Once‐daily extended‐release levetiracetam as adjunctive treatment of partial‐onset seizures in patients with epilepsy: A double‐blind, randomized, placebo‐controlled trial

Abstract

SUMMARYPurpose: Double-blind randomized trial to assess efficacy and tolerability of once-daily extendedrelease levetiracetam (LEV XR) tablets (2 · 500 mg) as add-on therapy in patients (12-70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs. Methods: After an 8-week prospective baselineperiod, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders ( ‡50% reduction in POS-frequency/week), seizurefreedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram. Results: Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9% %) LEV XR and 72 (91.1% %) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% % on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p = 0.038). Thirty-four (43%) LEV XR and 23 (29.1% %) placebo patients experienced ‡50% % reduction in POS-frequency/week. Eight (10.1% %) patients receiving LEV XR and one (1.3% %) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2% %) LEV XR and 43 (54.4% %) placebo patients reported ‡1 adverse event. Adverse events reported with an incidence >5% % and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea. Discussion: Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.

Levetiracetam Prevents Perforin Mediated Neuronal Injury Induced by Acute Cerebral Ischemia Reperfusion

“…However, its neuroprotection mechanism remains unclear. Recently, it was found from clinical trial that patients treated with LEV showed more susceptibility, mainly in cold [21][22][23][24][25]. This implied that LEV might have an influence on the immune system.…”

Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

“…Using the conventional oral dosage forms several drugs have to be administered quite frequently (i.e., 2–4 times-a-day) resulting, therefore, in high fluctuation in plasma drug levels causing saw-tooth kinetics. Controlled release (CR) systems are designed primarily for reducing the frequency of administration by regulating the drug concentration in the target tissue, ensuring patient compliance and consequently improving the efficacy of drugs [1, 2]. However, the development of a CR drug delivery system (DDS) is precluded by its inability to restrain and localize it within the desired region of gastrointestinal (GI) tract, and the highly variable nature of gastric emptying process [3].…”

Disposition of Extended Release Levetiracetam in Normal Healthy Dogs After Single Oral Dosing

“…Furthermore, drug concentrations will fluctuate >75% during a dosing interval,1 which may contribute to poor seizure control. An extended release levetiracetam product approved for use in humans has lengthened the dosing interval from 12 to 24 hours in human epileptic patients 17, 18, 19, 20. However, previous studies have indicated that dosing regimens for slow or extended release products approved for use in humans cannot accurately be extrapolated to dogs 21.…”