Brivaracetam

Brivaracetam is a third-generation anti-seizure medication and a potent analog of levetiracetam. It binds with high selectivity and 15-30 times greater affinity to synaptic vesicle protein 2A (SV2A) in the brain. By binding to SV2A, brivaracetam decreases pre-synaptic neurotransmitter release, suppressing abnormal neuronal activity and preventing seizure spread.

Brivaracetam can be used as monotherapy or adjunctive therapy for partial-onset seizures. Clinical trials and real-world studies have shown that brivaracetam significantly reduces seizure frequency and is generally well tolerated. It is available as oral tablets, oral solution, and intravenous injection.

• Partial-onset seizures in patients 1 month of age and older

Adults (16 years and older): Initial dose: 50 mg twice daily (100 mg/day). Maintenance: 25-100 mg twice daily (50-200 mg/day).

Children (weight ≥50 kg): Initial: 25-50 mg twice daily (50-100 mg/day). Maintenance: 25-100 mg twice daily (50-200 mg/day).

Children (weight 20 to <50 kg): Initial: 0.5-1 mg/kg twice daily (1-2 mg/kg/day). Maintenance: 0.5-2 mg/kg twice daily (1-4 mg/kg/day).

Children (weight 11 to <20 kg): Initial: 0.5-1.25 mg/kg twice daily (1-2.5 mg/kg/day). Maintenance: 0.5-2.5 mg/kg twice daily (1-5 mg/kg/day).

Children (weight <11 kg): Initial: 0.75-1.5 mg/kg twice daily (1.5-3 mg/kg/day). Maintenance: 0.75-3 mg/kg twice daily (1.5-6 mg/kg/day).

Hepatic impairment (all stages): Reduce starting dose to 25 mg twice daily and do not exceed 75 mg twice daily (150 mg/day).

Renal impairment: Mild-moderate: No dose adjustment. ESRD (dialysis): Not studied.

Elderly: Start at the low end of the dosing range.

IV administration: When oral administration is temporarily not feasible, same dose and frequency IV (up to 4 consecutive days).

Common side effects (≥5% and at least 2% more frequent than placebo): Somnolence/sedation, dizziness, fatigue, nausea/vomiting.

Other common: Headache, constipation, irritability, anxiety, nervousness, aggression, agitation, restlessness, depression, abnormal behavior.

Serious (rare): Stevens-Johnson syndrome, toxic epidermal necrolysis (potentially fatal skin reactions), bronchospasm, angioedema (hypersensitivity reactions), suicidal thoughts or behavior.

Side effects are more common during the first few weeks and usually lessen as the body adjusts to the medication.

• Antiepileptic drugs, including brivaracetam, increase the risk of suicidal thoughts or behavior; monitor patients for changes in mood or behavior.
• May cause somnolence, fatigue, dizziness, and coordination disturbances; advise patients not to drive or operate machinery.
• Psychiatric adverse reactions (non-psychotic: irritability, anxiety, aggression, agitation, depression; psychotic: hallucinations, paranoia) may occur; monitor patients.
• Do not stop abruptly due to risk of increased seizure frequency and status epilepticus; withdraw gradually.
• Caution in hepatic impairment (dose adjustment may be needed).
• Use during pregnancy only if clearly needed (animal studies show potential fetal harm).
• Limited data on breastfeeding; brivaracetam is excreted in breast milk; monitor exclusively breastfed infants for drowsiness, agitation, weight gain, and developmental milestones.

• Known hypersensitivity to brivaracetam or any component (bronchospasm and angioedema have occurred)

• Rifampin (CYP2C19 inducer): Decreases brivaracetam plasma concentrations; dose increase by up to 100% may be needed.
• Carbamazepine: Increases carbamazepine-epoxide (active metabolite) levels up to 2-fold; consider reducing carbamazepine dose if tolerability issues arise.
• Phenytoin: May increase phenytoin plasma concentrations; monitor phenytoin levels during concomitant administration.
• CYP2C19 inhibitors (fluconazole, fluvoxamine): May increase brivaracetam plasma concentrations.
• Levetiracetam: Brivaracetam provides no added therapeutic benefit when co-administered with levetiracetam.
• Alcohol: Doubles the effect on psychomotor function, attention, and memory; avoid alcohol consumption.