Cenobamate: A Review in Focal-Onset Seizures

Declarations

Funding The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest Tina Nie and Sheridan M. Hoy are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability Not applicable.

Additional information about this Adis Drug Review can be found here.

Abstract

Cenobamate (Ontozry®) is a once-daily oral antiseizure medication (ASM) approved in the EU for the adjunctive treatment of focal-onset seizures, with or without secondary generalisation, in adults with epilepsy that have not been adequately controlled despite previous treatment with ≥ 2 anti-epileptic drugs. In clinical studies, its short-term use significantly reduced seizure frequency and was associated with significantly higher odds of achieving a ≥ 50% reduction in seizure frequency in adults with uncontrolled focal-onset seizures despite treatment with 1–3 concomitant ASMs. Seizure freedom rates were also improved. All these benefits were sustained over up to 48 months. Cenobamate was generally well tolerated across both the short- and longer-term (up to 94 months) clinical studies, with its low starting dosage (12.5 mg/day) and slow (12-week) titration schedule appearing to result in fewer severe treatment-emergent adverse events (TEAEs) during the titration period. Somnolence, dizziness and fatigue were the most frequently reported TEAEs. The effectiveness and adverse events of cenobamate in real-world studies were consistent with those seen in the clinical studies. Thus, cenobamate continues to represent a useful adjunctive treatment option in adults with uncontrolled focal-onset seizures.

© Springer Nature Switzerland AG 2025