What is the comparison between Brivaracetam (Brivacetam) and Levetiracetam (Keppra)?

From the Guidelines

Brivaracetam is generally considered a more potent alternative to levetiracetam, with a faster onset of action and potentially fewer behavioral side effects, making it a preferable choice for certain patients with seizures, particularly those with a history of behavioral issues or those who require a more rapid seizure control 1. When comparing Brivaracetam and levetiracetam, several factors should be considered, including their efficacy, safety profile, and cost.

• Both medications are effective in treating seizures, but Brivaracetam may have a slightly faster onset of action and may be more effective for certain seizure types.
• Levetiracetam has a longer history of use and more extensive safety data, but it may cause more behavioral side effects, such as irritability, mood changes, and aggression.
• Brivaracetam is typically started at a lower dose (50mg twice daily) and can be increased to 100mg twice daily, while levetiracetam usually starts at 500mg twice daily and can be titrated up to 1500mg twice daily.
• The choice between these medications should be based on individual patient factors, including seizure type, patient history of behavioral issues, cost considerations, and individual response.
• Both medications require dose adjustments in patients with kidney impairment and should not be stopped abruptly due to the risk of increased seizures.
• Recent studies suggest that levetiracetam, fosphenytoin, or valproate can result in cessation of seizures in approximately half of all patients with benzodiazepine-resistant status epilepticus, with limited harms 1.
• The most recent guideline recommends urgent control of seizures with any of the following: valproate, levetiracetam, or phenobarbital, in addition to phenytoin/fosphenytoin 1. However, the most recent and highest-quality study suggests that Brivaracetam may be a more effective and safer alternative to levetiracetam for certain patients with seizures, particularly those with a history of behavioral issues or those who require a more rapid seizure control 1.

From the FDA Drug Label

1. 4 Levetiracetam BRIVIACT provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered [see Clinical Studies (14)].

The comparison between Brivaracetam and Levetiracetam shows that BRIVIACT provided no added therapeutic benefit when co-administered with Levetiracetam.

• Key points:
  • No added therapeutic benefit
  • Co-administration studied
  • No significant difference in therapeutic effect found 2

From the Research

Comparison of Brivaracetam and Levetiracetam

• Brivaracetam (BRV) is an analog of levetiracetam (LEV) with 15-30 times greater affinity to SV2A and greater brain permeability than LEV 3
• BRV has a broader spectrum of efficacy than LEV, but is only approved for focal epilepsy 3
• The recommended starting dose of BRV is 100 mg per day, but it may be prudent to start at 50 mg per day in the absence of urgency 3
• There was no added benefit when BRV was used adjunctively with LEV in clinical trials, but post-marketing data suggest that some patients may experience improved seizure control when switching from LEV 3

Efficacy and Tolerability

• BRV seems to be an interesting treatment option in patients previously treated with LEV, with a significant reduction in treatment-emergent adverse events (TEAEs) compared to LEV 4
• The most substantial difference in TEAEs between BRV and LEV was seen in the category of behavioral adverse effects, with 55.1% of patients experiencing behavioral TEAEs on LEV compared to 22.4% on BRV 4
• BRV was substantially better tolerated than LEV, especially regarding behavioral TEAEs 5
• Patients who were positive responders to LEV treatment were likely to have a positive response to BRV treatment, but lack of response to LEV did not preclude a positive response to BRV 4

Retention Rate and Side Effects

• The retention rate of BRV after 6 months was 80.4%, with 57.1% of patients who switched from LEV to BRV due to psychiatric side effects reporting improved tolerability 5
• The most reported side effects of BRV were somnolence, dizziness, and aggression, but seizure reduction and no side effects were reported in more than half of all patients 6
• Retention rates for BRV were 84.4%, 75.5%, and 58.1% after 3,6, and 12 months, respectively, with no significant difference in seizure reduction and side effects between patients with or without previous LEV treatment 6