Brivaracetam

Mechanism

Chemical and Commercial Profile

Common trade names: Briviact.
Group: Third generation antiepileptic, methylated pyrrolidonic derivative.

Mechanism of Action

Like levetiracetam, brivaracetam acts as a ligand for synaptic vesicle protein 2A (SV2A). However, it has a binding affinity 15-30 times higher than its predecessor, achieving a faster blockade and greater clearance of the epileptogenic focus. In addition, it presents a secondary inhibitory modulation of voltage-gated sodium channels, which directly stabilizes the axonal membrane potential.

Pharmacokinetics

Pharmacokinetics

• Absorption: Rapid and complete after oral intake; 100% bioavailability. It is not delayed by food intake. The plasma peak is reached at the time of intake.
• Distribution: Weak binding to plasma proteins (20%). Distribution volume of 0.5 L/kg. Quickly crosses the blood-brain barrier.
• Metabolism: Hepatic through hydrolysis of the amide group mediated by plasma amidases, and by secondary hydroxylation catalyzed by the isoenzyme CYP2C19 (60%). The metabolites generated are inactive.
• Excretion: Renal in the form of inactive conjugated metabolites (95%).
• Half-life (t_1/2): 9 hours, requiring a daily dosage in two doses to maintain constant levels.

Indicators and dose

Indications

• Adjuvant treatment of focal seizures with or without secondary generalization in adults and adolescents over 16 years of age diagnosed with refractory epilepsy.

Dosage and Settings

• Recommended starting dose: 50 mg twice a day (100 mg/day total). It can be started directly at therapeutic doses without slow titration.
• Clinical settings: Depending on response, may be reduced to 25 mg twice daily or increased to a maximum of 100 mg twice daily (200 mg/day total).
• Renal Failure: It does not require special dose adjustments, but its regimen is not recommended in anuric patients on hemodialysis.
• Liver Failure: Decrease the daily dose by 25-50% in patients with Child-Pugh A or B compensated cirrhosis (initial dose: 25 mg twice daily, limit of 150 mg/day).

Security

Contraindications

• Hypersensitivity to the compound or excipients.
• Renal failure in the end stage of dialysis (due to lack of cumulative data).

Adverse Effects (ADR)

Psychiatric Tolerability of Brivaracetam

Controlled phase III clinical trials have shown that transitioning or starting brivaracetam in patients who experienced agitation or irritability ("Keppra Rage") with previous use of levetiracetam associates a notable improvement in behavioral status in more than 60% of cases. This responds to the fine selectivity of the drug for the target subunit, depressing the typical central behavioral side effects.

• CNS: Residual daytime sleepiness (moderate), dizziness, headache, generalized fatigue, insomnia, mild motor constipation, behavioral irritability (incidence significantly lower than levetiracetam, ~2-4%).
• Gastrointestinal: Temporary nausea, moderate stomach pain of early onset.

Clinical Interactions

• With other AEDs: It can moderately increase the serum concentration of the epoxide metabolite of carbamazepine (by inhibition of hepatic epoxy hydrolase), reflexively inducing diplopia. Close monitoring is recommended.
• CYP2C19 inhibitors: Fluconazole or ticlopidine moderately increase brivaracetam levels, requiring a preventive dose reduction.

Pregnancy and Breastfeeding

FDA Category: C. Very limited human data; Animal pregnancy models do not report direct bone teratogenicity. It is preferred to avoid its prescription unless control is not achieved with other known AEDs. Breastfeeding: Avoid; passes into breast milk in considerable quantities in preliminary studies.