Brand Name Drug: Zonegran
Active Ingredient Drug: zonisamide
Indication: Adjunctive therapy in the treatment of partial seizures in adults with epilepsy
Company Name: Elan Corporation, plc
Availability: Approved by FDA on March 28, 2000; Zonegran has been marketed under the trade name Excegran since 1989 in Japan
Another new antiseizure medication has entered to drug arena, the latest in a spate of new drugs for partial onset epilepsy (see previous articles on Keppra and Trileptal). On March 28, 2000, the FDA approved Zonegran (zonisamide) as adjunctive therapy in the treatment of partial seizures in adults with epilepsy. Zonegran has been marketed under the trade name Excegran since 1989 in Japan, supporting the drug’s safety and efficacy and representing some one million patient years of exposures. Zonegran is manufactured by Elan Corporation, plc, an Ireland-based biotechnology company.
Zonegran (zonisamide) is available in 100 mg capsules. The initial dose should be 100 mg daily, and the dose may be increased to 200 mg/day after two weeks and for at least an additional two weeks. The dose can then be further increased to 300 mg/day and 400 mg/day as needed, with the dose stable for at least two weeks to achieve a steady state at each level.
Although the precise mechanism by which Zonegran is thought to exert its antiseizure effect is unknown, it is thought to act at sodium and calcium channels. In vitro studies suggest that Zonegran blocks sodium channels and reduces voltage-dependent, transient inward currents, consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. Zonegran may also suppress synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses or neuronal or glial uptake of [3H]-GABA. In vivo analyses indicate that Zonegran facilitates both dopaminergic and serotonergic neurotransmission.
Zonegran (zonisamide): Clinical Study Results
The efficacy of Zonegran was established in three multicenter, placebo-controlled, double-blind 3-month clinical trials in 499 patients (209 women and 290 men) with a history of at last four partial onset seizures per month in spite of receiving one or two antiepilepsy drugs at therapeutic concentrations. Zonegran or placebo was added to the existing therapy.
All three studies showed that patients who took Zonegran experienced a greater median percentage reduction in partial seizures and had a greater percentage of responders than those who took placebo. The median percentage reduction in partial seizures in Zonegran patients vs. placebo was 40.5% vs. 9.0%, respectively, in study 1; 29.6% vs. -3.2% in study 2; and 27.2% vs. -1.1% in study 3. The percentage of responders among Zonegran patients vs. placebo was 41.8% vs. 22.2%, respectively, in study 1; 29.0% vs. 15.0% in study 2; and 28.0% vs. 12.0% in study 3. The response to Zonegran (zonisamide) was significantly greater than that for placebo for all dose levels (100 mg/day, 200 mg/day, and 400-600 mg/day).
What the Patient Should Know
Zonegran (zonisamide) has been associated with side effects similar to those of other antiepileptic drugs. The most commonly observed adverse events are somnolence, dizziness, headache, nausea and vomiting, agitation/irritability, fatigue, difficulty concentrating, and weight loss. Many of these adverse events are dose-related. Patients should not drive a car or operate other complex machinery until they have gauged their experiences on Zonegran and determined how it affects their performance.
Patients should contact their physician immediately if they develop a skin rash or if their seizures worsen; if they develop signs or symptoms such as sudden back or abdominal pain or blood in the urine (which may indicate kidney stones); or if they develop a fever, sore throat, mouth sores, or easy bruising.
Since Zonegran may cause birth defects, patients should be advised to use contraceptives while taking the drug, and to notify their physicians if they become pregnant or intend to become pregnant during therapy. Patients should also notify their physicians if they intend to breastfeed an infant while taking Zonegran.
Zonegran has no effects on plasma concentrations of other AEDs, but phenytoin, carbamazepine, and phenobarbital may increase the metabolism and clearance of Zonegran and decrease its half-life. Since Zonegran is metabolized by the liver and eliminated by the kidneys, caution should be exercised when administering Zonegran to patients with impaired hepatic or renal function
Because Zonegran (zonisamide) is a sulfonamide, patients who are allergic to sulfa drugs should not take Zonegran.