Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy—expert opinion

Bernhard J Steinhoff,William E Rosenfeld,José M Serratosa,Christian Brandt,Pavel Klein,Manuel Toledo,Gregory L Krauss

doi:10.1016/j.yebeh.2021.108270

Abstract

Clinical trial results have demonstrated that adjunctive cenobamate (CNB) substantially decreases seizure frequency in adults with uncontrolled focal onset seizures with an acceptable and well-identified safety profile. This manuscript summarizes an expert panel’s recommendations regarding optimized CNB treatment of epilepsies with focal onset seizures. Cenobamate, when slowly titrated to the target maintenance dose, represents an effective new antiseizure medication (ASM) with a comparatively high rate of seizure freedom relative to existing treatment options. This paper reviews selection of suitable CNB treatment candidates, realistic treatment expectations and goals, appropriate CNB target doses, and methods to mitigate or avoid potential adverse events. Cenobamate can be a promising therapeutic choice for adult people with epilepsy with focal onset seizures who do not reach adequate seizure control despite treatment with conventional ASMs.

Highlights

IntroductionCenobamate backgroundCenobamate (CNB) preferentially blocks voltage-dependent sodium channels, by preferentially inhibiting the persistent sodium current, and acts as a positive allosteric modulator of c-aminobutyric acid (GABAA) receptors at a site distinct from benzodiazepines [1,2,3]
In the United States (US) prescribing information (PI), Cenobamate backgroundCenobamate (CNB) is indicated for the treatment of partial-onset seizures in adults [20]
The use of CNB is not recommended when the creatinine clearance (Clcr) falls below 15 mL/min or in patients with end-stage renal disease undergoing dialysis

Summary

Introduction

CNB preferentially blocks voltage-dependent sodium channels, by preferentially inhibiting the persistent sodium current, and acts as a positive allosteric modulator of c-aminobutyric acid (GABAA) receptors at a site distinct from benzodiazepines [1,2,3]. This dual mechanism of Abbreviations: ASM, antiseizure medication; C013, C017, C021: Clinical studies YKP3089C013, YKP3089C017, YKP3089C021; Clcr, creatinine clearance; CNB, cenobamate; CNS, central nervous system; DRE, drug-resistant epilepsy; DRESS, drug reaction with eosinophilia and systemic symptoms; GABAA, c-aminobutyric acid; ILAE, International League Against Epilepsy; OLE, open-label extension; TEAEs, treatment-emergent adverse events. Long-term outcomes were examined in their open-label extensions (OLEs), and long-term safety was assessed in an open-label study in over 1300 patients (C021, Sperling, et al.) [11,12,13]

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