Comparative real-world safety profiles of caspofungin, micafungin, and anidulafungin: a disproportionality analysis based on FAERS and VigiAccess databases.

Background: Caspofungin, micafungin, and anidulafungin are three commonly used echinocandins recommended for the treatment of invasive candidiasis. This study aimed to comprehensively evaluate the safety profiles of these three agents to assist clinicians in making appropriate therapeutic decisions. Methods: A cross-sectional pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) database was performed. Adverse event (AE) reports were collected from January 2004 to March 2025. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were used to identify, assess, and compare AE signals of the three echinocandins. Data from the VigiAccess database were used for external validation. Results: A total of 2343, 2338, and 406 cases associated with caspofungin, micafungin, and anidulafungin, respectively, were extracted from the FAERS database. Caspofungin exhibited a tendency toward higher reporting frequencies of hepatobiliary disorders and skin and subcutaneous tissue disorders compared with micafungin and anidulafungin. Hepatobiliary signals observed for anidulafungin should be interpreted cautiously, as they may reflect confounding by indication related to preferential use in patients with underlying hepatic dysfunction rather than direct drug toxicity. A range of AEs that were not highlighted in the labels were identified. Logistic regression analyses indicated that skin and subcutaneous tissue disorders associated with caspofungin or micafungin were significantly associated with hospitalization reporting. Supplementary PT-level analyses further identified several clinically relevant AEs associated with hospitalization, including drug reaction with eosinophilia and systemic symptoms for caspofungin, renal failure for micafungin, and hepatic failure for anidulafungin. Higher disproportionality signals related to caspofungin and micafungin were observed in patients aged≥65 years and females. Additionally, the sensitivity analyses demonstrated that this study possessed good robustness. The median time-to-onset of AEs was significantly longer for caspofungin at 4 days (IQR: 0-11 days) than for micafungin at 2 days (IQR: 0-8 days, Conclusion: This study provides a comparative pharmacovigilance overview of the safety profiles of three echinocandins using FAERS and VigiAccess data. Further prospective studies are needed to validate these observations.