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Oxcarbazepine & Paediatric Partial-onset Seizures
New data presented to the American Epilepsy Society at their 55th annual meeting in Philadelphia, Pennsylvania in December 2001 seem to show oxcarbazepine (Trileptal®) to be a safe and effective long-term adjunctive therapy for children with partial seizures.
The study analyzed data from a 13-month trial which included a 40-week open-label extension. The initial 16-week, double-blind, placebo-controlled study of oxcarbazepine as adjunctive therapy progressed to an open-label extension to evaluate its long-term safety and efficacy. The study involved 229 participants, 3 - 17 years of age (mean 11.2 years).
Dosages of oxcarbazepine and concomitant anti-seizure medications (AEDs) were adjusted as needed by individual clinical responses. During the first 56 weeks, 50.2% of participants experienced a greater than 50% reduction in seizure frequency, and 7% had no seizures during this period. Typical side effects were mild to moderate, lasting an average of 1 day. Most commonly reported side effects included headache (31%), vomiting (27%) and dizziness (26%).
66% of participants (150 people) completed at least 1 year of the open label therapy period. Withdrawal included 18% due to poor seizure control, 6% due to adverse events and 10% for other reasons.
Paediatric Monotherapy
Researchers presented a pharmacokinetic model which suggests an effective dose for monotherapy in children with epilepsy. Few such options now exist, and they may be limited by side effects and/or drug interactions.
Pharmacokinetic profiling suggests that plasma levels associated with seizure control in adults receiving oxcarbazepine adjunctive therapy are similar to effective plasma levels in children. Analysis of data from 20 safety and efficacy studies of oxcarbazepine which included paediatric patients less than 17 years of age and using a pharmacokinetic model which extrapolated dosages which would produce steady-state plasma concentrations in children equal to effective levels in adults on monotherapy, an efficacious dose range of oxcarbazepine as a monotherapy in children was found to be 20-55 mg/kg/day. Meta-analysis of seizure data from double-blind monotherapy studies confirmed this hypothesis.
Safety & Tolerability
Side effects of oxcarbazepine as adjunctive therapy in children were similar to adults, mild to moderate in severity, and tended to resolve during the course of treatment. The most common adverse events (occurring 5% more frequently than from placebo) with oxcarbazepine as monotherapy or adjunctive therapy in adults previously treated with AEDs were dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, and abnormal gait.
In controlled trials, clinically significant hyponatremia [deficiency of sodium in the blood] was observed in 2.5% of persons treated with oxcarbazepine: measurement of serum sodium levels should be considered for people at risk of hyponatremia.
25 - 30% of persons with hypersensitivity to carbamazepine may experience a reaction to oxcarbazepine.
In Canada, oxcarbazepine is approved as adjunctive therapy in treating adults and children 6 years of age and older with partial-onset seizures, and as monotherapy in adults with partial-onset seizures. In December 2001, the American Food and Drug Administration (FDA) approved oxcarbazepine tablets and oral suspension for use as monotherapy in the treatment of partial seizures in children as young as 4 years of age. Oxcarbazepine is approved in more than 50 countries.
Sources
Novartis Pharmaceuticals Canada Inc.
Novartis AG
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