Brivaracetam

Brivaracetam (brand name Briviact) is a prescription medication in the anticonvulsant class approved by the U.S. Food and Drug Administration (FDA) for the management of partial-onset seizures in patients with epilepsy.

It is indicated as adjunctive therapy in adults and children one month of age and older who experience focal seizures. Brivaracetam binds selectively to synaptic vesicle glycoprotein 2A (SV2A) in the brain, modulating neurotransmitter release and stabilizing neuronal activity to reduce seizure frequency.

Brivaracetam has a favorable pharmacokinetic profile with rapid absorption, minimal protein binding, and a low potential for drug–drug interactions, making it a widely used option in epilepsy management.

The primary gene involved in the metabolism of brivaracetam is CYP2C19, a member of the cytochrome P450 enzyme family. CYP2C19 is responsible for the hepatic biotransformation of many drugs by adding a chemical group that facilitates excretion.

Genetic variations in CYP2C19 can lead to different metabolizer phenotypes—normal, intermediate, or poor—depending on how much functional enzyme is produced. These differences can influence how quickly brivaracetam is cleared from the body and thus affect overall drug exposure.

Patients with reduced CYP2C19 activity (intermediate or poor metabolizers) may have higher systemic concentrations of brivaracetam compared to normal metabolizers, potentially increasing the risk of adverse effects. Conversely, individuals with normal or enhanced CYP2C19 activity clear the drug at expected rates, maintaining standard efficacy and tolerability profiles.

Normal Metabolizer

• Effect on drug levels: Typical systemic concentrations, consistent with standard dosing.
• Clinical consequence: Expected seizure control and tolerability at recommended doses.
• Side effects: Usual side effects (e.g., somnolence, dizziness) at standard frequency and severity.

Intermediate Metabolizer

• Effect on drug levels: Moderately increased systemic concentrations compared to normal metabolizers.
• Clinical consequence: Potential for higher efficacy but increased risk of adverse reactions.
• Side effects: Possible mild to moderate somnolence or dizziness occurring more frequently; generally transient.

Poor Metabolizer

• Effect on drug levels: Significantly increased systemic concentrations due to reduced clearance.
• Clinical consequence: Elevated risk of dose-related adverse effects.
• Side effects: More pronounced central nervous system side effects (e.g., fatigue, headache) with higher severity; monitor closely.

Indeterminate

• Effect on drug levels: Unknown
• Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring.
• Side effects: Cannot predict genotype impact; monitor for typical adverse events.

Not Available

• Effect on drug levels: Unknown
• Clinical consequence: No FDA guidance for this phenotype.
• Side effects: Standard side effect profile; clinical monitoring recommended.

CYP2C19 Dosing Guideline

No alternative pharmacogenetic-based dosing recommendations are provided in current FDA guidelines for brivaracetam. Clinicians may consider other antiepileptic medications such as levetiracetam or lacosamide based on individual patient response and tolerability.

• FDA – Table of Pharmacogenetic Associations