What is Remdesivir?

What is Remdesivir?

Remdesivir is a broad-spectrum antiviral agent administered intravenously that was developed as a treatment for COVID-19, with demonstrated activity against SARS-CoV-2 by inhibiting viral RNA polymerase. 1

Mechanism of Action and Pharmacology

• Remdesivir is a nucleotide analogue that functions as a SARS-CoV-2 RNA polymerase inhibitor, blocking viral RNA replication 2
• Originally developed and studied as a potential treatment for Ebola virus disease and Marburg virus infection before being repurposed for COVID-19 1
• In vitro and in vivo preclinical studies demonstrated antiviral activity against various coronaviruses, including MERS-CoV, SARS-CoV-1, and SARS-CoV-2 1
• Administered as an intravenous infusion with a loading dose of 200 mg on day 1 followed by 100 mg daily for subsequent days 1

Clinical Use in COVID-19

• Received emergency use authorization from the US Food and Drug Administration for treating COVID-19 1
• Recommended treatment duration varies by disease severity 1:
  • 5-day course for patients with moderate COVID-19
  • 5-day course for patients with severe COVID-19 who do not require mechanical ventilation or ECMO
  • Consider extending to 10 days in patients with severe COVID-19 requiring mechanical ventilation or ECMO

Clinical Efficacy

• Remdesivir probably makes little or no difference to all-cause mortality at up to 28 days in hospitalized patients with COVID-19 (moderate certainty evidence) 3, 4
• May decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation 4
• In non-hospitalized individuals with mild COVID-19 at risk of progression, remdesivir probably decreases the risk of hospitalization 3
• Probably increases the chance of clinical improvement at up to day 28 slightly in hospitalized patients 3

Safety Profile

• Common adverse events include nausea (9%), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%) 5
• Remdesivir probably decreases the serious adverse events rate at up to 28 days compared to standard care 4
• The FDA recommends 1:
  • Assessing kidney and hepatic function at baseline and during treatment
  • Not using remdesivir in patients with eGFR <30 mL/min/1.73 m²
  • Discontinuing if ALT levels increase to ≥5 times the upper limit of normal or if any ALT elevation is accompanied by signs of liver inflammation

Pharmacokinetics

• Half-life of remdesivir is approximately 1 hour 2
• Metabolized primarily by CES1 (80%), Cathepsin A (10%), and CYP3A (10%) 2
• Primarily eliminated through metabolism, with approximately 10% excreted in urine 2
• High intracellular concentrations of the active triphosphate are achieved following infusion 6

Important Considerations

• Remdesivir is currently administered only by IV infusion, generally in hospital settings 1
• Evidence suggests that treatment may be more effective when initiated within 10 days of symptom onset in patients with severe COVID-19 1
• The effectiveness may not vary by age, sex, or race 1
• Pregnancy: Exposures of remdesivir and its circulating metabolites during pregnancy were similar to those in non-pregnant individuals 2