Uses
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Seizure Disorders
Levetiracetam is used orally in combination with other anticonvulsants in the management of partial onset, myoclonic, and primary generalized tonic-clonic seizures. The drug also is commercially available as an IV formulation for the management of such seizure disorders when oral therapy is temporarily not feasible. Efficacy of IV levetiracetam is supported by studies using oral formulations of the drug since the oral and parenteral formulations are bioequivalent.
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Partial Seizures
Levetiracetam conventional (immediate-release) tablets, oral solution, and injection are used in combination with other anticonvulsants in the management of partial onset seizures in adults and pediatric patients 1 month of age and older with epilepsy.
Efficacy of levetiracetam for this use was established in 3 double-blind, placebo-controlled trials in patients who had refractory partial onset seizures with or without secondary generalization while receiving a stable regimen of 1 or 2 anticonvulsants and had experienced at least 2 partial seizures during each 4-week interval of the baseline period (8-12 weeks). Patients received levetiracetam (1, 2, or 3 g daily as a conventional oral preparation) or placebo for 12 weeks after a 4- to 6-week titration period. The weekly frequency of partial seizures was reduced in patients receiving levetiracetam relative to placebo. More patients receiving levetiracetam experienced a reduction in seizure frequency of 50% or greater from baseline (i.e., responder rate) compared with placebo-treated patients. Clinical benefit was evident within 2 weeks in one study.
Data from open-label extension periods of phase 1, 2, and 3 studies with oral levetiracetam (as conventional preparations) in 1422 adult patients with epilepsy indicate that 39% of patients experienced a 50% or greater decrease in seizure frequency, while 13 and 8% of patients were seizure-free for at least 6 and 12 months, respectively, during therapy with the drug. Continuation rates for levetiracetam therapy in these patients were estimated to be 60, 37, and 32% after 1, 3, and 5 years, respectively.
Efficacy of levetiracetam as adjunctive therapy in pediatric patients with partial onset seizures was established in 2 randomized, double-blind, placebo-controlled studies. The first study was conducted in children 4-16 years of age who had refractory partial onset seizures with or without secondary generalization while receiving a stable regimen of 1 or 2 anticonvulsants and had experienced at least 4 partial seizures during the 4 weeks prior to screening as well as at least 4 partial seizures during each of the two 4-week baseline periods. Patients received levetiracetam (20-60 mg/kg daily as a conventional oral preparation) or placebo for 10 weeks after a 4-week titration period. Pediatric patients receiving levetiracetam experienced a reduction of 26.8% in mean weekly partial seizure frequency relative to placebo. The second study was conducted in infants and children 1 month to less than 4 years of age with refractory partial onset seizures (with or without secondary generalization). Seizures were assessed in this study using video electroencephalography (EEG). Patients who had experienced at least 2 partial seizures during a 48-hour baseline period while receiving a stable regimen of 1 or 2 anticonvulsants were randomized to receive levetiracetam oral solution (20-50 mg/kg daily based on age) or placebo; after an initial 1-day dose titration period, treatment was continued for an additional 4 days. The responder rate (i.e., proportion of patients experiencing a reduction in seizure frequency of 50% or greater from baseline) was substantially higher in pediatric patients receiving levetiracetam (43.1%) compared with those receiving placebo (19.6%), and these results were consistent across age groups in this study.
Levetiracetam also is commercially available as extended-release tablets for once-daily administration in the management of partial onset seizures in adults and pediatric patients 12 years of age and older. Efficacy of levetiracetam (as extended-release tablets) was established in a double-blind, placebo-controlled study in patients 12-70 years of age who had refractory partial onset seizures with or without secondary generalization. Patients who had experienced at least 8 partial seizures during an 8-week baseline period and at least 2 seizures during each 4-week interval of the baseline period while receiving a stable regimen of 1-3 anticonvulsants were randomized to receive levetiracetam 1 g daily (as extended-release tablets) or placebo for 12 weeks. The median percent reduction in weekly seizure frequency from baseline was 46.1% in patients receiving levetiracetam compared with 33.4% in those receiving placebo.
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Myoclonic Seizures
Levetiracetam conventional (immediate-release) tablets, oral solution, and injection are used in combination with other anticonvulsants in the management of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.
Efficacy of levetiracetam for this use was established in a randomized, double-blind, placebo-controlled study in patients who had myoclonic seizures while receiving a stable regimen of 1 anticonvulsant and had experienced at least one myoclonic seizure daily for at least 8 days during the 8-week baseline period. Patients received levetiracetam 3 g daily (as a conventional oral preparation) or placebo for 12 weeks after a 4-week titration period. More patients receiving levetiracetam (60.4%) experienced a reduction in seizure frequency of 50% or greater from baseline (i.e., responder rate) compared with placebo-treated patients (23.7%).
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Primary Generalized Tonic-Clonic Seizures
Levetiracetam conventional (immediate-release) tablets, oral solution, and injection are used in combination with other anticonvulsants in the management of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Efficacy of levetiracetam for this use was established in a randomized, double-blind, placebo-controlled study in patients who had primary generalized tonic-clonic seizures while receiving a stable regimen of 1 or 2 anticonvulsants and had experienced at least 3 primary generalized tonic-clonic seizures during the 8-week combined baseline period (4-week pre-prospective baseline period and 4-week prospective baseline period). Patients received levetiracetam 3 g daily (adult dosage) or 60 mg/kg daily (pediatric dosage) as a conventional oral preparation or placebo for 20 weeks after a 4-week titration period. The median percent reduction in weekly seizure frequency from baseline was 77.6% in patients receiving levetiracetam compared with 44.6% in those receiving placebo. In addition, more patients receiving levetiracetam (72.2%) experienced a reduction in seizure frequency of 50% or greater from baseline (i.e., responder rate) compared with placebo-treated patients (45.2%).
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