Evaluation of zonisamide for the treatment of focal epilepsy: a review of pharmacokinetics, clinical efficacy and adverse effects

Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above. Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics. Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.