Safety and Efficacy of Oxcarbazepine: Results of Randomized, Double-Blind Trials Ahmad Beydoun, M.D. Oxcarbazepine is approved as monotherapy and adjunctive therapy for partial seizures with and without secondarily generalized seizures in adults and as adjunctive therapy for partial-onset seizures in children aged 4–16 years. The clinical development of oxcarbazepine is different from the newer antiepileptic drugs (AEDs) in the extent and concordance of results across clinical trials. The safety and efficacy of oxcarbazepine was evaluated in adjunctive therapy trials, in comparative monotherapy trials with classic AEDs in adults and children with newly diagnosed epilepsy, in monotherapy therapeutic failure design trials in patients with refractory partial seizures, and in trigeminal neuralgia and affective disorder. The results of oxcarbazepine in treating epilepsy are discussed. (Pharmacotherapy 2000;20(8 Pt 2):152S–158S) Oxcarbazepine (10,11-dihydro-10-oxo-5H- dibenz[b,f]azepine-5-carboxamide) is approved in 54 countries and recently was approved in the United States as monotherapy and adjunctive therapy for partial seizures with and without secondarily generalized seizures in adults and as adjunctive therapy for partial-onset seizures in children aged 4–16 years. Oxcarbazepine is the keto analog of carbamazepine (Figure 1). 1 Although structurally related to carbamazepine, oxcarbazepine offers a number of clinically important pharmacokinetic advantages. One is its route of biotransformation. Unlike carbama- zepine, which is metabolized by cytochrome P450 oxidative processes, oxcarbazepine undergoes primarily reductive biotransformation by cytosolic enzymes to the 10-monohydroxy metabolite, MHD. 2 Although pharmacologically active, oxcarbazepine has a short half-life of only 1–2.5 hours versus a half-life of 8–10 hours for MHD, which is mainly responsible for the pharmacologic effect. 3, 4 At steady state, the plasma concentrations of MHD are 9-fold higher than those of the parent drug. 3 The lack of oxidative metabolism results in two attractive properties. First, the 10,11 epoxide that contributes to the adverse event profile of carbamazepine 5, 6 is not produced. In addition, oxcarbazepine has a lower propensity to inhibit or induce hepatic oxidative enzymes and therefore a diminished potential for drug-drug interactions. 2 Also, whereas carbamazepine induces its own metabolism and undergoes autoinduction, the elimination of oxcarbazepine and its metabolites does not change significantly over time. 3 Similar to carbamazepine, the anticonvulsant properties of oxcarbazepine probably are mediated in part by blockage of the voltage-dependent sodium channel. 1, 2 The clinical development of oxcarbazepine is different from the newer antiepileptic drugs (AEDs) in the extent and concordance of clinical trial results. The results obtained from clinical trials with oxcarbazepine for the treatment of epilepsy are discussed. All trials were approved by the institutional review boards of the participating centers, and all patients and legal guardians gave informed consent. Adjunctive Therapy Trials Two double-blind, placebo-controlled trials evaluated the efficacy and safety of oxcarbazepine as adjunctive therapy. 7, 8 The first was a From the University of Michigan Medical Center, Ann Arbor, Michigan. Address reprint requests to Ahmad Beydoun, M.D., University of Michigan Medical Center, University Hospital 1B300/0036, 1500 East Medical Center Drive, Ann Arbor, MI 48109; e-mail: Beydoun@umich.edu.