remdesivir

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.

Therapeutic effects:

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.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	11 days	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

Endo: hyperglycemia

GI: nausea, ↑liver enzymes, constipation

GU: acute kidney injury

Hemat: anemia

Resp: RESPIRATORY FAILURE

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), infusion reactions

Interactions ⬆ ⬇

Drug-drug:

Chloroquine or hydroxychloroquine may ↓ antiviral effects; avoid concurrent use.

Route/Dosage ⬆ ⬇

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.
IV (Children ≥28 days and 1.5–<3 kg): Hospitalized patients: 2.5 mg/kg on Day 1, then 1.25 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: 2.5 mg/kg on Day 1, then 1.25 mg/kg once daily on Days 2 and 3.
IV (Children <28 days and ≥1.5 kg): Hospitalized patients: 2.5 mg/kg on Day 1, then 1.25 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: 2.5 mg/kg on Day 1, then 1.25 mg/kg once daily on Days 2 and 3.

Availability ⬆ ⬇

Lyophilized powder for injection: 100 mg/vial

Assessment ⬆ ⬇

Monitor for signs/symptoms of COVID-19 infection (fever, cough, shortness of breath) before and periodically during therapy.
Monitor for signs/symptoms of hypersensitivity reactions (hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, shivering) during therapy and for ≥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:

Implementation ⬆ ⬇

Administer remdesivir only in settings in which health care providers 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.

IV Administration:

Remdesivir is a vesicant. May be administered through a peripheral or central line. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry warm compresses.
Intermittent Infusion: Reconstitution: Reconstitute vial with 19 mL of sterile water for injection. The powder for injection is the only approved formulation of remdesivir for patients weighing 1.5–40 kg. 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. Reconstituted solution is stable for 4 hr at room temperature or 24 hr if refrigerated.Concentration: 5 mg/mL.Diluent: For 100-mg dose, withdraw and discard 20 mL from a 250-mL or 100-mL 0.9% NaCl infusion bag. Withdraw 20 mL of reconstituted solution and inject into infusion bag. For 200-mg dose, withdraw and discard 40 mL from a 250-mL or 100-mL 0.9% NaCl infusion bag. Withdraw 40 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.
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.
Y-Site Compatibility:
- fentanyl
- furosemide
- heparin
- hydromorphone
- morphine
- octreotide

Patient/Family Teaching ⬆ ⬇

Explain purpose of remdesivir to patient.
Advise patient to notify health care provider 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other Rx, OTC, or herbal products, especially chloroquine or hydroxychloroquine.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇