A systematic review of the safety profile of levetiracetam: a new antiepileptic drug

Purpose: This report provides detailed review of safety information on leve tiracetam (LEV) (Keppra (TM)), a new antiepileptic drug. Methods: The integ rated summary of safety report submitted for regulatory review was examined to collate information about abnormal laboratory tests values and adverse event reports collected during the overall LEV development program. Analyse s included 3347 patients exposed to LEV in clinical trials for epilepsy, co gnition, and anxiety disorders. Results: Safety data from all studies depic t a similar pattern of adverse effects, predominantly somnolence, asthenia, and dizziness that occurred most frequently during the first month of LEV treatment. Changes in laboratory test values from placebo-controlled trials that were statistically significant remained in the normal range (red bloo d cells, hematocrit. hemoglobin, white blood cells, and neutrophils). Repor ts of the coding term 'infection' (common cold, upper respiratory infection ) were not preceded by low neutrophil counts that might suggest impaired im munological status. Selection of adverse event coding terms probably contri buted to the high rate of adverse effects termed 'infection.' Higher incide nces of adverse effects, particularly behavioral effects, were found among epilepsy patients than in elderly patients with cognitive disorders or pati ents with anxiety disorders given lower doses. Conclusions: This review of patients evaluated during the clinical development program suggests that LE V was well tolerated and safe for patients with seizure., cognitive and anx iety disorders. Overall incidence of adverse effects in the LEV groups was little higher than reports from the placebo groups. Of course, this data wa s derived from clinical trials that are of relatively short duration, and p rovide data on only several thousand patients. Therefore, long-term ;side e ffects, and/or rare side effects cannot be ruled out on the basis of this a nalysis. (C) 2001 Elsevier Science B.V. All rights reserved.