Real-world safety of zonisamide: Mining and analysis of adverse events related to zonisamide based on FAERS database

PurposeTo investigate the real-world adverse event signals associated with zonisamide and provide a foundation for its safe clinical use. MethodsAdverse event reports involving zonisamide as the primary suspected drug were collected from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were analyzed utilizing the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods of the proportional imbalance technique. ResultsA total of 3205 adverse event reports involving zonisamide as the primary suspected drug were identified, resulting in 260 positive signals for preferred terms (PTs). These signals, derived from both the ROR and BCPNN methods, encompassed 27 systems and organs (SOCs), with a predominant focus on nervous system disorders and skin and subcutaneous tissue disorders. The most frequently reported PTs included seizures, drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, rash, and dizziness. Notably, the top PTs in terms of signal intensity included perinephritis, epilepsy with myoclonic-atonic, ocular mucocutaneous syndrome, ocular choroidal leakage, tonsillar exudate, and ovarian granulosa vesicular cell tumor. Interestingly, ten of the top 30 risk signals for adverse events, based on signal strength, were not detailed in the package inserts. Thses included perinephritis, myoclonic dystonic epilepsy, ovarian granulosa vesicular cell tumor, positive human herpesvirus 6 serology, and positive lymphocyte stimulation test. ConclusionCommon adverse reactions to zonisamide in real-world settings are generally in line with the established specification, with the most frequently observer signals related to neurological, skin, and subcutaneous tissue disorders. However, several newly suspected adverse reactions have been identified, including perinephritis, infectious pneumonitis, ovarian granulosa vesicular cell tumor, positive serology for human herpesvirus 6, and positive lymphocyte stimulation test. These findings indicate that these potential adverse reactions should be closely monitored in clinical practice.