What is the use and dosage of Briviact (brivaracetam) in treating epilepsy?

Brivaracetam (Briviact) for Epilepsy Treatment

Brivaracetam (Briviact) is indicated for the treatment of partial-onset seizures in patients 1 month of age and older, with a recommended starting dosage of 50 mg twice daily (100 mg per day) in adults, which can be adjusted based on clinical response and tolerability. 1

Mechanism of Action and Pharmacology

• Brivaracetam is a selective, high-affinity ligand for synaptic vesicle protein 2A (SV2A) with 15-30 fold higher affinity than levetiracetam 2
• It has high lipid solubility and rapid brain penetration, engaging the SV2A target molecule within minutes of administration 2
• The drug demonstrates potent broad-spectrum antiepileptic activity in animal models 2
• Brivaracetam has a favorable pharmacokinetic profile with linear and dose-proportional pharmacokinetics at therapeutic doses 3

Dosing Guidelines

Adults (16 years and older):

• Initial dosage: 50 mg twice daily (100 mg per day) 1
• Maintenance dosage range: 25-100 mg twice daily (50-200 mg per day) 1
• No titration is required when initiating treatment 1, 2

Pediatric Patients:

• For patients weighing ≥50 kg: Same as adult dosing 1
• For patients weighing 20 kg to <50 kg: 0.5-1 mg/kg twice daily initially, with maintenance of 0.5-2 mg/kg twice daily 1
• For patients weighing 11 kg to <20 kg: 0.5-1.25 mg/kg twice daily initially, with maintenance of 0.5-2.5 mg/kg twice daily 1
• For patients weighing <11 kg: 0.75-1.5 mg/kg twice daily initially, with maintenance of 0.75-3 mg/kg twice daily 1

Hepatic Impairment:

• Dose adjustment is recommended for all stages of hepatic impairment 1

Administration Options

• Oral tablets: Can be taken with or without food, should be swallowed whole 1
• Oral solution: 10 mg/mL, no dilution necessary 1
• Intravenous injection: Can be administered over 2-15 minutes when oral administration is temporarily not feasible, at the same dosage as oral formulations 1

Clinical Efficacy

• Phase III studies have demonstrated promising efficacy across doses of 50-200 mg/day in the adjunctive treatment of refractory focal seizures 2
• Responder rates (≥50% seizure reduction) range from 32.7% to 55.8% for 50 mg/day, 36% to 38.9% for 100 mg/day, and 37.8% for 200 mg/day 4
• Efficacy is seen on day 1 of oral use in a significant percentage of patients 2
• Long-term data indicate that the response to brivaracetam is sustained, with good tolerability and retention rate 2
• Brivaracetam is highly effective in patients experiencing secondarily generalized tonic-clonic seizures 2

Safety and Tolerability

• Most common adverse reactions in adults include somnolence/sedation, dizziness, fatigue, and nausea/vomiting 1
• Pediatric patients experience similar adverse reactions to adults 1
• Brivaracetam has a favorable psychiatric adverse effect profile in controlled studies 2
• Rare adverse effects include mild somnolence (6.4%), psychosis (3.2%), and nausea (3.2%) 5

Drug Interactions

• Brivaracetam has few clinically relevant drug-drug interactions 3
• Rifampin: Consider increasing brivaracetam dosage when used concomitantly 1
• Carbamazepine: Consider reducing carbamazepine dosage if tolerability issues arise 1
• Phenytoin: Monitor phenytoin levels when used with brivaracetam 1
• Levetiracetam: No added therapeutic benefit when co-administered 1

Special Considerations

• Avoid abrupt withdrawal to minimize risk of increased seizure frequency and status epilepticus 1
• Monitor patients for suicidal behavior and ideation 1
• Watch for neurological adverse reactions like somnolence and fatigue 1
• Be alert for psychiatric adverse reactions including psychotic symptoms, irritability, depression, aggressive behavior, and anxiety 1
• Brivaracetam can be used in pediatric patients as young as 1 month of age 1
• Switching from levetiracetam to brivaracetam at a conversion ratio between 10:1 to 15:1 is feasible and might alleviate behavioral side effects associated with levetiracetam 4

Potential Use in Status Epilepticus

• The intravenous formulation may be a potential alternative for status epilepticus, though clinical experience in this setting is limited 4
• For refractory status epilepticus, other agents like valproate (30 mg/kg IV), levetiracetam (30 mg/kg IV), or phenobarbital are currently more established options 6, 7