Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 100mg/vial
injection, concentrated solution
- 100mg/20mL (5mg/mL)
Coronavirus Disease 2019 (COVID-19)
Indicated for treatment of COVID-19 in patients with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, requiring hospitalization, or are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death
Inpatient treatment
- Day 1 loading dose: 200 mg IV, THEN
- Day 2 and thereafter: 100 mg IV qDay
-
Treatment duration
- Not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; if clinical improvement not demonstrated, treatment may be extended up to 10 days total
- Requires invasive mechanical ventilation and/or ECMO: 10 days
Outpatient treatment
- Initiate as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset
- 200 mg IV on Day 1, then 100 mg IV on Days 2-3 (ie, 3 consecutive days)
Dosage Modifications
Renal impairment
- All severities, including patients on dialysis: No dosage adjustment necessary
- May administer without regard to timing of dialysis
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, or C): No dosage adjustment necessary
Dosing Considerations
Laboratory tests
- Obtain before initiating in all patients and while receiving as clinically appropriate
- Perform hepatic laboratory testing
- Determine prothrombin time
Additional Resources
-
NIH
-
Medscape COVID-19 references are available
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 100mg/vial
- Note: Use lyophilized powder to prepare dose for children weighing 3 to <40 kg
injection, concentrated solution
- 100mg/20mL (5mg/mL) for children ≥40 kg
Coronavirus Disease 2019 (COVID-19)
Indicated for treatment of COVID-19 in adults and pediatric patients aged ≥28 days who weigh ≥3 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, requiring hospitalization, or are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death
Inpatient treatment
-
Weight ≥40 kg
- Day 1 loading dose: 200 mg IV, THEN
- Day 2 and thereafter: 100 mg IV qDay
-
Weight 3 kg to <40 kg
- Day 1 loading dose: 5 mg/kg mg IV infused, THEN
- Day 2 and thereafter: 2.5 mg/kg IV qDay
-
Inpatient treatment duration
- Not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; if clinical improvement not demonstrated, treatment may be extended up to 10 days total
- Requires invasive mechanical ventilation and/or ECMO: 10 days
Outpatient treatment
- Initiate as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset
- Weight ≥40 kg: 200 mg IV on Day 1, then 100 mg IV on Days 2-3 (ie, 3 consecutive days)
- Weight 3-40 kg: 5 mg/kg IV on Day 1, then 2.5 mg/kg IV on Days 2-3
Dosage Modifications
Renal impairment
- eGFR ≥30 mL/min: No dose adjustment
- Pediatric patients (aged >28 days) with eGFR <30 mL/min: Not recommended
- Full-term neonates (aged ≥7 days to ≤28 days) with serum creatinine >1 mg/dL: Not recommended
- Sulfobutylether-beta-cyclodextrin sodium salt (SBECD) excipient in the concentrated solution is renally cleared and accumulates in patients with decreased renal function
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, or C): No dosage adjustment necessary
Dosing Considerations
Administer only in a hospital or healthcare setting capable of providing acute care comparable to inpatient hospital care
Use lyophilized powder to prepare dose for children aged <12 years or weight <40 kg according to EUA for this group
Laboratory tests
- Obtain before initiating in all patients and while receiving as clinically appropriate
- Determine eGFR for patients aged >28 days
- Measure serum creatinine for all full-term neonates aged 7-28 days
- Perform hepatic laboratory testing
- Determine prothrombin time
Additional Resources
-
NIH
-
Medscape COVID-19 references are available
No dosage adjustment required in patients aged ≥65 yr
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (2)
- chloroquine
chloroquine decreases effects of remdesivir by unspecified interaction mechanism. Avoid or Use Alternate Drug. Coadministration not recommended owing to antagonistic effect on remdesivir?s intracellular metabolic activation and antiviral activity.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate decreases effects of remdesivir by unspecified interaction mechanism. Avoid or Use Alternate Drug. Coadministration not recommended owing to antagonistic effect on remdesivir?s intracellular metabolic activation and antiviral activity.
Monitor Closely (2)
- ublituximab
ublituximab decreases effects of remdesivir by immunosuppressive effects; risk of infection. Use Caution/Monitor.
- warfarin
remdesivir increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
eGFR decreased* (18%)
Decreased CrCl* (calculated by Cockcroft-Gault) (10-18%)
Creatinine increased* (5-15%)
Hemoglobin decreased* (6-15%)
Glucose increased* (11-12%)
Lymphocytes decreased* (11%)
1-10%
Prothrombin time increased (9%)
ALT increased* (3-8%)
AST increased* (6-7%)
Nausea (3-5%)
Bilirubin increased* (2%)
Hypersensitivity reactions (<2%)
Generalized seizure (<2%)
Rash (<2%)
Warnings
Contraindications
Hypersensitivity to drug or any ingredient
Cautions
Hypersensitivity, including infusion-related reactions
Hypersensitivity, including infusion-related reactions observed during and following administration; most occur within 1 hr of administration
Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering
Consider slowing infusion rate (up to 120 minutes) to potentially prevent these signs and symptoms; observe patient for 1 hr after completing administration
If clinically significant reaction occurs, discontinue immediately and implement appropriate treatment
Hepatic transaminases
- Increased hepatic transaminases reported in healthy volunteers and patients with COVID-19
- Because transaminase elevations are reported as a clinical feature of COVID-19, and the incidence in clinical trials was similar in patients receiving placebo versus remdesivir, it is challenging to discern the contribution of remdesivir to transaminase elevations in patients with COVID-19
- ALT levels increase to >10x ULN: Consider discontinuing remdesivir
- ALT elevation accompanied by signs or symptoms of liver inflammation: Discontinue remdesivir
Drug interaction overview
- Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans
- In vitro, remdesivir is a substrate of CYP2C8, CYP2D6, and CYP3A4 enzymes; and a substrate of OAPT1B1 and P-glycoprotein transporters
- In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP
- Clinical relevance of these in vitro assessments has not been established
-
Coadministration with chloroquine or hydroxychloroquine
- Coadministration of remdesivir is not recommended with chloroquine or hydroxychloroquine
- Based on in vitro data, chloroquine demonstrated an antagonistic effect on the intracellular metabolic activation and antiviral activity of remdesivir
Pregnancy & Lactation
Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy; pregnant and recently pregnant individuals can go to https://covid-pr.pregistry.com to enroll or call 1-800-616-3791 to obtain information about the registry
Available data from a clinical trial (IMPAACT 2032), published reports, the ongoing COVID-PR pregnancy exposure registry, and compassionate use of remdesivir in pregnant individuals have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following exposure in second and third trimester
There are insufficient pregnancy data available to evaluate risk of remdesivir exposure during first trimester; a study evaluating pharmacokinetics of remdesivir during pregnancy demonstrated no clinically relevant differences between pregnant and non-pregnant individuals; no dose adjustments are recommended in patients who receive this drug during pregnancy
Animal studies
- In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose
Clinical considerations
- There are maternal and fetal risks associated with untreated COVID-19 in pregnancy; COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death
Lactation
A published case report describes presence of remdesivir and active metabolite GS-441524 in human milk; available data from pharmacovigilance reports do not indicate adverse effects on breastfed infants from exposure to remdesivir and its metabolite through breastmilk; there are no available data on effects of remdesivir on milk production
Animal studies
- Remdesivir and metabolites detected in plasma of nursing rat pups, likely owing to presence of remdesivir in milk following daily IV remdesivir to pregnant rats from gestation day 6 to lactation day 20
- Exposures in nursing pups were ~1% that of maternal exposure on lactation day 10
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication
Adenosine nucleotide prodrug that distributes into cells, where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite
Metabolism of remdesivir to remdesivir triphosphate (RDV-TP) demonstrated in multiple cell types
RDV-TP acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA
Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity
Antiviral activity
- Remdesivir retained similar antiviral activity against clinical isolates of SARS-CoV-2 variants compared to an earlier lineage SARS-CoV-2 (lineage A) isolate, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Epsilon (B.1.429), Zeta (P.2), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C.37), and Omicron variants (including B.1.1.529/BA.1, BA.2, BA.2.12.1, BA.2.75, BA.4, BA.4.6, BA.5, BF.5, BF.7, BQ.1, BQ.1.1, CH.1.1, XBB, and XBB.1.5)
- For these variants, EC50 fold change values ranged between 0.2 and 2.3 compared to the SARS-CoV-2 (lineage A) isolate
Absorption
Peak plasma time
- Remdesivir: 0.67-0.68 hr
- GS-441524: 1.51-2 hr
- GS-704277: 0.75 hr
Peak plasma concentration
- Remdesivir: 2229 ng/mL
- GS-441524: 145 ng/mL
- GS-704277: 246 ng/mL
Trough concentration
- Remdesivir: Not detectable (24-hr post dose)
- GS-441524: 69.2 ng/mL
- GS-704277: Not detectable (24-hr post dose)
AUC
- Remdesivir: 1585 nghr/mL
- GS-441524: 2229 nghr/mL
- GS-704277: 452 nghr/mL
Distribution
Protein bound
- Remdesivir: 88-93.6%
- GS-441524: 2%
- GS-704277: 1%
Metabolism
Remdesivir: CES1 (80%); cathepsin A (10%); CYP3A (10%)
GS-441524: Not significantly metabolized
GS-704277: HINT1
Elimination
Half-life
- Remdesivir: 1 hr
- GS-441524: 27 hr
- GS-704277: 1.3 hr
Excretion
-
Major route
- Remdesivir: Metabolism
- GS-441524: Glomerular filtration and active tubular secretion
- GS-704277: Metabolism
-
Urine
- Remdesivir: 10%
- GS-441524: 49%
- GS-704277: 2.9%
-
Feces
- Remdesivir: Not detected
- GS-441524: 0.5%
- GS-704277: Not detected
Administration
IV Preparation
Pediatric patients weighing 3 kg to <40 kg: Prepare dose with only lyophilized powder product
Do not use concentrated solution 100 mg/20 mL (5 mg/mL) for pediatric patients <40 kg or patients with eGFR <30 mL/min owing to the higher amount of sulfobutylether-beta-cyclodextrin sodium salt (SBECD) present and resulting higher tonicity compared with the lyophilized powder formulation
Reconstitution of lyophilized powder
- Aseptically reconstitute lyophilized powder by adding 19 mL of sterile water for injection (SWI)
- Discard vial if a vacuum does not pull the SWI into the vial
- Immediately shake vial for 30 seconds
- Allow vial contents to settle for 2-3 minutes; resulting solution should appear clear
- If not completely dissolved, shake vial again for 30 seconds and allow the contents to settle for 2-3 minutes; repeat this procedure as necessary until the contents of the vial are completely dissolved
- Following reconstitution, resulting concentration/vial is 100 mg/20 mL (5 mg/mL)
- Inspected visually for particulate matter and discoloration
- Use reconstituted product immediately to prepare diluted solution
Further dilution required
-
Adults and pediatric patients weighing ≥40 kg
- Dilute further by adding reconstituted solution to 0.9% NaCl infusion bag (100-mL or 250-mL volume) or the concentrated solution to 250-mL 0.9% NaCl infusion bag
- Withdraw 20 mL (for 100-mg dose) or 40 mL (for 200-mg dose) of saline from the IV bag using an appropriately sized syringe and needle; discard the saline withdrawn from bag
- Withdraw required dosage volume of reconstituted or concentrated remdesivir solution from vial; discard any unused portion remaining in the vial
- Transfer required dosage volume to selected infusion bag
- Gently invert the bag 20 times to mix the solution in the bag; do not shake
-
Pediatric patients weighing 3 to <40 kg
- Prepare an IV bag or infusion syringe of 0.9% NaCl with volume equal to the total infusion volume minus the volume of reconstituted remdesivir solution to achieve a 1.25-mg/mL solution
- Gently invert IV bag or infusion syringe 20 times to mix; do not shake
IV Administration
Do not administer simultaneously in IV line with any other medication
Infuse IV over 30-120 minutes
Also see prescribing information for infusion rate charts
Rate of infusion may be adjusted based on total volume infused
Storage
Does not contain preservatives
Lyophilized powder
- Unopened vial: Store <30ºC (<86ºF)
- Reconstituted vial: Use reconstituted product immediately to prepare diluted solution
- Diluted solution: Stable for 24 hr at 20-25ºC (68-77ºF) or 48 hr refrigerated at temperature 2-8ºC (36-46ºF)
Solution for injection
- Unopened vial: Refrigerate at 2-8ºC (36-46ºF); may store at room temperature up to 12 hr before dilution
- Diluted solution: Stable for 24 hr at 20-25ºC (68-77ºF) or 48 hr refrigerated at temperature 2-8ºC (36-46ºF)
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Formulary
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