Acetylcysteine for the Treatment of Suspected Remdesivir-Associated Acute Liver Failure in COVID-19: A Case Series

Pharmacotherapy. 2020 Nov;40(11):1166-1171. doi: 10.1002/phar.2464. Epub 2020 Oct 27.

Abstract

Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.

Keywords: COVID-19; Remdesivir; SARS-CoV-2; acetylcysteine; acute liver failure; adverse drug reactions; coronavirus; toxicology.

Publication types

  • Case Reports

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / therapeutic use*
  • Adenosine Monophosphate / administration & dosage
  • Adenosine Monophosphate / adverse effects
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Aged
  • Aged, 80 and over
  • Alanine / administration & dosage
  • Alanine / adverse effects
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment*
  • Fatal Outcome
  • Female
  • Humans
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / diagnosis
  • Liver Failure, Acute / drug therapy*
  • Liver Function Tests
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine
  • Acetylcysteine