OBJECTIVE To study and analyze liver injury associated with azole antifungals in children based on the FDA Adverse Event Reporting System(FAERS), aiming to provide reference for clinical drug safety.

METHODS Adverse event reports of fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole were extracted. Disproportionality analysis, comprehensive standard method and Multi-item Gamma Poisson Shrinker method were used to detect adverse event signals, with further analysis conducted on liver injury reports associated with azole antifungals in children.

RESULTS A total of 360 liver injury reports related to 5 azole antifungals in children were extracted. Voriconazole and fluconazole were reported most frequently, with 185 and 87 cases respectively. Adolescents comprised the majority of the reports(43.06%), except for itraconazole. The onset of liver injury primarily occurred within 30 d. The most commonly reported concomitant medications were amphotericin B, methotrexate, and cyclosporine. Positive signals for liver injury were detected in all azole antifungals. The top signal was steatohepatitis with voriconazole(6 cases, ROR 172.80, PRR 171.85, EBGM₀₅ 47.65) and acute liver failure with isavuconazole(8 cases, ROR 77.49, PRR 65.01, EBGM₀₅ 30.21). Steatohepatitis was a new signal.

CONCLUSION All azole antifungals have the risk of causing liver injury in children, primarily occurring within 30 d. Co-administration of hepatotoxic or interacting drugs may increase the risk of liver injury, specific phenotypes and risk factors still need to be verified by clinical studies.