Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 20. doi: 10.1007/s00210-025-04746-z. Online ahead of print.
ABSTRACT
This study utilizes data from the FDA Adverse Event Reporting System (FAERS) to identify and compare adverse events (AEs) signals related to hepatobiliary disorders associated with triazole antifungal agents (TAAs), aiming to inform clinical selection and risk assessment of these drugs. AE reports related to TAAs submitted to the FAERS database from 2004Q1 to 2024Q4 were collected. Data mining was performed using multiple signal detection methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN). The incidence of hepatobiliary-related AEs associated with the five TAAs was highest among individuals aged 45-64. Compared with other TAAs, the proportion of adverse events occurring in children is higher with voriconazole. For AEs related to voriconazole and isavuconazole, the proportion of males is higher than that of females, whereas for others, the proportion of male and female patients is roughly equal. Based on the prescribing information for each drug, a total of 11 novel AEs were identified across all TAAs, including hepatolysis (ROR = 11.73, PRR = 11.71), vanishing bile duct syndrome (ROR = 26.95, PRR = 26.94), hepatic fibrosis (ROR = 3.6, PRR = 3.6), venoocclusive liver disease (ROR = 7.6, PRR = 7.59), hepatosplenomegaly (ROR = 5.17, PRR = 5.17), hepatorenal syndrome (ROR = 4.85, PRR = 4.85), hepatic cysts (ROR = 6.59, PRR = 6.59), hepatomegaly (ROR = 3.5, PRR = 3.5), mixed liver injury (ROR = 7.71, PRR = 7.71), steatohepatitis (ROR = 22.49, PRR = 22.48), and hepatorenal failure (ROR = 11.02, PRR = 11.02). This study analyzed the clinical traits of hepatobiliary adverse event reports related to triazole antifungal agents, conducted a detailed comparative analysis of PT, and identified 11 novel PTs not mentioned in the drug labeling, such as vanishing bile duct syndrome, steatohepatitis, and hepatolysis. Clinicians should be alert to these novel risks and strengthen liver function monitoring during the clinical use of these drugs.
PMID:41111132 | DOI:10.1007/s00210-025-04746-z
