Title:Cenobamate: A Review of its Pharmacological Properties, Clinical Efficacy
and Tolerability Profile in the Treatment of Epilepsy
Volume: 22
Issue: 3
Author(s): Maria Antonietta Barbieri*, Emilio Perucca, Edoardo Spina, Paola Rota and Valentina Franco
Affiliation:
- Department of Clinical and Experimental Medicine, University of Messina, Torre Biologica 5th floor, "AOU" Policlinico
G. Martino Via C. Valeria, Gazzi 98125 Messina, Italy
Keywords:
Cenobamate, epilepsy, pharmacology, pharmacokinetics, efficacy, safety.
Abstract: Cenobamate is a novel antiseizure medication (ASM) commercially available in Europe
and in the U.S. for the treatment of focal seizures in adults. The mechanisms responsible for its antiseizure
activity include enhancement of the inactivated state of voltage-gated sodium channels with
blockade of the persistent sodium current and positive allosteric modulation of GABAA receptors at
a non-benzodiazepine binding site. Cenobamate has a high oral bioavailability that is not influenced
by food intake. The terminal half-life is 50-60 hours, allowing for once-daily dosing. Cenobamate
is a CYP2C19 inhibitor and an inducer of CYP3A4 and CYP2B6, and consequently, it can
cause a number of drug-drug interactions. Efficacy and safety have been evaluated in two randomized,
double-blind, placebo-controlled adjunctive therapy trials in adults with focal seizures. In
both trials, cenobamate decreased significantly the frequency of focal seizures, with relatively high
seizure freedom rates. Adverse events most commonly reported in double-blind trials included
dizziness, somnolence, headache, fatigue, and diplopia. The occurrence of three cases of drug reaction
with eosinophilia and systemic symptoms (DRESS) during early clinical development led to
the conduction of a Phase 3 open-label long-term safety study in a total of 1339 patients. In this
study, no serious idiosyncratic adverse reactions were observed using a start-low and go-slow approach.
Further studies are required to determine whether the clinical activity profile of cenobamate
extends to protection against other seizure types and to evaluate its efficacy and safety profile
in special patient groups such as infants, children, the elderly, and patients with comorbid conditions.
