Topiramate

General Information

Topiramate is a relatively new anticonvulsant drug with a fructopyranose-sulphamate chemical structure, which has been licensed for adjunctive therapy in patients with intractable partial epilepsy. It has recently been approved for expanded seizure indications, including adjunctive therapy in children with partial onset seizures and for monotherapy. Topiramate is rapidly and efficiently absorbed from the GI tract after which it is eliminated, predominantly unchanged, via the renal route with a plasma t½ of 20-30 hrs. However, a proportion of the drug undergoes hepatic metabolism by oxidative pathways and the clearance is increased by enzyme inducing drugs. Topiramate is only 15% protein bound, and is a weak carbonic anhydrase inhibitor and is thus also bound to a high affinity, low capacity binding site on erythrocytes. Since large inter-individual differences exist between the dose required to achieve safe and effective plasma concentrations and topiramate is often prescribed together with other AED’s which have similar CNS side-effects, the measurement of serum or plasma topiramate levels is a valuable aid to individualisation of treatment. A reference range is established within which topiramate is likely to be effective without causing toxicity. Therapeutic drug monitoring is particularly useful when non-compliance or toxicity is suspected, but should also be applied when modifying treatment in any way or to establish baseline values during successful treatment.