Cenobamate 25mg tablets

BACKGROUND Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. This drug can enhance the inactivated state of voltage-gated sodium channels, preferentially inhibiting the persistent component of the sodium channel current, and acts as a positive allosteric modulator of GABAA receptors, binding at a non-benzodiazepine site. OBJECTIVE We assessed the efficacy and safety of adjunctive cenobamate for the treatment of focal-onset seizures in adult patients with epilepsy using meta-analytical techniques. METHODS We systematically searched (May, week 4, 2020) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomized, placebo-controlled, single or double-blinded, add-on trials of cenobamate in adult patients with uncontrolled focal-onset seizures were identified. Main outcomes included the proportion of patients with ≥ 50 and 100% reduction in seizure frequency during the maintenance treatment period compared with baseline and the incidence of treatment withdrawal and adverse events (AEs). Risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome. RESULTS Two trials were included, overall enrolling 659 patients (442 for the add-on cenobamate group and 217 for the add-on placebo group). Seizure frequency reduction by at least 50% occurred during the maintenance phase in 50.1% of the patients randomized to cenobamate and 23.5% of the placebo-treated participants (RR 2.18, 95% CI 1.67-2.85; p < 0.001). The pooled estimated RR to achieve seizure freedom for the cenobamate group in comparison with placebo was 3.71 (95% CI 1.93-7.14; p < 0.001). Withdrawal from randomized treatment occurred in 16.7 and 11.1% of participants receiving cenobamate and placebo, respectively (RR 1.34, 95% CI 0.85-2.09; p = 0.205). Treatment was discontinued due to AEs in 12.2 and 4.1% of the patients in the active and control arms (RR 2.27, 95% CI 1.08-4.79; p = 0.031). AEs were reported in 76.9 and 66.8% of the patients during treatment with cenobamate and placebo (RR 1.14, 95% CI 1.02-1.26; p = 0.021). The cenobamate-associated AEs included somnolence, dizziness, fatigue, balance disorder, and diplopia. CONCLUSIONS Adjunctive cenobamate in adult patients with uncontrolled focal-onset seizures is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo

Abstract licence: CC BY-NC 4.0

ObjectivesAntiseizure medications (ASMs) can induce the activity of drug-metabolizing enzymes and drug transporters, including cytochrome P450 (CYP)2C9 and P-glycoprotein (P-gp). Our objective was to comparatively assess the effects of ASMs on exposure to clinical CYP2C9 and P-gp substrates.MethodsThis systematic review and network meta-analysis (NMA) was registered in PROSPERO (CRD42023473609) and performed following PRISMA 2020 guidelines. MEDLINE, EMBASE, and Cochrane Library were searched until October 22, 2025, with additional searches conducted in the FDA and EMA databases and ClinicalTrial.gov. Studies were included if they were prospective and the ASM was used as monotherapy for ≥5 days. The primary endpoint was the substrate area under the curve ratio (AUCR) with/without the ASM. Treatments were ranked by P-scores (range 0-1, higher values reflect stronger induction). The point estimate for indirect pairwise comparisons was the standardized mean difference (SMD). Bias risk was assessed using the PKclin tool.ResultsTwelve and six interventional pharmacokinetic studies with 227 and 97 participants were included in the CYP2C9 and P-gp NMAs, respectively. The ASM with the greatest CYP2C9 induction potential was carbamazepine (600 mg/day, P-score .78). The only statistically significant effect size estimate for CYP2C9 was obtained in the comparison between carbamazepine 600 mg/day and cenobamate 200 mg/day (SMD -.42; CI -.76, -.09). Carbamazepine (300 or 600 mg/day) was also the strongest P-gp inducer (P-scores, .79 and .55, respectively). The effects of its two doses did not differ, and 300 mg/day had a stronger effect on P-gp compared with the other ASMs.SignificanceDespite variability in populations, substrate drugs, and doses, our findings demonstrate that carbamazepine is an inducer at 300 mg/day, and that ASMs can rank differently as CYP2C9 versus P-gp inducers. Therefore, the safety of ASM polytherapy cannot be extrapolated from one pathway to another for treatment selection, for example, for post-stroke epilepsy.

Abstract licence: CC BY-NC-ND

ObjectiveAntiseizure medications (ASMs) are the cornerstone of epilepsy treatment. However, evidence on direct comparison of ASMs is lacking. This network meta-analysis evaluated the comparative efficacy and safety of approved and investigational add-on third-generation ASMs for focal epilepsy in adolescents and adults.MethodsData were retrieved through an extensive literature search of PubMed, Embase, Cochrane Library, and ClinicalTrial.gov databases from inception through August 2025. Findings were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline (CRD420251180027). Primary efficacy outcomes were ≥50 % and 100 % responder rates at 12-weeks maintenance duration. Secondary outcomes were corresponding responder rates at 8-weeks maintenance duration. Tolerability was assessed as retention rate. Treatment-emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were the safety outcomes.ResultsThe literature search retrieved 345 studies, of which 35 studies were included. All ASMs showed significantly higher responder rates compared with placebo. Significantly higher 100 % responder rate was observed with cenobamate (CNB; 400mg/d: Risk ratio [RR] 15; 95 % CI, 7.0-39; 200mg/d: RR 8.7; 95 % CI, 3.9-22) at a maintenance duration of 12 weeks and 8 weeks (400mg/d: RR 15; 95 % CI, 7.0-41; 200mg/d: RR 8.6; 95 % CI, 4.0-24). All ASMs showed a patient retention rate comparable with placebo. For overall TEAEs, brivaracetam (BRV; 50mg/d) and BRV ranked the lowest for individual and pooled doses, respectively; placebo ranked the highest in both cases. For TEAEs leading to treatment discontinuation, CNB ranked lower than the placebo.SignificanceAll approved and investigational ASMs were effective add-on treatments for focal epilepsy, with CNB demonstrating the greatest likelihood of achieving seizure freedom.

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BackgroundStatus epilepticus (SE) is a neurologic emergency characterized by prolonged or recurrent seizures leading to significant secondary brain injury, complications, morbidity and mortality. Timely and aggressive management is paramount to mitigate this disease burden, but response rates to first- and second-line antiseizure medications (ASMs) remain suboptimal. Cenobamate (CBM), a novel ASM, has shown great promise in clinical trials as an adjunctive agent for patients with refractory focal epilepsy, but little is known about its efficacy and safety for SE.ObjectiveThis systematic review aims to evaluate the efficacy and safety of CBM for managing SE, refractory SE and super-refractory SE (SRSE).MethodsPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A literature search was conducted across MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL. Original research involving adult patients with SE treated with CBM were included, and study quality was assessed. Data on patient demographics, treatment protocols and outcomes were extracted.ResultsOf 62 articles screened, 4 studies met the inclusion criteria, comprising 2 full manuscripts and 2 conference abstracts. A total of five patients with SRSE were treated with CBM. Seizure cessation was observed in two patients (40%). Reported adverse events included somnolence and gastrointestinal disturbances.ConclusionsEvidence supporting the use of CBM for the management of patients with SE is limited. Further structured studies are needed to establish optimal dosing, efficacy and safety of CBM for patients with SE.

Abstract licence: CC BY

AbstractObjectiveCenobamate is a recently approved antiseizure medication that proved to be safe and effective in randomized controlled trials. However, little is known about its impact on some areas frequently affected by epilepsy. For this reason, we explored the effects of cenobamate on cognitive performance, as well as on negative affectivity and quality of life in a sample of patients with drug‐resistant epilepsy.MethodsTwo prospective cohort studies were carried out. In Study 1, 32 patients (22 men and 10 women) underwent a baseline (T0) and a short‐term (T1) neuropsychological assessment after 3 months of cenobamate administration. In Study 2, 22 patients (16 men and 6 women) from the T1 sample also underwent a baseline and a follow‐up evaluation (T2) 6 months after T0.ResultsNo significant differences were found in cognitive variables, negative affectivity, and quality of life either in Study 1 or Study 2. Similarly, based on the reliable change index, it was found that most patients showed no changes in these variables.SignificanceThese results suggest that cenobamate is a safe antiseizure medication in terms of cognition, negative affectivity, or quality of life since no adverse events have been found after 3 and 6 months of treatment.Plain Language SummaryCenobamate is a new antiseizure medication. In patients with epilepsy, cenobamate seems to not affect cognition, anxiety, depression, or quality of life.

Abstract licence: CC BY-NC-ND 4.0