Abstracts

RATIONALE: Levetiracetam (LEV) (Keppra), a new antiepileptic drug (AED) was approved by the Food And Drug Administration in 2000 as adjunctive therapy in adults. Efficacy in children has not been reported. In light of LEV[ssquote]s pharmacokinetic profile, efficacy and ease of titration, we felt this AED would be useful in children. To evaluate its role in pediatric epilepsy, we review our experience.
METHODS: Thirty-nine children under 16 years of age with refractory seizures (partial and generalized) were prospectively treated with LEV as adjunctive, open-label medication to their existing AED regimen. At routine clinic follow-up; seizure counts, adverse events, drug dosages and their neurologic exam were documented.
RESULTS: Data analysis of the 39 patients showed a mean initiation age of 8.6 years (range 0.5 to 14.1 years). Twenty-two were female. Eleven were normal and 28 had developmental delay or mental retardation. The patients were on an average of 1.6 AEDs at the time LEV was added. LEV was initially titrated over three weeks (average) to 45.7 mg/kg/day (mean) (range 11.7 to 80 mg/kg/d) given bid or tid. The average maintenance/plateau dose was 53.3 mg/kg/day (range 13.6 to 100.0 mg/kg/day). In these 39 patients, 52 distinct seizure types were identified and analyzed, of which, four (7.7%) became seizure-free. Eight (15.4%) and six (11.5%) had greater than 90% and 50% reduction in seizure frequency respectively. Twenty-six (50%) of the seizure types had less than 50% improvement with eight (15.4%) worsening. Better efficacy was noted in partial seizures. The mean follow-up was 5.9 months (range 2 to 9 months), excluding eight children who had LEV discontinued in [lte]6 weeks due to inefficacy/increased seizures or adverse effects. Adverse effects encountered were mainly behavioral i.e. hyperactivity, agitation, positive psychotropic effect or sedation. Other adverse effects included transient hypotonia and abnormal breathing in a six-month-old, transient arthralgias (n=2) and headaches (n=3).
CONCLUSIONS: Levetiracetam appears to be a useful, adjunctive AED in children with refractory seizures, and is well-tolerated. Side-effects encountered were primarily behavioral, cognitive or sedative. We suggest initiating the drug at 10 to 20 mg/kg/day (given bid) and increasing the dose by this amount weekly to 40 to 60 mg/kg/day as a first plateau. If patients do not show a response at this dose, it does not appear that higher doses are beneficial.
Support: This abstract summarizes work done without the financial support of commercial interests.
Disclosure: Grant - UCB