General Information

Trileptal (oxcarbazepine) is an anti-convulsant.

Trileptal is specifically indicated for:

Adults: Monotherapy or adjunctive therapy in the treatment of partial-onset seizures

Pediatrics:

Monotherapy in the treatment of partial-onset seizures in children 4-16 years
Adjunctive therapy in the treatment of partial-onset seizures in children 2-16 years

Trileptal is supplied as tablets and as an oral suspension. The recommended dosing is as follows:

Adults: initiate with a dose of 600 mg/day, given twice a day

Adjunctive Therapy: Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day

Conversion to Monotherapy: withdrawal concomitant over 3 to 6 weeks; reach maximum dose of TRILEPTAL in 2 to 4 weeks with increments of 600 mg/day at weekly intervals to a recommended daily dose of 2400 mg/day

Initiation of Monotherapy: Increments of 300 mg/day every third day to a dose of 1200 mg/day

Initiate at one-half the usual starting dose and increase slowly in patients with a creatinine clearance < 30 mL/min

Pediatrics: initiation with 8 to 10 mg/kg/day, given twice a day. For patients aged 2 to < 4 years and under 20 kg, a starting dose of 16 to 20 mg/kg/day may be considered. Recommended daily dose is dependent upon patient weight.

Adjunctive Patients (Aged 2-16 Years): For patients aged 4 to 16 years, target maintenance dose should be achieved over 2 weeks. For patients aged 2 to < 4 years, maximum maintenance dose should be achieved over 2 to 4 weeks and should not to exceed 60 mg/kg/day.

Conversion to Monotherapy for Patients (Aged 4-16 Years): Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs (AEDs) can be completely withdrawn over 3 to 6 weeks

Initiation of Monotherapy for Patients (Aged 4-16 Years): Increments of 5 mg/kg/day every third day

Mechanism of Action

The pharmacological activity of Trileptal (oxcarbazepine) is primarily exerted through the 10-monohydroxy metabolite (MHD) of oxcarbazepine… The precise mechanism by which oxcarbazepine and MHD exert their antiseizure effect is unknown; however in vitro electrophysiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in the stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and dimunition of propagation of synaptic impulses. These actions are thought to be important in the prevention of seizure spread in the intact brain. In addition, increased potassium conduction and modulation of high-voltage activated calcium channels may contribute to the anticonvulsive effects of the drug. No significant interactions of oxcarbazepine or MHD with brain neurotransmitter or modulator receptor sites have been demonstrated.

Clinical Trial Results

In studies in which the drug was compared to a placebo, patients given the drug lasted significantly longer without having certain seizures than did those patients not taking the drug.

Furthermore, a higher dosage of the drug yielded a significantly longer period before the patient demonstrated specific seizure symptoms.

In addition, two trials, one in which patients were ages 15-66 and the other in which patients were ages 3-17, examined Trileptal as an adjunctive therapy. Every patient in these trials was on 1-3 concomitant Anti-Epileptic Drugs. In both studies, dosage was increased over a period of two weeks until the patient reached the assigned dose or experienced an intolerance to the dosage.

Results of the pediatric trial indicated that compared to a placebo, patients taking the study medication experienced over 25% greater reduction of frequency of partial seizures.

In the adult study, the reduction of frequency of partial seizures for those taking the study drug at the lowest dose was over 18% greater than those taking the placebo, while at the highest dose was over 42% greater than those taking the placebo.