Hepatic Disorders in Adults Associated with the Use of Ivermectin for SARS-CoV-2 Infection: A Pharmacovigilance Study in VigiBase

ABSTRACT

Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective(s) To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID- 19. Method(s) We extracted, in men or women aged >= 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as ''serious'' associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in Vigi- Base associated with Ivermectin, of which 60 (4.3%) were registered as ''serious'';in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 +/- 9.7 years. Ivermectin was administered during a mean of 2.5 +/- 2.4 days, and the mean daily dose was 14.3 +/- 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion(s) The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19.