Brands, Medical Use, Clinical Data
Brands / Synonyms
Aleviatin; Exceglan; Excegram; Excegran; Zonegran; Zonisamida [Spanish]; Zonisamide [Usan:Ban:Inn:Jan]; Zonisamidum [Latin]
For use as adjunctive treatment of partial seizures in adults with epilepsy.
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium channels which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). Likewise zonisamide has also been found not to potentiate syanptic activity by GABA (gamma amino butyric acid).
Mechanism of Action
Zonisamide binds to sodium channels, voltage sensitive calcium channels and to a lesser extent carbonic anhydrase. This blocks or suppresses neuronal depolarization and hypersynchronization.
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.
Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
Biotrnasformation / Drug Metabolism
Primarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2–sulfamoylacetyl phenol, respectively.
ZONEGRAN is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or
Effects of ZONEGRAN on the pharmacokinetics of other antiepilepsy drugs (AEDs): Zonisamide had no
appreciable effect on the steady state plasma concentrations of phenytoin, carbamazepine, or valproate during
clinical trials. Zonisamide did not inhibit mixed-function liver oxidase enzymes (cytochrome P450), as measured in
human liver microsomal preparations, in vitro. Zonisamide is not expected to interfere with the metabolism of other
drugs that are metabolized by cytochrome P450 isozymes.
Effects of other drugs on ZONEGRAN pharmacokinetics:
Drugs that induce liver enzymes increase the metabolism and clearance of zonisamide and decrease its
half-life. The half-life of zonisamide following a 400 mg dose in patients concurrently on enzyme-inducing AEDs such
as phenytoin, carbamazepine, or phenobarbital was between 27-38 hours; the half-life of zonisamide in patients
concurrently on the non-enzyme inducing AED, valproate, was 46 hours. Concurrent medication with drugs that either
induce or inhibit CYP3A4 would be expected to alter serum concentrations of zonisamide.
Interaction with cimetidine: Zonisamide single dose pharmacokinetic parameters were not affected by
cimetidine (300 mg four times a day for 12 days).