IDStewardship

Remdesivir (Veklury)

Remdesivir photo

KEY POINTS

  • Remdesivir (RDV, GS-5734, Veklury) is a direct acting nucleoside RNA polymerase inhibitor and antiviral drug developed by Gilead Sciences
    • It is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to the active nucleoside triphosphate metabolite. Remdesivir triphosphate acts as an analog of ATP and competes with natural ATP substrate for incorporation into RNA chains by the SARS-CoV-2 RNA-
      dependent polymerase, which results in delayed chain termination during replication of viral RNA.
  • Remdesivir was granted FDA Emergency Use Authorization (EUA) on May 1, 2020
  • Remdesivir was FDA-approved on October 22, 2020 for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization.
  • Remdesivir gained a second FDA approval on January 21, 2022 for treatment of non-hospitalized patients at high risk for COVID-19 disease progression
    • Approval was based upon the PINETREE RCT which includes a 3 day course
  • Has broad-spectrum antiviral activity
    • Is being investigated for use against Ebola virus
    • Shown to have activity versus MERS and SARS (which are both coronaviruses)
      • Has potent in vitro activity versus SARS-CoV-2 (the cause of COVID-19), including the Omicron variant
  • Recommended dosage:
    • Adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of 200 mg on day 1 followed by once-daily maintenance doses of 100 mg daily
  • Duration:
    • For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days.
      • If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days.
    • For patients requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days
    • For outpatient use with the 2022 FDA approval, duration is 3 days
  • Administer via intravenous (IV) infusion over 30 to 120 minutes.
    • Some experts prefer the 30 minute infusion time to achieve the maximal Cmax, however the clinical impact of this strategy on efficacy or the rate of adverse drug reactions is unknown
  • Not recommended for eGFR falls below 30 mL/min (the SBECD excipient can accumulate)
    • Many experts disagree with this as an exclusion criteria due to experience with voriconazole IV
  • Not recommended to be continued if ALT goes above 5x the upper limit of normal
  • There have been reports of extravasation
  • There have been reports of bradycardia
  • Can cause infusion-mediated reactions
  • There are limited data on RDV drug-drug interactions, but there may be interactions via the liver
    • There is a potential drug-drug interaction with chloroquine or hydroxychloroquine
    • In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP.
  • Cost is $520 per vial with private insurance, which is typically wrapped into the cost of hospitalization (as of October 2020)

RESOURCES

RECOMMENDED TO YOU

 

 

Recent