Remdesivir

Remdesivir is an intravenous nucleotide analogue prodrug with activity against SARS-CoV-2 and several other RNA viruses. It is given to patients with COVID-19 who are at high risk of progression (outpatient 3-day course) and to selected hospitalised patients needing oxygen. Benefit is modest and greatest early in illness; it does not help ventilated patients. It is not an effective treatment for Ebola or other viruses outside licensed use.

Class. RNA polymerase inhibitor antiviral; nucleotide analogue prodrug.

Mechanism. Metabolised to the active triphosphate, an adenosine analogue that is incorporated into viral RNA by RNA-dependent RNA polymerase and causes delayed chain termination.

Pharmacokinetics. Intravenous only. The parent half life is about 1 hour; the nucleoside metabolite GS-441524 has a half life of about 25 hours. Renal excretion of metabolites. Contains a cyclodextrin vehicle.

Hospitalised adults with COVID-19 requiring supplemental oxygen (not ventilated).

• Loading: 200 mg intravenously on day 1.
• Maintenance: 100 mg once daily for 4 more days (5 days total); extend to 10 days if not improving.
• Maximum: 200 mg on day 1; 100 mg daily thereafter.

Non-hospitalised high-risk adults and children aged 12 years and over (40 kg or more). 200 mg on day 1 then 100 mg on days 2 and 3 (3 days total), started within 7 days of symptom onset.

Children. Weight-based: 3 kg to under 40 kg: 5 mg/kg on day 1 then 2.5 mg/kg daily; 40 kg or more: adult doses.

Immunocompromised patients. Extended courses are used in specialist practice.

Main alternatives. Nirmatrelvir with ritonavir (oral), or neutralising antibody products where active.

Contraindications. Hypersensitivity to remdesivir or its components.

Serious adverse effects. Infusion-related and hypersensitivity reactions including anaphylaxis, bradycardia, and hepatotoxicity.

Common adverse effects. Nausea, raised transaminases, headache and rash.

Interactions. Chloroquine and hydroxychloroquine may reduce its antiviral activity (avoid); few CYP-mediated interactions.

Common prescribing errors. Starting late in illness or in ventilated patients, omitting the loading dose, and not checking liver tests.

Special groups.

• Pregnancy: used in COVID-19 when indicated.
• Breastfeeding: acceptable; low oral bioavailability in the infant.
• Children: weight-based from 3 kg.
• Older adults: no adjustment.
• Kidney impairment: no adjustment is required in current labelling, but cyclodextrin accumulates in severe impairment, so benefit is weighed against risk.
• Liver impairment: monitor liver tests; no adjustment.

Formulations. Powder for infusion 100 mg vial; solution 5 mg/mL.

Administration. Dilute in 0.9% sodium chloride and infuse over 30 to 120 minutes; observe for hypersensitivity.

Baseline. Liver tests, creatinine, pregnancy test, heart rate.

Monitoring. Liver tests at baseline and daily while inpatient; heart rate during infusion.

Stopping thresholds. Stop for ALT over 10 times the upper limit of normal, ALT rise with signs of liver injury, anaphylaxis or symptomatic bradycardia.

Referral and escalation. Specialist review for immunocompromised patients and persistent infection.