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Cenobamate


Authors: prof. MUDr. Milan Brázdil, Ph.D.
Authors place of work: 1. neurologická klinika ;  LF MU a FN u sv. Anny v Brně ;  Centrum pro epilepsie Brno
Published in the journal: Cesk Slov Neurol N 2022; 85(5): 417-420
Category: Lékový profil

Summary

Cenobamate (CNB) is a novel antiepileptic drug with a dual mechanism of action indicated for the adjunctive treatment of focal-onset seizures in adult patients with epilepsy inadequately controlled despite prior treatment with at least two antiepileptic drugs. In therapeutic doses, it most likely acts through positive allosteric modulation of γ-aminobutyric acid type A (GABAA) receptors at the non-benzodiazepine binding site, as well as preferential inhibition of persistent sodium currents and enhancement of the deactivated state of voltage-gated sodium channels. Numerous clinical experiences with cenobamate testify to its high effectiveness in terms of achieving seizure-freedom, even in patients who are still drug-resistant. At the same time, CNB appears to be a well-tolerated drug with a minimum of adverse events. However, attention must be paid to potential pharmacokinetic interactions and gradual titration when starting treatment. It is contraindicated in patients with a rare familial occurrence of a short QT interval. Its recommended dosage is 200–400 mg/d taken in one daily dose.

Keywords:

pharmacoresistance – Epilepsy – cenobamate – adjunctive treatment


Zdroje

1. Latimer DR, Edinoff AN, Ruff RD et al. Cenobamate, a sodium channel inhibitor and positive allosteric modulator of GABAA ion channels, for partial onset seizures in adults: a comprehensive review and clinical implications. Neurol Int 2021; 13 (2): 252–265. doi: 10.3390/neurolint13020026.

2. Darpo B, Sager PT, Xue H et al. A phase 1 clinical study evaluating the effects of cenobamate on the QT interval. Clin Pharmacol Drug Dev 2022; 11 (4): 523–534. doi: 10.1002/cpdd.1077.

3. Summary of product characteristics. Ontozry (Cenobamate) Angelini Pharma S.p.A., 26. 3. 2021.

4. Roberti R, De Caro C, Iannone LF et al. Pharmacology of cenobamate: mechanism of action, pharmacokinetics, drug-drug interactions and tolerability. CNS Drugs 2021; 35 (6): 609–618. doi: 10.1007/s40263-021-00 819-8.

5. Chung SS, French JA, Kowalski J et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology 2020; 94 (22): e2311–e2322. doi: 10.1212/WNL.0000000000009530.

6. Krauss GL, Klein P, Brandt C et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol 2020; 19 (1): 38–48. doi: 10.1016/S1474-4422 (19) 30399-0.

7. Sperling MR, Klein P, Aboumatar S et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open-label safety study. Epilepsia 2020; 61 (6): 1099–1108. doi: 10.1111/epi.16525.

8. Sander L, Rosenfeld WE, Halford JJ et al. Long-term individual retention in cenobamate in adults with focal seizures: Pooled data from the clinical development program. Epilepsia 2022; 63 (1): 139–149. doi: 10.1111/epi.17134.

9. Elliott T, Ridley-Pryor T, Gienapp AJ et al. Initial real -⁠ -world experience with cenobamate in adolescents and adults: a single center experience. Pediatr Neurol 2022; 129 : 19–23. doi: 10.1016/j.pediatrneurol.2022.01.001.

10. Connor GS, Williamson A. Effectiveness and safety of adjunctive cenobamate for focal seizures in adults with developmental disability treated in clinical practice. Epilepsy Behav Rep 2022; 18 : 100533. doi: 10.1016/j.ebr.2022.100533.

11.Rosenfeld WE, Ferrari L, Kamin M. Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study. Epilepsy Res 2022; 183 : 106940. doi: 10.1016/j.eplepsyres.2022.106940.

12. Steinhoff BJ, Rosenfeld WE, Serratosa JM et al. Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy –⁠ expert opinion. Epilepsy Behav 2021; 123 : 108270. doi: 10.1016/j.yebeh.2021.108270.

Štítky
Dětská neurologie Neurochirurgie Neurologie

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 5

2022 Číslo 5
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