BRIVIACTÂ® (brivaracetam) CV is indicated for the treatment of partial-onset (focal) seizures in patients 4Â years of ageÂ andÂ 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 ageÂ andÂ older).
IMPORTANT SAFETY INFORMATION
BRIVIACT is associated with important warnings and precautions including suicidal behavior and ideation, somnolence, fatigue, dizziness, disturbance in gait and coordination, psychiatric adverse reactions including non-psychotic and psychotic symptoms, and hypersensitivity reactions (bronchospasm and angioedema). BRIVIACT is contraindicated in patients with a prior hypersensitivity reaction to brivaracetam or any of the inactive ingredients.
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.
Choose BRIVIACTÂ® for your partial-onset seizure patients
BRIVIACT offers a therapeutic dose on DAY ONE1
- Gradual dose escalation is not required
BRIVIACT is a new molecular entity that targets SV2A1
- Based on in vitro studies, BRIVIACT displays a 15- to 30-fold higher affinity for SV2A2; implications for clinical efficacy and tolerability are not known
- The precise mechanism by which BRIVIACT exerts its anticonvulsant activity is unknown1
The efficacy of BRIVIACT was established in adults in 3 fixed-dose, randomized, double-blind, placebo-controlled, multicenter studies, which included 1550 patients1
- In Study 3, approximately 54% of patients had prior exposure to levetiracetam and were evaluated in a pre-specified analysis1,3
- In the pre-specified analysis of patients with prior levetiracetam exposure, efficacy over placebo was observed among patients taking BRIVIACT3
Safety and tolerability of BRIVIACT were established without utilizing a titration period1
- Most common adverse reactions are somnolence and sedation, dizziness, fatigue, and nausea and vomiting symptoms
BRIVIACTÂ® is a new molecular entity in the racetam class that targets SV2A
IN A PRECLINICAL DISCOVERY PROGRAM, THE AFFINITY OF RACETAM ANALOGS FOR SYNAPTIC VESICLE PROTEIN 2A (SV2A) STRONGLY CORRELATED TO THEIR ANTICONVULSANT ACTIVITY IN AN ANIMAL MODEL4-6
The most promising compounds were profiled in a broad range of animal models of seizuresÂ andÂ epilepsy4,5
Agents with an animal model profile similar to levetiracetam* were not pursued through Phase III clinicalÂ trials5
BRIVIACT displayed anticonvulsant activity in numerous animal models of seizures and epilepsy including classicalÂ screeningÂ models4,5
BRIVIACT displays a high and selective affinity for SV2A inÂ theÂ brain,Â whichÂ may contribute to the anticonvulsantÂ effect1
The precise mechanism by which BRIVIACT exerts itsÂ anticonvulsantÂ activityÂ is unknown1
*Levetiracetam is a product manufactured by UCB.
SV2A binding is proposed to be the primary mechanism of action (MOA) for BRIVIACTÂ® andÂ levetiracetam*â 5-11
Based on in vitro studies:
- BRIVIACT displays a 15- to 30-fold higher affinityÂ forÂ SV2A2
- BRIVIACT does not display activity at HVA Ca2+ channelsâ¡ orÂ AMPAÂ receptors5
- Implications for clinical efficacy and tolerability areÂ notÂ known
- *The precise mechanism by which levetiracetam exerts its anticonvulsant activity is unknown.
- â Not all proposed mechanisms of levetiracetam are depicted.
- â¡High-voltage-activated calcium channel.
IMPORTANT SAFETY INFORMATION
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.
Efficacy was established in trialsÂ that did not utilize a titrationÂ period
PERCENT REDUCTION OVER PLACEBO IN PARTIAL-ONSET SEIZURE FREQUENCY ADJUSTED TO 28 DAYS DURING THEÂ TREATMENTÂ PERIOD1
Statistically significant based on testing procedure with alpha = 0.05.
- Effectiveness was established in adults in 3 fixed-dose, randomized, double-blind, placebo-controlled, multicenter
studies, which included 1550 patients
- Enrolled patients had partial-onset seizures that were not adequately controlled by 1 to 2 concomitant antiepileptic
BRIVIACTÂ® was studied in a challenging patient population
IMPORTANT SAFETY INFORMATION
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 50Â 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.
Efficacy was observed among patients taking BRIVIACTÂ® who had previously discontinued levetiracetam
PERCENT REDUCTION OVER PLACEBO IN PARTIAL-ONSET SEIZURE FREQUENCY ADJUSTED TO 28 DAYS DURING THEÂ TREATMENTÂ PERIOD3
Statistically significant based on testing procedure with alpha = 0.05.
Patients had to discontinue levetiracetam use more than 90 days priorÂ toÂ screening.
- In Study 3, approximately 54% of patients had prior exposure to levetiracetam and were evaluated in a pre-specified analysisâ 1,3
- Of prior levetiracetam patients, approximately 68% had failed levetiracetam due to efficacy, 14% had discontinued for an adverse drug reaction, and 20% had discontinued for other reasons3
- Patients taking concomitant levetiracetam were excluded from the study1
Patients with prior levetiracetam exposure presented with more severe baseline characteristics
IMPORTANT SAFETY INFORMATION
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.
Download complimentary pivotalÂ trialÂ publications
Brivaracetam as adjunctive treatment for uncontrolled partial epilepsyÂ inÂ adults:
A phase III randomized, double-blind, placebo-controlled trial - Victor Biton et al. Epilepsia, 55(1):57â66,Â 2014
Adjunctive brivaracetam in adults with uncontrolled focalÂ epilepsy:
Results from a double-blind, randomized, placebo-controlled trial - Phillippe Ryvlin et al. Epilepsia,Â 55(1):47â56,Â 2014
A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures - Pavel Klein et al. Epilepsia,Â 56(12):1890â1898, 2015
BRIVIACTÂ® 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 50Â 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 BRIVIACTÂ® 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
- 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 50Â MG/DAY THAN PLACEBO IN POOLED PLACEBO-CONTROLLED ADJUNCTIVE THERAPY STUDIES1
- *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 50Â mg/day: 5%
- BRIVIACT 100Â mg/day: 8%
- BRIVIACT 200Â mg/day: 7%
The most common adverse reaction leading to discontinuation was dizziness.3
General drug interactions1
- Rifampin: Co-administration with rifampin decreases BRIVIACTÂ® 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)
- BRIVIACT was studied with an oral contraceptive containing ethinylestradiol (0.03Â mg) and levonorgestrel (0.15Â mg)
- BRIVIACT 50 mg twice daily (100Â mg/day) did not significantly influence the pharmacokinetics of either substance of the oral contraceptive
- BRIVIACT 200 mg twice daily (400Â 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
Dosing IN ADULT PATIENTS (16Â YEARS ANDÂ OLDER)
BRIVIACTÂ® offers a therapeutic dose on DAY ONE
The recommended starting dose for monotherapy and adjunctive therapy is 50 mg twice daily (100 mg/day) and is initiated without titration1
Gradual dose escalation is not required with BRIVIACT
- Based on individual patient response, the dose may be adjusted between 25 mg twice daily (50Â mg/day) and 100Â mg twice daily (200Â mg/day)
- Avoid abrupt withdrawal from BRIVIACT in order to minimize the risk of increased seizure frequency and status epilepticus
Dosing in specific adult populations
- For all stages of hepatic impairment, the recommended starting dosage is 25Â mg twice daily (50Â mg/day) and the recommended maximum dosage is 75Â mg twice daily (150Â mg/day)
- Dose adjustments are not required for patients with impaired renal function; there are no data in patients with end-stage renal disease undergoing dialysis, and use of BRIVIACT is not recommended in this patient population
DOSING IN PEDIATRIC PATIENTS (4Â YEARSÂ TOÂ <16Â YEARS)
The recommended dosing regimen is dependent upon body weight and is only recommended to be administered orally. Please click here for the dosing information in the Prescribing Information.
BRIVIACTÂ® is available in multiple formulations, allowing for dosing flexibility
Considerations for tablets and oral solution1
- BRIVIACT can be given with or without food
- Tablets should be swallowed whole with liquid; they should not be chewed or crushed; tablets are not scored
Considerations for intravenous (IV) use*1
BRIVIACT injection may be used when oral administration is temporarily not feasible.
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 (16Â years of ageÂ andÂ older).
- BRIVIACT injection can be administered intravenously without further dilution or may be mixed with diluents listed below:
- 0.9% sodium chloride injection, USP
- Lactated Ringer's injection
- 5% dextrose injection, USP
- BRIVIACT injection should be administered intravenously over 2 to 15Â minutes
Adverse reactions with BRIVIACT injection are generally similar to those observed with BRIVIACT tablets and also include dysgeusia, euphoric mood, feeling drunk, and infusion site pain.
â 10-mg tablets are available for down titration.
- No blood-level monitoring required
- Approximately 100% oral bioavailability
- Linear pharmacokinetics
- The half-life (t1/2) is approximately 9Â hours, steady-state reached after 2Â days
- BRIVIACT is weakly bound (â¤20%) to plasma proteins
- No pharmacologically active metabolites
- *Clinical study experience limited to 4Â consecutive days of treatment.
Affordability and accessibility matter
UCB is committed to making BRIVIACT accessible for the majority of eligible patients across the US
9 out of 10 commercial patients have formulary access to BRIVIACTÂ® (brivaracetam)Â CV and most have unrestricted access.3
BRIVIACTÂ® Patient Savings Program
Eligible patients* pay as little as $20 per 30-day supply of BRIVIACT with the BRIVIACT Patient Savings Program
Ask your sales representative for details about the program.
- *Patients are responsible for a minimum of $20 out-of-pocket expense per 30-day supply. This card will then be applied toward any remaining out-of-pocket expense up to a maximum of $100. Most patients who have commercial prescription insurance are eligible. If you have any questions regarding your eligibility or benefits or if you wish to discontinue your participation, call the BRIVIACT Savings Program at 7602629557 (8:30 AM â 5:30 PM EST, Monday-Friday and 8:30 AM â 2:30 PM EST, Saturday). This savings card is not valid for use by patients who are covered by any federal or state funded healthcare program (including, but not limited to, Medicare [Part D and Medigap], Medicaid, any state pharmaceutical assistance program TRICARE, VA, or DoD). Offer good only in the U.S., including Puerto Rico. This card is good for use only with a valid BRIVIACT prescription at the time the prescription is filled by the pharmacist and dispensed to the patient. The maximum annual benefit amount is $1300 per calendar year. Void where prohibited by law, taxed, or restricted. This offer cannot be combined with any other promotional offer. UCB, Inc. reserves the right to rescind, revoke, or amend this offer without notice at any time. No cash value. Not eligible for sale, purchase, trade, or counterfeit.
When a prior authorization is required, PARx SolutionsÂ® and CoverMyMedsÂ® can provide assistance
PARx Solutions and CoverMyMeds offer prior authorization (PA) assistance through an electronic-based system that standardizes the medical necessity request process for most insurance providers, and for patients with commercial, Medicare Part D, and Medicaid coverage*
When a prior authorization is needed, PARx Solutions and CoverMyMeds can provide assistance.
PARx Support Solutions for Prescribers (PASS)
- PARx Solutions helps prescribers easily navigate the PA process by providing digital PAs via secure web-based and pharmacy-driven support
Get started in 4 simple steps:
- Physician completes and submits universal insurance PA request form.
- PARx completes proper PA health plan form.
- PARx submits form to proper health plan.
- PARx works with office if additional information is needed and follows up on outcome of submission.
For more information, visit www.parxsolutions.com.
Pharmacy-initiated PA requests
- If a prescription is submitted to a participating pharmacy and requires a PA, CoverMyMeds facilitates the approval process by delivering a PA to your office for completion, signature, and submission to the health plan
- More than 90%14 of retail pharmacies participate in CoverMyMeds
- CoverMyMeds also offers a web-based portal that can help your office by automating the PA process, saving prescribers and staff time and ensuring patients receive their medication faster
- *Currently, Medi-Cal, Washington State Medicaid, and Wisconsin State Medicaid require the pharmacy to submit prior authorization forms and may not be applicable to this program. This list is subject to change based on plan requirements.
- â Year-to-date average does not indicate or guarantee an individualâs approval for BRIVIACT.
Financial assistance may be available for BRIVIACTÂ® patients
The BRIVIACT Patient Assistance Program may be able to help if your patients do not have health insurance or if they are a Medicare Part D recipient and cannot afford BRIVIACT. Eligible patients are provided a free 6-month supply of medicine and can reapply every six months for continuing support.
To learn more about the BRIVIACT Patient Assistance Program or to find out if your patient might be eligible for assistance, please contact UCBCares at 1-844-599-CAREÂ (2273) or (678) 312-9268, or click below to get started.