Topiramate: a new antiepileptic drug

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage of topiramate are reviewed. Topiramate is indicated for use in the adjunctive treatment of adult partial-onset epilepsy. A sulfamate-substituted monosaccharide, it is structurally distinct from other antiepileptic agents. Topiramate acts by blocking the spread of seizures. Oral topiramate has high bioavailability and low protein binding, and as monotherapy its half-life permits once- or twice-daily administration. The drug is excreted largely unchanged in the urine. Clinical trials have shown that topiramate is effective as adjunctive therapy in treating adult partial-onset epilepsy with or without secondarily generalized seizures. In adults with refractory partial epilepsy, topiramate has shown efficacy when carbamazepine or phenytoin has failed. Topiramate may also be effective against partial-onset epilepsy and Lennox-Gastaut syndrome in children, but more pediatric studies are needed. CNS adverse effects are the most common; weight loss and nephrolithiasis have also been reported. The drug does not appear to interact significantly with other antiepileptic agents, but enzyme inducers like phenytoin and carbamazepine can decrease serum topiramate levels by 50%. The initial dosage is 50 mg nightly for seven nights, followed by an increase weekly to 400 mg/day in two divided doses. Topiramate is more costly than other anticonvulsants; however, drug therapy accounts for less than 10% of the total direct cost of epilepsy treatment. Topiramate offers an effective, well-tolerated option in patients with adult partial-onset seizures.