BRIVIACT® (brivaracetam) CV is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.

As the safety of BRIVIACT injection in pediatric patients has not been established, BRIVIACT injection is indicated for the treatment of partial-onset seizures only in adult patients (16 years of age and older).

Approved For Pediatric Patients (4 Years of Age and Older)

BRIVIACT® (brivaracetam) CV is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.

As the safety of BRIVIACT injection in pediatric patients has not been established, BRIVIACT injection is indicated for the treatment of partial-onset seizures only in adult patients (16 years of age and older).

Approved For Pediatric Patients (4 Years of Age and Older)

Safety

Safety

BRIVIACT® Warnings and Precautions

Antiepileptic drugs, including BRIVIACT, increase the risk of suicidal behavior and ideation

  • Monitor patients for the emergence or worsening of depression; unusual changes in mood or behavior; or suicidal thoughts, behavior, or self-harm
  • Advise patients, their caregivers, and/or families to be alert for these changes and report them immediately to a healthcare provider

Causes somnolence, fatigue, dizziness, and disturbance in gait and coordination

  • Somnolence and fatigue-related adverse reactions reported in 25% of adult patients taking at least 50 mg per day of BRIVIACT compared to 14% of adult patients taking placebo
  • Dizziness and disturbance in gait and coordination reported in 16% of adult patients taking at least 50 mg per day of BRIVIACT compared to 10% of patients taking placebo
  • Risk is greatest early in treatment but can occur at any time
  • Monitor patients and advise them not to drive or operate machinery until they have sufficient experience on BRIVIACT

Causes psychiatric adverse reactions, including non-psychotic and psychotic symptoms

  • Events reported in approximately 13% of adult patients taking at least 50 mg per day of BRIVIACT compared to 8% of adult patients taking placebo
  • 1.7% of adult patients taking BRIVIACT discontinued treatment due to psychiatric reactions compared to 1.3% of patients taking placebo
  • Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults
  • Advise patients to report these symptoms immediately to a healthcare provider

Can cause hypersensitivity reactions; bronchospasm and angioedema have been reported

  • Discontinue BRIVIACT if a patient develops a hypersensitivity reaction after treatment
  • Contraindicated in patients with prior hypersensitivity to brivaracetam or any of the inactive ingredients in BRIVIACT

Withdrawal of antiepileptic drugs

  • As with all antiepileptic drugs, BRIVIACT should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus

Safety and tolerability of BRIVIACT® were evaluated without utilizing a titration period

The most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) are1:

  • somnolence and sedation
  • dizziness
  • fatigue
  • nausea and vomiting symptoms

Adverse reactions reported in clinical studies of pediatric patients 4 years to less than 16 years of age were generally similar to those in adult patients.

ADVERSE REACTIONS THAT OCCURRED AT LEAST 2% MORE FREQUENTLY FOR BRIVIACT DOSES OF AT LEAST 50 MG/DAY THAN PLACEBO IN POOLED PLACEBO-CONTROLLED ADJUNCTIVE THERAPY STUDIES1

BRIVIACT® (brivaracetam) CV Adverse Reactions Table
BRIVIACT® (brivaracetam) CV Adverse Reactions Table
  • *Cerebellar coordination and balance disturbances include ataxia, balance disorder, coordination abnormal, and nystagmus.

There was no apparent dose-dependent increase in adverse reactions with the exception of somnolence and sedation1

Most adverse events in trials were reported to be mild to moderate3

Across all 3 trials, discontinuation rates due to adverse events were1:

  • Placebo: 4%
  • BRIVIACT 50 mg/day: 5%
  • BRIVIACT 100 mg/day: 8%
  • BRIVIACT 200 mg/day: 7%

The most common adverse reaction leading to discontinuation was dizziness.3

Drug Interactions

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  • General drug interactions1

    • Rifampin: Co-administration with rifampin decreases BRIVIACT® plasma concentrations likely because of CYP2C19 induction. Increase the BRIVIACT dosage in patients on concomitant rifampin by up to 100% (i.e., double the dosage)
    • Oral contraceptives:
      • BRIVIACT was studied with an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg)
      • BRIVIACT 50 mg twice daily (100 mg/day) did not significantly influence the pharmacokinetics of either substance of the oral contraceptive
      • BRIVIACT 200 mg twice daily (400 mg/day, twice the recommended maximum daily dosage) reduced estrogen and progestin AUCs by 27% and 23%, respectively, but did not affect suppression of ovulation
      • The interaction is not expected to be of clinical significance

    BRIVIACT and other AEDs1

    None of the interactions listed below requires changes in the dose of BRIVIACT, but interactions with carbamazepine and phenytoin can be clinically important

    • Carbamazepine: Co-administration may increase exposure to carbamazepine-epoxide (the active metabolite of carbamazepine). Available data did not reveal any safety concerns, but dose reduction should be considered if tolerability issues arise
    • Phenytoin: BRIVIACT can increase plasma concentrations of phenytoin, so levels should be monitored during co-administration
      • At a supratherapeutic dose of 400 mg/day brivaracetam, there was a 20% increase in phenytoin plasma concentration
    • Levetiracetam: BRIVIACT provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered
Safety

Important Safety Information

WARNINGS AND PRECAUTIONS

  • Suicidal Behavior and Ideation: Antiepileptic drugs, including BRIVIACT, increase the risk of suicidal behavior and ideation. Monitor patients taking BRIVIACT for the emergence or worsening of depression; unusual changes in mood or behavior; or suicidal thoughts, behavior, or self-harm. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.
  • Neurological Adverse Reactions: BRIVIACT causes somnolence, fatigue, dizziness, and disturbance in coordination. Somnolence and fatigue-related adverse reactions were reported in 25% of adult patients taking at least 50 mg per day of BRIVIACT compared to 14% of adult patients taking placebo. Dizziness and disturbance in gait and coordination were reported in 16% of adult patients taking at least 50 mg per day of BRIVIACT compared to 10% of adult patients taking placebo. The risk is greatest early in treatment but can occur at any time. Monitor patients for these signs and symptoms and advise them not to drive or operate machinery until they have gained sufficient experience on BRIVIACT.
  • Psychiatric Adverse Reactions: BRIVIACT causes psychiatric adverse reactions, including non-psychotic and psychotic symptoms. These events were reported in approximately 13% of adult patients taking at least 50 mg per day of BRIVIACT compared to 8% of adult patients taking placebo. A total of 1.7% of adult patients taking BRIVIACT discontinued treatment due to psychiatric reactions compared to 1.3% of patients taking placebo. Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults. Advise patients to report these symptoms immediately to a healthcare provider.
  • Hypersensitivity: BRIVIACT can cause hypersensitivity reactions. Bronchospasm and angioedema have been reported. Discontinue BRIVIACT if a patient develops a hypersensitivity reaction after treatment. BRIVIACT is contraindicated in patients with a prior hypersensitivity reaction to brivaracetam or any of the inactive ingredients.
  • Withdrawal of Antiepileptic Drugs: As with all antiepileptic drugs, BRIVIACT should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus.

DOSING CONSIDERATIONS

  • Dose adjustments are recommended for patients with all stages of hepatic impairment.
  • When BRIVIACT is co-administered with rifampin, an increase in the BRIVIACT dose is recommended.

ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical trials, the most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) were somnolence and sedation, dizziness, fatigue, and nausea and vomiting symptoms. Adverse reactions reported in clinical studies of pediatric patients 4 years to less than 16 years of age were generally similar to those in adult patients.

BRIVIACT is a Schedule V controlled substance.

Please see full Prescribing Information.

To report suspected adverse reactions, contact UCB, Inc. at UCBCares® (1-844-599-2273) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. BRIVIACT (brivaracetam): US prescribing information. Smyrna (GA): UCB, Inc., May 2018.
  2. Gillard M, Fuks B, Leclercq K, Matagne A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol. 2011;664(1-3):36–44.
  3. Data on file. UCB, Inc.
  4. Matagne A, Margineanu DG, Kenda B, Michel P, Klitgaard H. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for synaptic vesicle protein, SV2A. Br J Pharmacol. 2008;154(8):1662-1671.
  5. Klitgaard H, Matagne A, Nicolas JM, et al. Brivaracetam: Rationale for discovery and preclinical profile of selective SV2A ligand for epilepsy treatment. Epilepsia. 2016;57(4):538-548.
  6. Noyer M, Gillard M, Matagne A, Hénichart J-P, Wülfert E. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol. 1995;286;137-146.
  7. Yan HD, Ishihara K, Seki T, et al. Inhibitory effects of levetiracetam on the high-voltage-activated L-type Ca2+ channels in hippocampal CA3 neurons of spontaneously epileptic rat (SER). Brain Res Bull. 2013;90:142-148.
  8. Niespodziany I, Klitgaard H, Margineanu DG. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurons of rat hippocampal slices. Neurosci Lett. 2001;306(1-2):5-8.
  9. Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 2002;43(1):9-18.
  10. Carunchio I, Pieri M, Ciotti MT, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia. 2007;48(4):654-662.
  11. Rigo JM, Nguyen L, Hans G, et al. UCB 34714: effect on inhibitory and excitatory neurotransmission. Epilepsia. 2004;45(3):56.
  12. PARx Solutions, Inc., November 2017.
  13. CoverMyMeds, LLC, December 2017.
  14. CoverMyMeds. CoverMyMeds website: https://www.covermymeds.com/main/. Accessed October 9, 2017.