Abstracts

Epilepsy in very young children (e.g. [lt]2 yrs old) is especially difficult to manage. Not only is the nature of epilepsy different in this age group, pharmacokinetics and toxicity may have age-related differences. We report on findings from topiramate (TPM) use in very young children ([le]2 yrs old). Data from 3 studies involving 57 children [le]2 yrs old with refractory infantile spasms or refractory epilepsy were analyzed. Open-label TPM was added to existing therapy at 1 mg/kg/day and titrated to an optimal dosage. In Study 1, TPM pharmacokinetics were evaluated in 8 young children (0.8-1.8 yrs) receiving TPM twice a day (7.0-8.9 mg/kg/day). At steady state, apparent oral clearance was 30.5-60.2 ml/hr/kg and half-life was 7.4-9.9 hrs in patients receiving non-enzyme-inducing AEDs; in those receiving enzyme-inducing AEDs, oral clearance and half life were 76.8-121 ml/hr/kg and 4.4-5.0 hrs, respectively. In Study 2, 21 children with infantile spasms (median age, 8.8 months; range, 0.8-25.8 months) were treated with a median dose of 17.3 mg/kg/day TPM. Monthly rates of spasms and other seizures appeared to decline over time with TPM treatment; 11 patients were spasm-free [ge]7 days. In Study 3, 7 of 8 children with infantile spasms had a clinically significant response ([ge]50% seizure reduction). Among children with other forms of refractory epilepsy, seizures were reduced [ge]50% in 8/20 patients. Overall, few patients in these 3 studies experienced treatment-limiting adverse events (4/57 discontinued). The most common adverse event was irritability, a common occurrence in children with infantile spasms. Children [le]2 yrs old with refractory epilepsy or infantile spasms who were treated with open-label TPM had fewer spasms and other seizure types. Because TPM clearance is higher in infants than in older children, higher mg/kg doses may be needed, especially in those also taking enzyme-inducing AEDs. (Supported by Johnson [amp] Johnson Pharmaceutical Research [amp] Development, L.L.C. and Janssen-Cilag.)