The Food and Drug Administration approved a new pediatric indication for an antiepileptic drug as adjunctive treatment of partial-onset seizures in patients 4 years of age and older.
Levetiracetam (Keppra, UCB Pharma Inc.) effectively reduced seizure frequency in this population, judging from findings from a double-blind, multicenter study. The FDA considered data from the study during its priority review for the new indication.
Investigators randomized 101 patients to levetiracetam and 97 to placebo. Children taking levetiracetam for 14 weeks experienced a 27% reduction in weekly partial seizure frequency, compared with no reduction in children taking placebo. All participants were 4–16 years old, with refractory partial-onset seizures.
The initial daily dose for pediatric patients 4–15 years old is 20 mg/kg, given as twice-daily dosing (10 mg/kg b.i.d.). Increase the daily dose every 2 weeks by 20-mg/kg increments to the recommended daily dose of 60 mg/kg (30 mg/kg b.i.d.). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced, according to the package insert.
Although other agents are approved for pediatric seizure control, the levetiracetam study is the first to include only treatment-resistant seizures, according to Tracy A. Glauser, M.D., lead author of the study (in press). He added that about 30% of children do not achieve adequate seizure control with existing drugs, which include oxcarbazepine (Trileptal), lamotrigine (Lamictal), gabapentin (Neurontin), and topiramate (Topamax).
Partial-onset seizures account for approximately two-thirds of epilepsy among 4- to 16-year-old children.
FDA approval “allows neurologists and pediatricians who treat children with partial seizures to know it is efficacious and well tolerated. It validates its use in children,” said Dr. Glauser, of Cincinnati Children's Hospital Medical Center.
Somnolence, fatigue, and behavioral abnormalities (including agitation, anxiety, and apathy) were associated with levetiracetam use in the study.
Keppra has been approved for use in U.S. adults since 1999. Dr. Glauser is a consultant for UCB Pharma.