Safety of Drugs Used in Difficult-to-Treat Epileptic Syndromes: A Disproportionality Analysis Using the...

Background/Objectives: Difficult-to-treat epileptic syndromes include conditions typically emerging in the first years of life and are characterized by a high rate of drug refractoriness. This study aimed to better define the safety profile of drugs used as adjunctive therapies for seizures associated with these syndromes using real-world pharmacovigilance data. Methods: We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting stiripentol, cannabidiol, or fenfluramine as suspected drugs, reported on the Eudravigilance database until the third quarter of 2024. Data were evaluated with descriptive analyses and then with disproportionality measures, including the reporting odds ratio. Results: A total of 5986 ICSRs met the inclusion criteria (71.6% from cannabidiol, 14.5% fenfluramine, and 13.9% stiripentol). Significantly higher probabilities of reporting Cardiac disorders, Vascular disorders, and Respiratory, thoracic, and mediastinal disorders were observed with fenfluramine. Cannabidiol was associated with Product issues, whereas stiripentol was associated with injury, poisoning, procedural complications, Metabolism and nutrition disorders, and Blood and lymphatic system disorders. Conclusions: Our analysis did not highlight new and unexpected serious safety signals but confirmed the need to strictly monitor patients for the risk of adverse events. However, further prospective studies are required to better clarify the safety profile of these drugs in order to optimize their use.