Hepatic safety of the antifungal triazole agent posaconazole: characterization of adverse event reports in a manufacturer's safety database

Background Second generation triazoles including posaconazole are efficacious for prophylaxis and salvage treatment of life-threatening invasive fungal diseases but have been associated with hepatic adverse events (AEs). This report evaluated hepatic AEs in posaconazole-treated patients. Research design and methods Hepatobiliary AEs occurring after posaconazole exposure in the company's global safety database were analyzed to characterize underlying medical conditions and concomitant drug exposure. Results As of October 2019, 516 cases (168 from clinical trials, 348 from postmarketing use) containing 618 hepatobiliary AEs were reported regardless of causality. Frequently reported terms were hyperbilirubinemia, hepatic failure, and hepatic function abnormal (clinical trial reports) and hepatotoxicity, hepatocellular injury, and hepatic function abnormal (postmarketing reports). Cases reporting concurrent medications associated with drug-induced liver injury (DILI) included 8% with verified severe DILI (vMost-DILI) concern, 24% with verified mild to moderate DILI (vLess-DILI) concern, and 37% received both vMost-DILI and vLess-DILI-concern medications in the DILIrank data set. Conclusions Use of concomitant medications with known risks for hepatic injury appears to be an important contributor for the development of hepatotoxicity in patients treated with posaconazole.