A retrospective non-interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam.

Cenobamate is an antiseizure medication (ASM) approved for treatment of partial onset seizures in adults. As both inductor and inhibitor of hepatic enzymes, cenobamate affects metabolism of other ASMs, amongst which is clobazam. To our knowledge, the extent of interaction between cenobamate and clobazam and its clinical significance have not been studied yet. In this retrospective study we assessed serum concentrations of clobazam and N- desmethylclobazam in 5 patients before and after co-medication with cenobamate and calculated the percentage increase in concentration-to-dose ratio (CDR) of both. We were able to demonstrate that addition of cenobamate resulted in an increase in serum concentration and consequently in CDR of N-desmethylclobazam in all patients. However this occurred in variable degrees: NCLB concentration showed an increase of 1208 μg/l (CDR145%) in one patient and between 1691μ/l (CDR 819 %) and 3995 μ/l (CDR 1,852%) in the other four. This resulted in fatigue, which improved after dose reduction of CLB. Hence, it is to be concluded that concomitant administration of cenobamate and clobazam can lead to a substantial increase in serum concentrations of N-desmethylclobazam. This can have a positive therapeutic effect on one hand. However, on the other hand, this can lead to unwanted fatigue.