Abstracts

Head injury is the cause of 5% of all epilepsy. Past attempts at preventing epilepsy by treatment with older antiepileptic drugs (AEDs) have been unsuccessful. Levetiracetam is a new generation AED with a favorable side-effect and pharmacokinetic profile that has potent anti-epileptogenic effects in animal models of epilepsy. It may thus be useful in preventing the development of epilepsy following traumatic brain injury (TBI). However, there has been no experience in administering levetiracetam rapidly to individuals with acute TBI. In this pilot study, we are evaluating the safety, tolerability, pharmacokinetics and feasibility of acute and chronic administration of levetiracetam to individuals with head injury with a high risk for developing post-traumatic epilepsy.Here, we report preliminary findings of tolerability., Male and female subjects aged 6 years and older are enrolled in a fixed dose, open label study with a sample size goal of 60. All have head injury with a high risk for developing post-traumatic epilepsy (injury with intracranial hemorrhage, penetrating wound injury, depressed skull fracture or early post-traumatic seizure). Subjects receive levetiracetam 55 mg/kg/day by mouth or via orogastric tube if unable to swallow. Treatment starts within 8 hours of head injury at full dose and continues for 30 days, with one additional month of post-treatment follow up. In addition, individuals receive phenytoin for one week following head injury as standard clinical care., 30 subjects (24 adult, 6 children) have been enrolled to-date.
18/30 (60%) subjects (14/24 adult, 4/6 pediatric) have completed the 30 day treatment phase of the study. 3 subjects (1 adult, 2 pediatric) are currently in active treatment follow up. 3 subjects (all adults) have died, all of medication unrelated causes. There have been no medication-related serious adverse events.
6 subjects (all adults) have discontinued treatment early: 2 because of medication- related toxicity (somnolence,n=1; and combined fatigue, somnolence, irritability,emotional lability, headaches, n=1) and 4 for medication-unrelated reasons.Thus, excluding death and subjects still in active follow up, 18/24 (75%) subjects completed treatment as expected. Only 2/24 (8%) of subjects discontinued medication because of poor tolerability. An update of this data and of interim compliance and adverse event data will be presented., Acute and chronic treatment with high dose (55mg/kg/day) levetiracetam has been well tolerated in 18 subjects with acute head injury with high risk for developing post-traumatic epilepsy., (Supported by NIH grant 1 R01 NS45656-01A1.)