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Remdesivir | COVID

Remdesivir

Last Updated: November 3, 2020

Remdesivir is an intravenous nucleotide prodrug of an adenosine analog. Remdesivir binds to the viral RNA-dependent RNA polymerase, inhibiting viral replication through premature termination of RNA transcription. It has demonstrated in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 In a rhesus macaque model of SARS-CoV-2 infection, remdesivir treatment was initiated soon after inoculation; the remdesivir-treated animals had lower virus levels in the lungs and less lung damage than the control animals.2

Remdesivir is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 in hospitalized adult and pediatric patients (aged ≥12 years and weighing ≥40 kg). It is also available through an FDA Emergency Use Authorization (EUA) for the treatment of COVID-19 in hospitalized pediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg.

Remdesivir has been studied in several clinical trials for the treatment of COVID-19. The recommendations from the COVID-19 Treatment Guidelines Panel (the Panel) are based on the results of these studies. See Remdesivir: Selected Clinical Data for more information.

The safety and efficacy of combination therapy of remdesivir with corticosteroids have not been rigorously studied in clinical trials; however, there are theoretical reasons that the combination therapy may be beneficial in some patients with severe COVID-19. For the Panel’s recommendations on using remdesivir with or without dexamethasone in certain hospitalized patients, see Therapeutic Management of Patients with COVID-19.

Monitoring, Adverse Effects, and Drug-Drug Interactions

Remdesivir can cause gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time, and hypersensitivity reactions.

Liver function tests and prothrombin time should be obtained in all patients before remdesivir is administered and during treatment as clinically indicated. Remdesivir may need to be discontinued if alanine transaminase (ALT) levels increase to >10 times the upper limit of normal and should be discontinued if an increase in ALT level and signs or symptoms of liver inflammation are observed.3

Because the remdesivir formulation contains renally cleared sulfobutylether-beta-cyclodextrin sodium, patients with an estimated glomerular filtration rate (eGFR) of <50 mL/minute were excluded from some clinical trials; other trials had an eGFR cutoff of <30 mL/minute. Remdesivir is not recommended for patients with eGFR <30 mL/minute. Renal function should be monitored in patients before and during remdesivir treatment as clinically indicated.3

Clinical drug-drug interaction studies of remdesivir have not been conducted. In vitro, remdesivir is a substrate of cytochrome P450 (CYP) 3A4 and of the drug transporters organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein. It is also an inhibitor of CYP3A4, OATP1B1, OATP1B3, and MATE1.3

Minimal to no reduction in remdesivir exposure is expected when remdesivir is coadministered with dexamethasone, according to information provided by Gilead Sciences (written communication, July 2020). Chloroquine or hydroxychloroquine may decrease the antiviral activity of remdesivir; coadministration of these drugs is not recommended.3 Remdesivir is not expected to have any significant interactions with oseltamivir or baloxavir, according to information provided by Gilead Sciences (written communications, August and September 2020).

See Table 2: Characteristics of Antiviral Agents That Are Approved or Under Evaluation for Treatment of COVID-19 for more information.

Considerations in Pregnancy

  • Pregnant patients were excluded from the clinical trials that evaluated the safety and efficacy of remdesivir for the treatment of COVID-19, but preliminary reports of use in pregnant patients through the remdesivir compassionate use program are reassuring.
  • Among 86 pregnant and postpartum hospitalized patients with severe COVID-19 who received compassionate use remdesivir, the therapy was well tolerated, with a low rate of serious adverse events.4
  • Remdesivir should not be withheld from pregnant patients if it is otherwise indicated.

Considerations in Children

  • The safety and effectiveness of remdesivir for the treatment of COVID-19 have not been evaluated in pediatric patients aged <12 years or weighing <40 kg.
  • Remdesivir is available through an FDA EUA for the treatment of COVID-19 in hospitalized pediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg.
  • A clinical trial is currently evaluating the pharmacokinetics of remdesivir in children (ClinicalTrials.gov identifier NCT04431453).

Clinical Trials

Several clinical trials that are evaluating remdesivir for the treatment of COVID-19 are currently underway or in development. Please see ClinicalTrials.gov for the latest information.

References

  1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32020029.
  2. Williamson BN, Feldmann F, Schwarz B, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32516797.
  3. Remdesivir (VEKLURY) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214787Orig1s000lbl.pdf. Accessed: October 25, 2020.
  4. Burwick RM, Yawetz S, Stephenson KE, et al. Compassionate use of remdesivir in pregnant women with severe COVID-19. Clin Infect Dis. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33031500.
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