remdesivir in Covid treatment

Remdesivir is a prodrug for a nucleotide analogue that impairs the function of the SARS-CoV-2 RNA polymerase. In the pivotal ACTT-1 trial, remdesivir was shown to improve the time to recovery among patients hospitalized with hypoxemia but was not powered to show a mortality benefit. The moderate-sized GS-US-540-5773 trial suggested noninferiority for a 5-day vs a 10-day course of remdesivir. Subsequent large pragmatic trials among inpatients with COVID-19 were not designed to test time to recovery but showed no large improvement in mortality. The PINETREE trial among outpatients at high risk early in the disease course showed that a 3-day course prevented hospitalization (no early deaths were observed in either group).

In the use of remdesivir, possible contraindications are important to know and are the focus of this question. Remdesivir has also been shown occasionally to induce liver injury. Patients with transaminases >10× the upper limit of normal are considered to have a contraindication to remdesivir administration, which is true of this patient (choice B is correct). An excipient used in IV remdesivir (sulfobutylether-β-cyclodextrin) can accumulate in patients with a glomerular filtration rate <30 mL/min who are not receiving dialysis, so remdesivir is considered to be relatively contraindicated in that group. However, this patient has a glomerular filtration rate >30 mL/min (choice A is incorrect). Pregnancy, particularly after the first trimester, is not a contraindication, although a conversation about risk vs benefit is indicated before using in patients who are pregnant (choice C is incorrect). Finally, although it is theoretically possible that a patient who is severely obese may receive an insufficient dose with the standard dosing regimen, there is no contraindication to use among patients who are severely obese (choice D is incorrect).1234

  • source
  • for patients hospitalized
  • not on O2 and at risk of progressing (high risk patients))
  • On O2
  • within first 10 days of sx onset and until discharge
  • benefit: faster time to recovery
  • side effect: nausea, increased liver enzyme levels, anaphylaxis
  • discontinue if baseline ALT increases > 10x or if ALT level increases
  • renal dysfunction: may increase liver/renal toxicity. GFR 30 cut off
  • may be safe in GFR < 30 with CATCO trial
  • should be given in pregnant patients

Footnotes

  1. SEEK Questionnaires ↩

  2. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19—final report. N Engl J Med. 2020;383(19):1813-1826. PubMed ↩

  3. Goldman JD, Lye DCB, Hui DS, et al; GS-US-540-5773 Investigators. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med. 2020;383(19):1827-1837. PubMed ↩

  4. Gottlieb RL, Vaca CE, Paredes R, et al; GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2022;386(4):305-315. PubMed ↩