: 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.

Cenobamate: A Review of its Pharmacological Properties, Clinical Efficacy and Tolerability Profile in the Treatment of Epilepsy / M. Antonietta Barbieri, E. Perucca, E. Spina, P. Rota, V. Franco. - In: CNS & NEUROLOGICAL DISORDERS. DRUG TARGETS. - ISSN 1871-5273. - (2022). [Epub ahead of print] [10.2174/1871527321666220113110044]

Cenobamate: A Review of its Pharmacological Properties, Clinical Efficacy and Tolerability Profile in the Treatment of Epilepsy

P. Rota
Penultimo
;
2022

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.
Cenobamate; efficacy; epilepsy; pharmacokinetics; pharmacology; review; safety
Settore BIO/14 - Farmacologia
Settore BIO/10 - Biochimica
2022
13-gen-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
BMS-CNSNDDT-2021-140.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 838.11 kB
Formato Adobe PDF
838.11 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/901845
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact