Oxcarbazepine is used as monotherapy or adjunctive therapy (i.e., in combination with other anticonvulsants) in the management of partial seizures.
Oxcarbazepine conventional (immediate-release) tablets and oral suspension are used as monotherapy of partial seizures in adults and pediatric patients 4 years of age or older.
Efficacy of oxcarbazepine monotherapy in patients with partial seizures has been established in several multicenter, randomized controlled studies using immediate-release preparations of the drug. In one placebo-controlled study in patients 11-62 years of age with refractory partial seizures (undergoing evaluation for epilepsy surgery) who had been withdrawn from anticonvulsants prior to randomization, oxcarbazepine at dosages up to 2.4 g daily for 10 days was more effective than placebo. Results of another placebo-controlled study in previously untreated patients 8-69 years of age with newly diagnosed or recent-onset partial seizures indicated that oxcarbazepine dosages up to 1.2 g daily for 84 days were more effective than placebo. In 2 conversion-to-monotherapy studies, therapy with oxcarbazepine 2.4 g daily for up to 126 days was substantially more effective than oxcarbazepine 300 mg daily in patients 11-66 years of age with partial seizures who had been withdrawn from previous therapy with 1 or 2 anticonvulsants because of inadequate control. An additional evaluator-blinded monotherapy trial was conducted in pediatric patients 1 month to 16 years of age with inadequately controlled or new-onset partial seizures. In this study, oxcarbazepine 40-60 mg/kg daily was not more effective than oxcarbazepine 10 mg/kg daily; however, due to several limitations in the study design, the results were considered uninterpretable. Efficacy of oxcarbazepine monotherapy in pediatric patients 4 years of age or older is based on pharmacokinetic and pharmacodynamic data.
Results of several multicenter, randomized, double-blind monotherapy trials in patients with newly diagnosed or previously untreated partial or generalized seizures indicate that oxcarbazepine exhibits anticonvulsant activity similar to carbamazepine, phenytoin, or valproic acid.
Oxcarbazepine conventional (immediate-release) tablets and oral suspension are used as adjunctive therapy (i.e., in combination with other anticonvulsants) of partial seizures in adults and pediatric patients 2 years of age or older. Efficacy of oxcarbazepine for this use was established in 2 multicenter, randomized, double-blind, placebo-controlled studies (one in adults and one in children 3-17 years of age) and an additional evaluator-blinded study that compared 2 dosages of oxcarbazepine in infants and children 1 month to less than 4 years of age. In the placebo-controlled studies, patients initially were stabilized on optimum dosages of 1-3 anticonvulsants during an 8-week baseline period; those experiencing at least 8 (minimum 1-4 per month) partial seizures during this phase were randomized to receive oxcarbazepine (as an immediate-release preparation) or placebo during a dosage titration period of 2 weeks followed by a 14- or 24-week maintenance period in children or adults, respectively. Efficacy of oxcarbazepine in these studies was evaluated in terms of the change in seizure frequency (i.e., the median decrease [or increase] in average monthly [28-day] seizure rate). Adults receiving oxcarbazepine 600 mg, 1.2 g, or 2.4 g daily or placebo experienced a median decrease in seizure frequency of about 26, 40, 50, or 8%, respectively, while pediatric patients receiving oxcarbazepine dosages ranging from 30-46 mg/kg daily (depending on baseline body weight) or placebo experienced a median decrease in seizure frequency of about 35 or 9%, respectively. In the dose comparison study, infants and children who were receiving stable dosages of up to 2 anticonvulsants prior to study entry and who had experienced at least 2 partial seizures during a 72-hour baseline period were randomized to receive adjunctive therapy with low-dose oxcarbazepine (10 mg/kg daily with no titration period) or high-dose oxcarbazepine (60 mg/kg daily after a 26-day titration period) as an oral suspension. Patients in both groups received their target dosage for 9 days and seizures were assessed during the last 72 hours of the maintenance period with video electroencephalography (EEG). Oxcarbazepine 60 mg/kg daily was substantially more effective than oxcarbazepine 10 mg/kg daily in reducing seizure frequency. Efficacy of oxcarbazepine was not demonstrated in children younger than 2 years of age in this study.
Oxcarbazepine also is commercially available as extended-release tablets for once-daily administration in the adjunctive management of partial seizures in adults and pediatric patients 6 years of age and older. Efficacy of the extended-release tablets in adults was evaluated in a randomized, double-blind, placebo-controlled study in patients 18-65 years of age with refractory partial epilepsy. Patients who experienced at least 3 partial seizures every 28 days during an 8-week baseline period despite receiving stable dosages of 1-3 anticonvulsants were randomized to receive adjunctive therapy with oxcarbazepine (1.2 or 2.4 g daily as extended-release tablets) or placebo. Patients receiving oxcarbazepine 1.2 g daily, oxcarbazepine 2.4 g daily, or placebo experienced a median decrease in seizure frequency of about 38, 43, or 29%, respectively. Although the comparison between the 1.2-g daily dosage and placebo did not reach statistical significance in this study, the effectiveness of this dosage is supported by exposure-response analyses. Efficacy of oxcarbazepine extended-release tablets in pediatric patients is based on a pharmacokinetic study in children 4-16 years of age and studies with the immediate-release preparation in pediatric patients in addition to clinical studies performed in the adult population with both immediate-release and extended-release preparations of the drug.
(See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Oxcarbazepine has been used alone or in combination with other drugs (e.g., antipsychotic agents) for the treatment and prevention of acute manic or mixed episodes in patients with bipolar disorder. Limited data suggest that oxcarbazepine may have equivalent efficacy and better tolerability than carbamazepine for this indication. The American Psychiatric Association (APA) considers oxcarbazepine an alternative treatment option for patients who do not respond adequately to first-line therapies such as lithium, valproic acid, and antipsychotic agents (e.g., olanzapine). For additional information on the management of bipolar disorder,