BRIVIACT is indicated for the treatment of partial-onset (focal) 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) when oral administration is temporarily not feasible.1

With an undiluted bolus injection, BRIVIACT offers rapid administration

  • icon minutes
    Can be administered intravenously over 2 to 15 minutes1
  • median
    Median Tmax following a 2-minute bolus (administered undiluted) is <5 minutes2
  • syringe
    Can be administered with or without dilution1
    • May be used with common diluents: sodium chloride (0.9%) injection, USP; lactated Ringer’s injection; dextrose 5% injection, USP
  • pill bottle
    No loading dose or titration required1
  • fridge
    No refrigeration required1
    • Can be stored in PyxisTM or Omnicell systems
  • warning
    No blood level, respiratory, or cardiac monitoring required

BRIVIACT is a molecular entity in the racetam class that targets SV2A 

  • The precise mechanism by which BRIVIACT exerts its anticonvulsant activity is unknown1
  • BRIVIACT is the result of a large rational discovery effort in which UCB screened ~12,000 compounds in an effort to find another synaptic vesicle protein (SV2A) ligand as a new addition to the racetam class3
  • BRIVIACT displays a high and selective affinity for SV2A in the brain, which may contribute to the anticonvulsant effect1 
     

SV2A BINDING IS PROPOSED TO BE THE PRIMARY MECHANISM OF ACTION (MOA) FOR BRIVIACT4-6

BINDING IS PREPOSED TO BE THE PRIMARY MECHISM OF ACTION (MOA) FOR BRIVIACT

*The precise mechanism by which levetiracetam exerts its anticonvulsant activity is unknown. Not all proposed mechanisms of levetiracetam are depicted.

High-voltage-activated calcium channel.

  • Depiction of proposed MOA based on in vitro studies 
  • BRIVIACT displays 15-30x higher affinity for SV2A than levetiracetam4
  • Implications for efficacy and safety are not known

 

 

Levetiracetam is a product manufactured by UCB.

BRIVIACT exhibits a linear and time-independent pharmacokinetic profile1

Pharmacokinetic profiles

BRIVIACT allows administration flexibility with multiple formulations and a 1:1 dose conversion

Dose conversion
  • The recommended starting dose for monotherapy and adjunctive therapy in adult patients (16 years and older) is 50 mg twice daily (100 mg/day) and is initiated without titration1
  • The maximum maintenance dose is 100 mg twice daily (200 mg/day)1
  • When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability1

§10 mg tablets are available for down titration. Products not shown at actual size.

BRIVIACT injection may be used for adult patients when oral administration is temporarily not feasible. The use of BRIVIACT injection in pediatric patients has not been studied. BRIVIACT injection should be administered intravenously to adult patients at the same dosage and same frequency as BRIVIACT tablets and oral solution. The clinical study experience with BRIVIACT injection is limited to 4 consecutive days of treatment.1

dose_adjustments
Drug interaction considerations

IICo-administration with carbamazepine and phenytoin does not require changes in the dose of BRIVIACT, but interactions may be clinically important.

Adult efficacy was established in pivotal trials

PIVOTAL TRIAL PROGRAM DESIGN AND RESULTS1

Trial design

  • Effectiveness was established in 3 fixed-dose, randomized, double-blind, placebo-controlled, multicenter studies, which included 1550 adult patients1
  • Enrolled adult patients had partial-onset seizures that were not adequately controlled by 1 to 2 concomitant antiepileptic drugs (AEDs)1
  • Adult patients taking concomitant levetiracetam were excluded from Study 31

Trial results

  • 25.2% and 25.7% reduction over placebo with BRIVIACT 100 mg/day (n=252) and 200 mg/day (n=249) respectively in partial-onset seizure frequency adjusted to 28 days during the treatment period in Study 3, when added to current therapy1
  • ≥50% response achieved by 30.0%, 38.1%, and 37.8% of patients with BRIVIACT 50 mg/day, 100 mg/day, and 200 mg/day vs. 20.2% with placebo in pooled results from all three studies8

BRIVIACT WAS EFFICACIOUS IN PATIENTS WHO HAD PRIOR LEVETIRACETAM EXPOSURE

In Study 3, approximately 54% of adult patients had prior exposure to levetiracetam and were evaluated in a pre-specified analysis. Adult patients taking concomitant levetiracetam were excluded from the study.1

  • 18.2% and 21.3% reduction over placebo with BRIVIACT 100 mg/day and 200 mg/day, respectively, in partial-onset seizure frequency adjusted to 28 days during the treatment period in Study 3 in patients with prior levetiracetam exposure8 

 Reasons for discontinuing levetiracetam prior to inclusion in Study 38:

•	BRIVIACT studies showed no additional benefit when co-administered with levetiracetam
  • BRIVIACT studies showed no additional benefit when co-administered with levetiracetam1

BRIVIACT safety profile was established in phase III pivotal trials

  • In adult adjunctive placebo-controlled trials, the most common adverse reactions (≥5% for BRIVIACT and ≥2% more frequently than placebo) were somnolence and sedation, dizziness, fatigue, and nausea and vomiting1
  • 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 moderate8

ADULT ADVERSE REACTIONS THAT OCCURRED AT LEAST 2% MORE FREQUENTLY FOR BRIVIACT THAN PLACEBO

adverse_reactions

For BRIVIACT doses of ≥50 mg/day in pooled placebo-controlled adjunctive therapy studies.

BRIVIACT injection safety

CONSISTENT SAFETY PROFILE ACROSS FORMULATIONS
 

IV safety trial design7 

  • Safety and tolerability were established in a phase III, multicenter, randomized, four-arm, parallel-group study of adults with uncontrolled seizures 
  • Enrolled epilepsy patients (n=105) received BRIVIACT injection administered as a 2-minute bolus or a 15-minute infusion twice daily 
  • Following a 7-day run-in period, patients were evaluated for 4.5 days 
  • Patients were randomized 1:1:1:1 to placebo/BRIVIACT bolus; placebo/BRIVIACT infusion; BRIVIACT/BRIVIACT bolus; BRIVIACT/BRIVIACT infusion
     

IV safety trial results7

  • BRIVIACT injection was generally well-tolerated. Tolerability was similar when given as a bolus or infusion, and as de novo administration or conversion 
  • Somnolence, dizziness, headache, and fatigue were the most frequently reported adverse events (>5%) 
  • Incidence of injection-related treatment-emergent adverse events was low and the most frequently reported were injection site erythema (5%) and infusion/injection site pain (4%) 
  • <2% patients discontinued due to an adverse event

IMPORTANT SAFETY INFORMATION

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. Adverse reactions with BRIVIACT injection in adult patients are generally similar to those observed with BRIVIACT tablets and also include dysgeusia, euphoric mood, feeling drunk, and infusion site pain. The safety of BRIVIACT injection in pediatric patients has not been established.

BRIVIACT provides patients with a smooth transition from hospital to home

1:1 DOSE CONVERSION BETWEEN IV AND ORAL FORMULATIONS1

THE BRIVIACT Discharge Kit contains:
 

A trial voucher for eligible patients for 30 days of free medication when they leave the hospital
 

Briviact IV voucher

A savings card to help minimize out-of-pocket costs for eligible patients who may pay as little as $10 for a 30-day supply of BRIVIACT#

Briviact IV savings card

Direct your patients to www.BRIVIACT.com/savings to download a Patient Savings Card or request a Hospital Discharge Kit from ucbCARES® at 1-844-559-2273.

#ELIGIBILITY CRITERIA AND TERMS
Savings card is not valid for use by patients who are covered by any federally funded or state-funded healthcare program (including, but not limited to, Medicare [Part D and Medigap] and those who are Medicare-eligible and enrolled in an employer-sponsored health plan for retirees, Medicaid, any state pharmaceutical assistance program, TRICARE, VA, or DoD), or for cash-paying patients. A valid BRIVIACT prescription consistent with the approved FDA labeling is required. Other Eligibility Criteria and Terms apply. Full Eligibility Criteria and Terms are available here or upon request by calling ucbCARES® at 1-844-599-CARE (2273).
 

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. Adverse reactions with BRIVIACT injection in adult patients are generally similar to those observed with BRIVIACT tablets and also include dysgeusia, euphoric mood, feeling drunk, and infusion site pain. The safety of BRIVIACT injection in pediatric patients has not been established.

BRIVIACT is a Schedule V controlled substance.

Please see full Prescribing Information.

References

  1. BRIVIACT® (brivaracetam) [package insert]. Smyrna, GA: UCB, Inc. 
  2. Stockis A, Hartstra J, Mollet M, Hadi S. Bioavailability and bioequivalence comparison of brivaracetam 10, 50, 75, and 100 mg tablets and 100 mg intravenous bolus. Epilepsia. 2016;57(8):1288-1293.
  3. Kaminski RM, Gillard M, Klitgaard H. Targeting SV2A for discovery of antiepileptic drugs. In: Noebels JL, Avoli M, Rogawski MA, eds. Jasper’s Basic Mechanisms of the Epilepsies. 4th ed. Bethesda, MD: National Center for Biotechnology Information (US); 2012:1-12.
  4. 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;664:36-44. 
  5. Nicolas JM, Hannestad J, Holden D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016;57:201-209. 
  6. Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin Pharmacol. 2018;10:1-22. 
  7. Klein P, Biton V, Dilley D, Barnes M, Schiemann J, Lu S. Safety and tolerability of adjunctive brivaracetam as intravenous infusion or bolus in patients with epilepsy. Epilepsia. 2016;57(7):1130-1138. 
  8. Data on file. UCB, Inc.