Topiramate

Abstract

Clinical evidence is emerging that topiramate (TPM) may be effective in pediatric epilepsies. Topiramate pharmacokinetics appear to be linear in children when administered in dosages up to 9 mg/kg/d. Mean oral clearance is 44% to 54% higher in children when compared with historical data from adults; steady-state plasma TPM concentrations for the same mg/kg dose are expected to be 33% lower in children. While double-blind, placebo-controlled trials of adjunctive TPM therapy in Lennox-Gastaut syndrome, primary generalized tonic-clonic seizures, and refractory partial-onset seizures in children are ongoing, preliminary results of pilot studies and the open-label extension phases of these double-blind studies suggest TPM may be effective as adjunctive therapy in a broad range of seizure disorders. In the open-label extension phase of a double-blind trial, the proportion of patients with Lennox-Gastaut syndrome experiencing 50% or greater reduction in seizures was 47%. Likewise, seizures were reduced 50% or more with TPM adjunctive therapy in 64% of children with partial-onset seizures and in 67% of patients with primary generalized tonic-clonic seizures treated with open-label during the extension phase of two separate double-blind studies. Preliminary experience suggests that TPM monotherapy can be successfully substituted for another antiepileptic drug in some children. The results of the well-controlled trials are needed to confirm these preliminary observations of TPM effectiveness in pediatric epilepsies.