Brivaracetam: Mechanism of Action, Indications and Important Notes
Brivaracetam is an antiepileptic drug approved for the treatment of focal seizures in adults and children from the age of two years. The active substance belongs to the same substance class as levetiracetam, but has a significantly higher affinity for its molecular target and has been pharmacologically further developed. Brivaracetam has been available in Europe as an add-on therapy for focal epilepsy since 2016.
Epilepsy is one of the most common chronic neurological disorders. Focal seizures originate in a circumscribed area of the brain and can manifest clinically in very different ways, from barely noticeable perceptual changes to pronounced motor symptoms and loss of consciousness. Not all patients achieve complete seizure freedom with a single antiepileptic drug, which makes combination therapies clinically significant.
Mechanism of Action
The primary mechanism of action of brivaracetam consists in high-affinity binding to synaptic vesicle protein 2A (SV2A). SV2A is a transmembrane protein involved in the release of neurotransmitters from presynaptic vesicles. Binding to SV2A modulates the excessive, seizure-related neurotransmitter release. This leads to stabilisation of neuronal activity and a reduction in seizure susceptibility.
Compared to levetiracetam, brivaracetam shows up to 15-fold higher affinity for SV2A. In addition, brivaracetam inhibits voltage-dependent sodium channels, which represents a further seizure-suppressing mechanism. This dual action pharmacologically distinguishes brivaracetam from levetiracetam and may be clinically relevant in some patients who do not respond adequately to levetiracetam.
Brivaracetam crosses the blood-brain barrier very rapidly, contributing to a rapid onset of action. Oral bioavailability is almost complete, and the active substance shows consistent pharmacokinetics with low variability between patients.
Indications
Focal Seizures With and Without Secondary Generalisation
Brivaracetam is approved as add-on therapy for focal seizures that may occur with or without secondary generalisation. Focal seizures limited to one brain region respond particularly well to brivaracetam. The active substance can also be used when a seizure spreads to the entire brain during its course (secondary generalisation). Combination with other antiepileptic drugs is often necessary and is well established in clinical practice.
Drug-Resistant Focal Epilepsy
In patients for whom other antiepileptic drugs are insufficiently effective or not tolerated, brivaracetam represents a therapeutic option. Clinical studies have shown that some patients experience a significant reduction in seizure frequency under brivaracetam, even if they have not responded adequately to levetiracetam or other antiepileptic drugs.
Use in Children
Since the extension of its authorisation, brivaracetam is also available for children from two years of age. An oral solution is available for younger children, which facilitates dosing in small children. Dosing is weight-adapted and determined by the treating paediatric neurologist.
Dosage Forms and Dosing
Brivaracetam is available as film-coated tablets, as an oral solution and as a concentrate for solution for injection. Tablets and solution are taken twice daily. In patients who are temporarily unable to take oral medication, the intravenous dosage form enables uninterrupted continuation of therapy.
The starting dose for adults is generally 50 mg twice daily and can be increased to up to 100 mg twice daily depending on individual response. The minimum dose is 25 mg twice daily. A dose adjustment may be required in patients with hepatic impairment. All dosing decisions are made by the treating neurologist.
Important Notes
Antiepileptic drugs must never be abruptly discontinued without medical consultation, as this can trigger status epilepticus (prolonged or rapidly repeated seizures). A gradual dose reduction under medical supervision is required when discontinuing brivaracetam.
Brivaracetam may impair the ability to drive and operate machinery, particularly at the start of therapy or when doses are changed. Patients should refrain from driving until this question has been individually clarified. In Germany, specific regulations regarding driving licences apply to patients with epilepsy, which the treating physician can explain.
Adverse Effects
Brivaracetam is overall well tolerated. Compared to levetiracetam, clinical studies show a more favourable profile with regard to psychiatric side effects such as irritability and aggressiveness, which are observed more frequently with levetiracetam. Possible adverse effects of brivaracetam include:
- Somnolence and fatigue, especially at the beginning of treatment
- Dizziness and coordination difficulties (ataxia)
- Nausea and vomiting
- Irritability, anxiety and mood swings (less frequent than with levetiracetam)
- More rarely: behavioural changes, depressive mood
- With intravenous administration: local reactions at the injection site
Drug Interactions
Brivaracetam is metabolised in the liver by hydrolysis and hydroxylation. The enzyme CYP2C19 plays a role in its breakdown. Potent inducers of liver enzymes such as rifampicin or certain other antiepileptic drugs such as carbamazepine, phenytoin and phenobarbital can lower brivaracetam blood levels and may require dose adjustment. Brivaracetam itself can increase carbamazepine-epoxide levels, contributing to enhanced toxicity of carbamazepine. The treating neurologist monitors possible interactions during regular check-ups.
Brivaracetam on Sanoliste
On Sanoliste you will find neurologists and epileptologists who specialise in the diagnosis and treatment of epilepsy. For patients with drug-resistant focal epilepsy, treatment by an epilepsy-specialised neurologist or at an epilepsy centre is particularly important in order to exploit all therapeutic possibilities.
The information on this page is for general information purposes only and does not replace consultation with a physician. Brivaracetam is a prescription-only medicine and may only be used following medical prescription.
Frequently Asked Questions about Brivaracetam
What distinguishes brivaracetam from levetiracetam?
Brivaracetam and levetiracetam share the same mechanism of action via SV2A, but differ significantly in binding affinity: brivaracetam binds to SV2A with much higher affinity. In addition, brivaracetam inhibits sodium channels, which levetiracetam does not do. In clinical practice, brivaracetam shows a more favourable profile with regard to psychiatric side effects. In patients who cannot take levetiracetam due to psychiatric tolerability problems, brivaracetam can be an alternative. Conversely, brivaracetam can also be effective in patients who have not achieved adequate seizure control with levetiracetam.
Can brivaracetam be taken during pregnancy?
Sufficient data from studies with pregnant women are not available for brivaracetam. Animal studies showed reproductive toxicity at high doses. However, since the risk of untreated epileptic seizures during pregnancy is also considerable, benefits must be weighed against potential risks individually. This decision should be made exclusively in close consultation with the treating neurologist, ideally before a planned pregnancy.
How quickly does brivaracetam act after administration?
Brivaracetam is rapidly absorbed after oral administration and reaches maximum blood concentration after approximately one hour. Crossing of the blood-brain barrier occurs quickly. A clinically relevant reduction in seizure frequency is seen in clinical studies already in the first weeks of treatment. Complete assessment of the efficacy of antiepileptic drug therapy generally requires an observation period of several months, as seizure frequency can be subject to natural fluctuations.