| アブストラクト | BACKGROUND: Invasive aspergillosis (IA) poses significant mortality risks, particularly in immunocompromised patients. The safety profiles of FDA-approved antifungal agents, triazoles (Voriconazole, Posaconazole, Isavuconazole), polyenes (Amphotericin B), and echinocandins (Caspofungin), are not yet fully characterized in real-world settings. This study employed pharmacovigilance data to systematically evaluate the comparative safety profiles of these agents, providing evidence-based insights for clinical practice. METHODS: A retrospective analysis of the FDA Adverse Event Reporting System (FAERS) data (2004Q1-2024Q3) was conducted. Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS), were employed to identify adverse event (AE) signals. Duplicate entries were identified and removed using CASE_ID and FDA_DT criteria, after which AE signals were classified according to MedDRA System Organ Classes (SOCs) and Preferred Terms (PTs). RESULTS: Among 26,004 antifungal-associated AE reports, Amphotericin B exhibited the strongest renal toxicity signals (nephropathy toxic (i.e., nephrotoxicity): ROR = 24.86; renal tubular disorder: ROR = 46.46), while voriconazole was associated with hepatobiliary disorders (ROR = 4.61) and ocular toxicity (toxic optic neuropathy: ROR = 228.80). Caspofungin demonstrated marked hepatotoxicity (cholestasis: ROR = 23.79), whereas Posaconazole and Isavuconazole showed lower mortality rates (19.56% and 22.70%, respectively). Amphotericin B demonstrated the highest mortality rate (47.14%), which was statistically significantly higher compared to other agents (chi(2) test, p < 0.001), and life-threatening AE rates (4.97%), contrasting with Isavuconazole's favorable safety profile (1.89% life-threatening AEs). Time-to-onset analysis revealed delayed AE onset for Isavuconazole (median: 19.5 days) versus Caspofungin (6 days). CONCLUSION: Significant safety variations exist among antifungal agents for IA. Amphotericin B and Caspofungin are associated with severe renal/hepatic toxicities and higher mortality, while Isavuconazole and Posaconazole may offer safer alternatives with delayed AE onset. Clinicians should prioritize drug-specific risks when tailoring treatment for IA patients. |
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| 組織名 | Department of Pharmacy, Tonglu Branch Hospital, Hangzhou First People's Hospital,;Hangzhou, Zhejiang, China.;Department of Orthopaedics, Tonglu Branch Hospital, Hangzhou First People's;Hospital, Hangzhou, Zhejiang, China. |
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