Remdesivir
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.
| 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.
| 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 | 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.
| 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.
| Infusion bag volume | Infusion time | Rate of infusion |
|---|---|---|
| 250 mL | 30 min | 8.33 mL/min |
| 60 min | 4.17 mL/min | |
| 120 min | 2.08 mL/min | |
| 100 mL | 30 min | 3.33 mL/min |
| 60 min | 1.67 mL/min | |
| 120 min | 0.83 mL/min |
B. Remdesivir Injection, 100 mg/20 mL (5 mg/mL), Solution
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.
- Remove the required number of single-dose vial(s) from storage. Each vial contains 100 mg of remdesivir. For each vial:
- Equilibrate to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
- Inspect the vial to ensure the container closure is free from defects and the solution is free of particulate matter.
- Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag
| 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 mg (1 vial) | 250 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 remdesivir injection solution from the remdesivir vial using an appropriately sized syringe.
- Pull the syringe plunger rod back to fill the syringe with approximately 10 mL of air.
- Inject the air into the remdesivir injection vial above the level of the solution.
- Invert the vial and withdraw the required volume of remdesivir injection solution into the syringe. The last 5 mL of solution requires more force to withdraw.
- Discard any unused solution remaining in the remdesivir vial.
- Transfer the required volume of remdesivir injection solution to the 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 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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Dose Preparation and Administration, Pediatric Patients Weighing 3.5 kg to Less Than 40 kg
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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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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.