Zonisamide: a new antiepileptic drug

Abstract

Zonisamide (ZNS) is a relatively new antiepileptic medication currently available in Japan. Attempts to market the drug in the United States were thwarted by reports of nephrolithiasis by European and American investigators. However, successful marketing of the drug in Japan has resulted in a renewed interest in bringing the drug to the United States. Japanese experience with ZNS showed a broad spectrum of efficacy in the treatment of seizures, including infantile spasms and myoclonic seizures. A neuroprotective role and an antimanic effect have also been reported. The exact antiepileptic mechanism of action of ZNS is not known, but it has dose-dependent sodium channel blocking and T-type calcium channel blocking properties and free radical scavenging actions. Recommended initial adult dosage in Japan is 100-200 mg/d, increased if necessary to 200-400 mg/d, up to a maximum of 600 mg/d. In children, initial dosage is 2-4 mg/kg/d, increased if necessary to 4-8 mg/kg/d up to a maximum of 12 mg/kg/d. The recommended therapeutic plasma ZNS concentration is 10-20 mg/L. Adverse events, most notably drowsiness, loss of appetite, gastrointestinal problems, and CNS toxicity, have been noted with plasma ZNS concentrations of > 30 mg/L. A drug rash also has been reported.