From the Research
The combination of felbamate, clobazam (Onfi), and brivaracetam is used for refractory epilepsy, with therapeutic ranges of 30-100 mcg/mL for felbamate, 0.2-2.0 mcg/mL for brivaracetam, and 30-300 ng/mL for clobazam, and these levels should be checked at trough. With a felbamate level of 140 mcg/mL, the patient is above the therapeutic range and at risk for concentration-dependent adverse effects including hepatotoxicity and aplastic anemia, so a dose reduction should be considered, as supported by a study from 1 which found that high felbamate levels were associated with increased side effects. The brivaracetam level of 2.9 mcg/mL is slightly above the typical therapeutic range, which may be acceptable if the patient is tolerating it well without side effects like dizziness, fatigue, or behavioral changes, but if the patient is experiencing adverse effects, consider reducing the brivaracetam dose as well. Regular monitoring of complete blood counts and liver function tests is essential with felbamate therapy due to its serious potential adverse effects, as highlighted in a study from 2 which found that felbamate was not associated with an increased risk of drug-induced liver injury. Dose adjustments should be made gradually to avoid breakthrough seizures. Some key points to consider when managing this combination include:
- Monitoring for adverse effects such as hepatotoxicity and aplastic anemia with felbamate
- Regularly checking trough levels to ensure therapeutic ranges are maintained
- Gradually adjusting doses to avoid breakthrough seizures
- Considering the potential for cognitive effects with antiseizure medications, as discussed in a study from 3, although the evidence for felbamate, clobazam, and brivaracetam is limited. It is also important to note that breastfeeding while on treatment with antiseizure medications is generally encouraged, but individualized counseling is necessary, as discussed in a study from 4.