What is the indication for use of Brivaracetam (brivaracetam) in patients with epilepsy?

Indications for Brivaracetam in Epilepsy

Brivaracetam is indicated as adjunctive therapy for the treatment of partial-onset (focal) seizures in adults and adolescents aged 16 years and older with epilepsy. 1

Mechanism of Action and Efficacy

Brivaracetam is a high-affinity synaptic vesicle protein 2A (SV2A) ligand, similar to levetiracetam but with greater receptor binding affinity. It also has inhibitory effects on sodium channels, contributing to its antiseizure properties 2. In clinical trials:

• Significant median seizure reduction rates of 30.5% to 53.1% for 50 mg/day
• 50% responder rates ranging from 32.7% to 55.8% at 50 mg/day 3
• Efficacy appears to be sustained during long-term therapy (up to 96 months) 4

Dosing and Administration

• FDA-approved dose: 50 mg twice daily (100 mg/day total)
• No titration is required, though dose can be adjusted based on clinical response
• Available in multiple formulations:
  • Oral tablets
  • Oral solution
  • Intravenous solution (as bolus or infusion) 2, 4
• Dose range: 50-200 mg/day divided into two doses 5

Pharmacokinetic Properties

Brivaracetam has favorable pharmacokinetic properties:

• Rapid absorption when administered orally
• Linear and dose-proportional pharmacokinetics at therapeutic doses
• Minimal drug-drug interactions with most medications
• No dose adjustment needed for renal impairment 2, 5

Special Considerations

Switching from Levetiracetam

• Immediate switch from levetiracetam to brivaracetam is feasible
• Conversion ratio between 10:1 to 15:1 (levetiracetam:brivaracetam)
• May alleviate behavioral side effects associated with levetiracetam 3

Drug Interactions

• Few clinically relevant drug-drug interactions
• Strong enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital) may moderately lower brivaracetam plasma concentrations, but no dose adjustment is typically needed
• No clinically significant interactions with oral contraceptives 5

Adverse Effects

The most common adverse effects include:

• Somnolence and sedation (16% vs 8% placebo)
• Dizziness (12% vs 7% placebo)
• Fatigue (9% vs 4% placebo)
• Nausea/vomiting (5% vs 3% placebo)
• Psychiatric adverse reactions (13% vs 8% placebo) 1

Brivaracetam carries warnings for:

1. Suicidal behavior and ideation (common to all antiepileptic drugs)
2. Neurological adverse reactions (somnolence, fatigue, dizziness, coordination disturbances)
3. Psychiatric adverse reactions (irritability, anxiety, depression, psychotic symptoms)
4. Hypersensitivity reactions (bronchospasm and angioedema)
5. Withdrawal effects if discontinued abruptly 1

Potential Role in Status Epilepticus

While brivaracetam has an intravenous formulation that could potentially be used in status epilepticus, current guidelines do not specifically recommend it for this indication. For refractory status epilepticus, guidelines recommend:

• Level A: Additional antiepileptic medication after failed benzodiazepines
• Level B: IV phenytoin, fosphenytoin, or valproate
• Level C: IV levetiracetam, propofol, or barbiturates 6

Clinical Pearls

• Brivaracetam should generally be withdrawn gradually to avoid increased seizure frequency or status epilepticus
• Patients should be monitored for neurological and psychiatric adverse reactions
• Advise patients not to drive or operate machinery until they have gained sufficient experience with brivaracetam to gauge its effects
• Consider brivaracetam as an alternative to levetiracetam in patients experiencing behavioral side effects

Brivaracetam represents a viable adjunctive therapeutic option for patients with refractory partial-onset seizures who have failed conventional therapies, with advantages of minimal drug interactions, no required titration, and multiple administration routes.