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Authors Klein P, Diaz A, Gasalla T, Whitesides J
Received 31 May 2017
Accepted for publication 23 August 2017
Published 19 January 2018 Volume 2018:10 Pages 1—22
DOI https://doi.org/10.2147/CPAA.S114072
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 3
Editor who approved publication: Professor Arthur Frankel
Abstract: Brivaracetam
(BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive
treatment of focal (partial-onset) seizures in adults. BRV is a selective,
high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher
affinity than levetiracetam, the first AED acting on SV2A. It has high lipid
solubility and rapid brain penetration, with engagement of the target molecule,
SV2A, within minutes of administration. BRV has potent broad-spectrum
antiepileptic activity in animal models. Phase I studies indicated BRV was well
tolerated and showed a favorable pharmacokinetic profile over a wide dose range
following single (10–1,000 mg) and multiple (200–800 mg/day) oral dosing. Three
pivotal Phase III studies have demonstrated promising efficacy and a good
safety and tolerability profile across doses of 50–200 mg/day in the adjunctive
treatment of refractory focal seizures. Long-term data indicate that the
response to BRV is sustained, with good tolerability and retention rate. BRV is
highly effective in patients experiencing secondarily generalized tonic–clonic
seizures. Safety data to date suggest a favorable psychiatric adverse effect
profile in controlled studies, although limited postmarketing data are
available. BRV is easy to use, with no titration and little drug–drug
interaction. It can be initiated at target dose with no titration. Efficacy is
seen on day 1 of oral use in a significant percentage of patients. Intravenous
administration in a 2-minute bolus and 15-minute infusion is well tolerated.
Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.
Keywords: brivaracetam, efficacy, epilepsy, focal seizures,
pharmacokinetics, tolerability