Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy

Abstract

Background Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. Aims To assess the long-term safety and efficacy of zonisamide in children and adolescents. Methods Zonisamide-naïve patients ( n=109, aged 3–15 years, weight ⩾12.5 kg) with a clinical diagnosis of epilepsy (⩾4 seizures/month, receiving 1–2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1 mg/kg/day, increased by 2 mg/kg/day every 1–2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. Results The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months’ treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant ( p=0.033) median reduction in ‘all seizure’ frequency of 2.60 seizures per week was observed. Additionally, a significant ( p=0.029) median reduction of 1.80 seizures/week in ‘complex partial’ seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. Conclusions Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.