Brivaracetam Therapy and CYP2C19 Genotype

Review
In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
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Excerpt

Brivaracetam (brand name Briviact) is an antiseizure drug used in the treatment of partial-onset (focal) epilepsy in adults. It is thought to act by binding to a synaptic vesicle glycoprotein, SV2A, and reducing the release of neurotransmitters.

Brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation.

Individuals who have no CYP2C19 enzyme activity, “CYP2C19 poor metabolizers”, will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea.

The recommended starting dosage for brivaracetam monotherapy or adjunctive therapy is 50 mg twice daily (100 mg per day). Based on how the individual responds, the dose of brivaracetam may be decreased to 25 mg twice daily (50 mg per day) or increased up to 100 mg twice daily (200 mg per day) (1).

The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction (Table 1). Approximately 2% of Caucasians, 4% of African Americans, and 14% of Chinese are CYP2C19 poor metabolizers (1).

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