Introduction
Briviact (brivaracetam) is an antiepileptic drug (AED) approved by the FDA in 2016 for the treatment of partial-onset seizures in patients 4 years of age and older. It is a structural analog of levetiracetam with higher affinity for synaptic vesicle protein 2A (SV2A). Briviact represents an important addition to the armamentarium for epilepsy management, particularly for patients who have not achieved adequate seizure control with other AEDs.
Mechanism of Action
Brivaracetam demonstrates a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which is believed to mediate its anticonvulsant effects. Unlike levetiracetam, brivaracetam shows approximately 15- to 30-fold higher affinity for SV2A. The exact mechanism by which SV2A binding confers anticonvulsant activity remains incompletely understood, but it is thought to modulate neurotransmitter release and stabilize neuronal excitability. Brivaracetam also demonstrates inhibitory activity at neuronal voltage-gated sodium channels, which may contribute to its antiepileptic properties.
Indications
- Adjunctive therapy for partial-onset seizures in patients 4 years of age and older
- Monotherapy for partial-onset seizures in patients 16 years of age and older (following initial adjunctive therapy)
Dosage and Administration
Adults and adolescents (16 years and older):- Starting dose: 50 mg twice daily (100 mg/day)
- May be increased to 100 mg twice daily (200 mg/day) based on clinical response and tolerability
- Maximum recommended dose: 200 mg twice daily (400 mg/day)
- Weight-based dosing: 2 mg/kg/day divided twice daily
- Maximum dose: 200 mg/day
- Available as tablets (10 mg, 25 mg, 50 mg, 75 mg, 100 mg), oral solution (10 mg/mL), and intravenous injection (50 mg/5 mL)
- Oral forms may be taken with or without food
- IV administration should be administered as a 2-15 minute bolus
- Renal impairment: Dose adjustment recommended for CrCl < 50 mL/min
- Hepatic impairment: Dose adjustment recommended for moderate to severe impairment
Pharmacokinetics
Absorption: Rapid and almost complete (>95%) with median Tmax of 1 hour (fasting) Distribution: Volume of distribution approximately 0.5 L/kg; plasma protein binding ≤20% Metabolism: Primarily hydrolyzed via hepatic amidase-mediated metabolism; CYP2C8 and CYP2C19 play minor roles Elimination: Terminal half-life approximately 9 hours; primarily renal excretion (∼90% of administered dose) Special populations: Exposure increased in elderly patients and those with hepatic impairmentContraindications
- Hypersensitivity to brivaracetam or any component of the formulation
Warnings and Precautions
Suicidal Behavior and Ideation: AEDs increase the risk of suicidal thoughts and behavior Neurological Effects: Somnolence, fatigue, dizziness, and coordination difficulties may occur Psychiatric Symptoms: May cause irritability, aggression, and psychotic symptoms Withdrawal: Abrupt discontinuation may increase seizure frequency; taper gradually Hematologic Effects: May cause decreased white blood cell count Hepatic Effects: Monitor liver function tests periodicallyDrug Interactions
Strong CYP2C19 Inducers: Rifampin may decrease brivaracetam concentrations CNS Depressants: Additive effects with alcohol, benzodiazepines, and other sedatives Carbamazepine: May increase carbamazepine-epoxide levels Phenytoin: Brivaracetam may increase phenytoin concentrations in poor metabolizers of CYP2C9Adverse Effects
Common (≥10%): Somnolence, dizziness, fatigue, nausea, vomiting Less common (1-10%): Irritability, aggression, anxiety, insomnia, coordination difficulties Serious: Suicidal ideation, psychiatric reactions, hypersensitivity reactions, neutropeniaMonitoring Parameters
- Seizure frequency and type
- Neurological status (somnolence, coordination)
- Psychiatric symptoms (mood changes, aggression)
- Complete blood count (at baseline and periodically)
- Liver function tests (at baseline and periodically)
- Signs of hypersensitivity reactions
- Suicidal ideation and behavior
Patient Education
- Take medication exactly as prescribed; do not discontinue abruptly
- May cause drowsiness or dizziness; avoid driving or operating machinery until effects are known
- Avoid alcohol and other CNS depressants
- Report any mood changes, depression, or suicidal thoughts immediately
- Use effective contraception; discuss pregnancy planning with healthcare provider
- Keep all follow-up appointments for monitoring
- Notify healthcare provider of all other medications being taken
References
1. FDA Prescribing Information: Briviact (brivaracetam). Revised 2023. 2. Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of brivaracetam in adult patients with partial-onset seizures. Epilepsia. 2015;56(12):1890-1898. 3. Biton V, Berkovic SF, Abou-Khalil B, et al. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55(1):57-66. 4. Ryvlin P, Werhahn KJ, Blaszczyk B, et al. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55(1):47-56. 5. Lattanzi S, Brigo F, Grillo E, et al. Adjunctive brivaracetam in focal epilepsy: a systematic review and meta-analysis. CNS Drugs. 2019;33(4):335-345. 6. Stockis A, Rolan P. Clinical pharmacokinetics of brivaracetam. Clin Pharmacokinet. 2022;61(10):1357-1372.