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


OBJECTIVE
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 >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=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 1mg/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.
Shinnar
Shlomo
S
Departments of Neurology, Pediatrics and Epidemiology and Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA. sshinnar@aol.com
Pellock
John M
JM
Conry
Joan A
JA
D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000503:physiopathology; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced; D012640:Seizures / Q000188:drug therapy*; D012720:Severity of Illness Index; D013546:Sweating / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014717:Vertigo / Q000139:chemically induced; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide