Brivaracetam, sold under the brand names Briviact and Brivajoy among others, a chemical analog of

levetiracetam Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formu ...

, is a

racetam Racetams are a class of drugs that share a pyrrolidone nucleus. Some, such as piracetam, aniracetam, oxiracetam, pramiracetam and phenylpiracetam are considered nootropics. Others such as levetiracetam, brivaracetam, and seletracetam are ant ...

derivative with

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

(antiepileptic) properties. It is marketed by the pharmaceutical company UCB. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

Medical uses

Brivaracetam is used to treat partial-onset seizures with or without secondary generalisation, in combination with other antiepileptic drugs. No data are available for its effectiveness and safety in people younger than 16 years of age.

Drugs.com Drugs.com is an online pharmaceutical encyclopedia that provides drug information for consumers and healthcare professionals, primarily in the United States. It self-describes its information as "accurate and independent" yet limited to being " ...

Adverse effects

The most common adverse effects include sleepiness,

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

and vomiting. More rarely, coordination problems and changes in behaviour (such as severe depression, aggression, hostility, impatience, rage, depression, suicide ideology, etc.) can occur.

Interactions

Coadministration of brivaracetam with

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...

may increase exposure to carbamazepine-epoxide, the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

of carbamazepine, and could theoretically lead to reduced tolerability. Coadministration of brivaracetam with

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

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.

Pharmacology

Mechanism of action

Brivaracetam is believed to act by binding to the ubiquitous synaptic vesicle glycoprotein 2A (SV2A), like levetiracetam. but with 20-fold greater affinity. There is some evidence that racetams including levetiracetam and brivaracetam access the luminal side of recycling synaptic vesicles during vesicular endocytosis. They may reduce excitatory neurotransmitter release and enhance synaptic depression during trains of high-frequency activity, such as is believed to occur during epileptic activity.

Pharmacokinetics

Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of seven to eight hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the

acetamide Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dime ...

group, and secondarily through hydroxylation mediated by the liver enzyme

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...

. The three major metabolites (hydroxy, acid, and hydroxyacid) are pharmacologically inactive. Brivaracetam is eliminated as urinary metabolites, with over 95% of a radioactive test dose recovered in the urine within 72 hours, including only 8.6% as unchanged brivaracetam.

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. 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.

Chemical and physical properties

Brivaracetam is the 4''R''-propyl analogue of the anticonvulsant levetiracetam.

History

Positive preliminary results from stage III trials were recorded in 2008, 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. On 14 January 2016, the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...

, and on 12 May 2016, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) approved brivaracetam under the trade name ''Briviact''. The

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic en ...

(DEA) issued an interim final rule placing brivaracetam into schedule V of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...

(CSA) effective 9 March 2017. , brivaracetam is not approved in some other countries. It was approved in Australia in August 2016. In Canada it was approved on 9 March 2016 under the trade name ''Brivlera''.

Legality

Australia

Brivaracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).Poisons Standard February 2020
. comlaw.gov.au A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."

References

External links

* {{Portal bar , Medicine Anticonvulsants Carboxamides Racetams