Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability

Abstract

Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusually high seizure-free rates. 
 We sought to investigate the serum trough levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not.
 We analyzed samples from 101 PWEs treated with adjunct cenobamate under steady-state conditions. In all, 36 PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. 
 We found a linear correlation between the daily doses (range: 100 mg – 400 mg) and the plasma levels (3.8 mg/l – 54.6 mg/l). 
 Neither the daily doses nor the plasma levels differed significantly between seizure-free and non-responding PWEs or between PWEs with a satisfactory tolerability and those who experienced adverse events. 
 The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Still, to evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful.