Newer Antiepileptic Drugs

Three new medicines for epilepsy have been added to the U.S. Market in the year 2000: levetiracetam (Keppra®), oxcarbazepine (Trileptal®), and zonisamide (Zonegran®).

MINCEP participated in the clinical drug trials for all three of these new medications and has hands-on experience with all of them.

Levetiracetam is a novel AED marked by UCB Pharma. Its actual mechanism of action is not known. In animal models, it has a unique profile which would predict activity in a broad range of epilepsy syndromes. It may also have some neural protective effects. It has been approved by the FDA as an add-on medicine for simple partial and complex partial seizures. Its clinical spectrum appears to be broader. Sixty-six percent of levetiracetam is excreted by the kidneys. It is not metabolized by the cytrochrome P450 system in the liver, and it lacks drug/drug interactions. It can be added to existing AEDs without altering their concentrations. Its major role will initially be as a safe, effective drug which can be started at effective doses and titrated upward if needed.

Oxcarbazepine is presently available in over 60 countries and has been sold in Denmark for a decade. It is structurally similar to carbamazepine (Tegretol®, Carbatrol®), but has fewer side effects and fewer interactions. It is FDA-approved for localization-related epilepsy with and without secondary generalization, for both monotherapy as well as add-on treatment. The major advantages of oxcarbazepine are:

* Tolerated better by most patients
* Possible broader spectrum of action than carbamazepine
* Fewer drug interactions than carbamazepine

Zonisamide is unique among antiepileptic drugs because it is a sulfonamide derivative. Therefore, if you have a sulfa allergy, zonisamide is not for you. It has been used widely in Japan for over a decade and has been used with 1 million patients. Because zonisamide was originally studied in the U.S. during the mid-1980's, MINCEP has been treating patients with this drug for more that 15 years. Although zonisamide has a broad spectrum of activity, it appears to be especially effective for certain specific epilepsy syndromes such as Baltic myoclonic epilepsy. Even though it is FDA-approved only as an add-on therapy for partial epilepsy, it has also shown activity against absence and myoclonic seizures. Zonisamide is metabolized by the liver; therefore medications like Dilantin®, Tegretol® and phenobarbital will decrease zonisamide levels if used together.

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