苯巴那酯(cenobamate)的作用和副作用？

The role of cenobamate

It is suitable for the treatment of partial-onset epilepsy in adult patients. Its mode of action is believed to be mediated by blocking voltage-gated sodium channels and interacting with the GABAergic system. By activating the PI3K/Akt-CREB-BDNF pathway, it leads to an increase in the levels of anti-apoptotic factors and a decrease in the levels of pro-apoptotic factors, thereby inducing the inhibition of apoptosis and increasing neuronal survival.

Cenobamate significantly improves seizure control in focal drug-resistant epilepsy (DRE).

cenobamate

1. Heart disease: palpitations.

2. Ear and labyrinth diseases: dizziness.

3. Eye diseases: double vision, blurred vision.

4. Gastrointestinal diseases: nausea, constipation, diarrhea, vomiting, dry mouth, abdominal pain, and indigestion.

5. Infections and invasive diseases: nasopharyngitis, pharyngitis, urinary tract infection.

6. Metabolic and nutritional disorders: decreased appetite.

7. Musculoskeletal and connective tissue diseases: back pain, musculoskeletal pain, chest pain.

8. Nervous system diseases: drowsiness, dizziness, fatigue, headache, migraine, taste disorder, memory impairment, sedation, and tremor.

9. Skin and subcutaneous tissue diseases: itching, rash, papules.

Treatment with cenobamate

Fifty-seven patients received phenobarate for at least 3 months (median duration, 11 months), with a median dose of phenobarate of 250 mg/day. Six patients discontinued phenobarate due to poor efficacy and/or adverse events, and 1 patient died from factors unrelated to phenobarate.

Among patients who continued taking phenabate, 3 patients achieved seizure freedom (5.3% of the cohort), 24 patients experienced a 75%-99% reduction in seizures (42.1% of the cohort), and 16 patients experienced a 50%-74% reduction in seizures (28.1% of the cohort). Phenobarate resulted in the disappearance of focal to bilateral tonic-clonic seizures in 55.6% (20/36) of patients.

Among treatment responders, 67.4% (29/43) received phenidate doses ≥250 mg/day, and three-quarters of patients reported at least one side effect, most commonly fatigue and somnolence. The most common adverse events occurred at doses of ≥250 mg/day. Side effects can be partially controlled by reducing the overall burden of ASM.

While patients with highly active and ultra-refractory focal epilepsy have experienced meaningful seizure outcomes after taking phenobarnate, adverse events occurring at doses above 250 mg/day may limit the potential for further improvement in epilepsy control at higher doses of phenobarnate.

References:

Peña-Ceballos J, Moloney PB, Munteanu T, Doyle M, Colleran N, Liggan B, Breen A, Murphy S, El-Naggar H, Widdess-Walsh P, Delanty N. Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A "real-world" retrospective study. Epilepsia. 2023 May;64(5):1225-1235. doi: 10.1111/epi.17549. Epub 2023 Feb 27. PMID: 36790345.

Recommended related articles: