Hepatobiliary adverse drug reactions during treatment with olaparib: an analysis of data from the EudraVigilance reporting system.

Background: olaparib is a Poly ADP-Ribose Polymerase inhibitor approved for the treatment of BRCA-mutated tumors, and has been associated with hepatotoxicity, as highlighted by the Pharmacovigilance Risk Assessment Committee. Objectives and methods: to describe Drug-Induced Liver Injury (DILI) cases related to olaparib stratifying them by liver damage origin in "cholestatic", "cytolytic", "mixed", "liver related investigation" and "not specified" cases, by analyzing data from EudraVigilance (EV) database. Results: 344 Individual Case Safety Reports (ICSRs) reporting olaparib-induced liver injury cases were retrieved from the EV. They referred more frequently to female patients belonging to the age group 18-64 years. The majority of ICSRs (66.0%) reported serious Adverse events (AEs), classified as "Other Medically Important Condition", while 23 ICSRs reported fatal AEs. Among the 344 DILI cases, 19.5% were classified as "cytolytic", 3.5% as "cholestatic" and 1.5% as "mixed" origin. Most DILI cases were temporally associated with "liver-related investigations" (39.8%) and 15.1% were classified as "not specified". A further 20.6% of cases involved PTs related to liver neoplasms (benign or malignant). Conclusion: Further pharmacovigilance studies are needed to evaluate the hepatic safety profile of olaparib. Investigating the pathophysiological mechanisms underlying olaparib-induced liver injury could offer clinicians valuable insights for its prevention and management.