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| |  Sustained Benefits Seen with Trileptal (Oxarbazapine) as Adjunctive Therapy in Pediatric Partial-onset Seizures PHILADELPHIA, PA -- December 5, 2001 -- Trileptal (oxcarbazepine) appears to be safe and effective for long-term use as adjunctive therapy in children with partial seizures. The new data on Trileptal, marketed by Novartis Pharmaceuticals Corporation, were presented today at the 55th annual meeting of the American Epilepsy Society, in Philadelphia, Pennsylvania. The study, which analyzed data from a 13-month trial that included a 40-week open-label extension, found that Trileptal significantly reduced seizure frequency when used as adjunctive therapy during long-term management of partial-onset seizures in children. In addition, side effects noted in study participants were mild to moderate and tended to resolve during the course of treatment. "These findings are particularly important given that this is a relatively new product," stated Ahmad Beydoun, MD, director of the epilepsy program at the University of Michigan Medical Center, Ann Arbor, Michigan. "It’s reassuring to see the first set of long-term safety data for any new treatment, and the data from this study should give confidence to physicians that adjunctive oxcarbazepine therapy is a safe and effective treatment option for pediatric patients with partial-onset seizures," he added. Following a 16-week, double-blind, placebo-controlled study of oxcarbazepine adjunctive therapy, 229 subjects, aged three to 17 years (mean 11.2 years), transitioned to an open-label extension to evaluate the long-term safety and efficacy of adjunctive oxcarbazepine therapy. Patient dosages of Trileptal and concomitant antiepileptic medications (AEDs) were adjusted according to individual clinical response. Through the first 56 weeks, half of the subjects (50.2 percent) experienced a greater than 50 percent reduction in seizure frequency. Additionally, 7 percent of patients had no seizures during this period. Side effects were typically mild to moderate and had an average duration of one day. The most commonly reported side effects were headache (31 percent), vomiting (27 percent) and dizziness (26 percent). One-hundred-and-fifty subjects (66 percent) completed at least one year of open label therapy. Eighteen percent dropped out due to poor seizure control, 6 percent because of adverse events and 10 percent for other reasons. Pharmacokinetic Modeling Supports Pediatric Monotherapy In addition to the data supporting long-term safety and efficacy for Trileptal as an adjunctive therapy, researchers presented a pharmacokinetic model that suggests an effective dose as a monotherapy in children with epilepsy. Currently, there are few monotherapy options for children with epilepsy and these existing treatments can be limited in use by side effects and/or drug interactions. Trileptal is currently approved as monotherapy in adults with partial-onset seizures and as adjunctive therapy in adults and children with partial-onset seizures. Previous pharmacokinetic profiling suggests that plasma levels associated with seizure control in adults receiving adjunctive therapy with this agent are similar to effective plasma levels in children. Given this correlation, it was hypothesized that plasma levels that are effective in adult monotherapy patients should yield similar results in a pediatric population. "This model provides an accurate framework for determining effective dosing for monotherapy in children," said Dr. Beydoun, who participated in the research. "The suggestion is that these findings support the effective use of oxcarbazepine as monotherapy in pediatric epilepsy." The investigators analyzed data from 20 safety and efficacy studies of oxcarbazepine that included pediatric patients less than 17 years of age. A pharmacokinetic model was used that extrapolated the dose levels that would produce steady-state plasma concentrations in children equal to effective levels in adults on monotherapy. Based on this model, an efficacious dose range of oxcarbazepine as a monotherapy in children was found to be 20-55 mg/kg/day. A meta-analysis of seizure data from double-blind monotherapy studies confirmed this hypothesis. Established Safety and Tolerability As monotherapy or adjunctive therapy in adults previously treated with AEDs, the most common (>5 percent) adverse events occurring substantially more frequently than in placebo patients were dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, and abnormal gait-these were typically mild to moderate in severity. As add-on therapy in pediatric patients, adverse events with Trileptal were similar to adults. Clinically significant hyponatremia (sodium <125 mmol/L) has been observed in 2.5 percent of Trileptal-treated patients in controlled clinical trials. Measurement of serum sodium levels should be considered for patients at risk of hyponatremia. (Please see WARNINGS section of complete prescribing information.) Of patients who have had hypersensitivity to carbamazepine, 25 percent to 30 percent will experience a reaction to oxcarbazepine. Caution should be exercised when prescribing Trileptal for patients with a history of hypersensitivity to carbamazepine. (Please see WARNINGS section of complete prescribing information.) *NOTE: Oxcarbazepine is not approved for use as monotherapy in children with epilepsy. Novartis has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for permission to market Trileptal as a pediatric monotherapy in children four-years-of-age and older with partial-onset seizures. The file is currently under review.
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