Comprehensive Monograph on Brivaracetam

I. Executive Summary

Brivaracetam, marketed as Briviact®, is a third-generation antiepileptic drug (AED) developed as a chemical analog of levetiracetam.[1] Its primary mechanism of action is characterized by a high-affinity, selective binding to the synaptic vesicle glycoprotein 2A (SV2A), a key protein in the modulation of neurotransmitter release.[3] This interaction is significantly more potent than that of its predecessor, with a 15- to 30-fold greater affinity for the SV2A target, which is believed to underpin its potent anticonvulsant effects.[4]

Clinically, brivaracetam is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of partial-onset seizures, with indications spanning from monotherapy to adjunctive treatment in both adult and pediatric populations as young as one month of age.[7] Its efficacy has been robustly demonstrated in several pivotal Phase III clinical trials, where it significantly reduced seizure frequency compared to placebo.[10] A key clinical advantage is its favorable pharmacokinetic profile, which includes rapid and near-complete oral absorption, high bioavailability approaching 100%, low plasma protein binding, and rapid penetration into the central nervous system.[1] This profile allows for the initiation of treatment at a therapeutic dose without the need for gradual titration, facilitating a rapid onset of clinical effect.[4]