- Design
- Retrospective single-centre cohort with historical comparison
- Population
- 213 patients on brivaracetam; 891 serum samples
- Primary outcome
- Serum brivaracetam concentration with and without cenobamate
- Effect
- +32% with cenobamate 12.5–50 mg/day (p=0.001); −21% with 250–450 mg/day (p<0.001)
A single-centre retrospective study compared routine serum brivaracetam concentrations in patients taking cenobamate with those in patients not taking it, using 891 samples from 213 patients and adjusting for enzyme-inducing co-medication.
At low cenobamate doses of 12.5 to 50 mg a day, brivaracetam concentrations were 32% higher. At high doses of 250 to 450 mg a day, they were 21% lower. Cenobamate inhibits CYP2C19, which metabolises brivaracetam, and at higher doses is known to induce CYP3A4 and other enzymes, which plausibly explains the reversal.
The combination is increasingly common in refractory epilepsy. The interaction matters most during cenobamate's long titration: early on, brivaracetam exposure rises and sedation may appear; later, as cenobamate reaches maintenance, brivaracetam may fall and seizure control could slip. The control group came from an earlier period and clinical outcomes were not measured, so the clinical impact needs prospective study.
- Consider measuring brivaracetam levels before starting cenobamate and again during titration.
- Watch for sedation or dizziness early in cenobamate titration in patients on brivaracetam.
- Review seizure control once cenobamate reaches higher maintenance doses, when brivaracetam may fall.
- Expect similar CYP2C19-mediated effects on other substrates, such as clobazam and phenytoin.
Why it matters
An interaction that reverses during titration will not be caught by a single level at the start.
Don't overread it
Serum level changes were shown, not changes in seizure control or side effects.
The statistics, in plain English
A 32% rise and a 21% fall are moderate changes and could matter for drugs with a narrow window of benefit and tolerability. Because the comparison group was treated in an earlier period, other changes in practice could contribute.
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