title: Levetiracetam and bleeding disorders.
abstract: 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.
authors.affiliation: Department of Neurology, Reference Center for Refractory Epilepsy, Ghent University Hospital, Belgium. Paul.Boon@UGent.be
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
authors.forename: Réginald
authors.initials: R
authors.lastname: Hulhoven
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D001241:Aspirin / Q000494:pharmacology; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D020141:Hemostatic Disorders / Q000209:etiology; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives*; D010919:Placebos; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D000077287:Levetiracetam; D001241:Aspirin; D010889:Piracetam