FDA approves Brivaracetam to treat partial onset seizures.

February 19, 2016

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UCB Inc, Georgia
  • The U.S. Food and Drug Administration approved Briviact (brivaracetam) as an add-on treatment to other medications to treat partial onset seizures in patients age 16 years and older with epilepsy.

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DESCRIPTION

  • The chemical name of BRIVIACT (brivaracetam) is
  • (2S)-2-[(4R)-2-oxo-4-propyltetrahydro  -1H-pyrrol-1-yl]  butanamide.
  • Its molecular formula is C11H20N2O2 and its molecular weight is 212.29.
  • The chemical structure is:
bri1
BRIVARACETAM

CLINICAL PHARMACOLOGY

Mechanism of Action

  • The precise mechanism by which BRIVIACT exerts its anticonvulsant activity is not known.
  • Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect.
  • Brivaracetam is a high-affinity synaptic vesicle protein 2A (SV2A) ligand.
  • It is not entirely clear how SV2A affects neuro-transmission, but animal studies suggest that it is potentially a good target for seizure control.Mice deficient in SV2A have seizures.
  • Among animal models of epileptogenesis as well as in humans with epilepsy, pathologic reduced SV2A expression is evident.
  •  In addition, studies find that SV2A binding strongly correlates with antiepileptic potency.
  • Interestingly, levetiracetam, which is one of the most commonly used AEDs worldwide, has SV2A binding affinity. Brivaracetam by comparison, has a >30-fold affinity for SV2A than levetiracetam suggesting that brivaracetam may be a very effective AED.
  • As with most AEDs, brivaracetam likely has multiple mechanisms of action. Not only is it an SV2A ligand, it displays inhibitory activity at neuronal voltage-dependent sodium channels (1).BR2

INDICATIONS AND USAGE

  • BRIVIACT is indicated as adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy.

DOSAGE AND ADMINISTRATION

  • The recommended starting dosage is 50 mg twice daily.
  • Based on individual patient tolerability and therapeutic response, the dosage may be adjusted down to 25 mg twice daily (50 mg per day) or up to 100 mg twice daily (200 mg per day).
  • BRIVIACT injection may be used when oral administration is temporarily not feasible.
  • Hepatic Impairment: For all stages of hepatic impairment, the recommended starting dosage is 25 mg twice daily; maximum dosage is 75 mg twice daily.

DOSAGE FORMS AND STRENGTHS

  • Tablets: 10 mg, 25 mg, 50 mg, 75 mg, and 100 mg
  •  Oral solution: 10 mg/mL.
  • Injection: 50 mg/5 mL single-dose vial.

Efficacy and Safety

The efficacy and safety of Briviact were based on data from three clinical trials of 1,550 patients with partial-onset seizures not adequately controlled with 1 to 2 concomitant antiepileptic drugs (AEDs).

In studies 1 and 2, the primary endpoint was the % reduction in 7-day partial-onset seizure frequency vs. placebo while study 3 evaluated the 28-day partial-onset seizure frequency vs. placebo.

  • In study 1, the Briviact 50 mg and 100 mg treatment groups demonstrated a 9.5% and 17% reduction in the primary endpoint, respectively.
  • In study 2, the Briviact 50 mg treatment group demonstrated a 16.9% statistically significant reduction in the primary endpoint.
  • In study 3, the Briviact 100 mg and 200 mg treatment groups demonstrated a 25.2% and 25.7% statistically significant reduction in the primary endpoint, respectively.

CONTRAINDICATIONS

  • Hypersensitivity to brivaracetam or any of the inactive ingredients in BRIVIACT

WARNINGS AND PRECAUTIONS

  • Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and ideation.
  • Neurological Adverse Reactions: Monitor for somnolence and fatigue, and advise patients not to drive or operate machinery until they have gained sufficient experience on BRIVIACT.
  • Psychiatric Adverse Reactions: Behavioral reactions including psychotic symptoms, irritability, depression, aggressive behavior, and anxiety; monitor patients for symptoms.
  • Hypersensitivity: Bronchospasm and Angioedema: Advise patients to seek immediate medical care. Discontinue and do not restart BRIVIACT if hypersensitivity occurs.
  • Withdrawal of Antiepileptic Drugs: BRIVIACT should be gradually withdrawn.

ADVERSE REACTIONS

Most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) are somnolence/sedation, dizziness, fatigue, and nausea/vomiting.

DRUG INTERACTIONS

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Briviact is marketed by UCB, Inc. of Smyrna, Georgia.

REFERENCES:

  1. Pack AM. Brivaracetam, a Novel Antiepileptic Drug: Is it Effective and Safe? Results from One Phase III Randomized Trial. Epilepsy Currents. 2014 Jul;14(4):196-8.
  2. FDA News
  3. PIL