topiramate and fosphenytoin

In this review study, second-generation antiepileptic drugs (AEDs) (levetiracetam, gabapentin, topiramate, lamotrigine, zonisamide, oxcarbazepine, vigabatrin, pregabalin, rufinamide, tiagabine, lacosamide, and felbamate) and injectable AEDs (levetiracetam, lacosamide, fosphenytoin, lorazepam, and valproic acid) available in North America were compared with those available in Japan. Three second-generation AEDs (gabapentin, topiramate, and lamotrigine) were recently approved in Japan. Levetiracetam is currently under review for approval by the Japanese regulatory agency. An ideal AED would have a broad-spectrum activity to control multiple types of seizures, favorable safety profile, limited potential for drug-drug interaction, many bioequivalent formulations, long half life to allow infrequent administration, and antiepileptogenic effects that may provide a fundamental cure of epileptic patients by suppressing the development of epileptogenic network and neutralizing previously established epileptogenic foci in the brain. The second-generation AEDs have been developed to possess some of these ideal properties. All the second-generation AEDs are efficacious for the treatment of patients with partial seizures. In addition, levetiracetam, topiramate, lamotrigine, and zonisamide are effective for the treatment of patients with generalized tonic-clonic seizures, absences, myoclonic seizures, Lennox-Gastaut syndrome, and West syndrome; however, lamotrigine is not effective for the treatment of patients with myoclonic seizures. Rufinamide and felbamate are useful for the treatment of patients with Lennox-Gastaut syndrome; however owing to its serious adverse effects, including aplastic anemia and hepatic failure, felbamate is used as the last resort for the treatment of patients with intractable seizures. Vigabatrin is particularly effective for the treatment of patients with West syndrome; however, the patients need to be regularly monitored for the development of peripheral visual field defect. Gabapentin, oxcarbazepine, vigabatrin, and tiagabine are ineffective for the treatment of patients with absences and/or myoclonic seizures and may aggravate these conditions. Treatment with levetiracetam or topiramate (off-label use) is the new option for patients with refractory status epilepticus, which is characterized by downregulation of the inhibitory gamma-aminobutyric acid system, because these drugs act via different mechanisms and are rapidly titratable, espec

Topics: Anticonvulsants; Carbamazepine; Drug Approval; Fructose; Humans; Japan; Lamotrigine; Levetiracetam; Lorazepam; North America; Phenytoin; Piracetam; Topiramate; Triazines

The introduction of these new antiepileptic drugs, from felbamate to levetiracetam, raised hope of control of epilepsy with fewer adverse effects and improved quality of life. Unfortunately, many patients continue to experience refractory epilepsy despite the use of these new agents, and dose-related adverse effects and idiosyncratic reactions continue to be problematic. A recent report describes six new compounds in preclinical development, and five in clinical trials [131]. As the number of available, effective, but imperfect antiepileptic drugs increases, many challenges remain. These include: choosing the drug appropriate for the epileptic syndrome, assessing accurately the range of a drug's adverse effects in an individual patient, and considering carefully the drug's interactions in combination drug therapy. In considering drug combinations, differing mechanisms of drug action and favorable pharmacodynamic interactions (an area requiring additional studies) are of importance. Clinicians caring for children who have epilepsy anticipate further advances in the pharmacogenetics and molecular pathophysiology of epilepsy, leading to individually tailored, effective, and safe therapy.

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Dioxolanes; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Phenytoin; Piracetam; Propylene Glycols; Thiazines; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

Epilepsy affects 1.2% to 4.4% of the general population. Given the clinical profile of the newer antiepileptic agents, it is likely their usage will increase in the coming years, thus increasing the emergency physician's exposure to these medications and their side effects. Several of these side effects can have high morbidity, such as the aplastic anemia and hepatotoxicity caused by felbamate, and the Stevens-Johnson syndrome associated with lamotrigine. Overdoses of these medications also could increase, as will our knowledge of recognizing and managing them. The clinical spectrum of the newer medications is the treatment of partial seizures. None of the newer medications can be orally loaded nor are they available in an i.v. preparation. Serum drug levels are not available in most institutions and are not routinely measured in the ED. The new preparations of phenytoin, diazepam, and valporic acid add increased efficiency in drug administration, providing a new method for prehospital treatment of seizures and a more tolerable means of administration in the ED.

Topics: Acetates; Administration, Rectal; Age Factors; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Diazepam; Drug Overdose; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Injections, Intravenous; Lamotrigine; Phenylcarbamates; Phenytoin; Propylene Glycols; Topiramate; Triazines; Valproic Acid

Twenty-five to 40 percent of patients with epilepsy continue to have seizures despite optimal treatment with traditional antiepileptic drugs. Treatment with standard anticonvulsants such as phenytoin, carbamazepine, valproic acid and phenobarbital is often complicated by side effects and by failure to adequately control seizures. Up to 61 percent of patients with seizures report having side effects with antiepileptic drugs. After a 15-year hiatus since the last new antiepileptic drug was marketed, five new drugs have been approved by the U.S. Food and Drug Administration for the control of seizures. Three of these, gabapentin, lamotrigine and topiramate, are approved for use in adults with partial seizures with or without generalization. Felbamate is approved for the above indication and also for use in children with Lennox-Gastaut syndrome, a rare childhood seizure disorder. Felbamate and lamotrigine have the potential of significant side effects and should be prescribed by physicians experienced in managing patients with complicated epilepsy. Fosphenytoin is a parenteral prodrug of phenytoin that is more tolerable than parenteral phenytoin.

Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Phenylcarbamates; Phenytoin; Propylene Glycols; Topiramate; Triazines

Treatment options for epilepsy, especially using antiepileptic drugs, have increased substantially in the past five years. Since 1993, four novel antiepileptic drugs have been approved and marketed in the United States: felbamate, gabapentin, lamotrigine, and topiramate. Two others, tiagabine and vigabatrin, are likely to be approved in the near future. For many patients, these agents offer the realistic promise of improved seizure control, often with fewer adverse effects and less significant drug interactions compared with older agents. In addition, fosphenytoin, a water-soluble phenytoin prodrug with a number of advantages over intravenous phenytoin, has been released. There are new administration options for carbamazepine, diazepam, and valproic acid. For drug-resistant or -intolerant patients, there has been renewed interest in alternative therapies, especially the ketogenic diet. Taken together, these represent significant therapeutic advances that are benefiting patients with epilepsy. At the same time, improved understanding of the basic mechanisms of epileptogenesis, and of the cellular and molecular actions of available antiepileptic drugs, creates a framework for designing unique therapeutic strategies that are targeted at key sites of vulnerability involved in the development and maintenance of the epileptic state.

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Diazepam; Drug Approval; Drug Design; Drug Interactions; Drug Resistance; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Injections, Intravenous; Ketones; Lamotrigine; Neurotransmitter Uptake Inhibitors; Nipecotic Acids; Phenylcarbamates; Phenytoin; Prodrugs; Propylene Glycols; Tiagabine; Topiramate; Triazines; United States; Valproic Acid; Vigabatrin

Topics: Acetates; Amines; Anticonvulsants; Biological Availability; Cyclohexanecarboxylic Acids; Drug Interactions; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Half-Life; Humans; Lamotrigine; Phenylcarbamates; Phenytoin; Propylene Glycols; Topiramate; Triazines

This article reviews selected medical and surgical advances that the authors view as important to improving the treatment of patients with epilepsy. This includes a review of six new antiepileptic drugs (fosphenytoin, felbamate, gabapentin, lamotrigine, toprimimate, and vigabatrin), recent studies of the surgical technique of Multiple Subpial Transections, and a summary of a prospective longitudinal study on anterior temporal lobectomy.

Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Neurosurgery; Phenylcarbamates; Phenytoin; Pia Mater; Propylene Glycols; Temporal Lobe; Topiramate; Triazines; Vigabatrin

Topics: Adolescent; Adult; Age Factors; Amitriptyline; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Child; Drug Industry; Duodenal Ulcer; Female; France; Gastroesophageal Reflux; Humans; Male; Migraine Disorders; Pharmacovigilance; Phenytoin; Plasma Substitutes; Polygeline; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Stomach Ulcer; Topiramate

We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT).. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT; i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders.. TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders).. The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.

Topics: Amygdala; Animals; Anticonvulsants; Disease Models, Animal; Drug Resistance; Electric Stimulation; Epilepsy; Female; Fructose; Kindling, Neurologic; Phenytoin; Prodrugs; Rats; Rats, Wistar; Topiramate