- Coronavirus 2019 (COVID-19) infection in patients who are hospitalized.
- COVID-19 infection in patients who are not hospitalized, have mild to moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.
As an adenosine nucleotide prodrug, remdesivir is metabolized to an active nucleoside triphosphate metabolite, after being distributed into cells. Remdesivir triphosphate acts as an adenosine triphosphate (ATP) analog and competes with ATP for incorporation into RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during viral RNA replication.
- Reduced time to recovery in hospitalized patients (hospital discharge, hospitalized but not requiring supplemental oxygen and no longer requiring ongoing care) from COVID-19 infection.
- Reduction in risk of hospitalization or all-cause mortality in nonhospitalized patients.
Absorption: IV administration results in complete bioavailability.
Metabolism and Excretion: Remdesivir is a prodrug that is metabolized intracellularly to the active metabolite, remdesivir triphosphate. Primarily excreted in urine (74%, 10% as unchanged drug), with 18% of drug being excreted in feces.
Half-life: Nucleoside triphosphate metabolite: 20 hr.
TIME/ACTION PROFILE (median time to recovery)
Use Cautiously in:
- OB: Safety not established in pregnancy;
- Lactation: Safety not established in breastfeeding;
- Pedi: Children <28 days or weighing <3 kg (safety and effectiveness not established).
Adverse Reactions/Side Effects
GI: nausea, ↑ liver enzymes, constipation
GU: acute kidney injury
Resp: RESPIRATORY FAILURE
Misc: fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema), infusion reactions
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IV (Adults and Children ≥40 kg): Hospitalized patients: 200 mg on Day 1, then 100 mg once daily starting on Day 2. Treatment duration = 10 days (patients requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation [ECMO]); 5 days (patients not requiring invasive mechanical ventilation and/or ECMO) (if these patients are not improving after 5 days, treatment may be continued for another 5 days). Nonhospitalized patients: 200 mg on Day 1, then 100 mg once daily on Days 2 and 3.
IV (Children ≥28 days and 3–<40 kg): Hospitalized patients: 5 mg/kg on Day 1, then 2.5 mg/kg once daily starting on Day 2. Treatment duration = 10 days (patients requiring invasive mechanical ventilation and/or ECMO); 5 days (patients not requiring invasive mechanical ventilation and/or ECMO) (if these patients are not improving after 5 days, treatment may be continued for another 5 days). Nonhospitalized patients: 5 mg/kg on Day 1, then 2.5 mg/kg once daily on Days 2 and 3.
Lyophilized powder for injection: 100 mg/vial
Solution for injection: 5 mg/mL
- Monitor for signs and symptoms of COVID-19 infection (fever, cough, shortness of breath) before and periodically during therapy.
Monitor for signs and symptoms of hypersensitivity reactions (hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, shivering) during therapy and for at least 1 hr after infusion is complete. Slowing infusion rate to maximum time of 120 min may prevent reactions. If clinically significant symptoms occur, immediately discontinue infusion and begin symptomatic treatment.
Lab Test Considerations:
- Monitor hepatic function before starting and during therapy as clinically appropriate. If ALT ≥5 × upper limit of normal (ULN), do not start remdesivir therapy. If ALT ≥5 × ULN during therapy or ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR, hold dose. Resume when ALT <5 × ULN.
- Monitor prothrombin time before starting and during therapy as clinically appropriate.
- Do not administer with chloroquine or hydroxychloroquine; may decrease antiviral activity.
- Administer remdesivir only in settings in which health care professionals have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system.
- Intermittent Infusion: Remdesivir powder for Injection, 100 mg: Reconstitution: Reconstitute lyophilized powder with 19 mL of Sterile Water for Injection. Discard vial if vacuum does not pull Sterile Water for Injection into vial. Shake vial for 30 sec. Allow contents to settle for 2–3 min for a clear solution. If contents not completely dissolved, shake for 30 sec and allow to settle for 2–3 min. Repeat until solution is clear. Concentration: 5 mg/mL. Reconstituted solution is stable for 4 hr at room temperature or 24 hr if refrigerated. Dilution: Dilute with 100 mL or 250 mL of 0.9% NaCl. For 200 mg dose, withdraw and discard 40 mL from the 250 mL or 100 mL 0.9% NaCl infusion bag. Withdraw 40 mL of reconstituted solution and inject into infusion bag. For 100 mg dose, withdraw and discard 20 mL from the 250 mL or 100 mL 0.9% NaCl infusion bag. Withdraw 20 mL of reconstituted solution and inject into infusion bag. Gently invert bag 20 times to mix; do not shake. Solution is stable for 24 hr at room temperature or 48 hr if refrigerated. Remdesivir solution for Injection, 100 mg/20 mL (5 mg/mL): Allow vials to reach room temperature; stable for 12 hr at room temperature before dilution. Solution is clear and colorless to yellow; do not use solutions that are cloudy, discolored, or contain particulate matter. Dilution: For 200 mg dose, withdraw and discard 40 ml from 250 mL infusion bag of 0.9% NaCl. Inject 5 mL air into vial and withdraw 40 mL remdesivir solution; last 5 mL may require force to withdraw. Inject remdesivir solution into infusion bag. For 100 mg dose, withdraw and discard 20 ml from 250 mL infusion bag of 0.9% NaCl. Inject 10 mL air into vial and withdraw 20 mL remdesivir solution; last 5 mL may require force to withdraw. Inject remdesivir solution into infusion bag. Gently invert bag 20 times to mix; do not shake. Solution is stable for 24 hr at room temperature or 48 hr if refrigerated.
- Rate: Infuse 250 mL over 30 min for rate of 8.33 mL/min, over 60 min for rate of 4.17 mL/min, or over 120 min for rate of 2.08 mL/min. Infuse 100 mL over 30 min for rate of 3.33 mL/min, over 60 min for rate of 1.67 mL/min, or over 120 min for rate of 0.83 mL/min.
- Explain purpose of remdesivir to patient.
- Advise patient to notify health care professional immediately if signs and symptoms of hypersensitivity reactions (low blood pressure, changes in heartbeat, shortness of breath, wheezing, swelling of lips, face, or throat, rash, nausea, vomiting, sweating, shivering) occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products, especially chloroquine or hydroxychloroquine.
- Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding during therapy.
Reduced time to recovery (hospital discharge, hospitalized but not requiring supplemental oxygen and no longer requiring ongoing care) from COVID-19 infection.