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| |  Keppra (Levetiracetam) Reduces Frequency Of Partial Onset Seizures In Adults SMYRNA, GA -- July 25, 2000 -- Keppra™ (levetiracetam), a new anti-epileptic drug (AED) for the adjunctive treatment of partial onset seizures in adults with epilepsy, is effective, well tolerated and is easy to use, according to a study published in the July 25th issue of Neurology, the journal of the American Academy of Neurology. The U.S. Food and Drug Administration approved Keppra 250 mg, 500 mg and 750 mg tablets, in November 1999. Partial onset seizures are caused by excessive electrical activity in just one hemisphere of the brain, resulting in a range of symptoms that may include sudden, jerky movements of one part of the body, distorted hearing, sense of smell or vision, numbness and a sudden sense of fear. The publication reports results of a 38 week multi-center parallel-group, placebo-controlled clinical evaluation of 294 adult patients with more than a two-year history of refractory partial seizure epilepsy. Patients were randomized to one of three groups (Keppra 3000 mg/day, Keppra 1000 mg/day or placebo) and entered a 12 week single-blind placebo baseline period. This was followed by a four week double-blind titration period, and a 14 week double-blind evaluation period (18 week treatment period). Study medication was added to an established regimen of 1-2 AEDs. Patients completed the study and either entered an eight week double-blind withdrawal period or a one-year open label follow-up study. Only two out of the 268 patients completing the study did not choose to continue Keppra (levetiracetam) therapy on an open-label basis after completing the initial part of the study. "Patients treated with Keppra, either in high or low dose, showed improvement," said lead investigator James J. Cereghino, M.D., Professor of Neurology of Oregon Health Sciences University. "Although not fully elucidated, one must presume a novel mechanism of action for levetiracetam, thus permitting a larger group of patients to perhaps achieve better seizure control." The primary report of effectiveness was a between group comparison of the percent reduction in weekly partial seizure frequency relative to placebo for the entire treatment period. Both groups treated with Keppra showed significant reductions over placebo. The percent reduction in partial seizure frequency over placebo was 30.1 percent and 26.1 percent in the Keppra 3000 mg/day and 1000 mg/day groups, respectively (p<0.001). The secondary efficacy measures included median percent reduction in seizure frequency from baseline and responder rate (incidence of patients with greater than or equal to 50 percent reduction from baseline in partial onset seizure frequency) for the entire treatment period. Both Keppra treated groups showed significant reductions in seizure frequency from baseline compared to the placebo group; 38.1 percent in the 3000 mg/day group, 36.9 percent in the 1000 mg/day group compared to 6.9 percent in the placebo group (p<0.001). Responder rates observed for both Keppra-treated groups were higher than those observed for the placebo group; 39.6 percent in the 3000 mg/day group, 37.1 percent in the 1000 mg/day group compared to 7.4 percent in the placebo group (p<0.001). "A significant reduction in weekly seizure frequency was observed for patients in the Keppra (levetiracetam) treatment groups during the first two weeks of the titration period, indicating the drug may have a rapid clinical effect," said Ilo E. Leppik, M.D., Director of Research at MINCEP Epilepsy Care in Minneapolis. "Keppra may prove to be a significant advance in AED therapy by providing a unique combination of clinical efficacy, tolerability and ease of use, as demonstrated by an effective starting dose and a favorable pharmacokinetic profile." The publication reports that few adverse events were considered severe (less than or equal to 4 percent in each of the three treatment groups). Treatment emergent adverse events (greater than or equal to 10 percent) with incidences higher than placebo were infection, headache, somnolence, dizziness, asthenia (weakness), rhinitis and flu syndrome. Only 6.1 percent of patients withdrew from the study due to an adverse event with similar numbers from each of the three treatment groups. Overall, in controlled clinical studies, Keppra was generally well tolerated by patients. Keppra use is associated with the occurrence of central nervous system adverse events classified as somnolence and fatigue, coordination difficulties and behavioral abnormalities. When Keppra was given with other AEDs, the most frequently reported adverse events were somnolence, asthenia (weakness), infection and dizziness. Minor, but statistically significant, decreases compared to placebo in total mean red blood cell count, mean hemoglobin and mean hematocrit were seen in Keppra treated patients in controlled trials. A total of 3.2 percent of treated and 1.8 percent of placebo patients had at least one possibly significant decreased white blood cell count, and 2.4 percent of treated and 1.4 percent of placebo patients had at least one possibly significant decreased neutrophil count. Fifteen percent (15 percent) of patients receiving Keppra and 11.6 percent of patients receiving placebo discontinued therapy or had a dose reduction as a result of an adverse event. Because levetiracetam is substantially excreted by the kidney, caution should be taken in dosing patients with moderate and severe renal impairment and patients undergoing hemodialysis.
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