Brief Communication| Volume 142, 109156, May 2023

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The cenobamate-clobazam interaction- evidence of synergy in addition to pharmacokinetic interaction


      • Clobazam dose should be reduced 2–4 weeks after addition of cenobamate.
      • There may be a synergistic interaction between cenobamate and clobazam.
      • Addition of small clobazam dose can be considered in patients not seizure-free on cenobamate.



      Report insights into the pharmacokinetic and pharmacodynamic interaction between cenobamate (CNB) and clobazam (CLB), derived from data in patients enrolled at our center in a global multicenter open-label safety study of CNB.

      Materials & Methods

      Patients in this study either took CLB at baseline (n = 6) or had CLB added after CNB titration to maximal dose (n = 5) in addition to other antiseizure medications. Clobazam was always administered as a single bedtime dose. Random serum concentrations of CLB and N-desmethylclobazam (N-CLB) were obtained.


      Baseline daily CLB doses were 20–50 mg. Sedation began in the six baseline CLB patients at CNB doses of 25–100 mg. The N-CLB/ CLB ratio increased proportionally to the CNB dose. CLB was stopped in all six patients, five of whom were ≥50% responders. Seizure control deteriorated after stopping CLB, with only one remaining responder. Clobazam was restarted at 5 mg/d in five of the six patients. At the last follow-up, four of these patients were continuing CLB; two were seizure-free and 2 were ≥50% responders. Among the five patients that added 5 mg/d CLB de novo, three were responders. All patients were still on CNB at the end of the study.


      Data suggest starting CLB dose reduction at CNB doses of 25–100 mg/d. Due to possible synergy, the addition of low-dose CLB could be considered in patients with incomplete response to CNB.


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