Brivaracetam
Clinical data | |
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Pronunciation | /ˌbrɪvəˈræsətəm/ BRIV-ə-RASS-ə-təm |
Trade names | Briviact, Nubriveo, Brivajoy |
AHFS/Drugs.com | Monograph |
MedlinePlus | a616027 |
License data |
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Pregnancy category |
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Routes of administration | By mouth, intravenous |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | Nearly 100% |
Protein binding | ≤20% |
Metabolism | Hydrolysis by amidase, CYP2C19-mediated hydroxylation |
Metabolites | 3 inactive metabolites |
Elimination half-life | ≈9 hours |
Excretion | Kidneys (>95%)[4] |
Identifiers | |
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JSmol) | |
Specific rotation | [α]D −60° |
Melting point | 72 to 77 °C (162 to 171 °F) |
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Brivaracetam, sold under the brand name Briviact among others, is a chemical analog of levetiracetam, a racetam derivative with anticonvulsant (antiepileptic) properties.[5][6] It is marketed by the pharmaceutical company UCB.[7][8]
A generic version of brivaracetam has been approved by the Food and Drug Administration (FDA) in the United States, but it is not yet available as a generic medication.[9][10]
Medical uses
Brivaracetam is used to treat partial- onset seizures with or without secondary generalization, in combination with other antiepileptic drugs. No data are available for its effectiveness and safety in people younger than 16 years of age.[11][12][13]
Adverse effects
The most common adverse effects include sleepiness, dizziness, nausea and vomiting. More rarely, coordination problems and changes in behaviour (such as severe depression, aggression, hostility, impatience, rage, suicidal ideation, etc.) can occur.[11][12]
No clinically relevant differences in adverse effects incidence for the starting doses were observed, except for a dose–response relationship for somnolence and fatigue.[14]
Interactions
Coadministration of brivaracetam with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine, and could theoretically lead to reduced tolerability. Coadministration of brivaracetam with phenytoin may increase phenytoin levels. Coadministration of other antiseizure drugs are unlikely to affect brivaracetam exposure. Brivaracetam provides no added therapeutic benefit when administered in conjunction with levetiracetam that acts on the same protein.[15]
No pharmacokinetic interaction was observed between single-dose 200mg brivaracetam and 0.6g/L ethanol in healthy subjects. However, brivaracetam approximately doubled the effect of alcohol on psychomotor function, attention and memory. Alcohol use while under brivaracetam treatment is not recommended.[12]
Pharmacology
Mechanism of action
Brivaracetam is believed to act by binding to the ubiquitous
Pharmacokinetics
Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an
Pharmacogenetics
As noted above, brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, "CYP2C19 poor metabolizers", will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea.[20] The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction.[4]
Chemical and physical properties
Brivaracetam is the 4R-propyl
History
Positive preliminary results from stage III trials were recorded in 2008,[21] along with evidence that it is around ten times more potent for the prevention of certain types of seizure in mouse models than its analogue levetiracetam.[22]
On 14 January 2016, the European Commission,[12] and on 18 February 2016, the U.S. Food and Drug Administration (FDA)[23] approved brivaracetam under the trade name Briviact. The Drug Enforcement Administration (DEA) issued an interim final rule[clarification needed] placing brivaracetam into schedule V of the Controlled Substances Act (CSA) effective 9 March 2017.[24] As of May 2016[update], brivaracetam is not approved in some other countries. It was approved in Australia in August 2016.[25] In Canada it was approved on 9 March 2016 under the trade name Brivlera.[26]
Society and culture
Brand names
It is sold under the brand name Brivlera in Canada.[27] In Argentina, it is sold under the brand Brivaxon from Raffo Laboratories and Briviact from Biopas Argentina. [28] [29]
References
- ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
- ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
- ^ "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
- ^ a b c "Briviact- brivaracetam tablet, film coated Briviact- brivaracetam solution Briviact- brivaracetam injection, suspension". DailyMed. U.S. National Library of Medicine. 15 May 2018. Archived from the original on 21 March 2021. Retrieved 25 January 2019.
- PMID 17199019.
- PMID 16044671.
- ^ "Briviact Product Page". UCB. Archived from the original on 19 September 2020. Retrieved 1 January 2020.
- ^ "Brivaracetam". DrugBank. Archived from the original on 10 January 2020. Retrieved 1 January 2020.
- ^ "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
- ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
- ^ a b Briviact Drugs.com
- ^ a b c d "Briviact". European Medicines Agency. Archived from the original on 10 June 2016. Retrieved 30 May 2016.
- PMID 35285519.
- PMID 29403319.
- PMID 18341673.
- PMID 18590620.
- ^ Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
- PMID 27768878.
- S2CID 14972675.
- from the original on 26 October 2020. Retrieved 7 February 2020.
- PMID 18552880.
- PMID 18500360.
- ^ "FDA approves Briviact to treat partial onset seizures". U.S. Food and Drug Administration (FDA). 19 February 2016. Archived from the original on 23 April 2019. Retrieved 20 May 2023.
- PMID 27192732.
- ^ "Australian Public Assessment Report for brivaracetam" (PDF). Therapeutic Goods Administration. 2017. Archived (PDF) from the original on 14 August 2021. Retrieved 13 June 2020.
- ^ UCB Canada Inc. (29 July 2020). "Health Canada Approves BRIVLERA® (brivaracetam) to treat partial-onset seizures in pediatric epilepsy patients". Cision Canada. Archived from the original on 19 October 2021. Retrieved 16 October 2021.
- ^ UCB Canada Inc. (29 July 2020). "Health Canada Approves BRIVLERA® (brivaracetam) to treat partial-onset seizures in pediatric epilepsy patients". Cision Canada. Archived from the original on 19 October 2021. Retrieved 16 October 2021.
- ^ "Brivaxon". Laboratorios Raffo. Retrieved 12 April 2024.
- ^ "Biopas Portal para Médicos". Biopas Colombia. Retrieved 12 April 2024.
Further reading
- Dean L (2018). "Brivaracetam Therapy and CYP2C19 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. PMID 29763212. Bookshelf ID: NBK500036.