From the Research
When initiating cenobamate therapy in a patient already on clobazam, it is recommended to reduce the dose of clobazam to 5-10 mg to minimize potential adverse effects and optimize seizure control. This adjustment is based on the most recent and highest quality study available, which suggests that maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial 1. The reduction in clobazam dose is necessary due to the pharmacokinetic interaction between cenobamate and clobazam, where cenobamate inhibits CYP2C19, an enzyme involved in clobazam metabolism, potentially leading to increased levels of N-desmethylclobazam and enhanced sedative effects 2, 3.
Some key points to consider when adjusting clobazam doses during cenobamate initiation include:
- Monitor the patient closely for increased sedation, dizziness, or other side effects
- Adjust the clobazam dose further based on clinical response and, if available, plasma levels of clobazam and its active metabolite N-desmethylclobazam
- Regular follow-ups during the first few weeks of co-administration are crucial to ensure optimal dosing and minimize side effects
- Be prepared to make further dose adjustments as needed based on the patient's individual response to the combination therapy
It is also important to note that the primary goal of the recommended dose reductions of concomitant antiseizure medications, including clobazam, is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control 2. Additionally, some studies suggest that the addition of low-dose clobazam could be considered in patients with incomplete response to cenobamate, due to possible synergy between the two medications 4.