Cardiotoxicity associated with antifungal agents: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

OBJECTIVE

The aim of this study was to analyze the cardiotoxicity associated with antifungal agents based on data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

MATERIALS AND

METHODS

We extracted and evaluated cardiac adverse events (CAEs) linked to antifungals in the FAERS database (2004 - 2023). Signal strength for five antifungal classes was assessed using the reporting odds ratio (ROR) and information component (IC).

RESULTS

Among 50,603 cases, triazoles, polyenes, and imidazoles showed significant associations with Torsade de Pointes (TdP)/QT prolongation (QTP), with fluconazole exhibiting the strongest link (ROR: 11.96, 95% CI: 10.62 - 13.46; IC: 2.19, 95% CI: 1.92 - 2.44). Triazoles were notably connected to arrhythmias, particularly itraconazole (ROR: 3.31, 95% CI: 2.88 - 3.79; IC: 1.67, 95% CI: 1.20 - 2.11). Fluconazole also demonstrated strong associations with conduction defects (ROR 6.44, 95% CI 5.60 - 7.39; IC 2.65, 95% CI 2.16 - 3.08) and ventricular tachyarrhythmias (ROR 9.09, 95% CI 7.84 - 10.54; IC 3.15, 95% CI 2.60 - 3.58). Notably, only itraconazole showed significant signals for cardiac failure (ROR 4.04, 95% CI 3.52 - 4.64; IC 1.96, 95% CI 1.48 - 2.40) and cardiomyopathy (ROR 6.34, 95% CI 5.04 - 7.96; IC 2.64, 95% CI 1.79 - 3.30). In contrast, echinocandins did not exhibit significant CAE signals.

CONCLUSION

These findings highlight that azoles and polyenes show substantial associations with CAEs, particularly for TdP/QTP and arrhythmias. Itraconazole showed a significant association with cardiac failure and cardiomyopathy, while the signal for isavuconazole was weaker than for other triazoles. No significant cardiotoxicity signals were detected for echinocandins.