Comparative risk of arrhythmias associated with systemic antifungal agents: a disproportionality analysis of the FAERS database.

OBJECTIVE

The real-world cardiac safety profile of systemic antifungal agents has not been thoroughly investigated. Based on the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System database, this study analyzed the arrhythmogenic toxicity of nine systemic antifungal drugs, aiming to provide references for clinical safe medication practices.

RESEARCH DESIGN AND

METHODS

Adverse events were described and classified using arrhythmogenic toxicity-related Standardized MedDRA Queries (SMQs) from the MedDRA. To identify the association between systemic antifungal agents and arrhythmogenic toxicity, this study used four algorithms: Reporting odds ratio (ROR), Proportional reporting ratio (PRR), Multi-item gamma-poisson shrinker (MGPS), and Bayesian confidence propagation Neural Network (BCPNN).

RESULTS

A total of 42,393 reports were included. The ranking of the number of positive signals across four types of SMQs was as follows: Itraconazole (4), Fluconazole (3), Posaconazole (3), Voriconazole (2), Caspofungin (1), Amphotericin B (1), Flucytosine (0), Isavuconazole (0), Micafungin (0). Itraconazole demonstrated the strongest ROR value of 2.95 in "Cardiac arrhythmia terms, nonspecific". The highest ROR values in "Bradyarrhythmias" were 5.53 for both posaconazole and fluconazole. Fluconazole exhibited higher ROR values than other drugs in both "Tachyarrhythmias" and "Torsade de pointes/QT prolongation", with values of 3.53 and 14.55, respectively.

CONCLUSION

This study employed four disproportionality analysis methods to analyze the association between systemic antifungal agents and arrhythmogenic toxicity signals. Itraconazole, fluconazole, and posaconazole demonstrated stronger arrhythmogenic risks, whereas micafungin, flucytosine, and isavuconazole showed negative signals across all four SMQs. In clinical practice, individual patient risk should be comprehensively assessed to guide personalized drug selection.