A recently published case series reports on 2 patients who were successfully treated with acetylcysteine for acute liver failure (ALF) associated with remdesivir, a novel antiviral agent that is increasingly being used to manage patients with coronavirus disease 2019 (COVID-19).
Although remdesivir has not been approved by the Food and Drug Administration (FDA) to treat COVID-19, it is available for clinical use via an Emergency Use Authorization (EUA) program. The EUA requires monitoring of both aspartate transaminase (AST) and alanine transaminase (ALT) in patients who receive remdesivir as studies have noted elevations of these enzymes following drug administration.
In their report, the authors presented the cases of 2 patients, a 68-year-old female and an 80-year-old female, with suspected remdesivir-associated ALF. Both patients were initiated on remdesivir following a positive COVID-19 test and increasing oxygen requirements over several days. Between day 3 and 10 of treatment with remdesivir, significant increases in transaminases as well as coagulopathy and encephalopathy were observed in both patients.
“In the 2 cases we present, the time course of COVID-19 infection, remdesivir administration, and liver function abnormalities appears to point to remdesivir as a possible contributing cause of ALF,” the authors explained. They added, “When utilizing the Naranjo algorithm to determine the possibility of a drug-induced effect, both cases scored as a ‘probable’ adverse drug reaction with a score of 6 each.”
Remdesivir was immediately discontinued in both patients and a continuous infusion of acetylcysteine was initiated. Dosing of acetylcysteine followed the 21-hour acetaminophen toxicity protocol (150mg/kg over 1 hour, 50mg/kg over 4 hours, then 100mg/kg over 16 hours).
The authors stated that they observed rapid improvements in both patients’ transaminase levels following acetylcysteine administration and discontinuation of remdesivir. While the younger female patient fully recovered after a 24-day hospital stay, the older female patient died of suspected septic shock on day 17 of her stay.
“The use of the novel antiviral remdesivir in the treatment of COVID-19 pneumonia may put patients at risk of drug-associated acute liver failure,” the authors concluded. They emphasized the need for additional research in this area in order to fully assess the risk of remdesivir-associated ALF as well as the utility of acetylcysteine in its management.
Carothers C, Birrer K, Vo M. Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in COVID-19: a case series [published online October 2, 2020]. Pharmacotherapy. doi: 10.1002/PHAR.2464.