Abstracts

RATIONALE: The most rigorous method of adverse event assessment for new compounds is via randomized controlled regulatory trials (RCT). However populations enrolled in such trials are highly selected; post-approval trials are less rigorous, but include broader population who may have different risks for adverse events (AEs). In this study we wish to compare adverse event data from these two methods of AE ascertainment.
METHODS: We analyzed data on adverse events (AEs) from patients initiating levetiracetam in the PADS (Post-marketing Antiepileptic Drug Survey) database. PADS is a prospective registry provided by a consortium of 16 epilepsy centers to study the population treated with new AEDs. Patients at each center are prospectively and consecutively entered. Initiation forms include demographic data, as well as data on seizure type/frequency, past behavioral and psychiatric disturbances, and current/past antiepileptic drug use. Follow-up forms include seizure outcome, adverse events, reason for discontinuation, if applicable, dose and titration rate. We compared results to a pooled safety analysis of patients enrolled in RCTs.
RESULTS: We studied 288 patients; with a mean follow up of 240 [plusminus] 135.6 days. Males 135, females 153. Age range was 8-months to 83 years (mean 38.2 [plusminus] 15.7 years). The average dose of levetiracetam was 1767[plusminus] 1013 mg, and the average highest dose was 1919 [plusminus]1045 mg.
The most reported AEs were included in this table for comparison with those reported during the premarketing phase.[table1]Increased seizure frequency was reported in 2.4% vs 14% in premarketing studies, insomnia in 3.8% vs 5.5% in premarketing, and weight change in 5.6% vs 8.5 in premarketing phase. There was no report of infection in our group vs (13.4%) in premarketing phase. Most of the AEs reported in this study were mild to moderate, however 16.9% of patients described their symptoms as severe, vs 14.7% in the premarketing group. Only 14.2% discontinued levetiracetam due to AEs vs 15% in premarketing studies. AEs that lead to discontinuation include Dizziness 0.3%, ataxia 0.7%, diplopia 0.3% nausea 1%, insomnia 0.7%, rash 0.3%, psychomotor slowing 0.7%, weight change 0.3%, increase in seizure frequency 2.4% and behavioral changes 4.9%.
CONCLUSIONS: Levetiracetam is well-tolerated antiepileptic drug. Postmarketing data is consistent with pooled premarketing safety data of levetiracetam. The main AEs noted are fatigue, somnolence, headache and dizziness as well as behavioral AEs. Most of the AEs reported were relatively mild to moderate and discontinuation was noted only in few patients.
[Supported by: The PADS survey has received contributions from: Ortho-McNeil, Cyberonics, Abbott, Glaxo-Wellcome, Novartis, Elan, and UCB Pharma]; (Disclosure: Other - The PADS survey has received contributions from: Ortho-McNeil, Cyberonics,Abbott, Glaxo-Wellcome, Novartis, Elan, and UCB Pharma)