Brivaracetam


Generic Medicine Info
Indications and Dosage
Intravenous
Adjunct in partial seizures
Adult: Partial onset seizures with or without secondary generalisation: Initially, 50 mg or 100 mg daily based on required seizure reduction versus potential side effects. Doses may be adjusted in the range of 50-200 mg daily according to individual response and tolerability. Administer all doses via bolus or infusion over 15 minutes in 2 equally divided doses for up to 4 days. Discontinuation: Gradually reduce dose by 50 mg daily on a weekly basis, then reduce to 20 mg daily for the final week of treatment.
Child: ≥4 years <50 kg: Initially, 1 mg/kg or 2 mg/kg daily based on the need for seizure control. Doses may be adjusted in the range of 1-4 mg/kg daily according to individual response. Maintenance dose: 2 mg/kg daily; ≥50 kg: Initially, 50 mg or 100 mg daily based on the need for seizure control. Doses may be adjusted in the range of 50-200 mg daily according to individual response. Maintenance dose: 100 mg daily. May administer all doses via bolus or infusion over 15 minutes in 2 equally divided doses for up to 4 days.

Oral
Adjunct in partial seizures
Adult: Partial onset seizures with or without secondary generalisation: Initially, 50 mg or 100 mg daily based on required seizure reduction versus potential side effects. Doses may be adjusted in the range of 50-200 mg daily according to individual response and tolerability. All doses are given in 2 equally divided doses. Discontinuation: Gradually reduce dose by 50 mg daily on a weekly basis, then reduce to 20 mg daily for the final week of treatment.
Child: ≥4 years <50 kg: Initially, 1 mg/kg or 2 mg/kg daily based on the need for seizure control. Doses may be adjusted in the range of 1-4 mg/kg daily according to individual response. Maintenance dose: 2 mg/kg daily; ≥50 kg: Initially, 50 mg or 100 mg daily based on the need for seizure control. Doses may be adjusted in the range of 50-200 mg daily according to individual response. Maintenance dose: 100 mg daily. All doses are given in 2 equally divided doses.
Special Patient Group
Patients taking rifampicin: Increase brivaracetam dose by up to 100%.

Pharmacogenomics:

Brivaracetam is primarily metabolised via hydrolysis by hepatic and extrahepatic amidases to form inactive carboxylic acid metabolite, and to a lesser extent via hydroxylation by CYP2C19 isoenzyme to form inactive hydroxy metabolite. Individuals who have no CYP2C19 enzyme activity, known as CYP2C19 poor metabolisers, may experience altered pharmacokinetic response to brivaracetam. The prevalence of CYP2C19 poor metabolisers is estimated at approx 2% in Caucasians, 4% in African Americans, and 14% in the Chinese population. Genetic testing for CYP2C19 may be considered as a guide prior to brivaracetam treatment initiation.

CYP2C19 poor metabolisers (carriers of 2 no function alleles e.g. *2/*2, *2/*3, *3/*3)
Patients with ineffective mutations of CYP2C19 may require brivaracetam dose reduction due to a greater exposure to its standard doses and an increased risk of its adverse effects (e.g. dizziness, somnolence, nausea, and fatigue). Published studies indicate that subjects possessing genetic variations in CYP2C19 have decreased production of the hydroxy metabolite by 2-fold or 10-fold, while the blood levels of brivaracetam itself is increased by 22% or 42% respectively, in individuals with 1 or both mutated alleles.
Renal Impairment
ESRD undergoing dialysis: Not recommended.
Hepatic Impairment
Mild to severe (Child Pugh classes A, B, and C): Initially, 50 mg daily. Max: 150 mg daily. All doses are given in 2 equally divided doses.
Administration
May be taken with or without food. Oral soln does not need to be diluted before swallowing. May be administered via nasogastric tube or gastrostomy tube.
Reconstitution
IV infusion: May be mixed with compatible diluents (e.g. 0.9% NaCl inj, Lactated Ringer’s inj, or 5% dextrose in water).
Special Precautions
CYP2C19 poor metabolisers. Avoid abrupt withdrawal. Not recommended in patient with ESRD undergoing dialysis. Hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation and behaviour, psychiatric symptoms (e.g. psychosis, paranoia, hallucinations, behavioural symptoms), CNS effects (e.g. somnolence, dizziness, fatigue, ataxia, impaired coordination, abnormal gait), haematologic abnormalities (e.g. significant decrease in WBC and neutrophil counts).
Blood and lymphatic system disorders: Neutropenia.
Eye disorders: Nystagmus.
Gastrointestinal disorders: Nausea, vomiting, constipation.
General disorders and admin site conditions: Asthenia, malaise, inj site pain, feeling drunk (IV).
Immune system disorders: Type I hypersensitivity.
Infections and infestations: Influenza.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Vertigo, convulsion, balance disorder, dysgeusia (IV).
Psychiatric disorders: Depression, anxiety, insomnia irritability, aggression, agitation, euphoria (IV).
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infections, cough.
Potentially Fatal: Hypersensitivity reactions including bronchospasm, angioedema, and multiorgan hypersensitivity syndrome known as drug rash with eosinophilia and systemic symptoms (DRESS).
Patient Counseling Information
This drug may cause dizziness, somnolence or impaired coordination, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC with differential, LFT, and renal function; signs of depression or suicidality at baseline and as clinically indicated.
Overdosage
Symptoms: Somnolence, dizziness, vertigo, balance disorder, fatigue, diplopia, nausea, anxiety and bradycardia. Management: Symptomatic and supportive treatment.
Drug Interactions
Significantly reduced systemic exposure with rifampicin. Plasma concentration may be increased when given with strong CYP2C19 inhibitors (e.g. fluconazole, fluvoxamine). Decreased plasma level with strong enzyme inducers (e.g. carbamazepine, phenytoin, phenobarbital). May increase the plasma concentrations of phenytoin, carbamazepine-epoxide, lansoprazole, omeprazole, diazepam. May decrease plasma level of efavirenz.
Food Interaction
High fat meals may delay rate but not the extent of absorption. May increase the CNS effects (e.g. psychomotor function, attention, memory) of alcohol. Systemic exposure may be reduced by St. John’s wort.
Action
Description: Brivaracetam is an analogue of levetiracetam. The exact mechanism is not yet fully elucidated; however, it displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may modulate the exocytotic release of neurotransmitters contributing to its anticonvulsant activity.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Delayed rate of absorption by approx 3 hours with high-fat meal. Bioavailability: Approx 100%. Time to peak plasma concentration: Approx 1 hour (fasting).
Distribution: Rapidly and evenly distributed into most body tissues. Volume of distribution: 0.5 L/kg. Plasma protein binding: ≤20%.
Metabolism: Metabolised in the liver primarily via hydrolysis of the amide moiety by hepatic and extrahepatic amidases to form carboxylic acid metabolite, and secondarily via hydroxylation on the propyl side chain mainly by CYP2C19 isoenzyme to form hydroxy metabolite. Both metabolites are inactive including the additional hydroxy acid metabolite.
Excretion: Mainly via urine (>95%; <10% as unchanged drug); faeces (<1%). Elimination half-life: Approx 9 hours.
Chemical Structure

Chemical Structure Image
Brivaracetam

Source: National Center for Biotechnology Information. PubChem Database. Brivaracetam, CID=9837243, https://pubchem.ncbi.nlm.nih.gov/compound/Brivaracetam (accessed on Jan. 21, 2020)

Storage
Store at 25°C. Oral solution/IV: Store at 25°C. Do not freeze.
MIMS Class
ATC Classification
N03AX23 - brivaracetam ; Belongs to the class of other antiepileptics.
References
Dean L. Brivaracetam Therapy and CYP2C19 Genotype. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). 2018 May. Accessed 10/07/2019. PMID: 29763212

Annotation of EMA Label for Brivaracetam and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 10/07/2019.

Annotation of FDA Label for Brivaracetam and CYP2C19. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 10/07/2019.

Anon. Brivaracetam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/07/2019.

Briviact Tablet, Film-Coated; Solution; Injection, Suspension (UCB, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/07/2019.

Buckingham R (ed). Brivaracetam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/07/2019.

Disclaimer: This information is independently developed by MIMS based on Brivaracetam from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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