Brivaracetam “Briviact”

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10/16/2020 Highlights Michigan State Medical Society Annual Scientific Meeting 10/23/2020 Seizures and Epilepsy in Non-Neurologic Specialties: . Why more new seizure medications? Newer Anti-Seizure Medications . The newer AEDs, their MOA, advantages, disadvantages, and SE . Any other new option beside medications? Mounzer Kassab, M.D., M.A. Professor and Vice Chairman Department of Neurology Michigan State University Sparrow Health System 1 2 Oxcarbazepine Zonisamide Why Newer AEDs? Levetiracetam Some FDA approved Available AEDs Pregabalin Still no magic pill for epilepsy Lacosamide Clobazam Still SE and drug-drug-interaction Aptiom Fycompa Still inconveniences in administration and preparations Potiga 10 topiramate Targets for newer AEDs: tiagabine lamotrigine gabapentin Better efficacy?? felbamate Less SE and drug-drug interactions valproate 5 carbamazepine More friendly with better titration schedule, administration routs, and preparations ethosuximide phenytoin phenobarbital 1900 1920 1940 1960 1980 2000 3 4 The problem: brivaracetam “Briviact” . Seizure freedom: . MOA: selective affinity for the target synaptic vesicle protein 2A. The . After first AED: 47% selectivity exclude AMPA receptors = less irritability SE . After second AED 13% . Dosing: initial dosage is 25mg or 50mg twice daily. Target dose is 100mg . After third AED 3% twice daily . Metabolism: in blood, renal excretion. Adv: Renal failure . SE: somnolence, dizziness and fatigue. Adv: No labs for toxicity . Formulations: pills, oral solution, IV injection solution 5 6 1 10/16/2020 cenobamate (Xcopri) Nasal Sprays • MOA: inhibiting voltage-gated sodium currents and is a positive allosteric Seizure Clusters.. modulator of the γ-aminobutyric acid (GABAA) ion channel • SE: somnolence, dizziness, fatigue, diplopia, and headaches. • Dosage • Week 1 and 2: 12.5 mg once daily • Week 3 and 4: 25 mg once daily • Week 5 and 6: 50 mg once daily • Week 7 and 8: 100 mg once daily • Week 9 and 10: 150 mg once daily • Week 11 and thereafter 200 mg once daily 7 8 Nasal Spray midazolam (Nayzilam) Nasal Spray diazepam (Valtoco) • MOA and indications: Is a benzodiazepine indicated for the acute treatment of acute repetitive seizures that are distinct from the patient’s usual seizure pattern . MOA and indications: is a benzodiazepine for the acute treatment of • No priming or assembly necessary intermittent frequent clusters of seizures. • Can be administered by almost anyone . Dose: 5, 10, 15, or 20 mg based on weight. Second dose may be given • SE: Somnolence and nasal discomfort no sooner than 4 hours after the first dose if needed. • Dose: one spray (5mg) into one nostril. If needed after 10 minutes, one spray (5mg) can be administered in the other nostril. SE: nasal discomfort, epistaxis, cough, throat irritation somnolence in 1.5 to 5% of subjects 9 10 Other new options in treatment? . Resective surgery . VNS . RNS . DBS . Diet 11 2.

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Attachment: Product Information Brivaracetam
Attachment 1: Product information for AusPAR AusPAR Briviact UCB Australia Pty Ltd PM- 2015-01568-1-1 Final 7 March 2017. This Product Information was approved at the time this AusPAR was published. PRODUCT INFORMATION BRIVIACT (brivaracetam) Solution for Injection NAME OF THE MEDICINE Non-proprietary name: Brivaracetam Chemical name: (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide Chemical structure: Molecular formula: C11H20N2O2 MW: 212.29 CAS number: [357336-20-0] DESCRIPTION The active ingredient brivaracetam is a white to off-white crystalline powder. It is very soluble in water, buffer (pH 1.2, 4.5 and 7.4), ethanol, methanol, and glacial acetic acid. It is freely soluble in acetonitrile and acetone and soluble in toluene. It is very slightly soluble in n-hexane. BRIVIACT solution for injection contains the following excipients: sodium acetate trihydrate, glacial acetic acid, sodium chloride, water for injections. PHARMACOLOGY Mechanism of action Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain. Binding to SV2A is considered to be the primary mechanism for brivaracetam anticonvulsant activity, however, the precise mechanism by which brivaracetam exerts is anticonvulsant activity has not been fully elucidated. Effects on QT interval The effect of brivaracetam on QTc prolongation was evaluated in a randomized, double-blind, positive-controlled (moxifloxacin 400 mg)- and placebo-controlled parallel group study of brivaracetam (150 mg/day and 800 mg/day in two daily intakes) in 184 healthy subjects. There was no evidence that brivaracetam prolongs the QT interval. Seizure frequency Briviact Solution for injection PI g2016-263 Page 1 Attachment 1: Product information for AusPAR AusPAR Briviact UCB Australia Pty Ltd PM- 2015-01568-1-1 Final 7 March 2017.
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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.
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Patient Brochure Your Guide to Better Understanding Partial
Melanie is an actual person living with epilepsy, currently taking BRIVIACT for partial-onset seizures. Learn about ® BRIVIACT (brivaracetam) DON’T LET EPILEPSY ROB YOU OF YOUR TIME. Discover how you may experience fewer partial-onset seizures by taking BRIVIACT alone or adding to your current treatment. BRIVIACT® (brivaracetam) CV is a prescription medicine that can be used to treat partial-onset seizures in people 4 years of age and older. BRIVIACT injection is only for use in people 16 years of age and older. Please see Important Safety Information on pages 12-14, and enclosed Patient Medication Guide in back pocket. SAVE ON BRIVIACT See inside for details. Are you still waiting for your personal best in partial-onset seizure control? Epilepsy is a thief that can rob you of moments big and small. If you have been diagnosed with partial-onset seizures, you know the impact that epilepsy can have. Seizures can be unpredictable and can get in the way of everyday life and long-term plans. If you are still having partial-onset seizures on your current medicine, ask yourself if you could be doing better. Achieving your personal best in seizure control could mean reducing the number of partial-onset seizures you are having. When taken alone or added to your current medicine, BRIVIACT® (brivaracetam) CV may help reduce your partial-onset seizures. It’s your time; take your time back from seizures. In this brochure, you will find information to help you learn more about epilepsy and treatment with BRIVIACT. You will also find resources for patients and caregivers, as well as BRIVIACT savings offers.
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Teratogenic Potential of Third-Generation Antiepileptic Drugs: Current
Pharmacological Reports 71 (2019) 491–502 Contents lists available at ScienceDirect Pharmacological Reports journal homepage: www.elsevier.com/locate/pharep Review article Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs K.P. Singh*, Niharika Verma Neurobiology Lab, Department of Zoology, University of Allahabad, Allahabad, India A R T I C L E I N F O A B S T R A C T Article history: The aim of this review was to scrutinize the current literature available on teratogenic safety of third- Received 28 August 2018 generation antiepileptic drugs (TGAEDs) considering their clinical implications and to highlight for Received in revised form 27 December 2018 further research need in the interest of the diseased population in general and women with epilepsy in Accepted 29 January 2019 particular. For evaluation of the teratogenic potential of TGAEDs, this review summarized the existing Available online 31 January 2019 information on controlled clinical trials conducted by the pharmaceutical companies, case reports, scholarly articles (prospective and retrospective studies), and experimental tests carried out so far. Keywords: Firstly, clinical reports have reviewed on each drug followed by non-clinical studies reported hitherto. Antiepileptic drugs The Pub-Med and Google search engine was used to explore the relevant articles with pertinent Pregnancy Teratogenicity keywords like pregnancy, epilepsy, seizures, women with epilepsy, antiepileptic or anticonvulsant drugs, ﬁ Birth defects rst-second/new and third/ newest generation antiepileptic drugs, teratogenicity, teratological potential, Congenital anomalies birth defects, congenital anomalies, epilepsy and pregnancy registries, malformation surveillance program. The search was also carried out by the individual name of 20 third-generation AEDs.
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Schedules of Controlled Substances (.Pdf)
PURSUANT TO THE TEXAS CONTROLLED SUBSTANCES ACT, HEALTH AND SAFETY CODE, CHAPTER 481, THESE SCHEDULES SUPERCEDE PREVIOUS SCHEDULES AND CONTAIN THE MOST CURRENT VERSION OF THE SCHEDULES OF ALL CONTROLLED SUBSTANCES FROM THE PREVIOUS SCHEDULES AND MODIFICATIONS. This annual publication of the Texas Schedules of Controlled Substances was signed by John Hellerstedt, M.D., Commissioner of Health, and will take effect 21 days following publication of this notice in the Texas Register. Changes to the schedules are designated by an asterisk (*). Additional information can be obtained by contacting the Department of State Health Services, Drugs and Medical Devices Unit, P.O. Box 149347, Austin, Texas 78714-9347. The telephone number is (512) 834-6755 and the website address is http://www.dshs.texas.gov/dmd. SCHEDULES Nomenclature: Controlled substances listed in these schedules are included by whatever official, common, usual, chemical, or trade name they may be designated. SCHEDULE I Schedule I consists of: -Schedule I opiates The following opiates, including their isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, unless specifically excepted, if the existence of these isomers, esters, ethers, and salts are possible within the specific chemical designation: (1) Acetyl-α-methylfentanyl (N-[1-(1-methyl-2-phenethyl)-4-piperidinyl]-N- phenylacetamide); (2) Acetylmethadol; (3) Acetyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide); (4) Acryl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-phenylacrylamide) (Other name:
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A Systematic Review of Perioperative Seizure Prophylaxis During Brain Tumor Resection: the Case for a Multicenter Randomized Clinical Trial
NEUROSURGICAL FOCUS Neurosurg Focus 43 (5):E18, 2017 A systematic review of perioperative seizure prophylaxis during brain tumor resection: the case for a multicenter randomized clinical trial Vyshak Chandra, MS,1 Andrew K. Rock, MHS, MS,1 Charles Opalak, MD, MPH,1 Joel M. Stary, MD, PhD,1 Adam P. Sima, PhD,2 Matthew Carr, BS,1 Rafael A. Vega, MD, PhD,1 and William C. Broaddus, MD, PhD1 1Department of Neurosurgery, Virginia Commonwealth University Health System, Medical College of Virginia; and 2Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia OBJECTIVE The majority of neurosurgeons administer antiepileptic drugs (AEDs) prophylactically for supratentorial tumor resection without clear evidence to support this practice. The putative benefit of perioperative seizure prophylaxis must be weighed against the risks of adverse effects and drug interactions in patients without a history of seizures. Con- sequently, the authors conducted a systematic review of prospective randomized controlled trials (RCTs) that have evalu- ated the efficacy of perioperative seizure prophylaxis among patients without a history of seizures. METHODS Five databases (PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL/Academic Search Complete, Web of Science, and ScienceDirect) were searched for RCTs published before May 2017 and investi- gating perioperative seizure prophylaxis in brain tumor resection. Of the 496 unique research articles identified, 4 were selected for inclusion in this review. RESULTS This systematic review revealed a weighted average seizure rate of 10.65% for the control groups. There was no significant difference in seizure rates among the groups that received seizure prophylaxis and those that did not. Further, this expected incidence of new-onset postoperative seizures would require a total of 1258 patients to enroll in a RCT, as determined by a Farrington-Manning noninferiority test performed at the 0.05 level using a noninferiority differ- ence of 5%.
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Brivaracetam – Benefit Assessment According to §35A Social Code Book V1
IQWiG Reports – Commission No. A16-08 Brivaracetam – Benefit assessment according to §35a Social Code Book V1 Extract 1 Translation of Sections 2.1 to 2.6 of the dossier assessment Brivaracetam – Nutzenbewertung gemäß § 35a SGB V (Version 1.0; Status: 12 May 2016). Please note: This translation is provided as a service by IQWiG to English-language readers. However, solely the German original text is absolutely authoritative and legally binding. Extract of dossier assessment A16-08 Version 1.0 Brivaracetam – Benefit assessment acc. to §35a Social Code Book V 12 May 2016 Publishing details Publisher: Institute for Quality and Efficiency in Health Care Topic: Brivaracetam – Benefit assessment according to §35a Social Code Book V Commissioning agency: Federal Joint Committee Commission awarded on: 11 February 2016 Internal Commission No.: A16-08 Address of publisher: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen Im Mediapark 8 50670 Köln Germany Phone: +49 221 35685-0 Fax: +49 221 35685-1 E-mail: [email protected] Internet: www.iqwig.de Institute for Quality and Efficiency in Health Care (IQWiG) - i - Extract of dossier assessment A16-08 Version 1.0 Brivaracetam – Benefit assessment acc. to §35a Social Code Book V 12 May 2016 Medical and scientific advice: . Arnfin Bergmann, Neurological Practice, Neuburg/Donau, Germany IQWiG thanks the medical and scientific advisor for his contribution to the dossier assessment. However, the advisor was not involved in the actual preparation of the dossier assessment. The responsibility for the contents of the dossier assessment lies solely with IQWiG. IQWiG employees involved in the dossier assessment2: . Cornelia Rüdig . Ulrich Grouven .
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Epilepsy in Pregnancy
Practice Current: Epilepsy in Pregnancy 11 While recognizing each case is different, please choose the answer that best reflects your common practice and limit free text to strategies that are not included. Estimated Time: 2 Minutes 10 CASE 1 A 21-year-old woman is newly diagnosed with focal epilepsy of unknown etiology. Brain MRI is normal and EEG reveals sporadic right temporal sharp waves. She has no current plans to get pregnant, but says she may want to have a family in the future. Show/hide trigger exists. 5 1. Do you recommend folic acid supplementation for this patient? * Yes No Hidden unless: #1 Question "Do you recommend folic acid supplementation for this patient?" is one of the following answers ("Yes") 6 2. What dosage of folic acid supplementation do you recommend? * 0.4 mg 0.8 mg 2 mg 4 mg 8 mg Other 7 3. Which antiepileptic medication (AED) would you prescribe first? * Brivaracetam Carbamazepine Clobazam Clonazepam Diazepam Eslicarbazepine Ethosuximide Ezogabine Felbamate Gabapentin Lacosamide Lamotrigine Levetiracetam Lorazepam Oxcarbazepine Perampanel Phenobarbital Phenytoin Pregabalin Primidone Rufinamide Tiagabine Topiramate Valproate Vigabatrin Zonisamide 46 Several years later, after continuously taking AEDs and remaining seizure-free for 24 months, the patient returns to your office and states she is interested in becoming pregnant, but is concerned about becoming pregnant while on AEDs. 8 4. What is your foremost concern regarding AEDs and pregnancy? * Obstetric complications Teratogenicity Seizure control Breastfeeding Show/hide trigger exists. 31 5. Do you change how frequently you monitor AED levels in pregnant patients? * Yes No Hidden unless: #5 Question "Do you change how frequently you monitor AED levels in pregnant patients?" is one of the following answers ("Yes") 37 6.
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Term Effects of Brivaracetam and Brivaracetam–
FULL-LENGTH ORIGINAL RESEARCH Acute and long-term effects of brivaracetam and brivaracetam–diazepam combinations in an experimental model of status epilepticus *Jerome Niquet, *Lucie Suchomelova, *1Kerry Thompson, †Henrik Klitgaard, †Alain Matagne, and *‡Claude Wasterlain Epilepsia, 58(7):1199–1207, 2017 doi: 10.1111/epi.13787 SUMMARY Objective: To evaluate acute and long-term effects of intravenous brivaracetam (BRV) and BRV + diazepam (DZP) combination treatment in a rat model of self- sustaining status epilepticus (SSSE). Methods: Rats were treated with BRV (10 mg/kg) 10 min after initiation of perforant path stimulation (PPS) as early treatment; or BRV (10–300 mg/kg), DZP (1 mg/kg), or BRV (0.3–10 mg/kg) + DZP (1 mg/kg) 10 min after the end of PPS (established SSSE). Seizure activity was recorded electrographically for 24 h posttreatment (acute effects), and for 1 week at 6–8 weeks or 12 months’ posttreatment (long-term effects). All treatments were compared with control rats using one-way analysis of variance (ANOVA) and Bonferroni’s test, or Kruskal-–Wallis and Dunn’s multiple comparison tests, when appropriate. Results: Treatment of established SSSE with BRV (10–300 mg/kg) resulted in dose- dependent reduction in SSSE duration and cumulative seizure time, achieving statisti- cal signiﬁcance at doses ≥100 mg/kg. Lower doses of BRV (0.3–10 mg/kg) + low-dose DZP (1 mg/kg) signiﬁcantly reduced SSSE duration and number of seizures. All con- trol rats developed spontaneous recurrent seizures (SRS) 6–8 weeks after SSSE, Jerome Niquet is an whereas seizure freedom was noted in 2/10, 5/10, and 6/10 rats treated with BRV + – associate researcher 200 mg/kg, 300 mg/kg, and BRV 10 mg/kg DZP, respectively.
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Antiepileptic Drugs for Epilepsy
Antiepileptic Drugs for Epilepsy EDUCATIONAL OBJECTIVES After completing this activity, participants should be better able to: 1. Define the difference between a seizure and epilepsy. 2. Identify causes and risk factors associated with epilepsy. 3. Understand the proposed pathophysiology of seizures. 4. Describe the mechanism of action of AEDs used in the management of epilepsy. 5. Assess adverse effects and potential drug-drug interactions associated with the use of AEDs CE EXAM RATIONALE 1. Epilepsy is: A. The most common neurologic disorder worldwide B. A chronic condition in which patients experience recurrent, unprovoked seizures*** C. An isolated event resulting from abnormal electrical disturbances in the brain D. Not classified based on seizure type Correct answer: B Epilepsy is defined as a chronic condition in which patients experience recurrent, unprovoked seizures that range from short-lived intervals of inattention or muscle jerking to severe and elongated convulsions. It is the fourth most common neurologic disorder, affecting approximately 65 million people worldwide. The International Classification of Epileptic Seizures classifies seizures as partial (focal) or generalized. 2. Possible causes of epilepsy and seizures include: A. Stroke B. Head trauma C. Medications such as antidepressants and antipsychotics D. All of the above*** Correct answer: D The cause of epilepsy is idiopathic in origin in approximately half of all patients. However, several medical conditions have an associated risk or causation with epilepsy, including traumatic brain injury (TBI), CNS infections, hypoglycemia, eclampsia, fever, and stroke. In addition, many medications have been associated with precipitating seizures (Table 1). 3. Mechanisms of seizure control include all of the following except: A.
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Prescribing Information
HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------WARNINGS AND PRECAUTIONS------------------------ These highlights do not include all the information needed to use Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and BRIVIACT® safely and effectively. See full prescribing information for ideation. (5.1) BRIVIACT. Neurological Adverse Reactions: Monitor for somnolence and fatigue, and advise patients not to drive or operate machinery until they have gained BRIVIACT® (brivaracetam) tablets, for oral use, CV sufficient experience on BRIVIACT. (5.2) BRIVIACT® (brivaracetam) oral solution, CV Psychiatric Adverse Reactions: Behavioral reactions including psychotic BRIVIACT® (brivaracetam) injection, for intravenous use, CV symptoms, irritability, depression, aggressive behavior, and anxiety; Initial U.S. Approval: 2016 monitor patients for symptoms. (5.3) Hypersensitivity: Bronchospasm and Angioedema: Advise patients to seek ----------------------------RECENT MAJOR CHANGES-------------------------- immediate medical care. Discontinue and do not restart BRIVIACT if Indications and Usage (1) 8/2021 hypersensitivity occurs. (5.4) Dosage and Administration (2.1, 2.5) 8/2021 Withdrawal of Antiepileptic Drugs: BRIVIACT should be gradually withdrawn. (5.5) ----------------------------INDICATIONS AND USAGE--------------------------- BRIVIACT is indicated for the treatment of partial-onset seizures in patients 1 ------------------------------ADVERSE REACTIONS------------------------------- month of age and older.
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Stembook 2018.Pdf
The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
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