Highlights
- •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.
Abstract
Objectives
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.
Results
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.
Discussion
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.
Keywords
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Article info
Publication history
Published online: April 08, 2023
Accepted:
February 21,
2023
Received in revised form:
February 21,
2023
Received:
January 9,
2023
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
