Zonisamide (Zonegran, Athena-Elan)
Zonisamide (Zonegran) is a sufonamide-related drug, similar in many ways to topiramate. Zonegran is a broad-spectrum antiepileptic drug, useful for partial, secondarily generalized, absence, and myoclonic seizure types. Zonisamide may control myoclonic seizures in cases for which all other drugs have failed.
Early clinical trials with zonisamide in the U.S. were halted because of a high incidence of kidney stones. Trials continued in Japan and elsewhere, whereby the kidney stone risk was determined to be between two and four percent. U.S. trials were resumed and the drug was shown to be relatively safe and effective. Because of the theoretical additive risk for kidney stones, zonisamide should not be used in conjunction with topiramate (Topamax), acetazolamide (Diamox), or other drugs know to provoke stones.
Zonisamide, like topiramate, can cause cognitive (thinking) problems in a significant minority of those taking the drug, but the incidence of cognitive problems probably is a little lower than with topiramate (at least in the approved dosages). Weight loss is common, viewed favorably by some patients; unfavorably by others.
Summary Data for Zonisamide
Pill sizes: 100 mg red-white capsule.
Liquid for oral: none.
Injectable: none.
Typical adult dose: start with 100 mg at night for 2 weeks, then increase by 100 mg daily every 2 weeks to a target dose of 200 - 600 mg/d in 1 or 2 daily doses. Half-life would permit daily dosing, but GI side effects might require splitting the dose.
Typical pediatric dose: Pediatric dosing is difficult because of the limited dosage forms. In older children, can start with 2 - 4 mg/kg/d and increase over weeks to a few months to a target of 4 - 8 mg/kg/d.
Metabolism: one-third excreted unchanged in the kidney, two-thirds metabolized in the liver by the CYP 3A4 system and acetylation.
Half-life: In monotherapy 2 - 3 days. With enzyme inducers (Dilantin, Tegretol, phenobarbital, etc.) 1 - 2 days.
Serum levels: 10 - 30 mcg/ml.
Pregnancy: Category C - can cause birth defects in animals, unknown in humans.
Drugs that lower ZNS levels: Dilantin, phenobarbital, primidone, Tegretol.
ZNS decreases effects of other drugs: Since it is metabolized by the CYP 3A system, it could theoretically inactivate oral contraceptives.
Dangerous Side Effects
Kidney stones in 2 - 4%; birth control pill failure; rare blood count or liver problems; serious rash (Stevens-Johnson syndrome or toxic epidermal necrolysis), rare heat stroke.
Common Side Effects
Cognitive (thinking) problems, sleepiness, dizziness, unsteadiness, double vision, GI upset, weight loss.
Other Side Effects
Ordinary skin rash, personality change, depression, headaches, insomnia.