Remdesivir

Remdesivir
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Overview

Remdesivir is an adenosine nucleotide prodrug that is FDA approved for the treatment of suspected or laboratory confirmed SARS-CoV-2 infection in adults and pediatric patients hospitalized with severe disease under an Emergency Use Authorization (EUA). Common adverse reactions include nausea, constipation, acute respiratory failure, anemia (decreased hemoglobin), acute kidney injury (decreased eGFR, decreased creatinine clearance, or increased blood creatinine), hyperglycemia (increased blood glucose), and increased transaminases.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease

Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.

Dosage

• The recommended dosage in adults is a single loading dose of remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of remdesivir 100 mg from Day 2 via IV infusion.

• For patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.

• For patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).

• Administer remdesivir via IV infusion in a total volume of up to 250 mL 0.9% sodium chloride over 30 to 120 minutes.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Remdesivir in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Remdesivir in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease

Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.

Dosage

For pediatric patients weighing 3.5 kg to less than 40 kg, the dose should be calculated using the mg/kg dose according to the patient’s weight.

• For pediatric patients weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Do not use remdesivir injection, 100 mg/20 mL (5 mg/mL), for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of sulfobutylether-β-cyclodextrin sodium salt (SBECD) present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.

• Refer to the table below for recommended dosage form and dosage in pediatric patients according to weight.

Recommended Dosage Form and Dosage in Pediatric Patients

Body weight	Recommended Dosage Form	Loading dose on Day 1	Maintenance dose from Day 2
3.5 kg to <40 kg	Lyophilized Powder for Injection Only	5 mg/kg	2.5 mg/kg
≥40 kg	Lyophilized Powder for Injection OR Injection	200 mg	100 mg

• For pediatric patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.

• For pediatric patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Remdesivir in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Remdesivir in pediatric patients.

Contraindications

Remdesivir is contraindicated in patients with known hypersensitivity to any ingredient of remdesivir.

Warnings

There are limited clinical data available for remdesivir. Serious and unexpected adverse events may occur that have not been previously reported with remdesivir use.

Hypersensitivity Including Infusion-Related and Anaphylactic Reactions

Hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of remdesivir. Signs and symptoms may include hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. The use of remdesivir is contraindicated in patients with known hypersensitivity to remdesivir.

Increased Risk of Transaminase Elevations

Transaminase elevations have been observed in healthy volunteers who received 200 mg of remdesivir followed by 100 mg doses for 5-10 days. Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir in clinical trials. As transaminase elevations have been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir, discerning the contribution of remdesivir to transaminase elevations in this patient population is challenging.

Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.

• Remdesivir should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal at baseline.

• Remdesivir should be discontinued in patients who develop:

• ALT greater than or equal to 5 times the upper limit of normal during treatment with remdesivir. Remdesivir may be restarted when ALT is less than 5 times the upper limit of normal.

OR

• ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.

Risk of Reduced Antiviral Activity When Coadministered with Chloroquine or Hydroxychloroquine

Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.

Adverse Reactions

Clinical Trials Experience

1. Overall Safety Summary

In healthy subjects and hospitalized patients with PCR-confirmed SARS-CoV-2 infection, graded elevations in ALT and AST have been observed with a loading dose of remdesivir 200 mg administered intravenously on Day 1 followed by 100 mg administered intravenously once daily for up to 9 days. The mechanism of these elevations is unknown.

Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. The decision to continue or discontinue remdesivir after development of an adverse event should be made based on the clinical risk benefit assessment for the individual.

1.1 Clinical Studies in Healthy Adults

Remdesivir was evaluated in four Phase 1 studies in 138 healthy adult volunteers (Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US-399-5505). In these studies, transient graded elevations in ALT and AST were observed at repeated once-daily doses of remdesivir.

1.2 NIAID ACTT-1 Trial

In a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) of remdesivir in 1,063 hospitalized subjects with COVID-19 treated with remdesivir (n=541) or placebo (n=522) for 10 days, serious adverse events (SAEs) were reported in 21% and 27% of subjects, respectively, and Grade ≥3 non-serious adverse events were reported in 29% and 33% of subjects, respectively. The most common SAE was respiratory failure reported in 5% of subjects treated with remdesivir and 8% of subjects treated with placebo. The most common Grade ≥3 non-serious adverse events in the remdesivir treatment arm are shown below.

Most Common Grade ≥3 Non-Serious Adverse Events in Subjects Receiving Remdesivir—NIAID ACTT-1 Trial

Grade ≥3 Non-Serious Adverse Events	Remdesivir (N=538)	Placebo (N=521)
Anemia or decreased hemoglobin	43 (8%)	47 (9%)
Acute kidney injury, decreased eGFR or creatinine clearance, or increased blood creatinine	40 (7%)	38 (7%)
Pyrexia	27 (5%)	17 (3%)
Hyperglycemia or increased blood glucose	22 (4%)	17 (3%)
Increased transaminases, including ALT and/or AST	22 (4%)	31 (6%)

1.3 Study GS-US-540-5773

In a randomized, open-label clinical trial (Study GS-US-540-5773) of remdesivir in 397 hospitalized subjects with severe COVID-19 treated with remdesivir for 5 (n=200) or 10 days (n=197), adverse events were reported in 70% and 74% of subjects, respectively, SAEs were reported in 21% and 35% of subjects, respectively, and Grade ≥3 adverse events were reported in 30% and 43% of subjects, respectively. The most common adverse events were nausea (10% in the 5-day group vs 9% in the 10-day group), acute respiratory failure (6% vs 11%), ALT increased (6% vs 8%), and constipation (7% in both groups). Nine (4%) subjects in the 5-day group and 20 (10%) subjects in the 10-day group discontinued treatment due to an adverse event. All-cause mortality at Day 28 was 10% vs 13% in the 5- and 10-day treatment groups, respectively.

2. Hepatic Adverse Reactions

2.1 Experience in Healthy Volunteers

Grade 1 and 2 transaminase elevations were observed in healthy volunteers in Study GS-US-399-5505 (200 mg followed by 100 mg dosing for 5–10 days) and Study GS-US-399-1954 (150 mg daily for 7 or 14 days), which resolved after discontinuation of remdesivir.

2.2 NIAID ACTT-1 trial

Grade ≥3 non-serious adverse events of increased aminotransferase levels including ALT, AST, or both were reported in 4% of subjects receiving remdesivir compared with 6% receiving placebo.

2.3 Study GS-US-540-5773

Grade ≥3 hepatic laboratory abnormalities reported in subjects treated with remdesivir for 5 (n=200) or 10 days (n=197) are shown below.

Hepatic Laboratory Abnormalities—Study GS-US-540-5773

Hepatic Laboratory Abnormalities		Remdesivir for 5 Days	Remdesivir for 10 Days	Total
ALT Increased	Grade 3	8/194 (4%)	11/191 (6%)	19/385 (5%)
	Grade 4	4/194 (2%)	5/191 (3%)	9/385 (2%)
AST Increased	Grade 3	11/194 (6%)	7/190 (4%)	18/384 (5%)
	Grade 4	3/194 (2%)	4/190 (2%)	7/384 (2%)
Total Bilirubin Increased	Grade 3	1/193 (1%)	3/190 (2%)	4/383 (1%)
	Grade 4	0	1/190 (1%)	1/383 (<1%)

2.4 Compassionate Use Experience

In the compassionate use program in patients with severe or critical illness with COVID-19, liver function test abnormalities were reported in 12% (19/163) of patients. Time to onset from first dose ranged from 1-16 days. Four of these patients discontinued remdesivir treatment with elevated transaminases occurring on Day 5 of remdesivir treatment as per protocol.

Seven cases of serious liver-related laboratory abnormality were identified. There was one SAE of blood bilirubin increased in a critically ill patient with septic shock and multiorgan failure. None of the other cases had reported adverse events suggestive of hyperbilirubinemia or symptoms of hepatitis.

Postmarketing Experience

There is limited information regarding Remdesivir Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Remdesivir Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Remdesivir should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Remdesivir in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Remdesivir during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Remdesivir in women who are nursing.

Pediatric Use

See Pediatric Indications and Dosage

Geriatic Use

There is no FDA guidance on the use of Remdesivir with respect to the geriatric population.

Gender

There is no FDA guidance on the use of Remdesivir with respect to specific gender.

Race

There is no FDA guidance on the use of Remdesivir with respect to specific race.

Renal Impairment

Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing and daily while receiving remdesivir.

Adults

• eGFR, Male: (140 – age in years) × (weight in kg) / 72 × (serum creatinine in mg/dL)

• eGFR, Female: (140 – age in years) × (weight in kg) × 0.85 / 72 × (serum creatinine in mg/dL)

Pediatric patients (greater than 28 days old to less than 1 year of age)

• eGFR: 0.45 × (height in cm) / serum creatinine in mg/dL

Pediatric patients (at least 1 year of age to less than 18 years of age)

• eGFR = 0.413 x (height or length)/Scr) if height/length is expressed in centimeters OR 41.3 x (height or length)/Scr) if height/length is expressed in meters

Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD [such as remdesivir is not recommended in adults and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old)] with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.

Hepatic Impairment

It is not known if dosage adjustment is needed in patients with hepatic impairment, and remdesivir should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk.

Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Remdesivir in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Remdesivir in patients who are immunocompromised.

Administration and Monitoring

Administration

Important Testing Prior to and During Treatment and Route of Administration

• Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing of remdesivir and daily while receiving remdesivir.

• Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.

• Remdesivir should be administered via IV infusion only. Do not administer as an intramuscular (IM) injection.

Dose Preparation and Administration, Adults and Pediatric Patients Weighing 40 kg and Higher

Adults and pediatric patients weighing 40 kg and higher can use remdesivir for injection, 100 mg, lyophilized powder and remdesivir injection, 100 mg/20 mL (5 mg/mL), solution. See below for different preparation and administration instructions for the two dosage formulations.

A. Remdesivir for Injection, 100 mg, Lyophilized Powder

Reconstitution Instructions

Remove the required number of single-dose vial(s) from storage. For each vial:

• Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.

• Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.

• Immediately shake the vial for 30 seconds.

• Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.

• If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.

• Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

• After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

Dilution Instructions

Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.

• The reconstituted remdesivir lyophilized powder for injection, containing 100 mg/20 mL remdesivir solution, should be further diluted in 100 mL or 250 mL 0.9% sodium chloride infusion bags.

• Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag.

Recommended Dilution Instructions Using Reconstituted Remdesivir for Injection Lyophilized Powder in Adults and Pediatric Patients Weighing 40 kg and Higher

Dose	0.9% sodium chloride infusion bag volume to be used	Volume to be withdrawn and discarded from 0.9% sodium chloride infusion bag	Required volume of reconstituted remdesivir for injection
200 mg (2 vials)	250 mL	40 mL	40 mL (2 × 20 mL)
	100 mL	40 mL	40 mL (2 × 20 mL)
100 mg (1 vial)	250 mL	20 mL	20 mL
	100 mL	20 mL	20 mL

• Withdraw and discard the required volume of 0.9% sodium chloride from the bag using an appropriately sized syringe and needle.

• Withdraw the required volume of reconstituted remdesivir for injection from the remdesivir vial using an appropriately sized syringe. Discard any unused portion remaining in the remdesivir vial.

• Transfer the required volume of reconstituted remdesivir for injection to the selected infusion bag.

• Gently invert the bag 20 times to mix the solution in the bag. Do not shake.

• The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).

Administration Instructions

The prepared diluted solution should not be administered simultaneously with any other IV medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.

Administer the diluted solution with the infusion rate described in the table below.

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B. Remdesivir Injection, 100 mg/20 mL (5 mg/mL), Solution

Monitoring

There is limited information regarding Monitoring of Remdesivir in the drug label.

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IV Compatibility

There is limited information regarding IV Compatibility of Remdesivir in the drug label.

Overdosage

There is limited information regarding Remdesivir overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Remdesivir Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Remdesivir Mechanism of Action in the drug label.

Structure

There is limited information regarding Remdesivir Structure in the drug label.

Pharmacodynamics

There is limited information regarding Remdesivir Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Remdesivir Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Remdesivir Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Remdesivir Clinical Studies in the drug label.

How Supplied

There is limited information regarding Remdesivir How Supplied in the drug label.

Storage

There is limited information regarding Remdesivir Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Remdesivir Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Remdesivir interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Remdesivir Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Remdesivir Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.