S. Mcevoy GK. stavudine and zidovudine appear unaffected). Warfarin: ribavirin may decrease warfarin’s anticoagulant effect. WHO model formulary.com. avoid combination. Bethesda. ADMINISTRATION Give by slow intravenous infusion (over 10–15 minutes). Lexi-Comp. Kraus DM. seek specialist advice. Geneva.g. The selection and use of essential medicines: report of the WHO expert committee. 16th ed. 2009. diabetes. impaired concentration. hypothyroidism. Drugdex system. 2009. WHO expert committee on the selection and use of essential medicines. London.tg. 2009. accessed 10 February 2010). aplastic anaemia. AHFS drug information. WHO Technical Report Series.org. interstitial pneumonitis. Hill SR. 2010. Notes: Oral ribavirin should be taken with food. Thomson Micromedex. headache. References: eTG complete. treatment with other drugs which also have this effect may worsen this. 2009. e. American Society of Health-System Pharmacists. Hepatic impairment: Dose reduction not necessary. monitor INR and increase warfarin dose if needed. World Health Organization. insomnia. hypersensitivity. pancreatitis. BMJ Group RBS Publishing. irritability. myalgia. eds. Australian medicines handbook. Therapeutic Guidelines Limited. Stuart MC. depression.int/medicines/publications/essentialmeds_committeereports/TRS_950. Pediatric dosage handbook. pruritus. Taketomo CK. anaemia. with peginterferon alfa treatment (more frequent in children)). nausea. cough. ed. thrombotic thrombocytopenic purpura. (http://www. Melbourne. dyspnoea. ed. increases in serum bilirubin and liver enzymes. colitis. Greenwood Village. 950 (http://www. myocardial infarction. OTHeR ADVeRSe eFFeCTS Neutropenia. rigors. Australian Medicines Handbook. ed. retinal thrombosis. Rare Reticulocytosis. Hudson. 2009 (http://etg. vomiting. fever. 2008.au/ip/.6 Anti-infective medicines Renal impairment: Avoid use in all degrees of renal impairment. Azathioprine: increased risk of azathioprine induced myelotoxicity. fatigue. avoid in severe hepatic dysfunction or decompensated cirrhosis. alopecia. autoimmune disorders. suicidal ideation (in combination (patients with pre-existing cardiac disease are at increased risk). diarrhoea. arrhythmias.

Asymptomatic carriers are common in endemic areas. except possibly in households with immunocompromised patients. Hepatic impairment: Dose reduction not required. Notes: Diloxanide is not effective against hepatic amoebiasis. but a 10-day course should be given at the completion of metronidazole or tinidazole treatment to destroy any amoebae in the gut. Renal impairment: Dose reduction not required.1 Antiprotozoal medicines Antiamoebic and antigiardiasis medicines Amoebiasis Amoebic dysentery is caused by Entamoeba histolytica. pruritus and urticaria. Adverse effects: Common Flatulence. Larger epidemics are difficult to eradicate because of the high proportion of symptomless carriers and because excreted cysts can survive for long periods outside the human host. Contraindications: Pregnancy (defer treatment until after first trimester). Indications: Amoebiasis (asymptomatic carriers in non-endemic areas. extra-intestinal amoebiasis most commonly involves the liver. Oral: Child over 25 kg 7 mg/kg (maximum 500 mg) three times daily for 10 days. Treatment should be offered to all infected patients. and requires treatment. Intestinal forms of amoebiasis include amoebic dysentery and non-dysenteric amoebic colitis. Giardiasis Giardiasis is acquired by oral ingestion of Giardia cysts. Treatment of asymptomatic carriers is generally not recommended. Uncommon Vomiting.6. but in some cases may involve the skin. The course of treatment may be repeated if necessary. Invasive amoebiasis is more likely in malnutrition and immunosuppression. eradication of residual luminal amoebae after treatment of invasive disease with other drugs). In non-endemic areas. Dose: Amoebiasis. It is transmitted by the faeco-oral route and infection is usually caused by ingestion of cysts from contaminated food and drink.5. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concomitant use. Symptomatic (invasive) amoebiasis may be classified as either intestinal or extra-intestinal. Diloxanide ATC code: P01AC01 Tablet: 500 mg (furoate) Special Notes: WHO age/weight restriction: > 25 kg weight. the genitourinary tract.5 Antiprotozoal medicines 6. asymptomatic carriers should be treated to reduce the risk of transmission and protect the patient from invasive amoebiasis. the lung and the brain. WHO Model Formulary for Children 2010 199 . Several stool specimens should be examined when evaluating response to treatment.5 6. Treatment with diloxanide is regarded as successful if stools are free of Entamoeba histolytica for 1 month.

peripheral neuropathy. Dose adjustment is not usually necessary. WHO model formulary. Metronidazole ATC code: P01AB01 Injection: 500 mg in 100 ml vial Oral liquid: 40 mg (as benzoate)/ml Tablet: 200 mg to 500 mg Special Notes: This medicine is listed as a representative of its pharmacological class. stomatitis. The information in this monograph only applies to the medicine listed here. anorexia. 950 (http://www. Hill SR. 200 WHO Model Formulary for Children 2010 . RCPCH Publications. jaundice. ed. clinical and laboratory monitoring (including full blood count and hepatic function tests) in courses lasting longer than 10 days. Oral: Infant or Child 10 mg/kg three times daily for 3–7 days. Red Book: 2009 report of the committee on infectious diseases. seizures. Geneva. World Health Organization. Precautions: Hepatic impairment. 2005. The selection and use of essential medicines: report of the WHO expert committee. optic neuritis. Indications: Invasive amoebiasis and giardiasis.g. Rare Pancreatitis. Stuart MC. hypersensitivity reactions (e. metallic taste. erythema multiforme. abnormal liver function tests. thrombocytopenia. glossitis. eds. Clostridium difficile-associated disease. Uncommon Furry tongue.who.pdf ). fever). for example riding a bike or operating machinery. Sweetman SC. British national formulary for children 2009. 2003. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. 2nd ed. itch. London.int/medicines/publications/essentialmeds_committeereports/TRS_950. Kouimtzi M. flushing. Use with caution in hepatic encephalopathy. various dosage regimens are used and definitive recommendations should be based on local experience. hepatitis. 2008. eradication may take re-treatment and longer courses. London. Giardiasis. angioedema. Paediatric Formulary Committee. Royal College of Paediatrics and Child Health. rash. thrombophlebitis (if administered intravenously). vomiting. Renal impairment: Metabolites may accumulate in severe impairment possibly causing adverse effects. diarrhoea). The IV route should only be used if oral administration is not possible and only until the patient can complete the course orally. NOTe In amoebiasis and giardiasis. leukopenia. Martindale: the complete drug reference. 34th ed. 2009. 2009. Dose: Invasive amoebiasis. WHO Technical Report Series. London. Stevens-Johnson syndrome. Oral or IV: Infant or Child 10 mg/kg three times daily for 8–10 days. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. central nervous system effects (e. BMJ Group RBS Publishing. paraesthesia. October 2007 (including the model list of essential medicines for children).g. Pharmaceutical Press. elk Grove Village. Medicines for Children. Hepatic impairment: Severe impairment: reduce total daily dose to one third and give once daily. dizziness. abdominal pain. Adverse effects: Common Gastrointestinal intolerance (nausea. 28th ed.6 Anti-infective medicines References: American Academy of Pediatrics. headache). darkening of the urine. disulfiram-like reaction with alcohol consumption. American Academy of Pediatrics. 2008. WHO expert committee on the selection and use of essential medicines. for 24 hours. anaphylaxis.

int/medicines/publications/essentialmeds_committeereports/TRS_950. Leishmaniasis is caused by the parasitic protozoa. (http://www. Visceral leishmaniasis Visceral leishmaniasis (kala-azar) is caused by Leishmania donovani and L. 2008. metronidazole suspension should be taken 1 hour before a meal. and by L. 16th ed.5. Mebendazole: increased levels/effect of metronidazole. and mammals. ed. Taketomo CK. The parasites are transmitted by sandflies.pdf ). Humans are the incidental hosts of infection. chagasi (“New World” species). and children account for a significant proportion of those with visceral leishmaniasis in disease endemic areas.thomsonhc. WHO model formulary. ed. Kemp CA. Kraus DM. cutaneous or mucocutaneous.6. Fluorouracil: metabolism of fluorouracil inhibited (increased toxicity). Klasco RK. Pediatric dosage handbook. In some areas. Interactions with other medicines (* indicates severe): Contraceptives. 2008.who. * Warfarin: enhanced anticoagulant effect. Paediatric pharmacopoeia. British national formulary for children 2009. 2009. resistance to antimonials is widespread. BMJ Group RBS Publishing. are the reservoir hosts. McDowell JM. infuse over 20–30 minutes. to a fatal disease (visceral form). 13th ed. Amphotericin B or parenteral paromomycin may be useful in resistant cases. at least initially. infantum (“Old World” species). Leishmania. during or after a meal. Adelaide.2 Antileishmaniasis medicines The incidence of leishmania infection is increasing. It is usually responsive. WHO Model Formulary for Children 2010 201 . ADMINISTRATION For intravenous infusion. Paediatric Formulary Committee. PATIeNT ADVICe Metronidazole tablets should be swallowed whole with water. Phenobarbital: metabolism of metronidazole accelerated (reduced plasma concentration).com. Notes: Well absorbed orally and the intravenous route is normally reserved for severe infections or those unable to take or tolerate oral medication. References: Hill SR. 2010. Drugdex system. accessed 10 February 2010). Typhoid vaccine: reduced effectiveness of vaccine. 950 (http://www. Stuart MC. Ethanol: disulfiram-like reaction. 6. oral: contraceptive effect of estrogens possibly reduced (risk probably small). such as rodents and canids. to the pentavalent antimony compounds meglumine antimoniate or sodium stibogluconate. The selection and use of essential medicines: report of the WHO expert committee. 2009. London. Oral absorption from the suspension is lower than from the tablets. World Health Organization. 2009. * Phenytoin: metabolism of phenytoin inhibited (increased plasma phenytoin concentration). WHO expert committee on the selection and use of essential medicines. Greenwood Village. WHO Technical Report Series. Rossi S. Morbidity and mortality related to this infection is substantial. Melbourne. Australian medicines handbook. It may manifest as a self-limiting localized skin lesion. peripheral neuropathy (usually reversible) and/or central nervous system toxicity (including seizures) may occur. Kouimtzi M. Royal Children’s Hospital. Hudson. but can progress from this to mucosal involvement. Australian Medicines Handbook. without treatment. to disseminated progressive disease (cutaneous form) or. October 2007 (including the model list of essential medicines for children). Hodding JH. and is usually categorized as visceral. 2002. eds. Thomson Micromedex. Lexi-Comp. Lithium: increased lithium toxicity reported. Geneva.5 Antiprotozoal medicines HIGH-DOSe AND/OR PROLONGeD TReATMeNT Leukopenia is reversible and usually only occurs after prolonged treatment. Patients are considered to be parasitologically cured when no parasites are detected in splenic or bone marrow aspirates.

these should not be considered interchangeable and care should be taken to ensure that the form and dose are correct. L. below). avoid rapid infusion (risk of arrhythmias). Plastic surgery offers the only means of ameliorating disfiguring scars. Diffuse cutaneous leishmaniasis Diffuse cutaneous leishmaniasis usually occurs following infection with L. further extended courses of treatment are often successful. Anaphylaxis has been reported with amphotericin B. amazonensis. In this form of the disease. The Old World variety is caused by L. it is preferable to treat L.6 Anti-infective medicines Cutaneous leishmaniasis Cutaneous leishmaniasis comprises two conditions. mexicana. renal impairment. L. Antibiotics may also be needed to treat secondary infections. Precautions: Close medical supervision throughout treatment and initial test dose required (see Test dose. L. panamensis or L. tropica. L. Amphotericin B is available as the conventional deoxycholate complex and liposomal forms. tropica or L. infantum or L. However. 202 WHO Model Formulary for Children 2010 . Special Notes: Also referred to as amphotericin. The New World variety is caused by L. emergency use of corticosteroids may be needed to control pharyngeal or tracheal oedema produced by severe inflammation resulting from antigens liberated from dead parasites during the early phase of treatment. L. L. Mild lesions can often be left to heal spontaneously. L. L. major. tropica infections with a view to reducing transmission. braziliensis or L. mexicana. blood counts and plasma electrolyte (including potassium and magnesium concentration) monitoring required. Other lipid forms are also available (not included in the Second WHO Model List of essential Medicines for Children). It usually responds to antimonials and. when relapses occur. since humans seem to be the only host. major. Relapse is common and repeated courses may be required. Amphotericin B ATC code: J02AA01 Powder for injection: 50 mg in vial as deoxycholate or liposomal Amphotericin B is available as deoxycholate and as several lipid forms including a liposomal form. Infections caused by L.5 mg/kg. guyanensis. peruviana are responsive to intralesional injections of antimonial compounds. Single daily doses of conventional amphotericin B formulation never exceed 1. aethiopica. the primary lesions do not heal. Large overdoses have occurred when conventional formulations were dispensed inadvertently for lipid based or liposomal products. Liposomal amphotericin B: diabetes as each 50 mg vial of liposomal amphotericin B contains 900 mg of sucrose. peruviana. Indications: Visceral. monitor hepatic and renal function tests. aethiopica or L. L. braziliensis. The New World variety tends to be more severe and slower to heal. mucocutaneous and cutaneous leishmaniasis unresponsive to pentavalent antimony compounds. mexicana and should be treated. facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. panamensis. and spread to the mucosa may occur. amazonensis. Mucocutaneous leishmaniasis Mucocutaneous leishmaniasis is caused by L.

5 Antiprotozoal medicines TeST DOSe Amphotericin B deoxycholate A test dose of 1 mg. braziliensis and for relapse treatment by L. For New World cutaneous leishmaniasis by L. donovani. For New World mucocutaneous leishmaniasis (by all parasite species). IV: Child all ages 0. IV: Child all ages 3-5 mg/kg over 3–5 days. L. amazonensis. peruviana and L. is recommended followed by a full dose 4–6 hours later. 31 and 38). For New World mucocutaneous leishmaniasis (by all parasite species). IV: Child all ages 3–5 mg/kg daily or intermittently for 10 doses (days 1–5. IV: Child all ages 0. infantum. Hepatic impairment: Dose reduction not necessary. No dosage reduction is necessary. Liposomal amphotericin B Initial test dose 100 mcg/kg (maximum 1 mg) infused intravenously over 10 minutes. up to 40–60 mg/kg total cumulative dose. given by infusion. donovani in east Africa. Renal impairment: Mild: use only if no alternative. braziliensis and for relapse treatment by L. but further impairment is likely with conventional (as deoxycholate) amphotericin B. Adverse effects: Adverse effects are similar for all amphotericin B formulations. Visceral leishmaniasis by L.7 mg/kg/day for 25–30 doses. IV: Child all ages 3–5 mg/kg/day over 6–10 days. venezuelensis. The patient should be observed for at least 30 minutes after the test dose. IV: Child all ages 0. 24. daily or on alternate days for 20–30 doses. IV: Child all ages 2–3 mg/kg/day over 6–10 days. up to a 40 mg/kg total cumulative dose. Visceral leishmaniasis by L. IV: Child all ages 2–3 mg/kg/day. L. up to a total cumulative dose of 15 mg/kg or 10 mg/kg single dose. LIPOSOMAL AMPHOTeRICIN B Visceral leishmaniasis by L. WHO Model Formulary for Children 2010 203 . IV: Child all ages 3–5 mg/kg/day over 3–6 days. Nephrotoxicity may be reduced with use of liposomal formulations. up to 30 mg/kg total cumulative dose. IV: Child all ages 0. up to 18–21 mg/kg total cumulative dose. infantum.75–1 mg/kg/day. peruviana and L.6. Visceral leishmaniasis by L. 17. up to 30 mg/kg total cumulative dose.7–1 mg/kg on alternate days up to 25–45 doses. venezuelensis. Visceral leishmaniasis in HIV coinfected patients. daily or on alternate days for 15–20 doses. Dose: CONVeNTIONAL AMPHOTeRICIN B (AS DeOXyCHOLATe) Visceral leishmaniasis by L. For New World cutaneous leishmaniasis by L. the liposomal formulation is generally better tolerated. the rates depend on the formulation used. 10. amazonensis.75-1 mg/kg/day. donovani in the Indian subcontinent.

hypokalaemia. Flucytosine: renal excretion of flucytosine decreased and cellular uptake increased (flucytosine toxicity possibly increased). malaise. headache. Prophylactic antipyretics or hydrocortisone should only be used in patients who have previously experienced acute adverse reactions (in whom continued treatment with amphotericin B is essential). magnesium and sodium) at least three times weekly and complete blood picture and hepatic function twice weekly during treatment and until stable after treatment stops. infusion reactions (see below). hyperkalaemia (especially in renal impairment). muscle and Uncommon Hypotension or hypertension. cardiac arrest.g. * Dexamethasone: increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions). Notes: Check renal function before starting treatment. seizures. Interactions with other medicines (* indicates severe): Amikacin: increased risk of nephrotoxicity. epigastric pain. chills. Streptomycin: increased risk of nephrotoxicity. Nephrotoxicity may be associated with sodium depletion. tinnitus). nephrotoxicity (see below). hypotension. flushing and urticaria) may occur. gastrointestinal bleeding. * Hydrocortisone: increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions). Common Fever. Risk is greater in those with renal impairment or when used with other nephrotoxic drugs. * Digoxin: hypokalaemia caused by amphotericin B increases cardiac toxicity of digoxin. Continuous infusion of conventional (as deoxycholate) amphotericin B reduces infusion reactions. Hydrochlorothiazide: increased risk of hypokalaemia. one or more acute infusion reactions (chest pain. anorexia. diarrhoea. hearing loss. With liposomal amphotericin B. elevated liver enzymes. Rare Anaphylactoid reactions. neurological effects (e. frequency is very variable. hypomagnesaemia. Anuria or oliguria may occur. * Prednisolone: increased risk of hypokalaemia (avoid concomitant use unless prednisolone needed to control reactions). 204 WHO Model Formulary for Children 2010 . dyspnoea. hypoxia. flank or leg pain. changes are dose related and generally reversible (except with cumulative doses > 3–5 g). Gentamicin: increased risk of nephrotoxicity. INFUSION ReACTIONS Include fever. * Ciclosporin: increased risk of nephrotoxicity. arrhythmias (rapid infusion of conventional amphotericin B).6 Anti-infective medicines joint pain. Paromomycin: possible increased risk of nephrotoxicity. renal tubular acidosis. Fluconazole: possible antagonism of effect of amphotericin B. headache. eCG changes). vomiting. hepatotoxicity. severe abdominal. blurred vision. Vancomycin: possible increased risk of nephrotoxicity. anaemia. Furosemide: increased risk of hypokalaemia. rash. these may be related to the liposomal component. blood dyscrasias. Miconazole: possible antagonism of effects of amphotericin B. nausea. anorexia. Distal tubular damage may lead to loss of concentrating ability. hypokalaemia and hypomagnesaemia. Liposomal amphotericin B is less nephrotoxic than conventional (deoxycholate) amphotericin B. usually lessen with continued treatment. nephrocalcinosis. monitor renal function and electrolytes (especially potassium. NePHROTOXICITy Conventional (as deoxycholate) amphotericin B affects renal function in all patients. cardiovascular toxicity (including arrhythmias. confusion. muscle and joint pain. Pentamidine: possible increased risk of nephrotoxicity. thrombophlebitis. nausea and vomiting.

WHO Model Formulary for Children 2010 205 . Paromomycin ATC code: A07AA06 Solution for intramuscular injection: 750 mg of paromomycin base present as the sulfate Indications: Visceral leishmaniasis. 2009. impaired renal function. ed.1002/14651858. American Society of Health-System Pharmacists. 950 (http://www. WHO Technical Report Series. Then infuse subsequent doses over 30–60 minutes.com. Do not mix with any other drugs. Sweetman SC. Interventions for American cutaneous and mucocutaneous leishmaniasis. possible or proven bowel lesions. Precautions: Impaired gastrointestinal motility. Australian medicines handbook. Treatment should always be given in hospital to enable continuous monitoring of patients. Reconstitute as per product instructions including further dilution with glucose 5% to produce a final concentration of 0.who. Cochrane Database of Systematic Reviews. Hudson. which may allow a shorter infusion. ed. The selection and use of essential medicines: report of the WHO expert committee. London. 2008. Initial test dose should be given over 10 minutes. flush existing line with glucose 5% or use a separate line. Lexi-Comp. No. Australian Medicines Handbook.int/medicines/publications/essentialmeds_committeereports/TRS_950. WHO model formulary. WHO expert committee on the selection and use of essential medicines. Visceral leishmaniasis in the Indian subcontinent. Hill SR. Dose: All doses are in terms of paromomycin base. Geneva. Kraus DM. IM: Child over 5 kg 11 mg/kg daily for 17 days. 2008. 2 (Art. Pediatric dosage handbook. BMJ Group RBS Publishing. and infusing over longer periods. 2009. ed.1 mg/ml (in fluid restricted children up to 0. Drugdex system.pub2). do not administer without further dilution.2–2 mg/ml. Greenwood Village. 16th ed.CD004834.6. 2009. Stuart MC. 2009. ed. Rossi S. AHFS drug information. Conventional amphotericin B (as deoxycholate) Reduce risk of thrombophlebitis by using large peripheral veins or a central venous catheter. Initial test dose should be given over 20–30 minutes. Klasco RK. accessed 10 February 2010). changing venous access sites frequently. Taketomo CK. 2005. hypersensitivity to aminoglycosides. Hodding JH. concurrent administration with nephrotoxic or ototoxic drugs including aminoglycosides. Pharmaceutical Press. Mcevoy GK. London. 2009. References: González U et al.: CD004834. To minimize infusion-related reactions. IM: Child over 5 kg 11 mg/kg daily for 21 days. British national formulary for children 2009.thomsonhc. Martindale: the complete drug reference. Thomson Micromedex. October 2007 (including the model list of essential medicines for children).pdf ).4 mg/ml if given via a central line). eds. Kouimtzi M. however. DOI: 10. Bethesda. Visceral leishmaniasis in east Africa. Paediatric Formulary Committee. Contraindications: Intestinal obstruction. World Health Organization. ADMINISTRATION ADVICe Incompatible with sodium chloride solutions. do not give over less than 2 hours. infuse the initial treatment dose slowly over 4–6 hours or continuously over 24 hours. (http://www. previous course of paromomycin treatment in preceding 3 months. Adelaide. tolerance to infusion reactions increases with subsequent doses. 34th ed. After initial reconstitution.5 Antiprotozoal medicines Proper hydration and potassium supplementation are important. 2010. Only use in combination with pentavalent antimonials. Liposomal amphotericin B Reconstitute as per product instructions including filtering through a 5 micron filter and further dilute with glucose 5% to produce a final concentration of 0.

2009. Stockley’s drug interactions. nephrotoxic. Hudson. tetany. raised liver enzymes. diarrhoea. Hodding JH. ed. The selection and use of essential medicines: report of the WHO expert committee.thomsonhc. allergic reaction. * Suxamethonium: possible enhanced effects of suxamethonium. renal toxicity. WHO Technical Report Series. renal. Both agents are similarly effective in leishmaniasis and their pharmacokinetics are similar. 8th ed. London. Rossi S. ed. October 2007 (including the model list of essential medicines for children). 2009. Adelaide. Klasco RK. 2009. abdominal cramps. Please be aware that the two compounds do not contain equivalent amounts of pentavalent antimony. Interactions with other medicines (* indicates severe): Amphotericin B: possible increased risk of nephrotoxicity. 34th ed. ed. 16th ed.g. 2010. dizziness. Sodium stibogluconate or Meglumine antimoniate ATC code: P01CB01.pdf ).int/medicines/publications/essentialmeds_committeereports/TRS_950. Mcevoy GK. 2008. * Pyridostigmine: possible antagonism of pyridostigmine. mucocutaneous and post-kala-azar dermal leishmaniasis. Furosemide: increased risk of ototoxicity. pregnancy. vomiting. Kouimtzi M. hypocholesterolaemic and malabsorptive effects. pancreas or haematological morbidities. of xylose and sucrose. Contraindications: Pre-existing severe cardiac. Hill SR. accessed 10 February 2010). Pediatric dosage handbook. Please ensure doses are calculated on the compound available. Thomson Micromedex. American Society of Health-System Pharmacists. Sweetman SC. Greenwood Village. Australian medicines handbook. London. 2005. anorexia. Stuart MC.6 Anti-infective medicines Renal impairment: Mild: avoid or use with caution. Pharmaceutical Press. steatorrhoea and precipitation of bile salts. cutaneous. Digoxin: reduced digoxin absorption and subsequent reduced digoxin serum concentrations and efficacy. reversible ototoxicity. Martindale: the complete drug reference. AHFS drug information. * Neostigmine: possible antagonism of neostigmine. (http://www. Vancomycin: increased risk of ototoxicity. compounds used to treat all forms of leishmaniasis. Drugdex system. Hepatic impairment: Dose reduction not required. Methotrexate: may reduce gastrointestinal absorption of methotrexate. Cisplatin: increased risk of ototoxicity. Adverse effects: Common Nausea. e.who. World Health Organization. Geneva. Taketomo CK. 2008. 2008. References: Baxter K. Bethesda. 950 (http://www. Pharmaceutical Press.com. injection site pain. Indications: Visceral. fever. ed. Kraus DM. 206 WHO Model Formulary for Children 2010 Special Notes: Meglumine antimoniate and sodium stibogluconate are the pentavalent antimony . ed. WHO expert committee on the selection and use of essential medicines. Lexi-Comp. Australian Medicines Handbook. Meglumine antimoniate is also referred to as meglumine antimonate. Uncommon Rash. P01CB02 Sodium stibogluconate IV/IM injection: 100 mg of pentavalent antimony per ml Meglumine antimoniate IV/IM injection: 81 mg of pentavalent antimony per ml Sodium stibogluconate and meglumine antimoniate are not the same compound. headache. WHO model formulary. liver. eds.

pancreatitis. vertigo. every 3–7 days (1–5 infiltrations). leukopenia. anaemia. Mucocutaneous leishmaniasis. Rare Cardiotoxicity and sudden death (see below). Antiprotozoal medicines MUCOCUTANeOUS DISeASe Successful treatment of mucocutaneous leishmaniasis may induce severe inflammation around lesions (may be life threatening if pharyngeal or tracheal involvement). or if local therapy has been tried and failed. Prolongation of corrected QT interval (greater than 0. abdominal pain. IV/IM: Child all ages 20 mg/kg (minimum 200 mg) daily for 28 days in L. malaise. infantum infections and for 30 days in L. pain on intramuscular injection. CARDIOTOXICITy electrocardiographic changes are dependent on dose and duration of treatment. pain and thrombosis on intravenous administration. anaphylaxis. Systemic treatment is acceptable if the patient suffers from numerous lesions (typically greater than four). Interactions with other medicines (* indicates severe): Furosemide: increased risk of toxicity. fever. flushing. renal impairment and/or damage. increased risk of liver damage and hepatic failure. may require systemic corticosteroids.5 seconds) signals the likely onset of serious and potentially fatal cardiac arrhythmias or death. Hepatic impairment: Mild to moderate impairment: use with caution. Severe: contraindicated. Dose: Doses are expressed in terms of pentavalent antimony. vomiting. Meglumine antimoniate IV/IM injection contains 81 mg of pentavalent antimony per ml. Vancomycin: increased risk of toxicity. WHO Model Formulary for Children 2010 207 . thrombocytopenia. nausea. IM/IV: Child all ages 20 mg/kg daily for 30 days. Adverse effects: Common Anorexia. Cardiotoxicity and sudden deaths are serious but uncommon side-effects. Renal impairment: Moderate: increased adverse effects. the addition of paromomycin may be necessary. hepatotoxicity. lethargy. the most common being T-wave inversion. aethiopica. hepatic impairment. donovani infections. substernal pain or cough.5 Precautions: Renal impairment. Visceral leishmaniasis. elevated pancreatic and liver enzymes. headache. IV/IM: Child all ages 20 mg/kg daily for 10–20 days. Cutaneous leishmaniasis.6. face-disfiguring or complicated lesion(s). metallic taste. IV/IM: Child all ages 20 mg/kg (minimum 200 mg) daily for 30–60 days. rash. if the size or localization of the lesion makes local therapy impossible. arthralgia. Post-kala-azar dermal leishmaniasis. prolonged QT interval and arrhythmias. peripheral neuropathy. Intralesional: Child all ages 1–5 ml per session. Sodium stibogluconate IV/IM injection contains 100 mg of pentavalent antimony per ml. bleeding from nose or gum. Cisplatin: increased risk of toxicity. sweating. For diffuse cutaneous forms by L. myalgia.

5. is caused by four species of plasmodial parasites.5 mm) to avoid any risk of subsequent thrombosis. Sanofi-Aventis Farmacêutica. 0. which is transmitted by anopheline mosquitoes. The quality of pentavalent antimonials should be assured. Ampoules should be stored in well-closed containers. which causes the least severe but most persistent infections. falciparum or P. Recrudescence of these infections results from persistent blood forms in inadequately treated or untreated patients. 950 (http://www. P. Sweetman SC. 208 WHO Model Formulary for Children 2010 . Royal College of Paediatrics and Child Health. and causes the most severe infections. The selection and use of essential medicines: report of the WHO expert committee. ed.6 Anti-infective medicines Amphotericin B: possibly increased risk of nephrotoxicity. American Academy of Pediatrics. American Academy of Pediatrics. 34th ed. * Suxamethonium: possibly enhanced effects of suxamethonium. RCPCH Publications. If the volume of injection exceeds a suitable size for the patient. * Neostigmine: possible antagonism.1 For curative treatment Malaria. Infusions should be ceased if coughing or substernal pain occurs. WHO expert committee on the selection and use of essential medicines. AHFS drug information. World Health Organization. Intravenous injection should be given either by infusion (over 5–10 minutes) or slow injection through a fine needle (23–25 gauge. Such latent forms are not generated by P.3. 2005. Stuart MC. Intramuscular injection should be given deep into the muscle. elk Grove Village. Kouimtzi M. Glucantime Product Information. Parenteral antimalarials are also used to initiate treatment in patients unable to take oral treatment. and sometimes years. Red Book: 2009 report of the committee on infectious diseases. Geneva. malariae. Certain tissue forms of P. while P.and cardiotoxicity). If serious side-effects arise (in most cases related to hepato. ovale.who. London. one in each buttock or thigh. Medicines for Children. P. 2009. 2008. Hill SR. Notes: Monitoring of patients with serum chemistry. Plasmodium vivax is extensively distributed. It should be noted that antimonial compounds are polymers that may deteriorate with age. 2nd ed. Pharmaceutical Press. British national formulary for children 2009. which can persist in the liver for many months. American Society of Health-System Pharmacists. BMJ Group RBS Publishing. * Pyridostigmine: possible antagonism. Mcevoy GK. protected from light. References: 6. Paediatric Formulary Committee. are responsible for relapses. Treatment of severe falciparum malaria requires parenteral therapy. Substandard drugs are known to cause severe toxicity and death. The following recent key recommendations regarding antimalarial therapy have been endorsed: First-line treatment for malaria should be with combinations of medicines rather than single drug therapy. London. Martindale: the complete drug reference. 2008. the treatment should be changed to another drug.5.pdf. ed.3 Antimalarial medicines 6. ADMINISTRATION The injection should be filtered immediately before administration using a 5 micron or less filter. vivax and P. October 2007 (including the model list of essential medicines for children). malariae. • Artemisinin-containing combination therapy (ACT) is recommended as first-line curative treatment for uncomplicated malaria. WHO model formulary. which are responsible for nearly all malaria-related deaths. also occurs widely. complete blood count and electrocardiography should be done. eds. it should be divided into two doses. Bethesda. London. 2003. ovale is mainly confined to Africa and is less prevalent. Brazil (accessed April 14 2010). WHO Technical Report Series. 2009.6–0. 2009. 28th ed. falciparum is also widespread.int/medicines/publications/essentialmeds_committeereports/TRS_950.

falciparum. Artemether ATC code: P01Be02 Oily injection: 80 mg/ml in 1 ml ampoule Indications: Management of severe malaria. WHO Model Formulary for Children 2010 209 . asthenia. Occasionally abbreviated to AQ. then 1. high-dose therapy). falciparum malaria in areas where quinine is ineffective. Adverse effects: Blood disorders including leukopenia and agranulocytosis. Dose: Treatment of uncomplicated falciparum malaria. Interactions with other medicines (* indicates severe): Chlorpromazine: plasma concentration of chlorpromazine increased (consider reducing chlorpromazine dose). Geneva. PATIeNT ADVICe Patients and their carers should be told how to recognize the signs of blood disorders and advised to seek medical attention as soon as possible if symptoms such as fever. Kouimtzi M. Notes: Concern has been expressed about higher rates of neutropenia in children and the drug has twice been removed from the adult formulary because of safety concerns but has since been reinstated (1988). 2008.6. rarely. Stuart MC.5 Antiprotozoal medicines Amodiaquine ATC code: P01BA06 Tablet: 153 mg or 200 mg (as hydrochloride) Special Notes: Recommended for children over 5 months only. World Health Organization. purpura. ovale and P. pruritus. sore throat. P. abdominal pains. falciparum malaria in areas of quinine resistance. fever. neuromyopathy. mouth ulcers. abnormal weight loss. retinopathy. eds. skin pigmentation. rash. Dose: Treatment of severe P. Precautions: G6PD deficiency. gastrointestinal disturbances. Intramuscular injection: Infant or Child over 6 months loading dose of 3. this is followed by a complete treatment course of an effective artemisinin-based combination therapy to effect a radical cure. hepatitis. blood disorders. References: Hill SR. They should also be told how to recognize signs of hepatitis and advised to seek medical attention if symptoms such as anorexia. Contraindications: Hepatic impairment. Precautions: SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Treatment of severe P. malariae infections. nausea or vomiting develop. To be used (a) in combination with artesunate or (b) may be used alone for the treatment of P. Hepatic impairment: Avoid use.6 mg/kg daily until patient can tolerate oral medication or to maximum of 7 days. Oral: Infant or Child over 5 months 10 mg/kg daily for 3 days. bruising or bleeding develop.2 mg/kg. Indications: Treatment of uncomplicated malaria caused by P. WHO model formulary. visual disturbances (retinopathy associated with long-term. vivax. Renal impairment: No information available. rash. for example riding a bike or operating machinery. Contraindications: First trimester of pregnancy. avoid concurrent therapy with hepatotoxic drugs. for 24 hours.

Ciprofloxacin: manufacturer of artemether with lumefantrine advises avoid concomitant use. monitor eCG and plasma potassium. Fluconazole: manufacturer of artemether with lumefantrine advises avoid concomitant use. nausea. Primaquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. monitor eCG and plasma potassium.who. neurotoxicity in animal studies. Ofloxacin: manufacturer of artemether with lumefantrine advises avoid concomitant use. Sulfadoxine + pyrimethamine: manufacturer of artemether with lumefantrine advises avoid concomitant use. World Health Organization. Pyrimethamine: manufacturer of artemether with lumefantrine advises avoid concomitant use. Geneva. diarrhoea. 2006 (http://whqlibdoc. vomiting.int/ publications/2006/9241546948_eng. accessed 10 February 2010). Grapefruit juice: metabolism of artemether and lumefantrine may be inhibited (avoid concomitant use). Hepatic impairment: Caution in severe impairment. Adverse effects: Common Headache. Lopinavir: manufacturer of artemether with lumefantrine advises avoid concomitant use.pdf. a 1 ml syringe should be used to ensure correct dosage. Rare Cardiotoxicity (after high doses). Haloperidol: manufacturer of artemether with lumefantrine advises avoid concomitant use. Care should be taken in patients with known peanut allergy. Proguanil: manufacturer of artemether with lumefantrine advises avoid concomitant use. Uncommon Neutropenia. Quinine: risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use). Fluoxetine: avoid concomitant use. Chlorpromazine: manufacturer of artemether with lumefantrine advises avoid concomitant use. elevated liver enzyme values. dizziness. Oily injection currently formulated in arachis (peanut) oil.6 Anti-infective medicines Renal impairment: Caution in severe impairment. abdominal pain. Mefloquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. Notes: ADMINISTRATION Since small volumes are required for children. tinnitus. Azithromycin: manufacturer of artemether with lumefantrine advises avoid concomitant use. Chloroquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. 210 WHO Model Formulary for Children 2010 . References: Guidelines for the treatment of malaria. Saquinavir: manufacturer of artemether with lumefantrine advises avoid concomitant use. Erythromycin: manufacturer of artemether with lumefantrine advises avoid concomitant use. Ritonavir: manufacturer of artemether with lumefantrine advises avoid concomitant use. Interactions with other medicines (* indicates severe): * * * * * * * * * Amitriptyline: manufacturer of artemether with lumefantrine advises avoid concomitant use.

* Amitriptyline: manufacturer of artemether with lumefantrine advises avoid concomitant use. Hepatic impairment: Severe: caution. Adverse effects: Common Abdominal pain. 24. cough. Fluoxetine: avoid concomitant use. severe renal impairment or hepatic impairment. Erythromycin: manufacturer of artemether with lumefantrine advises avoid concomitant use. arthralgia. falciparum and other Plasmodium malaria. * Chlorpromazine: manufacturer of artemether with lumefantrine advises avoid concomitant use. anorexia. Infrequent Paraesthesia. 36. headache. history of arrhythmias. Rare Hepatitis. Precautions: electrolyte disturbances. history of clinically relevant bradycardia. hypersensitivity. 48 and 60 hours (total 24 tablets over 60 hours). * Chloroquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. 24. monitor eCG and plasma potassium. Grapefruit juice: metabolism of artemether and lumefantrine may be inhibited (avoid concomitant use). monitor patients unable to take food (greater risk of recrudescence).6. 36. over 34 kg initially 4 tablets followed by 5 further doses of 4 tablets each at 8. Fluconazole: manufacturer of artemether with lumefantrine advises avoid concomitant use. 48 and 60 hours (total 18 tablets over 60 hours).5 Antiprotozoal medicines Artemether + Lumefantrine ATC code: P01Be52 Tablet: 20 mg/120 mg Dispersible tablet: 20 mg/120 mg Special Notes: Not for use in children under 5 kg. myalgia. concomitant administration of drugs that prolong QT Dose: Treatment of uncomplicated P. 48 and 60 hours (total 6 tablets over 60 hours). falciparum alone or with other Plasmodium spp. 24. palpitation. nausea and vomiting. pruritus. 25–34 kg initially 3 tablets followed by 5 further doses of 3 tablets each at 8. 24. family history of sudden death or of congenital prolongation of QTc interval (also see Precautions). 15–24 kg initially 2 tablets followed by 5 further doses of 2 tablets each at 8. Contraindications: First trimester of pregnancy. 36. monitor eCG and plasma potassium. * Ciprofloxacin: manufacturer of artemether with lumefantrine advises avoid concomitant use. WHO Model Formulary for Children 2010 211 . Interactions with other medicines (* indicates severe): dizziness. Indications: Treatment of uncomplicated malaria caused by P. fatigue. 48 and 60 hours (total 12 tablets over 60 hours). ataxia. 36. history of congestive heart failure accompanied by reduced left ventricular ejection fraction. in areas with significant drug resistance. * Azithromycin: manufacturer of artemether with lumefantrine advises avoid concomitant use. diarrhoea. Oral: Infant or Child 5–14 kg initially 1 tablet followed by 5 further doses of 1 tablet each at 8. interval. asthenia. rash. Renal impairment: Severe: caution. sleep disorders.

cdc. Primaquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. WHO model formulary. Sulfadoxine + pyrimethamine: manufacturer of artemether with lumefantrine advises avoid concomitant use. British Medical Association and Royal Pharmaceutical Society of Great Britain. Geneva. Lopinavir: manufacturer of artemether with lumefantrine advises avoid concomitant use. Centers for Disease Control and Prevention. Hill SR. Levofloxacin: manufacturer of artemether with lumefantrine advises avoid concomitant use. London.gov/malaria/. References: Guidelines for treatment of malaria in the United States. 2008. Kouimtzi M. Ofloxacin: manufacturer of artemether with lumefantrine advises avoid concomitant use. Contraindications: First trimester of pregnancy. Stuart MC. World Health Organization. for example. eds. 2009 (http://www. Proguanil: manufacturer of artemether with lumefantrine advises avoid concomitant use. 212 WHO Model Formulary for Children 2010 . Atlanta. accessed 10 February 2010). If the dose is vomited within 1 hour of taking. the dose should be repeated. 2008. Intravenous treatment of severe malaria. for 24 hours. falciparum. Joint formulary committee. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. British national formulary 2008. Mefloquine: manufacturer of artemether with lumefantrine advises avoid concomitant use. Artesunate ATC code: P01Be03 Injection: ampoules. Notes: Non-dispersible tablets may be crushed. this is a particular risk in children. BMJ Group RBS Publishing. Quinine: risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use).6 Anti-infective medicines Haloperidol: manufacturer of artemether with lumefantrine advises avoid concomitant use. Saquinavir: manufacturer of artemether with lumefantrine advises avoid concomitant use. containing 60 mg anhydrous artesunic acid with a separate ampoule of 5% sodium bicarbonate solution Tablet: 50 mg Rectal capsules: 50 mg and 200 mg Indications: Oral treatment of uncomplicated malaria caused by P. Precautions: Risk of recurrence if used as oral monotherapy in non-immune patients. Pyrimethamine: manufacturer of artemether with lumefantrine advises avoid concomitant use. 55th ed. Rectal pre-referral emergency treatment of suspected severe malaria. Ritonavir: manufacturer of artemether with lumefantrine advises avoid concomitant use. riding a bike or operating machinery. in combination with other antimalarials.

ed. Pharmaceutical Press. Australian medicines handbook. diarrhoea. neurotoxicity in animal studies. IV or IM: Child 2. This can be administered intramuscularly or then further diluted in 5 ml of glucose 5% solution for injection before intravenous administration by bolus injection. 2005. abdominal pain. Give a full course of artemisinin-based combination therapy (see artemether + lumefantrine) or oral quinine after initial parenteral artesunate. vomiting. World Health Organization. 950 (http://www. consult manufacturer’s literature. The selection and use of essential medicines: report of the WHO expert committee.6. Stuart MC. 24 hours then once daily until oral treatment is possible. Geneva. Adverse effects: Common Headache. There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use.5 Dose: Antiprotozoal medicines Treatment of uncomplicated malaria caused by P. 2009. References: Hill SR. falciparum. 13–42 months (9–19 kg) 100 mg.who. Using available suppositories: Neonate–Child 1 year (5–8 kg) 50 mg. eds. Uncommon Neutropenia. falciparum malaria in areas of multiple drug resistance. Solutions should be freshly prepared prior to administration. Rare eCG abnormalities. Give a full course of artemisinin-based combination therapy (see artemether + lumefantrine) or oral quinine after initial rectal artesunate. including prolongation of QT interval. Not recommended as monotherapy and should be used in combination with either amodiaquine. London. Notes: Artesunate monotherapy is not recommended for uncomplicated malaria due to the risk of developing drug resistance. Australian Medicines Handbook. 6–12 years (30–39 kg) 300 mg. dizziness. ReCONSTITUTION OF PAReNTeRAL FORMS Artesunic acid should be dissolved in 1 ml of sodium bicarbonate 5% solution for injection (to form sodium artesunate). Renal impairment: No information available. Rossi S. WHO Model Formulary for Children 2010 213 . WHO model formulary. nausea. Oral: Infant or Child over 5 months 4 mg/kg daily for 3 days. Adelaide. Rectal: Child all ages approximately 10 mg/kg. Pre-referral treatment of severe malaria only (patients should be taken to an appropriate health facility for follow-up care). elevated liver enzyme values. 34th ed. WHO expert committee on the selection and use of essential medicines. temporary suppression of Interactions with other medicines (* indicates severe): reticulocyte response and induction of blackwater fever reported.4 mg/kg given at 0.int/medicines/publications/essentialmeds_committeereports/TRS_950. 43–60 months (20–29 kg) 200 mg. Hepatic impairment: No information available. mefloquine or sulfadoxine + pyrimethamine. Sweetman SC.pdf ). Treatment of severe P. 12. tinnitus. WHO Technical Report Series. October 2007 (including the model list of essential medicines for children). 2008. Martindale: the complete drug reference. ed. Kouimtzi M. 2008.

Contraindications: Retinal damage or impaired visual field. Alternatively. anxiety. magnesium hydroxide): reduced absorption of chloroquine. followed by 5 mg/kg daily on day 3. Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. avoid concurrent therapy with hepatotoxic drugs. neurological disorders (avoid for prophylaxis if history of epilepsy). Praziquantel: plasma concentration of praziquantel possibly reduced. 150 mg base (as phosphate or sulfate) Indications: Only for use in the treatment of P. high-dose therapy or inappropriate selfmedication). Digoxin: plasma digoxin concentration possibly increased. vivax infection from areas where the parasite remains sensitive. porphyria and psoriasis in susceptible individuals. hearing loss. Uncommon Psychotic episodes. Mefloquine: increased risk of convulsions. Adverse effects: Common Headache. atrioventricular block (may be result of inappropriate self-medication). Carbamazepine: possible increased risk of convulsions. Interactions with other medicines (* indicates severe): * * * * Antacids (aluminium hydroxide. Dose: Treatment of P. visual disturbances (retinopathy associated with long-term. Hepatic impairment: extensively liver metabolized. Precautions: If patient continues to deteriorate after chloroquine. vivax malaria. may aggravate myasthenia gravis.6 Anti-infective medicines Chloroquine ATC code: P01BA01 Oral liquid: 10 mg base (as phosphate or sulfate)/ml Tablet: 100 mg. photosensitivity. suspect resistance and administer quinine intravenously as emergency measure. NOTe Doses expressed as base. 10 mg/kg for 2 days. Oral: Child 10 mg/kg (maximum 600 mg) followed by 5 mg/kg (maximum 300 mg) 6–8 hours later. blue-black pigmentation of mucous membranes and skin. WHO Model Formulary for Children 2010 214 . hypersensitivity reactions such as urticaria and angioedema. Ciclosporin: increased plasma ciclosporin concentration (increased risk of toxicity). skin reactions and itch which can be severe enough to affect compliance. monitor liver function tests. tinnitus. then 5 mg/kg daily on next 2 days. Phenytoin: possible increased risk of convulsions. bone marrow suppression. G6PD deficiency. Renal impairment: Dose reduction not necessary. seizures. use with caution in liver impairment. personality changes. may exacerbate psoriasis. Neostigmine: chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish effect of neostigmine. Avoid concurrent therapy with hepatotoxic drugs. Rare Depigmentation or loss of hair. reversible corneal opacities. gastrointestinal disturbances. Ethosuximide: possible increased risk of convulsions. Total dose 25 mg/kg over 3 days. severe gastrointestinal disorders.

Precautions: Avoid exposure to sunlight or sunlamps. nausea. bone deformity. accessed 10 February 2010). Adverse effects: Common Gastrointestinal disturbances. Geneva. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide. follow with primaquine oral treatment. British Medical Association and Royal Pharmaceutical Society of Great Britain. 2008. ed. photosensitivity. WHO Model Formulary for Children 2010 215 . Guidelines for treatment of malaria in the United States. Kouimtzi M. Uncommon Rash. WHO model formulary. absorption of doxycycline reduced by oral ferrous salts. If vomiting occurs within 1 hour of taking dose. Pharmaceutical Press.who.6. PATIeNT ADVICe Take with food to reduce GI side effects. Adelaide. Contraindications: Pregnancy. Dose: Supplement to quinine or artesunate treatment for multiple drug-resistant malaria. Methotrexate: increased risk of methotrexate toxicity. dose may be repeated. Rossi S. hypersensitivity reactions including StevensJohnson syndrome. hepatitis. 2009 (http://www. Clostridium difficile infection. Australian Medicines Handbook. Carbamazepine: accelerated metabolism of doxycycline (reduced effect). porphyria. fatty liver degeneration. Ferrous salts: absorption of oral ferrous salts reduced by doxycycline. London. headache and visual disturbances which may indicate benign intracranial hypertension. BMJ Group RBS Publishing. References: Guidelines for the treatment of malaria. 34th ed. Quinine: increased risk of ventricular arrhythmias. anorexia. vivax.gov/malaria/. Notes: To eliminate liver forms of P. Sweetman SC. Hill SR. flushing. Valproic acid: possible increased risk of convulsions.pdf. ed. World Health Organization. * Ciclosporin: possibly increased plasma ciclosporin concentration. Stuart MC. Rare Photo-onycholysis. Hepatic impairment: Avoid (or use with caution). 2005. Australian medicines handbook. diarrhoea. systemic lupus erythematosus. fungal overgrowth. vomiting.5 Antiprotozoal medicines Pyridostigmine: chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish effect of pyridostigmine.int/ publications/2006/9241546948_eng. Atlanta. Renal impairment: Dose reduction not necessary. Joint formulary committee. 55th ed. Doxycycline ATC code: J01AA02 Capsule: 100 mg (as hydrochloride) Tablet (dispersible): 100 mg (as monohydrate) Indications: Supplement to quinine or artesunate treatment for multiple drug-resistant P. stomatitis. falciparum malaria. London. 2006 (http://whqlibdoc. 2008. Martindale: the complete drug reference. eds. World Health Organization. tinnitus. oesophageal ulcers (due to partly swallowed tablets). Geneva. Centers for Disease Control and Prevention.cdc. 2009. British national formulary 2008. nail discoloration. accessed 10 February 2010). magnesium hydroxide): reduced absorption of doxycycline. photosensitivity reported. Oral: Child over 8 years 2 mg/kg (maximum 100 mg) twice daily for 7–10 days.

disturbances in liver function tests. tremor. Stevens-Johnson syndrome. bradycardia. For use only in combination with quinine or artesunate. ataxia. Oxford. seizures.gov/malaria/. headache. muscle weakness. leukopenia. eds. suicidal ideation. tachycardia. Hill SR. somnolence. Kouimtzi M. myalgia. alopecia. Centers for Disease Control and Prevention. 2008. visual disturbances. Notes: PATIeNT ADVICe Capsules should be swallowed whole with plenty of fluid while sitting or standing to prevent oesophageal irritation. 2009. Adverse effects: Common Nausea. References: Ashley C. panic attacks. Phenytoin: increased metabolism of doxycycline (reduced plasma concentration). Australian medicines handbook. It should be used in caution in patients with disorders of the biliary system who may not be able to clear the drug. Dose: Treatment of uncomplicated P. for 24 hours. Round to the nearest quarter of a tablet. Precautions: Avoid use in cardiac conduction disorders. Should be given with food or milk. leukocytosis. 216 WHO Model Formulary for Children 2010 . Guidelines for treatment of malaria in the United States. 2009 (http://www. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. NOTe Doses expressed as salt. to counter gastric irritation. Paediatric Formulary Committee.6 Anti-infective medicines Phenobarbital: metabolism of doxycycline accelerated (reduced plasma concentration). thrombocytopenia. British national formulary for children 2009. Radcliffe Publishing. confusion. vestibular disorders. cdc. London. Rare Hyperpyrexia. depression. These include sensory and motor neuropathies. atrioventricular block and encephalopathy. loss of balance. anxiety. falciparum malaria in combination with artesunate. arthralgia. Australian Medicines Handbook. 2009. anorexia. cardiac conduction disorders. Rifampicin: plasma doxycycline concentration possibly reduced. Neuropsychiatric disorders occur in at least 1:10 000 patients treated with mefloquine and the incidence is thought to be up to 1:1000 when used at treatment doses. Atlanta. Rossi S. urticaria. agitation and psychoses. WHO model formulary. hypersensitivity to quinine. Stuart MC. emotional instability. abdominal pain. eds. pruritus. Mefloquine ATC code: P01BC02 Tablet: 250 mg (as hydrochloride) Indications: Used in combination with artesunate for the treatment of uncomplicated falciparum malaria. epilepsy. hallucinations. for example riding a bike or operating machinery. World Health Organization. tinnitus. Oral: Child over 3 months or 5 kg 25 mg/kg usually given over 2–3 days. dizziness (can be severe). diarrhoea. Renal impairment: Dose reduction not necessary. vomiting. * Warfarin: anticoagulant effect possibly enhanced. rash. aggression. Contraindications: History of neuropsychiatric disorders including depression or convulsions. accessed 10 February 2010). Hepatic impairment: Mefloquine is metabolized by the liver and eliminated by the biliary system. 2009. 3rd ed. BMJ Group RBS Publishing. Uncommon Circulatory disorders. ed. Currie A. insomnia and abnormal dreams. Adelaide. The renal drug handbook. Geneva.

Oral: Child 250 micrograms/kg daily for 14 days. Dose: Radical cure of P. headache. * Carbamazepine: antagonism of anticonvulsant effect.5 Interactions with other medicines (* indicates severe): Antiprotozoal medicines * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. dizziness. The renal drug handbook. * Ethosuximide: antagonism of anticonvulsant effect. nausea and vomiting. Kouimtzi M. Rossi S. eds. 2009. Australian medicines handbook. Radcliffe Publishing. London. Contraindications: Conditions that predispose to granulocytopenia including active rheumatoid arthritis and lupus erythematosus. Mefloquine should not be used for treatment if it was used for prophylaxis and failed to prevent infection. Notes: Mefloquine monotherapy is no longer recommended as this is likely to result in increasing levels of parasite resistance to this drug. severe G6PD deficiency. vivax and P. * Valproic acid: antagonism of anticonvulsant effect. World Health Organization. Pharmaceutical Press. Phenytoin: antagonism of anticonvulsant effect. Hepatic impairment: Primaquine is metabolized by the liver. Sweetman SC. but should not prevent the use of intravenous quinine in severe cases. WHO Model Formulary for Children 2010 217 . Geneva. Propranolol: increased risk of bradycardia. In mild to moderate G6PD deficiency use 500–750 micrograms/kg once a week for 8 weeks. Hill SR. ed. abdominal pain. Australian Medicines Handbook. 2009. ovale infections after standard chloroquine or artemisinin-based combination therapy.6. * Chloroquine: increased risk of convulsions. ed. * Quinine: increased risk of convulsions. 3rd ed. 34th ed. * Quinidine: increased risk of ventricular arrhythmias. Currie A. WHO model formulary. ovale infections. Renal impairment: Dose reduction not necessary. Adverse effects: Common Anorexia. Stuart MC. Atenolol: increased risk of bradycardia. if methaemoglobinaemia or haemolysis occur.5 mg. Martindale: the complete drug reference. Because of the high incidence of neuropsychiatric disorders other drugs should be used in preference to mefloquine where possible. 2005. Oxford. Tablets may be crushed and mixed with food such as jam or honey just before administration. 15 mg (as diphosphate) Indications: Only for use to achieve radical cure of P. withdraw treatment and consult physician. mild to moderate G6PD deficiency. eds. Adelaide. Digoxin: possibly increased risk of bradycardia. 2008. vivax and P. use with caution in patients with liver impairment and monitor liver function tests. References: Ashley C. Precautions: Monitor blood count. Primaquine ATC code: P01BA03 Tablet: 7.

eds. Quinine ATC code: P01BC01 Injection: 300 mg quinine hydrochloride/ml in 2 ml ampoule Tablet: 300 mg (quinine sulfate) or 300 mg (quinine bisulfate) Indications: Multiple drug-resistant P. granulocytopenia and leukopenia. falciparum malaria. Kouimtzi M. 2009.6 Anti-infective medicines Infrequent Acute haemolytic anaemia (frequently in G6PD deficiency). headache. Oral: Child 10 mg/kg (quinine sulfate) every 8 hours for 3. rashes. British national formulary 2008.gov/malaria/. Renal impairment: Reduce parenteral maintenance dose for malaria treatment. Hill SR. 2009. eds. gastrointestinal disturbances. 34th ed. The renal drug handbook. ed. myasthenia gravis. Uncommon Hypoglycaemia. Rossi S. altered auditory acuity. WHO model formulary. Sweetman SC. World Health Organization. especially after parenteral administration. Pharmaceutical Press. 3rd ed. Martindale: the complete drug reference. blurred vision. London. CNS disturbances. ed. asthma. The initial dose should be halved in patients who have received quinine. Precautions: Atrial fibrillation. Joint formulary committee. References: Ashley C. Atlanta. Radcliffe Publishing. blood disorders. angioedema. confusion). 218 WHO Model Formulary for Children 2010 . 2008. prolonged QT interval. NOTe Very toxic in overdosage. agranulocytosis. Hepatic impairment: Dose reduction not necessary. Rare Hypertension. British Medical Association and Royal Pharmaceutical Society of Great Britain. Adelaide. 55th ed. falciparum and whether or not additional antimalarials are being or have been used. diarrhoea. nausea. methaemoglobinaemia. Oxford. 7 or 10 days. 2005. G6PD deficiency. Adverse effects: Common Cinchonism (tinnitus. 2008. tinnitus. caused by increased insulin release (also associated with severe malaria and therefore a poor prognostic sign). immediate medical attention required. 2009 (http://www. Interactions with other medicines (* indicates severe): * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. haemoglobinuria. quinidine or mefloquine during the previous 12–24 hours. temporary blindness. Mild impairment: administer every 8 hours. London. Give a lower dose at increased intervals with oral therapy. Guidelines for treatment of malaria in the United States. Australian Medicines Handbook. optic neuritis. Contraindications: Haemoglobinuria. Dose: Treatment of multiple drug-resistant P. BMJ Group RBS Publishing. Geneva. IV (only in patients unable to take quinine by mouth): Child 20 mg/kg (quinine dihydrochloride) followed by 10 mg/kg (quinine hydrochloride) every 12 hours. hot and flushed skin. Currie A. renal impairment. Australian medicines handbook. conduction defects. severe impairment: administer every 24 hours. moderate impairment: administer every 12 hours. heart block. The duration of treatment is dependent on local susceptibility of P. falciparum malaria. Rare Haemorrhage and renal damage (culminating in acute renal failure and anuria). monitor for signs of cardiac toxicity and hypoglycaemia during intravenous use.cdc. Centers for Disease Control and Prevention. accessed 10 February 2010). hypersensitivity reactions. Stuart MC.

Oxford. Radcliffe Publishing. British national formulary 2008. 11–20 kg 1 tablet as a single dose. IV administration: give by slow intravenous infusion over 4 hours. G6PD deficiency. Joint formulary committee. discontinue immediately if blood disorder occurs. headache. 21–30 kg 1½ tablets as a single dose. but should not prevent the use of intravenous quinine in severe cases. rash. mouth ulcers or shortness of breath. eds. Atlanta. World Health Organization. pruritus. PATIeNT ADVICe If all or part of a dose is vomited within 1 hour. Sulfadoxine + Pyrimethamine ATC code: P01BD51 Tablet: 500 mg + 25 mg Indications: Treatment of P.gov/malaria/. Dose: Treatment of P. Quinine (anhydrous base) 100 mg ≡ quinine bisulfate 169 mg ≡ quinine dihydrochloride 122 mg ≡ quinine sulfate 121 mg. Suxamethonium: possibly enhanced effects of suxamethonium. severe hepatic or renal impairment (except where no alternative treatment available). Stuart MC. Currie A. falciparum malaria in combination with other antimalarials. slight hair loss. quinine should always be used in combination with either doxycycline (not in children under 8 years). 2009. gastrointestinal disturbances including nausea. To avoid resistance. fatigue.5 Interactions with other medicines (* indicates severe): Antiprotozoal medicines * Artemether + lumefantrine: risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises to avoid concomitant use). * Digoxin: plasma concentration of digoxin increased. 3rd ed. Precautions: Avoid in blood disorders unless under specialist supervision. WHO Model Formulary for Children 2010 219 . stomatitis. the same amount must be re-administered immediately. 31–45 kg 2 tablets as a single dose. 2009 (http://www. BMJ Group RBS Publishing. Hill SR. Adverse effects: Common Rashes. cdc. Renal impairment: Dose reduction not necessary. Clindamycin dose for combination therapy: 7–13 mg/kg (maximum 450 mg) every 8 hours for 7 days. Contraindications: Hypersensitivity to sulfonamides or pyrimethamine.6. Oral: Child 5–10 kg half a tablet. London. Centers for Disease Control and Prevention. predisposition to folate deficiency. polyneuritis. 2008. Guidelines for treatment of malaria in the United States. sore throat. References: Ashley C. eds. Kouimtzi M. Notes: Use only in the management of severe malaria. The renal drug handbook. fever. Chloroquine: increased risk of ventricular arrhythmias. accessed 10 February 2010). British Medical Association and Royal Pharmaceutical Society of Great Britain. Hepatic impairment: No information available. vomiting. * Mefloquine: increased risk of convulsions. 2008. Geneva. 55th ed. WHO model formulary. falciparum malaria in combination with artesunate. clindamycin or sulfadoxine/pyrimethamine (SP) where there is no SP resistance.

Contraindications: Not for prophylaxis of P. 2005. toxic epidermal necrolysis. 220 WHO Model Formulary for Children 2010 . British national formulary 2008. World Health Organization. rarely erythema multiforme (Stevens-Johnson syndrome). London. * Methotrexate: antifolate effect of methotrexate increased. 2008. leukopenia. Geneva. Oxford. Martindale: the complete drug reference. Thiopental: enhanced effects of thiopental. hepatitis. Precautions: Chloroquine resistance is now widespread in Africa. WHO model formulary. Adelaide. thrombocytopenia. Currie A. long pants and long-sleeved shirts. Sweetman SC. British Medical Association and Royal Pharmaceutical Society of Great Britain. Australian Medicines Handbook. Chloroquine ATC code: P01BA01 Oral liquid: 10 mg (as phosphate or sulfate)/ml Tablet: 150 mg (as phosphate or sulfate) Indications: Only for use in the prophylaxis of P. megaloblastic anaemia and purpura. falciparum. vivax infection from areas where the parasite remains sensitive. * Sulfamethoxazole + trimethoprim: increased antifolate effect. Rossi S.5. mosquito nets (preferably impregnated with an insecticide). Current guidelines should be consulted to inform management of malaria. * Warfarin: enhanced anticoagulant effect. Asia and the Pacific so is no longer the prophylaxis drug of choice. for example. Stuart MC. withdraw treatment).2 For prophylaxis No drug regimen gives assured protection to everybody. Rare Pulmonary infiltrates such as eosinophilic or allergic alveolitis (if symptoms of cough or Interactions with other medicines (* indicates severe): * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. BMJ Group RBS Publishing. risk of methotrexate toxicity increased. * Sulfadiazine: increased antifolate effect. ed. References: Ashley C. London. and door and window screens are important preventative strategies. 2008. * Trimethoprim: increased antifolate effect. Avoidance of mosquito bites using insect repellents. Joint formulary committee.6 Anti-infective medicines shortness of breath. * Phenytoin: plasma phenytoin concentration possibly increased. 55th ed. Radcliffe Publishing. 2009. and indiscriminate use of antimalarials can increase the risk of inducing resistance. Kouimtzi M. 34th ed. increased antifolate effect. eds.3. Australian medicines handbook. * Ciclosporin: increased risk of nephrotoxicity. Notes: Sulfadoxine + pyrimethamine monotherapy is no longer recommended as this is likely to result in increasing levels of parasite resistance to this drug. the WHO guidelines for the treatment of malaria. 3rd ed. Hill SR. ed. 6. * Folate/folic acid: concurrent use should be avoided as folate may antagonize the effect of sulfadoxine + pyrimethamine. 2009. Pharmaceutical Press. The renal drug handbook. eds.

Adelaide. Currie A. Rossi S. Renal impairment: Severe renal impairment GFR < 10 ml/minute: reduce dose by half. Quinine: increased risk of ventricular arrhythmias. * Digoxin: plasma digoxin concentration possibly increased. Praziquantel: plasma concentration of praziquantel possibly reduced. the same amount must be immediately re-administered. Hepatic impairment: No information available. magnesium hydroxide): reduced absorption of chloroquine. hypersensitivity reactions such as urticaria and angioedema. * Ciclosporin: increased plasma ciclosporin concentration (increased risk of toxicity). * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. tinnitus. 34th ed. and importance of immediate visit to doctor if ill within 1 year and especially within 3 months of return. 16–25 kg 150 mg once weekly. Interactions with other medicines (* indicates severe): Antacids (aluminium hydroxide. BMJ Group RBS Publishing. if part or all of a dose is vomited. eds. 6–10 kg 75 mg once weekly. 10–16 kg 112. Oxford. The renal drug handbook. reversible corneal opacities. Radcliffe Publishing. 2009. Adverse effects: Common Headache. Valproic acid: possible increased risk of convulsions. Australian Medicines Handbook. hearing loss. ed. British national formulary for children 2009. Notes: PATIeNT ADVICe Oral chloroquine should be taken after meals to minimize nausea and vomiting. References: Ashley C. personality changes. Geneva. Pyridostigmine: chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish effect of pyridostigmine. Sweetman SC. Carbamazepine: possible increased risk of convulsions. skin reactions and itch which can be severe enough to affect compliance. high-dose therapy or inappropriate selfmedication). Phenytoin: possible increased risk of convulsions. anxiety. Paediatric Formulary Committee. 2009.5 Dose: Antiprotozoal medicines Prophylaxis for P. Oral: Child up to 12 weeks and under 6 kg 37. Warn travellers about importance of avoiding mosquito bites. seizures. eds. ed. * Mefloquine: increased risk of convulsions. Neostigmine: chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish effect of neostigmine. 12 weeks–1 year.6. 2009. 3rd ed. Dose expressed as chloroquine base and should be started 1 week before entering endemic area and continued for 4 weeks after leaving. porphyria and psoriasis in susceptible individuals. bone marrow suppression. blue-black pigmentation of mucous membranes and skin. Australian medicines handbook. importance of taking prophylaxis regularly. Hill SR. photosensitivity. London. 8–13 years. 25–45 kg 225 mg once weekly. 2005. vivax in central American regions. 2008. Uncommon Psychotic episodes. over 13 years and 45 kg 310 mg once weekly. Stuart MC. Kouimtzi M. atrioventricular block (may be result of inappropriate self-medication). visual disturbances (retinopathy associated with long-term.5 mg once weekly. 1–4 years. WHO model formulary. 4–8 years. Martindale: the complete drug reference. London. Ethosuximide: possible increased risk of convulsions.5 mg once weekly. Pharmaceutical Press. gastrointestinal disturbances. Rare Depigmentation or loss of hair. WHO Model Formulary for Children 2010 221 . World Health Organization.

S. flushing. 2008. Interactions with other medicines (* indicates severe): * Ciclosporin: possibly increased plasma ciclosporin concentration. Australian Medicines Handbook. Department of Health and Human Services. anorexia. fungal overgrowth. References: Ashley C. Contraindications: Pregnancy. 2009. Indications: Short-term prophylaxis of multiple drug-resistant P. Phenytoin: increased metabolism of doxycycline (reduced plasma concentration). bone deformity. Australian medicines handbook. doxycycline should be started on the day before exposure and continued for 4 weeks after last risk of exposure. Atlanta. 222 WHO Model Formulary for Children 2010 . hypersensitivity reactions including StevensJohnson syndrome. eds. BMJ Group RBS Publishing. WHO model formulary. absorption of doxycycline reduced by oral ferrous salts. Radcliffe Publishing. falciparum malaria. Precautions: Avoid exposure to sunlight or sunlamps. 2009. to counter gastric irritation. falciparum malaria. Paediatric Formulary Committee. Antacids (aluminium hydroxide. The renal drug handbook. World Health Organization. stomatitis. Oxford. porphyria. Geneva. oesophageal ulcers (due to partly swallowed tablets). Hill SR. 2009. British national formulary for children 2009. systemic lupus erythematosus. Rossi S. Carbamazepine: accelerated metabolism of doxycycline (reduced effect). Renal impairment: Dose reduction not necessary. Hepatic impairment: Avoid (or use with caution). Rare Photo-onycholysis. Rifampicin: plasma doxycycline concentration possibly reduced. hepatitis. photosensitivity reported. Adelaide. nail discoloration. tinnitus. 2009. May be given with food or milk. CDC health information for international travel 2010. Methotrexate: increased risk of methotrexate toxicity. Clostridium difficile infection. Oral: Child over 8 years 2 mg/kg (maximum 100 mg) daily for up to 8 weeks.6 Anti-infective medicines Doxycycline ATC code: J01AA02 Solid dosage form: 100 mg (as hydrochloride) Special Notes: WHO age/weight restriction: > 8 years. London. Ferrous salts: absorption of oral ferrous salts reduced by doxycycline. 3rd ed. Dose: Short-term prophylaxis of multiple drug-resistant P. Stuart MC. magnesium hydroxide): reduced absorption of doxycycline. vomiting. Currie A. Kouimtzi M. diarrhoea. Should not be used in children under 8 years: deposition of tetracyclines in growing bones and teeth (by binding to calcium) causes staining and occasionally dental hypoplasia. Phenobarbital: metabolism of doxycycline accelerated (reduced plasma concentration). headache and visual disturbances which may indicate benign intracranial hypertension. nausea. fatty liver degeneration. * Warfarin: anticoagulant effect possibly enhanced. photosensitivity. Public Health Service. Uncommon Rash. eds. Notes: PATIeNT ADVICe Capsules should be swallowed whole with plenty of fluid while sitting or standing to prevent oesophageal irritation. Centers for Disease Control and Prevention. U. Adverse effects: Common Gastrointestinal disturbance. ed.

anorexia. WHO Model Formulary for Children 2010 223 . cardiac conduction disorders. Neuropsychiatric disorders occur in at least 1:10 000 patients treated with mefloquine and the incidence is thought to be up to 1:1000 when used at treatment doses. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Indications: Prophylaxis of malaria for travellers to areas with high risk of multiple resistant P. atrioventricular block and encephalopathy. Phenytoin: antagonism of anticonvulsant effect. hallucinations. tachycardia. Uncommon Circulatory disorders. thrombocytopenia. panic attacks. urticaria. falciparum. arthralgia. otherwise dose reduction not needed. Digoxin: possibly increased risk of bradycardia. alopecia. vestibular disorders. Oral: Child over 3 months or 5 kg 5 mg/kg (maximum 250 mg) once a week. It * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. * Carbamazepine: antagonism of anticonvulsant effect. Round dose to the nearest quarter of a tablet. agitation and psychoses. confusion. Contraindications: History of neuropsychiatric disorders including depression or convulsions. rash. bradycardia. dizziness (can be severe). anxiety. aggression. leukopenia. for example riding a bike or operating machinery. Renal impairment: Use with caution in severe renal impairment. falciparum. somnolence. * Quinidine: increased risk of ventricular arrhythmias. Stevens-Johnson syndrome.6. Dose: Prophylaxis of malaria for travellers to areas with high risk of multiple resistant P. abdominal pain. pruritus. Atenolol: increased risk of bradycardia. emotional instability. disturbances in liver function tests. prophylaxis should start 1–3 weeks before departure and continue for 4 weeks after last exposure. Avoid use for prophylaxis in severe liver disease.5 Antiprotozoal medicines Mefloquine ATC code: P01BC02 Tablet: 250 mg (as hydrochloride) Special Notes: WHO age/weight restriction: > 5 kg or > 3 months. Rare Hyperpyrexia. vomiting. muscle weakness. insomnia and abnormal dreams. tremor. These include sensory and motor neuropathies. depression. suicidal ideation. headache. Interactions with other medicines (* indicates severe): Hepatic impairment: Mefloquine is metabolized by the liver and eliminated by the biliary system. Precautions: Avoid use in cardiac conduction disorders and in epilepsy. loss of balance. leukocytosis. * Ethosuximide: antagonism of anticonvulsant effect. Propranolol: increased risk of bradycardia. * Chloroquine: increased risk of convulsions. Adverse effects: Common Nausea. for 24 hours. seizures. myalgia. hypersensitivity to quinine. visual disturbances. diarrhoea. should be used with caution in patients with disorders of the biliary system who may not be able to clear the drug. ataxia. tinnitus.

reversible alopecia. eds. 2009. Severe: quarter dose once weekly. Warfarin: isolated reports of enhanced anticoagulant effect. World Health Organization. and importance of an immediate visit to doctor if ill within 1 year and especially within 3 months of potential exposure. advised to seek medical advice on alternative antimalarials. WHO model formulary. Australian Medicines Handbook. 224 WHO Model Formulary for Children 2010 . Hepatic impairment: Metabolized by the liver to the active metabolite so unlikely to be effective in patients with severe liver impairment. 2009. Moderate: quarter dose every 48 hours. vomiting. diarrhoea. 1–4 years 50 mg daily. 2009. Public Health Service. Rare Megaloblastic anaemia and pancytopenia (more likely with renal impairment). Stuart MC. Pyrimethamine: increased antifolate effect. Mefloquine tablets may be crushed and mixed with food such as jam or honey just before administration. Geneva. Adverse effects: Common Mild gastric intolerance. eds. Notes: PATIeNT ADVICe Warn travellers about the importance of avoiding mosquito bites. hepatitis. British national formulary for children 2009. skin reactions. 9–12 years 150 mg daily. London. The renal drug handbook. BMJ Group RBS Publishing. * Valproic acid: antagonism of anticonvulsant effect. 3rd ed. Proguanil ATC code: P01BB01 Tablet: 100 mg (hydrochloride) Indications: Prophylaxis of malaria in areas of low resistance in combination with chloroquine. constipation. 1 tablet = 228 mg base (250 mg salt). CDC health information for international travel 2010. Renal impairment: Mild: half dose. Infrequent Mouth ulcers. Oxford. Paediatric Formulary Committee. Hill SR. ed.6 Anti-infective medicines * Quinine: increased risk of convulsions. Centers for Disease Control and Prevention. vertigo. Department of Health and Human Services. 5–8 years 100 mg daily. importance of taking prophylaxis regularly. stomatitis. References: Ashley C.S. seizures. U. Dose: Prophylaxis of malaria in areas of low resistance in combination with chloroquine. but should not prevent the use of intravenous quinine in severe cases. cholestasis. Start taking 1–2 days before entering and continue for 4 weeks after leaving an endemic area. Radcliffe Publishing. psychosis. Atlanta. 2009. Rossi S. Patients should be informed about adverse effects associated with mefloquine and if they occur. Currie A. Adelaide. nausea. Interactions with other medicines (* indicates severe): * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use. Kouimtzi M. hypersensitivity reactions such as urticaria and angioedema. 2008. Australian medicines handbook. Oral: Child under 1 year 25 mg daily. vasculitis.

2009. Approximately 3% of Caucasians cannot metabolize proguanil to cycloguanil. P. and the most frequent immediate cause of death in these patients. the active metabolite. Oxford. history of seizures (avoid large loading doses). However.int/hiv/pub/paediatric/en/). Contraindications: Megaloblastic anaemia. However. it is also used for prophylaxis in HIV-infected. HIV-exposed and other immunocompromised children. London. WHO model formulary. Hill SR. carinii) is a common cause of pneumonia in people with AIDS. jiroveci (P. Precautions: Folate deficiency.g. 3rd ed. Geneva. 2008. eds. Toxoplasmosis Toxoplasmosis is caused by infection with the protozoan parasite. in people with AIDS) in a previously infected person may cause reactivation. The treatment of choice for toxoplasmosis is a combination of pyrimethamine and sulfadiazine. Currie A. Radcliffe Publishing. 2009. debilitated or malnourished patients. These patients also have an increased risk of adverse effects. World Health Organization. Australian medicines handbook. in immunodeficiency. References: Ashley C. Paediatric Formulary Committee. blood counts required with prolonged treatment. resulting in encephalitis or meningoencephalitis. The renal drug handbook.6. 2009. Most infections are self-limiting and do not require treatment. British national formulary for children 2009. myocarditis or pneumonitis. carinii) pneumonia. it is a frequent cause of opportunistic infection in immunosuppressed. expert advice essential. Rossi S. Tablets may be crushed and mixed with food such as milk. Kouimtzi M. importance of taking prophylaxis regularly. ed. and importance of immediate visit to doctor if ill within 1 year and especially within 3 months of return. Australian Medicines Handbook. Sulfamethoxazole + trimethoprim (co-trimoxazole) is the treatment of choice for P.5 Antiprotozoal medicines Notes: PATIeNT ADVICe Warn travellers about the importance of avoiding mosquito bites. supplement folate throughout treatment to prevent haematological toxicity. renal impairment. eds. Pyrimethamine ATC code: P01BD01 Tablet: 25 mg Indications: Treatment and prophylaxis of toxoplasmosis. WHO Model Formulary for Children 2010 225 . Refer to the WHO guidelines Co-trimoxazole prophylaxis for HIV-exposed and HIV-infected infants and children (available from https://www. 6. jam or honey just before administration. especially GI side effects. BMJ Group RBS Publishing. Impairment of immunity (e.who. prophylaxis of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia. Local antimicrobial sensitivity patterns need to be taken into account.5. and these people are effectively only receiving the chloroquine component of their therapy. jiroveci (P. Toxoplasma gondii.4 Antipneumocystosis and antitoxoplasmosis medicines Pneumocystosis Pneumocystis jiroveci (Pneumocystis carinii) is classified as a protozoan which in otherwise healthy people rarely produces signs of infection. hepatic impairment. Adelaide. primary infection may result in encephalitis. Stuart MC. a folate supplement is also given to counteract the inhibition of folate synthesis associated with these drugs.

Maximum 25 mg daily. Dosage adjustment not considered to be necessary in renal impairment. megaloblastic anaemia. Oral: Neonate 1 mg/kg twice daily for 2 days. insomnia. Notes: Pyrimethamine-associated reversible bone marrow suppression warrants that a complete blood count be performed at least weekly while the patient is on daily pyrimethamine and at least monthly while on less than daily dosing. then 1 mg/kg once daily for 6 months. Maximum 50 mg daily. If without overt disease but born to mother infected during pregnancy. treat for 4 weeks. Due to the long half-life of pyrimethamine. Zidovudine: increased antifolate effect. Treatment of toxoplasmosis (in combination with sulfadiazine and calcium folinate). * Trimethoprim: increased antifolate effect. followed by further courses if infection confirmed. then 1 mg/ kg three times weekly for a further 6 months. 226 WHO Model Formulary for Children 2010 . It is also important that calcium folinate be always administered with pyrimethamine and increased doses of calcium folinate may be necessary if marrow suppression occurs. increased antifolate effect. Adverse effects: Depression of haematopoiesis (with high doses). Oral: Child over 1 month 1 mg/kg (maximum 25 mg/dose) twice daily for 3 days. rashes. Renal impairment: Use with caution. * Sulfamethoxazole + trimethoprim: increased antifolate effect. Oral: Child over 1 month 1 mg/kg once daily. Duration of treatment depends on whether the neonate has overt disease. Primary prophylaxis of toxoplasmosis (in combination with dapsone (not on eMLc for this indication) and calcium folinate). Treatment of congenital toxoplasmosis (in combination with sulfadiazine and calcium folinate). Proguanil: increased antifolate effect.6 Anti-infective medicines Dose: NOTe Calcium folinate must always be administered with pyrimethamine to prevent haematological toxicity. Secondary prophylaxis of toxoplasmosis in addition to prophylaxis of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia (in combination with sulfadiazine and calcium folinate). * Methotrexate: antifolate effect of methotrexate increased. Interactions with other medicines (* indicates severe): * Artemether + lumefantrine: manufacturer of artemether with lumefantrine advises avoid concomitant use. gastrointestinal disturbances. * Silver sulfadiazine: increased antifolate effect. calcium folinate administration should be continued for 1 week after pyrimethamine has been discontinued. Oral: Infant or Child 1 mg/kg once daily. then 1 mg/kg (maximum 25 mg) once daily for at least 6 weeks. NOTe Clindamycin (not on the eMLc for this indication) may be used instead of sulfadiazine in patients intolerant of sulfonamides. Administer pyrimethamine with food to minimize vomiting. * Sulfadiazine: increased antifolate effect. * Phenytoin: antagonism of anticonvulsant effect. Hepatic impairment: Use with caution in patients with hepatic impairment.

hepatic impairment. 2009. MIMS Online. Geneva. WHO Model Formulary for Children 2010 227 . * Sulfadoxine + pyrimethamine: increased antifolate effect. Rare Hepatitis.com. Oral: Child all ages 25–50 mg/kg (maximum 1–1. blood dyscrasia. Pediatric dosage handbook. Phenytoin: plasma phenytoin concentration possibly increased. * Warfarin: enhanced anticoagulant effect.thomsonhc. Thiopental: enhanced effects of thiopental. Hill SR. London. high risk of crystalluria. Thomson Micromedex. Drugdex system. American Academy of Pediatrics. 2009 (https://www. prophylaxis of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia in combination with pyrimethamine. Hepatic impairment: Use with caution. increased risk of nephrotoxicity. Contraindications: Hypersensitivity to any sulfa drug. 2008.aspx). accessed 10 February 2010). Sulfadiazine ATC code: J01eC02 Tablet: 500 mg Indications: Toxoplasmosis in combination with pyrimethamine. porphyria. followed by secondary prophylaxis therapy. expert advice essential. Taketomo CK. World Health Organization. British national formulary for children 2009. Dose: Treatment of congenital toxoplasmosis (in combination with pyrimethamine and calcium folinate). Methotrexate: risk of methotrexate toxicity increased. BMJ Group RBS Publishing. Treatment of toxoplasmosis (in combination with pyrimethamine and calcium folinate). 2010 (http://www. Renal impairment: Use with caution in renal impairment. Local antimicrobial sensitivity patterns need to be taken into account.com. ed. eds. pancreatitis. Red Book: 2009 report of the committee on infectious diseases. Stevens-Johnson syndrome. 28th ed. elk Grove Village.au/Search/Search. abdominal pain. Severe renal impairment: avoid. Oral: Child all ages 85–120 mg/kg daily in 2–4 divided doses. Paediatric Formulary Committee. Oral: Neonate 50 mg/kg twice daily for 12 months. Hudson. Sydney. WHO model formulary.5 g per dose) four times daily.6. 2009. * Pyrimethamine: increased antifolate effect. Hodding JH. UBM Medica. Greenwood Village. G6PD deficiency. blood dyscrasias. 2009. NOTe Clindamycin (not on the eMLc for this indication) may be used instead of sulfadiazine in patients intolerant of sulfonamides. Stuart MC.5 References: Antiprotozoal medicines American Academy of Pediatrics. crystalluria. urinary obstruction. Uncommon Vomiting. Lexi-Comp. rash. Precautions: Renal impairment. Kraus DM. Kouimtzi M. 16th ed. Adverse effects: Common Nausea. Klasco RK. Interactions with other medicines (* indicates severe): * Ciclosporin: plasma ciclosporin concentration possibly reduced.mimsonline. Secondary prophylaxis of toxoplasmosis in addition to prophylaxis of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia (in combination with pyrimethamine and calcium folinate).

2010. diarrhoea. severe hepatic impairment. 6 months–5 years 40 mg once daily. Klasco RK. ed. methaemoglobinaemia). drowsiness. Sulfamethoxazole + Trimethoprim ATC code: J01ee01 Injection: 80 mg + 16 mg/ml in 5 ml ampoule. Precautions: Mild to moderate renal impairment. thrombocytopenia. Red Book: 2009 report of the committee on infectious diseases. Total daily dose may alternatively be given in 3–4 divided doses. Greenwood Village. 2009. discontinue immediately if blood disorder develops. Drugdex system. 228 WHO Model Formulary for Children 2010 . thrombocytopenia. Local antimicrobial patterns need to be taken into account. (http://www. fever. Treatment of P. 2009. hyperkalaemia. 400 mg + 80 mg Special Notes: Also referred to as co-trimoxazole. Taketomo CK. nausea. American Academy of Pediatrics. Hepatic impairment: Severe impairment: avoid use. The IV route is preferred. leukopenia. 2009. rash. Incidence of some adverse effects (rash. blood disorders (including neutropenia. jiroveci (P. Hudson. megaloblastic anaemia. anorexia. predisposition to folate deficiency. vomiting. 6–12 years 80 mg once daily. Dose: Doses are expressed in terms of the trimethoprim component. megaloblastic anaemia. Contraindications: Hypersensitivity to sulfonamides or trimethoprim. Renal impairment: Severe impairment: avoid use. Thomson Micromedex. photosensitivity. Paediatric Formulary Committee. 16th ed. BMJ Group RBS Publishing. carinii) infections. nausea. Oral: Infant or Child under 6 months 20 mg once daily. Lexi-Comp. Kraus DM. Pediatric dosage handbook. thrombocytopenia. Hodding JH. 80 mg + 16 mg/ml in 10 ml ampoule Oral liquid: 40 mg + 8 mg/ml Tablet: 100 mg + 20 mg. London. Oral or IV: Infant or Child over 1 month 10 mg/kg every 12 hours for 14–21 days. porphyria. stomatitis. severe renal impairment. 28th ed.thomsonhc. G6PD deficiency. Common Fever.6 Anti-infective medicines References: American Academy of Pediatrics. raised hepatic aminotransferases) is substantially higher in patients with AIDS. asthma. monitor blood counts on prolonged treatment. eosinophilia. maintain adequate fluid intake (to avoid crystalluria). jaundiced neonates. accessed 10 February 2010). Indications: Treatment and prophylaxis of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia.com. British national formulary for children 2009. elk Grove Village. neutropenia. Prophylaxis for P. carinii) infections. rash (discontinue immediately). itch. seek expert advice. avoid in blood disorders (unless under specialist supervision). Uncommon Headache. Adverse effects: Some adverse effects may be hypersensitivity reactions (see below). jiroveci (P. Plasma monitoring may be required with high doses in renal impairment. Moderate impairment: use half normal dose.

Hodding JH. Trimethoprim with sulfamethoxazole can cause nephrotoxicity. lowered mental acuity. HyPeRSeNSITIVITy May present with fever. Taketomo CK. systemic vasculitis and pancytopenia. References: Centers for Disease Control and Prevention. Notes: Oral dose is best given with or after food. Hudson. Kraus DM. eds. 2008. Trimethoprim can cause hyperkalaemia. WHO Model Formulary for Children 2010 229 . toxic epidermal necrolysis. pneumonitis. risk of methotrexate toxicity increased. ataxia (after IV use in HIV patients). Hill SR.9% or Ringer’s intravenous solution. the HIV Medicine Association of the Infectious Diseases Society of America. urinary obstruction with anuria/oliguria. Thiopental: enhanced effects of thiopental. hypoglycaemia. 58(RR-11):1–176. dyspnoea. the Pediatric Infectious Diseases Society. crystalluria. Check container for haze or precipitant during administration. Stevens-Johnson syndrome. Stuart MC. * Phenytoin: antifolate effect and plasma phenytoin concentration increased. eosinophilia. 13th ed. Digoxin: plasma concentration of digoxin possibly increased. hyponatraemia.g. 16th ed. 5 ml may be diluted with 75 ml of glucose 5% and the required dose infused over a maximum of 60 minutes. Paediatric pharmacopoeia. vasculitis. Pediatric dosage handbook. hepatitis. * Pyrimethamine: increased antifolate effect. 2002. pancreatitis. * Azathioprine: increased risk of haematological toxicity. DILUTION AND ADMINISTRATION For intermittent intravenous infusion may be further diluted in glucose 5% and 10% or sodium chloride 0. * Sulfadoxine + pyrimethamine: increased antifolate effect. * Warfarin: enhanced anticoagulant effect. pyrimethamine. Procainamide: increased plasma procainamide concentration. rash. jaundice. Kouimtzi M. e. If fluid restriction necessary. plasma ciclosporin concentration possibly reduced by intravenous trimethoprim. hepatic necrosis. McDowell JM. In severe fluid restriction may be given undiluted via a central venous line. * Ciclosporin: increased risk of nephrotoxicity. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from CDC. Geneva. Attention should be paid to the folate status of the patient should treatment be prolonged or high dose. the most serious effects include anaphylaxis. and the American Academy of Pediatrics. administration with potassium supplements or other drugs which also cause potassium retention can further increase potassium concentration. tremor. Infuse over 60–90 minutes (but may be adjusted according to fluid requirements). Morbidity and Mortality Weekly Report. dilute each 5 ml of injection solution to 125 ml.6. Clostridium difficileassociated disease. antibiotic-associated colitis. Lamivudine: plasma concentration of lamivudine increased (avoid concomitant use of high-dose sulfamethoxazole + trimethoprim). * Mercaptopurine: increased risk of haematological toxicity. the National Institutes of Health. WHO model formulary. 2009. giving with other nephrotoxic drugs may cause additional renal adverse effects. Must be further diluted. cough. 2009. Interactions with other medicines (* indicates severe): Trimethoprim is a folate antagonist and will add to the effects on bone marrow of other folate antagonists. lupuslike syndrome. Lexi-Comp. interstitial nephritis. Melbourne. Royal Children’s Hospital. Kemp CA.5 Antiprotozoal medicines Rare erythema. depression. aseptic meningitis. hepatitis. * Methotrexate: antifolate effect of methotrexate increased (avoid concomitant use). serum sickness-like syndrome. * Dapsone: plasma concentration of both dapsone and trimethoprim may increase with concomitant use. World Health Organization.

Strengthening health services to fight HIV/AIDS: guidelines on co-trimoxazole prophylaxis for HIV-related infections among children. World Health Organization. adolescents and adults: recommendations for a public health approach. 2008. Paediatric Formulary Committee. leukopenia (< 1000 cells/mm3). Two subspecies of Trypanosoma brucei (T.com. or sleeping sickness. ed. October 2007 (including the model list of essential medicines for children).7–2%. brucei gambiense infection constitutes 95% of all human African trypanosomiasis cases. Eflornithine ATC code: P01CX03 Injection: 200 mg (hydrochloride)/ml in 100 ml bottle Iatrogenic mortality from 0. The second meningoencephalitic stage results from infection of the central nervous system.pdf. 2006 (http://www. The early stage of African trypanosomiasis results from infection of the blood stream and lymph nodes. ed. Rossi S. WHO expert committee on the selection and use of essential medicines. Special Notes: Also referred to as (alpha)-difluoromethylornithine and DFMO. The selection and use of essential medicines: report of the WHO expert committee. patients should be followed up at 6-monthly intervals for 24 months. is a protozoan infection which is transmitted by Glossina spp. 2009. accessed 28 April 2010). brucei rhodesiense with suramin sodium and T. Monitoring of leukocytes. Following treatment of African trypanosomiasis. 950 (http://www. BMJ Group RBS Publishing. Drugdex system.5.int/medicines/publications/essentialmeds_committeereports/TRS_950. Greenwood Village. First-stage disease Treatment of early-stage infections of T. since both medications reach therapeutic levels in the central nervous system.who. London. T. Medicine for the treatment of second-stage African trypanosomiasis. 2009. 6.pdf ). Adverse effects occur frequently during its use. brucei gambiense with pentamidine can be curative if started before the central nervous system has become involved. accessed 10 February 2010). Reactions requiring immediate corrective measures and withdrawal of treatment include severe anaemia (8 g/dl). eflornithine is a toxic drug. Geneva.5 Antitrypanosomal medicines 6.5. brucei gambiense infection. Adelaide. brucei gambiense and T. Second-stage disease Eflornithine and melarsoprol are used for the treatment of second-stage (neurological) trypanosomal infections. brucei rhodesiense) produce distinctive clinical forms of the disease.5. thrombocytopenia (< 20 000 cells/mm3). eflornithine should therefore be used only for approved indications where close observation can be maintained. (http://www. total protein content and trypanosome presence in cerebrospinal fluid is recommended in order to evaluate treatment efficacy. (tsetse flies). 230 WHO Model Formulary for Children 2010 .who. British national formulary for children 2009.6 Anti-infective medicines Klasco RK.thomsonhc. Australian medicines handbook.1 African trypanosomiasis African trypanosomiasis. 2010. int/hiv/pub/guidelines/ctxguidelines. Australian Medicines Handbook. Thomson Micromedex. and are sometimes fatal. Signs of the later stage develop within a few weeks in T. WHO Technical Report Series. brucei rhodesiense infection but only after several months or years in T.

336:679–680. African trypanosomiasis (sleeping sickness). Bags containing diluted eflornithine should be stored at 4 °C (39 °F) to minimize the risk of microbial proliferation. seizures. The Medical Letter. Checchi F. thrombocytopenia. abdominal pain. Drugs for parasitic infections. anaemia. Dose: Treatment of second-stage Trypanosoma brucei gambiense infection. NOTe These doses are based on clinical experience and limited evidence. 2009 (http://emedicine. 2008. 340:652–655. Hill SR. pyomyositis and generalized sepsis. bacterial infection at the catheter site with risk of phlebitis. Geneva. Adverse effects: Common Diarrhoea. After dilution with sterile water for injection. New york. impaired hearing (usually with longer courses used for cancer treatment). 2008. Geneva. death. pruritus. WHO Model Formulary for Children 2010 231 . Monitoring should continue for up to 4 weeks after finishing treatment. References: Abramowicz M. cellulitis.5 Antiprotozoal medicines Indications: Treatment of second-stage Trypanosoma brucei gambiense infection. muscle pain.who. British Medical Journal. 1992. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concurrent use. Milord F et al. Notes: eflornithine hydrochloride concentrate for injection is hypertonic and must be diluted with sterile water for injection before infusion. 2004. World Health Organization. In: Abramowicz M. African sleeping sickness. concurrent bacterial infections. eflornithine in combination with nifurtimox has been recently introduced to reduce duration and workload of eflornithine monotherapy and may delay the appearance of drug resistance. Uncommon Anorexia.medscape.int/trypanosomiasis_african/drugs/ en/index. leukopenia or thrombocytopenia requires an interruption in treatment until there is evidence of bone marrow recovery). accessed 10 February 2010).html. eMedicine. eflornithine is safer than melarsoprol for the treatment of second-stage Trypanosoma brucei gambiense human African trypanosomiasis. 41:748–751. monitor complete blood and platelet counts for bone marrow suppression (severe anaemia. renal impairment. eflornithine is 80% renally excreted. Rare Alopecia. World Health Organization. nausea. WHO model formulary. The Medical Letter on Drugs and Therapeutics. practical perspectives. Clinical Infectious Diseases. Barrett MP. vomiting. WebMD. Lancet. headache. Chappuis F et al. Developpement et Sante. Human African trypanosomiasis. leukopenia. Stuart MC. Odero RO. eflornithine must be used within 24 hours. ed. Currently. 171:41–47. there is a multicentre trial being conducted which includes assessing the safety and efficacy in children at the same dose as adults. Strict aseptic technique should be used when administering. confusion. with frequent replacement of IV cannulas (at least every 2 days). 2005. 2000:1–12. tremor. Renal impairment: Dosage adjustment may be required in all degrees of renal impairment. oedema.com/ article/228613-overview. eds. 2010 (http://www.6. over 35 kg 100 mg/kg over 2 hours every 6 hours for 14 days. Slow IV infusion: Child under 35 kg 150 mg/kg over 2 hours every 6 hours for 14 days. eflornithine for the treatment of human African trypanosomiasis. Contraindications: Ineffective in the treatment of Trypanosoma brucei rhodesiense human African trypanosomiasis. Kouimtzi M. Precautions: Hospitalization and close supervision throughout treatment. New Rochelle. Chappuis F et al. accessed 10 February 2010). dizziness. injection site reaction. efficacy and toxicty of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness. eosinophilia.

com/mmx/ornidyl. resulting from trypanosome destruction). is characterized by fever. 374:56–64. avoid use during influenza epidemics (increased risk of reactive encephalopathy in febrile patients).2 mg/kg daily for 10 days. Priotto G et al.2 mg/kg to maximum of 3. haemorrhagic encephalopathy. hyperthermia. Herxheimer reaction (fever and chills may also occur. Treatment of second-stage Trypanosoma brucei gambiense infection.6%) solution. reactive encephalopathy (immediate treatment suspension essential). fever. NOTe Prednisolone 1 mg/kg once daily should be administered concurrently to all patients for the duration of melarsoprol therapy. peripheral neuropathy. FATAL ReACTIVe eNCePHALOPATHy Also known as “arsenical encephalopathy”. headache. Dose: Treatment of second-stage Trypanosoma brucei rhodesiense infection. 2008. aplastic anaemia. hypersensitivity reactions (especially on second or subsequent doses). malnutrition (if possible. leprosy (may precipitate erythema nodosum). Rare Agranulocytosis.html. Precautions: Hospitalization and close medical supervision required throughout treatment. albuminuria. hypertension. correct with protein-rich diet). Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study. accessed 10 February 2010). WHO expert committee on the control and surveillance of African trypanosomiasis. avoid extravasation. Adverse effects: Common Fatal reactive encephalopathy (see below). 2009. seizures and ultimately coma (occurs in 3–10% of patients treated with melarsoprol.6 Anti-infective medicines Ornidyl Product Information. thrombocytopenia. Indications: Treatment of second-stage Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense infection. urticaria. Special Notes: Also referred to as Mel B or Melarsen Oxide-BAL. Reactive encephalopathy appears to be more frequent in children.6 mg/kg daily in courses of 3–4 days with intervals of 7–10 days between courses. headache. 336(7646):705–708. phase III. tremor. thrombophlebitis. diarrhoea. Slow IV infusion: Child all ages 2. exfoliative dermatitis. slurred speech. vomiting. Melarsoprol ATC code: P01CD01 Injection: 36 mg/ml (3. 1998. Treatment of second-stage African trypanosomiasis. It should therefore be used only for the approved indications where close observation can be maintained and it can be administered by experienced personnel. Pritti G et al. 881:1–114. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre. British Medical Journal. Uncommon Myocardial damage. 5 ml ampoule (180 mg of active compound) Melarsoprol is very toxic with a 3–10% lethality. arthralgia. treat intercurrent infections such as pneumonia and malaria before melarsoprol administration. Lancet. WHO Technical Report Series. 1995 (http://www. non-inferiority trial. G6PD deficiency. Control and surveillance of African trypanosomiasis.drugs. randomised. Jarisch- 232 WHO Model Formulary for Children 2010 . fever. Melarsoprol is strictly for intravenous use only. Slow IV infusion: Child all ages dose gradually increased from 1. and is fatal in approximately 50% of those who experience it). skin reactions. Marion Merrell Dow. Contraindications: Ingestion of alcohol during treatment.

2008.6% solution in propylene glycol. 2010 (http://www. Pentamidine ATC code: P01CX01 Powder for injection: 300 mg (pentamidine isetionate) in vial Pentamidine isetionate is toxic and personnel should be adequately protected during handling and administration. Stuart MC. Rhone-Poulenc Rorer. 191(11):1922–1931. Fatalities have been documented following pentamidine administration. hypocalcaemia and ventricular tachycardia. World Health Organization. consult product literature.6. eflornithine therapy should be considered. WHO Technical Report Series. accessed 10 February 2010). Drugs for parasitic infections. WHO model formulary. 2010. 2005. ed. 2009 (http://emedicine. Trial of prednisolone for prevention of melarsoprol-induced encephalopathy in gambiense sleeping sickness.com/mmx/arsobal. Control and surveillance of African trypanosomiasis. 2000:1–12.html. care should be taken to avoid leakage into the surrounding tissues. Lancet. Pepin J et al.int/trypanosomiasis_african/drugs/ en/index. occur frequently during its use. extravasation during intravenous administration may result in extreme local tissue damage and destruction. Geneva. The Medical Letter on Drugs and Therapeutics. 1994 (http://www. Journal of Infectious Diseases. Re-treatment with melarsoprol in these patients has not been consistently effective and is not recommended. acute renal failure.medscape. 333(8649):1246–1250. Notes: Relapse has been reported in up to 20–30% of late-stage trypanosomiasis patients after treatment with melarsoprol. ADMINISTRATION Melarsoprol should be administered by slow intravenous injection as a 3. Human African trypanosomiasis. 1989. Pentamidine should. effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMeL II). sometimes fatal. Kouimtzi M. Geneva. 881:1–114. Greenwood Village. eds. be used only for the approved indications where close observation can be maintained. hypoglycaemia.5 Interactions with other medicines (* indicates severe): Antiprotozoal medicines Alcohol: combination contraindicated as increases toxicity of melarsoprol. Severe. The Medical Letter. accessed 10 February 2010). Indications: Treatment of first-stage Trypanosoma brucei gambiense infection. ed. African trypanosomiasis (sleeping sickness). Special Notes: Medicine for the treatment of first-stage African trypanosomiasis. pancreatitis and cardiac arrhythmias have been reported. New Rochelle.html. therefore. New york. eMedicine. The ratio of therapeutic to toxic dose of pentamidine is very low and adverse effects. some of which may be life threatening. accessed 10 February 2010). This appears related to resistance. Patients should remain supine and fasting for at least 2 hours after injection to reduce gastrointestinal side-effects. WHO expert committee on the control and surveillance of African trypanosomiasis. References: Abramowicz M. accessed 10 February 2010). 1998.drugs. In: Abramowicz M. World Health Organization.com. Arsobal Product Information. Other life-threatening reactions requiring immediate corrective measures and withdrawal of treatment have included leukopenia (< 1000 cells/mm3). WHO Model Formulary for Children 2010 233 . WebMD.com/ article/228613-overview. Klasco RK.thomsonhc. although reinfection or inadequate CSF concentrations of the drug may be responsible in some cases. Thomson Micromedex. This strength is no longer in production and a 300 mg vial is available. Drugdex system. thrombocytopenia (< 20 000 cells/mm3). Schmid C et al. Because melarsoprol injection is intensely irritating due to its propylene glycol content. Odero RO. hypotension. The WHO Model List of essential Medicines for Children 2009 has the 200 mg vial listed. (http://www. Hill SR.who.

leukopenia. hyperkalaemia. Control and surveillance of African trypanosomiasis. Greenwood Village. Klasco RK. IM: Infant or Child 4 mg/kg daily for 7 days. hallucinations. arrhythmias. Stevens-Johnson syndrome. World Health Organization.g. renal or pancreatic function. Pediatric dosage handbook. pain. Hill SR. 55(6):586–588. or trypanosomes detected in cerebrospinal fluid). Artemether: increased level and toxicity of pentamidine. 2009. interrupt or discontinue treatment). gastrointestinal disturbances. Administer by deep intramuscular injection and preferably into the buttock. ReCONSTITUTION AND ADMINISTRATION Reconstitute vial with water for injection to a final concentration of 100 mg/ml. establish baseline blood pressure and administer with patient lying down. 881:1–114. Precautions: Cerebrospinal fluid examination before treatment (pentamidine not likely to be Dose: Treatment of first-stage T. ed. immunodeficiency (if acute deterioration in bone marrow. American Journal of Tropical Medicine and Hygiene. rash. half an hour before administration. nausea. Avoid concomitant use. eds. accessed 10 February 2010). Monitor blood pressure and cardiac rhythm during administration and treatment period. Typhoid vaccine: pentamidine may decrease the effect of typhoid vaccine. 2010. London. abnormal liver function tests. References: Doua F. Stuart MC. World Health Organization. Interactions with other medicines (* indicates severe): Amphotericin B: possibly increased risk of nephrotoxicity.int/trypanosomiasis_african/drugs/ en/index.6 Anti-infective medicines effective if leukocyte count greater than 5–10 cells/mm3. Human African trypanosomiasis.html. Paediatric Formulary Committee. Thomson Micromedex. (http://www. Hypoglycaemia post-administration is easily prevented by administering oral sugar. acute hypotension. British national formulary for children 2009.com. Renal impairment: Severe impairment: reduce dose interval (e. renal impairment. thrombocytopenia. hepatic impairment. Avoid concomitant use. Hudson. local induration. hypotension or hypertension. Periodic eCG is desirable. 2010 (http://www. Lexi-Comp. they should remain lying for 1–2 hours after administration. 1996. WHO Technical Report Series. Geneva. Rare Diarrhoea. The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis. brucei gambiense infection. Quinine: increased level and toxicity of pentamidine and quinine. thrombocytopenia. Taketomo CK.who. anaemia. anaemia. Notes: A cerebrospinal fluid examination before treatment is required as pentamidine is not effective if trypanosomes are detected in the cerebrospinal fluid or the leukocyte count is above 5–10 cells/mm3. WHO expert committee on the control and surveillance of African trypanosomiasis. accessed 10 February 2010). confusion. risk of severe hypotension following administration. 2009. care is required to protect personnel during handling and administration. hypoglycaemia (may be followed by hyperglycaemia and type I diabetes mellitus). 2008. Pentamidine isetionate is toxic. also hypocalcaemia. Before administration. WHO model formulary. Geneva.thomsonhc. Kouimtzi M. hypoglycaemia or hyperglycaemia. 1998. Hepatic impairment: Use with caution. Kraus DM. extreme care should be taken to ensure aseptic technique when administering to avoid the risk of abscess or necrosis at the injection site. Adverse effects: Common Pain at injection site. sterile abscess and muscle necrosis at injection site. 234 WHO Model Formulary for Children 2010 . Hodding JH. pancreatitis. Drugdex system. in tea or similar. 16th ed. nephrotoxicity. every alternate day). leukopenia. BMJ Group RBS Publishing.

Notes: Suramin is only effective in the early stages of the illness. FIRST (TeST) DOSe Administer first dose with particular caution. Suramin crosses the blood-brain barrier poorly. anorexia. a test dose is recommended before starting treatment. so correct with a protein-rich diet and maintain satisfactory food and fluid intake during treatment. 24 and 31. abdominal pain. peripheral neuropathy. inject the remainder over several minutes. raised liver enzyme values. Slow IV injection: Child all ages 5 mg/kg on day 1 (as a test dose) followed by 20 mg/kg on day 3. Indications: Treatment of the initial phase of Trypanosoma brucei rhodesiense infection. Severe impairment: avoid use. reduce dose if moderate albuminuria. malaise. polyuria. The compound deteriorates quickly in air and so should be injected immediately after preparation. may result in toxic serum suramin levels due to an increased free fraction of the drug in the plasma. Poor nutritional status increases frequency of adverse reactions. in which no CNS involvement has occurred. paraesthesia and hyperaesthesia of palms and soles. Hepatic impairment: Severe impairment: avoid use. exfoliative dermatitis. inject next 0. severe diarrhoea. Cerebrospinal fluid examination should be conducted before treatment. rash. Renal impairment: Mild to moderate impairment: use with caution. tiredness. Drug can be excreted in the urine unchanged for 3 months following doses of suramin. ReCONSTITUTION OF INJeCTION Reconstitute in water for injections to produce a final concentration of 10%. severe liver impairment.5 Antiprotozoal medicines Suramin sodium ATC code: P01CX02 Powder for injection: 1 g in vial A potentially fatal immediate hypersensitivity reaction is estimated to occur in 1 per 20 000 patients. albuminuria. mild proteinuria.6. vomiting. shock and loss of consciousness during first dose (see First (test) dose). thrombocytopenia. wait at least 1 minute after injecting the first few microlitres. Suramin sodium should only be administered by experienced staff. Dose: Treatment of the initial phase of Trypanosoma brucei rhodesiense infection. Adverse effects: Common Fever. Suramin is excreted renally at a slow rate due to extensive protein binding. Administration of suramin in individuals with significant hepatic dysfunction. severe renal impairment. Special Notes: Medicine for the treatment of first-stage African trypanosomiasis.5 ml over 30 seconds and wait 1 minute. 10. onchocerciasis. and in later stages where the organism has penetrated the CNS. Rare Immediate and potentially fatal allergic reaction with nausea. 17. Contraindications: Previous anaphylaxis or suramin sensitivity. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concurrent use. vomiting. other agents must be used. thirst. WHO Model Formulary for Children 2010 235 . transient hyperbilirubinaemia. discontinue immediately if severe albuminuria or casts in urine. nausea and metallic taste. stomal ulceration. Conduct urine tests before treatment and weekly during treatment. in whom serum albumin levels may be reduced. albuminuria. Precautions: Debilitated or malnourished patients. Administer only under close medical supervision in hospital and with general condition improved as far as possible before treatments.

Precautions: Hepatic impairment. 1998. Odero RO. Approximately 30% will develop serious complications including cardiac and gastrointestinal manifestations of the disease. accessed 10 February 2010). Whitehouse Station. World Health Organization. 2000:1–12. 236 WHO Model Formulary for Children 2010 .5. especially leukocytes.com/ article/228613-overview. ed. allergic condition to imidazoles. New york.html. Geneva. cruzi. After this. In: Abramowicz M. WHO model formulary. Control and surveillance of African trypanosomiasis. 40 kg and over 5 mg/kg daily in 2–3 divided doses for 60 days. NOTe Acute meningoencephalitis may require a dose of up to 25 mg/kg daily.html. Merck Manual Online. Full-term neonate initially 5 mg/kg daily. renal impairment. Dose must be given in 2–3 divided doses for 60 days. WebMD. ©2006–2008 (http://www. Chagas disease can reactivate and potentially cause severe disease. WHO Technical Report Series. Chagas disease has an acute and a chronic phase. 881:1–114.5 mg/kg daily in 2–3 divided doses for 60 days. eds. HIV/AIDS). if no leucopenia or thrombocytopenia. increasing after 3 days to 10 mg/kg daily. throughout treatment. Oral: Infant or Child 5 mg/kg daily in 2–3 divided doses for 60 days. most people enter a chronic phase. If Chagas disease is not treated. haematological conditions. infection is lifelong. WHO expert committee on the control and surveillance of African trypanosomiasis. 2010 (http://www. accessed 10 February 2010). The Medical Letter. Symptoms include fever or swelling at the inoculation site. Drugs for parasitic infections.g. Contraindications: Pregnancy. Hill SR.5. Porter RS. New Rochelle.2 American trypanosomiasis Chagas disease is a disease caused by the parasite T.who. NOTe The treating physician should determine the age limits and clinical suitability of this specific therapy. Geneva. accessed 10 February 2010). The Medical Letter on Drugs and Therapeutics. Benznidazole ATC code: P01CA02 Tablet: 100 mg Indications: Treatment of Chagas disease (American trypanosomiasis).medscape. 2008.int/trypanosomiasis_african/drugs/ en/index. World Health Organization. Dose: Treatment of congenital acute phase or early chronic phase of Chagas disease (American trypanosomiasis). Stuart MC. Oral: Infant or Child under 40 kg 7. Kouimtzi M. 2009 (http://emedicine. The acute illness (which occurs immediately after inoculation and lasts weeks to months) may be mild or asymptomatic.merck. Human African trypanosomiasis. Treatment of acute phase or early chronic phase of Chagas disease (American trypanosomiasis). ed. 6.6 Anti-infective medicines References: Abramowicz M. African trypanosomiasis (sleeping sickness). Treatment of chronic phase of Chagas disease (American trypanosomiasis). monitor blood count. during which most people are asymptomatic. eMedicine. It is transmitted to humans by insect vectors that are found only in the Americas (mainly in rural areas of Latin America where poverty is widespread). In people with immunosuppresssion (e. history of neurological clinical manifestations. Merck Research Laboratories.com/ mmpe/index.

Adverse effects: Common Rash. Indications: Treatment of Chagas disease (American trypanosomiasis). Nifurtimox ATC code: P01CC01 Tablet: 30 mg. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concomitant use. Administer every 8 hours after meals.int/trs/WHO_TRS_905. headache. WebMD. Oral: Infant or Child 8–10 mg/kg daily in three divided doses for 60 days. eMedicine.who. renal impairment. Treatment of chronic phase of Chagas disease (American trypanosomiasis).pdf ). headache. gastric pain.medscape. Kirchhoff LV. anorexia. myalgia. Rare Agranulocytosis. porphyria. Precautions: Close medical supervision required in patients with history of cerebral damage or predisposition to seizures. Thomson Micromedex. Control of Chagas disease: second report of the WHO expert committee. NOTe The treating physician should determine the age limits and clinical suitability of this specific therapy. nausea. WHO Model Formulary for Children 2010 237 . nausea. leukopenia. WHO model formulary. fatigue. Greenwood Village. vertigo. Antiprotozoal medicines Adverse effects: Common Rashes (discontinue treatment if severe and accompanied by fever and purpura). co-administer aluminium hydroxide to reduce gastrointestinal irritation. WHO Technical Report Series. World Health Organization. loss of weight. Hepatic impairment: Avoid use in hepatic failure (limited data available). increasing the risk of side-effects. New york. 120 mg. 2010. Child 40 kg or over 12. bone marrow depression. Drugdex system. peripheral neuritis. ed.com/article/214581-treatment. Klasco RK.5–15 mg/kg daily in three divided doses for 60 days. hypersensitivity to hydantoin. Administer every 8 hours after meals. Kouimtzi M. accessed 10 February 2010).com. 905 (http://whqlibdoc.5 Renal impairment: Avoid use in renal failure (limited data available). vomiting. (http://www. vomiting and abdominal pain. 250 mg Special Notes: Not all tablet strengths listed may be commercially available. dizziness. accessed 10 February 2010). allergic afflictions (particularly those involving skin manifestations). Infant or Child under 40 kg 15–20 mg/kg daily in three divided doses for 60 days.thomsonhc. Contraindications: Pregnancy. WHO expert committee on the control of Chagas disease. Chagas disease (American trypanosomiasis): treatment & medication. 2002. psychosis or serious behavioural alterations. hepatic impairment. Renal impairment: Mild and moderate impairment: dosage adjustment may be required due to increased serum levels and toxicity of nifurtimox. Oral: Neonate. Stuart MC.6. Dose: Treatment of acute phase or early chronic phase of Chagas disease (American trypanosomiasis). eds. 2009 (http:// emedicine. 2008. arthralgia. Geneva. Hepatic impairment: Hepatic function impairment may increase blood concentrations of this medication. peripheral neuropathy. Uncommon Paraesthesia. Severe impairment/failure: avoid use (limited data available). Administer every 8 hours after meals. References: Hill SR.

Chagas disease (American trypanosomiasis): treatment & medication.int/trs/WHO_TRS_905.pdf ). ed. WHO Technical Report Series. Infants may take it crushed and mixed with a small amount of food. Drugdex system. 905 (http://whqlibdoc. arthralgia. Control of Chagas disease: second report of the WHO expert committee. eMedicine. accessed 10 February 2010). Kirchhoff LV.thomsonhc. eds. World Health Organization. Tablets should be taken three times daily.drugs. Greenwood Village. accessed 10 February 2010). 2008. WebMD. psychotic reactions. excitability. 2010. Klasco RK. References: Hill SR. at noon and at night. Lampit Product Information.6 Anti-infective medicines (may require discontinuation). In this case it is convenient to give the medication before the full meal.com/article/214581-treatment.com. Kouimtzi M. Bayer. preferably in the morning. peripheral neuritis Rare Tremors. WHO model formulary.who. accessed 10 February 2010). sleep disturbances. 238 WHO Model Formulary for Children 2010 .com/mmx/lampit. myalgia. New york. after meals. WHO expert committee on the control of Chagas disease. 1995 (http://www. Geneva. (http://www. 2009 (http:// emedicine.medscape. Stuart MC. Uncommon Memory loss. Notes: Nifurtimox is best taken with or after meals to minimize gastrointestinal irritation.html. Interactions with other medicines (* indicates severe): There are no known interactions where it is recommended to avoid concomitant use. 2002. seizures. Thomson Micromedex. suicidality.

1 For treatment of acute attack .........................................................2 For prophylaxis ........ 240 7........ 242 WHO Model Formulary for Children 2010 239 ...................SECTION 7: Antimigraine medicines 7.....................................

Treatment of migraine in children consists of three components: general measures. Oral: Infant or Child over 3 months 5–10 mg/kg three or four times daily with or after food. cardiac disease. General measures include appropriate reassurance and avoidance of any identified trigger factors. 400 mg Special Notes: WHO age/weight restriction: > 3 months. Migraines with aura or prolonged neurological symptoms are uncommon in young children. active peptic ulceration or upper gastrointestinal bleeding. but is characterized by periodic episodes of paroxysmal headache often accompanied by pallor. such as in gastroenteritis or dehydration (increased risk of renal impairment). allergic disorders. 7. In children. Maximum dose is 40 mg/kg/day. and. in some cases.g. severe renal failure. angioedema.7 Antimigraine medicines 7 Antimigraine medicines Migraine is the most common identifiable cause of recurrent or chronic headache in childhood. acute measures. The following features are suggestive of an alternative diagnosis or possible intracranial pathology warranting further investigation or referral: • recurrent early morning headaches • headaches that are prolonged and incapacitating • progressive change in personality or behaviour • abnormal neurological examination findings • failure to respond to usual treatment measures. nausea. volume depletion. alternative causes of headache including raised intracranial pressure (e. 240 WHO Model Formulary for Children 2010 . the presentation of migraine is influenced by the age of the child. urticaria or rhinitis) to acetylsalicylic acid or any other NSAIM. A careful history. vomiting and relief with sleep. Indications: Acute migraine attack. Precautions: Asthma. preventive treatment. In adolescents. hepatic impairment. examination and follow-up help guide the correct diagnosis. renal impairment. hepatic failure or cardiac failure. Dose: Treatment of acute migraine attack. Contraindications: Hypersensitivity (including asthma. Prior to diagnosing migraine in a child. dehydration.1 For treatment of acute attack For treatment of an acute attack early use of simple analgesics are often effective. due to a space-occupying lesion or meningitis) or systemic illness must also be considered. coagulation defects. Ibuprofen ATC code: M01Ae01 Tablet: 200 mg. the presentation of migraine is often similar to that of adults. concomitant use of drugs that increase risk of bleeding. previous peptic ulceration.

Penicillamine: possible increased risk of nephrotoxicity. WHO model formulary. MIMS Online. Sydney.au/Search/Search. * Warfarin: anticoagulant effect possibly enhanced and risk of bleeding increased. Spironolactone: risk of nephrotoxicity of ibuprofen increased. aseptic meningitis. Furosemide: risk of nephrotoxicity of ibuprofen increased. UBM Medica. 13th ed. eds. alveolitis. Dexamethasone: increased risk of gastrointestinal bleeding and ulceration.aspx. erythema multiforme (Stevens-Johnson syndrome). * Ciclosporin: increased risk of nephrotoxicity. Rare Angioedema. Hodding JH. Kemp CA. renal impairment. 2008.int/medicines/publications/essentialmeds_committeereports/TRS_950. accessed 10 February 2010). Severe impairment: avoid use. dizziness. 2009 (http://www.who. 950 (http://www.com. * Phenytoin: effect of phenytoin possibly enhanced. Royal Children’s Hospital. Geneva. Kouimtzi M. Lexi-Comp. Taketomo CK. abdominal pain.7. References: Hill SR. avoid in severe liver disease. Ritonavir: plasma concentration possibly increased by ritonavir. raised blood pressure. Propranolol: antagonism of hypotensive effect.pdf ). Hydrocortisone: increased risk of gastrointestinal bleeding and ulceration. antagonism of diuretic effect. BMJ Group RBS Publishing. bronchospasm. as may deterioration in renal function possibly leading to renal failure. 16th ed. Stuart MC. Kraus DM. Interactions with other medicines (* indicates severe): Renal impairment: Mild and moderate impairment: use lowest effective dose and monitor renal * Acetylsalicylic acid: avoid concomitant use (increased adverse effects). diarrhoea. Enalapril: antagonism of hypotensive effect. London. World Health Organization. Notes: Give with or after food. colitis. headache. WHO Model Formulary for Children 2010 241 . gastrointestinal ulceration and bleeding. increased risk of gastrointestinal bleeding and can cause fluid retention. possible increased risk of hyperkalaemia.1 For treatment of acute attack function. Hudson. dyspepsia. * Fluoxetine: increased risk of bleeding. toxic epidermal necrolysis (Lyell syndrome). urticaria. Hepatic impairment: Use with caution. fluid retention. * Methotrexate: excretion of methotrexate reduced (increased risk of toxicity). reduced renal function and increased plasma digoxin concentration.mimsonline. hepatic damage. * Lithium: reduced excretion of lithium (increased risk of toxicity). Prednisolone: increased risk of gastrointestinal bleeding and ulceration. Adverse effects: Common Nausea. photosensitivity. Zidovudine: increased risk of haematological toxicity. The selection and use of essential medicines: report of the WHO expert committee. Digoxin: possible exacerbation of heart failure. Heparin: possible increased risk of bleeding. McDowell JM. 2002. sodium and water retention may occur. Paediatric Formulary Committee. 2009. Uncommon Rash. Melbourne. visual disturbances. WHO Technical Report Series. Paediatric pharmacopoeia. 2008. WHO expert committee on the selection and use of essential medicines. pancreatitis. Pediatric dosage handbook. increased risk of renal impairment. 2009. antagonism of diuretic effect. pulmonary eosinophilia. October 2007 (including the model list of essential medicines for children). British national formulary for children 2009.

World Health Organization. WHO Model Formulary for Children 2010 242 .7 Antimigraine medicines Paracetamol ATC code: N02Be01 Oral liquid: 25 mg/ml Tablet: 300 mg to 500 mg Special Notes: Also referred to as acetaminophen. severe peripheral arterial disease. 7. uncontrolled heart failure. 2009 (http://www. pancytopenia. thrombocytopenia. HePATOTOXICITy Hepatotoxicity (and less frequently renal damage) can occur after paracetamol overdosage.who.2 For prophylaxis For frequent or severe migraine. with specialist consultation where possible. Notes: Shake suspension well before use. have a febrile illness. phaeochromocytoma.2 for more information on paracetamol toxicity. so additional symptomatic treatment is still needed. References: Hill SR. Geneva. Adverse effects: Rare Rash. WHO expert committee on the selection and use of essential medicines.pdf ). Precautions: Hepatic impairment. MIMS Online. WHO model formulary. hypersensitivity. UBM Medica. Warfarin: prolonged regular use of paracetamol possibly enhances anticoagulant effect. Interactions with other medicines (* indicates severe): Metoclopramide: increased absorption of paracetamol. The selection and use of essential medicines: report of the WHO expert committee. cardiogenic shock. neutropenia. have not eaten for a few days or are taking liver enzymeinducing drugs may be at an increased risk of liver damage from paracetamol overdosage. eds.au/Search/Search. accessed 10 February 2010).aspx. history of bronchospasm. every 4–6 hours as necessary. Dose: Treatment of acute migraine attack. Prophylaxis can reduce the severity and frequency of attacks but does not eliminate them completely. hypotension. marked bradycardia. Indications: Acute migraine attack. October 2007 (including the model list of essential medicines for children). second or third-degree atrioventricular block. Kouimtzi M.mimsonline. 950 (http://www. Children who are malnourished. Hepatic impairment: Dose-related toxicity. Propranolol ATC code: C07AA05 Tablet: 20 mg. avoid large doses. sick sinus syndrome. Sydney. 40 mg (as hydrochloride) Indications: Migraine prophylaxis. Stuart MC. metabolic acidosis. WHO Technical Report Series. 2008. Oral: Infant or Child 15 mg/kg. up to 1 g. Contraindications: Asthma. overdosage.int/medicines/publications/essentialmeds_committeereports/TRS_950. Maximum 60 mg/kg in 24 hours. preventive medications may be appropriate.com. 2008. Refer to section 4.

Digoxin: increased risk of atrioventricular block and bradycardia. Halothane: enhanced hypotensive effect. exacerbation of Raynaud syndrome. Adverse effects: Common Nausea. Enalapril: enhanced hypotensive effect. Usual dose 10–20 mg 2–3 times daily. Furosemide: enhanced hypotensive effect. * Lidocaine: increased myocardial depression. maximum 4 mg/kg daily. Dexamethasone: antagonism of hypotensive effect. conduction disorders. peripheral vasoconstriction. WHO Model Formulary for Children 2010 243 . * Procainamide: increased myocardial depression. Prednisolone: antagonism of hypotensive effect. renal impairment. diarrhoea. * Epinephrine: severe hypertension. bradycardia. history of obstructive airways disease. Dose: Migraine prophylaxis. may reduce renal blood flow and adversely affect renal function. nightmares. Mefloquine: increased risk of bradycardia. Ketamine: enhanced hypotensive effect. oral: antagonism of hypotensive effect by estrogens. Hydrocortisone: antagonism of hypotensive effect. alopecia. higher plasma concentrations after oral administration. cardiac arrest. Renal impairment: Severe: start with small dose. portal hypertension. fatigue. Oral: Child over 2 years 200–500 micrograms/kg three times daily. history of hypersensitivity (increased reaction to allergens. increased risk of lidocaine toxicity (interaction less likely when lidocaine used topically). liver function abnormality. Hydrochlorothiazide: enhanced hypotensive effect. * Nifedipine: enhanced hypotensive effect. liver disease. thrombocytopenic purpura. insomnia. Hepatic impairment: Reduce oral dose. hypotension. myasthenia gravis. dry eyes. bronchospasm. exacerbation of psoriasis. muscle cramp. Diazepam: enhanced hypotensive effect. propranolol may mask warning signs of hypoglycaemia such as tremor.2 For prophylaxis Precautions: Avoid abrupt withdrawal. Uncommon Rash. Ibuprofen: antagonism of hypotensive effect. also reduced response to epinephrine (adrenaline)). Neostigmine: antagonism of effect of neostigmine. dyspnoea. heart failure. diabetes mellitus. first-degree atrioventricular block. Contraceptives. Nitrous oxide: enhanced hypotensive effect. Insulins: enhanced hypoglycaemic effect. enhanced hypotensive effect.7. Interactions with other medicines (* indicates severe): * Bupivacaine: increased risk of bupivacaine toxicity. Possible severe hypotension and heart failure. Rare Hypersensitivity reaction. * Chlorpromazine: concomitant administration may increase plasma concentration of both drugs.

244 WHO Model Formulary for Children 2010 . Suxamethonium: enhanced muscle relaxant effect. London. Hodding JH. Paediatric Formulary Committee. eds. 2009. Geneva. 16th ed. Rossi S.7 Antimigraine medicines Pyridostigmine: antagonism of effect of pyridostigmine. 2009. * Quinidine: increased myocardial depression. Stuart MC. Kraus DM. Vecuronium: enhanced muscle relaxant effect. References: Hill SR. Spironolactone: enhanced hypotensive effect. Taketomo CK. Rifampicin: metabolism of propranolol accelerated (significantly reduced plasma concentration of propranolol). Australian Medicines Handbook. Thiopental: enhanced hypotensive effect. WHO model formulary. World Health Organization. Notes: Advise patient or carer not to discontinue abruptly. Sodium nitroprusside: enhanced hypotensive effect. Kouimtzi M. severe hypotension and heart failure. ed. Give with food. Hudson. Pediatric dosage handbook. Australian medicines handbook. 2008. BMJ Group RBS Publishing. British national formulary for children 2009. 2009. Lexi-Comp. * Verapamil: asystole. Adelaide.

............. 246 Cytotoxic medicines ........ 251 Hormones and antihormones .....SECTION 8: Antineoplastic....................................... 280 WHO Model Formulary for Children 2010 245 .............1 8..........3 8........................2 8............................. immunosuppressives and medicines used in palliative care 8..................................... 274 Medicines used in palliative care................4 Immunosuppressive medicines ............................

Contraindications: Hypersensitivity to azathioprine or mercaptopurine. Severe: 50–100% of normal dose. nausea and vomiting. Indications: To prevent rejection in organ transplant recipients in combination with other medications. BONe MARROW SUPPReSSION Patients should be warned to report immediately any signs or symptoms of bone marrow suppression. and the dose should be adjusted to prevent bone marrow toxicity. mouth ulcers. immunosuppressives and medicines used in palliative care 8 8. oesophagitis. full Organ transplantation.1 Antineoplastic. individualization of dosage and special equipment are required for their proper use. blood counts necessary every week (or more frequently with higher doses and in renal or hepatic impairment) for first 4 weeks of treatment. anorexia. anaemia. infection. renal impairment. Specific expertise. adjusted according to response. they are also used as second-line drugs in chronic inflammatory conditions. Uncommon Hepatitis. immunosuppressives and medicines used in palliative care Immunosuppressive medicines NOTE. alopecia. and at least every 3 months thereafter. diarrhoea. Careful monitoring of blood counts is required in patients receiving immunosuppressive drugs. for example unexplained bruising or bleeding. WHO advises that this class of drugs is for use only when adequate resources and specialist care are available. increased susceptibility to infections due to immunosuppression. 246 WHO Model Formulary for Children 2010 . Azathioprine ATC code: L04AX01 Powder for injection: 100 mg (as sodium salt) in vial Tablet: 50 mg Special Notes: Also referred to as AZT (Note: this abbreviation is also used for zidovudine). Moderate: 75–100% of normal dose. Immunosuppressive drugs are used in organ transplant recipients to suppress rejection. diagnostic precision. Oral or IV: Child 1 month–12 years initially 3–5 mg/kg once daily beginning at the time of transplant. Hepatic impairment: May need dose reduction.8 Antineoplastic. Total daily dose may alternatively be given in two divided doses. Patients with genetic deficiency of the enzyme thiopurine methyltransferase (TPMT) which metabolizes azathioprine are at greater risk of myelosuppressive effects. photosensitivity. maintenance 1–3 mg/kg once daily. Dose: Precautions: Liver disease. thrombocytopenia. Monitor for toxicity throughout treatment. Immunosuppressed patients are particularly prone to atypical infections. Treatment should only be initiated by a specialist. Renal impairment: Mild: dose as in normal renal function. Adverse effects: Common Leukopenia.

rash. ADDITIONAL CAUTIONS IN NePHROTIC SyNDROMe Reduce dose by 25–50% if serum creatinine more than 30% above baseline at more than one measurement. fever. monitor serum potassium. for example unexplained bruising or bleeding.9% or sodium chloride and glucose. diagnostic precision. WHO model formulary. Ciclosporin ATC code: L04AA01 Capsule: 25 mg Concentrate for injection: 50 mg/ml in 1 ml ampoule for organ transplantation Special Notes: Also referred to as cyclosporine. Kraus DM. Oxford. liver. live: avoid use of live vaccines with azathioprine (impairment of immune response). Interactions with other medicines (* indicates severe): * Allopurinol: effects of azathioprine enhanced and toxicity increased. Precautions: Monitor kidney function (dose-dependent increase in serum creatinine and urea during first few weeks may necessitate dose reduction. heart or bone marrow transplantation. Indications: For use in organ transplant recipients in kidney. Use appropriate precautions for handling and disposal. breastfeeding. eds. dizziness. For intravenous injection give over at least 1 minute. HAZARDOUS AGeNT Azathioprine is an immunosuppressive agent. Lexi-Comp. exclude rejection if kidney transplant). hypotension or interstitial nephritis call for immediate withdrawal. Taketomo CK. increased incidence of malignancies and lymphoproliferative disorders. Phenytoin: possibly reduced absorption of phenytoin. malaise. pneumonitis. Pediatric dosage handbook. British national formulary for children 2009. The renal drug handbook. Stuart MC. * Vaccine. For intravenous infusion dilute to a concentration of 0. monitor serum magnesium.5 mg/ml in glucose 5% or sodium chloride 0. arthralgia. Geneva. Radcliffe Publishing. * Warfarin: anticoagulant effect possibly reduced. infection. 16th ed. individualization of dosage or special equipment required for proper use.25–2. PATIeNT INFORMATION Patients should be warned to report immediately any signs or symptoms of bone marrow suppression. * Trimethoprim: increased risk of haematological toxicity. Specific expertise. hypersensitivity reactions. 2008. polyoxyl 35 castor oil in injection or polyoxyl 40 hydrogenated castor oil in capsules). Kouimtzi M. BMJ Group RBS Publishing.g. avoid in porphyria. World Health Organization. London. pancreatitis. * Sulfamethoxazole + trimethoprim: increased risk of haematological toxicity. 2009. WHO Model Formulary for Children 2010 247 . Paediatric Formulary Committee. measure blood lipids before and during treatment. give over 30–60 minutes.1 Immunosuppressive medicines Rare Hepatic veno-occlusive disease. muscular pains. Notes: Intravenous injection is alkaline and very irritant. colitis in patients also receiving corticosteroids. Hudson. hyperuricaemia. particularly if marked renal impairment (risk of hyperkalaemia). the intravenous route should therefore only be used if oral administration is not possible. perform renal biopsies at yearly intervals. reduce dose of azathioprine. eds. monitor blood pressure (discontinue if hypertension cannot be controlled by antihypertensives). graft-versus-host disease and nephrotic syndrome. Currie A. References: Ashley C. Contraindications: Hypersensitivity to ciclosporin or any component of formulations (e. monitor liver function (adjust dosage according to bilirubin and liver enzymes). 2009.8. 2009. contraindicated in uncontrolled infections and malignancy. Hodding JH. 3rd ed. cholestatic jaundice. Hill SR.

neuropathy. initial dose should not exceed 2. Hepatic impairment: May need dose adjustment based on bilirubin or liver enzyme levels. seizures. hyperuricaemia. * Amiloride: increased risk of hyperkalaemia. hirsutism. IV: Child over 3 months 3–5 mg/kg 4–12 hours before surgery. specialist transplant protocols should be consulted. Bone marrow transplantation or graft-versus-host disease (GVHD). Discontinue after 3 months if no improvement (after 6 months in membranous glomerulonephritis). Rare Confusion. proteinuria and serum creatinine measurements. Oral: Child over 3 months 12. increased insulin requirements. psychosis. hepatic dysfunction. starting on day before transplantation (or at the onset of GVHD). myopathy or muscle weakness. increased susceptibility to infections due to immunosuppression. Solid organ transplantation. hyperglycaemia. Interactions with other medicines (* indicates severe): Aciclovir: increased risk of nephrotoxicity. starting on the day before transplantation (or at the onset of GVHD). diabetes. dysmenorrhoea or amenorrhoea. Allopurinol: plasma ciclosporin concentration possibly increased (risk of nephrotoxicity). Adverse effects: Common Nephrotoxicity (dose-related and reversible increases in serum creatinine and urea unrelated to tissue rejection). 248 WHO Model Formulary for Children 2010 . dose-dependent increase in serum creatinine and urea during first few weeks may necessitate dose reduction (exclude rejection if kidney transplant).6–2 mg/kg/day for maintenance (adjust dose according to blood ciclosporin concentration and kidney function). hypomagnesaemia. * Amikacin: increased risk of nephrotoxicity.5–15 mg/kg daily for 2 weeks.5 mg/kg/day in 1–2 doses for 3–6 months. followed by oral maintenance doses. pancreatitis. allergic reactions. hypertension (especially in heart transplant patients). coma. electrolyte disturbances including hyperkalaemia. thrombocytopenia (sometimes with haemolytic uraemic syndrome). * Amphotericin B: increased risk of nephrotoxicity. In renal impairment. immunosuppressives and medicines used in palliative care Dose: NOTe Lower doses are required when ciclosporin is used with other immunosuppressants. headache. then 10–15 mg/kg/day in 1–2 doses for 1–2 weeks. however.8 Antineoplastic. then gradually tailed off (may take up to 1 year after transplant). also mild anaemia. Serum level monitoring is required. reducing to 2–6 mg/kg/day in 1–2 doses for maintenance (adjust dose according to blood ciclosporin concentration and kidney function). hypercholesterolaemia. reducing to 0. burning sensation in hands and feet during initial therapy. then 3–5 mg/kg/day in 1–2 doses for 1–2 weeks.5 mg/kg/day. For maintenance treatment. gingival hyperplasia. fatigue. Nephrotic syndrome. Oral: Child all ages 3 mg/kg/dose twice daily. a guide (based on adult recommendations) is provided in Notes. IV: Child over 3 months 3–5 mg/kg/day in 1–2 doses for 2 weeks. Oral: Child over 3 months 10–15 mg/kg 4–12 hours before surgery. Uncommon Gastrointestinal disturbances. increased incidence of malignancies and lymphoproliferative disorders. Renal impairment: Monitor kidney function. slowly reduce to lowest effective dose according to whole blood ciclosporin concentrations. followed by 12. gout. tremor.

Spironolactone: increased risk of hyperkalaemia. * Ofloxacin: increased risk of nephrotoxicity. * Doxorubicin: increased risk of neurotoxicity. * Carbamazepine: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). * Medroxyprogesterone: inhibition of ciclosporin metabolism (increased plasma ciclosporin concentration).1 Immunosuppressive medicines * Azithromycin: plasma concentration of ciclosporin possibly increased. * Contraceptives. * Chloroquine: increased plasma ciclosporin concentration (increased risk of toxicity). * Metoclopramide: plasma ciclosporin concentration increased. oral: plasma ciclosporin concentration increased by progestogens and possibly increased by estrogens. * Erythromycin: increased plasma ciclosporin concentration (inhibition of metabolism of ciclosporin). Griseofulvin: plasma ciclosporin concentration possibly reduced. * Rifampicin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). * Doxycycline: possibly increased plasma ciclosporin concentration.8. * Methotrexate: increased toxicity. * Silver sulfadiazine: increased risk of nephrotoxicity. * Levofloxacin: increased risk of nephrotoxicity. * Chloramphenicol: plasma concentration of ciclosporin possibly increased. Etoposide: possibly increased plasma concentration of etoposide (increased risk of toxicity). * Phenytoin: accelerated metabolism of ciclosporin (reduced plasma ciclosporin concentration). * Levonorgestrel: inhibition of ciclosporin metabolism (increased plasma ciclosporin concentration). * Fluconazole: metabolism of ciclosporin inhibited (increased plasma concentration). * Saquinavir: plasma concentration of both ciclosporin and saquinavir increased. * Norethisterone: inhibition of ciclosporin metabolism (increased plasma ciclosporin concentration). possibly reduced plasma concentration of ciclosporin. * Potassium salts: increased risk of hyperkalaemia. * Digoxin: increased plasma concentration of digoxin (increased risk of toxicity). Prednisolone: increased plasma concentration of prednisolone. * Ciprofloxacin: increased risk of nephrotoxicity. * Ibuprofen: increased risk of nephrotoxicity. WHO Model Formulary for Children 2010 249 . * Ritonavir: plasma concentration possibly increased by ritonavir. * Grapefruit juice: increased plasma ciclosporin concentration (risk of toxicity). Hydrochlorothiazide: increased risk of nephrotoxicity and possibly hypermagnesaemia. * Simvastatin: increased risk of myopathy. * Phenobarbital: metabolism of ciclosporin accelerated (reduced effect). * Enalapril: increased risk of hyperkalaemia. * Gentamicin: increased risk of nephrotoxicity. * Nelfinavir: possibly increased plasma ciclosporin concentration.

C2 concentrations Collect sample 2 hours (± 15 minutes) after a dose of ciclosporin. Recommended C2 whole blood concentrations for Neoral® brand in adults Liver transplant: 600– 1000 micrograms/l. PATIeNT INFORMATION Swallow capsules whole and take them 12 hours apart at the same times each day. 2009.9%. Use appropriate precautions for handling and disposal. 2009. Kouimtzi M. 16th ed. * Sulfadiazine: plasma ciclosporin concentration possibly reduced. There is evidence to suggest that C2 is a better indicator of adequate immunosuppression. which has been associated with anaphylaxis. Trough concentrations (C0) Whole blood specific assay. They depend on assay technique. 2009. observe patient for 30 minutes after starting infusion and then at frequent intervals. Aim for higher concentrations in the first 3 months after transplant and where rejection has occurred and lower concentrations where adverse effects are experienced. plasma ciclosporin concentration possibly reduced by intravenous trimethoprim. Clean your teeth and gums regularly. * Verapamil: increased plasma ciclosporin concentration. Stuart MC. * Vancomycin: increased risk of nephrotoxicity. London. World Health Organization. NOTe Concentrate for infusion may contain polyethoxylated castor oil. infuse IV over 2–6 hours (more slowly if facial flushing occurs). not from a central line. Continuous IV infusion Whole blood specific assay. immunosuppressives and medicines used in palliative care Streptomycin: increased risk of nephrotoxicity. INTRAVeNOUS ADMINISTRATION ADVICe Dilute injection to 1:20 to 1:100 in glucose 5% or sodium chloride 0. The following concentrations are a guide. Geneva. 2008. SeRUM CONCeNTRATION MONITORING Draw blood for ciclosporin measurement by venepuncture. 250 WHO Model Formulary for Children 2010 . Kidney transplant: 800–1500 micrograms/l. Hudson. * Vaccine. Kraus DM. and the manufacturer’s product information consulted for further advice. Consult local protocols or specialist advice for use in children. Pediatric dosage handbook. increased risk of nephrotoxicity. Avoid using nonspecific assays which measure ciclosporin plus metabolites. The ciclosporin concentration 2 hours after a dose (C2) correlates better with area under the curve (AUC) than the 12 hour trough concentration (C0). time since transplant and use of other immunosuppressants. Australian medicines handbook. HAZARDOUS AGeNT Ciclosporin is an immunosuppressive agent. Paediatric Formulary Committee. Concentrations obtained from nonspecific assays are not interchangeable with the results from a specific assay. References: Hill SR. plasma ciclosporin concentration possibly reduced by intravenous trimethoprim. transplant type. Rossi S. WHO model formulary. * Sulfadoxine + pyrimethamine: increased risk of nephrotoxicity. use a glass bottle and non-PVC administration set to avoid phthalate stripping and use short giving sets to reduce amount adsorbed. BMJ Group RBS Publishing. Adelaide. * Trimethoprim: increased risk of nephrotoxicity. * Sulfamethoxazole + trimethoprim: increased risk of nephrotoxicity. 100–300 micrograms/l. 300–500 micrograms/l. British national formulary for children 2009. Taketomo CK. eds. Australian Medicines Handbook. ed. Lexi-Comp. Hodding JH.8 Antineoplastic. Notes: CONVeRSION Any conversion between brands should be undertaken very carefully. live: avoid use of live vaccines with ciclosporin (impairment of immune response).

2. Such drugs include hormone agonists and antagonists. Nausea and vomiting following administration of cytotoxic drugs and abdominal radiotherapy are often distressing and may compromise further treatment. WHO advises that while cytotoxic medicines are essential for the treatment of malignancy in children. radiotherapy and surgery is complex and should only be undertaken by specialists in this field. specialist literature should be consulted. adequate resources and specialist supervision are a prerequisite for the introduction of this class of drugs. however. There is no drug treatment. corticosteroids and immunosuppressant drugs (section 8.4) should be considered. particularly with fluorouracil. Treatment involves regular use of saline mouthwashes. Fever associated with neutropenia requires immediate treatment with antibiotics. For this reason. diagnostic precision. but for most malignancies. individualization of dosage and special equipment are required for their proper use. There are many differences in the spectrum and management of childhood cancers. methotrexate and anthracyclines. Cytotoxic drugs are often combined with other classes of drugs in the treatment of malignant conditions. WHO Model Formulary for Children 2010 251 . Adverse effects Cytotoxic drugs have a considerable potential to damage normal tissue.8. more toxic than single drugs. but the condition often reverses spontaneously once treatment has stopped. Brushing teeth with a soft brush two to three times daily and rinsing the mouth frequently are probably the most effective preventative measures. such as bone marrow and immunological suppression. specialist literature should be consulted for further information. Specific expertise. Combinations are. alternative palliative treatment (section 8. Specific adverse effects apply. precautions and adverse effects for the individual cytotoxic drugs have been omitted in the following section since treatment should be undertaken by specialists using approved regimens. Any pain caused by mucositis should be dealt with effectively. and hyperuricaemia may be managed with allopurinol. Hyperuricaemia may complicate treatment of conditions such as non-Hodgkin lymphomas and leukaemia. For some tumours. Patients should be adequately hydrated. the following information is provided merely as a guide.3). Generally mucositis is self-limiting. Prevention of a sore mouth is important. a combination of drugs provides the best response. Cytotoxic medications should be used with great care and close monitoring. and the treatment of malignancy in children with drugs. Renal damage may result from the formation of uric acid crystals. Chemotherapy may be curative or used to alleviate symptoms or prolong life (palliative). but it can be a focus for blood-borne infection in the absence of good oral hygiene. Alopecia is common during treatment with cytotoxic drugs. Specific doses and details of contraindications. Symptoms may be acute (occurring within 24 hours of treatment). The concomitant use of immunosuppressive drugs will enhance susceptibility to infections. When the condition can no longer be managed with cytotoxic therapy.2 Cytotoxic medicines 8. Antiemetic medicines are further discussed in section 17. delayed (first occurring more than 24 hours after treatment) or anticipatory (occurring before subsequent doses). Oral mucositis is common during cancer chemotherapy. compared to adult cancers. single-drug chemotherapy may be adequate.2 Cytotoxic medicines NOTE. because once it has developed treatment is much less effective. but a number are common to all cytotoxics.

thrombocytopenia. Rare Hypersensitivity reactions including fever. Theophylline: increased risk of theophylline toxicity. Severe: 30% of usual dose. Contraindications: Acute gout. RASH Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin. renal impairment. hepatitis. Interactions with other medicines (* indicates severe): * * * * * Amoxicillin: increased risk of rash and hypersensitivity. Doses > 300 mg should be administered as divided doses. headache. allopurinol should be started before cancer therapy. neuropathy. The risk of hypersensitivity may also be increased in patients receiving thiazides or ACe inhibitors. visual and taste disturbance. Adverse effects: Common Rash (see Precautions above). alopecia. Renal impairment: Mild: no dosage reduction necessary. blood disorders (including leukopenia. paraesthesia. malaise. Cyclophosphamide: increased risk of cyclophosphamide toxicity. treatment may be reintroduced if the rash is mild but discontinue immediately if it recurs. lymphadenopathy. vasculitis. Uncommon Hypertension. hepatic impairment. immunosuppressives and medicines used in palliative care Allopurinol ATC code: M04AA01 Tablet: 100 mg to 300 mg Indications: Prophylaxis of hyperuricaemia associated with cancer chemotherapy. renal impairment. vertigo. Moderate: 50% of usual dose. Precautions: ensure adequate fluid intake. Dose: Prophylaxis of hyperuricaemia associated with cancer chemotherapy beginning 1–2 days before chemotherapy. Ampicillin: increased risk of rash and hypersensitivity. haemolytic anaemia and aplastic anaemia). Oral: Child 1 month–12 years 10–20 mg/kg daily (maximum 400 mg) preferably after food. drowsiness. treatment should be stopped. If a rash occurs. Very rare Seizures. previous allopurinol-induced rash. Azathioprine: effects of azathioprine enhanced and toxicity increased. * Warfarin: anticoagulant effect possibly enhanced. Mercaptopurine: effects of mercaptopurine enhanced and toxicity increased. hepatotoxicity.8 Antineoplastic. especially in renal impairment. Hepatic impairment: Reduce dose and monitor liver function. withdraw treatment if rash occurs (see below). gastrointestinal intolerance. reduce dose of mercaptopurine. 252 WHO Model Formulary for Children 2010 . Didanosine: increased plasma concentration of didanosine leading to didanosine toxicity. reduce dose of azathioprine. Hydrochlorothiazide: increased risk of hypersensitivity. erythema multiforme (Stevens-Johnson syndrome) or toxic epidermal necrolysis. gynaecomastia. Ciclosporin: plasma ciclosporin concentration possibly increased (risk of nephrotoxicity). For hyperuricaemia associated with cancer therapy. arthralgia. Enalapril: increased risk of hypersensitivity. eosinophilia.

Risk factors include intravenous administration. Interactions with other medicines (* indicates severe): Vaccines. 16th ed. Kraus DM. elevated transaminases and bilirubin. Rare Intracranial haemorrhage or thrombosis. false negative rates of up to 80% are reported. history of thrombosis or haemorrhagic events with previous asparaginase therapy. pregnancy. Adelaide. appropriate measures should be taken to prevent hyperuricaemia and uric acid nephropathy (consider allopurinol. Hepatic impairment: Use with caution. 2009. peripheral venous and arterial thrombosis. live: avoid use of live vaccines with asparaginase (impairment of immune response). transient myelosuppression. Australian Medicines Handbook. Hodding JH. Serious allergic reactions can occur. test dose recommended (see below). Contraindications: Allergy to asparaginase. reduced fibrinogen and clotting factors (resulting in prolonged clotting times). 2008. Asparaginase ATC code: L01XX02 Powder for injection: 10 000 IU in vial Allergic reactions to asparaginase are frequent and can be fatal. Geneva. Prednisolone: increased hyperglycaemic effect. prior exposure to asparaginase and intervals of even a few days between doses. Pediatric dosage handbook. Desensitization may be performed in patients who are found to be hypersensitive from the intradermal test dose. Kouimtzi M. Indications: Acute lymphoblastic leukaemia.. Solimando DA Jr. Methotrexate: decreased antineoplastic effect if given prior to methotrexate. Dose: See specialist treatment protocols. discontinue at the first sign of renal failure or pancreatitis. oral mucositis. Precautions: Underlying coagulopathy. Renal impairment: Use with caution. Lexi-Comp. WHO model formulary. eds. Different brands of asparaginase may not be interchangeable and the units may be expressed differently. nausea. CNS effects including depression or hyperexcitability. WHO Model Formulary for Children 2010 253 . increased blood ammonia. Uncommon Transient proteinuria. Paediatric Formulary Committee. Special Notes: Also referred to as crisantaspase. diarrhoea. 2004. Australian medicines handbook. Cytarabine: decreased antineoplastic effect if given prior to cytarabine. vomiting. Lexi-Comp. intradermal testing should only be done in a hospital setting with adequate monitoring and resuscitation facilities. acute renal failure. Rossi S. large doses.2 References: Cytotoxic medicines Hill SR. decreased albumin and calcium concentrations. history of pancreatitis. Adverse effects: Children appear to tolerate asparaginase better than adults. London. hydration and urinary alkalinization). uraemia. L-asparaginase and colaspase. Lexi-Comp’s drug information handbook for oncology. impaired renal function. Taketomo CK. ed. Common Allergic reactions. fatty changes in the liver. chills and fever (possibly caused by bacterial endotoxins in the preparation). World Health Organization. Parkinsonian-like syndrome. hyperglycaemia (rarely leading to diabetic ketoacidosis). British national formulary for children 2009. TeST DOSe An intradermal test dose of 2 international units is often recommended prior to the first dose of asparaginase or prior to restarting therapy after a hiatus of several days. 4th ed. BMJ Group RBS Publishing. Hudson. However. Stuart MC. increased fibrin degradation products. 2009.8. pre-existing liver impairment. Hudson. T-cell non-Hodgkin lymphoma. pancreatitis. ed. An intradermal test dose may be administered (see Precautions). consult specialist texts for details. 2009.

choriocarcinoma and teratoma. WHO model formulary. Severe: 50% of normal dose (100% for malignant effusions). larynx. eds. Renal impairment: Monitor plasma creatinine at baseline and before each cycle. oral mucositis. 2009. pregnancy. alopecia. Notes: Can be produced by either Erwinia chrysanthemi or Escherichia coli. high fever. Adverse effects: Common Rash. Rossi S. pulmonary toxicity (see below). Asparaginase is a contact irritant. Kraus DM. Corticosteroids are used although evidence is limited. Moderate: 75% of normal dose (100% for malignant effusions). Consult specialist protocols. confusion and wheezing. immunosuppressives and medicines used in palliative care hypersensitive to asparaginase derived from one organism may tolerate asparaginase derived from another organism but cross-sensitivity occurs in 20–30% of individuals. Mild: dose as in normal renal function. Paediatric Formulary Committee. neck. the affected area should be flushed with water for at least 15 minutes. itch. Indications: Adjunct to surgery and radiotherapy in palliative treatment of Hodgkin and non- Hodgkin lymphomas. HyPeRSeNSITIVITy Occurs in about 1% of lymphoma patients but otherwise appears to be rare. World Health Organization. chills. initial symptoms include dyspnoea. 254 WHO Model Formulary for Children 2010 . cough and sometimes fever. cervix. vesiculation. Care should be taken to avoid contact with skin or mucous membranes (especially eyes). London. skin. Kouimtzi M. breastfeeding. Stop bleomycin if pneumonitis is suspected. Onset may be delayed for up to 6 months after the last dose. ed. carcinomas of the head. Adelaide. Contraindications: Acute pulmonary infection or significantly reduced lung function. Geneva. Australian medicines handbook. malignant effusions. Australian Medicines Handbook. May be immediate or delayed and usually occurs with the first or second dose. Lexi-Comp. 2009. Precautions: Renal impairment. Hodding JH. Rare Acute chest pain during infusion. allergy to bleomycin. Children who are Bleomycin ATC code: L01DC01 Powder for injection: 15 mg (as sulfate) in vial Handle as a cytotoxic. pulmonary impairment. 2009. 16th ed. penis. hyperkeratosis. vulva. Kaposi sarcoma. Taketomo CK. Pneumonitis may progress to pulmonary fibrosis and death. Pediatric dosage handbook. testicles and including embryonal cell carcinoma. PULMONARy TOXICITy Occurs in approximately 10% of patients. British national formulary for children 2009. pre-exisiting lung disease and oxygen supplementation. Hudson. hypersensitivity (see below). Hepatic impairment: Dosage reduction not necessary. Risk factors include high cumulative dose.8 Antineoplastic. 2008. Dose: Maximum cumulative dose for adults is 300 000–400 000 international units. renal impairment. If accidental contact occurs. BMJ Group RBS Publishing. Uncommon Raynaud phenomenon. nail changes. References: Hill SR. Stuart MC. fever and chills (usually occur within 4–10 hours of a dose and last 4–12 hours or longer). hyperpigmentation (particularly of skin folds). mediastinal radiotherapy. nausea and vomiting. Usually presents with hypotension. erythema.

Contraindications: Intrathecal injection of calcium folinate is contraindicated. 2008. London.5 mg (by potency) or 1 mg (by weight). Vaccines. baseline and monthly evaluation of carbon monoxide diffusion capacity. WHO model formulary. World Health Organization. vitamin B12 deficiency. Currie A. then each week during and for 4 weeks after treatment. Doses and length of treatment may be based on methotrexate concentration. British national formulary for children 2009. Digoxin: bleomycin may decrease digoxin absorption. * Vinblastine: increased risk of cardiovascular toxicity. Oxford. 2009. Avoid simultaneous administration of methotrexate.5 USP bleomycin units and approximately 1. live: avoid use of live vaccines with bleomycin (impairment of immune response). The renal drug handbook. Adelaide. Australian Medicines Handbook. Indications: Reduction of methotrexate-induced toxicity associated with high-dose methotrexate therapy (folate rescue). References: Ashley C. WHO Model Formulary for Children 2010 255 . 2009. Renal impairment: Dose reduction not necessary. Usually started 24 hours after beginning the methotrexate infusion. 1500 international units of bleomycin are equivalent to 1. eds. needs to be administered with care. Paediatric Formulary Committee. Dose: Precautions: Not for use in patients with pernicious anaemia or other megaloblastic anaemias due to Consult specialist protocols. Rossi S. Stuart MC. folinic acid or leucovorin. Hepatic impairment: Dose reduction not necessary. Radcliffe Publishing. * Oxygen: serious pulmonary toxicity in patients exposed to conventional oxygen concentrations during anaesthesia. Amphotericin B: concurrent bleomycin may increase nephrotoxicity and risk of hypotension and bronchospasm. Geneva. Australian medicines handbook. 2009. monitoring may include: chest X-ray at baseline. ed. pulmonary function tests (particularly total lung volume and forced vital capacity). BMJ Group RBS Publishing. Caution is required when converting from mg to international units as protocols or trials may state bleomycin doses in terms of mg-potency rather than mg-weight. 3rd ed. eds. stop treatment if it falls to < 30–35% of pretreatment value. Phenytoin: possibly reduced absorption of phenytoin.2 Interactions with other medicines (* indicates severe): Cytotoxic medicines * Cisplatin: increased pulmonary toxicity. Kouimtzi M. Notes: No single monitoring test reliably predicts bleomycin pulmonary toxicity. Hill SR. Calcium folinate ATC code: V03AF03 Injection: 3 mg/ml in 10 ml ampoule Tablet: 15 mg Special Notes: Also referred to as calcium leucovorin. Irritant to tissues.8.

Renal impairment: Renal function is often factored into dose calculations for carboplatin. weakness. peripheral neuropathy. mild and reversible electrolyte abnormalities (hyponatraemia. Hill SR. Australian medicines handbook. low-grade gliomas (including astrocytomas). 2009. hypomagnesaemia). Fluorouracil: toxicity enhanced but used for this purpose intentionally. pregnancy. Interactions with other medicines (* indicates severe): Phenobarbital: plasma concentration of phenobarbital possibly reduced. breastfeeding. 3rd ed. WHO model formulary. Precautions: Renal impairment. Currie A. Contraindications: Hypersensitivity to carboplatin. ed. British national formulary for children 2009.36 x body weight in kilograms)].8 Antineoplastic. Doses frequently calculated according to individual patient’s renal function and ability to clear the drug. eds. neuroectodermal tumours (including medulloblastoma). If renally- adjusted doses are not being used and the patient is renally impaired. Stuart MC. fainting. The renal drug handbook. Rossi S. Carboplatin ATC code: L01XA02 Injection: 10 mg/ml solution 5 ml. References: Ashley C. soft tissue sarcomas. avoid if creatinine clearance less than 20 ml/minute. Australian Medicines Handbook. taste abnormality. 2009. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. 15 ml. high-risk Wilms tumour. immunosuppressives and medicines used in palliative care Adverse effects: Uncommon Allergic reactions. Phenytoin: plasma phenytoin concentration possibly reduced. 2008. Trimethoprim: reduced therapeutic effect. hypokalaemia. Indications: Stage 4 neuroblastoma. London. Dose: See specialist treatment protocols. Oxford. rhabdomyosarcoma (metastatic and nonmetastatic disease). vomiting. Geneva. eds. Modified Calvert formula for children: Total dose (mg) = [target AUC (mg. liver transaminases and bilirubin. Hepatic impairment: Dosage reduction not necessary. The information in this monograph only applies to the medicine listed here. Calvert formula for carboplatin dosing in adults: Total dose (mg) = target AUC (mg. cisplatin. fatigue. hypersensitivity reactions including anaphylaxis (risk increases with repeated exposure). Rare Seizures. 256 WHO Model Formulary for Children 2010 . reversible elevation of serum creatinine. Adverse effects: Common Myelosuppression (see below).minute/ml) x [GFR (ml/minute) + 25]. other platinum containing compounds or mannitol. fever. germ cell tumours. BMJ Group RBS Publishing. nausea. alopecia. 2009. Special Notes: This medicine is listed as a representative of its pharmacological class. 45 ml and 60 ml vials Handle as a cytotoxic agent. World Health Organization. Kouimtzi M. Adelaide. severe bone marrow suppression or excessive bleeding. Paediatric Formulary Committee. consider reducing dose and monitor haematological parameters and renal function. some liver tumours. mild elevations of ALP. hypocalcaemia. myalgia.minute/ml)] x [GFR (ml/minute) + (0. retinoblastoma. Radcliffe Publishing.

16th ed. Dose reduction not usually necessary. pregnancy. 2009. WHO Model Formulary for Children 2010 257 . Taketomo CK. Adverse effects: Common Rash. affects fertility (see Adverse effects). oral mucositis. Reduce initial dose if a patient has received radiation therapy. 2009. Kraus DM. oral mucositis. London. dose-limiting myelosuppression (nadir 14 days). histiocytosis. Australian Medicines Handbook. World Health Organization. Interactions with other medicines (* indicates severe): Aminoglycosides: increased ototoxicity and nephrotoxicity. Nephrotoxic drugs: increased renal toxicity. BMJ Group RBS Publishing. bone marrow suppression. loss of vision (at higher than usually recommended doses). Nadir of platelet and neutrophil counts occurs 14–28 days after a dose. Rossi S. Rare Acute renal failure. Indications: Non-Hodgkin lymphomas. Australian medicines handbook. Notes: Needle or intravenous administration sets containing aluminium parts should not be used in the administration or preparation of carboplatin as an interaction may cause precipitate formation and loss of potency. haemolytic uraemic syndrome. Adelaide. Chlorambucil ATC code: L01AA02 Tablet: 2 mg Handle as a cytotoxic. Stuart MC. 2009. Paediatric Formulary Committee. abdominal pain. Hepatic impairment: Consider dose reduction in severe hepatic impairment. seizure disorders. Clozapine: increased risk of agranulocytosis. References: Hill SR. increased risk of myelosuppression. with recovery usually within 28 days. effective contraception is advised in both men and women. constipation. Uncommon Abdominal discomfort. myelosuppressive drugs. cross-hypersensitivity (skin rash) may occur with other alkylating agents. Kouimtzi M. Lexi-Comp.2 Cytotoxic medicines Uncommon Ototoxicity. Thrombocytopenia is more common and pronounced than leukopenia. Anaemia may be cumulative and require transfusion. breastfeeding. eds. Pediatric dosage handbook. Phenytoin: decreased serum levels of phenytoin. diarrhoea. diarrhoea. WHO model formulary. Precautions: Severe hepatic impairment. Dose: Consult specialist protocols. Hodgkin disease. Renal impairment: Moderate or severe: use with caution and monitor response. Hodding JH. Hudson. renal impairment. transient elevations in liver enzymes. it may be cumulative and sometimes requires platelet transfusion.8. Contraindications: Hypersensitivity to chlorambucil or any component. Digoxin: reduced absorption of digoxin. or has reduced baseline leukocyte or platelet count within the previous 4 weeks. 2008. ed. MyeLOSUPPReSSION Major dose-limiting effect. British national formulary for children 2009. Geneva.

London. infant brain tumours. sterile cystitis. nasal congestion (with rapid injection). Moderate: 75–100% of normal dose depending on clinical indication and local protocol. ewing tumour. Avoid contact with skin. 4th ed. Kouimtzi M. non-Hodgkin lymphoma. retinoblastoma. peripheral neuropathy. irreversible bone marrow suppression. 2009. Lexi-Comp. 258 WHO Model Formulary for Children 2010 . eds. Precautions: Renal impairment. immunosuppressives and medicines used in palliative care Johnson syndrome. 3rd ed. soft tissue sarcomas. anorexia. Contraindications: Haemorrhagic cystitis. Cyclophosphamide ATC code: L01AA01 Powder for injection: 500 mg in vial Tablet: 25 mg Handle as a cytotoxic. Paediatric Formulary Committee. ed. Hill SR. ed. Geneva. 2009. Store tablets at 2–8 °C (36–46 °F). Australian medicines handbook. Phenobarbital: increased toxicity of chlorambucil. Indications: Acute lymphoblastic leukaemia. leukopenia (nadir at 8–15 days). ependymona. nausea. eds.8 Antineoplastic. Adverse effects: Common Alopecia. pulmonary fibrosis. Avoid the need to cut tablets by using different doses on alternate days. live: avoid use of live vaccines with chlorambucil (impairment of immune response). References: Ashley C. Currie A. 2009.. British national formulary for children 2009. Oxford. Hudson. Severe: 50–100% of normal dose depending on clinical indication and local protocol. Radcliffe Publishing. haemorrhagic cystitis (see below). breastfeeding. Rare Hallucinations. Rossi S. Adelaide. neuroblastoma. World Health Organization. 2008. gonadal suppression (amenorrhoea). impairment of fertility (may be irreversible). bone marrow suppression. drug fever. 2004. neuroectodermal tumours (including medulloblastoma). Stuart MC. Dose: See specialist treatment protocols. severe pneumonitis. chewed or crushed. as part of high-dose conditioning therapy for bone marrow transplantation. Notes: Tablets should be swallowed whole on an empty stomach and not broken. Solimando DA Jr. Vaccines. seizures. Uncommon Hyperpigmentation of skin and nails. Mild: dose as in normal renal function. tremor. May cause infertility (see Adverse effects). Australian Medicines Handbook. hepatotoxicity. vomiting. The renal drug handbook. BMJ Group RBS Publishing. pregnancy. Renal impairment: Reduce dose in moderate to severe impairment. WHO model formulary. Stevens- Interactions with other medicines (* indicates severe): Phenytoin: possibly reduced absorption of phenytoin. Hepatic impairment: Reduce dose. toxic epidermal necrolysis. metallic taste. rhabdomyosarcoma. Lexi-Comp’s drug information handbook for oncology. jaundice. Tablets may be stored at room temperatures up to 30 °C (86 °F) for up to 1 week. sterility in pre-pubertal and pubertal males (less likely in females). loss of taste. hepatic impairment.

Rossi S. hepatic veno-occlusive disease (high dose). may be reversible). 3rd ed. Intravenous hydration may be required.8. References: Ashley C. mesna is given for the same duration as cyclophosphamide. WHO Model Formulary for Children 2010 259 . live: avoid use of live vaccines with cyclophosphamide (impairment of immune response). Patients should be advised to drink plenty of fluids during therapy. Hodding JH. Interactions with other medicines (* indicates severe): * Allopurinol: increases the myelotoxicity of cyclophosphamide. Phenytoin: possibly reduced absorption of phenytoin. breastfeeding. Australian medicines handbook.2 Cytotoxic medicines Rare Heart failure (acute onset days after high-dose treatment. Precautions: Hepatic impairment. * Warfarin: increased INR and increased risk of bleeding. mesna reacts specifically with acrolein in the urinary tract. * Ondansetron: reduced cyclophosphamide effectiveness. Australian Medicines Handbook. Mesna (not included on the 2nd WHO Model list of essential medicines for children) may be used. pulmonary fibrosis (with longterm treatment). The renal drug handbook. 2008. acute myeloid leukaemia. Geneva. London. Oxford. meningeal neoplasms. Adelaide. Vaccines. Hill SR. eds. often 125%. meningeal leukaemia. Cytarabine ATC code: L01BC01 Powder for injection: 100 mg in vial Handle as a cytotoxic. Toxicity is caused by the metabolite acrolein. preventing toxicity. Symptoms range from mild irritation on voiding to life-threatening haemorrhagic cystitis. Contraindications: Pregnancy. ed. Kraus DM. Lexi-Comp. World Health Organization. water retention resembling syndrome of inappropriate antidiuretic hormone secretion (SIADH) resulting in hyponatraemia and seizures (more common in high doses). British national formulary for children 2009. BMJ Group RBS Publishing. Radcliffe Publishing. Indications: Acute lymphoblastic leukaemia. * Ciclosporin: decreased ciclosporin concentration. more common in older adult patients and those previously exposed to anthracyclines. non-Hodgkin lymphoma. Dose: See specialist treatment protocols. renal impairment. Suxamethonium: enhanced effect of suxamethonium. Taketomo CK. Paediatric Formulary Committee. HAeMORRHAGIC CySTITIS Occurs as a result of accumulation of active metabolites in the bladder. void frequently. Stuart MC. 2009. 2009. 16th ed. and avoid taking the drug at night. Currie A. Phenobarbital: may increase conversion of cyclophosphamide to active metabolites. Special Notes: Also referred to as Ara-C. WHO model formulary. 2009. Hudson. Carbamazepine: may increase conversion of cyclophosphamide to active metabolites. the dose of mesna is equal to or greater than that of cyclophosphamide. 2009. Kouimtzi M. It is generally given intravenously. * Chloramphenicol: reduced cyclophosphamide effectiveness. eds. * Hydrochlorothiazide: increased myelotoxicity of cyclophosphamide. Pediatric dosage handbook.

As prophylaxis. ed. WHO model formulary. MyeLOSUPPReSSION Major dose-limiting adverse effect.. For high-dose therapy the following information should be considered: elevated baseline serum creatinine (> 106 micromol/l ) is an independent risk factor for the development of neurotoxicity during treatment. The renal drug handbook. Currie A. diarrhoea. Adelaide. elevated liver function tests. the incidence of neurotoxicity is increased following administration of high-dose cytarabine to patients with even mildly impaired renal function. retrospective analysis implicates impaired renal function as an independent risk factor for high-dose cytarabine-induced cerebral and cerebellar toxicity. severe spinal cord toxicity following intrathecal administration. Conjunctivitis (which occurs more frequently in high-dose therapy) is preventable and treatable with a corticosteroid eye drop. oesophagitis. nausea. ed. Vaccines. References: Ashley C. fever. renal impairment. Interactions with other medicines (* indicates severe): Digoxin: decreases digoxin oral tablet absorption. eye drops should be started 6–12 hours before initiation of cytarabine and continued for 24 hours following the last dose. 2008. Suggested dose reductions for high-dose therapy in patients with renal impairment. includes neutropenia. Australian Medicines Handbook. Reversible corneal toxicity leading to haemorrhagic conjunctivitis or keratitis can occur (prophylactic corticosteroid or lubricant eye drops may help). Moderate or severe: avoid use of cytarabine high-dose. cellulitis at injection site. Solimando DA Jr. gastrointestinal ulceration. Stuart MC. adverse effects include peripheral neuropathy. 2009. eds. Paediatric Formulary Committee. more severe after high doses or continuous infusions. eds. HIGH-DOSe THeRAPy Associated with severe and sometimes fatal gastrointestinal. Recovery generally occurs after a further 10 days. 2009. thrombocytopenia and anaemia. Lexi-Comp’s drug information handbook for oncology. Rare Palmar-plantar erythrodysaesthesia. Radcliffe Publishing. Mild: 50–60% of normal dose.8 Antineoplastic. jaundice. Geneva. Hudson. anaphylaxis. Neutropenia is biphasic with a nadir 7–9 days after the dose and a more severe nadir at 15–24 days. urinary retention. World Health Organization. Flucytosine: plasma flucytosine concentration possibly reduced. Notes: Based on weight or body surface area. Kouimtzi M. cardiomyopathy. 260 WHO Model Formulary for Children 2010 . Rossi S. 3rd ed. oral mucositis. British national formulary for children 2009. Platelet nadir is 12–15 days after dose. Hepatic impairment: Reduce dose. cerebral and cerebellar dysfunction. Australian medicines handbook. alopecia. immunosuppressives and medicines used in palliative care Renal impairment: For low-dose regimens dose reductions are not necessary. vomiting. Lexi-Comp. Adverse effects: Common Myelosuppression (see below). neurological and pulmonary toxicity. rash. London. 4th ed. 2004. Uncommon Conjunctivitis. gastrointestinal haemorrhage. dizziness. live: avoid use of live vaccines with cytarabine (impairment of immune response). Hill SR. chest pain. Phenytoin: reduced absorption of phenytoin. pulmonary oedema. children may tolerate higher doses of cytarabine than adults. 2009. BMJ Group RBS Publishing. ocular discomfort. Oxford.

8.2

Cytotoxic medicines

Dacarbazine
ATC code: L01AX04

Powder for Injection: 100 mg in vial Highly irritant to tissues, inject with care. Handle as a cytotoxic.
Indications: Hodgkin disease; rhabdomyosarcoma; neuroblastoma; fibrosarcomas; soft tissue

sarcomas; bone marrow transplant. female patients); breastfeeding.

Contraindications: Pregnancy (avoid for 6 months after treatment completed in both male and Precautions: Renal and hepatic impairment; bone marrow depression; ensure adequate contraception

during and for 6 months after treatment in men and women.

Dose:

Consult specialist protocols.
Renal impairment: Mild: 75–80% of dose.

Moderate to severe: 70% of dose; use with caution.
Hepatic impairment: Dose reduction may be required in mild to moderate liver disease; avoid if

severe.

Adverse effects: Common Diarrhoea, flu-like syndrome (fever, myalgia, malaise), transient increases

in hepatic transaminases and ALP, facial flushing, pain along injected vein, nausea and vomiting. and maculopapular rash, photosensitivity, hypotension (infusion related).

Uncommon Agranulocytosis, blurred vision, seizures, confusion, headache, alopecia, erythematous Rare Intractable nausea and vomiting, hepatic vein thrombosis and hepatocellular necrosis, tissue

damage due to extravasation.

Interactions with other medicines (* indicates severe):

Phenytoin: possibly reduced absorption of phenytoin. Vaccines, live: avoid use of live vaccines with dacarbazine (impairment of immune response). Phenobarbital: may induce dacarbazine metabolism.
Notes: INTRAVeNOUS INFUSION For intravenous infusion, further dilute reconstituted solution in 125–250 ml glucose 5% or sodium chloride 0.9%, give over 15–30 minutes. Protect infusion set from light throughout administration to reduce pain.
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

References:

WHO Model Formulary for Children 2010

261

8

Antineoplastic, immunosuppressives and medicines used in palliative care

Dactinomycin
ATC code: L01DA01

Powder for injection: 500 micrograms in vial Handle as a cytotoxic. Highly irritant to tissues; inject with care.
Special Notes: Also referred to as actinomycin D. Indications: Trophoblastic tumours; Wilms tumour; testicular tumours; ewing sarcoma;

rhabdomyosarcoma; other soft tissue sarcomas.

Contraindications: Pregnancy; breastfeeding. Precautions: Hepatic or biliary impairment; concurrent or previous radiotherapy; vesicant

(extravasation during intravenous use can cause severe tissue damage).

Dose:

Consult specialist protocols.
Renal impairment: No dose reductions necessary. Hepatic impairment: Consider dose reduction if raised serum bilirubin or biliary obstruction. Adverse effects: Common Myelosuppression (see below), nausea and vomiting, oral mucositis,

oesophagitis, pharyngitis, diarrhoea, fever, malaise, myalgia, alopecia, rash, acne.

Rare Anaphylaxis, hepatotoxicity, hepatic veno-occlusive disease (common in Wilms tumour). MyeLOSUPPReSSION Affects mainly white cells and platelets; nadir of white cell and platelet count occurs 14–21 days after dose with recovery in 21–25 days. Interactions with other medicines (* indicates severe):

Phenytoin: possibly reduced absorption of phenytoin. Vaccines, live: avoid use of live vaccines with dactinomycin (impairment of immune response).
Notes: Current radiotherapy: radiation effects (including skin, gastrointestinal and bone marrow

toxicity) may be potentiated.

Previous radiotherapy: erythema and pigmentation may recur at site of previous radiation. Children may experience increased risk of toxicity and are at greater risk of hepatic veno-occlusive disease. Vesicant; avoid extravasation. extremely damaging to soft tissue and will cause a severe local reaction if extravasation occurs. Administer slow intravenous push over 10–15 minutes. Do not give intramuscularly or subcutaneously. Care should be taken with units: chemotherapy protocols can list dactinomycin doses in mg (e.g. mg/kg or mg/m2), but medication orders are often written in micrograms.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

262

WHO Model Formulary for Children 2010

8.2

Cytotoxic medicines

Daunorubicin
ATC code: L01DB02

Powder for injection: 50 mg (as hydrochloride) Handle as a cytotoxic.
Special Notes: Daunorubicin hydrochloride (conventional formulation) should not be confused with

daunorubicin liposomal formulation. Indications: Acute myelogenous leukaemia; acute lymphocytic leukaemia; neuroblastoma; rhabdomyosarcoma. Contraindications: Pregnancy; breastfeeding; congestive heart failure, left ventricular ejection fraction < 30–40%; arrhythmias; pre-existing bone marrow suppression. Precautions: Hepatic and renal impairment; cardiac disease; reduced cardiac reserve or treatment with other cardiotoxic drugs; highly irritant to tissues (inject with extreme care); previous treatment to maximum cumulative dose with another anthracycline.
Dose:

Consult specialist protocols. Maximum cumulative dose (irreversible myocardial toxicity may occur as total dosage approaches): Child under 2 years 10 mg/kg (300 mg/m2); over 2 years 300 mg/m2.
Renal impairment: Mild to moderate: reduce dose. Hepatic impairment: Reduce dose according to serum bilirubin concentration; see specialist

protocols for details.

Adverse effects: Common Rash, itch, nausea, vomiting, diarrhoea, alopecia, oral mucositis, Rare Secondary malignancies.

oesophagitis, myelosuppression (see below), cardiac toxicity (see below), fatigue, headache.

MyeLOSUPPReSSION Occurs commonly, affecting white cells and to a lesser degree, platelets and red cells. The white count nadir occurs about 10 days after a dose with recovery by about 21 days. CARDIAC TOXICITy May be acute, chronic or delayed. Acute toxicity (eCG changes and arrhythmias) occurs during or immediately after a dose and is not dose related. It is usually transient but may rarely result in myopericarditis and cardiac failure. Chronic toxicity usually occurs within a year of stopping treatment and is related to cumulative dose. Cardiomyopathy may result in heart failure. Delayed toxicity occurs years to decades after treatment and is thought to be dose related. It may present as ventricular dysfunction, heart failure, conduction disturbances or arrhythmias. Interactions with other medicines (* indicates severe):

Phenytoin: possibly reduced absorption of phenytoin. Vaccines, live: avoid use of live vaccines with daunorubicin (impairment of immune response). Notes: Daunorubicin is a vesicant; severe local tissue necrosis will result if extravasation occurs. Do not give intramuscularly or subcutaneously. Give by intravenous injection or short infusion into a side arm of a fast running infusion to reduce the risk of irritation or extravasation. Monitor eCG and left ventricular ejection fraction at baseline and during treatment. WHO Model Formulary for Children 2010 263

8

Antineoplastic, immunosuppressives and medicines used in palliative care

References:

Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

Doxorubicin

ATC code: L01DB01

Powder for injection: 10 mg, 50 mg (as hydrochloride) in vial Handle as a cytotoxic.
Special Notes: Also referred to as adriamycin or ADR. Doxorubicin hydrochloride (conventional formulation) should not be confused with doxorubicin liposomal formulation. Indications: Malignancies including ewing sarcoma, osteogenic sarcoma, Wilms tumour, neuroblastoma, retinoblastoma, some liver tumours, acute lymphoblastic leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell tumours of the testis. Contraindications: Pregnancy and breastfeeding; congestive heart failure, left ventricular ejection fraction < 30–40%; arrhythmias; pre-existing bone marrow suppression. Precautions: Avoid extravasation (highly irritant to the tissues); previous treatment to maximum cumulative dose with another anthracycline; hepatic impairment; renal impairment; cardiac disease; treatment with other cardiotoxic drugs; previous mediastinal or pericardial irradiation. Dose:

Consult specialist protocols.
Renal impairment: Mild to moderate: use with caution; avoid excessive doses.

Severe: use 75% of normal dose; use with caution. Hepatic impairment: Reduce dose according to serum bilirubin concentration. Do not use doxorubicin if bilirubin > 85 micromol/l. Bilirubin 20–50 micromol/l: reduce dose by 50%. Bilirubin > 50 micromol/l: reduce dose by 75%. Adverse effects: Common Rash, itch, myelosuppression (see below), cardiac toxicity (see below), red coloured urine, nausea, vomiting, stomatitis, gastrointestinal ulceration. Uncommon Conjunctivitis, lacrimation and facial flushing, hyperpigmentation of nails, buccal mucosa and skin folds, fever, chills, palmar-plantar erythrodysaesthesia. Rare Secondary malignancies.
CARDIAC TOXICITy May be acute, chronic or delayed. Acute toxicity (eCG changes and arrhythmias) occurs during or immediately after a dose and is not dose related. It is usually transient but may rarely result in myopericarditis and cardiac failure. Chronic toxicity usually occurs within a year of stopping treatment and is related to cumulative dose. Cardiomyopathy may result in heart failure. Delayed toxicity occurs years to decades after treatment and is thought to be dose-related. It may present as ventricular dysfunction, heart failure, conduction disturbances or arrhythmias.

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Cytotoxic medicines

MyeLOSUPPReSSION Occurs commonly, affecting white cells and, to a lesser degree, platelets and red cells. The white cell count nadir occurs about 10 days after a dose, with recovery by about 21 days. Interactions with other medicines (* indicates severe):

* Ciclosporin: increased risk of neurotoxicity. Phenytoin: possibly reduced absorption of phenytoin. Phenobarbital: increases elimination of doxorubicin. Stavudine: doxorubicin may inhibit effect of stavudine. Vaccines, live: avoid use of live vaccines with doxorubicin (impairment of immune response). * Warfarin: increased INR and increased risk of bleeding. Notes: Doxorubicin is a vesicant; severe local tissue necrosis will result if extravasation occurs. Do not give intramuscularly or subcutaneously. Monitor eCG and left ventricular ejection fraction at baseline and during treatment.
References:
Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

Etoposide

ATC code: L01CB01

Capsule 100 mg Injection 20 mg/ml in 5 ml ampoule Handle as a cytotoxic.
Special Notes: Also known as VP-16. This entry is for etoposide not etoposide phosphate which is not equivalent. Indications: Stage 4 neuroblastoma; germ cell tumours; intracranial germ cell tumours; rhabdomyosarcoma; soft tissue sarcomas; neuroectodermal tumours (including medulloblastoma); relapsed Hodgkin disease; non-Hodgkin lymphoma; ewing tumour; acute lymphoblastic leukaemia; acute myeloid leukaemia. Contraindications: Pregnancy; breastfeeding; severe hepatic impairment; allergy to polysorbate 80, etoposide, benzyl alcohol; intrathecal administration. Precautions: Hepatic and renal impairment. Dose:

Consult specialist protocols.
Renal impairment: Consider dose reduction.

Mild impairment: 80–85% of normal dose. Moderate to severe impairment: 50–75% of normal dose. Hepatic impairment: Reduce dose according to serum bilirubin concentration. Do not use etoposide in severe hepatic impairment or if bilirubin > 85 micromol/l. Bilirubin 20–50 micromol/l: reduce dose by 50%. Bilirubin > 50 micromol/l: reduce dose by 75%. WHO Model Formulary for Children 2010 265

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Adverse effects: Common Anorexia, constipation, abdominal pain, taste alteration, weakness,

malaise, myelosuppression (see below), alopecia, nausea, vomiting, oral mucositis, diarrhoea, hypersensitivity reactions. Uncommon Hypotension (with rapid infusion), peripheral neuropathy. Rare Heart failure, cardiac arrest, radiation recall, dermatitis, Stevens-Johnson syndrome, secondary malignancies.
MyeLOSUPPReSSION Major dose-limiting adverse effect. Mainly affects white cells but platelets and red cells are also affected. Neutrophil nadir occurs 7–14 days after administration. Recovery of bone marrow usually takes about 20 days. Interactions with other medicines (* indicates severe):

Ciclosporin: possibly increased plasma concentration of etoposide (increased risk of toxicity). Phenobarbital: possibly reduced plasma concentration of etoposide. Phenytoin: possibly reduced absorption of phenytoin and possibly reduced plasma concentration of etoposide. Vaccines, live: avoid use of live vaccines with etoposide (impairment of immune response). * Warfarin: possibly enhanced anticoagulant effect. Notes: For oral therapy it may be necessary to give different doses on different days in order to administer dose within whole capsule units. Capsules should be swallowed whole on an empty stomach.
ADMINISTRATION Do not administer by rapid intravenous injection. Administer by continuous intravenous infusion or by intravenous intermittent infusion via an in-line 0.22 micron filter over at least 60 minutes at a rate not to exceed 100 mg/m2 per hour (or 3.3 mg/kg per hour) to minimize the risk of hypotensive reactions.
Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

References:

Fluorouracil

ATC code: L01BC02

Injection: 50 mg/ml 5 ml vial Handle as a cytotoxic.
Special Notes: Also referred to as 5-fluorouracil or 5FU. Indications: Treatment and palliation of solid tumours. Contraindications: Pregnancy; breastfeeding; dihydropyrimidine dehydrogenase deficiency. Precautions: Pre-existing cardiac disease; hepatic impairment. Dose:

Consult specialist protocols.
Renal impairment: Dose reduction not required. Hepatic impairment: Severe: not recommended. Adverse effects: Adverse effects differ depending on whether fluorouracil is given as a bolus dose or

by continuous infusion. Myelotoxicity is common with bolus doses but unusual with continuous infusions. Palmar-plantar erythrodysaesthesia is common with continuous infusion. WHO Model Formulary for Children 2010

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Cytotoxic medicines

Common Myelosuppression (see below), gastrointestinal effects including nausea, vomiting, oral mucositis

and diarrhoea (see below), alopecia, itch, maculopapular rash, ovarian failure, amenorrhoea.

Uncommon Oesophagitis, gastrointestinal ulceration and bleeding, proctitis, palmar-plantar

erythrodysaesthesia, photosensitivity, confusion, ataxia, nystagmus, headache, acute cerebellar syndrome, lacrimation, visual changes, photophobia. Rare Myocardial ischaemia, arrhythmias, anaphylaxis and allergic reactions, fever without signs of infection, vein pigmentation.
MyeLOSUPPReSSION Includes neutropenia, thrombocytopenia and anaemia. Neutropenic nadir occurs 9–14 days, but may be as late as 25 days, after first course. Platelet nadir occurs about 7–17 days after a dose, with recovery after about a further 10 days. DIARRHOeA May be dose limiting and is more severe if given with calcium folinate. Consider fluid and electrolyte replacement. Interactions with other medicines (* indicates severe):

Metronidazole: metabolism of fluorouracil inhibited (increased toxicity). Phenytoin: metabolism of phenytoin possibly inhibited (increased risk of toxicity). Vaccines, live: avoid use of live vaccines with fluorouracil (impairment of immune response). * Warfarin: anticoagulant effect possibly enhanced.
References:
Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

Mercaptopurine
ATC code: L01BB02

Tablet 50 mg Handle as a cytotoxic.
Special Notes: Also known as 6-MP or 6-mercaptopurine. Indications: Acute lymphoblastic leukaemia; lymphoblastic lymphomas. Contraindications: Pregnancy; breastfeeding; severe liver disease; severe bone marrow suppression;

patients whose disease showed prior resistance to mercaptopurine or thioguanine.

Precautions: Renal or hepatic failure; concurrent treatment with allopurinol (see Interactions). Dose:

Consult specialist protocols.
Renal impairment: Moderate to severe: reduce dose. Hepatic impairment: May need dose reduction; use with caution and monitor liver function tests. Adverse effects: Common Oral mucositis, myelosuppression (dose-dependent), cholestatic jaundice

(may be reversible, but may progress to hepatic necrosis with continued treatment; onset is more common with daily doses > 2.5 mg/kg). Uncommon Anorexia, nausea, vomiting. Rare Hypersensitivity syndrome (e.g. fever, pancreatitis, rash, arthralgia), gastrointestinal ulceration, alopecia, hyperpigmentation, secondary leukaemia or myelodysplasia. WHO Model Formulary for Children 2010 267

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Interactions with other medicines (* indicates severe):

* Allopurinol: effects of mercaptopurine enhanced and toxicity increased; reduce dose of mercaptopurine to 25%. * Azathioprine: increased risk of myelosuppression, impaired renal function, and hepatotoxicity. * Mesalazine: increased risk of myelosuppression. * Olsalazine: increased risk of myelosuppression. Phenytoin: possibly reduced absorption of phenytoin. * Sulfamethoxazole + trimethoprim: increased risk of haematological toxicity. * Sulfasalazine: increased risk of myelosuppression. * Trimethoprim: increased risk of haematological toxicity. Vaccines, live: avoid use of live vaccines with mercaptopurine (impairment of immune response). * Warfarin: anticoagulant effect possibly reduced. Notes: 1 in 300 patients lack functional thiopurine methyltransferase (TPMT) activity and are at risk of severe myelosuppression unless the dose is drastically reduced. These patients may tolerate doses one tenth of normal or less; TPMT genotyping is available on a limited basis. Mercaptopurine is best taken in the evening on an empty stomach (1 hour before or 2 hours after a meal).
References:
Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

Methotrexate
ATC code: L04AX03

Powder for injection: 50 mg (as sodium salt) in vial Tablet: 2.5 mg (as sodium salt) Handle as a cytotoxic.
Special Notes: Also referred to as MTX. Indications: Maintenance and remission of acute lymphoblastic leukaemia, lymphoblastic

lymphoma; treatment of early stage Burkitt lymphoma, non-Hodgkin lymphoma, osteogenic sarcoma, some neurological tumours including infant brain tumours, meningeal leukaemia; treatment and prevention of neurological involvement of leukaemia. Contraindications: Pregnancy; breastfeeding; severe renal impairment; severe hepatic impairment. Precautions: Monitor renal and hepatic function; peptic ulceration; ulcerative colitis; diarrhoea; ulcerative stomatitis; porphyria; pre-existing bone marrow suppression; concurrent use of other hepatotoxic drugs.
Dose:

Consult specialist protocols. High-dose methotrexate requires specialist supportive care, such as alkalinization of the urine and calcium folinate rescue; consult specialist protocols. 268 WHO Model Formulary for Children 2010

8.2
Renal impairment: Accumulates; nephrotoxic.

Cytotoxic medicines

Mild: 50–100% of normal dose. Moderate: 50% of normal dose. Severe: contraindicated. Or refer to instructions in specialist protocols. Hepatic impairment: Dose-related toxicity: avoid in severe hepatic impairment. Adverse effects: Common Myelosuppression (see below), nausea and vomiting (more frequent with high doses), oral mucositis, pulmonary toxicity (see below), hepatotoxicity (see below), rash, itch, urticaria, photosensitivity, neurotoxicity (e.g. aseptic meningitis, encephalopathy, leukoencephalopathy) with high-dose or intrathecal use. Uncommon Malaise, fatigue, chills, fever, headache, dizziness, tinnitus, blurred vision, alopecia, ocular irritation, oligospermia (transient). Rare Anaphylactic/anaphylactoid reactions, severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis), nephrotoxicity including renal failure, osteoporosis, skin and bone necrosis, macrocytic anaemia.
MyeLOSUPPReSSION Includes neutropenia, thrombocytopenia and anaemia. Neutrophil and platelet nadirs occur about 5–13 days after a bolus dose with recovery between 14 and 28 days. Neutropenia may sometimes be biphasic with the first nadir 4–7 days after a dose and the second at 12–21 days. Pancytopenia may occur and is potentially fatal. HePATOTOXICITy Increased aminotransferases are common and usually transient and asymptomatic. Chronic hepatotoxicity (including necrosis, fatty change, periportal fibrosis or cirrhosis) generally occurs with long-term therapy and is also dependent on cumulative dose. PULMONARy TOXICITy Can develop rapidly and may be fatal. Often occurs as fever, dyspnoea, chest pain and dry, non-productive cough. Lesions such as pneumonitis and pulmonary fibrosis can occur at all doses at any time during treatment. Pulmonary toxicity may not be fully reversible; corticosteroids may relieve symptoms. Also consider the possibility of infection. Interactions with other medicines (* indicates severe):

* Acetylsalicylic acid: reduced excretion of methotrexate (increased toxicity). Amoxicillin: reduced excretion of methotrexate (increased risk of toxicity). Ampicillin: reduced excretion of methotrexate (increased risk of toxicity). Benzylpenicillin: reduced excretion of methotrexate (increased risk of toxicity). * Ciclosporin: increased toxicity. * Cisplatin: risk of toxicity, particularly pulmonary. * Dexamethasone: increased risk of haematological toxicity. Doxycycline: increased risk of methotrexate toxicity. * Hydrocortisone: increased risk of haematological toxicity. * Ibuprofen: excretion of methotrexate reduced (increased risk of toxicity). * Nitrous oxide: increased antifolate effect (avoid concomitant use). Omeprazole: increased risk of methotrexate toxicity. Phenoxymethylpenicillin: reduced excretion of methotrexate (increased risk of toxicity). Phenytoin: reduced absorption of phenytoin; antifolate effect of methotrexate increased. * Prednisolone: increased risk of haematological toxicity. * Pyrimethamine: antifolate effect of methotrexate increased. Silver sulfadiazine: increased risk of methotrexate toxicity. Sulfadiazine: risk of methotrexate toxicity increased. * Sulfadoxine + pyrimethamine: antifolate effect of methotrexate increased; risk of methotrexate toxicity increased. WHO Model Formulary for Children 2010 269

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Antineoplastic, immunosuppressives and medicines used in palliative care

* Sulfamethoxazole + trimethoprim: antifolate effect of methotrexate increased (avoid concomitant use); risk of methotrexate toxicity increased. * Trimethoprim: antifolate effect of methotrexate increased (avoid concomitant use). Vaccines, live: avoid use of live vaccines with methotrexate (impairment of immune response). * Warfarin: increased risk for elevated INR and subsequent bleeding. Notes: High-dose methotrexate may cause precipitation of methotrexate or its metabolites in renal tubules. A high fluid throughput and alkalinization of urine, using sodium hydrogen carbonate if necessary, is recommended. Patients or their carers should be advised to report any feature of blood disorders (e.g. sore throat, bruising and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort and dark urine) and respiratory toxicity (e.g. dry cough, shortness of breath). Advise patients to avoid sunlight; wear protective clothing, wide-brimmed hats, sunglasses and lip sunscreen. Calcium folinate rescue is required for high-dose methotrexate doses; refer to specialist protocols.
References:
Ashley C, Currie A, eds. The renal drug handbook. 3rd ed. Oxford, Radcliffe Publishing, 2009. Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009. Rossi S, ed. Australian medicines handbook. Adelaide, Australian Medicines Handbook, 2009. Solimando DA Jr., ed. Lexi-Comp’s drug information handbook for oncology. 4th ed. Hudson, Lexi-Comp, 2004.

Procarbazine
ATC code: L01XB01

Capsule: 50 mg (as hydrochloride) Handle as a cytotoxic.
Indications: Hodgkin disease, gliomas, non-Hodgkin lymphoma. Contraindications: Pregnancy; breastfeeding. Precautions: Renal or hepatic impairment; may potentiate CNS depression if used with other

sedating drugs.

Dose:

Consult specialist treatment protocols.
Renal impairment: Severe: avoid. Hepatic impairment: Severe: avoid. Adverse effects: Common Myelosuppression (see below), anorexia, neurotoxicity (e.g. somnolence,

depression, confusion, headache, sleep disturbances, dizziness, hallucinations, ataxia, peripheral neuropathy), nausea, vomiting, infertility (see below). Uncommon or rare Diarrhoea, oral mucositis, alopecia, skin reactions (e.g. rash, itch, hyperpigmentation), pulmonary fibrosis, pneumonitis, haemolysis, hepatic dysfunction, fever, myalgia, arthralgia, nystagmus, diplopia, orthostatic hypotension, tachycardia, secondary malignancies (see below).

MyeLOSUPPReSSION Neutrophil and platelet nadirs occur about 28 days after a dose; recovery takes about 2 weeks. Anaemia is less common. INFeRTILITy Gonadal suppression resulting in amenorrhoea or azoospermia may not be reversible and is related to dose and duration of treatment. Consider measures to preserve fertility (even when used as an immunosuppressant).

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Interactions with other medicines (* indicates severe): Amitriptyline: risk of serotonin syndrome (hypertensive crisis. Lexi-Comp’s drug information handbook for oncology. Solid tumours have also been reported including ovarian. Pediatric dosage handbook. Indications: Disseminated Hodgkin and non-Hodgkin lymphomas. Hodding JH. Oxford. vesicant. Handle as a cytotoxic. tremor. Paediatric Formulary Committee. tremor. Tricyclic antidepressants (TCAs): risk of serotonin syndrome (hypertensive crisis. Opioids: additive CNS depression. 2004. Selective serotonin reuptake inhibitors (SSRIs): risk of serotonin syndrome (hypertensive crisis. 3rd ed.8. References: Ashley C. excitation. Myelodysplastic syndrome.2 Cytotoxic medicines SeCONDARy MALIGNANCIeS All alkylating agents. which is usually fatal. excitation. cardiac palpitations. The renal drug handbook. WHO Model Formulary for Children 2010 271 . a precursor of acute leukaemia. Rossi S. British national formulary for children 2009. excitation. angina). Contraindications: Pregnancy. liver impairment. 4th ed. For intravenous administration only. cardiac palpitations. Australian Medicines Handbook. tremor. ed. Precautions: Recent exposure to radiotherapy. have been associated with secondary malignancies. Notes: Procarbazine is a weak monoamine oxidase inhibitor. excitation. coffee. pre-existing neurotoxicity. palliative treatment of Kaposi sarcoma. Taketomo CK. and acute myeloid leukaemia have been reported. some references suggest dietary restrictions limiting foods with a high tyramine content such as cheese. avoid extravasation (see Adverse effects). advanced testicular carcinoma. Hudson. Vaccines. cola drinks. ed. Kouimtzi M. Geneva. Epinephrine: risk of serotonin syndrome (hypertensive crisis. live: avoid use of live vaccines with procarbazine (impairment of immune response). 16th ed. Vinblastine ATC code: L01CA01 Powder for injection: 10 mg (sulfate) in vial IMPORTANT Intrathecal injection is contraindicated. Currie A. and particularly combinations of alkylating agents. trophoblastic tumours. Lexi-Comp. Ethanol: disulfiram-like reaction. Median time to development of acute leukaemia is 3–4 years after chemotherapy. Solimando DA Jr. excitation. bladder and gastric cancers. eds.. London. Lexi-Comp. Hill SR. pre-existing pulmonary disease. World Health Organization. Kraus DM. 2009. cardiac palpitations. tremor. BMJ Group RBS Publishing. angina). Phenytoin: reduced absorption of phenytoin. Fluoxetine: risk of serotonin syndrome (hypertensive crisis. angina). angina). Phenobarbital: increases cytotoxic activity and CNS depression. wine and bananas. 2008. angina). cardiac palpitations. cardiac palpitations. eds. Inadvertent intrathecal injection causes severe neurotoxicity. Australian medicines handbook. breastfeeding. Radcliffe Publishing. 2009. tea. Stuart MC. Adelaide. 2009. WHO model formulary. 2009. tremor. Hudson.

Rossi S. 2009. WHO model formulary. vomiting. attempt to aspirate residual drug and start extravasation treatment according to local protocol. sloughing and necrosis. 272 WHO Model Formulary for Children 2010 . References: Hill SR. Australian medicines handbook. Vaccines. neurotoxicity (see below). paralytic ileus. Uncommon Gastrointestinal bleeding. Related to both cumulative and individual doses. Solimando DA Jr. NeUROTOXICITy Less severe with vinblastine than other vinca alkaloids. Other adverse effects related to neurotoxicity may include malaise. weakness. urinary retention. Thrombocytopenia and anaemia are less frequent. paraesthesia. cortical blindness. headache. Taketomo CK. Lexi-Comp. alopecia. Lexi-Comp’s drug information handbook for oncology. Phenytoin: possibly reduced absorption of phenytoin. Interactions with other medicines (* indicates severe): * Bleomycin: increased risk of cardiovascular toxicity. Vestibular and auditory nerve damage may result in dizziness. Paediatric Formulary Committee. MyeLOSUPPReSSION Common and major dose-limiting effect for vinblastine. Hudson. 16th ed. 2004.g. Rare Acute shortness of breath and bronchospasm (may be progressive). stop infusion/injection immediately. administration by any other route may be fatal”. muscle pain. eXTRAVASATION extravasation may cause cellulitis. London. paralysis) and autonomic neuropathy (e. Australian Medicines Handbook. Geneva. orthostatic hypotension). Itraconazole: increased risk of neurotoxicity and paralytic ileus. Injections should be dispensed with the label “For intravenous use only. Hudson. 2008. depression. ataxia. hoarseness. Includes peripheral neuropathy (e.g. If extravasation is suspected. constipation. nystagmus. Renal impairment: Dose reduction not necessary. Kouimtzi M. Adelaide.8 Antineoplastic. Voriconazole: increased plasma concentration and toxicity of vinblastine. jaw pain. Lexi-Comp. abdominal pain. live: avoid use of live vaccines with vinblastine (impairment of immune response). constipation. Vinblastine vials should be stored under refrigeration and protected from light. Kraus DM. vertigo or deafness (may be temporary or permanent). * Erythromycin: increased toxicity of vinblastine (avoid concomitant use). 2009. Injections of vinblastine should not be in the same room when any intrathecal medication is to be administered. Notes: For children over 10 years. Pediatric dosage handbook. Hepatic impairment: Dose reduction may be necessary. seizures. ed. World Health Organization. Reduce according to bilirubin concentration. immunosuppressives and medicines used in palliative care Dose: Consult specialist treatment protocols.. 2009. ed. Mainly affects neutrophils with the nadir occurring about 5–10 days after a dose and recovery after a further 7–14 days. Hodding JH. Motor function impairment may occur if severe. Stuart MC. nausea. oral mucositis. 4th ed. syndrome of inappropriate antidiuretic hormone secretion (SIADH). paralytic ileus. British national formulary for children 2009. loss of deep tendon reflexes. dilute to at least 20 ml to avoid inadvertent intrathecal use. eds. Adverse effects: Common Myelosuppression (see below). myocardial infarction. BMJ Group RBS Publishing. abdominal pain.

headache. to minimize the risk of accidental intrathecal administration of vincristine. paralytic ileus. Many centres do not give vincristine and intrathecal medication on the same day. Voriconazole: increased plasma vincristine and risk of toxicity. Special Notes: Also known by the brand name Oncovin. Itraconazole: increased plasma vincristine and risk of toxicity. demyelinating Charcot-Marie-Tooth syndrome. Renal impairment: Dose reduction not necessary. 5 mg (sulfate) in vial IMPORTANT Intrathecal injection is contraindicated. Give prophylactic therapy for constipation (e. Contraindications: Pregnancy. seizures. paralytic ileus. nystagmus. alopecia. attempt to aspirate residual drug and start extravasation treatment according to local protocol. constipation. For intravenous administration only.g. Vaccines. Injections should be dispensed with the label “For intravenous use only.g. Inadvertent intrathecal injection causes severe neurotoxicity. vomiting. chest pain. If extravasation is suspected. convulsions. Notes: For children over 10 years. Rare Nausea. related to both cumulative and individual doses. Precautions: Use with caution in patients with hepatic impairment. acute shortness of breath and bronchospasm (may be progressive). Dose: Consult specialist treatment protocols. which is usually fatal. constipation. WHO Model Formulary for Children 2010 273 . Interactions with other medicines (* indicates severe): Asparaginase: may decrease vincristine clearance. Injections of vincristine should not be in the same room when any intrathecal medication is to be administered. sloughing and necrosis. myelosuppression. ataxia. urinary retention. Nifedipine: possibly reduced metabolism of vincristine. vertigo or deafness (may be temporary or permanent). syndrome of inappropriate antidiuretic hormone secretion (SIADH). Administration by any other route may be fatal”. NeUROTOXICITy Common and major dose-limiting effect for vincristine. Hepatic impairment: Dose reduction may be necessary. orthostatic hypotension). Phenytoin: possibly reduced absorption of phenytoin. depression. avoid extravasation. Motor function impairment may occur if severe. jaw pain.8. Indications: Acute leukaemias. abdominal pain. loss of deep tendon reflexes. hoarseness. * Warfarin: increased INR and risk of subsequent bleeding. paraesthesia. eXTRAVASATION extravasation may cause cellulitis. neurotoxicity (see below). dilute to at least 20 ml to avoid inadvertent intrathecal use. lymphomas and paediatric solid tumours. breastfeeding. docusate with senna).2 Cytotoxic medicines Vincristine ATC code: L01CA02 Powder for injection: 1 mg. cortical blindness. Other adverse effects related to neurotoxicity may include malaise. anaphylaxis. Adverse effects: Common Oral mucositis. paralysis) and autonomic neuropathy (e. Includes peripheral neuropathy (e. weakness. stop infusion/injection immediately.g. live: avoid use of live vaccines with vincristine (impairment of immune response). Vestibular and auditory nerve damage may result in dizziness. Handle as a cytotoxic.

The renal drug handbook. Lexi-Comp. eds. Geneva. patients may be more susceptible to infections. CNS effects ranging from euphoria to psychosis may occur. pre.8 Antineoplastic. Hill SR. Kraus DM. Precautions: Abrupt withdrawal (see below). administration of live virus vaccines. oedema. particularly haematological malignancies. Consult local protocols. However. Hodding JH. hypertension. skin atrophy. Kouimtzi M. Taketomo CK. delayed wound healing. Renal impairment: Dose reduction not necessary. avoid exposure to measles (normal immunoglobulin possibly required if exposed). 2009. chronic use of steroids is associated with a range of side-effects which are covered in more detail in section 18. dyslipidaemia. World Health Organization.3 Hormones and antihormones The corticosteroids prednisolone. Indications: Used with antineoplastic drugs for acute lymphoblastic leukaemias. Acute myopathy may occur with high doses.. increased susceptibility to and severity of infection. dyspepsia. sodium and water retention.1. avoid exposure to chickenpox and measles. osteoporosis. eds. British national formulary for children 2009. Pediatric dosage handbook. Hudson. Currie A. immunosuppressives and medicines used in palliative care References: Ashley C. 2004. London. Stuart MC. Short high- dose courses cause fewer adverse effects than prolonged courses of lower doses. Common Adrenal suppression. hypokalaemia. 3rd ed. Dose: See specialist treatment protocols. hyperglycaemia. Corticosteroids may activate latent opportunistic infections or exacerbate systemic fungal infections. especially in younger children or those on high doses for prolonged periods. diabetes mellitus. Adverse effects: Incidence of adverse effects is related to dose and duration of treatment. 16th ed. Paediatric Formulary Committee. Lexi-Comp. amoebiasis. for inflammatory or allergic reactions including those to other antineoplastic drugs. Contraindications: Untreated systemic infection (unless condition life threatening). 274 WHO Model Formulary for Children 2010 . Hodgkin disease and non-Hodgkin lymphomas. dexamethasone and hydrocortisone are synthetic hormones which may be given at pharmacological doses for certain malignancies. masking of signs of infection. elevated intraocular pressure may occur (especially with prolonged use). increased appetite. ABRUPT WITHDRAWAL Dexamethasone may cause suppression of hypothalamic-pituitary-adrenal (HPA) axis. dose reduction not necessary. Hepatic impairment: Metabolized by the liver but also by other tissues. Radcliffe Publishing.2). Lexi-Comp’s drug information handbook for oncology. fractures. 2008. 4th ed. Oxford. hypertension. Dexamethasone ATC code: H02AB02 Oral liquid: 0. increased susceptibility to infection. 8. Solimando DA Jr. BMJ Group RBS Publishing. WHO model formulary. Withdrawal and discontinuation of dexamethasone should be done slowly and carefully. strongyloidiasis. 2009. activation or exacerbation of tuberculosis. ed. Hudson. risk of severe chickenpox in non-immune patient (varicella zoster immunoglobulin required if exposed to chickenpox).and post-chemotherapy as an antiemetic (see Section 17. peptic ulcer.4 mg/ml Injection: 4 mg dexamethasone phosphate (as disodium salt) in 1 ml ampoule Immunosuppression may occur. 2009.

Albendazole: plasma albendazole concentration possibly increased. sleep and behaviour. Hydrochlorothiazide: antagonism of diuretic effect. Propranolol: antagonism of hypotensive effect. Ritonavir: plasma concentration possibly increased by ritonavir. acne. Calcium salts: reduced absorption of calcium salts. Vaccine. psychiatric effects (see below). Metformin: antagonism of hypoglycaemic effect. Delirium or psychosis are less common. * Phenobarbital: metabolism of dexamethasone accelerated (reduced effect). * Phenytoin: metabolism of dexamethasone accelerated (reduced effect). posterior subcapsular cataracts. WHO Model Formulary for Children 2010 275 . growth retardation in children. PSyCHIATRIC eFFeCTS Include euphoria. increased risk of hypokalaemia. Spironolactone: antagonism of diuretic effect. Uncommon Osteonecrosis. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. Enalapril: antagonism of hypotensive effect.3 Hormones and antihormones bruising. fluid and electrolyte balance and blood glucose concentration throughout treatment in order to detect serious side-effects early. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose dexamethasone enhances anticoagulant effect). Contraceptives. Insulins: antagonism of hypoglycaemic effect. influenza: high doses of dexamethasone impair immune response. blood pressure. dexamethasone reduces plasma salicylate concentration. * Lopinavir: possibly reduced plasma lopinavir concentration. amenorrhoea. myopathy. Rare Peptic ulceration. oral: oral contraceptives containing estrogens increase plasma concentration of dexamethasone. muscle weakness and wasting. Notes: Monitor body weight. disturbances of mood. fat redistribution (producing cushingoid appearance). Erythromycin: erythromycin possibly inhibits metabolism of dexamethasone. Digoxin: increased risk of hypokalaemia. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with dexamethasone. Vaccine. Interactions with other medicines (* indicates severe): Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. depression. weight gain. * Rifampicin: accelerated metabolism of dexamethasone (reduced effect). increased risk of hypokalaemia. Praziquantel: plasma praziquantel concentration reduced. hypomania. * Carbamazepine: accelerated metabolism of dexamethasone (reduced effect). glaucoma. Saquinavir: possibly reduced plasma saquinavir concentration. hirsutism. cognition. particularly of the femoral and humeral heads. * Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions).8. * Methotrexate: increased risk of haematological toxicity. live: high doses of dexamethasone impair immune response. avoid use of live vaccines. Furosemide: antagonism of diuretic effect. hypersensitivity reactions.

Pediatric dosage handbook. hypersensitivity reactions. hyperglycaemia. Indications: Synthetic hormone used as an adjuvant in treatment of malignancy. May cause osteoporosis (at any age) or inhibition of bone growth in paediatric patients. eds. muscle weakness and wasting. Australian medicines handbook. Kouimtzi M. reduced bone mineral density. World Health Organization. 2009. hypertension. delayed wound healing. depression. avoid exposure to chicken pox and measles. 2009. patients may be more susceptible to infections. Adelaide. suppression of linear growth (i. reduction of growth velocity). amenorrhoea. BMJ Group RBS Publishing. cirrhosis. adrenal suppression. hypomania. acne. 2008.g. myasthenia gravis. dyspepsia. Adverse effects: The incidence of adverse effects is related to dose and duration of treatment. increased appetite. Corticosteroids may activate latent opportunistic infections or exacerbate systemic fungal infections. Immunosuppression may occur. Uncommon Osteonecrosis. Hudson. use with caution in patients with thyroid dysfunction. Precautions: Avoid using higher than recommended doses. Delirium or psychosis are less common. Stuart MC. weight gain. 276 WHO Model Formulary for Children 2010 . ed. myopathy. Renal impairment: Dose reduction not necessary. during and after unusual stress (e. London. immunosuppressives and medicines used in palliative care References: Hill SR. Kraus DM. Taketomo CK. acute adrenal insufficiency (adrenal crisis) may occur with abrupt withdrawal after long-term therapy or with stress. withdrawal and discontinuation of steroids should be done carefully. oedema. suppression of HPA function. diabetes. increased appetite. British national formulary for children 2009.e. bruising. Short high-dose courses cause fewer adverse effects than prolonged courses of lower doses. Rossi S. Dose: See specialist treatment protocols. administration of live virus vaccines. psychiatric effects (see below). disturbances of mood. Australian Medicines Handbook. surgery). glaucoma. Hodding JH. glaucoma.8 Antineoplastic. hirsutism. masking of signs of infection. posterior subcapsular cataracts. fractures. patients with HPA axis suppression may require doses of systemic glucocorticosteroids prior to. Lexi-Comp. Contraindications: Untreated systemic infection (unless condition life threatening). Paediatric Formulary Committee. PSyCHIATRIC eFFeCTS Include euphoria. osteoporosis. Common Nausea. particularly of the femoral and humeral heads. sleep and behaviour. dyslipidaemia. increased susceptibility to infection. hypertension. growth retardation in children. fat redistribution (producing cushingoid appearance). sodium and water retention. WHO model formulary. Rare Peptic ulceration. nonspecific ulcerative colitis. hypercorticism (Cushing syndrome). hyperglycaemia or glycosuria may occur. Hepatic impairment: Dose reduction not needed. skin atrophy. hypokalaemia. elevated intraocular pressure may occur (especially with prolonged use). 2009. and CNS effects (ranging from euphoria to psychosis) may occur. Hydrocortisone ATC code: H02AB09 Powder for injection: 100 mg (as sodium succinate) in vial Hypothalamic-pituitary-adrenal (HPA) suppression may occur. titrate to lowest effective dose. cognition. 16th ed. Acute myopathy may occur with high doses. Use with extreme caution in patients with respiratory tuberculosis or ocular herpes simplex. Geneva.

increased risk of hypokalaemia. Kouimtzi M. * Phenytoin: metabolism of hydrocortisone accelerated (reduced effect). avoid use of live vaccines. Digoxin: increased risk of hypokalaemia. eds. fluid and electrolyte balance. Geneva. Ritonavir: plasma concentration possibly increased by ritonavir. Taketomo CK. Rossi S. and blood glucose concentration throughout treatment in order to detect serious side-effects early. Adelaide. Notes: Monitor body weight. Stuart MC. WHO model formulary. ed. Australian Medicines Handbook. Insulins: antagonism of hypoglycaemic effect. 16th ed. Pediatric dosage handbook. Paediatric Formulary Committee. World Health Organization. 2009. Hydrochlorothiazide: antagonism of diuretic effect. 2008. increased risk of hypokalaemia. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration.8.3 Interactions with other medicines (* indicates severe): Hormones and antihormones Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. blood pressure. Furosemide: antagonism of diuretic effect. 2009. * Rifampicin: accelerated metabolism of hydrocortisone (reduced effect). Hudson. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose hydrocortisone enhances anticoagulant effect). Lexi-Comp. Vaccine. * Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions). * Methotrexate: increased risk of haematological toxicity. live: high doses of hydrocortisone impair immune response. influenza: high doses of hydrocortisone impair immune response. References: Hill SR. Kraus DM. * Vaccines. 2009. Spironolactone: antagonism of diuretic effect. Erythromycin: erythromycin possibly inhibits metabolism of hydrocortisone. Australian medicines handbook. hydrocortisone reduces plasma salicylate concentration. British national formulary for children 2009. WHO Model Formulary for Children 2010 277 . * Carbamazepine: accelerated metabolism of hydrocortisone. * Phenobarbital: metabolism of hydrocortisone accelerated (reduced effect). Enalapril: antagonism of hypotensive effect. Propranolol: antagonism of hypotensive effect. London. Metformin: antagonism of hypoglycaemic effect. Hodding JH. BMJ Group RBS Publishing. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with hydrocortisone.

Precautions: Avoid using higher than recommended doses. 278 WHO Model Formulary for Children 2010 . bruising. Uncommon Osteonecrosis. Hepatic impairment: Adverse effects more common. delayed wound healing. hyperglycaemia. dyslipidaemia. patients with HPA axis suppression may require doses of systemic glucocorticosteroids prior to. Common Adrenal suppression. then 10–20 mg daily. muscle weakness and wasting. Use with extreme caution in patients with respiratory tuberculosis or ocular herpes simplex. growth retardation in children. then 5–10 mg daily. Short high- dose courses cause fewer adverse effects than prolonged courses of lower doses. osteoporosis. glaucoma. Contraindications: Untreated systemic infection (unless condition life threatening). 2–7 years initially up to 50 mg. disturbances of mood. diabetes. Rare Peptic ulceration. fractures. Dose: Oral: Child less than 1 year initially up to 25 mg. psychiatric effects (see below). 25 mg Oral liquid: 5 mg/ml Hypothalamic-pituitary-adrenal (HPA) suppression may occur. Renal impairment: Dose reduction not needed. 8–12 years initially up to 75 mg. Hodgkin disease and non-Hodgkin lymphomas. titrate to lowest effective dose. acute adrenal insufficiency (adrenal crisis) may occur with abrupt withdrawal after long-term therapy or with stress. sodium and water retention. dyspepsia. hypertension. hypokalaemia. increased susceptibility to infection. hypomania.g. The above doses are only a guide and should only be used as part of a treatment protocol which includes other antineoplastic drugs and under specialist advice. fat redistribution (producing cushingoid appearance). myopathy. use with caution in patients with thyroid dysfunction. increased appetite. May cause osteoporosis (at any age) or inhibition of bone growth in paediatric patients. Adverse effects: Incidence of adverse effects is related to dose and duration of treatment. sleep and behaviour. hypersensitivity reactions. posterior subcapsular cataracts. withdrawal and discontinuation of steroids should be done carefully. cognition. suppression of HPA function.e. reduced bone mineral density. Delirium or psychosis are less common. patients may be more susceptible to infections. Corticosteroids may activate latent opportunistic infections or exacerbate systemic fungal infections. masking of signs of infection. administration of live virus vaccines. Immunosuppression may occur.8 Antineoplastic. during and after unusual stress (e. hypercorticism (Cushing syndrome). particularly of the femoral and humeral heads. oedema. Acute myopathy may occur with high doses. hirsutism. amenorrhoea. cirrhosis. surgery). PSyCHIATRIC eFFeCTS Include euphoria. then 15–30 mg daily. hyperglycaemia or glycosuria may occur. avoid exposure to chickenpox and measles. skin atrophy. depression. reduction of growth velocity). immunosuppressives and medicines used in palliative care Prednisolone ATC code: H02AB06 Tablet: 5 mg. elevated intraocular pressure may occur (especially with prolonged use) and CNS effects (ranging from euphoria to psychosis) may occur. glaucoma. Indications: In conjunction with antineoplastic drugs for acute lymphoblastic and chronic lymphocytic leukaemias. non-specific ulcerative colitis. weight gain. acne. myasthenia gravis. hypertension. suppression of linear growth (i.

Enalapril: antagonism of hypotensive effect. Ritonavir: plasma concentration possibly increased by ritonavir. Hydrochlorothiazide: antagonism of diuretic effect. antagonism of diuretic effect. * Phenytoin: metabolism of prednisolone accelerated (reduced effect). eds. increased risk of hypokalaemia. increased risk of hypokalaemia. * Phenobarbital: metabolism of prednisolone accelerated (reduced effect). London. eds. Calcium salts: reduced absorption of calcium salts. * Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless prednisolone needed to control reactions). WHO Model Formulary for Children 2010 279 . References: Ashley C. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose prednisolone enhances anticoagulant effect). Hudson. 2009. Australian Medicines Handbook. Hill SR. Notes: Monitor body weight. Hodding JH. Kouimtzi M. Spironolactone: antagonism of diuretic effect. WHO model formulary. Oxford. Paediatric Formulary Committee. The renal drug handbook. Rossi S. Atenolol: antagonism of hypotensive effect. Insulins: antagonism of hypoglycaemic effect. * Carbamazepine: accelerated metabolism of prednisolone (reduced effect). Erythromycin: erythromycin possibly inhibits metabolism of prednisolone. 2009. Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. Adelaide. * Rifampicin: accelerated metabolism of prednisolone (reduced effect). live: high doses of prednisolone impair immune response. Contraceptives. Radcliffe Publishing. Digoxin: increased risk of hypokalaemia. 16th ed. Taketomo CK. influenza: high doses of prednisolone impair immune response. Lexi-Comp. Metformin: antagonism of hypoglycaemic effect. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. Kraus DM. avoid use of live vaccines. * Methotrexate: increased risk of haematological toxicity. Vaccine. * Vaccine. Furosemide: antagonism of diuretic effect. Geneva. and blood glucose concentration throughout treatment in order to detect serious side-effects early. Propranolol: antagonism of hypotensive effect. 2009.8. 3rd ed.3 Interactions with other medicines (* indicates severe): Hormones and antihormones Acetazolamide: increased risk of hypokalaemia. BMJ Group RBS Publishing. blood pressure. Australian medicines handbook. ed. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with prednisolone. prednisolone reduces plasma salicylate concentration. World Health Organization. fluid and electrolyte balance. Stuart MC. Ciclosporin: increased plasma concentration of prednisolone. Currie A. British national formulary for children 2009. 2008. 2009. Pediatric dosage handbook. oral: oral contraceptives containing estrogens increase plasma concentration of prednisolone.

Oral: Child 2–12 years initially 200–500 micrograms/kg (maximum 25 mg) once daily at night. Systematic evidence for the safety and efficacy of these medicines in paediatric populations is often lacking. psychoses or depression (may aggravate psychotic or depressive symptoms). manic phase in bipolar disorders. taste disturbances. movement disorders and dyskinesias. hypomania or mania. anaesthesia (increased risk of arrhythmias and hypotension). Contraindications: Recent myocardial infarction. dry mouth. history of mania. breathlessness. hepatic impairment. sweating. phaeochromocytoma. recommendations have been based on current best available evidence which may be extrapolated from adult studies or. cardiovascular adverse effects particularly with high dosage including eCG changes. gynaecomastia and galactorrhoea. Globally. tremor. syncope. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. thyroid disease. for 24 hours. based on expert opinion. depression. A range of medications may be used to treat these symptom clusters. tinnitus. angle closure glaucoma. Hepatic impairment: Sedative effects increased (avoid in severe liver disease}.8 Antineoplastic. avoid abrupt withdrawal. difficulty in micturition. interference with sexual function. arrhythmias (especially heart block). nausea and vomiting. endocrine adverse effects such as testicular enlargement. rash and hypersensitivity reactions (urticaria. WHO Model Formulary for Children 2010 Uncommon Behavioural disturbances. concurrent electroconvulsive therapy. porphyria. immunosuppressives and medicines used in palliative care 8. increased appetite and weight gain (occasional weight loss).4 Medicines used in palliative care Access to appropriate medicines is needed to ensure adequate management of the most prevalent and distressing symptoms in children with life-threatening and life-limiting conditions. fever. increased intraocular pressure). In the absence of randomized controlled trials in paediatric populations. blood sugar changes. delirium and agitation. paraesthesia. increased if necessary to a maximum of 1 mg/kg twice daily. for example riding a bike or operating machinery. dysarthria. constipation. postural hypotension. arrhythmias. Renal impairment: Dose reduction not necessary. tachycardia. Adverse effects: Common Sedation. blurred vision (disturbance of accommodation. photosensitivity). abnormal liver function tests. severe liver disease. Amitriptyline ATC code: N06AA09 Tablet: 10 mg. 280 . constipation. malignancy and HIV/AIDS have been identified as the most common causes of childhood mortality requiring palliative care. Precautions: History of epilepsy. nausea. the 10 most frequent symptoms or symptom clusters requiring pharmacological management for palliative care include fatigue and weakness. in some instances. Dose: Neuropathic pain. history of urinary retention. confusion or delirium. anorexia and weight loss. 25 mg Indications: Neuropathic pain in palliative care. Based on available data. pain. headache. excess respiratory tract secretions and anxiety.

In overdose (high rate of fatality). * Epinephrine: increased risk of hypertension and arrhythmias (but local anaesthetics with epinephrine appear to be safe). seizures. * Warfarin: enhanced or reduced anticoagulant effect. severe symptoms including unconsciousness. Spironolactone: increased risk of postural hypotension. purpura and * Alcohol: enhanced sedative effect. hepatitis. * Ritonavir: plasma concentration possibly increased by ritonavir. eosinophilia. Atropine: increased antimuscarinic adverse effects. Morphine: possibly increased sedation. * Valproic acid: antagonism of anticonvulsant effect (convulsive threshold lowered). * Ethosuximide: antagonism of anticonvulsant effect (convulsive threshold lowered). paralytic ileus. * Atemether + lumefantrine: manufacturer of artemether with lumefantrine advises to avoid concomitant use.8. * Carbamazepine: antagonism of anticonvulsant effect (convulsive threshold lowered). possibly increased risk of ventricular arrhythmias. syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) with hyponatraemia. acidosis. possibly reduced plasma amitriptyline concentration. prolonged QT interval. Ketamine: increased risk of arrhythmias and hypotension. Chlorphenamine: increased antimuscarinic and sedative effects. Levothyroxine: enhanced effects of amitriptyline. Hydrochlorothiazide: increased risk of postural hypotension. hyper-reflexia. hypotension. * Chlorpromazine: increased risk of antimuscarinic adverse effects. Diazepam: enhanced sedative effect. possibly increased risk of ventricular arrhythmias. Halothane: increased risk of arrhythmias and hypotension. * Phenytoin: antagonism of anticonvulsant effect (convulsive threshold lowered). reduced antidepressant effect). possibly increased risk of ventricular arrhythmias. leukopenia. Interactions with other medicines (* indicates severe): Rare Blood dyscrasias including agranulocytosis. Nitrous oxide: increased risk of arrhythmias and hypotension. Codeine: possibly increased sedation. * Phenobarbital: antagonism of anticonvulsant effect (convulsive threshold lowered). myoclonus. increased plasma amitriptyline concentration. Haloperidol: increased amitriptyline concentration.4 Medicines used in palliative care thrombocytopenia. oral: antagonism of antidepressant effect by estrogens but adverse effects of amitriptyline possibly increased due to increased plasma concentration of amitriptyline. restlessness. increased plasma amitriptyline concentration. Contraceptives. Thiopental: increased risk of arrhythmias and hypotension. metabolism of amitriptyline possibly accelerated (reduced plasma concentration). convulsions. WHO Model Formulary for Children 2010 281 . Furosemide: increased risk of postural hypotension. Rifampicin: plasma concentration of amitriptyline possibly reduced. * Fluphenazine: increased risk of antimuscarinic adverse effects. marked anticholinergic effects. excitement. accelerated metabolism of amitriptyline (reduced plasma concentration. Isoniazid: increased plasma concentration of isoniazid. respiratory and cardiac depression with arrhythmias.

mean arterial pressure and pulmonary wedge pressure). Hudson. apnoea. Kouimtzi M. rash. blurred vision. constipation. Rare Cholestatic jaundice has occurred in association with cyclizine. have been reported in association with cyclizine. hepatic dysfunction and agranulocytosis.5–1 mg/kg up to three times daily.8 Antineoplastic. extrapyramidal motor disturbances. restlessness. severe heart failure (cyclizine may cause a fall in cardiac output associated with increases in heart rate. Cyclizine ATC code: R06Ae03 Injection: 50 mg/ml Tablet: 50 mg Indications: Nausea and vomiting in palliative care including after radiotherapy or chemotherapy. Stuart MC. London. Radcliffe Publishing. twitching. anaesthetics. Pediatric dosage handbook. muscle spasms. World Health Organization. Pethidine: cyclizine enhances the soporific effect of pethidine. Renal impairment: Dose reduction not necessary. Oxford. 6–12 years 75 mg over 24 hours. Kraus DM. Dose: Oral or IV injection: Infant or Child 1 month–6 years 0. BMJ Group RBS Publishing. generalized chorea. decreased consciousness. hypnotics. 282 WHO Model Formulary for Children 2010 . the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. eds. Adverse effects: Common Urticaria. seizures. particularly when dosage recommendations have been exceeded. Hodding JH. disorientation. tremor. 2008. hypersensitivity hepatitis. The renal drug handbook. drowsiness. Currie A. transient speech disorders. dyskinesia. cyclizine may enhance the sideeffects of other anticholinergic drugs. dryness of the mouth. Interactions with other medicines (* indicates severe): Alcohol: cyclizine may have additive effects with alcohol and other central nervous system depressants. porphyria. angioedema. eds. 2009. headache. Patients with rare hereditary problems of galactose intolerance. 2009. British national formulary for children 2009. hypertension and paraesthesia. Paediatric Formulary Committee. 3rd ed. urinary retention. glaucoma. Other central nervous system effects include dystonia. insomnia and auditory and visual hallucinations have been reported. tachycardia. There have also been a few reports of fixed drug eruption. Geneva.g. Continuous intravenous or subcutaneous infusion: Child 1 month–2 years 3 mg/kg over 24 hours. allergic skin reactions and bronchospasm. Anticholinergic drugs: because of its anticholinergic activity. e. Taketomo CK. maximum single dose 25 mg. WHO model formulary. 2–5 years 50 mg over 24 hours. 6–12 years 25 mg up to three times daily. obstructive disease of the gastrointestinal tract. 16th ed. Lexi-Comp. hepatic disease. Hepatic impairment: Causes sedation in liver impairment (avoid). Rare reports of cholestatic hepatitis and hypersensitivity reactions. Precautions: May counteract haemodynamic effects of opioids. tranquillizers. immunosuppressives and medicines used in palliative care References: Ashley C. Hill SR. dizziness. nose and throat. 2009. including anaphylaxis. nervousness. epilepsy.

malaise. Oral. Common Nausea. then decrease by 1 mg daily. There have been reports of abuse of cyclizine.aspx?documentId=14783. over 35 kg initially 25 mg then 4 mg every 2 hours for 3 days. sodium and water retention. hyperglycaemia. hypertension. then 4 mg every 4 hours for 1 day. oedema. risk of severe chickenpox in non-immune patient (varicella zoster immunoglobulin required if exposed to chickenpox). increased appetite. for its euphoric or hallucinatory effects. accessed 10 February 2010). delayed wound healing. Dose: Life-threatening cerebral oedema. fat redistribution (producing cushingoid appearance). GlaxoSmithKline. masking of signs of infection. 2009. IM or IV: 1–2 mg/kg as a single dose. Adverse effects: Consider relevance of adverse effects in palliative care. since the antiemetic effect of cyclizine may increase the toxicity of alcohol. skin atrophy. hirsutism. fractures. bruising. London. perineal irritation after intravenous administration. avoid exposure to measles (normal immunoglobulin possibly required if exposed). References: Paediatric Formulary Committee.4 Medicines used in palliative care Notes: For administration by mouth. adrenal suppression. either oral or intravenous. Oral or IV: Child all ages 10 mg/m2 (maximum 20 mg) before chemotherapy. then 2 mg every 6 hours for 4 days.medicines. followed by a maintenance dose of 1–1. Renal impairment: Dose reduction not necessary. 2009 (http://emc. then 5 mg/m2 every 6 hours. dyspepsia. strongyloidiasis. hypokalaemia. IV: Child under 35 kg initially 20 mg then 4 mg every 3 hours for 3 days. Contraindications: Untreated systemic infection (unless cerebral oedema is life-threatening). British national formulary for children 2009. Hepatic impairment: Dose reduction not necessary. peptic ulcer. Nausea and vomiting (chemotherapy induced). growth retardation in children. amenorrhoea. then 4 mg every 6 hours for 1 day. increased susceptibility to infection. corneal perforation. hiccups. Valoid Product Information. Dexamethasone ATC code: H02AB02 Injection: 4 mg/ml Tablet: 2 mg Indications: Life-threatening cerebral oedema. amoebiasis. dexamethasone may be administered subcutaneously as either a bolus or via a syringe driver as an infusion. activation or exacerbation of tuberculosis.uk/document. then 4 mg every 6 hours for 4 days. BMJ Group RBS Publishing. NOTe If patients are unable to swallow tablets and the intravenous route is not suitable. hypertension. cerebral oedema and nausea and vomiting (chemotherapy induced). muscle weakness and wasting. Increased susceptibility to and severity of infection. then decrease by 2 mg daily. myopathy. Cerebral oedema. 283 WHO Model Formulary for Children 2010 . acne. The concomitant misuse of cyclizine with large amounts of alcohol is particularly dangerous. diabetes mellitus.5 mg/kg (maximum 16 mg) daily in four to six divided doses. osteoporosis. Direct intravenous injection may be given over 3–5 minutes.8. weight gain. Precautions: Consider the relevance of these listed precautions in palliative care. psychiatric effects (see below). dyslipidaemia.org. tablets may be crushed.

PSyCHIATRIC eFFeCTS Include euphoria. Delirium or psychosis is less common. Calcium salts: reduced absorption of calcium salts. posterior subcapsular cataracts. Notes: When used in a syringe driver with other medications. * Phenytoin: metabolism of dexamethasone accelerated (reduced effect). Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with dexamethasone. Erythromycin: erythromycin possibly inhibits metabolism of dexamethasone. * Lopinavir: possibly reduced plasma lopinavir concentration. cognition.8 Antineoplastic. avoid use of live vaccines. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose dexamethasone enhances anticoagulant effect). particularly of the femoral and humeral heads. Rare Peptic ulceration. Furosemide: antagonism of diuretic effect. Vaccine. When started for symptom control. sleep and behaviour. * Amphotericin B: increased risk of hypokalaemia. Insulins: antagonism of hypoglycaemic effect. particularly the order of addition. Saquinavir: possibly reduced plasma saquinavir concentration. Albendazole: plasma albendazole concentration possibly increased. Consult specialist references. increased risk of hypokalaemia. * Vaccine. cease treatment if no improvement seen after the first week. dexamethasone reduces plasma salicylate concentration. oral: oral contraceptives containing estrogens increase plasma concentration of dexamethasone. depression. increased risk of hypokalaemia. Enalapril: antagonism of hypotensive effect. Tablets can be dissolved in water prior to administration. Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. Metformin: antagonism of hypoglycaemic effect. glaucoma. Praziquantel: plasma praziquantel concentration reduced. * Phenobarbital: metabolism of dexamethasone accelerated (reduced effect). Contraceptives. live: high doses of dexamethasone impair immune response. Spironolactone: antagonism of diuretic effect. Interactions with other medicines (* indicates severe): Consider the relevance of the listed interactions in palliative care. hypersensitivity reactions including anaphylaxis. Digoxin: increased risk of hypokalaemia. to avoid precipitation. immunosuppressives and medicines used in palliative care Uncommon Osteonecrosis. 284 WHO Model Formulary for Children 2010 . influenza: high doses of dexamethasone impair immune response. Ritonavir: plasma concentration possibly increased by ritonavir. Hydrochlorothiazide: antagonism of diuretic effect. * Rifampicin: accelerated metabolism of dexamethasone (reduced effect). * Methotrexate: increased risk of haematological toxicity. disturbances of mood. special care is needed in preparation. Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. Propranolol: antagonism of hypotensive effect. hypomania. * Carbamazepine: accelerated metabolism of dexamethasone (reduced effect).

3 mg/kg/dose repeated 1–4 hourly as required to a maximum of 0. Royal Children’s Hospital. Precautions: Consider the relevance of these listed precautions in palliative care. Thomson Micromedex. Paediatric pharmacopoeia. 2008.4 mg/kg repeated once after 10 minutes if necessary. Adelaide. sleep apnoea. McDowell JM. 2005. 3rd ed.5 mg repeated once after 10 minutes if necessary. Prolonged intravenous infusion may lead to accumulation and delay recovery. ed. avoid prolonged use and abrupt withdrawal. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.thomsonhc. porphyria.1–0. 2010.5 mg. PR: Neonate 1. 2009. Martindale: the complete drug reference. Oral: Child all ages 0. Currie A. facilities for reversing respiratory depression with mechanical ventilation must be at hand (see below). World Health Organization.3–0.25–2.05–0.3 mg/kg/dose 8–12 hourly. 34th ed. Geneva. muscle spasm and anxiety. Radcliffe Publishing. when given intravenously. myasthenia gravis. IV: Child all ages 0. Oxford. 10 mg (can be made as an extemporaneous product in countries where a commercial product is not available) Tablet: 5 mg. accessed 10 February 2010). reduce dose in debilitated patients and in hepatic impairment (avoid if severe) and renal impairment. 13th ed.8. severe hepatic impairment. Infant or Child 1 month–2 years 5 mg repeated once after 10 minutes if necessary. Rossi S. Hill SR. ed. marked personality disorder. Klasco RK. Contraindications: Respiratory depression. 2002. The renal drug handbook. 2009. acute pulmonary insufficiency. Melbourne. Stuart MC. IV: Child all ages 0. (http://www. history of alcohol or drug abuse. ed. Dose: Seizures. 2–12 years 5–10 mg repeated once after 10 minutes if necessary. WHO model formulary. Greenwood Village. PReCAUTIONS FOR INTRAVeNOUS INFUSION Intravenous infusion of diazepam is potentially hazardous (especially if prolonged) calling for close and constant observation and it is best to be carried out in a specialist centre with intensive care facilities. 5 mg. London. Diazepam ATC code: N05BA01 Injection: 5 mg/ml Oral liquid: 0.4 mg/ml Rectal solution: 2. Australian medicines handbook. for example riding a bike or operating machinery. for 24 hours.com. Kouimtzi M. Muscle spasm and anxiety. Respiratory disease. muscle weakness. Drugdex system.6 mg/kg within 8 hours. WHO Model Formulary for Children 2010 285 . Sweetman SC. eds. 10 mg Indications: Seizures. eds. Kemp CA. Australian Medicines Handbook.4 References: Medicines used in palliative care Ashley C. Pharmaceutical Press.

British national formulary for children 2009. Furosemide: enhanced hypotensive effect. Kouimtzi M. Radcliffe Publishing. BMJ Group RBS Publishing. 286 WHO Model Formulary for Children 2010 . vertigo. salivation changes. Chlorphenamine: enhanced sedative effect. Stuart MC. tremor. Melbourne. London. Moderate to severe impairment: use small doses and titrate to response. pain and thrombophlebitis. dysarthria. Currie A. (http://www. gastrointestinal disturbances. accessed 10 February 2010). Mild impairment: dosage reduction not necessary. eds. Hepatic impairment: Can precipitate coma. Paediatric Formulary Committee. paradoxical increase in aggression. Halothane: enhanced sedative effect. 3rd ed. Spironolactone: enhanced hypotensive effect. Codeine: enhanced sedative effect. 2009. incontinence. muscle weakness. Klasco RK. Geneva. ed. Paediatric pharmacopoeia. amnesia. changes in libido. hypotension and apnoea. 13th ed. Propranolol: enhanced hypotensive effect. Greenwood Village. confusion and ataxia. Common Drowsiness and lightheadedness. Ketamine: enhanced sedative effect. 2009. Uncommon Dependence. Rare Blood disorders and jaundice. WHO model formulary. Alcohol: enhanced sedative effect.thomsonhc. avoid concomitant use). Oxford. occasionally headache. McDowell JM. * Ritonavir: plasma concentration possibly increased by ritonavir (risk of extreme sedation and respiratory depression. Chlorpromazine: enhanced sedative effect. Hydrochlorothiazide: enhanced hypotensive effect. immunosuppressives and medicines used in palliative care Renal impairment: Start with small doses due to increased cerebral sensitivity. Kemp CA.com. Phenytoin: plasma phenytoin concentrations possibly increased or decreased by diazepam. Interactions with other medicines (* indicates severe): Consider the relevance of the listed interactions in palliative care.8 Antineoplastic. eds. Hill SR. 2002. Low doses could be used but a shorter acting agent would be preferable. References: Ashley C. Royal Children’s Hospital. Amitriptyline: enhanced sedative effect. Drugdex system. skin reactions. Thiopental: enhanced sedative effect. visual disturbances. World Health Organization. urinary retention. Adverse effects: Consider relevance of adverse effects in palliative care. 2008. Clomipramine: enhanced sedative effect. Isoniazid: metabolism of diazepam inhibited. Rifampicin: metabolism of diazepam accelerated (reduced plasma concentration). Morphine: enhanced sedative effect. Thomson Micromedex. The renal drug handbook. Nitrous oxide: enhanced sedative effect. Haloperidol: enhanced sedative effect. 2010.

2009. Adverse effects: Rare Abdominal cramps. ed. Oral liquid may be given with milk. Renal impairment: Dose reduction not necessary. for example riding a bike or operating machinery. Hyoscine hydrobromide ATC code: A04AD01 Injection: 400 micrograms/ml. Pediatric dosage handbook. Adelaide. Interactions with other medicines (* indicates severe): Mineral oil: may increase absorption of mineral oil. for 24 hours. concomitant use of mineral oils (do not give with liquid paraffin). Take with plenty of fluid.5 mg three times daily. Lexi-Comp. nausea. rash. London.8. Notes: Oral preparations may take 1–2 days to act. vomiting. Taketomo CK. Australian medicines handbook. Contraindications: Hypersensitivity. Rossi S. Kraus DM. Hudson. WHO Model Formulary for Children 2010 287 . diarrhoea. intestinal obstruction. myasthenia gravis. Acetylsalicylic acid: may increase the gastrointestinal toxicity of acetylsalicylic acid. 2009.4 Medicines used in palliative care Docusate sodium ATC code: A06AA02 Capsule: 100 mg Oral liquid: 10 mg/ml Indications: Constipation particularly when caused by opioid use.5–25 mg three times daily. Paediatric Formulary Committee. intestinal obstruction. BMJ Group RBS Publishing. Precautions: Acute abdominal pain. 600 micrograms/ml Transdermal patches: 1 mg/72 hours Indications: excessive respiratory secretions. fruit juice (not grapefruit) or infant formula to mask bitter taste. 2009. Hepatic impairment: Dose reduction not necessary. local throat irritation. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination. Closed-angle glaucoma. British national formulary for children 2009. Australian Medicines Handbook. 2–12 years 12. 16th ed. Precautions: Consider the relevance of these listed precautions in palliative care. urinary obstruction. Dose: As a laxative. Contraindications: Consider the relevance of these listed contraindications in palliative care. Oral: Infant or Child 6 months–2 years 12. References: Hodding JH. nausea.

Australian Medicines Handbook. Oral or sublingual (injection solution can be used by these routes): Child 2–12 years 10 micrograms/kg. If less than whole patch is required. References: Ashley C. Oxford. angioedema. hepatic impairment. dry and/or flushed skin. Kemp CA. SC or IV infusion: Child all ages 40–60 micrograms/kg daily as a continuous infusion. Hepatic impairment: Use with caution as central nervous system side-effects occur more often in patients with hepatic impairment. McDowell JM. Ibuprofen ATC code: M01Ae01 Oral liquid: 20 mg/ml Tablet: 200 mg. difficulty in micturition. Royal Children’s Hospital. Paediatric Formulary Committee. immunosuppressives and medicines used in palliative care Dose: excessive respiratory secretions. confusion. 13th ed. 2009. Interactions with other medicines (* indicates severe): Consider the relevance of these listed interactions in palliative care. Australian medicines handbook. memory impairment. coagulation defects.8 Antineoplastic. blurred vision. Radcliffe Publishing. allergic disorders. urticaria or rhinitis). eds. active peptic ulceration. maximum 300 micrograms four times daily. Renal impairment. Adverse effects: Consider the relevance of these listed adverse effects in palliative care. Rare Fever due to anhidrosis. Injection solution may be given orally. Atropine: may increase therapeutic effect and risk of side-effects. London. Indications: Specific use for management of bone pain. Contraindications: Hypersensitivity to acetylsalicylic acid or any other NSAIM (including asthma. Rossi S. BMJ Group RBS Publishing. Transdermal: Infant or Child 1 month–3 years 250 micrograms every 72 hours (quarter of a patch). 2002. Neostigmine: may antagonize anticholinergic effect. British national formulary for children 2009. arrhythmia. 10–12 years 1 mg every 72 hours (one patch). ed. 2009. insomnia. preferably avoid if history of peptic ulceration. The renal drug handbook. hallucinations. Precautions: Consider the relevance of listed precautions in palliative care. 3–10 years 500 micrograms every 72 hours (half a patch). Paediatric pharmacopoeia. Currie A. Common Drowsiness. Transdermal patch may contain metal. Renal impairment: Dose reduction not necessary. 3rd ed. dizziness. 400 mg. either cut with scissors along full thickness ensuring the membrane is not peeled away or cover portion to prevent contact with the skin. 2009. Melbourne. remove before MRI. Notes: Administration of the patch: apply to a hairless area of skin behind the ear. cardiac disease. anaphylaxis. Uncommon Tachycardia. Adelaide. Pyridostigmine: may antagonize anticholinergic effect. 288 WHO Model Formulary for Children 2010 . 600 mg Special Notes: WHO age/weight restriction: > 3 months.

angioedema and bronchospasm. toxic epidermal necrolysis (Lyell syndrome). haematuria. Common Gastrointestinal disturbances including nausea. Oral: Infant or Child over 3 months 5–10 mg/kg three or four times daily with or after food. * Phenytoin: effect of phenytoin possibly enhanced. Moderate to severe impairment: avoid unless on dialysis. Interactions with other medicines (* indicates severe): Renal impairment: Mild impairment: use lowest effective dose and monitor for sodium and water Consider the relevance of the listed interactions in palliative care. Hydrocortisone: increased risk of gastrointestinal bleeding and ulceration. tinnitus. Maximum daily dose is 40 mg/kg/day. Heparin: possibly increased risk of bleeding. * Methotrexate: excretion of methotrexate reduced (increased risk of toxicity). raised blood pressure. Propranolol: antagonism of hypotensive effect. visual disturbances. pulmonary eosinophilia. fluid retention. Adverse effects: Consider relevance of adverse effects in palliative care. nervousness. * Glibenclamide: possibly enhanced effect of glibenclamide. * Acetylsalicylic acid: avoid concomitant use (increased adverse effects). * Fluoxetine: increased risk of bleeding. WHO Model Formulary for Children 2010 289 . Rare Hepatic damage. Uncommon Dyspepsia. Furosemide: risk of nephrotoxicity of ibuprofen increased. Ritonavir: plasma concentration possibly increased by ritonavir. Zidovudine: increased risk of haematological toxicity.8. reduced renal function. Enalapril: antagonism of hypotensive effect. antagonism of diuretic effect. * Warfarin: anticoagulant effect possibly enhanced. insomnia.4 Dose: Medicines used in palliative care Treatment of bone pain. * Ciclosporin: increased risk of nephrotoxicity. Hepatic impairment: Severe impairment: not recommended. diarrhoea. erythema multiforme (Stevens-Johnson syndrome). dizziness. pancreatitis. vertigo. alveolitis. Penicillamine: possible increased risk of nephrotoxicity. * Ofloxacin: possible increased risk of seizures. colitis. photosensitivity. increased risk of renal impairment. Digoxin: possibly exacerbation of heart failure. retention. and increased plasma digoxin concentration. * Ciprofloxacin: possibly increased risk of seizures. Dexamethasone: increased risk of gastrointestinal bleeding and ulceration. possibly increased risk of hyperkalaemia. ulceration and haemorrhage. aseptic meningitis. depression. deterioration in renal function possibly leading to renal failure. headache. Prednisolone: increased risk of gastrointestinal bleeding and ulceration. drowsiness. antagonism of diuretic effect. Spironolactone: risk of nephrotoxicity of ibuprofen increased. Hydrochlorothiazide: risk of nephrotoxicity of ibuprofen increased. renal failure. hypersensitivity reactions including rash. antagonism of diuretic effect.

anxiety and agitation. prolonging its sedative and respiratory depressant effects. Lopinavir: inhibits metabolism. initially. Radcliffe Publishing. bitter taste can be disguised in apple juice or chocolate sauce. myasthenia gravis.05–0. BMJ Group RBS Publishing. Interactions with other medicines (* indicates severe): Atazanavir: inhibits metabolism. Midazolam ATC code: N05CD08 Injection: 1 mg/ml.15 mg/kg every 1–2 hours.8 Antineoplastic.2–0. SC or IV injection: Child all ages 0. rash. Dose: For all indications in a palliative care setting. 290 WHO Model Formulary for Children 2010 . Bolus doses preferred. Continuous SC or IV infusion: Child all ages 10 micrograms/kg/hour by continuous SC or IV infusion. immunosuppressives and medicines used in palliative care Notes: Advise patient or carer that ibuprofen should be taken after food or milk. eds. Oral: Child all ages 0. 2008. eds. Hepatic impairment: Central nervous system side-effects increased.3–0. cough. decreasing therapeutic effects. Adverse effects: Common Hypotension. Geneva. Use the parenteral form. The renal drug handbook. prolonging sedation and respiratory depressant effects. prolonging sedation and respiratory depressant effects. confusion. Rifampicin: increases metabolism. Buccal or intranasal: Child all ages 0. Stuart MC. Hill SR. prolonging sedation and respiratory depressant effects. London. hiccup. Fluconazole: inhibits the metabolism of midazolam. decreasing therapeutic effects. Carbamazepine: may increase midazolam’s metabolism and decrease its effect. Severe impairment: use sparingly and titrate according to response. 2009. WHO model formulary. Paediatric Formulary Committee. Acute or severe pulmonary insufficiency. severe liver disease. World Health Organization. British national formulary for children 2009. prolonging sedation and respiratory depressant effects. Oxford. 5 mg/ml Indications: Palliative situations such as seizures. Renal impairment: Mild to moderate impairment: no dosage reduction necessary. Contraindications: Consider the relevance of these listed contraindications in palliative care. 3rd ed. Patients with renal impairment may be more susceptible to central nervous system side-effects. apnoea or respiratory depression (particularly with IV administration). Phenytoin: may increase metabolism. References: Ashley C. Rare Arrhythmias. cardiorespiratory arrest. Ritonavir: inhibits metabolism. anaphylactic reactions. 2009. avoid in severe impairment as can precipitate coma. Kouimtzi M. sleep apnoea syndrome. Use the parenteral form.5 mg/kg per dose (maximum 10 mg) as required. There is considerable variability in the dose required. Uncommon erythema. and titrate to effect. Oral suspension should be shaken before use.5 mg/kg (maximum 15 mg) as a single dose. Saquinavir: inhibits metabolism. Currie A. Erythromycin: inhibits metabolism and prolongs sedation and respiratory depressant effects.

60 mg Tablet (immediate release): 10 mg Special Notes: Drug subject to international control under the Single Convention on Narcotic Drugs (1961). adjusted according to response. Nottingham. 30 mg. Morphine ATC code: N02AA01 Granules (modified release) (to mix with water): 20 mg. Palliative care formulary. adjusted according to response. Melbourne. for 24 hours. adjusted according to response. 6 months–12 years initially 100 micrograms/kg every 4 hours. palliativedrugs. Adelaide. Hill SR. Wilcock A. decreased respiratory reserve. adjusted according to response. Renal and hepatic impairment. Infant or Child 1–6 months initially 100–200 micrograms/kg every 6 hours.8. buccally or intranasally.tg. for example riding a bike or operating machinery. acute alcoholism and where risk of paralytic ileus. Kouimtzi M. hypothyroidism. 200 mg Injection: 10 mg/ml Oral liquid: 2 mg/ml Tablet (controlled release): 10 mg.au/ip/. Onset of action: subcutaneous 5–10 minutes. Dose: Severe pain. SKILLeD TASKS Warn patient or carer about the risk of undertaking tasks requiring attention or coordination.org. 2–12 years initially 200 micrograms/kg every 4 hours. Australian medicines handbook. buccal within 15 minutes. 30 mg. increased doses will be required if using long-term. Indications: Severe pain. 6 months–2 years initially 100–200 micrograms/kg every 4 hours. severe withdrawal symptoms if withdrawn abruptly. adjusted according to response.com. 60 mg.4 Medicines used in palliative care Notes: Midazolam injection can be administered orally. Contraindications: Consider the relevance of these listed contraindications in palliative care. Precautions: Consider the relevance of these listed precautions in palliative care. Twycross R. eds. due to physiological tolerance. 2007. Therapeutic Guidelines Limited. 2008. 3 months–12 years 20 micrograms/kg/hour. Adjust dose according to response. adjusted according to response. SC injection: Neonate initially 100 micrograms/kg every 6 hours. convulsive disorders. Geneva. accessed 10 February 2010). Stuart MC. Compatible with most drugs commonly administered via syringe driver. adjusted according to response. 100 mg. 3rd ed. avoid injection in phaeochromocytoma. ed. References: eTG complete. 2009 (http://etg. Rossi S. also avoid in raised intracranial pressure or head injury (affects pupillary responses vital for neurological assessment). WHO Model Formulary for Children 2010 291 . IV injection: Neonate initially 50 micrograms/kg every 6 hours. eds. WHO model formulary. Australian Medicines Handbook. Infant or Child 1–6 months initially 100 micrograms/kg every 6 hours. Avoid in acute respiratory depression. oral 60 minutes. 2009. World Health Organization. Continuous SC infusion: Infant or Child 1–3 months 10 micrograms/kg/hour.

Taketomo CK. sweating. seizure. eds. vertigo. Kraus DM. Mild impairment: 75% of normal dose. Titrate to response.8 Antineoplastic. Hodding JH. 16th ed. vomiting (particularly in initial stages). miosis. Lexi-Comp. note the oral doses are approximately half as effective as parenteral doses. British national formulary for children 2009.6 mg/kg/dose every 12 hours (all ages). 2008. increased cerebral Consider the relevance of these listed interactions in palliative care. Adverse effects: Consider the relevance of these listed adverse effects in palliative care. adjusted according to response. Stuart MC. London. confusion. anorexia. Notes: When changing routes of administration in chronically treated patients. Amitriptyline: possibly increased sedation. Diazepam: enhanced sedative effect. decreased libido. Ciprofloxacin: manufacturer of ciprofloxacin advises to avoid premedication with morphine (reduced plasma ciprofloxacin concentration) when ciprofloxacin used for surgical prophylaxis. Australian medicines handbook. Hepatic impairment: Avoid or reduce dose. spasm of urinary and biliary tract. 2009. References: Hill SR. adjusted to response. euphoria. Paediatric Formulary Committee. palpitation. 1–2 years initially 200–400 micrograms/kg every 4 hours. Australian Medicines Handbook. Infant or Child 1–6 months initially by intravenous injection (over at least 5 minutes) 100–200 micrograms/kg then by continuous infusion 10–30 micrograms/kg/hour. rash. Rare Syndrome of inappropriate antidiuretic hormone secretion. urticaria. adjusted according to response. Moderate or severe impairment: use small doses and extended dosing intervals. tachycardia. facial flushing. adjusted according to response. drowsiness. Hudson. hypotension and muscle rigidity. Pediatric dosage handbook. * Ritonavir: possibly increases plasma concentration of morphine. anaphylaxis. pruritus. Rossi S. Alcohol: enhanced sedative and hypotensive effect. headache. larger doses produce respiratory depression. sensitivity. BMJ Group RBS Publishing. constipation. 6 months–12 years initially by intravenous injection (over at least 5 minutes) 100–200 micrograms/kg then by continuous intravenous infusion 20–30 micrograms/kg/hour. 2009. postural hypotension. Haloperidol: enhanced sedative and hypotensive effect. Uncommon Bradycardia. hypothermia. ed. hallucinations. Geneva. adjusted according to response. Common Nausea. World Health Organization. dependence. Kouimtzi M. 2009. Oral: Infant or Child 1–12 months initially 80–200 micrograms/kg every 4 hours. increased and prolonged effect. Chlorpromazine: enhanced sedative and hypotensive effect. Interactions with other medicines (* indicates severe): Renal impairment: Reduce dose or avoid. Controlled release tablets may be used at a dose of 0. immunosuppressives and medicines used in palliative care IV infusion: Neonate initially by intravenous injection (over at least 5 minutes) 25–100 micrograms/kg then by continuous intravenous infusion 10–30 micrograms/kg/hour. also dry mouth. WHO model formulary. Adelaide. may precipitate coma. 2–12 years initially 200–500 micrograms/kg (maximum 20 mg) every 4 hours. adjusted according to response. Metoclopramide: antagonism of effect of metoclopramide on gastrointestinal activity. 292 WHO Model Formulary for Children 2010 .3–0.

discoloration of urine. 2009. Currie A. References: Ashley C. British national formulary for children 2009. Paediatric Formulary Committee. ed. Contraindications: Intestinal obstruction. May be mixed with water. WHO Model Formulary for Children 2010 293 . eds. Interactions with other medicines (* indicates severe): None known. Kraus DM. diarrhoea. 3rd ed. Geneva. Kouimtzi M.5 mg/ml Indications: Constipation. Pediatric dosage handbook. eds. Australian medicines handbook.5 mg at bedtime. Radcliffe Publishing. BMJ Group RBS Publishing.5 mg at bedtime. Hepatic impairment: Dose reduction not necessary. Hudson. 2008. Hill SR. Stuart MC. 2009. 2009. Rare Melanosis coli (benign reversible. Renal impairment: Dose reduction not necessary.8. Hodding JH.4 Medicines used in palliative care Senna ATC code: A06AB06 Oral liquid: 1. occurs with chronic use). nausea. Australian Medicines Handbook. 2009. Lexi-Comp.75–7. Rossi S. Uncommon Hypokalaemia (with prolonged use or overdosage). Notes: Useful in combination with docusate sodium.25–4. Adelaide. milk or food. Adverse effects: Common Abdominal discomfort. WHO model formulary. London. undiagnosed abdominal symptoms. 16th ed. Oxford. The renal drug handbook. Dose: Oral: Child 1 month–2 years 2.5–15 mg at bedtime. Taketomo CK. 2–5 years 3. inflammatory bowel disease. 6–12 years 7. World Health Organization.

SECTION 9: Antiparkinsonism medicines 294 WHO Model Formulary for Children 2010 .

9. WHO Model Formulary for Children 2010 295 . Antiparkinsonism medicines 9 Antiparkinsonism medicines This section has been deleted from the 2nd WHO Model List of Essential Medicines for Children.

...................................... 297 10.........2 Medicines affecting coagulation ......... 300 296 WHO Model Formulary for Children 2010 ...................................SECTION 10: Medicines affecting the blood 10...........1 Antianaemia medicines ........

int/nutrition/publications/micronutrients/anaemia_iron_deficiency/1-57881-020-5/en/index. For further details on prevention of anaemia see Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anaemia. hookworm). Oral: Child under 5 years 1–2 mg/kg (maximum 30 mg) of elemental iron daily. Infant and Child 3–6 mg/kg (maximum 200 mg) of elemental iron daily. haemoglobinopathies (e.who. intestinal strictures.10.1 Medicines affecting the blood Antianaemia medicines Anaemia occurs when the blood haemoglobin concentration falls below the reference range for the age and gender of the individual.html. Prevention of iron deficiency anaemia (in those at particular risk). Precautions: Should not be administered for longer than 6 months. The main risk factors for iron deficiency anaemia (IDA) in children include inadequate intake of iron-containing food. Renal impairment: Dose reduction not necessary. ulcerative colitis. Other contributing factors include malaria. and parasitic infections (e. diverticula. found at (http://www. Contraindications: Haemosiderosis.who. micronutrient deficiencies (e. WHO Model Formulary for Children 2010 297 . haemochromatosis. patients receiving repeated blood transfusions. Adequate precautions including the use of child-resistant containers should be taken to store iron preparations to prevent such overdoses. any form of anaemia not caused by iron deficiency.html).1 Antianaemia medicines 10 10. B03AB Oral liquid: equivalent to 25 mg of elemental iron (as sulfate)/ml Tablet: equivalent to 60 mg of elemental iron Iron preparations are an important cause of accidental overdose in children and as little as 20 mg/kg of elemental iron can lead to symptoms of toxicity. Anaemia is a major global public health problem with major consequences for child health and development. regional enteritis. over 5 years 30–60 mg of elemental iron daily. Oral: Neonate 2–4 mg/kg of elemental iron daily.g. parenteral iron therapy. overdosage (see section 4. given in 2–3 divided doses. Indications: Used for iron deficiency anaemia or as nutritional supplement. Hepatic impairment: Dose reduction not necessary. given in 2–3 divided doses.g.int/child_adolescent_health/documents/9241546700/en/index.g. and anaemia of chronic disorders such as HIV infection or tuberculosis. folate). found at http://www. The most significant contributor to the onset of anaemia is iron deficiency. Dose: Treatment of iron deficiency anaemia. Ferrous salt ATC code: B03AA. especially during periods of rapid growth when iron requirements are high. peptic ulcer. sickle cell anemia or thalassemia). For detailed clinical guidelines regarding management of anaemia in children see the WHO Pocket Book of Hospital Care for Children.2).

2009. Geneva. Temporary discoloration of the teeth can be minimized by brushing the teeth with baking soda. Kouimtzi M.int/hq/2001/WHO_NHD_01. References: Hill SR. eds. WHO model formulary. However. 2001 (http://whqlibdoc. Levothyroxine: absorption of levothyroxine reduced by oral ferrous salts (give at least 2 hours apart). Compliance may be increased by giving the total daily dose as a single daily dose. gastrointestinal side-effects are increased and split daily doses may be better tolerated. 1 mg elemental iron = approximately 3 mg dried ferrous sulfate = approximately 9 mg ferrous gluconate. London. They may discolour stools. prevention and control . Doxycycline: absorption of oral ferrous salts reduced by doxycycline. 2002. Levodopa: absorption of levodopa may be reduced by oral ferrous salts. megaloblastic anaemia. Contraindications: Should never be given without vitamin B12 in undiagnosed megaloblastic anaemia or other vitamin B12 deficiency states because of risk of precipitating subacute combined degeneration of the spinal cord. diarrhoea. Increase fibre in diet to minimize constipation. World Health Organization. prevention of folate deficiency in haemolytic anaemia.pdf. Penicillamine: oral ferrous salts reduce absorption of penicillamine. 2008.a guide for programme managers. Liquid preparations containing iron salts should be well diluted with water. folate-dependent malignant disease. Melbourne. Royal Children’s Hospital. Levofloxacin: absorption of levofloxacin reduced by oral ferrous salts. gastrointestinal irritation. Ofloxacin: absorption of ofloxacin reduced by oral ferrous salts.who. 5 mg Indications: Treatment of folate deficiency. McDowell JM. If possible. 298 WHO Model Formulary for Children 2010 . 13th ed. Paediatric pharmacopoeia. Stuart MC. Notes: Iron content in artificial formula feeds should be taken into account when considering iron supplementation.3. epigastric pain. Ciprofloxacin: absorption of ciprofloxacin reduced by oral ferrous salts. Methyldopa: oral ferrous salts reduce hypotensive effect of methyldopa. Although iron preparations are best absorbed on an empty stomach. Kemp CA. dark stools. BMJ Group RBS Publishing. absorption of doxycycline reduced by oral ferrous salts. Uncommon Long-term or excessive administration may cause haemosiderosis. swallow through a drinking straw and brush teeth after administration to prevent discoloration of the teeth. Geneva. * Dimercaprol: avoid concomitant use. nausea.10 Medicines affecting the blood Adverse effects: Common Constipation. accessed 10 February 2010). Folic acid ATC code: B03BB01 Tablet: 1 mg. British national formulary for children 2009. Zinc sulfate: absorption of zinc and of oral ferrous salts reduced. Interactions with other medicines (* indicates severe): Calcium salts: reduced absorption of oral ferrous salts. Iron deficiency anaemia: assessment. World Health Organization. they may be taken after food to reduce gastrointestinal adverse effects. Paediatric Formulary Committee.

Haemolytic anaemia. Up to 15 mg daily may be required in malabsorption states. accessed 10 February 2010). References: Hill SR. Dose: Megaloblastic anaemia without neurological involvement. Precautions: Should not be given before diagnosis confirmed except in emergencies. World Health Organization. then 1 mg every 2 months. British national formulary for children 2009. Renal impairment: Dose reduction not necessary. IM: Child 1 month–12 years initially 1 mg on alternate days until no further improvement occurs. London. 2010. megaloblastic anaemia. BMJ Group RBS Publishing. Up to 10 mg once daily may be required in malabsorption states. subacute combined degeneration of the spinal cord if given without vitamin B12 for vitamin B12 deficiency states. then 1 mg every 3 months if required. Paediatric Formulary Committee. over 1 year 5 mg daily for 4 months. Oral: Child 1 month–12 years 2.thomsonhc. Indications: Used in the treatment of megaloblastic anaemia due to vitamin B12 deficiency (pernicious anaemia).10. Stuart MC. Interactions with other medicines (* indicates severe): * Phenobarbital: plasma concentration of phenobarbital possibly reduced. 2009. Thomson Micromedex. ed.com. Klasco RK. * Phenytoin: plasma phenytoin concentration possibly reduced. Adverse effects: Rare Gastrointestinal disturbances. Hydroxocobalamin ATC code: B03BA03 Injection: 1 mg/1ml ampoule Special Notes: Also referred to as vitamin B12. WHO Model Formulary for Children 2010 299 . Oral: Neonate to Child 1 year initially 500 micrograms/kg (maximum 5 mg) once daily for up to 4 months. Sulfasalazine: possibly reduced absorption of folic acid. Geneva. 2008. (http://www.5–5 mg once daily. IM: Child 1 month–12 years initially 250 micrograms–1 mg three times weekly for 2 weeks. WHO model formulary. * Sulfadoxine + pyrimethamine: possibly reduced efficacy of sulfadoxine + pyrimethamine. Renal impairment: Dose reduction not necessary. Hepatic impairment: Dose reduction not necessary.1 Dose: Antianaemia medicines Treatment of folate deficiency. eds. Kouimtzi M. Greenwood Village. Hepatic impairment: Dose reduction not necessary. Drugdex system. Megaloblastic anaemia with neurological involvement. then 250 micrograms once weekly until the blood count is normal. monitor serum potassium levels (arrhythmias secondary to hypokalaemia in early therapy).

Anticoagulation in children should only be undertaken with specialist supervision and careful monitoring. NOTe The IV route is preferred by some in pre-term neonates of very low birth weight. coagulation systems of children and adults are different. WHO model formulary. Uncommon Fever. prophylaxis against haemorrhagic disease of the newborn. London. 2009. IM: Neonate 0. hot flushes. Interactions with other medicines (* indicates severe): Chloramphenicol: response to hydroxocobalamin reduced. anaphylaxis. Dose: Prophylaxis of haemorrhagic disease of the newborn. IV: Pre-term neonate 400 micrograms/kg (maximum 1 mg). Kouimtzi M. Indications: Antagonist to warfarin. World Health Organization. eds. or extension of an existing thrombus. pain at injection site. not an antidote to heparin. 10. However. a third dose after 1 month.10 Medicines affecting the blood Adverse effects: Common Nausea. Precautions: Hepatic impairment.5–1 mg as single dose at birth. References: Hill SR. 300 WHO Model Formulary for Children 2010 . 2008. British national formulary for children 2009. for breastfed babies. Oral: Neonate 2 mg followed by a second dose after 4–7 days and. acneiform and bullous eruptions. Special Notes: Also referred to as vitamin K1. Thromboembolic disease is increasingly recognised in neonates and children. Stuart MC. but it does not provide the prolonged protection of the IM injection. phytonadione. in the slower moving venous side of the circulation. headache. above). any babies receiving IV vitamin K should be given subsequent oral doses (as per oral dosing. 10 mg/ml in 5 ml ampoule Tablet 10 mg Intravenous injections should be given very slowly (risk of vascular collapse). BMJ Group RBS Publishing. chills. with important implications for use of anticoagulant medications in children. hypokalaemia during initial treatment. Geneva. Phytomenadione ATC code: B02BA01 Injection: 1 mg/1 ml. Paediatric Formulary Committee. Rare Hypersensitivity reactions including rash and pruritus.2 Medicines affecting coagulation Anticoagulants are used to prevent thrombus (blood clot) formation. dizziness.

Short- acting injectable anticoagulant. World Health Organization. Adverse effects: Uncommon Hypersensitivity reactions including flushing. Intravenous preparations can usually be given orally.2 Medicines affecting coagulation Treatment of haemorrhagic disease of the newborn. IV: Neonate 1 mg with further doses if necessary every 8 hours. haemophilia and other haemorrhagic disorders. acidosis. vitamin K must be given either intramuscularly or intravenously because oral absorption is likely to be impaired. Contraindications: Hypersensitivity to heparin. 2008. Warfarin-induced hypoprothrombinaemia with no or minor bleeding. Notes: In infants with cholestatic disease. Heparin sodium ATC code: B01AB01 Injection: 1000 units/ml. British national formulary for children 2009. WHO model formulary. BMJ Group RBS Publishing. References: Hill SR. Paediatric Formulary Committee.10. bronchospasm. treatment of haemorrhage associated with vitamin K deficiency. Hepatic impairment: Higher doses may be required for adequate response. repeated as necessary. Interactions with other medicines (* indicates severe): * Warfarin: vitamin K antagonizes anticoagulant effect of warfarin. heparins. Please check specific product information. Stuart MC. hypotension and respiratory or circulatory collapse which may be due to polyethoxylated castor oil surfactant in some injection formulations. peptic ulcer. Geneva. dizziness. dyspnoea. hypersensitivity to low molecular weight WHO Model Formulary for Children 2010 301 . eds. London. after major trauma or recent surgery (especially to eye or nervous system). recent cerebral haemorrhage. concomitant potassium-sparing drugs (increased risk of hyperkalaemia). diabetes mellitus. IV: Child 1 month–12 years 15–30 micrograms/kg (maximum 1 mg) as a single dose. Warfarin-induced hypoprothrombinaemia: reversal of anticoagulation or if significant bleeding. 2009. Indications: Treatment and prophylaxis of deep-vein thrombosis and pulmonary embolism. 5000 units/ml in 1 ml ampoules Special Notes: Also referred to as UFH (unfractionated heparin) or standard heparin. spinal or epidural anaesthesia (risk of spinal haematoma). IV: Child 1 month–12 years 250–300 micrograms/kg (maximum 10 mg) as a single dose. severe hypertension. Kouimtzi M. acute bacterial endocarditis. thrombocytopenia. rather than due to phytomenadione. Tablets may be chewed. Precautions: Hepatic impairment and renal failure. severe liver or renal disease. Renal impairment: Dose reduction not necessary.

10

Medicines affecting the blood

Dose:

Treatment of deep-vein thrombosis and pulmonary embolism. IV: Neonate to Child 1 year initially 75 units/kg (50 units/kg if < 35 weeks corrected age), then by continuous IV infusion, 25 units/kg/hour, adjusted according to activated partial thromboplastin time (APTT) or anti-Factor Xa; 1–12 years initially 75 units/kg, then by continuous IV infusion 20 units/kg/hour, adjusted according to APTT or anti-Factor Xa. SC: Child 1 month–12 years 250 units/kg every 12 hours adjusted according to APTT or anti-Factor Xa. Prophylaxis in general surgery. SC: Child 1 month–12 years 100 units/kg (maximum 5000 units) twice daily, adjusted according to APTT or anti-Factor Xa.
Renal impairment: Dose reduction not necessary. Hepatic impairment: Hepatic impairment with impaired haemostasis: increased risk of haemorrhage.

Reduce dose in severe impairment.

Adverse effects: Common Hyperkalaemia, injection site reactions, haematoma if given IM. Uncommon Haemorrhage, haematuria, thrombocytopenia. Rare Immune-mediated thrombocytopenia usually developing 6–10 days after commencement

of therapy (requires immediate withdrawal of heparin), skin necrosis, hypersensitivity reactions including urticaria, angioedema and anaphylaxis, osteoporosis after prolonged use, alopecia, rebound hyperlipidaemia after withdrawal, priapism.

Interactions with other medicines (* indicates severe):

* Acetylsalicylic acid: enhanced anticoagulant effect of heparin. Enalapril: increased risk of hyperkalaemia. * Glyceryl trinitrate: anticoagulant effects reduced by infusion of glyceryl trinitrate. Ibuprofen: possibly increased risk of bleeding.
Notes: For continuous intravenous infusion, dilute with glucose 5% or sodium chloride 0.9%.

Laboratory monitoring of coagulation activity, preferably on a daily basis, involves determination of the APTT or of the anti-Factor Xa concentration. Local guidelines on recommended APTT for neonates and children should be followed. If haemorrhage occurs, it is usually sufficient to withdraw heparin, but if rapid reversal of heparin effects is required, protamine sulfate is a specific antidote.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Klasco RK, ed. Drugdex system. Greenwood Village, Thomson Micromedex, 2010. (http://www.thomsonhc.com, accessed 10 February 2010). Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009.

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10.2

Medicines affecting coagulation

Protamine sulfate
ATC code: V03AB14

Injection: 10 mg/ml in 5 ml ampoule
Indications: Used to treat heparin overdose. If used in excess it has an anticoagulant effect. Precautions: If used in excess, protamine has an anticoagulant effect; allergic reactions increased in

persons at risk including previous treatment with protamine or protamine insulin; fish allergies; rapid administration or high dose.

Dose:

Heparin overdose by IV injection or IV infusion. IV: Child 1 month–12 years 1 mg of protamine neutralizes approximately 100 units of heparin if less than 30 minutes has elapsed since overdose; 500–750 micrograms if 30–60 minutes has elapsed; 375–500 micrograms if 60–120 minutes has elapsed; 250–375 micrograms if over 120 minutes has elapsed. Maximum dose 50 mg. Do not exceed a rate of 5 mg/minute. Heparin overdose by SC injection. IV: Child 1 month–12 years 1 mg neutralizes approximately 100 units of heparin. Give 50–100% of the total dose by IV injection (rate not exceeding 5 mg/minute); then give any remainder of the dose by intravenous infusion over 8–16 hours. Maximum total dose 50 mg.
Renal impairment: Dose reduction not necessary. Hepatic impairment: Dose reduction not necessary. Adverse effects: Uncommon Nausea, vomiting, lassitude, flushing, hypotension/hypertension. Rare Bradycardia, dyspnoea, allergic reactions (including angioedema, anaphylaxis), cardiovascular

collapse, pulmonary vasoconstriction/hypertension.

Interactions with other medicines (* indicates severe):

There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use.
Notes: 1 mg neutralizes approximately 100 units of unfractionated heparin when given within

15 minutes; if longer time, less protamine is needed as heparin is rapidly excreted.

Monitor activated partial thromboplastin time (APTT) or other appropriate blood clotting parameters. Do not administer at a rate exceeding 5 mg/minute. May be diluted if necessary with sodium chloride 0.9%.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009.

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Warfarin

ATC code: B01AA03

Tablet: 0.5 mg; 1 mg; 2 mg; 5 mg (sodium salt) Serious and potentially fatal bleeding may occur, especially during initiation of treatment and with higher doses.
Special Notes: This medicine is listed as a representative of its pharmacological class. Other

medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. The information in this monograph only applies to the medicine listed here. Indications: Prophylaxis of embolization in rheumatic heart disease and atrial fibrillation; prophylaxis after insertion of prosthetic heart valve; prophylaxis and treatment of venous thrombosis and pulmonary embolism; transient ischaemic attacks. Contraindications: Pregnancy; peptic ulcer; severe hypertension; bacterial endocarditis. Precautions: Hepatic impairment or renal failure; recent surgery; avoid cranberry juice (risk of potentiating anticoagulant effect).
Dose: NOTe Wherever possible, the baseline prothrombin time should be determined before the initial dose is given, but the initial dose should not be delayed while awaiting the result. Induction dose may need to be altered according to condition (e.g. hepatic impairment, cardiac failure), concomitant interacting drugs, and if baseline INR is above 1.3.

Prophylaxis and treatment of thromboembolic disorders. Oral: Neonate (under specialist advice) 200 micrograms/kg as a single dose on day 1, then 100 micrograms/kg once daily for following 3 days. However, if INR is still below 1.4, continue to use 200 micrograms/kg once daily. If the INR is above 3, change to 50 micrograms/kg once daily, and if INR is above 3.5, omit dose. Adjust ongoing therapy in accordance with INR. Usual maintenance 100–300 micrograms/kg once daily (may need up to 400 micrograms/kg once daily, especially if bottle fed; see Notes). Child 1 month–12 years 200 micrograms/kg (maximum 10 mg) as a single dose on day 1, then 100 micrograms/kg (maximum 5 mg) once daily for the following 3 days. However, if INR is still below 1.4, continue to use 200 micrograms/kg (maximum 10 mg) once daily. If the INR is above 3, change to 50 micrograms/kg (maximum 2.5 mg) once daily, and if INR is above 3.5 omit dose. Adjust ongoing therapy in accordance with INR. Usual maintenance 100–300 micrograms/kg once daily (may need up to 400 micrograms/kg once daily especially if bottle fed; see Notes).
Renal impairment: Use with caution; avoid in severe impairment. Hepatic impairment: Avoid in severe impairment, especially if prothrombin time already prolonged. Adverse effects: Common Haemorrhage. Rare Hypersensitivity, rash, alopecia, diarrhoea, unexplained drop in haematocrit, systemic

cholesterol microembolism (‘purple toes syndrome’), skin necrosis, jaundice, hepatic dysfunction, nausea, vomiting, pancreatitis.

Interactions with other medicines (* indicates severe):

* Acetylsalicylic acid: increased risk of bleeding due to antiplatelet effect. * Alcohol: enhanced anticoagulant effect with large amounts of alcohol; major changes in alcohol consumption may affect anticoagulant control. 304 WHO Model Formulary for Children 2010

10.2

Medicines affecting coagulation

Allopurinol: anticoagulant effect possibly enhanced. * Amitriptyline: enhanced or reduced anticoagulant effect. Amoxicillin: studies have failed to demonstrate an interaction, but common experience in anticoagulant clinics is that INR can be altered by a course of amoxicillin. Ampicillin: studies have failed to demonstrate an interaction, but common experience in anticoagulant clinics is that INR can be altered by a course of ampicillin. * Azathioprine: anticoagulant effect possibly reduced. * Azithromycin: possibly enhanced anticoagulant effect of warfarin. * Carbamazepine: accelerated metabolism of warfarin (reduced anticoagulant effect). Cefazolin: possibly enhanced anticoagulant effect. * Cefixime: possibly enhanced anticoagulant effect. * Ceftazidime: possibly enhanced anticoagulant effect. * Ceftriaxone: possibly enhanced anticoagulant effect. * Chloramphenicol: enhanced anticoagulant effect. * Ciprofloxacin: enhanced anticoagulant effect. * Clomipramine: enhanced or reduced anticoagulant effect. * Contraceptives, oral: antagonism of anticoagulant effect by estrogens and progestogens. * Dexamethasone: anticoagulant effect possibly enhanced or reduced (high-dose dexamethasone enhances anticoagulant effect). * Doxycycline: anticoagulant effect possibly enhanced. * Erythromycin: enhanced anticoagulant effect. * Etoposide: possibly enhanced anticoagulant effect. * Fluconazole: enhanced anticoagulant effect. * Fluorouracil: anticoagulant effect possibly enhanced. * Fluoxetine: anticoagulant effect possibly enhanced. * Glibenclamide: possibly enhanced hypoglycaemic effects and changes to anticoagulant effect. * Griseofulvin: reduced anticoagulant effect. * Hydrocortisone: anticoagulant effect possibly enhanced or reduced (high-dose hydrocortisone enhances anticoagulant effect). * Ibuprofen: anticoagulant effect possibly enhanced. * Levamisole: anticoagulant effect possibly enhanced. * Levofloxacin: possibly enhanced anticoagulant effect. * Levonorgestrel: antagonism of anticoagulant effect. Levothyroxine: enhanced anticoagulant effect. * Medroxyprogesterone: antagonism of anticoagulant effect. * Mercaptopurine: anticoagulant effect possibly reduced. * Metronidazole: enhanced anticoagulant effect. * Miconazole: enhanced anticoagulant effect. * Nevirapine: enhanced or reduced anticoagulant effect. * Norethisterone: antagonism of anticoagulant effect. * Ofloxacin: enhanced anticoagulant effect. Paracetamol: prolonged regular use of paracetamol possibly enhances anticoagulant effect. WHO Model Formulary for Children 2010 305

10

Medicines affecting the blood

* Phenobarbital: metabolism of warfarin accelerated (reduced anticoagulant effect). * Phenytoin: accelerated metabolism of warfarin (possibility of reduced anticoagulant effect, but enhancement also reported). * Phytomenadione: antagonism of anticoagulant effect by phytomenadione. * Prednisolone: anticoagulant effect enhanced or reduced (high-dose prednisolone enhances anticoagulant effect). Proguanil: isolated reports of enhanced anticoagulant effect. * Quinidine: anticoagulant effect may be enhanced. * Rifampicin: accelerated metabolism of warfarin (reduced anticoagulant effect). * Ritonavir: plasma concentration possibly increased by ritonavir. Saquinavir: possibly enhanced anticoagulant effect. * Silver sulfadiazine: enhanced anticoagulant effect. * Simvastatin: enhanced anticoagulant effect. * Sulfadiazine: enhanced anticoagulant effect. * Sulfadoxine + pyrimethamine: enhanced anticoagulant effect. * Sulfamethoxazole + trimethoprim: enhanced anticoagulant effect. * Tamoxifen: enhanced anticoagulant effect. * Testosterone: enhanced anticoagulant effect. Trimethoprim: possibly enhanced anticoagulant effect. Vaccine, influenza: effect of warfarin occasionally enhanced. Valproic acid: anticoagulant effect possibly enhanced. Cranberry juice and products: enhanced anticoagulant effect (cranberry flavonoids inhibit CyP2C9). High doses of vitamin A, E or C: altered prothrombin time.
Notes: MONITORING It is essential that the INR be determined daily or on alternate days in the early days of treatment, and then at longer intervals (depending on response), then up to every 12 weeks.

Infant formula is supplemented with vitamin K, which makes formula fed infants resistant to warfarin; they may need higher doses. Breast milk contains low concentrations of vitamin K and breastfed infants are more sensitive to warfarin. Avoid switching warfarin brands once desired therapeutic response has been achieved. Target INR range: generally 2–3 for most indications; 2.5–3.5 for prosthetic heart valves and antiphospholipid antibody syndrome associated with thrombosis.
OTHeR CONSIDeRATIONS Warfarin antagonizes the effects of vitamin K and takes at least 48–72 hours for the anticoagulant effect to develop fully; if an immediate effect is required, heparin must be given concomitantly. Foods containing high amounts of vitamin K (such as beef liver, pork liver, green tea and green leafy vegetables) can reverse the anticoagulant effects of warfarin and affect therapeutic outcomes. A balanced diet is essential. Avoid large amounts of alfalfa, asparagus, broccoli, brussel sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress. High doses of vitamin A, e or C may alter prothrombin time, use fish oils or omega 3 with caution and avoid large amounts of liver, avocado, soy protein, soybean, papain. Avoid herbal teas or remedies (e.g. tonka beans, melilot, woodruff) as these contain natural coumarins and may increase the effect of warfarin. References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Kemp CA, McDowell JM. Paediatric pharmacopoeia. 13th ed. Melbourne, Royal Children’s Hospital, 2002. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009.

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SECTION 11: Blood products and plasma substitutes 11.1 Plasma substitutes ................................................................... 308 11.2 Plasma fractions for specific use............................................... 308

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11

Blood products and plasma substitutes

11
11.1

Blood products and plasma substitutes
Plasma substitutes

There are currently no medicines in this section of the 2nd WHO Model List of Essential Medicines for Children.

11.2

Plasma fractions for specific use

Blood coagulation factors
Factor VIII is essential for blood clotting and the maintenance of effective haemostasis. Von Willebrand factor is a mediator in platelet aggregation and also acts as a carrier for factor VIII. Blood coagulation factors VII, IX and X are essential for the conversion of factor II (prothrombin) to thrombin clot. Deficiency in any of these factors results in haemophilia, a group of X-linked bleeding disorders affecting 1 in 7000 males, most commonly presenting as bleeding into joints. Haemophilia A is factor VIII deficiency and haemophilia B is factor IX deficiency. Bleeding episodes in haemophilia require prompt treatment with replacement therapy.

Human normal immunoglobulin
Normal immunoglobulin solution is used as a source of antibody replacement in primary immunodeficiencies, and to modify the immune response in conditions such as Kawasaki disease.

Factor VIII concentrate
ATC code: B02BD02

Dried
Special Notes: Also known as antihaemophilic factor or Von Willebrand factor complex.

This medicine is listed as a representative of its pharmacological class. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. The information in this monograph only applies to the medicine listed here. Indications: Control of haemorrhage in haemophilia A. Contraindications: Previous anaphylactic reaction to factor VIII concentrate. Precautions: Intravascular haemolysis after large or frequently repeated doses in patients with blood groups A, B or AB (less likely with high potency, highly purified concentrates).
Dose:

Haemophilia A. Slow IV infusion: Administer according to patient’s needs and specific preparation used. For every 1 international unit per kg body weight of factor VIII activity administered, factor VIII level should increase by 2 international units/ml (or 2%); calculated dosage should be adjusted to the actual vial size. Calculation for units required, based on desired increase in factor VIII (% of normal). International units required = body weight (kg) x 0.5 x desired increase in factor VIII (international units/ml or % of normal).
NOTe This calculation assumes the patient’s baseline factor VIII level is < 1%. Renal impairment: Dose adjustment not required.

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11.2
Hepatic impairment: Dose reduction not required.

Plasma fractions for specific use

Adverse effects: Common Allergic reactions including chills and fever, headache, urticaria. Rare Pseudothrombocytopenia, elevated ALT. Interactions with other medicines (* indicates severe):

Activated prothrombin complex concentrates. Notes: IV compatibility: general advice is not to administer with any other drugs or IV fluids. All plasma fractions should comply with the WHO requirements for the collection, processing and quality control of blood, blood components and plasma derivatives (revised 1992). WHO expert Committee on Biological Standardization forty-third report, WHO Technical Report Series, No. 840, 1994, Annex 2.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009.

Factor IX complex (coagulation factors II, VII, IX, X) concentrate
ATC code: B02BD01

Dried
Special Notes: Both human and animal derived products are available.

This medicine is listed as a representative of its pharmacological class. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. The information in this monograph only applies to the medicine listed here.
Indications: Replacement therapy for factor IX deficiency in haemophilia B; bleeding due to

deficiencies of factors II, VII or X.

Contraindications: Disseminated intravascular coagulation; hypersensitivity to mouse or hamster

protein (if not the human form); fibrinolysis.

Precautions: Risk of thrombosis (probably less risk with highly purified preparations); because of

this risk, use with caution in liver dysfunction, postoperative period, neonates or disseminated intravascular coagulation.

Dose:

Replacement therapy for factor IX deficiency in haemophilia B or bleeding due to deficiencies of factors II, VII or X as well as IX. Slow IV infusion: administer according to patient’s needs and specific preparation used. Calculation for units required to raise blood level %. Using Benefix. Neonate, Infant or Child number of factor IX international units required = body weight (in kg) x desired factor IX level increase (% normal) x 1.4 international units/kg. Using AlphaNine SD, Mononine. Neonate, Infant or Child number of factor IX international units required = body weight (in kg) x desired factor IX level increase (% normal) x 1 international unit/kg.

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Blood products and plasma substitutes

GeNeRAL GUIDeLINeS Minor spontaneous haemorrhage, prophylaxis. Desired levels of factor IX for haemostasis: 15–25%. Initial loading dose to achieve desired level: up to 20–30 international units/kg. Frequency of dosing: every 12–24 hours. Duration of treatment: 1–2 days. Moderate haemorrhage. Desired levels of factor IX for haemostasis: 25–50%. Initial loading dose to achieve desired level: 25–50 international units/kg. Frequency of dosing: every 12–24 hours. Duration of treatment: 2–7 days. Major haemorrhage. Desired levels of factor IX for haemostasis: > 50%. Initial loading dose to achieve desired level: 30–50 international units/kg. Frequency of dosing: every 12–24 hours depending on half-life and measured factor IX levels (after 3–5 days, maintain at least 20% activity). Duration of treatment: 7–10 days, depending upon nature of insult. Surgery. Desired levels of factor IX for haemostasis: 50–100%. Initial loading dose to achieve desired level: 50–100 international units/kg. Frequency of dosing: every 12–24 hours, depending on half-life and measured factor IX levels. Duration of treatment: 7–10 days, depending upon nature of insult.
Renal impairment: Dose adjustment not necessary. Hepatic impairment: Dose adjustment not necessary. Adverse effects: Common Allergic reactions including chills and fever, flushing, headache, nausea,

vomiting, urticaria. B patients.

Uncommon Disseminated intravascular coagulation, thrombosis following high doses in haemophilia Notes: IV compatibility: general advice is not to administer with any other drugs or IV fluids.

All plasma fractions should comply with the WHO requirements for the collection, processing and quality control of blood, blood components and plasma derivatives (revised 1992). WHO expert Committee on Biological Standardization forty-third report, WHO Technical Report Series, No. 840, 1994, Annex 2.
References:
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009.

Human normal immunoglobulin
ATC code: J06BA02

Intramuscular administration: 16% protein solution* Intravenous administration: 5%; 10% protein solution** Subcutaneous administration: 15%; 16% protein solution* Intravenous human normal immunoglobulin may very rarely induce thromboembolic events and should be used with caution in those with risk factors for arterial or venous thrombotic events and in obese individuals. Normal immunoglobulin may interfere with the immune response to live virus vaccines which should therefore only be given at least 3 weeks before or 3 months after an injection of normal immunoglobulin (this does not apply to yellow fever vaccine since normal immunoglobulin does not contain antibody to this virus).

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11.2
Special Notes: *Indicated for primary immune deficiency. **Indicated for primary immune deficiency and Kawasaki disease.

Plasma fractions for specific use

NOTe Formulations from different manufacturers vary and should not be regarded as equivalent; consult individual manufacturer’s product literature. Indications: Replacement therapy in primary immunodeficiency; Kawasaki disease. Contraindications: Hypersensitivity to immunoglobulin or blood products. Precautions: IM PRePARATION Use with caution in patients with thrombocytopenia or coagulation disorders. Dose:

Consult individual manufacturer’s product literature for dose and administration recommendations for specific diseases; recommended doses may vary to those listed below. Replacement therapy in primary immune deficiencies. IV infusion: Child all ages initial loading dose, administer until serum IgG level is > 6 g/l. IV, IM or SC (depending on formulation): Child all ages maintenance dose, normally 400–800 mg/kg/month, titrated according to intercurrent infections or trough serum IgG level. IV doses may be given at 1, 2, 3 or 4 week intervals. SC doses may be given at 1, 2, 3, 4 or 7 day intervals. Kawasaki disease. IV infusion: Infant or Child 2 g/kg as a single dose, given over 10–12 hours; if signs and symptoms persist, re-treatment with a second 2 g/kg infusion should be considered. Must be used in combination with acetylsalicylic acid.
Renal impairment: Dose reduction not required. Hepatic impairment: Dose reduction not required. Adverse effects: Common Nausea, vomiting, headache (may develop 24 hours after infusion),

dizziness, dry mouth, chills, sweating, hypothermia, fever, eczema, rash, urticaria, hypotension, wheezing, anaphylactoid reactions. Rare Immune haemolysis, aseptic meningism, increased plasma viscosity, hypercoagulopathy, renal impairment.
Interactions with other medicines (* indicates severe):

Live virus vaccines (measles, mumps, rubella): see Warnings.
Notes: IV compatibility: general advice is not to administer with any other drugs or IV fluids.

IV infusion over 2–12 hours.
ADMINISTRATION Infusion rates of < 8 g per hour are recommended. Immunoglobulin should be administered under the supervision of an immunologist or other experienced physician. In general, this should be in a hospital with adequate facilities for monitoring the infusion as well as the condition for which it is being administered, until the patient is stable, when treatment at home can be considered after formal training in an expert centre.
Hill SR, Kouimtzi M, Stuart MC, eds. WHO model formulary. Geneva, World Health Organization, 2008. Hodding JH, Kraus DM, Taketomo CK. Pediatric dosage handbook. 16th ed. Hudson, Lexi-Comp, 2009. Paediatric Formulary Committee. British national formulary for children 2009. London, BMJ Group RBS Publishing, 2009.

References:

WHO Model Formulary for Children 2010

311

...............................6 Antianginal medicines ......1 12.................................. 313 Antiarrhythmic medicines ...................4 12........5 12..................................... 313 Medicines used in heart failure .......................................................... 316 Antithrombotic medicines .................... 321 Lipid-lowering agents ....2 12................... 313 Antihypertensive medicines ................3 12......................... 321 312 WHO Model Formulary for Children 2010 .....................SECTION 12: Cardiovascular medicines 12...........................................

12.g. seizures.g. 5 mmHg greater than the 99th percentile) or symptomatic requires urgent pharmacological management. management of obesity) should be considered. diabetes mellitus). Controlled reduction should therefore be undertaken in hospital with careful supervision and monitoring. chest pain).1 Cardiovascular medicines Antianginal medicines This section has been deleted from the 2nd WHO Model List of Essential Medicines for Children. Controlled reduction in blood pressure should occur over a period of 72–96 hours. since rapid reduction can cause “end organ damage”. Specialist assessment and advice should be sought when possible. Hypertension in children is therefore defined as either systolic and/or diastolic BP ≥ 95th percentile measured on three or more separate occasions.g.g. nonpharmacological measures (e. and associated conditions including other cardiovascular risk factors (e. gender and height. 12. WHO Model Formulary for Children 2010 313 .2 Antiarrhythmic medicines There are currently no medicines in this section of the 2nd WHO Model List of Essential Medicines for Children. dietary measures such as salt restriction. depending on duration of hypertension.1 Antianginal medicines 12 12. left ventricular hypertrophy or retinopathy). Management Hypertension which is severe (e. In hypertension which is mild to moderate and is not symptomatic. diabetes or obesity). The goals of initial management of children with hypertension are to: • establish whether it is secondary to an underlying cause which can be treated • manage hypertensive emergencies • determine if medication is required for blood pressure control • assess and manage any associated cardiovascular risk factors (e. Pharmacological management may also be required.12. respiratory distress.g. focal neurological symptoms or signs. Symptoms suggestive of a hypertensive emergency include headache. altered conscious state.g.3 Antihypertensive medicines Hypertension Blood pressure (BP) in children is classified according to centile charts according to age. any evidence of associated end organ damage (e. visual disturbance or clinical features suggestive of cardiac failure (e.

constipation. increased as necessary up to 500 micrograms/kg daily in 1–3 divided doses. fever. angioedema (early or delayed onset). Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. flushing. hoarseness. sore throat. Indications: Hypertension. Adverse effects: Common Hypotension. especially in patients on diuretics. Contraindications: Hypersensitivity to angiotensin-converting enzyme (ACe) inhibitors (including angioedema). cough. risk of pulmonary oedema). treatment should therefore be initiated with very low doses. itching. on a low-sodium diet. myalgia. also withhold before desensitization with wasp or bee venom. chest pain. neuropathy. renal impairment. palpitations. 5 mg Special Notes: This medicine is listed as a representative of its pharmacological class. visceral angioedema. on dialysis. haemolytic anaemia. USe WITH DIUReTICS Risk of very rapid falls in blood pressure in volume-depleted patients. Rare Hepatitis (cholestatic or hepatocellular).5 mg. nausea. increased as necessary up to a maximum of 1 mg/kg daily in 1–2 divided doses. headache. hypotension with first doses.12 Cardiovascular medicines Enalapril ATC code: C09AA02 Tablet: 2. eosinophilia. gynaecomastia. 314 WHO Model Formulary for Children 2010 . thrombocytopenia. The information in this monograph only applies to the medicine listed here. if dehydrated. heart failure. use with great care in severe or symptomatic aortic stenosis. anorexia. photosensitivity. hyponatraemia. renal impairment. fatigue. neutropenia. ANAPHyLACTOID ReACTIONS Avoid enalapril during dialysis with high-flux polyacrilonitrile membranes and during low-density lipoprotein apheresis with dextran sulfate. Monitor blood pressure carefully for 1–2 hours. If high-dose diuretic cannot be stopped. vomiting. pancreatitis. pregnancy. history of idiopathic or hereditary angioedema (use with care or avoid). Hepatic impairment: Closely monitor liver function in patients with hepatic impairment. Monitor blood pressure and urine output carefully for at least 2 hours following first dose and during dose escalation until blood pressure is stable. Infant or Child initially 100 micrograms/kg once daily. Dose: Hypertension and heart failure. peripheral vascular disease or generalized atherosclerosis (risk of clinically silent renovascular disease). agranulocytosis. arthralgia. pemphigus. High-dose diuretic therapy should be discontinued. hyperkalaemia. Raynaud syndrome. or with heart failure. possibly increased risk of agranulocytosis in collagen vascular disease. dizziness. muscle cramps. Uncommon Anaphylactoid reactions. Oral: Neonate initially 10 micrograms/kg once daily. at least 24 hours before starting enalapril (may not be possible in heart failure. stomatitis. Renal impairment: Use with caution in all degrees of impairment and monitor response. dry mouth. Start with a lower initial dose and adjust according to response. diarrhoea. Hyperkalaemia and other adverse effects more common. hepatic impairment. Precautions: Use with diuretics. paraesthesia. rash. monitor renal function before and during treatment. toxic epidermal necrolysis. renovascular disease. aplastic anaemia. taste disturbances. medical supervision advised for at least 2 hours after administration or until blood pressure is stable. abnormal dreams. psoriasis. proteinuria. elevated hepatic aminotransferases and bilirubin. or dose significantly reduced.

Sodium nitroprusside: enhanced hypotensive effect. Ibuprofen: antagonism of hypotensive effect. * Lithium: enalapril reduces excretion of lithium (increased plasma lithium concentration). * Potassium salts: increased risk of severe hyperkalaemia. Halothane: enhanced hypotensive effect. increased risk of renal impairment. Hydrocortisone: antagonism of hypotensive effect. particularly in preterm neonates. Diazepam: enhanced hypotensive effect. magnesium hydroxide): absorption of enalapril reduced. and some neonates develop profound hypotension with even small doses. WHO Model Formulary for Children 2010 315 . Notes: Tablets may be crushed and suspended in water immediately before use. Nitrous oxide: enhanced hypotensive effect. Heparin: encreased risk of hyperkalaemia. Atenolol: enhanced hypotensive effect. Kouimtzi M. Stuart MC. renal failure and severe unpredictable hypotension are very common in the first month of life and it is therefore recommended that ACe inhibitors are avoided whenever possible. Dexamethasone: antagonism of hypotensive effect. 2009. Ketamine: enhanced hypotensive effect. Propranolol: enhanced hypotensive effect.3 Interactions with other medicines (* indicates severe): Antihypertensive medicines * Acetazolamide: enhanced hypotensive effect. BMJ Group RBS Publishing. Prednisolone: antagonism of hypotensive effect. Thiopental: enhanced hypotensive effect. * Hydrochlorothiazide: enhanced hypotensive effect. Antacids (aluminium hydroxide. WHO model formulary. seizures. * Furosemide: enhanced hypotensive effect. * Ciclosporin: increased risk of hyperkalaemia. * Spironolactone: enhanced hypotensive effect. 2008. World Health Organization. Alcohol: enhanced hypotensive effect. The neonatal response to treatment with ACe inhibitors is very variable. * Amiloride: enhanced hypotensive effect. Adverse effects such as apnoea. risk of renal impairment when acetylsalicylic acid given in doses of over 300 mg daily. eds. London. Chlorpromazine: enhanced hypotensive effect. Acetylsalicylic acid: antagonism of hypotensive effect. British national formulary for children 2009. Fluphenazine: enhanced hypotensive effect. increased risk of severe hyperkalaemia. References: Hill SR. a test dose should be used initially and increased cautiously.12. Geneva. Insulins: hypoglycaemic effect possibly enhanced. Amlodipine: enhanced hypotensive effect. Haloperidol: enhanced hypotensive effect. increased risk of severe hyperkalaemia (monitor plasma potassium concentration with low-dose spironolactone in heart failure). Paediatric Formulary Committee.

sick sinus syndrome. Neonate over 2. Digoxin ATC code: C01AA05 Injection: 250 micrograms/ml in 2 ml ampoule Oral liquid: 50 micrograms/ml Tablet: 62.5 mg in three divided doses for 24 hours then 62. Oral: Neonate under 1. intermittent complete heart block. Child 5–10 years initially 25 micrograms/kg (maximum 500 micrograms) in three divided doses for 24 hours then 6 micrograms/kg/day (maximum 250 micrograms daily) in 1–2 divided doses.5 kg initially 25 micrograms/kg in three divided doses for 24 hours then 4–6 micrograms/kg/day in 1–2 divided doses. Child 2–5 years initially 35 micrograms/kg in three divided doses for 24 hours then 10 micrograms/kg/day in 1–2 divided doses.g.5 kg initially 30 micrograms/kg in three divided doses for 24 hours then 4–6 micrograms/kg/day in 1–2 divided doses. myocarditis.4 Medicines used in heart failure Heart failure in children is less common than in adults.5 kg initially 30 micrograms/kg in three divided doses for 24 hours then 4–6 micrograms/kg/day in 1–2 divided doses. over 10 years initially 0. in rheumatic heart disease).g. over 10 years initially 0.5 kg initially 20 micrograms/kg in three divided doses for 24 hours then 4–6 micrograms/kg/day in 1–2 divided doses. thyroid disease. renal impairment.5 kg or Child under 2 years initially 45 micrograms/kg in three divided doses for 24 hours then 10 micrograms/kg/day in 1–2 divided doses. severe pulmonary disease. valvular disease (e. Wolff-Parkinson-White syndrome and atrial fibrillation concurrently. myocardial dysfunction or highoutput heart failure (e. Intravenous: Neonate under 1.5–2. Dose: Chronic heart failure. second-degree atrioventricular block.5–250 micrograms/daily in 1–2 divided doses (higher doses may be necessary). constrictive pericarditis.5–2. 5–10 years initially 25 micrograms/kg (maximum 750 micrograms) in three divided doses for 24 hours then 6 micrograms/kg/day (maximum 250 micrograms daily) in 1–2 divided doses. 250 micrograms Indications: Chronic heart failure.75–1.5–1 mg in three divided doses for 24 hours then 62. ventricular tachycardia or fibrillation.12 Cardiovascular medicines 12. 316 WHO Model Formulary for Children 2010 .5 kg or Child under 5 years initially 35 micrograms/kg in three divided doses for 24 hours then 10 micrograms/kg/day in 1–2 divided doses. avoid rapid intravenous administration (nausea and risk of arrhythmias). septal defects). Precautions: Recent myocardial infarction. and can be due to left-to-right shunts (e.g. Rheumatic heart disease remains a very large cause of heart failure in the developing world.5–250 micrograms daily in 1–2 divided doses (higher doses may be necessary). anaemia). Contraindications: Hypertrophic obstructive cardiomyopathy (unless also atrial fibrillation and heart failure). Neonate over 2. Neonate 1. Neonate 1.5 micrograms. avoid hypokalaemia.

agitation. depression. Gentamicin: possibly increased plasma concentration of digoxin. visual disturbances. Calcium salts: large intravenous doses of calcium salts can precipitate arrhythmias. * Verapamil: increased plasma concentration of digoxin. seizures. * Quinine: plasma concentration of digoxin increased. * Hydrochlorothiazide: hypokalaemia caused by hydrochlorothiazide increases cardiac toxicity of digoxin. * Furosemide: hypokalaemia caused by furosemide increases cardiac toxicity of digoxin. Hydrocortisone: increased risk of hypokalaemia. Ibuprofen: possibly exacerbation of heart failure. dizziness. Phenytoin: plasma concentration of digoxin possibly reduced.4 disturbances. shortened QRS complex. Rare Xanthopsia (yellow vision). gynaecomastia (long-term use).12. amnesia. rash. Sulfasalazine: absorption of digoxin possibly reduced. Prednisolone: increased risk of hypokalaemia. blurred vision. atrial or ventricular extrasystoles. * Amphotericin B: hypokalaemia caused by amphotericin B increases cardiac toxicity of digoxin. * Chloroquine: plasma digoxin concentration possibly increased. toxicity increased by electrolyte Hepatic impairment: Dose reduction not necessary. Uncommon Acute psychosis. Salbutamol: possibly reduced plasma concentration of digoxin. Dexamethasone: increased risk of hypokalaemia. diarrhoea. confusion. Interactions with other medicines (* indicates severe): * Acetazolamide: hypokalaemia caused by acetazolamide increases cardiac toxicity of digoxin. * Ciclosporin: increased plasma concentration of digoxin (increased risk of toxicity). * Spironolactone: plasma concentration of digoxin increased. Trimethoprim: plasma concentration of digoxin possibly increased. paroxysmal atrial tachycardia with AV block. Erythromycin: increased plasma concentration of digoxin (increased risk of toxicity). Rifampicin: plasma concentration of digoxin possibly reduced. drowsiness. * Quinidine: plasma concentration of digoxin increased (halve dose of digoxin). Penicillamine: plasma concentration of digoxin possibly reduced. nightmares. Timolol: increased AV block and bradycardia. Mefloquine: possibly increased risk of bradycardia. Sulfamethoxazole + trimethoprim: plasma concentration of digoxin possibly increased. increased AV block and bradycardia. Antacids (aluminium hydroxide. Suxamethonium: risk of ventricular arrhythmias. WHO Model Formulary for Children 2010 317 . ventricular tachycardia or fibrillation. nausea. thrombocytopenia. Azithromycin: increased plasma concentration of digoxin (increased risk of toxicity). and increased plasma digoxin concentration. vomiting. delirium. * Nifedipine: possibly increased plasma concentration of digoxin. magnesium hydroxide): possibly reduced absorption of digoxin. Adverse effects: Common Anorexia. Medicines used in heart failure Renal impairment: Reduce dose in all degrees of impairment. Atenolol: increased risk of AV block and bradycardia. heart block. reduced renal function. Propranolol: increased risk of AV block and bradycardia.

When changing from intravenous to oral route. Infant or Child 0. preferably prior to next dose. Renal function is very important in determining digoxin dosage.5 mg/kg per minute (doses < 120 mg) or 4 mg/minute (doses ≥ 120 mg). 2008. Kraus DM. plasma digoxin concentration should be maintained in the range 0.5–3 micrograms/litre for digoxin. nausea.5–1 mg/kg (maximum 4 mg/kg) repeated every 8 hours as necessary. bradycardia and heart block. 2009.5 micrograms/ml. Indications: Oedema associated with heart failure. Doses may need to be reduced if digoxin (or another cardiac glycoside) has been given in the preceding 2 weeks. Adelaide. Also. eds.12 Cardiovascular medicines Notes: MONITORING For plasma digoxin concentration assay. Taketomo CK.9% or glucose 5% to a maximum concentration of 62.5–2 mg/kg 2–3 times daily. Patients at highest risk are those with renal impairment. It can sometimes be difficult to distinguish between toxic effects and clinical deterioration because the symptoms of both are similar. ADMINISTRATION For intravenous infusion. Pediatric dosage handbook. 16th ed. renal impairment.5–1 mg/kg every 12–24 hours (every 24 hours if corrected age under 31 weeks). oral solution must not be diluted. dizziness. London. Infant or Child 0. loading doses should be given over 30–60 minutes and maintenance doses over 10–20 minutes. Australian medicines handbook. WHO model formulary. Signs of digoxin toxicity may include: anorexia. hepatic impairment. Furosemide ATC code: C03CA01 Injection: 10 mg/ml in 2 ml ampoule Oral liquid: 4 mg/ml Tablet: 40 mg To avoid ototoxicity.8–2 micrograms/litre. Stuart MC. precomatose states associated with liver cirrhosis. may need to increase dose by 20–30% to maintain the same plasma digoxin concentration. Unwanted effects depend both on the concentration of digoxin in the plasma and on sensitivity of the conducting system or of the myocardium. Kouimtzi M. higher doses may be required in resistant oedema. World Health Organization. IV: Neonate 0. Special Notes: Also referred to as frusemide. 2009. Lexi-Comp. Hodding JH.5–2 mg/kg every 12–24 hours (every 24 hours if corrected age under 31 weeks). Rossi S. References: Hill SR. Precautions: Monitor electrolytes particularly potassium and sodium. dilute with sodium chloride 0. Protect from light. Geneva. Paediatric Formulary Committee. For oral administration. ed. BMJ Group RBS Publishing. Dose: Oedema in heart failure. Australian Medicines Handbook. maximum 12 mg/kg (80 mg) daily. which is often increased in heart disease. vomiting. Contraindications: Renal failure with anuria. British national formulary for children 2009. hypotension. blood should ideally be taken at least 6 hours after a dose. 318 WHO Model Formulary for Children 2010 . 2009. Plasma monitoring may be required when changing formulation to take into account varying bioavailabilities. Oral: Neonate 0. the plasma digoxin concentration alone cannot indicate toxicity reliably but the likelihood of toxicity increases progressively through the range 1. Hudson. intravenous doses should be given no faster than 0.

orthostatic hypotension. bullous eruptions. especially in renal impairment. Medicines used in heart failure Higher doses are usually required in impairment. Chlorpromazine: enhanced hypotensive effect. Insulins: antagonism of hypoglycaemic effect. Rare Tinnitus. hyperuricaemia. * Gentamicin: increased risk of ototoxicity. exfoliative dermatitis. Uncommon Dyslipidaemia. Diazepam: enhanced hypotensive effect. Treatment with nephrotoxic drugs increases risk of nephrotoxicity with loop diuretics. furosemide safer than hydrochlorothiazide. deafness (especially with rapid intravenous administration). * Digoxin: hypokalaemia caused by furosemide increases cardiac toxicity of digoxin. Salbutamol: increased risk of hypokalaemia with high doses of salbutamol. dizziness. * Vancomycin: increased risk of ototoxicity. hypokalaemia. hypocalcaemia.12.4 Renal impairment: Contraindicated in anuria. * Enalapril: enhanced hypotensive effect. Lidocaine: action of lidocaine antagonized by hypokalaemia caused by furosemide (interaction less likely when lidocaine used topically). Stevens-Johnson syndrome. Thiopental: enhanced hypotensive effect. Hydrocortisone: antagonism of diuretic effect. agranulocytosis. monitor electrolytes and creatinine. Carbamazepine: increased risk of hyponatraemia. Cisplatin: increased risk of nephrotoxicity and ototoxicity. Adverse effects: Most adverse effects are dose related. use combinations carefully. * Lithium: reduced lithium excretion (increased plasma lithium concentration and risk of toxicity). increased risk of hypokalaemia. increased risk of hypokalaemia. Common Hyponatraemia. antagonism of diuretic effect. * Quinidine: cardiac toxicity of quinidine increased by hypokalaemia caused by furosemide. Propranolol: enhanced hypotensive effect. thrombocytopenia. rash. interstitial nephritis. hypomagnesaemia. renal function may worsen. Amitriptyline: increased risk of postural hypotension. vertigo. Ethanol: enhanced hypotensive effect. Nitrous oxide: enhanced hypotensive effect. Hydrochlorothiazide: increased risk of hypokalaemia. increased risk of hypokalaemia. Ketamine: enhanced hypotensive effect. Amphotericin B: increased risk of hypokalaemia. jaundice. Ibuprofen: risk of nephrotoxicity of ibuprofen increased. syncope. Dexamethasone: antagonism of diuretic effect. * Streptomycin: increased risk of ototoxicity. Halothane: enhanced hypotensive effect. WHO Model Formulary for Children 2010 319 . Hepatic impairment: Hypokalaemia may precipitate coma (use potassium-sparing diuretic to prevent this). haemolytic anaemia. allergic reactions. Prednisolone: antagonism of diuretic effect. dehydration. gout. acute pancreatitis. Interactions with other medicines (* indicates severe): * Amikacin: increased risk of ototoxicity. increased creatinine concentration.

careful dose titration and monitoring are necessary. World Health Organization. Hudson. References: Notes: Advise patient or carer when taking furosemide twice daily. Australian Medicines Handbook. nausea. angina. Rossi S. Uncommon Abnormal ventricular conduction. Precautions: Correct hypovolaemia before initiating treatment. Interactions with other medicines (* indicates severe): Chlorpromazine: antagonism of hypertensive effect. palpitations. Infuse higher concentrations through central venous catheter using a syringe pump to avoid extravasation and fluid overload. Geneva. Infant or Child initially 5 micrograms/kg/minute adjusted according to response to a maximum of 20 micrograms/kg/minute. 320 WHO Model Formulary for Children 2010 . WHO model formulary. Fluphenazine: antagonism of hypertensive effect. Pediatric dosage handbook. phaeochromocytoma. dyspnoea. Consider the addition of potassium-sparing diuretics or potassium supplements. hypotension or hypertension. Haloperidol: antagonism of hypertensive effect. piloerection. Adverse effects: Common ectopic beats. Adelaide. hypercapnia and metabolic acidosis before or at same time as starting treatment. extravasation (may cause necrosis and sloughing of surrounding tissue). Continuous intravenous infusion: Neonate initially 3 micrograms/kg/minute adjusted according to response to a maximum of 20 micrograms/kg/minute. In neonates the response to inotropic sympathomimetics varies considerably. vasoconstriction. uraemia. Kouimtzi M. Ergometrine: increased risk of ergotism. Australian medicines handbook. Rare Allergic reaction (if sodium metabisulfite in product). manufacturer contraindicates treatment with halogenated hydrocarbon general anaesthetics or ergot alkaloids. headache. 16th ed. Hepatic impairment: Dose reduction not necessary. Paediatric Formulary Committee. particularly in those born prematurely. Stuart MC.9%. dilute to a maximum concentration of 3. to take the first dose in the Hill SR. Monitor potassium during therapy. mydriasis. tachycardia.2 mg/ml with glucose 5% or sodium chloride 0. bradycardia. ed. Kraus DM. history of peripheral vascular disease (increased risk of ischaemia of extremities). BMJ Group RBS Publishing. 2008. Hodding JH. Lexi-Comp. London.12 Cardiovascular medicines morning and the second dose before 18:00 to prevent overnight diuresis. Contraindications: Tachyarrhythmia. maintain blood volume during treatment. Dopamine ATC code: C01CA04 Injection: 40 mg/ml (hydrochloride) in 5 ml vial Indications: Cardiac failure. Notes: For continuous intravenous infusion. 2009. correct hypoxia. British national formulary for children 2009. vomiting. Incompatible with bicarbonate and other alkaline solutions. Dose: Cardiac failure. 2009. eds. Taketomo CK. Renal impairment: Dose reduction not necessary. 2009.

WHO Model Formulary for Children 2010 321 . Rossi S. WHO model formulary. Kouimtzi M.5 Antithrombotic medicines This section has been deleted from the 2nd WHO Model List of Essential Medicines for Children. Hudson. Australian medicines handbook. ed. Lexi-Comp. 12. British national formulary for children 2009. eds. BMJ Group RBS Publishing. Kraus DM.12. Hodding JH. 2009. London. Adelaide. Paediatric Formulary Committee. 2009.5 References: Antithrombotic medicines Hill SR. Stuart MC. Geneva. 2008. 12. Pediatric dosage handbook. 16th ed. Australian Medicines Handbook. World Health Organization. 2009. Taketomo CK.6 Lipid-lowering agents There are currently no medicines in this section of the 2nd WHO Model List of Essential Medicines for Children.

......................3 13..................SECTION 13: Dermatological medicines (topical) 13...................... 332 Medicines affecting skin differentiation and proliferation ..............................................4 13..1 13.......................................... 332 Scabicides and pediculicides ....2 13.. 325 Anti-inflammatory and antipruritic medicines ... 337 322 WHO Model Formulary for Children 2010 ..........................6 Antifungal medicines ....5 13............................. 329 Astringent medicines .................................................... 323 Anti-infective medicines ..

13. Indications: Mild fungal skin infections. Geneva. 2009 (http://etg. Local treatments are often effective. BMJ Group RBS Publishing.tg. Renal impairment: Dose reduction not required. headaches. The selection and use of essential medicines: report of the WHO expert committee. Hepatic impairment: Dose reduction not required. erosion. 2008. accessed 10 February 2010). Paediatric Formulary Committee. October 2007 (including the model list of essential medicines for children). ed. 2009. References: eTG complete. and the choice of agent is often dictated by local availability and price. WHO expert committee on the selection and use of essential medicines.pdf ). Australian Medicines Handbook. dizziness. Stuart MC. increasing risk of bleeding. World Health Organization. particularly in babies and young children when applied in large amounts or when used under occlusion. Precautions: Contact with eyes.org. eds. rapid breathing. large areas. can cause local skin infections as well as more serious systemic infections. Kouimtzi M. WHO model formulary. avoid combinations. systemic absorption. More severe infections may require systemic treatments. Topical: Infant or Child apply twice daily until the infected skin is shed (usually at least 4 weeks). Adverse effects: Uncommon Occasionally localized.who. WHO Technical Report Series. face and genitals. Hill SR. such as Candida. Therapeutic Guidelines Limited.int/medicines/publications/essentialmeds_committeereports/TRS_950. Australian medicines handbook. mild inflammatory reaction. 2008. Interactions with other medicines (* indicates severe): Warfarin: topical salicylates may be absorbed in sufficient amounts to cause an increase in INR. deaths have occurred. 2009. Rossi S. salicylate intoxication. Melbourne. particularly localized tinea pedis and tinea corporis. Notes: Benzoic acid + salicylic acid are both mild irritants and can themselves cause dermatitis. tinnitus. mucous membranes. Rare Skin ulceration. topical use of salicylic acid has resulted in salicylate intoxication.1 Antifungal medicines 13 13. prolonged use. Adelaide. Other fungi. British national formulary for children 2009. 950 (http://www. Benzoic acid + Salicylic acid ATC code: D01Ae20 Cream or ointment: 6% + 3% Special Notes: Also known as Whitfield’s ointment. WHO Model Formulary for Children 2010 323 . Administration: Fungal skin infections. Symptoms include confusion.au/ip/. London.1 Dermatological medicines (topical) Antifungal medicines “Tinea” refers to a skin or nail infection with a dermatophyte (ringworm) fungus. Salicylate intoxication Although rare.

discontinue if sensitization occurs. * Warfarin: enhanced anticoagulant effect. Paediatric Formulary Committee. The information in this monograph only applies to the medicine listed here. Melbourne. Rare Allergic reactions. Renal impairment: Dose reduction not required. seborrhoeic dermatitis. Australian medicines handbook. Administration: Fungal skin infections. 2002.13 Dermatological medicines (topical) Miconazole ATC code: D01AC02 Cream or ointment: 2% (nitrate) Special Notes: This medicine is listed as a representative of its pharmacological class. World Health Organization. Indications: Fungal skin infections. October 2007 (including the model list of essential medicines for children). Paediatric pharmacopoeia. Stuart MC. stinging. Topical: Child over 5 years apply with a small amount of water to the entire affected area and leave for 30 minutes. Adelaide. Hepatic impairment: Dose reduction not required. WHO expert committee on the selection and use of essential medicines. itch. Administration: Pityriasis versicolor. Adverse effects: Uncommon Occasional local irritation and burning. Notes: Continue using the treatment for 10 days after symptoms have gone. Kemp CA. Australian Medicines Handbook. Topical: Child all ages apply twice daily to clean dry lesions. Rossi S. do not use within 48 hours of applying preparations for hair colouring. London. WHO Technical Report Series. The selection and use of essential medicines: report of the WHO expert committee. Interactions with other medicines (* indicates severe): NOTe Drug interactions may occur rarely with miconazole as some absorption occurs from topical products. Amphotericin B: possible antagonism of effects of amphotericin B. References: Hill SR. Geneva. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. repeat course if necessary. WHO model formulary. Royal Children’s Hospital. Kouimtzi M. Contraindications: Children under 5 years. avoid contact with eyes. ed. continuing for at least 10 days after the condition has cleared. eds. 13th ed. Selenium sulfide ATC code: D01Ae13 Detergent based suspension: 2% Indications: Pityriasis versicolor. Apply 2–7 times over 2 weeks. BMJ Group RBS Publishing. 2009. Carbamazepine: plasma concentration of carbamazepine possibly increased. contact dermatitis. Precautions: Do not apply to damaged skin (risk of systemic toxicity). 324 WHO Model Formulary for Children 2010 . British national formulary for children 2009. straightening or permanent waving. 950 (http://www. 2008. 2008.int/medicines/publications/essentialmeds_committeereports/TRS_950.who. McDowell JM. 2009.pdf ).

London. Paediatric Formulary Committee. occasional vomiting (symptoms usually resolve within 10 days of discontinuing the medicine). References: Hill SR. Renal impairment: Dose reduction not required.int/medicines/publications/essentialmeds_committeereports/TRS_950. World Health Organization. Hepatic impairment: Dose reduction not required. Kouimtzi M. WHO model formulary. eds. WHO expert committee on the selection and use of essential medicines. WHO Technical Report Series. furunculosis.2. 2009. BMJ Group RBS Publishing. since selenium sulfide may damage it.2. weakness.2). Methylrosanilinium chloride (gentian violet) ATC code: D01Ae02 Aqueous solution: 0. October 2007 (including the model list of essential medicines for children). Topical: Child over 5 years massage 5–10 ml of suspension into wet hair and leave for 5–10 minutes before rinsing off thoroughly. 13. 950 (http://www.1 and 6. Stuart MC. treatment) or loss.13. Mcevoy GK. 2008.who. hair discoloration (minimized by careful rinsing after Rare Absorption may result in systemic toxicity including tremors. repeat twice weekly for 2 weeks. such as impetigo. 2008. Bethesda. if contact occurs. Geneva. British national formulary for children 2009.2 Anti-infective medicines Seborrhoeic dermatitis. skin discoloration (when applied topically for the treatment of tinea versicolor). Carcinogenic in animal studies and its use is restricted in some countries. American Society of Health-System Pharmacists. lethargy. Widespread superficial or deepseated skin infections associated with fever require treatment with a systemic antibiotic (sections 6. loss of appetite. The selection and use of essential medicines: report of the WHO expert committee. AHFS drug information. are very common. Contact with eyes should be avoided. rinse hair thoroughly after use and remove all traces from skin (including nails).2 Anti-infective medicines Staphylococcal and streptococcal infections of the skin. pain in lower abdomen.5% Tincture: 0. Minor localized infections can often be treated with local treatments. Uncommon Rebound oiliness of the scalp. Adverse effects: Common Local irritation. Patients should be advised to remove all jewellery before using the lotion. the affected eye(s) should be rinsed thoroughly with water.pdf ). then once weekly for 2 weeks and then as necessary. folliculitis. 2009. ed.5% Special Notes: Also known as gentian violet or crystal violet. Notes: To minimize absorption. erysipelas and cellulitis. WHO Model Formulary for Children 2010 325 . Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use.

Geneva. The information in this monograph only applies to the medicine listed here. London. Renal impairment: No dose reduction required. Sweetman SC. broken skin. Adverse effects: Common Hypersensitivity reactions (including contact dermatitis. 950 (http://www. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. Renal impairment: Any systemic absorption in patients with renal impairment may cause increased side effects. ototoxicity may be a hazard in children.13 Dermatological medicines (topical) This medicine is listed as a representative of its pharmacological class. LARGe AReAS If large areas of skin are being treated. Uncommon Severe irritation: discontinue treatment.who. Hepatic impairment: No dose reduction required. Contraindications: Neonates. temporary skin staining. October 2007 (including the model list of essential medicines for children). The selection and use of essential medicines: report of the WHO expert committee. eds. Mcevoy GK. WHO expert committee on the selection and use of essential medicines. 34th ed. porphyria. burning. occlusive dressings. Pharmaceutical Press. rash and urticaria). Kouimtzi M. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. mucous membranes. 2005. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Precautions: Avoid application to substantial areas of skin or to broken skin (risk of significant systemic absorption). 2008. Bethesda. erythema. Contraindications: excoriated or ulcerated lesions. WHO Technical Report Series. Stuart MC. 2008. Topical: Child apply two or three times daily for 3 days. Topical: Infant or Child apply a thin layer three times daily (short-term use). References: Hill SR. ed. Indications: Fungal and bacterial skin infections. American Society of Health-System Pharmacists. WHO model formulary. World Health Organization. ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. Hepatic impairment: No dose reduction necessary. Administration: Fungal and bacterial skin infections. The information in this monograph only applies to the medicine listed here. particularly in those with renal impairment. 2009. Martindale: the complete drug reference. particularly nephrotoxicity and ototoxicty. Adverse effects: Common Irritation and ulceration of mucous membranes if exposed to them.pdf. 326 WHO Model Formulary for Children 2010 . Indications: Bacterial skin infections. overgrowth of resistant organisms on prolonged use. Administration: Bacterial skin infections. Neomycin sulfate + Bacitracin ATC code: D06AX04 Ointment: 5 mg neomycin sulfate + 250 IU bacitracin zinc/g Special Notes: BACITRACIN This medicine is listed as a representative of its pharmacological class. AHFS drug information.

1). WHO expert committee on the selection and use of essential medicines. WHO Model Formulary for Children 2010 327 . 2008. BMJ Group RBS Publishing. The selection and use of essential medicines: report of the WHO expert committee. American Society of Health-System Pharmacists. WHO expert committee on the selection and use of essential medicines. AHFS drug information.01%) Indications: Assist healing of suppurating superficial wounds. Notes: Topical neomycin is a contact sensitizer. Topical: Child crusts should be gently separated with a 1:10 000 (0. pemphigus and impetigo. 2008.01%) solution. 2009. Geneva.pdf ).int/medicines/publications/essentialmeds_committeereports/TRS_950. Impetigo and superficial crusts. WHO Technical Report Series. Renal impairment: Dose reduction not required. Potassium permanganate ATC code: D08AX06 Aqueous solution: 1:10 000 (0. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. WHO Technical Report Series. WHO model formulary.2. especially when used for long periods of time. eds. British national formulary for children 2009.who. 2009. Bethesda. References: Hill SR.2 Anti-infective medicines Rare Anaphylactoid reactions. October 2007 (including the model list of essential medicines for children). Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. 950 (http://www. Mcevoy GK. Paediatric Formulary Committee. Precautions: Irritant to mucous membranes.01%) solution every 8 hours. World Health Organization. The selection and use of essential medicines: report of the WHO expert committee. 2008. Contraindications: Avoid occlusive dressings. changed two or three times daily. systemic absorption leading to nephrotoxicity and irreversible ototoxicity (particularly in renal impairment or in the presence of an occlusive dressing. tropical ulcers.13. Administration: Suppurating superficial wounds and tropical ulcers. tropical ulcers also require treatment for 2–4 weeks with procaine benzylpenicillin (section 6. London. including nappies). Geneva. Sensitivity has been reported to occur in 5–15% of patients treated with the drug. skin and fabrics stained brown. 2008. Notes: Potassium permanganate is sometimes supplied as an aqueous stock solution of 1 in 1000 (0. Hepatic impairment: Dose reduction not required. tinea pedis. Stuart MC. Topical: Child soak severe weeping lesions in 1:10 000 (0.01%) solution. eds. Kouimtzi M. October 2007 (including the model list of essential medicines for children). Adverse effects: Common Local irritation. Topical: Child wet dressings of 1:10 000 (0.who. References: Hill SR. World Health Organization.1%) for dilution before use. WHO model formulary. 950 (http://www.pdf ). Kouimtzi M. Tinea pedis. Stuart MC.int/medicines/publications/essentialmeds_committeereports/TRS_950. ed.

Notes: Some preparations may contain chlorhexidine 0. transient neutropenia. G6PD deficiency. Sulfadiazine can cause nephrotoxicity. Administration: Prophylaxis and treatment of infection in burns. argyria and sulfonamide induced systemic toxicity. e. burning. plasma sulfadiazine concentrations may approach therapeutic levels and when this occurs the interactions below apply. rash. transient leukopenia. Apply with sterile gloved hands or spatula in a 3–5 mm layer. large areas. Owing to the association of sulfonamides with severe blood and skin disorders. Chlorhexidine (cation) is inactivated by anionic agents such as soap. particularly those receiving treatment for extensive burns. < 2 months age. hypersensitivity reactions. Renal impairment: Use with caution in patients with impaired renal function. itching. Rare Necrosis of skin. Phenytoin: sulfadiazine inhibits metabolism of phenytoin. pregnancy.g. Contraindications: Hypersensitivity to sulfonamides. pyrimethamine. provided blood counts are monitored carefully to ensure return to baseline within a few days. do not use together. 328 WHO Model Formulary for Children 2010 . Indications: Prophylaxis and treatment of infection in burns. avoid combination. Hepatic impairment: Severe: use with caution. administration with other nephrotoxic drugs may result in additional renal adverse effects. development of bacterial resistance. increasing its concentration and risk of adverse effects. there is an increased risk of crystalluria with sulfonamides as they are poorly soluble at low pH. Leukopenia developing 2–3 days after starting treatment of burns patients is reported usually to be self limiting and silver sulfadiazine need not usually be discontinued. erythema multiforme.g. Precautions: Renal or hepatic impairment. Interactions with other medicines (* indicates severe): When used over large areas of skin. monitor phenytoin concentration and for adverse effects. Sulfadiazine is a folate antagonist and will add to the effects on bone marrow of other folate antagonists. treatment should be stopped immediately if blood disorders or rashes develop. monitor ciclosporin concentration and adjust dose as necessary. skin discoloration due to deposition of silver. Hexamine hippurate: hexamine requires low urine pH for effect. Plasma sulfadiazine concentrations may approach therapeutic levels with side-effects and interactions as for sulfonamides if large areas of skin are treated. decrease phenytoin dose if necessary. or until healing is complete. Topical: Child over 2 months apply using aseptic technique daily (more frequent if volume of exudate is large) while there is a possibility of infection. Adverse effects: Common Pain. Argyria may also occur if large areas of skin are treated (or if application is prolonged). chlorhexidine. Ciclosporin: sulfadiazine may decrease ciclosporin concentration and efficacy. e. Silver sulfadiazine may inactivate enzymatic debriding agents.2%. Special Notes: WHO age/weight restriction: > 2 months.13 Dermatological medicines (topical) Silver sulfadiazine ATC code: D06BA01 Cream: 1% Use with caution if allergic to sulfonamides or the preservative agent used.

delayed wound healing. Adverse effects: Common Folliculitis. Severe inflammatory skin conditions. psoriasis (may precipitate severe pustular psoriasis on withdrawal). 2002. Mcevoy GK. particularly with an occlusive dressing. Hepatic impairment: Dose reduction not required. Renal impairment: Dose reduction not required. topical steroids. 2009. Topical: Child apply a small quantity to the affected area one to two times daily. 13th ed.1% preparation likely to cause adrenal suppression. Paediatric pharmacopoeia. Use of more than 100 g per week of 0. The information in this monograph only applies to the medicine listed here. Adelaide. Treatments include local application emollients. Rossi S. skin atrophy.pdf ). adrenal suppression if used on a large area of the body or for a long time. 2009. 13. London. McDowell JM. Australian Medicines Handbook. formation of striae. telangiectasia. Kouimtzi M.3 Anti-inflammatory and antipruritic medicines eczema is a very common condition of infancy and childhood. WHO Model Formulary for Children 2010 329 . BMJ Group RBS Publishing. perioral dermatitis. Bethesda. when needed. Stuart MC. acne. rosacea. Uncommon Allergic contact dermatitis. acneiform eruptions at site of application. Treatment should be tailored to the degree of inflammation and dryness of the skin. Administration: NOTe Use the smallest amount for the shortest period of time to avoid adverse effects. Kemp CA. American Society of Health-System Pharmacists. World Health Organization. Betamethasone ATC code: D07AC01 Cream or ointment: 0. secondary infection requires treatment with an appropriate antimicrobial.3 Anti-inflammatory and antipruritic medicines References: Hill SR. Indications: Severe inflammatory skin conditions. October 2007 (including the model list of essential medicines for children). This medicine is listed as a representative of its pharmacological class. 2008. perioral dermatitis. Melbourne. Discontinue use once control is achieved. Any associated infection should also be treated. and. depigmentation. ed. Geneva.who. Contraindications: Untreated skin infections. WHO Technical Report Series. dilatation of superficial blood vessels.13. purpura. Precautions: Children (avoid prolonged use and use under specialist supervision). WHO model formulary. 2008. The selection and use of essential medicines: report of the WHO expert committee. Reduce use once improvement occurs. Paediatric Formulary Committee. broken skin. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. Topical steroids are available in a range of strengths and potencies. 2009. Australian medicines handbook. Royal Children’s Hospital. WHO expert committee on the selection and use of essential medicines. 950 (http://www. eds. AHFS drug information. use on the face or groin. steroid rosacea. viral skin lesions.1% (as valerate) Special Notes: WHO age/weight restriction: hydrocortisone preferred in neonates. British national formulary for children 2009. widespread plaque psoriasis. ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. Reassess diagnosis if no improvement is seen within 2 weeks.

pdf ). monitor clinical effect and increase corticosteroid dose if needed. References: Hill SR. Melbourne. eds. cataract. hyperglycaemia. McDowell JM. NSAIMs: oral corticosteroids increase risk of gastric ulceration with NSAIMs. monitor INR and decrease warfarin dose if necessary. systemic effects (growth retardation. Interactions with other medicines (* indicates severe): Use of topical corticosteroids is less likely to result in drug interactions than systemic use. Kouimtzi M. Royal Children’s Hospital. Hepatic impairment: Dosage reduction not needed. World Health Organization. Adverse effects: No adverse effects noted in literature. e. 330 WHO Model Formulary for Children 2010 . increase acetylsalicylic acid dose if necessary. WHO model formulary. 2009. Consider bone mineral density assessment for children receiving large and long-term doses of topical corticosteroids. use lowest effective dose for shortest period of time. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. glaucoma). Kemp CA. Geneva. 2 days off) may at times be appropriate.13 Dermatological medicines (topical) Rare Hyperaesthesia. BMJ Group RBS Publishing. 2008. Cushing syndrome. Intermittent use (i. Paediatric Formulary Committee. Renal impairment: Dosage reduction not needed. WHO expert committee on the selection and use of essential medicines. WHO Technical Report Series. increasing the risk of bleeding. 2 days on. Rifampicin: increased metabolism of corticosteroid and may reduce activity. Stuart MC.int/medicines/publications/essentialmeds_committeereports/TRS_950. 2008. October 2007 (including the model list of essential medicines for children). Topical: Child apply liberally 3–4 times daily. Acetylsalicylic acid: corticosteroids may decrease salicylate concentration when high-dose acetylsalicylic acid is used.who. monitor salicylate concentration and clinical effect. Use minimum amount necessary to control symptoms. but interactions may occur rarely. Calamine lotion ATC code: D04AX Lotion Indications: Mild pruritus. Notes: Shake bottle well before use. hypothalamic-pituitary-adrenal axis suppression with prolonged or widespread use (particularly under occlusion). The selection and use of essential medicines: report of the WHO expert committee. subcutaneous tissue atrophy. in Kawasaki disease. Tachyphylaxis may occur. Dermatologist consultation advisable if using on the face. consider need for an NSAIM carefully. London. Paediatric pharmacopoeia. be particularly careful to reduce the acetylsalicylic acid dose when withdrawing the corticosteroid. 13th ed. 950 (http://www.e.g. 2002. wet dressings (never plastic) may be used if condition is severe. British national formulary for children 2009. Administration: Mild pruritus. hypertrichosis. Notes: Occlusive. Warfarin: corticosteroids may increase warfarin’s anticoagulant effect. if an NSAIM cannot be avoided.

* Amphotericin B: increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions). glaucoma). increased risk of hypokalaemia. perioral dermatitis. References: Hill SR. Renal impairment: No dose reduction required. World Health Organization. Uncommon Allergic contact dermatitis. Hydrocortisone ATC code: D07AA02 Cream or ointment: 1% (acetate) Indications: Mild inflammatory skin disorders. subcutaneous tissue atrophy. adverse effects do not usually occur. telangiectasia. WHO model formulary. Geneva. Furosemide: antagonism of diuretic effect. Common Folliculitis. BMJ Group RBS Publishing. Topical: Neonate. occlusive dressings increase penetration into Administration: keratinized lesions. secondary infection requires treatment with an appropriate antimicrobial. delayed wound healing. Mild inflammatory skin disorders. 2009. purpura. depigmentation. Enalapril: antagonism of hypotensive effect. Digoxin: increased risk of hypokalaemia.3 Anti-inflammatory and antipruritic medicines Avoid contact with eyes. British national formulary for children 2009. increased risk of hypokalaemia. The selection and use of essential medicines: report of the WHO expert committee. Erythromycin: erythromycin possibly inhibits metabolism of hydrocortisone. eds. broken skin. 950 (http://www. Infant or Child apply a small quantity to the affected area 1–2 times daily until improvement occurs. Hydrochlorothiazide: antagonism of diuretic effect.int/medicines/publications/essentialmeds_committeereports/TRS_950. acne. then less frequently. steroid rosacea. Adverse effects: When used according to directions on small area of skin. cataract. WHO expert committee on the selection and use of essential medicines. formation of striae. 2008. systemic effects (growth retardation. * Carbamazepine: accelerated metabolism of hydrocortisone (reduced effect). Precautions: Children (avoid prolonged use). Do not use on open wounds or burns. WHO Technical Report Series. Stuart MC. perioral dermatitis. hyperglycaemia. rosacea. Acetylsalicylic acid: increased risk of gastrointestinal bleeding and ulceration. Calamine preparations are of little value for the treatment of insect stings or bites. Rare Hyperaesthesia. hydrocortisone reduces plasma salicylate concentration. Interactions with other medicines (* indicates severe): NOTe Interactions do not generally apply to hydrocortisone used for topical application. Kouimtzi M. London. Cushing syndrome. Hepatic impairment: No dose reduction required. Contraindications: Untreated skin infections. dilatation of superficial blood vessels.who.13. 2008. hypothalamic-pituitary-adrenal axis suppression with prolonged or widespread use (particularly under occlusion). Paediatric Formulary Committee. skin atrophy. acneiform eruptions at site of application. hypertrichosis. October 2007 (including the model list of essential medicines for children). WHO Model Formulary for Children 2010 331 .pdf ).

WHO Technical Report Series. * Phenobarbital: metabolism of hydrocortisone accelerated (reduced effect). BMJ Group RBS Publishing. Stuart MC.2. Royal Children’s Hospital. hydrocortisone is a mild corticosteroid. Geneva. Spironolactone: antagonism of diuretic effect. References: Hill SR.pdf ). eds. Paediatric Formulary Committee. avoid use of live vaccines. Ritonavir: plasma concentration possibly increased by ritonavir.who. The selection and use of essential medicines: report of the WHO expert committee. * Rifampicin: accelerated metabolism of hydrocortisone (reduced effect). Kemp CA. Notes: Tachyphylaxis to topical treatment may occur. Insulins: antagonism of hypoglycaemic effect. 332 WHO Model Formulary for Children 2010 . * Vaccine. London. 2008.5 Medicines affecting skin differentiation and proliferation Acne vulgaris Acne typically first appears during puberty when androgenic stimulation triggers excessive production of sebum. where there are more extensive pustules causing mild scarring. Vaccine. WHO expert committee on the selection and use of essential medicines. * Methotrexate: increased risk of haematological toxicity. 950 (http://www.int/medicines/publications/essentialmeds_committeereports/TRS_950. * Warfarin: anticoagulant effect possibly enhanced or reduced (high-dose hydrocortisone enhances anticoagulant effect). McDowell JM. Topically. Paediatric pharmacopoeia. therefore best used intermittently once control is achieved. Metformin: antagonism of hypoglycaemic effect. 2009. 13. Melbourne. * Phenytoin: metabolism of hydrocortisone accelerated (reduced effect). 2002. Propranolol: antagonism of hypotensive effect. 13th ed. Consider bone mineral density assessment for children receiving large and long-term doses of topical corticosteroids or any child supplemented with oral corticosteroids. October 2007 (including the model list of essential medicines for children). influenza: high doses of hydrocortisone impair immune response. Mild acne usually responds to topical therapy alone and heals without scarring. oral antibiotics such as a tetracycline or erythromycin (section 6. World Health Organization. In moderate acne. Kouimtzi M. British national formulary for children 2009. 2008. Salbutamol: increased risk of hypokalaemia if high doses of salbutamol given with hydrocortisone. Severe acne is a distressing condition that may warrant further treatment with systemic medications under specialist supervision.2) are commonly used. WHO model formulary. live: high doses of hydrocortisone impair immune response.13 Dermatological medicines (topical) Ibuprofen: increased risk of gastrointestinal bleeding and ulceration. 13.4 Astringent medicines There are currently no medicines in this section of the 2nd WHO Model List of Essential Medicines for Children.

Adelaide. lips and other sensitive areas. and mucous membranes. Management of psoriasis depends on the site and extent of the disease and the age of the child. 950 (http://www.13. World Health Organization. warts can often be effectively treated through application of a keratolytic agent such as salicylic acid.pdf ). 2008. Rossi S. avoid use of occlusive dressings. The selection and use of essential medicines: report of the WHO expert committee. BMJ Group RBS Publishing. Hepatic impairment: Dose reduction not required. mild stinging or erythema. lithium and NSAIMs). Rare Contact sensitivity occurs. British national formulary for children 2009. Avoid contact with hair and coloured fabric as bleaching or discoloration may occur.int/medicines/publications/essentialmeds_committeereports/TRS_950. WHO expert committee on the selection and use of essential medicines. 2009.g. may bleach fabrics. WHO model formulary. avoid excessive exposure to sunlight. Precautions: Avoid contact with eyes. Geneva. chloroquine. beta-blockers. occasionally even one application can cause severe irritation. Paediatric Formulary Committee. such as streptococcal or viral infection. Benzoyl peroxide ATC code: D10Ae01 Cream or lotion: 5% Indications: Mild to moderate acne. London. Apply a thin layer to the affected area and rub in gently. Stuart MC. Various biological events may trigger psoriasis. Avoid contact with eyes. Warts Warts are common. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. References: Hill SR. ed. Renal impairment: Dose reduction not required. mouth. When required. October 2007 (including the model list of essential medicines for children). Kouimtzi M. Adverse effects: Common Initial irritation but subsides with continued use (in some cases may need to reduce frequency or temporarily suspend use). Administration: Acne. Australian medicines handbook. Notes: If acne does not respond after 2 months then use of a topical antibacterial should be considered. Cleanse skin before applying and gently pat dry. adjunct to oral therapy in more severe cases. WHO Model Formulary for Children 2010 333 . WHO Technical Report Series. Australian Medicines Handbook.5 Medicines affecting skin differentiation and proliferation Psoriasis Psoriasis can occur at any age. Topical: Child initially apply to clean skin on alternate days. eds.who. hair and skin. increasing frequency to one to two times daily as tolerance to irritant effect develops. benign and self-limiting. Podophyllum resin is an alternative agent. taking care to protect the surrounding skin. Wash hands after application. 2009. feeling of warmth. skin dryness or peeling. 2008. psychological stress or medication (e.

Paediatric Formulary Committee. hair and fabrics discoloured. mucosa. ed. use once daily to once every 3 days for at least 10 baths. Kouimtzi M. 2008. allowing at least 24 hours between exposure and treatment with coal tar. A solution more dilute than 5% may be preferable to start. 34th ed. 2009. October 2007 (including the model list of essential medicines for children). Coal tar bath: Child use 100 ml of solution in an adult-size bath of tepid water (proportionally less for a child’s bath) and soak for 10–20 minutes. Other studies have found no conclusive evidence of this. WHO expert committee on the selection and use of essential medicines. irritant reactions. Coal tar is often alternated with ultraviolet (UVB) rays. pustular psoriasis. Australian Medicines Handbook. World Health Organization.who. Martindale: the complete drug reference. Psoriasis. broken or infected skin. 2008.int/medicines/publications/essentialmeds_committeereports/TRS_950. References: Hill SR. Some epidemiological studies have raised the possibility of skin malignancies in patients with psoriasis with very high exposure to tar and/or ultraviolet radiation. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Adelaide. may stain skin. hair (especially fair. Indications: Psoriasis. The selection and use of essential medicines: report of the WHO expert committee. Adverse effects: Common Mild stinging. Notes: Coal tar solutions are usually extemporaneous preparations and can be prepared in different strengths. ed. skin. Topical: Child apply 1–3 times daily. British national formulary for children 2009. acne-like eruptions. 950 (http://www. allergic reactions. Precautions: Avoid eyes. Preparations containing coal tar 10% may be used on children over 2 years with more severe psoriasis. WHO Technical Report Series. Different strengths of solution should be available on request from compounding pharmacies. eds. BMJ Group RBS Publishing. 334 WHO Model Formulary for Children 2010 . Rossi S. London. 2005. Rare Sterile folliculitis. Geneva. Renal impairment: No dose reduction required. Pharmaceutical Press.13 Dermatological medicines (topical) Coal tar ATC code: D05AA Solution: 5% Special Notes: Preparations containing up to 6% coal tar may be used on children 1 month–2 years. bleached or grey hair) and clothing. photosensitivity. CARCINOGeNICITy evidence is conflicting. Hepatic impairment: No dose reduction required. London.pdf ). Contraindications: Inflamed. Sweetman SC. Australian medicines handbook. 2009. hypersensitivity. presence of infection. genital or rectal areas. skin protection possibly required to reduce Administration: photosensitivity reactions. WHO model formulary. Stuart MC.

WHO model formulary. This medicine is listed as a representative of its pharmacological class. 2009. American Society of Health-System Pharmacists. WHO Model Formulary for Children 2010 335 . WHO Technical Report Series. Geneva. mucous membranes. Precautions: Avoid use on large areas. BMJ Group RBS Publishing. Bethesda.13. thrombocytopenia. keep away from face. children under 2 years. British national formulary for children 2009. Administration: NOTe Must be applied by a trained health-care professional. ataxia. eds. Uncommon Burning. abdominal pain. vomiting. external anogenital warts. coma. WHO expert committee on the selection and use of essential medicines. pain. Notes: An example of an application to treat warts.pdf ). erosion. World Health Organization. seizures. Indications: external anogenital warts. avoid contact with normal skin and open wounds. diarrhoea.5 Medicines affecting skin differentiation and proliferation Podophyllum resin ATC code: D06BB04 Solution: 10% to 25% Special Notes: Podophyllotoxin is the major active ingredient of podophyllum.int/medicines/publications/essentialmeds_committeereports/TRS_950. rinse off with soap and water after 6 hours. Rare Systemic effects resulting from cutaneous absorption or after ingestion include nausea. plantar warts. staining of skin. Stuart MC. Various drugs can serve as alternatives. renal failure. avoiding contact with normal tissue. may be repeated at weekly intervals but no more than 4 times in all. Kouimtzi M. 950 (http://www. 2008. ed. dizziness. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Often causes considerable irritation to the treated area and is therefore only suitable for children who are able to cooperate with treatment. confusion. leukopenia. References: Hill SR. 2008. very irritant to eyes. hepatotoxicity. 2009. London. breastfeeding. October 2007 (including the model list of essential medicines for children). Paediatric Formulary Committee. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. Hepatic impairment: No dose reduction required. hallucinations. Topical: Child over 2 years apply carefully to warts. hypotonia. peripheral and autonomic neuropathies. only a few warts to be treated at any one time. AHFS drug information. stupor. Mcevoy GK. plantar warts.who. Renal impairment: No dose reduction required. Contraindications: Pregnancy. The information in this monograph only applies to the medicine listed here. inflammation. The selection and use of essential medicines: report of the WHO expert committee. CNS effects including acute psychotic reactions. Adverse effects: Common Irritation.

2009. Geneva. Hepatic impairment: Dosage reduction not required. Different strength preparations can be requested from compounding pharmacies. WHO model formulary.int/medicines/publications/essentialmeds_committeereports/TRS_950. Adverse effects: Common Local irritation. dry area thoroughly and then apply solution. Notes: Protect surrounding skin and avoid broken skin. soak area in warm water for 5 minutes. 2008. BMJ Group RBS Publishing. Administration: Hyperkeratotic skin disorders. 950 (http://www. starting with lower strength preparations. eds. children under 2 years. Salicyclic acid preparations are usually prepared extemporaneously using salicyclic acid powder. Salicylic acid for the treatment of warts is usually prepared extemporaneously in an ointment using powdered salicyclic acid. patients with diabetes at risk of neuropathic ulcers. gradually increase strength until satisfactory response obtained. anogenital region and mucous membranes.pdf ).13 Dermatological medicines (topical) Salicylic acid ATC code: D01Ae12 Solution: 5% Salicylate toxicity may occur particularly with prolonged use. avoid application to large areas. Paediatric Formulary Committee. 336 WHO Model Formulary for Children 2010 . WHO expert committee on the selection and use of essential medicines. London. The selection and use of essential medicines: report of the WHO expert committee.who. October 2007 (including the model list of essential medicines for children). 2008. Contraindications: Broken or inflamed skin. British national formulary for children 2009. Stuart MC. different strengths can be prepared as required. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. application to large areas or if used on neonatal skin. salicylism on excessive application or treatment of large areas. WHO Technical Report Series. Indications: Hyperkeratotic conditions. For use on warts. Precautions: Significant peripheral neuropathy. avoid contact with eyes. References: Hill SR. dermatitis. mouth. Kouimtzi M. World Health Organization. Topical: Child over 2 years apply once daily. Renal impairment: Dosage reduction not required.

All members of the affected household (and sexual contacts) must be treated at the same time. Hepatic impairment: Dose reduction not required. preferably while skin is still moist after washing or bathing.who. Adverse effects: Common Transient stinging and local irritation. eds. October 2007 (including the model list of essential medicines for children). All are transmitted by person-to-person contact. scaling and itching skin conditions. which may also affect the eyelashes and brows. WHO expert committee on the selection and use of essential medicines. Pediculosis (lice) Pediculosis of the head and body is caused by Pediculus humanus capitis and Pediculus humanus corporis. 2008. 2009. hair brushes and combs should also be disinfected. Paediatric Formulary Committee. Kouimtzi M. Precautions: Avoid application to face or broken skin. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. 13. and may also contaminate clothing and bedding. British national formulary for children 2009. WHO Model Formulary for Children 2010 337 . Geneva.6 Scabies Scabicides and pediculicides Scabies is caused by a mite. Indications: Hydrating agent and keratolytic for dry. respectively. American Society of Health-System Pharmacists. WHO model formulary. that burrows into the skin. It is readily transmitted from person to person.13. Renal impairment: Dose reduction not required. and clothing and bedding should be washed or exposed to the air. WHO Technical Report Series. Mcevoy GK.pdf ). ed. Topical: Child apply twice daily. The selection and use of essential medicines: report of the WHO expert committee. 2009. scaling and itching skin conditions. Bethesda. Administration: Dry. avoid contact with eyes. 950 (http://www. Stuart MC. all clothing and bedding should be washed to prevent reinfection. and therefore the entire household must be treated at the same time to prevent re-infection. References: Hill SR. in head lice infestations. London. AHFS drug information. Although it is not necessary to take a bath before treatment with an acaricide. 2008. World Health Organization. BMJ Group RBS Publishing.6 Scabicides and pediculicides Urea ATC code: D02Ae01 Cream or ointment: 10% Special Notes: Also known as carbamide. Pubic lice (crab lice) infestations are caused by Pthirus pubis. Sarcoptes scabiei.int/medicines/publications/essentialmeds_committeereports/TRS_950.

The information in this monograph only applies to the medicine listed here. Paediatric Formulary Committee.pdf ). WHO Technical Report Series. Topical: Child over 2 years apply to affected area and wash off 24 hours later. WHO expert committee on the selection and use of essential medicines. This medicine is listed as a representative of its pharmacological class. Melbourne. so perform a 10 minute patch test prior to body application. body and pubic lice. Royal Children’s Hospital. head.int/medicines/publications/essentialmeds_committeereports/TRS_950. Precautions: Do not use on inflamed or broken skin. Bathing in hot water prior to application is no longer recommended as it may increase absorption and toxicity. 2002. 2008.13 Dermatological medicines (topical) Benzyl benzoate ATC code: P03AX01 Lotion: 25% Special Notes: WHO age/weight restriction: > 2 years. 2008. October 2007 (including the model list of essential medicines for children). McDowell JM. avoid contact with eyes and mucous membranes. Indications: Scabies. body and pubic lice. 13th ed. Other medicines in the same class may have similar clinical performance and may be selected for local formularies based on availability and price. particularly in children. eds. 20th ed. Thoroughly clean all clothing and bed linen. Topical: Child over 2 years apply over whole body with a brush (except for face and head). London. Head. Not the treatment of choice for scabies. Geneva. Adverse effects: Local irritation. Pharmaceutical Society of Australia. British national formulary for children 2009. repeat without bathing on the following day and wash off 24 hours later. 338 WHO Model Formulary for Children 2010 . Scabies itch is often worse in first 24 hours. Paediatric pharmacopoeia. Kemp CA. Stuart MC. Hepatic impairment: Dose reduction not required. WHO model formulary. 950 (http://www. Permethrin is preferred. Sansom L.who. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Further applications are possibly needed after 7 and 14 days. A third application may be needed in some cases. BMJ Group RBS Publishing. Avoid eye contact. ed. especially in patients with eczema. Renal impairment: Dose reduction not required. 2006. exclude treated patients from contact with hairy toys. References: Hill SR. 2009. Australian pharmaceutical formulary and handbook. Administration: Scabies. Kouimtzi M. World Health Organization. Notes: Can be irritant. The selection and use of essential medicines: report of the WHO expert committee. Curtin.

Kouimtzi M. scalp and ears. British national formulary for children 2009. Repeat in 7–10 days if necessary. do not use on secondarily infected skin. WHO model formulary. World Health Organization. Stuart MC. Head lice. neck. preferably made of metal. Paediatric Formulary Committee. if hands washed with soap within 8 hours of application. 950 (http://www. Adverse effects: Common Local irritation. treat again. Pay particular attention to the areas between the fingers and toes. axillae. 2008. WHO Technical Report Series. head and body lice. Rare Rashes and oedema. genital area and buttocks. Administration: Scabies and body lice. Topical: Child over 2 months apply cream over whole body including face. Kemp CA. Geneva. Repeat application after 7 days. 2002. Royal Children’s Hospital.pdf ). The selection and use of essential medicines: report of the WHO expert committee. October 2007 (including the model list of essential medicines for children). Notes: Avoid mucous membranes. stinging. exclude treated patients from contact with hairy toys. Interactions with other medicines (* indicates severe): There are no known interactions involving a significant change in effect or where it is recommended to avoid concomitant use. Renal impairment: No dosage reduction required. then remove eggs and dead lice from hair with a fine comb. Paediatric pharmacopoeia. avoid contact with eyes.who.13. BMJ Group RBS Publishing. 13th ed.int/medicines/publications/essentialmeds_committeereports/TRS_950. Thoroughly clean all clothing and bed linen. 2009. 2008. McDowell JM. References: Hill SR. Rinse completely. pruritus. erythema. WHO Model Formulary for Children 2010 339 . WHO expert committee on the selection and use of essential medicines. Melbourne. Precautions: Do not use on inflamed or broken skin. wash off after 8–12 hours. wrists. Topical: Child over 2 months apply lotion to clean damp hair and rinse off after 10 mi