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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacotherapy of seizure disorders has long relied on a few standard medications such as phenobarbital, phenytoin (Dilantin), valproate (Depakote), and others that represent the "first generation" of anticonvulsants. This article reviews the newer, "second-generation" anticonvulsants that were developed in the last decade. The addition of these second-generation agents has doubled the number of therapies available for the treatment of seizure disorders. They include felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran). This article describes the known side effects of the second-generation agents and reviews the adverse reactions of the first generation of anticonvulsants as a guide to potential toxicities. Reference tables are included that note usual dosages, available dosage forms, and tablet imprint. In addition, this article describes monitoring parameters and gives specific information regarding the use of these agents.
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PMID:Second generation anticonvulsant medications: their use in children. 1188 12

Overdose experience with the anti-epileptic agent zonisamide (Zonegran, ZNS) is limited. We present a case of suspected zonisamide overdose previously reported in abstract form, manifesting as seizures, dysrhythmias and death of an 18-y-o woman after single ingestion of 4.8 g ZNS in a suicide attempt. The patient experienced multiple generalized tonic-clonic seizures and copious airway secretions. En route to the emergency department, she sustained cardiopulmonary arrest from which she was resuscitated. CT scan of the head approximately 24 h after initial presentation revealed massive cerebral edema with tonsillar herniation; brain death was confirmed. Serum ZNS was 44 mg/L, and the case was officially deemed death secondary to ZNS overdose. Subsequently, a comprehensive urine drug screen demonstrated mirtazepine, diphenhydramine metabolites, and caffeine. Due to confounding factors, a definitive causal role for ZNS in this overdose death cannot be made, despite the county coroner's ruling.
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PMID:Acute zonisamide overdose: a death revisited. 1277 95

Zonisamide is a benzisoxazole-based compound first synthesized in the early 1970s by the research laboratories of Dainippon Pharmaceutical Company in Osaka, Japan. Identified as an anticonvulsant during exploratory research, zonisamide has since been characterized as having broad-spectrum antiepilepsy and neuroprotective effects. Early clinical studies in Japan demonstrated that zonisamide has a long elimination half-life and is well tolerated; Phase II and III clinical trials established the drug's efficacy and safety for the treatment of partial and generalized seizures. In 1989, zonisamide was approved and marketed in Japan under the trade name of Excegran. Data from postmarketing surveillance studies and clinical observations over 10 years of use have continued to support zonisamide's efficacy and safety, identified its usefulness as monotherapy, and characterized its effectiveness for various seizure types and epilepsy syndromes.
Seizure 2004 Dec
PMID:Review of zonisamide development in Japan. 1551 83

Zonisamide (Zonegran, Excegran) is a new-generation, broad-spectrum antiepileptic drug (AED) currently approved as adjunctive therapy for the treatment of medically refractory partial seizures in adults in the US and as adjunctive therapy or monotherapy in the control of partial and generalised seizures in adults and children in Japan and Korea. Either as adjunctive therapy or monotherapy, zonisamide effectively reduces the frequency of partial seizures, with or without secondary generalisation to tonic-clonic seizures, in adults and children with epilepsy. The drug is generally well tolerated and, additionally, has a favourable pharmacokinetic profile permitting once- or twice-daily administration. Direct head-to-head comparisons with other AEDs would be beneficial in fully defining the place of zonisamide in therapy. In the meantime, adjunctive therapy or monotherapy with zonisamide is a convenient, useful option for the management of partial seizures, including those refractory to other AEDs.
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PMID:Zonisamide: a review of its use in the management of partial seizures in epilepsy. 1581 51

Zonisamide (Zonegran, Eisai, Inc.) is a broad spectrum antiepileptic drug indicated for use as adjunctive therapy in the treatment of partial seizures. Zonisamide has multiple mechanisms of action, which may explain widespread reports of its utility in focal epilepsy and generalized epilepsy, and for nonseizure disorders such as headache and neuropathic pain. Zonisamide has been available in Japan since 1989 and became available in the USA in 2002. The rights to this drug in North America and Europe were recently acquired by Eisai Co. A review of the chemical properties, pharmacokinetics, metabolism, potential mechanisms of action, efficacy in seizure and nonseizure disorders, and tolerability was therefore thought to be timely.
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PMID:Zonisamide: newer antiepileptic agent with multiple mechanisms of action. 1585 20

Zonisamide (Zonegran) has been used extensively worldwide (>2 million patient-years experience) for the effective treatment of a broad range of epilepsy indications. Four randomised, placebo-controlled trials (duration <or=6 months) in the United States and Europe (848 patients in total) have shown doses of zonisamide >or=300 mg/day to be efficacious in treating refractory partial seizures in adults. In a pivotal European study, zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency. Pooled data from all four placebo-controlled trials demonstrate an excellent tolerability and safety profile; adverse events are generally of mild-moderate severity with few leading to discontinuation, and incidence of serious adverse events is comparable to placebo. These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures.
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PMID:Zonisamide as adjunctive therapy for refractory partial seizures. 1631 44

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved in Europe for the adjunctive treatment of refractory partial seizures in adults, has undergone extensive evaluation in pre- and post-marketing double-blind and open-label studies in Japan (where zonisamide is used widely to treat partial and generalised seizures in adults and children). These data indicate that the clinical benefit of zonisamide extends across a range of seizure types and patient ages. In an analysis based on a mixture of controlled and open studies in adults and children with partial seizures, 51-57% responded to zonisamide treatment (achieving >or=50% reduction in baseline seizure frequency). Efficacy extends across a range of generalised seizures and 22-66% of adults and children experiencing tonic-clonic, tonic, clonic, myoclonic or absence seizures responded to treatment. Even greater responder rates have been reported when zonisamide was used as monotherapy for partial seizures and generalised seizures in patients refractory to other AEDs or with newly diagnosed epilepsy. Zonisamide is also efficacious in paediatric epilepsy syndromes, including Lennox-Gastaut Syndrome, West Syndrome and Ohtahara Syndrome. Across the spectrum of epilepsy syndromes studied, zonisamide is well-tolerated with a low incidence of adverse events, which are generally mild and CNS-related. These data indicate that zonisamide represents a valuable broad-spectrum option for the treatment of epilepsy.
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PMID:Zonisamide in the management of epilepsy--Japanese experience. 1632 7

Long-term efficacy, tolerability and safety of antiepileptic drug (AED) therapy is essential given the chronic nature of epilepsy. Zonisamide (Zonegran), a novel AED with a broad range of mechanisms of action contributing to its antiseizure efficacy, has been evaluated extensively for the long-term management of epilepsy. Open-label extension studies in the United States and Europe suggest continued efficacy of zonisamide in long-term treatment without development of adverse events further to those seen in registration studies. Baseline seizure frequency is reduced by approximately 40-70% during long-term treatment for up to 2 years, and 30-50% of patients attain >or=50% reduction in seizure frequency across all categories of seizure and durations of treatment. Preliminary data indicate a progressive decline in seizure frequency with continued zonisamide treatment. Zonisamide is well tolerated in long-term use, with a trend towards decreasing incidence of generally mild adverse events over time and a low rate of withdrawal during chronic use. Nephrolithiasis and other serious adverse events are infrequent, and can be minimised by appropriate management and patient education. This profile of maintained efficacy, tolerability and safety during sustained administration in combination with other AEDs supports zonisamide as a valuable adjunctive agent in the long-term management of refractory partial epilepsy.
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PMID:Practical prescribing and long-term efficacy and safety of zonisamide. 1640 43

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved recently in Europe as adjunctive therapy for refractory partial seizures in adults, has been used extensively in Japan and the United States. A substantial body of clinical experience has accumulated over a 14-year period, allowing the properties and pharmacologic/clinical profiles of zonisamide to be clearly defined. Zonisamide is structurally distinct from other AEDs and has multiple and complementary mechanisms of action, which likely contribute to its efficacy across a broad range of epilepsy types. Zonisamide has a long T1/2 enabling once-daily dosing, linear pharmacokinetics and minimal interaction with other drugs; plasma levels of commonly administered AEDs and oral contraceptives are unaffected by concomitant zonisamide. Effective control of partial seizures (up to 51% decrease in seizure frequency) is attained at doses of >or=300 mg/day, and optimal titration and maintenance dosing schedules have been established. The adverse event profile is well defined; in common with most AEDs, most adverse events are central nervous system-related (e.g. somnolence, dizziness, tiredness). Adverse events may be minimised with appropriate patient management. Zonisamide therefore has many characteristics considered desirable in an AED and represents a valuable addition to the therapeutic options for treating epilepsy in Europe.
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PMID:Introduction to zonisamide. 1641 70

In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs) used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal), topiramate (Topamax), zonisamide (Zonegran), levetiracetam (Keppra), and oxcarbazepine (Trileptal). All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate) thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.
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PMID:[Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy]. 1924 7


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