Brivaracetam: a novel antiepileptic drug for focal-onset seizures

Linda J Stephen, Martin J Brodie, Linda J Stephen, Martin J Brodie

Abstract

Brivaracetam (BRV), the n-propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

Keywords: antiepileptic drug; brivaracetam; epilepsy; focal-onset; seizures; synaptic vesicle protein 2A.

Conflict of interest statement

Conflict of interest statement: Martin Brodie serves on the scientific advisory boards of Eisai Ltd, UCB Pharma, GlaxoSmithKline, Lundbeck, Bial, GW Pharmaceuticals and Takeda. He is on the speakers’ bureau for Eisai Ltd, UCB Pharma, GlaxoSmithKline and Lundbeck and has accepted travel grants for scientific meetings from Eisai Ltd, UCB Pharma and Lundbeck. Linda Stephen has received lecture fees and support for travel to congresses from UCB Pharma and Eisai Ltd.

Figures

Figure 1.
Figure 1.
Chemical structures of levetiracetam and brivaracetam.

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