The Dummies' Guide to Brivaracetam Vs Levetiracetam

Published 2016-07-27 06:00:00 epilepsy

Brivaracetam vs Levetiracetam

In the US, about 5.1 million people have a history of epilepsy and 2.9 million are active epileptics.

Antiepileptic drugs allow freedom from seizures in most patients (roughly 75%). But anticonvulsant drugs can cause a many unpleasant and rarely dangerous side effects. The the life-threatening Steven's Johnson Syndrome rash is one such example.

Adverse drug side efects are responsible for poor compliance and discontinuation of therapy. Pharmaceutical companies have focused their efforts on developing drugs with comparable effecicy but reduced adverse effects.

Levetiracetam, which was discovered in 1992, is a widely used antiepileptic drug that is used for treating partial-onset, myoclonic, or generalized tonic-clonic seizures in patients with epilepsy.

More recently an analogue of levetiracetam called brivaracetam was developed with the aim of optimizing the neuronal effects of the drug.

The US FDA recently approved brivaracetam as an adjunctive therapy for partial-onset seizures in patients aged 16 years and older.

Brivaracetam may be more potent than levetiracetam and have fewer adverse effects. Therefore, patients may benefit from switching from levetiracetam to brivaracetam. Such a switch may have a positive impact on patients' quality of life and health status.

Below is a general comparison chart to help you assess basic differences between levetiracetam and brivaracetam.

  Levetiracetam Brivaracetam
Brand Names Keppra / Keppra XR / Spritam Briviact
Drug type Antiepileptic Antiepileptic
Manufacturer UCB / Aprecia UCB
Date approved November 30th, 1999 (Spritam: August 3rd, 2015) February 19th, 2016
Approved uses Partial-onset seizures/Myoclonic Seizures/Primary Generalized Tonic-Clonic Seizures Partial-onset seizures
Dosages Tablet / Solution / Injectable form Tablet / Solution / Injectable form
Date approved Tablets: 250mg / 500 mg / 750 mg / 1000 mg Solution: 100 mg/ml Injection: 100 mg/ml Tablets: 10mg/25 mg/50 mg/75 mg/100 mg Solution: 10 mg/ml Injection: 50 mg/ml
Half life 1 to 7 hours 8 hours
Common side effects Sleepiness, fatigue, dizziness, anxiety, nervousness, irritability, depression, and other mood changes Nausea, vomiting, dizziness, drowsiness, and fatigue

Brivaracetam vs Levetiracetam Mechanism

Levetiracetam and brivaracetam are both anticonvulsants that are generally used in combination with other medicines and work by slowing abnormal nerve impulses in the brain.

Both drugs come in a tablet and solution form and are usually taken twice a day by mouth with or without food. The medication is also available in an injectable form to be given intravenously (IV) by a healthcare professional.

The drug levetiracetam, which has been the more widely researched, puts a ceiling on neuronal hyperexcitability.

More specifically, the main effect appears to be leviracetam's interaction with a novel brain-specific binding site that has been identified as the synaptic vesicle protein 2A (SV2A).

Because brivaracetam is chemically related to levetiracetam, the mechanism of action of brivaracetam is probably similar. Niether drug has been linked to clinically significant interactions with other antiepileptic drugs.

Despite this observation, brivaracetam and leviracetam have distinct pharmacological profiles.

Levetiracetam inhibits high voltage calcium channels and AMPA receptors, whereas brivaracetam partially inhibits sodium channels. Both of these mechanisms ultimately reduce neuronal hyperexcitability.

Brivaracetam vs Levetiracetam

Efficacy

Levetiracetam has been approved for the treatment of partial-onset, myoclonic, and generalized tonic-clonic seizures in patients with epilepsy. Whereas brivaracetam was recently approved for partial-onset seizures. Along with levetiracetam, brivaracetam is also effective in the treatment of myoclonic and generalized tonic-clonic seizures.

Researchers attribute brivaracetam's enhanced efficacy and potency to its activity at SV2A.

Brivaracetam's potency ranges 10- to 30-fold higher. Furthermore, brivaracetam also confers protection in traditional antiepileptic drug screening models (supramaximal electrical and chemical test), but levetiracetam does not. Although, this was at high doses of brivaracetam and associated with some motor impairment.

Side Effects

Series side effects can manifest with anticonvulsant treatment. Such adverse effects include:

  • suicidal ideation
  • feelings of agitation
  • new or worsening depression
  • aggression
  • panic attacks

But these adverse effects are very rarely observed with levetiracetam and brivaracetam. Common side effects for levetiracetam in particular include:

  • sleepiness
  • loss of strength and energy
  • dizziness
  • anxiety
  • nervousness
  • irritability
  • depression/other mood changes

Brivaracetam is associated with fewer side effects that often improve during the course of the treatment. These side effects mainly consist of central nervous system symptoms such as fatigue, dizziness, nausea, vomiting, and fatigue.

Neurocognitive Effects

Patients with epilepsy are at risk for cognitive impairments because of their condtion. These imparments include the underlying etiology, seizures, and side effects of treatments for seizures.

Nearly 50% of patients with epilepsy report difficulty with learning, memory, and attention. These are the most pronounced cognitive deficits reported in patients with temporal lobe epilepsy. Even in the absence of overt toxicity, patients who exhibit more symptoms of neurotoxicity have lower perceived quality of life.

Evidence suggests that both levetiracetam and brivaracetam have similar favorable cognitive profiles. When cognitive and neuropsychological tests were used to examine learning, memory, and attention, which have been shown to be sensitive to the effects of antiepileptic drugs, both drugs did not produce significant reductions in performance.

Tolerability

Drug tolerability is a significant limiting factor in the treatment of patients with epilepsy and long-term retention rates are often determined by adverse event profiles.

Levetiracetam treatment has been associated with nonpsychotic adverse behavioral events such as: agitation; antisocial reaction; anxiety; apathy; depersonalization; depression; emotional lability; euphoria; hostility; nervousness; neurosis; and personality disorder. One study examing the causes of discontinued treatment with levetiracetam found that these adverse behavioral events accounted for 40.4% of the discontinuations. Levetiracetam patients experience these adverse behavioral events, but brivaracetam patients do not.

Therefore, based on the evidence so far, which includes efficacy, side effects, and adverse behavioral events, patients may benefit from switching from levetiracetam to brivaracetam. Furthermore, research has suggested that a switch from levetiracetam to brivaracetam may have a positive impact on patients' quality of life and health status. Nonetheless, brivaracetam is still a relatively new drug and research into its efficacy is ongoing. Patients should always seek professional medical advice whenever they are considering to take or change any medication.

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