Brivaracetam (BRV), a high-affinity synaptic vesicle
protein 2A
ligand, reported to be 10-30-fold more potent than
levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and
generalized seizures. BRV and LEV similarly bind to synaptic vesicle
protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and
AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal
voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive
therapy for patients with
partial seizures. In patients with
photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with
focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the
acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other
antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling
seizures when used at doses between 50 and 200 mg/d. The
drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include
fatigue,
dizziness, and
somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical practice. Finally, pharmacological properties of BRV are summarized with a description of its pharmacokinetics, safety, and potential/known
drug-drug interactions.