VEKLURY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEKLURY (VEKLURY).
Remdesivir is a nucleotide analog prodrug that, after intracellular metabolism, incorporates into nascent viral RNA chains causing synthesis termination and inhibition of RNA-dependent RNA polymerase (RdRp). It targets the SARS-CoV-2 RdRp with selectivity over human RNA polymerases.
| Metabolism | Remdesivir is metabolized via hydrolysis to nucleoside monophosphate (GS-704277) and further processed intracellularly to the active triphosphate (GS-443902). Cytochrome P450 enzymes are not involved. It is a substrate of CES1, CES2, and cathepsin A. Approximately 90% of dose recovered in urine as metabolites, primarily GS-441524. |
| Excretion | Renal: 10% unchanged remdesivir; 49% as metabolite GS-441524; 18% as other metabolites. Fecal: 47.5% as metabolites. Biliary: minor. |
| Half-life | Remdesivir: ~1 hour (parent); GS-441524: ~27 hours (terminal). Context: GS-441524 accumulation may occur with daily dosing. |
| Protein binding | 88-90% bound to human plasma proteins (primarily albumin). |
| Volume of Distribution | Remdesivir Vd: 131 L (~1.87 L/kg for 70 kg); GS-441524 Vd: 113 L (~1.61 L/kg). Large Vd indicates extensive tissue distribution. |
| Bioavailability | Not applicable; only IV formulation available. |
| Onset of Action | IV: Antiviral effect within 24 hours based on viral load reduction in clinical trials. |
| Duration of Action | Dosing interval: once daily. Clinical effect duration depends on treatment course (5-10 days). |
200 mg IV on Day 1, then 100 mg IV once daily for 5 to 10 days.
| Dosage form | SOLUTION |
| Renal impairment | eGFR ≥30 mL/min: No adjustment. eGFR <30 mL/min: Not recommended (insufficient data). |
| Liver impairment | No adjustment required for mild or moderate hepatic impairment. Not studied in severe hepatic impairment. |
| Pediatric use | Weight ≥40 kg: same as adult. Weight 3.5 to <40 kg: 5 mg/kg IV on Day 1, then 2.5 mg/kg IV once daily for 5 to 10 days. |
| Geriatric use | No specific dose adjustment; clinical studies included patients ≥65 years; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VEKLURY (VEKLURY).
| Breastfeeding | Remdesivir is excreted into human breast milk in low amounts. The milk-to-plasma (M/P) ratio has not been formally determined. Based on limited data, relative infant dose is estimated to be <1% of maternal weight-adjusted dose, which is unlikely to cause adverse effects in breastfed infants. Caution is advised in preterm or ill infants. Consider developmental and health benefits of breastfeeding along with maternal need for therapy. |
| Teratogenic Risk | VEKLURY (remdesivir) is an antiviral agent with limited human pregnancy data. Animal reproduction studies showed no evidence of fetal harm at clinically relevant exposures. For first trimester, risk cannot be ruled out due to lack of human data; however, the drug should be used if clearly needed. In second and third trimesters, available data from case series and prospective registries suggest no increased risk of major birth defects or miscarriage, but data are insufficient to definitively characterize risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to remdesivir or any component of the formulation.","Concomitant use with chloroquine or hydroxychloroquine due to antagonism."]
| Precautions | ["Hypersensitivity reactions (including infusion-related reactions and anaphylaxis) have been reported. Discontinue if signs of infusion reaction occur.","Elevated hepatic transaminases observed; consider discontinuing if ALT elevation accompanied by signs of liver inflammation.","Risk of reduced antiviral activity with concomitant chloroquine or hydroxychloroquine due to antagonism.","Use during pregnancy only if potential benefit justifies potential risk; limited human data.","Nursing mothers: Consider risk of infant exposure; remdesivir present in breastmilk in animal studies."] |
Loading safety data…
| Fetal Monitoring | Monitor liver function tests (AST, ALT) before and during treatment due to potential for transaminase elevations. Monitor renal function (serum creatinine, eGFR) as remdesivir is excreted renally. In pregnant patients, assess fetal growth and well-being via appropriate obstetric ultrasonography as clinically indicated. Observe for infusion-related reactions (hypotension, nausea, vomiting) during administration. |
| Fertility Effects | Animal studies with remdesivir at doses up to 2.7 times the human exposure showed no adverse effects on male or female fertility (mating, fertility, sperm parameters, estrous cycling, conception). No human fertility studies are available. Based on mechanism and animal data, no significant impact on human fertility is expected. |