Safety of zonisamide therapy: prospective follow-up survey.

Zonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1-3 years. Nine hundred twenty-eight children and 584 adults (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1008 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (5.8%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hypohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis.