Profile of brivaracetam and its potential in the treatment of epilepsy

Brivaracetam (BRV) (UCB 34714) is currently under review by the US Food and Drug Administration and European Medicines Agency for approval as an add-on treatment for adult patients with partial seizures. Similar to levetiracetam (LEV), BRVacts as a high-affinity ligand of the synaptic vesicle protein 2A, however, ithas been shown to be 10- to 30-fold more potent than LEV. Moreover, BRV does not share the LEV inhibitory activity on the high voltage Ca(2+) channels and AMPAreceptors, and it has been reported to act as a partial antagonist on neuronalvoltage-gated sodium channels. The pharmacokinetic profile of BRV is favorableand linear, and it undergoes an extensive metabolism into inactive compounds,mainly through the hydrolysis of its acetamide group. Furthermore, it does notsignificantly interact with other antiepileptic drugs and more than 95% isexcreted through the urine, with an unchanged fraction of 8%-11%. BRV has ahalf-life of approximately 8-9 hours and it is usually given twice daily. Todate, a wide range of experimental studies have reported the effectiveness of BRVwith regards to partial and generalized seizures. In humans, six randomized,placebo-controlled trials and two meta-analyses highlighted the efficacy, or goodtolerability, of BRV as an add-on treatment for patients with uncontrolledpartial seizures. A wide dose range of BRV has been evaluated in those trials(5-200 mg), but the most suitable for clinical use appears to be 50-100 mg/day.The most common adverse reactions to BRV are mild to moderate, transient, oftenimprove during the course of the treatment, and mainly consist of central nervoussystem symptoms, such as fatigue, dizziness, and somnolence. The aim of thispaper is to critically review the literature data regarding experimental animalmodels and clinical trials on BRV, and to define its potential usefulness for theclinicians who manage patients with epilepsy.