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

From the Guidelines

Prescribing BRIBIACT (brivaracetam), carbamazepine, gabapentin, and Topamax (topiramate) together for a patient with myoclonus and migraines is not recommended due to the lack of evidence supporting the safety and efficacy of this combination, as well as concerns about polypharmacy and potential adverse effects. According to the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline for the management of headache 1, there is insufficient evidence to recommend for or against any specific combination of therapies for the prevention of headache.

Key Considerations

• The guideline suggests that topiramate has a "weak for" recommendation for the prevention of both episodic and chronic migraines, with statistically significant reductions in monthly migraine days 1.
• Gabapentin is not recommended for the prevention of episodic migraines due to a lack of evidence supporting its effectiveness 1.
• BRIBIACT (brivaracetam) and carbamazepine are not specifically mentioned in the guideline as treatments for migraines, but they may be considered for myoclonus symptoms.
• The use of multiple anticonvulsants, such as BRIBIACT, carbamazepine, gabapentin, and topiramate, may increase the risk of adverse effects, including central nervous system depression, cognitive impairment, and hyponatremia.

Alternative Approaches

• Consider using one or at most two medications, carefully selected based on the patient's specific symptoms and tolerability.
• For myoclonic symptoms, BRIBIACT or topiramate might be preferred.
• For migraine prevention, topiramate is FDA-approved and often effective at doses of 50-100mg twice daily.
• Gabapentin could be considered for pain modulation in migraines, but its use should be carefully evaluated due to the lack of evidence supporting its effectiveness for migraine prevention.

Monitoring and Titration

• If combination therapy is necessary, careful titration starting with low doses is essential, with close monitoring for side effects like dizziness, somnolence, cognitive impairment, and hyponatremia.
• The goal should be to achieve symptom control with the minimum effective medication regimen to reduce the risk of adverse effects and drug interactions.

From the FDA Drug Label

Brivaracetam has not been studied in patients undergoing hemodialysis [see Use in Specific Populations (8. 6)]. In Vivo Assessment of Drug Interactions Drug Interaction Studies with Antiepileptic Drugs (AEDs) Potential interactions between BRIVIACT (25 mg twice daily to 100 mg twice daily) and other AEDs were investigated in a pooled analysis of plasma drug concentrations from all Phase 2 and 3 studies and in a population exposure-response analysis of placebo-controlled, Phase 3 studies in adjunctive therapy in the treatment of partial-onset seizures. None of the interactions require changes in the dose of BRIVIACT. Interactions with carbamazepine and phenytoin can be clinically important [see Drug Interactions (7.2) and (7. 3)]. The interactions are summarized in Table 5. 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. † At a supratherapeutic dose of 400 mg/day brivaracetam, there was a 20% increase in phenytoin plasma concentration. Carbamazepine26% decrease in plasma concentrationNone for carbamazepine Increase of carbamazepine-epoxide metabolite* [see Drug Interactions (7. 2)] TopiramateNoneNone

The patient with myoclonus 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 change of BRIVIACT. However, when carbamazepine is added to this combination, there is a potential for a clinically important interaction, as brivaracetam can increase the concentration of carbamazepine epoxide, an active metabolite of carbamazepine. Additionally, there is no information about the interaction between gabapentin and BRIVIACT, so caution should be exercised when combining these medications. It is recommended to monitor the patient closely for any potential interactions or adverse effects when prescribing this combination of medications 2. Key considerations for the combination of these medications include:

• Monitoring for increased concentrations of carbamazepine epoxide
• Potential for decreased plasma concentration of carbamazepine
• Unknown interaction between gabapentin and BRIVIACT
• Close monitoring of the patient for adverse effects or interactions.

From the Research

Treatment of Myoclonus and Migraines

• The treatment of myoclonus requires an understanding of the physiopathology of the condition, and the first step is to determine if there is an epileptic component to the myoclonus and treat accordingly 3.
• Cortical myoclonus can be treated with levetiracetam, valproic acid, and clonazepam as first-line agents, while phenytoin and carbamazepine may paradoxically worsen myoclonus 3.
• For progressive myoclonus epilepsies (PMEs), traditional antiepileptic drugs such as valproate, clonazepam, and phenobarbital may improve overall performance, and newer drugs like piracetam, levetiracetam, topiramate, zonisamide, and perampanel may also be effective 4.
• However, certain drugs like phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin may aggravate myoclonus or myoclonic seizures 4.

Potential Interactions and Side Effects

• Topiramate has been reported to induce myoclonus and psychosis in some patients, particularly at higher doses 5.
• Gabapentin and pregabalin may also induce myoclonus, particularly in patients with renal insufficiency, and this side effect is reversible upon discontinuation of the medication 6.
• Carbamazepine may worsen myoclonus, and its use should be avoided in patients with this condition 3, 4.
• BRIBIACT (brivaracetam) has been studied in patients with Unverricht-Lundborg disease, a type of PME, but the results were disappointing 4.

Considerations for Combination Therapy

• The use of multiple antiepileptic drugs, including BRIBIACT (brivaracetam), carbamazepine, gabapentin, and Topamax (topiramate), in combination may increase the risk of adverse effects and interactions 7.
• Patients with myoclonus and migraines should be closely monitored for potential side effects and interactions when using combination therapy, and the dosage of each medication should be carefully adjusted to minimize the risk of adverse effects 7.