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.