Real-World safety profile of Fenfluramine in refractory epilepsy: a pharmacovigilance study based on FAERS database

The safety profile of Fenfluramine, a drug for refractory epilepsy, remains insufficiently characterized in real-world settings. This study aimed to evaluate post-marketing adverse events (AEs) associated with Fenfluramine using the FDA Adverse Event Reporting System (FAERS) database.

Our investigation collected all AE reports related to Fenfluramine from the third quarter of 2020 (Q3 2020) to the fourth quarter of 2024 (Q4 2024). We employed four established methodologies including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) to perform signal mining for these AEs.

A total of 20,474,269 AE reports were collected, among which 2,612 cases were associated with Fenfluramine. All AEs were categorized into 27 System Organ Classes (SOCs) and 172 Preferred Terms (PTs). Reports of nervous system disorders ranked highest among the 27 SOCs, followed by general disorders and administration site conditions, and psychiatric disorders. In addition to clinically common AEs such as decreased appetite, somnolence, and weight decrease, pulmonary valve incompetence and tricuspid valve incompetence-related AEs exhibited notable signal strength and high reporting frequency, remaining a primary clinical concern. This study also identified multiple novel AEs for the first time, including aggression, behavior disorder, and anger within psychiatric disorders, as well as pneumonia and decreased oxygen saturation, which notably require further investigation and clinical vigilance.

In conclusion, while Fenfluramine demonstrates clear therapeutic benefits for refractory epilepsy, these findings emphasize the necessity for comprehensive risk assessment in clinical practice.