Hepatic dysfunction events associated with voriconazole: a real-world study from FDA adverse event reporting system (FAERS) database

Aims: Although voriconazole-induced hepatotoxicity has been reported previously, the direct cause-effect relationship in the real world remains to be established. The aim of this study was to investigate the association between voriconazole and hepatic dysfunction based on the FAERS database. Methods: Data from January 2004 to March 2022 in FAERS were retrieved. We estimate the association between the hepatic dysfunction and voriconazole using reporting odds ratios (RORs) for mining the adverse event report signals and compare voriconazole with the full database and other antifungal drugs. Results: 646 reports of hepatic dysfunction related to voriconazole as the primary suspect drug were collected totally. The median time to event of the hepatic dysfunction events was 8 (interquartile range [IQR] 2-28) days. 62.20% hepatic-related adverse events appeared within the first 15 days since the initiation of voriconazole administration. The overall ROR (95% CI) for hepatic-related adverse events was 6.82 (95% CI 6.26-7.42). Comparing to other antifungal drugs, the RORs for hepatic-related adverse events of fluconazole, isavuconazole and amphotericin B were 2.19 (95% CI 1.94-2.47), 2.31 (95% CI 1.66-3.33) and 1.26 (95% CI 1.08-1.48), respectively. Conclusions: We observed strong signals of higher frequency of reporting hepatic dysfunction events associated with voriconazole in the events of hepatic dysfunction. Since the risk of developing liver injury and possible hepatic dysfunction by voriconazole depends on several factors including underlying hepatic disease, close clinical and laboratory monitoring, including therapeutic drug monitoring (TDM), are essential to prevent or promptly recognize further deterioration of the hepatic function.