Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levetiracetam has recently been licensed in Europe and the U.S.A. for use as an adjunctive agent in partial epilepsy with or without secondary generalization. The mode of action has yet to be elucidated, but may involve a new brain-specific binding site, the ligand for which is unknown. Levetiracetam has a favorable pharmacokinetic profile, with rapid and almost complete oral absorption, almost 100% bioavailability, linear, dose-dependent maximum plasma concentrations and minimal plasma protein binding. Excretion is mainly renal, with most of the drug being eliminated unchanged. Levetiracetam does not have an effect on the major drug-metabolizing hepatic enzymes, and thus is associated with a low incidence of interactions with other antiepileptic drugs (AEDs). These properties make it a well-tolerated drug, with the most common reported side effects being asthenia, somnolence, headache and dizziness. Antiepileptic properties of levetiracetam demonstrated in animal studies have been borne out by large double-blind, placebo-controlled clinical trials, with significantly improved responder rates (>/= 50% reduction in seizure frequency from baseline) and number of seizure- free patients versus placebo. In addition, efficacy appears to be maintained over the long term and no evidence for the development of tolerance to the effects of levetiracetam has been seen. (c) 2001 Prous Science. All rights reserved.
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PMID:Levetiracetam: A new antiepileptic drug for the adjunctive therapy of chronic epilepsy. 1273 64

In this open-label add-on study of levetiracetam in refractory childhood epilepsy syndromes, we studied the effect of a rapid introduction of levetiracetam on the total seizure frequency in 21 children, known to have partial and generalized seizures. Starting dosage was 10 mg/kg/day, increased every 4th day by 10 mg/kg up to a maximum of 60 mg/kg/day, depending on efficacy and tolerability. In this highly refractory population, 47% showed a seizure frequency reduction of more than 50%. Levetiracetam was effective both in partial and generalized seizures, with a significant effect on myoclonic seizures. Only mild side-effects were observed in four of 21 children, at a dosage of more than 40 mg/kg/day.
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PMID:Effect of levetiracetam in refractory childhood epilepsy syndromes. 1278 38

Selecting an appropriate anticonvulsant for treatment of recipients of orthostatic liver transplants who have new-onset epileptic seizures can be challenging because first-line agents may contribute to worsening encephalopathy, alter the plasma concentration of immunosuppressive agents, and result in hepatotoxicity. We describe the case of a 55-year-old man who underwent orthotopic liver transplantation because of end-stage liver disease due to alcoholic cirrhosis and hepatitis C. He required two repeat transplantation procedures. After the last procedure, epileptic seizures developed, which were initially managed with phenytoin. However, the patient remained stuporous and mental status fluctuated. Breakthrough seizures later developed in the setting of rejection. Levetiracetam (500 mg orally, twice a day) was chosen for its favorable pharmacokinetic properties as an alternative to phenytoin. By the third day of levetiracetam therapy, the patient became more responsive. At most recent follow-up, 3 months after the start of levetiracetam therapy, the patient was still treated with levetiracetam monotherapy, and seizure control was judged to be excellent.
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PMID:Levetiracetam monotherapy for liver transplant patients with seizures. 1282 99

Although short-term clinical trials provide important data regard-ing efficacy and tolerability, long-term studies are needed to address important aspects of clinical practice, such as long-term efficacy and safety. Long-term studies and post-marketing data show that the efficacy of levetiracetam is sustained over the long term and that this antiepileptic drug continues to be well tolerated, with low withdrawal rates and high retention rates. Patients continue to achieve significant reductions in seizure frequency and may achieve seizure freedom. Levetiracetam may allow patients to decrease the number of concomi-tant antiepileptic medications or withdraw to monotherapy. Add-on therapy with levetiracetam should be considered when additional control of seizures is needed.
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PMID:Long-term experience with levetiracetam. 1291 39

Levetiracetam is a novel antiepileptic drug (AED) with proven efficacy against partial seizures, but there is limited information about its effectiveness against generalized seizures. In animal models, levetiracetam protects against seizures in audiogenic susceptible rodents, and it is effective in the Genetic Absence Epilepsy Rat from Strasbourg, a model of absence seizures. In these models, levetiracetam has a therapeutic index that is higher than those of other AEDs. A number of small open-label studies suggest that levetiracetam reduces seizure frequency in patients with generalized seizures, including primarily generalized seizures and myoclonic seizures. Case reports provide additional information regarding the potential efficacy of levetiracetam in postanoxic, post-encephalitic and progressive myoclonus. Although random-ized controlled studies of patients with generalized seizures have not yet been conducted, on the basis of available information, levetiracetam may be prom-ising in the treatment of generalized seizures.
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PMID:Levetiracetam: preliminary efficacy in generalized seizures. 1291 40

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.
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PMID:Safety profile of levetiracetam. 1291 43

Physicians treating patients with epilepsy have a host of thera-peutic options. Drug choice is dictated first by the seizure(s) and/or epilepsy syndrome. Age is also a factor. Special considerations apply to women, particu-larly during their childbearing years, and to patients who are learning-disabled. Drug selection is further influenced by such characteristics as spectrum of activity, rapid response, low potential for drug-drug interactions, and ease of use. In addition to clinical trial data, postmarketing assessments of the new antiepileptic drugs provide useful clinical information on efficacy and safety. Levetiracetam has specific characteristics that make it an optimal choice for many patient populations.
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PMID:Role of levetiracetam in the treatment of epilepsy. 1291 44

The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study is a continuing phase IV open-label evaluation of the antiepileptic drug levetiracetam (Keppra) as an adjunctive therapy in adult patients with uncontrolled partial seizures. The study, which began in April 2000, is scheduled to include 1400 patients from 300 centres in 16 countries. An interim analysis of the first 731 patients from 117 centres in nine countries treated over a 16-week period showed that seizure frequency was reduced by half or more in 49% of patients across all seizure types. A substantial 17.2% of patients achieved complete freedom from seizures. Levetiracetam was well tolerated overall. Adverse events were predominantly mild to moderate and rarely led to discontinuation. The most commonly reported symptoms were asthenia, somnolence, headache and dizziness.
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PMID:The SKATE study: interim analysis. 1291 96

A 5-year-old girl with Landau-Kleffner syndrome is discussed. The child began having seizures at age 4 associated with language deterioration despite anticonvulsant therapy. With levetiracetam monotherapy to a dose of 60 mg/kg/day and discontinuation of carbamazepine and valproic acid, her language has improved and seizures are controlled. Levetiracetam should be considered as therapy for Landau-Kleffner syndrome.
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PMID:Landau-Kleffner syndrome responsive to levetiracetam. 1452 2

Levetiracetam (LEV) is the most recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Three randomised, double-blind, placebo-controlled trials enrolling 904 patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (> or = 50% reduction in seizure frequency) of 28-41%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for six months of the study and 8% seizure-free for one year. Adverse effects of LEV, including somnolence, lethargy and dizziness, were generally mild and the frequency of incidents was not significantly different between the active treatment and placebo groups in clinical trials. LEV has no clinically significant pharmacokinetic interactions (PKI) with other AEDs, or with commonly prescribed medications. Preliminary data suggest that LEV has efficacy in primary generalised epilepsy and further randomised trials are under way. The combination of potent antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive adjunctive therapy for partial seizures.
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PMID:Levetiracetam: a new therapeutic option for refractory epilepsy. 1452 64


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