levetiracetam and rufinamide

Recently, the treatment strategy for pediatric epilepsy has been dramatically changed in Japan, because of the approval of new-generation antiepileptic drugs. Since 2006, a total of 6 new antiepileptic drugs, including gabapentin (GBP; adults/pediatric patients: 2006/2011 [year of approval]), topiramate (TPM; 2007/2013), lamotrigine (LTG; 2008/2008), levetiracetam (LEV; 2010/2013), stiripentol (STP; 2012/2012), and rufinamide (RUF; 2013/2013), have been introduced. Thus far, valproate (VPA) and carbamazepine (CBZ) have been first indicated for "generalized" epilepsy and "focal" epilepsy syndromes/types, respectively, in Japan. However, the approval of these new drugs could allow us to choose more effective and less toxic ones at an early stage of treatment. In this chapter, we describe the latest domestic and foreign guidelines for the treatment of pediatric epilepsy.

Topics: Adolescent; Amines; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Dioxolanes; Drug Approval; Drug Substitution; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Infant; Lamotrigine; Levetiracetam; Patient Education as Topic; Piracetam; Practice Guidelines as Topic; Topiramate; Triazines; Triazoles; Valproic Acid

New antiepileptic drugs (AEDs) that have been used in many other countries for more than 10 years have only recently became available for use in Japan. Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs. Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide, and perampanel are in progress. In this review, the general characteristics of the new AEDs are discussed with regards to their effectiveness, tolerability, drug interaction, safety and mechanisms of action. The effectiveness, of the new AEDs compared with established AEDs is also discussed. Clinical applications of the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam are also discussed based on our domestic experience as well as overseas reports.

Topics: Amines; Anticonvulsants; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Dioxolanes; Drug Approval; Drug Interactions; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Japan; Lamotrigine; Levetiracetam; Piracetam; Safety; Topiramate; Triazines; Triazoles

Topics: Acetamides; Amines; Animals; Anticonvulsants; Benzodiazepines; Carbamates; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Design; Gabapentin; gamma-Aminobutyric Acid; Humans; Lacosamide; Levetiracetam; Phenylenediamines; Piracetam; Pregabalin; Pregnanolone; Pyrrolidinones; Triazoles

Rufinamide is a novel antiepileptic drug used as adjunctive therapy in patients with Lennox-Gastaut syndrome and provides seizure control especially in tonic and atonic seizures. Rufinamide is expected to be effective in intractable epilepsy when atonic and tonic seizures exist. However, rufinamide induced seizure aggravation has been reported in a few patients, which was not associated with a specific type of seizure.. A 12-year-old boy with intractable epilepsy had tonic and atonic seizures despite treatment with valproic acid (3000mg/day), levetiracetam (3000mg/day) and clobazam (40mg/day). Rufinamide was administered as adjuvant therapy. After 2weeks on rufinamide, he experienced atonic seizure worsening, and the frequency of epileptic discharges increased. The deterioration in seizure frequency and epileptiform discharges resolved when rufinamide was discontinued.. Rufinamide may aggravate atonic seizures in patients with intractable epilepsy.

Topics: Anticonvulsants; Benzodiazepines; Brain; Child; Clobazam; Drug Resistant Epilepsy; Drug Therapy, Combination; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Seizures; Triazoles; Valproic Acid

Drug Rash (or Reaction) with Eosinophilia and Systemic Symptoms (DRESS) is a potentially life-threatening hypersensitivity reaction to drugs characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and involvement of internal organs. Initially coined in 1996, the term is used to refer to an idiosyncratic reaction to several drugs, the most common of which are carbamazepine, allopurinol, sulfasalazine, and phenobarbital. We report the first case of DRESS related to rufinamide in a ten year old boy with a history of a complex seizure disorder.

Topics: Anti-Inflammatory Agents; Anticonvulsants; Child; Drug Hypersensitivity Syndrome; Epilepsy, Complex Partial; Fructose; Humans; Levetiracetam; Male; Piracetam; Prednisone; Topiramate; Triazoles

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; Triazoles; Vigabatrin

The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports and recent findings of newly marketed AEDs, the use of AEDs in special populations and their utilization in non-epileptic disorders. Over the last seven years, six new AEDs have been introduced worldwide and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate and vigabatrin. Drugs in development include those at an advanced stage, such as remacemide and tiagabine, as well as those just entering clinical trials, such as rufinamide (CGP 331010) and levetiracetam (ucb LO59). The following is a summary of the presentations for drugs in development and recent findings on newly marketed drugs.

Topics: Acetamides; Animals; Anticonvulsants; Azetidines; Carbamates; Drug Evaluation, Preclinical; Drugs, Investigational; Epilepsy; Humans; Israel; Levetiracetam; Nipecotic Acids; Phenylenediamines; Piracetam; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Thiazoles; Tiagabine; Triazoles