Bivara

• Adjunctive therapy for partial-onset seizures (focal seizures) with or without secondary generalization in patients aged 4 years and older with epilepsy.
• Used when seizures are inadequately controlled by other antiepileptic drugs (AEDs).
• Off-label uses include treatment of other seizure types as determined by specialist neurologists, but not widely established.

• Adults (≥16 years):
• Initial dose: 50 mg orally twice daily (100 mg/day total).
• Maintenance dose: 100 mg twice daily (200 mg/day), may be adjusted between 50 mg and 200 mg twice daily based on clinical response and tolerability.
• Pediatrics (4 to <16 years):
• Weight-based dosing recommended, e.g., 1 mg/kg/day divided twice daily, up to 200 mg/day max.
• Elderly:
• No specific dose adjustment required; monitor for tolerability.
• Renal Impairment:
• No dose adjustment necessary for mild to moderate renal impairment. Severe impairment: caution advised, no formal recommendation.
• Hepatic Impairment:
• Moderate to severe impairment: dose reduction by half recommended due to decreased clearance.
• Administration:
• Oral tablets or oral solution; tablets swallowed whole with or without food.

Brivaracetam is a high-affinity synaptic vesicle protein 2A (SV2A) ligand. By binding selectively to SV2A, it modulates synaptic neurotransmitter release, thereby reducing neuronal hyperexcitability and seizure activity. Unlike other AEDs, brivaracetam’s high SV2A affinity provides a rapid onset of action and effective seizure control without significant effects on other neurotransmitter systems.

• Absorption: Rapidly and almost completely absorbed; bioavailability >90%.
• Time to peak concentration: ~1 hour post-dose.
• Distribution: Volume of distribution approx. 0.5 L/kg; low plasma protein binding (<20%).
• Metabolism: Primarily via hepatic hydrolysis and CYP2C19-mediated hydroxylation; metabolites inactive.
• Half-life: Approximately 7–8 hours.
• Excretion: Mainly renal (~85%) as metabolites; <10% excreted unchanged.
• Steady state: Achieved within 2 days with twice-daily dosing.

• Pregnancy:
• No FDA pregnancy category assigned; animal studies indicate potential risk of fetal toxicity at high doses. Use only if benefits outweigh risks.
• Lactation:
• Unknown if excreted in human milk; caution advised during breastfeeding. Alternative AEDs preferred if possible.

• Primary Class: Antiepileptic Drug (AED)
• Subclass: SV2A ligand, second-generation anticonvulsant

• Known hypersensitivity to brivaracetam or any formulation excipients.

• Neuropsychiatric effects: Risk of irritability, depression, anxiety, psychosis, aggression; monitor closely especially in patients with psychiatric history.
• Suicidal ideation: Antiepileptic drugs may increase risk; patients should be monitored.
• Dizziness and somnolence: May impair ability to perform tasks requiring alertness; caution when driving or operating machinery.
• Withdrawal: Gradual dose reduction recommended to avoid increased seizure frequency.
• Hepatic impairment: Dose adjustment advised; monitor liver function tests periodically.

Common:

• CNS: Dizziness, somnolence, fatigue, headache
• Gastrointestinal: Nausea, vomiting
• Psychiatric: Irritability, anxiety

Less Common / Rare:

• Depression, aggression, psychosis, suicidal ideation
• Coordination difficulties, tremor
• Hypersensitivity reactions (rash, angioedema)

Onset & Dose-Dependence:

• Most CNS side effects appear early and may diminish over time.
• Psychiatric adverse events may be dose-related.

• CYP2C19 inhibitors (e.g., omeprazole): May increase brivaracetam levels; monitor and adjust dose if needed.
• CYP2C19 inducers (e.g., rifampin): May reduce brivaracetam plasma concentrations, potentially lowering efficacy.
• Other AEDs: No significant pharmacokinetic interactions; safe for adjunctive use.
• Alcohol: Concurrent use may increase CNS depression and dizziness.

• Recent epilepsy treatment guidelines include brivaracetam as an effective adjunctive therapy for focal seizures.
• Favorable safety profile compared to older AEDs highlighted in recent systematic reviews.
• FDA approval expanded to pediatric patients aged 4 years and above.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Keep out of reach of children.