Zonisamide: its pharmacology, efficacy and safety in clinical trials.
Author(s): Brodie MJ, Ben-Menachem E, Chouette I, Giorgi L.
Affiliation(s): Epilepsy Unit, Western Infirmary, Dumbarton Rd., Glasgow, Scotland.
mjb2k@clinmed.gla.ac.uk
Publication date & source: 2012, Acta Neurol Scand Suppl. , (194):19-28
Zonisamide is a benzisoxazole derivative, chemically unrelated to other
antiepileptic drugs, that appears to have multiple mechanisms of action,
including inhibition of Na(+) channels and reduction of T-type Ca(2+) currents.
It is currently licensed in Europe and the USA for adjunctive treatment of
partial seizures in adults, and in Europe as monotherapy for treatment of partial
seizures in adults with newly diagnosed epilepsy. Zonisamide displays
predictable, dose-dependent pharmacokinetics and has a half-life of ~60 h,
allowing once- or twice-daily administration. It has a low potential for
interactions with other medications, including oral contraceptives. The clinical
efficacy of adjunctive zonisamide therapy has been established in four pivotal,
phase III, randomized, double-blind, placebo-controlled trials, which together
included approximately 850 patients, aged 12-77 years, with refractory partial
epilepsy. In all four trials, zonisamide 300-600 mg/day resulted in significant
reductions in median total seizure rates vs placebo, and zonisamide was generally
well tolerated; the most frequently reported adverse events being somnolence,
dizziness and anorexia/weight loss. Subanalysis of the primary European trial
indicated that zonisamide was effective when administered as first-line
adjunctive treatment, and a long-term extension to the same trial demonstrated
that the efficacy and safety/tolerability of adjunctive zonisamide was sustained
for up to 36 months. Once-daily monotherapy with zonisamide (200-500 mg/day) has
been shown to be non-inferior to, and as well tolerated as, twice-daily
monotherapy with controlled-release carbamazepine (400-1200 mg/day) in adults
with newly diagnosed partial epilepsy. Zonisamide has also been shown to have
favourable long-term retention rates, an important indication of its overall
effectiveness.
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