Study Protocol SEP093-701
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STATUS EPILEPTICUS in ADULTS (Convulsive Seizures in Patients Aged > 16 Years Old) Link Consultant: Dr Hannah Cock
STATUS EPILEPTICUS IN ADULTS (Convulsive Seizures in patients aged > 16 years old) Link consultant: Dr Hannah Cock Status epilepticus (SE) is defined as continuous seizure activity which has failed to self- terminate leading to a risk of neurological damage. The risks are highest with generalised tonic/clonic (convulsive) seizures. Convulsive SE may present as either a run of discreet generalised tonic/clonic seizures without full recovery in between (ie without regaining consciousness), or continuous generalised tonic/clonic seizure activity. Most convulsive seizures terminate spontaneously within 3 minutes, and do NOT need emergency treatment. Convulsive seizures lasting longer than 5 minutes, or recurring without recovery should be managed as Convulsive SE, unless the patient is known to habitually have longer seizures with self-termination (eg information from relatives, friends, or the patient’s epilepsy card or diary). The mortality and morbidity of generalised status epilepticus is high, and it is important to control fits as soon as possible, to use adequate doses of 1st and 2nd line agents, but not to over-treat patients in whom seizures have terminated but are slow to recover. GENERAL MANAGEMENT 1st stage (0-10mins). Protect the patient e.g. padded bed rails. Do not restrain. Administer oxygen. During an inter-ictal period insert an airway and then administer oxygen. Do not attempt to insert anything in the patient’s mouth during a seizure, even if the tongue is injured. Place the patient in a semi-prone position with the head down to prevent aspiration. Establish iv access. Note the time. 2nd Stage (0-30mins). Institute regular monitoring (temperature, cardiac, respiration, BP). -
Inhibitory Effect of Eslicarbazepine Acetate and S-Licarbazepine on 2 Nav1.5 Channels
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.24.059188; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Inhibitory effect of eslicarbazepine acetate and S-licarbazepine on 2 Nav1.5 channels 3 Theresa K. Leslie1, Lotte Brückner 1, Sangeeta Chawla1,2, William J. Brackenbury1,2* 4 1Department of Biology, University of York, Heslington, York, YO10 5DD, UK 5 2York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK 6 * Correspondence: Dr William J. Brackenbury, Department of Biology and York Biomedical 7 Research Institute, University of York, Wentworth Way, Heslington, York YO10 5DD, UK. Email: 8 [email protected]. Tel: +44 1904 328284. 9 Keywords: Anticonvulsant, cancer, epilepsy, eslicarbazepine acetate, Nav1.5, S-licarbazepine, 10 voltage-gated Na+ channel. 11 Abstract 12 Eslicarbazepine acetate (ESL) is a dibenzazepine anticonvulsant approved as adjunctive treatment for 13 partial-onset epileptic seizures. Following first pass hydrolysis of ESL, S-licarbazepine (S-Lic) 14 represents around 95 % of circulating active metabolites. S-Lic is the main enantiomer responsible 15 for anticonvulsant activity and this is proposed to be through the blockade of voltage-gated Na+ 16 channels (VGSCs). ESL and S-Lic both have a voltage-dependent inhibitory effect on the Na+ current 17 in N1E-115 neuroblastoma cells expressing neuronal VGSC subtypes including Nav1.1, Nav1.2, 18 Nav1.3, Nav1.6 and Nav1.7. -
Eslicarbazepine Acetate Longer Procedure No
European Medicines Agency London, 19 February 2009 Doc. Ref.: EMEA/135697/2009 CHMP ASSESSMENT REPORT FOR authorised Exalief International Nonproprietary Name: eslicarbazepine acetate longer Procedure No. EMEA/H/C/000987 no Assessment Report as adopted by the CHMP with all information of a commercially confidential nature deleted. product Medicinal 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: [email protected] http://www.emea.europa.eu TABLE OF CONTENTS 1. BACKGROUND INFORMATION ON THE PROCEDURE........................................... 3 1.1. Submission of the dossier ...................................................................................................... 3 1.2. Steps taken for the assessment of the product..................................................................... 3 2. SCIENTIFIC DISCUSSION................................................................................................. 4 2.1. Introduction............................................................................................................................ 4 2.2. Quality aspects ....................................................................................................................... 5 2.3. Non-clinical aspects................................................................................................................ 8 2.4. Clinical aspects.................................................................................................................... -
Therapeutic Class Overview Anticonvulsants
Therapeutic Class Overview Anticonvulsants INTRODUCTION Epilepsy is a disease of the brain defined by any of the following (Fisher et al 2014): ○ At least 2 unprovoked (or reflex) seizures occurring > 24 hours apart; ○ 1 unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures, occurring over the next 10 years; ○ Diagnosis of an epilepsy syndrome. Types of seizures include generalized seizures, focal (partial) seizures, and status epilepticus (Centers for Disease Control and Prevention [CDC] 2018, Epilepsy Foundation 2016). ○ Generalized seizures affect both sides of the brain and include: . Tonic-clonic (grand mal): begin with stiffening of the limbs, followed by jerking of the limbs and face . Myoclonic: characterized by rapid, brief contractions of body muscles, usually on both sides of the body at the same time . Atonic: characterized by abrupt loss of muscle tone; they are also called drop attacks or akinetic seizures and can result in injury due to falls . Absence (petit mal): characterized by brief lapses of awareness, sometimes with staring, that begin and end abruptly; they are more common in children than adults and may be accompanied by brief myoclonic jerking of the eyelids or facial muscles, a loss of muscle tone, or automatisms. ○ Focal seizures are located in just 1 area of the brain and include: . Simple: affect a small part of the brain; can affect movement, sensations, and emotion, without a loss of consciousness . Complex: affect a larger area of the brain than simple focal seizures and the patient loses awareness; episodes typically begin with a blank stare, followed by chewing movements, picking at or fumbling with clothing, mumbling, and performing repeated unorganized movements or wandering; they may also be called “temporal lobe epilepsy” or “psychomotor epilepsy” . -
Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy
Original Article / Özgün Makale DODO I: 10.4274/ I: 10.4274/jtsm.xxxjtsm.69188 Journal of Turkish Sleep Medicine 2018;5:12-6 Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy Levetirasetam Monoterapisi Altında Epilepsi Hastalarında Huzursuz Bacak Sendromu Gülnihal Kutlu, Fatma Genç*, Yasemin Ünal, Dilek Aslan Öztürk, Abidin Erdal*, Yasemin Biçer Gömceli* Muğla Sıtkı Koçman University Faculty of Medicine, Department of Neurology, Muğla, Turkey *University of Health Sciences, Antalya Training and Research Hospital, Clinic of Neurology, Antalya, Turkey Abstract Öz Objective: Restless Legs syndrome (RLS) is a frequent neurological Amaç: Huzursuz Bacak sendromu (HBS) sık görülen bir nörolojik disease. Levetiracetam (LEV) is an effective and broad-spectrum hastalıktır. Levetirasetam (LEV) etkili ve geniş spektrumlu bir antiepileptik anticonvulsant drug. The aim of this study is to investigate the frequency ilaçtır. Bu çalışmanın amacı epilepsi tanısı ile LEV monoterapisi alan of RLS in patients diagnosed with epilepsy who took LEV monotherapy. hastalarda HBS sıklığını araştırmaktır. Materials and Methods: Two neurologists were reviewed the files of Gereç ve Yöntem: Epilepsi polikliniğinde takip edilen 1680 hastanın 1680 patients, who were followed in epilepsy outpatient clinic. One dosyası iki nörolog tarafından gözden geçirildi. En az 6 aydır LEV hundred seven patients under LEV monotherapy for at least six months monoterapisi alan 107 hasta ve 120 sağlıklı kontrol çalışmaya alındı. and 120 healthy controls were included in the study. The criteria for the International Restless Legs Syndrome Study Group were taken into HBS değerlendirmesi için Uluslararası Huzursuz Bacak Sendromu Çalışma consideration for the assessment of RLS. Grubu’nun kriterleri göz önüne alındı. Results: The mean age of patient group was 38.26±17.39 years, while Bulgular: Sağlıklı kontrollerin ortalama yaşı 39,17±16,12 yıl iken, the mean age of healthy controls was 39.17±16.12 years. -
Eslicarbazepine Acetate: a New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures
Drugs R D DOI 10.1007/s40268-017-0197-5 REVIEW ARTICLE Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures 1 1 1 Graciana L. Galiana • Angela C. Gauthier • Richard H. Mattson Ó The Author(s) 2017. This article is an open access publication Abstract Eslicarbazepine acetate is a new anti-epileptic drug belonging to the dibenzazepine carboxamide family Key Points that is currently approved as adjunctive therapy and monotherapy for partial-onset (focal) seizures. The drug Eslicarbazepine acetate is an effective and safe enhances slow inactivation of voltage-gated sodium chan- treatment option for partial-onset seizures as nels and subsequently reduces the activity of rapidly firing adjunctive therapy and monotherapy. neurons. Eslicarbazepine acetate has few, but some, drug– drug interactions. It is a weak enzyme inducer and it Eslicarbazepine acetate improves upon its inhibits cytochrome P450 2C19, but it affects a smaller predecessors, carbamazepine and oxcarbazepine, by assortment of enzymes than carbamazepine. Clinical being available in a once-daily regimen, interacting studies using eslicarbazepine acetate as adjunctive treat- with a smaller range of drugs, and causing less side ment or monotherapy have demonstrated its efficacy in effects. patients with refractory or newly diagnosed focal seizures. The drug is generally well tolerated, and the most common side effects include dizziness, headache, and diplopia. One of the greatest strengths of eslicarbazepine acetate is its ability to be administered only once per day. Eslicar- 1 Introduction bazepine acetate has many advantages over older anti- epileptic drugs, and it should be strongly considered when Epilepsy is a common neurological disorder affecting over treating patients with partial-onset epilepsy. -
Epilepsy & Behavior
Epilepsy & Behavior 80 (2018) 365–369 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh Brief Communication Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events Virupakshi Jalihal a, Rohit Shankar b,c,⁎, William Henley c, Mary Parrett d, Phil Tittensor e, Brendan N. McLean d, Ammad Ahmed f, Josemir W. Sander g,h,i a Ramaiah Medical College and Hospitals, Bengaluru, Karnataka 560054, India b Cornwall Partnership NHS Foundation Trust, Threemilestone Industrial Estate, Truro TR4 9LD, UK c Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK d Royal Cornwall Hospital, Truro, Cornwall TR1 3LJ, UK e Royal Wolverhampton NHS Trust, UK f Bial Pharma Ltd., Admiral House, Windsor SL4 3BL, UK g NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK h Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire SL9 0RJ, UK i Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, Netherlands article info abstract Article history: Background: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) Received 13 November 2017 withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized Revised 16 January 2018 with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly Accepted 17 January 2018 used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric Available online 5 February 2018 illnesses such as mood disorders, aggression, and anxiety. -
Mechanisms of Action of Antiepileptic Drugs
Review Mechanisms of action of antiepileptic drugs Epilepsy affects up to 1% of the general population and causes substantial disability. The management of seizures in patients with epilepsy relies heavily on antiepileptic drugs (AEDs). Phenobarbital, phenytoin, carbamazepine and valproic acid have been the primary medications used to treat epilepsy for several decades. Since 1993 several AEDs have been approved by the US FDA for use in epilepsy. The choice of the AED is based primarily on the seizure type, spectrum of clinical activity, side effect profile and patient characteristics such as age, comorbidities and concurrent medical treatments. Those AEDs with broad- spectrum activity are often found to exert an action at more than one molecular target. This article will review the proposed mechanisms of action of marketed AEDs in the US and discuss the future of AEDs in development. 1 KEYWORDS: AEDs anticonvulsant drugs antiepileptic drugs epilepsy Aaron M Cook mechanism of action seizures & Meriem K Bensalem-Owen† The therapeutic armamentarium for the treat- patients with refractory seizures. The aim of this 1UK HealthCare, 800 Rose St. H-109, ment of seizures has broadened significantly article is to discuss the past, present and future of Lexington, KY 40536-0293, USA †Author for correspondence: over the past decade [1]. Many of the newer AED pharmacology and mechanisms of action. College of Medicine, Department of anti epileptic drugs (AEDs) have clinical advan- Neurology, University of Kentucky, 800 Rose Street, Room L-455, tages over older, so-called ‘first-generation’ First-generation AEDs Lexington, KY 40536, USA AEDs in that they are more predictable in their Broadly, the mechanisms of action of AEDs can Tel.: +1 859 323 0229 Fax: +1 859 323 5943 dose–response profile and typically are associ- be categorized by their effects on the neuronal [email protected] ated with less drug–drug interactions. -
Chapter 25 Mechanisms of Action of Antiepileptic Drugs
Chapter 25 Mechanisms of action of antiepileptic drugs GRAEME J. SILLS Department of Molecular and Clinical Pharmacology, University of Liverpool _________________________________________________________________________ Introduction The serendipitous discovery of the anticonvulsant properties of phenobarbital in 1912 marked the foundation of the modern pharmacotherapy of epilepsy. The subsequent 70 years saw the introduction of phenytoin, ethosuximide, carbamazepine, sodium valproate and a range of benzodiazepines. Collectively, these compounds have come to be regarded as the ‘established’ antiepileptic drugs (AEDs). A concerted period of development of drugs for epilepsy throughout the 1980s and 1990s has resulted (to date) in 16 new agents being licensed as add-on treatment for difficult-to-control adult and/or paediatric epilepsy, with some becoming available as monotherapy for newly diagnosed patients. Together, these have become known as the ‘modern’ AEDs. Throughout this period of unprecedented drug development, there have also been considerable advances in our understanding of how antiepileptic agents exert their effects at the cellular level. AEDs are neither preventive nor curative and are employed solely as a means of controlling symptoms (i.e. suppression of seizures). Recurrent seizure activity is the manifestation of an intermittent and excessive hyperexcitability of the nervous system and, while the pharmacological minutiae of currently marketed AEDs remain to be completely unravelled, these agents essentially redress the balance between neuronal excitation and inhibition. Three major classes of mechanism are recognised: modulation of voltage-gated ion channels; enhancement of gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission; and attenuation of glutamate-mediated excitatory neurotransmission. The principal pharmacological targets of currently available AEDs are highlighted in Table 1 and discussed further below. -
Clinical Review, Adverse Events
Clinical Review, Adverse Events Drug: Carbamazepine NDA: 16-608, Tegretol 20-712, Carbatrol 21-710, Equetro Adverse Event: Stevens-Johnson Syndrome Reviewer: Ronald Farkas, MD, PhD Medical Reviewer, DNP, ODE I 1. Executive Summary 1.1 Background Carbamazepine (CBZ) is an anticonvulsant with FDA-approved indications in epilepsy, bipolar disorder and neuropathic pain. CBZ is associated with Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), closely related serious cutaneous adverse drug reactions that can be permanently disabling or fatal. Other anticonvulsants, including phenytoin, phenobarbital, and lamotrigine are also associated with SJS/TEN, as are members of a variety of other drug classes, including nonsteriodal anti-inflammatory drugs and sulfa drugs. The incidence of CBZ-associated SJS/TEN has been considered “extremely rare,” as noted in current U.S. drug labeling. However, recent publications and postmarketing data suggest that CBZ- associated SJS/TEN occurs at a much higher rate in some Asian populations, about 2.5 cases per 1,000 new exposures, and that most of this increased risk is in individuals carrying a specific human leukocyte antigen (HLA) allele, HLA-B*1502. This HLA-B allele is present in about 5- to 20% of many, but not all, Asian populations, and is also present in about 2- to 4% of South Asians/Indians. The allele is also present at a lower frequency, < 1%, in several other ethnic groups around the world (although likely due to distant Asian ancestry). About 10% of U.S. Asians carry HLA-B*1502. HLA-B*1502 is generally not present in the U.S. -
Mode of Seizure Inhibition by Sodium Channel Blockers, an SV2A Ligand
Epilepsy Research 154 (2019) 42–49 Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Mode of seizure inhibition by sodium channel blockers, an SV2A ligand, and T an AMPA receptor antagonist in a rat amygdala kindling model ⁎ Ting Wua, Katsutoshi Idoa, Makoto Ohgoha, Takahisa Hanadab, a Neurology Tsukuba Research Department, Discovery, Medicine Creation, Neurology Business Group, Eisai Co., Ltd. Japan b Clinical Science Department, Medical Division, Eisai Co., Ltd. Nishigokencho 13-1, Shinjuku-ku, Tokyo 162-0812, Japan ARTICLE INFO ABSTRACT Keywords: Purpose: A number of antiepileptic drugs (AEDs) with a variety of modes of action, are effective in treating focal AMPA receptor antagonist seizures. Several AEDs, such as perampanel (PER), levetiracetam (LEV), lacosamide (LCM), lamotrigine (LTG), Antiepileptic drug and carbamazepine (CBZ), have been shown to elevate the seizure threshold in kindling models. These AEDs are Mode of seizure inhibition clinically effective, but differences exist in the anti-seizure profiles of drugs with similar modes ofaction. Focal seizure Therefore, we hypothesized that there are differences in how these AEDs affect seizures. Here, we evaluated the Perampanel effects of AEDs on various seizure parameters in a rat amygdala kindling model upon stimulation attheafter- Synaptic transmission discharge threshold (ADT) and at three-times the ADT (3xADT) to characterize the differences in the effects of these AEDs. Methods: PER, LEV, LCM, LTG, CBZ, or vehicle was administered intraperitoneally to fully kindled rats. Changes in Racine seizure score, after-discharge duration (ADD), and latency to Racine score 4 generalized seizure (S4L) were measured to assess differences in the modes of seizure inhibition among the AEDs. -
Anticonvulsants
Clinical Pharmacy Program Guidelines for Anticonvulsants Program Prior Authorization - Anticonvulsants Medication Aptiom (eslicarbazepine), Briviact (brivaracetam), Fycompa (perampanel), Vimpat (lacosamide), Gabitril (tiagabine), Banzel (rufinamide), Onfi (clobazam), Epidiolex (cannabidiol), Sympazan (clobazam), Sabril, (vigabatrin), Diacomit (stiripentol), Xcopri (cenobamate), Fintepla (fenfluramine) Markets in Scope Arizona, California, Colorado, Hawaii, Nevada, New Jersey, New York, New York EPP, Pennsylvania- CHIP, Rhode Island, South Carolina Issue Date 6/2016 Pharmacy and 10/2020 Therapeutics Approval Date Effective Date 12/2020 1. Background: Aptiom (eslicarbazepine acetate), Briviact (brivaracetam), Vimpat (lacosamide) and Xcopri are indicated in the treatment of partial-onset seizures. Banzel (rufinamide), Onfi (clobazam), and Sympazan (clobazam) are indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS). There is some clinical evidence to support the use of clobazam for refractory partial onset seizures. Diacomit (stiripentol) is indicated for seizures associated with Dravet syndrome in patients taking clobazam. Epidiolex (cannabadiol) is indicated for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome or tuberous sclerosis complex. Fintepla (fenfluramine) is indicated for the treatment of seizures associated with Dravet syndrome. Fycompa (perampanel) is indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures and as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures. Gabitril (tiagabine) is indicated ad adjunctive therapy in the treatment of partial-onset seizures. Confidential and Proprietary, © 2020 UnitedHealthcare Services Inc. Sabril (vigabatrin) is indicated as adjunctive therapy for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for infantile spasms for whom the potential benefits outweigh the risk of vision loss.