Levetiracetam and bleeding disorders

Six studies were conducted in healthy male volunteers to evaluate the effect of levetiracetam on bleeding time. In three open-label studies, a single dose of levetiracetam (250, 500, or 1000 mg, respectively) was administered 12 hours after acetylsalicylic acid (aspirin). Bleeding time increased by 3.5% to 30% relative to baseline, but the effect was not dose-related and not clinically relevant. In a fourth open-label study, levetiracetam was administered twice daily for 4 days, with aspirin administered with the penultimate dose of levetiracetam. The other two studies had a double-blind, placebo-controlled crossover design: levetiracetam or placebo was administered twice daily for 4.5 days and then aspirin was coadministered with the final dose. In the open-label multiple-dose study, the bleeding time increase was more pronounced after repeated levetiracetam doses and ingestion of aspirin than after a single 250-mg dose. However; no clinically relevant change in bleeding time or difference from placebo was observed in the double-blind, crossover studies. Except for two subjects in a crossover study, one of whom received placebo, no absolute bleeding time value was above the normal range of 4-8 minutes. These results indicate that levetiracetam does not produce clinically significant increases in bleeding time in healthy male volunteers. Further a review of clinical trials suggests that levetiracetam does not appear to cause clinically significant or relevant hematological adverse events suggestive of underlying hematological disorders.