Abstract
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.
Keywords : voriconazole, hepatic dysfunction, invasive aspergillosis, real-world study, FAERS
INTRODUCTION
Invasive aspergillosis is a life-threatening infection among individuals with long-lasting or severe impairment of the immune system [1]. Compared with other triazole antifungals, voriconazole has enhanced activity against the Aspergillus species, and as an alternative therapy for candidemia, in individuals who do not have neutropenia [2, 3], so it remains the standard of care and is recommended by international guidelines for the primary treatment of invasive aspergillosis [4, 5]. Although voriconazole-induced hepatotoxicity has been reported previously, the direct cause-effect relationship remains to be established systematically based on the real world data.
The FAERS includes several million spontaneous reports of drug-associated adverse events and is used to evaluate drug safety profiles. The database includes all adverse drug events (ADEs) information and medication error information collected by the FDA. It is one of the primary tools used for post-marketing surveillance and pharmacovigilance [6]. We conducted this study to examine the association between voriconazole and hepatic dysfunction, and compared RORs of hepatic dysfunction caused by voriconazole and other antifungal drugs. All data analysis is based on FAERS database.