Brivaracetam efficacy and safety in focal epilepsy

ABSTRACT

Introduction: Brivaracetam (BRV) is an analog of levetiracetam (LEV) with 15–30 times greater affinity to SV2A and greater brain permeability than LEV. These properties have stimulated interest in its clinical trial data and post-marketing experience.

Areas covered: The authors provide a background on epilepsy and its treatment, discuss the racetam family of antiepileptic drugs to which BRV belongs, and then discuss BRV properties and its efficacy and tolerability in the treatment of epilepsy.

Expert opinion: While preclinical data suggest a broad spectrum of efficacy, BRV is only approved for focal epilepsy. The recommended starting dose is 100 mg per day, but in the absence of urgency, it may be prudent to start at 50 mg per day, considered the lowest effective dose. There was no added benefit when BRV was used adjunctively with LEV in clinical trials. However, post-marketing data suggest that some patients may experience improved seizure control when switching from LEV. Behavioral adverse effects seemed less common than with LEV, and most patients switched to BRV after experiencing behavioral adverse effects on LEV reported improvement. Prior or anticipated intolerability to LEV is the strongest indication for BRV in clinical practice.

KEYWORDS:

• Brivaracetam
• levetiracetam
• synaptic vesicle protein 2A
• focal seizures
• clinical trials
• efficacy
• tolerability
• safety

Article highlights

• Brivaracetam is an analog of levetiracetam acting on SV2A with greater affinity and selectivity.

• Brivaracetam has greater brain permeability than levetiracetam.

• Brivaracetam is metabolized by hydrolysis and to a lesser extent by hydroxylation via CYP2C19.

• Clinical trials have demonstrated the efficacy of brivaracetam at doses of 50 mg per day, 100 mg per day, and 200 mg per day.

• The most common adverse effects of brivaracetam were somnolence, dizziness, fatigue, nausea, irritability.

• Behavioral adverse effects may be less common with brivaracetam than levetiracetam.

• In the USA brivaracetam is approved for the treatment of focal seizures in patients 4 years of age and older.

• In the European Union, it is specifically indicated as adjunctive therapy of focal seizures in patients 4 years of age and older.

• A parenteral brivaracetam formulation is available for replacement therapy in patients 16 years of age and older.

Declaration of interest

B Abou-Khalil received grant support paid to Vanderbilt from Biogen, SK-Pharma, Sunovion, and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has received honoraria from UCB, the company which produces and sells brivaracetam. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.