Topiramate is a structurally new broad-spectrum antiepileptic drug with proven efficacy as monotherapy and combination therapy for the treatment of epilepsy in adults and children with both generalized and partial seizure types. The undesirable effects of Topiramate, particularly related to central nervous system effects, can be offset with slow titration in effective and well tolerated doses. Topiramate is effective when used with other drugs, which is associated with a low risk of drug interaction and good tolerability. Therefore, Topiramate is the drug of choice for both monotherapy and combination therapy in the treatment of epilepsy in adult and pediatric patients. Let’s talk about Med Topiramate (Topamax) in Epilepsy.
Pharmacokinetics and pharmacodynamics
Bioavailability is about 80%. Pharmacokinetics is linear (proportional to dose). Stable state is usually reached within 4-8 days. Topiramate is not extensively metabolized, with 70-80% of the dose excreted unchanged in the urine. Blood plasma protein binding is 13-17%. Low potential for clinically significant interactions with other drugs. When co-administration with enzyme inducing drugs (carbamazepine or phenytoin) metabolism of Topiramate increases up to 50-70%, which requires increasing the dose of the latter.
Efficacy of Topiramate in epilepsy monotherapy: results of studies
The efficacy of Topiramate monotherapy has been proven in a number of randomized controlled double-blind comparative and noncomparative studies in both partial and generalized types of seizures in children and adults. Results of randomized double-blind noncomparative studies of the efficacy of Topiramate monotherapy in persons with newly diagnosed epilepsy demonstrated that after 6-7 months, up to 83% of patients were seizure-free, and after 12-13 months, about 76% of patients were seizure-free. Subgroup analyses of adults and children yielded results similar to those for the entire patient population in these studies. Topiramate monotherapy was effective for the treatment of both partial and generalized seizure types.
The results of a randomized double-blind comparative study of Topiramate monotherapy in patients with newly diagnosed epilepsy demonstrated that the drug was not inferior to standard anticonvulsants (valproic acid and carbamazepine) in both the primary (time to exit) and secondary measures of effectiveness (time to first seizure and proportion of patients without seizures during the last 6 months of treatment). In addition, the use of Topiramate at a dose of 100 mg/day was associated with the lowest rate of patient withdrawal from the study due to adverse reactions compared to carbamazepine and valproate.
Topiramate has provided long-term seizure control in adult and pediatric patients with epilepsy in long-term noncomparative studies, some of which were extensions of placebo-controlled studies.