Earlier dose reductions of antiseizure meds linked to better cenobamate retention

Key takeaways:

• Researchers engaged in post hoc analysis of a phase 3 study examining four concomitant antiseizure meds to cenobamate.
• Earlier dose reductions of ASMs are beneficial during cenobamate titration.

ORLANDO — Earlier dose reductions of several concomitant antiseizure medications helped patients with uncontrolled focal seizures who require cenobamate administration, according to a poster at the American Epilepsy Society annual meeting.

“With a slower and lower titration, you could mitigate and decrease the risk,” William E. Rosenfeld, MD, a neurologist at the Comprehensive Epilepsy Care Center for Children and Adults in St. Louis, told Healio at the meeting.

Three prior studies of cenobamate established safety, efficacy and pharmacokinetics of the drug, while discovering that lowering doses of concomitant antiseizure medications (ASMs) were likely to lead to better retention of cenobamate when administration was necessary, the researchers wrote.

Rosenfeld and colleagues also reported that lowering strategic dose adjustments of concomitant ASMs may need to occur earlier than previously thought.

Researchers engaged in a separate dose-reduction study that aimed to determine when and how adjustments were necessary with six separate doses of cenobamate among a global population of 1,340 participants as well as a subset of 240 U.S.-based participants with uncontrolled focal seizures taking between one and three ASMs.

They increased doses of cenobamate from 12.5 mg to 200 mg per day biweekly, with additional increases to as much as 400 mg per day in biweekly 50 mg-per-day increments allowed, with adjustments to four main concomitant ASMs (clobazam, phenytoin, phenobarbital and lacosamide) allowed as well. Mean dosing by visit was tracked at 14 different intervals.

According to results, total mean clobazam reduction was 30% by visit 14, and the mean decrease in total dose for those taking more than 10 mg/day was 31% at visit nine in 109 patients and 37.9% at visit 14 in 100 patients.

Similarly, by visit nine, the mean total reduction for those taking phenytoin was 16.7%, and for those taking more than 100 mg/day, mean decrease was 20.2% among 71 patients. For phenobarbital, mean dose lowering from visit one to visit nine was from 71.4 to 53.3, and for lacosamide mean dose lowering went from 162.3 to 161.1.

“It’s consistent in the entire worldwide group of patients and in the post hoc group, both groups ended up lowering [the number of] concomitant medications,” Rosenfeld told Healio.