Brivaracetam

Brivaracetam

Systematic (IUPAC) name
(2S)-2-[(4R)-2-oxo- 4-propylpyrrolidin-1-yl] butanamide
Clinical data
Trade names	Briviact
AHFS/Drugs.com	entry
Pregnancy category	US: C (Risk not ruled out)
Legal status	US: V ℞ (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	Nearly 100%
Protein binding	<20%
Metabolism	Hydrolysis by amidase, CYP2C19-mediated hydroxylation
Biological half-life	8 hrs
Excretion	>75% renal
Identifiers
CAS Number	357336-20-0 Y[chemspider]
ATC code	N03AX23 (WHO)
PubChem	CID: 9837243
ChemSpider	8012964 Y
UNII	U863JGG2IA Y
KEGG	D08879
ChEMBL	CHEMBL607400 Y
Chemical data
Formula	C11H20N2O2
Molecular mass	212.15 g/mol
SMILES O=C(N)[C@@H](N1C(=O)C[C@@H](CCC)C1)CC
InChI InChI=1S/C11H20N2O2/c1-3-5-8-6-10(14)13(7-8)9(4-2)11(12)15/h8-9H,3-7H2,1-2H3,(H2,12,15)/t8-,9+/m1/s1 Y Key:MSYKRHVOOPPJKU-BDAKNGLRSA-N Y
Physical data
Melting point	72 to 77 °C (162 to 171 °F)
Specific rotation	[α]D −60°

Brivaracetam (trade name Briviact), a chemical analog of levetiracetam, is a racetam derivative with anticonvulsant (antiepileptic) properties. It is marketed by the pharmaceutical company UCB.

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 patients younger than 16 years.

Adverse effects

The most common adverse effects include sleepiness, dizziness, nausea and vomiting. More rarely, coordination problems and changes in behaviour can occur.

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.

Pharmacology

Mechanism of action

Brivaracetam is believed to act by binding to the ubiquitous synaptic vesicle glycoprotein 2A (SV2A), like levetiracetam. SV2A plays a role in exocytosis of various neurotransmitters. The exact mechanism is still unclear.

Pharmacokinetics

Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of 7 to 8 hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the acetamide group, and secondarily through hydroxylation mediated by the liver enzyme CYP2C19. 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.

Chemical and physical properties

Levetiracetam, for comparison

Brivaracetam is the 4R-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 10 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, and on 18 February 2016, the Food and Drug Administration approved brivaracetam under the trade name Briviact. The Drug Enforcement Administration (DEA) has issued an interim final rule placing brivaracetam into schedule V of the Controlled Substances Act (CSA) effective 12 May 2016. As of May 2016, brivaracetam is not approved in other countries, including Australia, Canada and Switzerland.