Can a patient with myoclonic seizure activity and migraines be prescribed BRIBIACT (brivaracetam), carbamazepine, gabapentin, and Topamax (topiramate) together?

From the Guidelines

No, a patient with myoclonic seizure activity and migraines should not be prescribed BRIBIACT (brivaracetam), carbamazepine, gabapentin, and Topamax (topiramate) together due to the potential for significant adverse effects and interactions. The combination of these medications may increase the risk of additive side effects, including dizziness, drowsiness, cognitive impairment, and hyponatremia. Additionally, carbamazepine can reduce the levels of both brivaracetam and topiramate through enzyme induction, which may lead to decreased efficacy or increased toxicity 1. According to the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline for the management of headache, gabapentin is not recommended for the prevention of episodic migraine due to insufficient evidence of its effectiveness and potential for misuse, dependence, and withdrawal 1. In contrast, topiramate is suggested for the prevention of episodic and chronic migraine, although the evidence is weak 1. Brivaracetam and carbamazepine may be considered for the treatment of myoclonic seizures, but their use in combination with topiramate and gabapentin requires careful consideration of the potential risks and benefits. A more appropriate approach may be to use a single medication or a combination of two medications with a more favorable safety profile, such as brivaracetam and topiramate, under close monitoring and with gradual dose adjustments as needed. Regular monitoring of drug levels, complete blood counts, liver function, electrolytes, and kidney function is essential to minimize the risk of adverse effects and interactions 1. Ultimately, the treatment plan should be individualized based on the patient's specific needs, medical history, and response to treatment, with careful consideration of the potential benefits and risks of each medication.

From the FDA Drug Label

Brivaracetam did not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, or 3A4. Brivaracetam weakly inhibited CYP2C19 and would not be expected to cause significant inhibition of CYP2C19 in humans. Table 5: Drug Interactions Between BRIVIACT and Concomitant Antiepileptic Drugs Concomitant AEDInfluence of AED on BRIVIACT Influence of BRIVIACT on AED

• Brivaracetam is a reversible inhibitor of epoxide hydrolase resulting in an increased concentration of carbamazepine epoxide, an active metabolite of carbamazepine The carbamazepine epoxide plasma concentration increased up to 198% at a BRIVIACT dose of 100 mg twice daily. Carbamazepine26% decrease in plasma concentrationNone for carbamazepine Increase of carbamazepine-epoxide metabolite* [see Drug Interactions (7. 2)] TopiramateNoneNone

The patient with myoclonic seizure activity and migraines can be prescribed BRIVIACT (brivaracetam) and Topamax (topiramate) together, as there are no known interactions between these two medications that would require a dose adjustment. However, when carbamazepine is added to the regimen, the patient's carbamazepine epoxide plasma concentration may increase up to 198% due to brivaracetam's inhibition of epoxide hydrolase. Additionally, gabapentin is not mentioned in the provided drug label as having any interactions with BRIVIACT (brivaracetam). Therefore, the combination of BRIVIACT (brivaracetam), carbamazepine, gabapentin, and Topamax (topiramate) may be prescribed together, but the patient should be closely monitored for any potential interactions, particularly with carbamazepine 2. Key considerations:

• Monitor carbamazepine levels and adjust the dose as needed to avoid toxicity.
• Closely monitor the patient for any signs of adverse reactions or interactions.
• Adjust the treatment regimen as needed to ensure the patient's safety and efficacy of treatment.

From the Research

Medication Interactions and Myoclonic Seizures

• The use of carbamazepine in patients with myoclonic seizures is generally not recommended, as it may aggravate myoclonic seizures 3, 4.
• Gabapentin is also listed as a medication that may exacerbate myoclonus or myoclonic seizures 4.
• Topiramate may be effective in treating myoclonic seizures, but there is still insufficient evidence for its use as monotherapy 3, 4.
• Brivaracetam is an antiepileptic drug that has shown promise in treating myoclonic seizures, but its use in combination with other medications such as carbamazepine may require careful consideration due to potential drug-drug interactions 5.

Potential Drug-Drug Interactions

• The combination of brivaracetam with carbamazepine may result in moderately lower brivaracetam plasma concentrations, but no dose adjustment is typically needed 5.
• The use of gabapentin and topiramate in combination with brivaracetam has not been extensively studied, and caution should be exercised when combining these medications.
• The potential for drug-drug interactions between these medications and other treatments, such as antidepressants, should also be considered, as some medications may increase the risk of myoclonic seizures or status epilepticus 6.