COVID-19

MEDICATIONS
According to
The last updated
protocol
By
Dr/ Shaimaa Moustafa
Clinical pharmacist ,NIDE.
Egyptian Fellowship of Clinical Pharmacy,
Critical Care Specialty, 2017-2020.
Clinical Pharmacy Diploma, ASU, 2008.
1 Mild Case
Moderate
Case 2

3 Severe Case
Critically ill
Case
4
 Administration
& Storage
Dose &
Dose Adverse Drug
Adjustment Reactions

Pregnancy Warnings &

& Lactation Precautions

Monitoring
Mild
Case
Mild Case
Protocol
 Mild Case Hydroxychloroquine

Renal Impairment
Mild to severe impairment:
With short-term use at recommended doses and durations, no dosage
adjustment necessary.
However, dosage reduction may be needed with prolonged use (eg,
systemic lupus erythematosus) ; use with caution.
Hemodialysis: Not dialyzable

Hepatic Impairment:
There are no dosage adjustments provided in the manufacturer's labeling;
use with caution.
 Mild Case Hydroxychloroquine

Administration: Oral
Administer with food or milk.
Do not crush or divide film-coated tablets per the manufacturer
In patients unable to swallow tablets, it has been recommended that tablets
may be crushed and mixed with a small amount of applesauce, chocolate
syrup, or jelly.

Storage/Stability
Store at 20°C to 25°C
Protect from light.
 Mild Case Hydroxychloroquine

Adverse Effects
QTc prolongation, Torsade de Pointes, ventricular arrythmia, and cardiac
deaths.
Baseline and follow-up electrocardiograms are recommended when
there are potential drug interactions with concomitant medications
(e.g., azithromycin) or underlying cardiac diseases.
The risk-benefit ratio should be assessed for patients with cardiac
disease, a history of ventricular arrhythmia, bradycardia (<50 bpm), or
uncorrected hypokalemia and/or hypomagnesemia.
Hypoglycemia, rash, nausea.
 Mild Case Hydroxychloroquine

Warnings/Precautions
Discontinue treatment promptly if signs and symptoms of
cardiomyopathy occur.
Hypoglycemia: Severe hypoglycemia, including life-threatening
loss of consciousness, has been reported in patients with and
without concomitant use of antidiabetic agents. Advise patients
of risk of hypoglycemia and associated signs/symptoms;
discontinue use in patients who develop severe hypoglycemia.
 Mild Case Hydroxychloroquine

Warnings/Precautions
Use with caution in
GIT
disorders
Renal Hepatic
impairment impairment
Psoriasis
G6PD Myasthenia
deficiency gravis
 Mild Case Hydroxychloroquine

Monitoring
CBC (with differential) at baseline and periodically
Liver function
Renal function (in patients at risk for ocular toxicity)
Blood glucose (if symptoms of hypoglycemia occur)
In patients at risk of torsades de pointes, monitor ECG at baseline and
periodically during therapy to assess for QTc prolongation.

Ophthalmologic exam at baseline

 Mild Case Hydroxychloroquine

Pregnancy
Data collection to monitor pregnancy and infant outcomes

following exposure to hydroxychloroquine is ongoing.

Adverse perinatal outcomes have not been associated with

daily maternal doses of hydroxychloroquine ≤400 mg.

Retinal toxicity is a known risk following long-term use or high

doses of hydroxychloroquine.
Mild Case Hydroxychloroquine

Contraindications
Canadian labeling
Preexisting retinopathy

Use in children <6 years or

weighing <35 kg
 Mild Case Favipiravir

Renal Impairment
Mild to severe impairment:
There are no specific dosage adjustments recommended.

Severe impairment: Use is contraindicated

Hepatic Impairment:
Mild to severe impairment:
There are no specific dosage adjustments recommended.

Severe impairment: Use is contraindicated

 Mild Case Favipiravir

Adverse Effects
Favipiravir is currently under investigation for Covid-19 treatment.
At this time, safety data is limited.

Frequency not defined:

Cardiovascular: Chest pain
Hyperuricemia
Gastrointestinal: Decreased appetite, diarrhea, nausea, vomiting.
Hematologic & oncologic: Decreased neutrophils.
Hepatic: Hepatic injury, increased serum transaminases
 Mild Case Favipiravir

Adverse Effects
 Mild Case Favipiravir

Warnings/Precautions
Severe renal or hepatic impairment.

Pregnancy & breastfeeding.

Hyperuricemia

Not effective against bacterial infections

Has not been administered to children

 Mild Case Favipiravir

Pregnancy
Teratogenic in animal studies.

Must confirm a negative pregnancy test before starting the

treatment.

For men: Favipiravin is distributed in sperm; so

Use the most effective contraceptive method in sexual

intercourse during & for 7 days after the end of the treatment
 Mild Case Ivermectin

Renal Impairment
There are no dosage adjustments provided in manufacturer’s
labeling.

Hepatic Impairment:
There are no dosage adjustments provided in manufacturer’s
labeling.

Administration: Oral
Administer on an empty stomach with water.
 Mild Case Ivermectin

Exclusion Criteria
Children under 5 years old
Pregnant or lactating patients
Patients with autoimmune disease
Renal impairment
Hepatic impairment
Symptomatic congestive heart failure patients
Previous reports of allergy
Moderate
case
Moderate Case
Protocol
 Moderate Case Lopinavir/Ritonavir

Renal impairment
There are no dosage adjustments
Hemodialysis: Avoid once-daily dosing in hemodialysis patients.

Hepatic impairment
Mild to moderate impairment: There are no dosage adjustments; however,
lopinavir is primarily metabolized by the liver and its AUC may be increased
~30%; use with caution.
Severe impairment: There are no dosage adjustments (has not been
studied); use with caution.
 Moderate Case Lopinavir/Ritonavir

Administration
Oral
May be taken with or without food.
Swallow whole, do not break, crush, or chew.

Storage/Stability
Exposure to high humidity outside of the original container or USP
equivalent tight container for >2 weeks is not recommended.
 Moderate Case Lopinavir/Ritonavir

Adverse Effects
Nausea, vomiting, diarrhea (common)
Nearly 14% of lopinavir/ritonavir recipients were unable to complete the full
14-day course of administration due primarily to gastrointestinal adverse
events, including anorexia, nausea, abdominal discomfort, or diarrhea, as
well as two serious adverse episodes of acute gastritis.

QTc prolongation
Hepatotoxicity
 Moderate Case Lopinavir/Ritonavir

Warnings/Precaution
May alter cardiac conduction and prolong the QTc and/or PR interval;
second- and third-degree AV block and torsade de pointes have been
observed.

Use with caution in patients with underlying structural heart disease,

preexisting conduction system abnormalities, ischemic heart disease or
cardiomyopathies.

Avoid use in combination with QTc- or PR-interval prolonging drugs or

in patients with hypokalemia or congenital long QT syndrome.
 Moderate Case Lopinavir/Ritonavir

Warnings/Precaution
May cause hepatitis and/or exacerbate pre-existing hepatic

dysfunction; use with caution in patients with underlying hepatic

disease, such as hepatitis B or C, cirrhosis, or unspecified hepatic

impairment.

Consider more frequent liver function test monitoring during

therapy initiation in patients with preexisting hepatic dysfunction.

 Moderate Case Lopinavir/Ritonavir

Warnings/Precaution
Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of
diabetes, DKA, and new-onset diabetes mellitus have been reported in
patients receiving protease inhibitors.
Hepatic impairment: Use with caution; lopinavir concentrations may be
increased.
Pancreatitis: Use with caution in patients with increased triglycerides;
pancreatitis has been observed.
Hemophilia A or B: Use with caution in patients with hemophilia A or B;
increased bleeding during protease inhibitor therapy has been reported.
 Moderate Case Lopinavir/Ritonavir

Monitoring
HIV antigen/antibody testing at baseline

Serum transaminase levels

Triglycerides and cholesterol

Consider monitoring ECG when LPV/RTV is

given with other QTc-prolonging medications.

 Moderate Case Remdesevir

Renal Impairment
eGFR ≥30 mL/minute: No dosage adjustment
necessary
eGFR <30 mL/minute: No formal safety or
pharmacokinetic data are available.

Remdesivir contains renally cleared

sulfobutylether-beta-cyclodextrin sodium
(SBECD) which accumulates in patients
with kidney dysfunction.
 Moderate Case Remdesevir

Hepatic impairment
Baseline hepatic impairment:
There are no dosage adjustments provided in the manufacturers
labeling (has not been studied)
Hepatoxicity during therapy:
ALT >10 times the ULN ( ≥5 times the ULN in EMC).
ALT elevation and signs or symptoms of liver inflammation.
Increase in conjugated bilirubin, alkaline phosphatase or INR
 Moderate Case Remdesevir

Administration
Administer as an IV infusion over 30 to 120 minutes.

Storage/Stability
Lyophilized powder:
Store intact vials at <30°C
After reconstitution, vials can be stored up to 4 hrs at room temperature
(20°C to 25°C ) or 24 hrs at refrigerated (2°C to 8°C); dilute within the same
day as administration.
Discard unused portion of the reconstituted vial.
 Moderate Case Remdesevir

Preparation for administration

Lyophilized powder:
Reconstitute vial with 19 mL SWFI
shake for 30 seconds.
Allow vial contents to settle for 2 to 3 minutes
If not completely dissolved, repeat process as necessary until vial contents
are completely dissolved.
Reconstituted vial contains 100 mg per 20 mL (5 mg/mL).
Further dilute in 100 or 250 mL NS.
Gently invert 20 times to mix the solution; do not shake.
 Moderate Case Remdesevir

Adverse Effects
Elevated transaminase levels (avoid use if ALT ≥5 times the ULN)

Increase in prothrombin time (without a change in the INR).

Gastrointestinal symptoms (e.g., nausea, vomiting)

 Moderate Case Remdesevir

Hypersensitivity
Infusion-related and anaphylactic reactions
Slowing infusion rate (maximum infusion time: 120 minutes)
may be considered to potentially prevent these reactions.
Discontinue administration and institute appropriate treatment
if a clinically significant hypersensitivity reaction occurs.
 Moderate Case Remdesevir

Monitoring
Baseline and during remdesivir administration when clinically
appropriate:
Hepatic function tests (ALT, AST, bilirubin, alkaline
phosphatase, prothrombin time)
Renal function tests (serum creatinine, CrCl)
Hematology
Signs/symptoms of infusion reaction.
 Moderate Case Remdesevir

Pregnancy
The safety and effectiveness have not been evaluated in pregnant
patients.
Only when the potential benefit justifies the potential risk to the
mother and the fetus.

Breast feeding
It is unknown whether remdesivir is excreted in human milk or the
effects on the breast-fed infant, or the effects on milk production.
 Moderate Case Dexamethasone

Renal Impairment
There are no dosage adjustments provided in the manufacturer’s
labeling; use with caution

Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s
labeling.
 Moderate Case Dexamethasone

Administration
May administer 4 mg/mL or 10 mg/mL concentration undiluted over ≤1 minute.
Rapid administration may be associated with perineal irritation (especially with
higher doses); consider further dilution with NS or G5W and administration by
IV intermittent infusion over 5 to 15 minutes.

Storage
Store intact vials at 20°C to 25°C .
Protect from light, heat, and freezing.
Do not autoclave.
Diluted solutions should be used within 24 hours.
 Moderate Case Dexamethasone

Warnings/Precautions
Cardiovascular disease: Use with caution in patients with heart failure and/or
hypertension; use has been associated with fluid retention, electrolyte
disturbances, and hypertension. Monitor BP.
Renal impairment: Use with caution in patients with renal impairment; fluid
retention may occur.
GI disease: Use with caution in patients with GI diseases due to GI perforation
risk. Signs of GI perforation may be masked in patients receiving
corticosteroid therapy.
 Moderate Case Dexamethasone

Warnings/Precautions
Diabetes: may alter glucose production/regulation leading to hyperglycemia.
May require addition or adjustment of antidiabetic therapy.
Adrenal suppression: particularly in younger children or in patients receiving
high doses for prolonged periods or with chronic use.
Seizure disorders: Use corticosteroids with caution in patients with a history
of seizure disorder; seizures have been reported with adrenal crisis.
Withdrawal and discontinuation of a corticosteroid should be done slowly
and carefully.
Discontinuation of therapy: Withdraw therapy with gradual tapering of
dose.
 Moderate Case Dexamethasone

Considerations in Pregnancy
A short course of betamethasone and dexamethasone, which are known to
cross the placenta, is routinely used to decrease neonatal complications of
prematurity in women with threatened preterm delivery.
Given the potential benefit of decreased maternal mortality and the low risk
of fetal adverse effects for a short course of dexamethasone therapy, the
Panel recommends using dexamethasone in hospitalized pregnant women
with COVID-19 who are mechanically ventilated (AIII) or who require
supplemental oxygen but who are not mechanically ventilated (BIII).
Severe
Case
Adjunctive Therapy
Severe Case
Protocol
 Severe Case Antithrombotic Therapy

Low molecular weight heparin or unfractionated heparin may be

preferred in hospitalized, critically ill patients because:

Shorter half-lives

Ability to be administered intravenously or subcutaneously

Fewer drug-drug interactions compared with oral anticoagulants.

 Severe Case Enoxaparin

Renal Impairment
CrCl >30 mL/minute:
No dose adjustment necessary.
CrCl <30 mL/minute:
VTE prophylaxis: SubQ: 30 mg once daily.
VTE treatment: SubQ: 1 mg/kg once daily.

Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling (has
not been studied); use with caution.
Severe Case Enoxaparin
 Severe Case Enoxaparin

Dosing: Obesity
VTE prophylaxis: SubQ: BMI ≥40 kg/m2

Initial: 40 mg twice daily .

Some experts suggest 60 mg twice daily in patients with more extreme forms

of obesity (BMI >47 kg/m2)

A weight-based approach can be used: 0.5 mg/kg twice daily (based on actual

body weight)
 Severe Case Enoxaparin

Warnings / Precautions
Bleeding

Hyperkalemia

Thrombocytopenia

Elderly: Use with caution in the elderly; delayed elimination may occur

Low weight patients: Risk of bleeding may be increased in women <45 kg and

in men <57 kg.

 Severe Case Enoxaparin

ALERT: [US Boxed Warning]

Epidural or spinal hematomas may occur in patients who are anticoagulated

with low molecular weight heparins (LMWH) or heparinoids and are

receiving neuraxial anesthesia or undergoing spinal puncture. These

hematomas may result in long-term or permanent paralysis.

 Severe Case Enoxaparin

Monitoring Parameters
Platelet count

Hemoglobin, hematocrit

Fecal occult blood

Signs and symptoms of bleeding

Serum creatinine at baseline and during therapy.

 Severe Case Convalescent Plasma

CP donor requirements:
Eligible donors include:
Individuals who have had symptoms of COVID-
19 and a positive result with a diagnostic test for
COVID-19 that has been approved, cleared, or
authorized by the FDA
or
Individuals who have not had a positive COVID-
19 diagnostic test or symptoms of COVID-19, but
who have a positive test for SARS-CoV-2
antibodies using two different tests approved,
cleared or authorized by the FDA.
 Severe Case Convalescent Plasma

CCP donor requirements:

Other donor requirements include:

❑ Complete resolution of symptoms at least 14 days

prior to donation (a negative diagnostic test for

COVID-19 is not required to qualify).

❑ Must meet all other requirements for standard

whole blood collection including testing for

infectious disease; additional requirements must

be met if plasma is collected by apheresis.

 Severe Case Convalescent Plasma

Existing data suggests that if a benefit

exists, CP is most useful when given early

(particularly when administered within 72

hours of COVID-19 diagnosis.) and with a

high titer of neutralizing antibodies.

 Severe Case Convalescent Plasma

Adverse effects
The available data suggest that serious
adverse reactions following the
administration of COVID-19 convalescent
plasma are infrequent and consistent with
the risks associated with plasma infusions
for other indications.
 Severe Case Convalescent Plasma

Adverse effects
These risks include:
Transfusion-transmitted infections (e.g.: [HIV],
hepatitis B, hepatitis C)
Allergic reactions, anaphylactic reactions
Hemolytic reactions.
Hypothermia
Metabolic complications
Post-transfusion purpura
 Severe Case Tocilizumab

Recommended dose
4 – 8 mg/kg/day for 2 doses 12 to 24 hr
apart after failure of steroid therapy to
improve the case for 24 hr
 Severe Case Tocilizumab

Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the
manufacturer's labeling (has not been studied)

Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling
(has not been studied).
Initiation of therapy in patients with active hepatic disease or hepatic
impairment or in rheumatoid arthritis (RA) and giant cell arteritis (GCA)

patients with baseline ALT or AST >1.5 × ULN is not recommended.

 Severe Case Tocilizumab

Storage/Stability
Store intact vials, prefilled syringes, and autoinjectors at 2°C to 8°C.
Do not freeze.
Protect vials, prefilled syringes, and autoinjectors from light (store in
the original package until time of use)
Solutions diluted for IV infusion in NS or 1/2 NS may be stored at 2°C to
8°C or room temperature for up to 24 hours
 Severe Case Tocilizumab

Administration: IV
Allow diluted solution for infusion to reach room temperature prior to
administration
infuse over 60 minutes using a dedicated IV line.
Do not infuse other agents through same IV line.
Do not administer IV push or IV bolus.
If additional doses are necessary for the management of cytokine
release syndrome, the interval between doses should be at least 8
hours.
Do not use if opaque particles or discoloration is visible.
 Severe Case Tocilizumab

ALERT: US Boxed Warning

Risk of serious infections: Patients treated with tocilizumab are at

an increased risk for developing serious infections that may lead to

hospitalization or death.

Most patients who developed these infections were taking concomitant

immunosuppressants, such as methotrexate or corticosteroids.

 Severe Case Tocilizumab

Warnings/Precautions
GI perforation: Use with caution in patients at increased risk for GI perforation

Hematologic effects: Neutropenia and thrombocytopenia may occur. Monitor

neutrophils and platelets. Do not initiate treatment in patients with giant cell

arteritis (GCA), polyarticular juvenile idiopathic arthritis, rheumatoid arthritis

(RA), or systemic juvenile idiopathic arthritis with an ANC <2,000/mm3 or

platelet count <100,000/mm3; discontinue treatment for ANC

<500/mm3 or platelet count <50,000/mm3.

 Severe Case Tocilizumab

Warnings/Precautions
Hepatic effects: Hepatic injury, resulting in liver transplant or death, has been
reported. May require treatment interruption, dose or interval modification, or
discontinuation.
Hyperlipidemia: Therapy is associated with increases in total cholesterol,
triglycerides, LDL, and/or HDL.
Hypersensitivity: May cause hypersensitivity or anaphylaxis
Elderly: Infection has been reported at a higher incidence in elderly patients
compared with younger adults; use with caution in elderly patients.
 Severe Case Tocilizumab

Considerations in Pregnancy
There are insufficient data to determine whether there is a drug-associated

risk for major birth defects or miscarriage.

Monoclonal antibodies are actively transported across the placenta as

pregnancy progresses (with greatest transfer during the third trimester) and

may affect immune responses in utero in the exposed fetus.

Critically
Ill
Cases
Severe Case Protocol
 References
NIH, National Institues of Health
Lexicomp
EMC
Drugs.com
FDA factsheet Remdesivir
IDSA guidelines
Medscape
Micromedix drug info
Micromedix drug interactions
Irwin & Rippe’s; intensive care medicine, 8th eddition