Briviact
Generic Name: brivaracetam
(BRIV a RA se tam)
Brand Names: Briviact
Indications and Usage for Briviact
Briviact is indicated for the treatment of
partial-onset seizures in patients 16 years of age and older with epilepsy.
Briviact Dosage and AdministrationDosage
Information
Monotherapy or Adjunctive Therapy
When initiating treatment, gradual dose
escalation is not required. The recommended starting dosage is 50 mg twice
daily (100 mg per day). 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) [see Clinical Studies (14)].
Briviact injection may be used
when oral administration is temporarily not feasible. Briviact injection should
be administered 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.
Administration
Instructions for Briviact Tablets and Briviact Oral Solution
Briviact can be initiated with
either intravenous or oral administration.
Briviact tablets and oral
solution may be taken with or without food.
Briviact Tablets
Briviact tablets should be
swallowed whole with liquid. Briviact tablets should not be chewed or crushed.
Briviact Oral Solution
A calibrated measuring device
is recommended to measure and deliver the prescribed dose accurately. A
household teaspoon or tablespoon is not an adequate measuring device.
When using Briviact oral
solution, no dilution is necessary. Briviact oral solution may also be
administered using a nasogastric tube or gastrostomy tube.
Discard any unused Briviact
oral solution remaining after 5 months of first opening the bottle.
Preparation
and Administration Instructions for Briviact Injection
Briviact injection is for
intravenous use only.
Preparation
Briviact injection can be
administered intravenously without further dilution or may be mixed with
diluents listed below.
Diluents
0.9% Sodium Chloride
injection, USP
Lactated Ringer's injection
5% Dextrose injection, USP
Administration
Briviact
injection should be administered intravenously over 2 to 15 minutes.
Parenteral
drug products should be inspected visually for particulate matter and
discoloration prior to administration, whenever solution and container permit.
Product with particulate matter or discoloration should not be used. Briviact
injection is for single dose only.
Storage and Stability
The
diluted solution should not be stored for more than 4 hours at room temperature
and may be stored in polyvinyl chloride (PVC) bags. Discard any unused portion
of the Briviact injection vial contents.
Discontinuation of Briviact
Avoid
abrupt withdrawal from Briviact in order to minimize the risk of increased
seizure frequency and status epilepticus [see Warnings
and Precautions (5.5) and Clinical Studies (14)].
Patients with Hepatic Impairment
For
all stages of hepatic impairment, the recommended starting dosage is 25 mg
twice daily (50 mg per day) and the recommended maximum dosage is 75 mg twice
daily (150 mg per day) [see Use in
Specific Populations (8.7) and Clinical Pharmacology
(12.3)].
Co-administration with Rifampin
Increase
the Briviact dosage in patients on concomitant rifampin by up to 100% (i.e.,
double the dosage) [see Drug
Interactions (7.1) and Clinical Pharmacology
(12.3)].
Dosage Forms and
Strengths
Tablets
·
10 mg: white to off white,
round, film-coated, and debossed with "u10" on one side.
·
25 mg: grey, oval,
film-coated, and debossed with "u25" on one side.
·
50 mg: yellow, oval,
film-coated, and debossed with "u50" on one side.
·
75 mg: purple, oval,
film-coated, and debossed with "u75" on one side.
·
100 mg: green-grey, oval,
film-coated, and debossed with "u100" on one side.
Oral Solution
·
10 mg/mL: slightly viscous,
clear, colorless to yellowish, raspberry-flavored liquid.
Injection
·
50 mg in 5 mL in one
single-dose vial. It is a clear, colorless, sterile solution.
Contraindications
Hypersensitivity
to brivaracetam or any of the inactive ingredients in Briviact (bronchospasm
and angioedema have occurred) [see Warnings
and Precautions (5.4)].
Warnings and
PrecautionsSuicidal Behavior and Ideation
Antiepileptic
drugs (AEDs), including Briviact, increase the risk of suicidal thoughts or
behavior in patients taking these drugs for any indication. Patients treated
with any AED for any indication should be monitored for the emergence or
worsening of depression, suicidal thoughts or behavior, and/or any unusual
changes in mood or behavior.
Pooled
analyses of 199 placebo-controlled clinical trials (mono- and adjunctive
therapy) of 11 different AEDs showed that patients randomized to one of the
AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2,
2.7) of suicidal thinking or behavior compared to patients randomized to
placebo. In these trials, which had a median treatment duration of 12 weeks,
the estimated incidence rate of suicidal behavior or ideation among 27,863
AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated
patients, representing an increase of approximately one case of suicidal
thinking or behavior for every 530 patients treated. There were four suicides
in drug-treated patients in the trials and none in placebo-treated patients,
but the number is too small to allow any conclusion about drug effect on
suicide.
The
increased risk of suicidal thoughts or behavior with AEDs was observed as early
as one week after starting drug treatment with AEDs and persisted for the
duration of treatment assessed. Because most trials included in the analysis
did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior
beyond 24 weeks could not be assessed.
The
risk of suicidal thoughts or behavior was generally consistent among drugs in
the data analyzed. The finding of increased risk with AEDs of varying
mechanisms of action and across a range of indications suggests that the risk
applies to all AEDs used for any indication. The risk did not vary
substantially by age (5-100 years) in the clinical trials analyzed. Table 1
shows absolute and relative risk by indication for all evaluated AEDs.
Table 1: Risk of Suicidal Thoughts or Behaviors by Indication for
Antiepileptic Drugs in the Pooled Analysis
|
|
Indication
|
Placebo
Patients with Events Per 1000 Patients
|
Drug
Patients with Events Per 1000 Patients
|
Relative
Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients
|
Risk
Difference: Additional Drug Patients with Events Per 1000 Patients
|
|
Epilepsy
|
1.0
|
3.4
|
3.5
|
2.4
|
|
Psychiatric
|
5.7
|
8.5
|
1.5
|
2.9
|
|
Other
|
1.0
|
1.8
|
1.9
|
0.9
|
|
Total
|
2.4
|
4.3
|
1.8
|
1.9
|
The
relative risk for suicidal thoughts or behavior was higher in clinical trials
in patients with epilepsy than in clinical trials in patients with psychiatric
or other conditions, but the absolute risk differences were similar for the
epilepsy and psychiatric indications.
Anyone
considering prescribing Briviact or any other AED must balance the risk of
suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and
many other illnesses for which AEDs are prescribed are themselves associated
with morbidity and mortality and an increased risk of suicidal thoughts and
behavior. Should suicidal thoughts and behavior emerge during treatment,
consider whether the emergence of these symptoms in any given patient may be
related to the illness being treated.
Neurological Adverse Reactions
Briviact
causes somnolence, fatigue, dizziness, and disturbance in coordination.
Patients should be monitored for these signs and symptoms and advised not to
drive or operate machinery until they have gained sufficient experience on
Briviact to gauge whether it adversely affects their ability to drive or
operate machinery.
Somnolence and Fatigue
Briviact
causes dose-dependent increases in somnolence and fatigue-related adverse
reactions (fatigue, asthenia, malaise, hypersomnia, sedation, and
lethargy) [see Adverse
Reactions (6.1)]. In the Phase 3 controlled adjunctive epilepsy trials, these
events were reported in 25% of patients randomized to receive Briviact at least
50 mg/day (20% at 50 mg/day, 26% at 100 mg/day, and 27% at 200 mg/day) compared
to 14% of patients who received placebo. The risk is greatest early in
treatment but can occur at any time.
Dizziness and Disturbance in Gait and Coordination
Briviact
causes adverse reactions related to dizziness and disturbance in gait and
coordination (dizziness, vertigo, balance disorder, ataxia, nystagmus, gait
disturbance, and abnormal coordination) [see Adverse
Reactions (6.1)]. In the Phase 3 controlled adjunctive epilepsy trials,
these events were reported in 16% of patients randomized to receive Briviact at
least 50 mg/day compared to 10% of patients who received placebo. The risk is
greatest early in treatment but can occur at any time.
Psychiatric Adverse Reactions
Briviact
causes psychiatric adverse reactions. In the Phase 3 controlled adjunctive
epilepsy trials, psychiatric adverse reactions were reported in approximately
13% of patients who received Briviact (at least 50 mg/day) compared to 8% of
patients who received placebo. Psychiatric events included both non-psychotic
symptoms (irritability, anxiety, nervousness, aggression, belligerence, anger,
agitation, restlessness, depression, depressed mood, tearfulness, apathy, altered
mood, mood swings, affect lability, psychomotor hyperactivity, abnormal
behavior, and adjustment disorder) and psychotic symptoms (psychotic disorder
along with hallucination, paranoia, acute psychosis, and psychotic behavior). A
total of 1.7% of adult patients treated with Briviact discontinued treatment
because of psychiatric reactions compared to 1.3% of patients who received
placebo.
Hypersensitivity: Bronchospasm and Angioedema
Briviact
can cause hypersensitivity reactions. Bronchospasm and angioedema have been
reported in patients taking Briviact. If a patient develops hypersensitivity
reactions after treatment with Briviact, the drug should be discontinued.
Briviact is contraindicated in patients with a prior hypersensitivity reaction
to brivaracetam or any of the inactive ingredients [see Contraindications
(4)].
Withdrawal of Antiepileptic Drugs
As
with most antiepileptic drugs, Briviact should generally be withdrawn gradually
because of the risk of increased seizure frequency and status epilepticus [see Dosage and
Administration (2.4) and Clinical Studies (14)]. But if withdrawal is needed
because of a serious adverse event, rapid discontinuation can be considered.
Adverse Reactions
The
following serious adverse reactions are described elsewhere in labeling:
·
Suicidal Behavior and
Ideation [see Warnings
and Precautions (5.1)]
·
Neurological Adverse
Reactions [see Warnings
and Precautions (5.2)]
·
Psychiatric Adverse Reactions [see Warnings and
Precautions (5.3)]
·
Hypersensitivity: Bronchospasm
and Angioedema [see Warnings
and Precautions (5.4)]
·
Withdrawal of Antiepileptic
Drugs [see Warnings and
Precautions (5.5)]
Clinical Trials Experience
Because
clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to
rates in the clinical trials of another drug and may not reflect the rates
observed in practice.
In all
controlled and uncontrolled trials performed in adult epilepsy patients, Briviact
was administered as adjunctive therapy to 2437 patients. Of these patients,
1929 were treated for at least 6 months, 1500 for at least 12 months, 1056 for
at least 24 months, and 758 for at least 36 months. A total of 1558 patients
(1099 patients treated with Briviact and 459 patients treated with placebo)
constituted the safety population in the pooled analysis of Phase 3
placebo-controlled studies in patients with partial-onset seizures (Studies 1,
2, and 3) [see Clinical
Studies (14)]. The adverse reactions presented in Table 2 are based on this
safety population; the median length of treatment in these studies was 12
weeks. Of the patients in those studies, approximately 51% were male, 74% were
Caucasian, and the mean age was 38 years.
In the
Phase 3 controlled epilepsy studies, adverse events occurred in 68% of patients
treated with Briviact and 62% treated with placebo. The most common adverse
reactions occurring at a frequency of at least 5% in patients treated with
Briviact doses of at least 50 mg/day and greater than placebo were somnolence
and sedation (16%), dizziness (12%), fatigue (9%), and nausea and vomiting
symptoms (5%).
The
discontinuation rates due to adverse events were 5%, 8%, and 7% for patients
randomized to receive Briviact at the recommended doses of 50 mg, 100 mg, and
200 mg/day, respectively, compared to 4% in patients randomized to receive
placebo.
Table 2 lists adverse
reactions for Briviact that occurred at least 2% more frequently for Briviact
doses of at least 50 mg/day than placebo.
Table 2: Adverse Reactions in Pooled Placebo-Controlled Adjunctive
Therapy Studies in Patients with Partial-Onset Seizures (Briviact 50 mg/day,
100 mg/day, and 200 mg/day)
|
|
Adverse
Reactions
|
Briviact
(N=803)
%
|
Placebo
(N=459)
%
|
|
*
Cerebellar coordination and balance disturbances
includes ataxia, balance disorder, coordination abnormal, and nystagmus.
|
|
Gastrointestinal disorders
|
|
|
|
Nausea/vomiting
symptoms
|
5
|
3
|
|
Constipation
|
2
|
0
|
|
Nervous system disorders
|
|
|
|
Somnolence and
sedation
|
16
|
8
|
|
Dizziness
|
12
|
7
|
|
Fatigue
|
9
|
4
|
|
Cerebellar
coordination and balance disturbances*
|
3
|
1
|
|
Psychiatric disorders
|
|
|
|
Irritability
|
3
|
1
|
There was no apparent
dose-dependent increase in adverse reactions listed in Table 2 with the
exception of somnolence and sedation.
Hematologic Abnormalities
Briviact can cause hematologic
abnormalities. In the Phase 3 controlled adjunctive epilepsy studies, a total
of 1.8% of Briviact-treated patients and 1.1% of placebo-treated patients had
at least one clinically significant decreased white blood cell count (<3.0 ×
109/L),
and 0.3% of Briviact-treated patients and 0% of placebo-treated patients had at
least one clinically significant decreased neutrophil count (<1.0 × 109/L).
Adverse Reactions with Briviact Injection
Adverse reactions with
Briviact injection were generally similar to those observed with Briviact
tablets. Other adverse events that occurred in at least 3% of patients who
received Briviact injection included dysgeusia, euphoric mood, feeling drunk,
and infusion site pain.
Comparison by Sex
There were no significant
differences by sex in the incidence of adverse reactions.
Drug InteractionsRifampin
Co-administration with
rifampin decreases Briviact plasma concentrations likely because of CYP2C19
induction [see Clinical
Pharmacology (12.3)]. Prescribers should increase
the Briviact dose by up to 100% (i.e., double the dosage) in patients while
receiving concomitant treatment with rifampin [see Dosage
and Administration (2.6)].
Carbamazepine
Co-administration with
carbamazepine may increase exposure to carbamazepine-epoxide, the active
metabolite of carbamazepine. Though available data did not reveal any safety
concerns, if tolerability issues arise when co-administered, carbamazepine dose
reduction should be considered [see Clinical
Pharmacology (12.3)].
Phenytoin
Because Briviact can increase
plasma concentrations of phenytoin, phenytoin levels should be monitored in
patients when concomitant Briviact is added to or discontinued from ongoing
phenytoin therapy [see Clinical
Pharmacology (12.3)].
Levetiracetam
Briviact provided no added
therapeutic benefit to levetiracetam when the two drugs were
co-administered [see Clinical
Studies (14)].
USE IN SPECIFIC POPULATIONSPregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure
registry that monitors pregnancy outcomes in women exposed to antiepileptic
drugs (AEDs), such as Briviact, during pregnancy. Encourage patients who are
taking Briviact during pregnancy to enroll in the North American Antiepileptic
Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334
or visiting http://www.aedpregnancyregistry.org/.
Risk Summary
There are no adequate data on
the developmental risks associated with use of Briviact in pregnant women. In
animal studies, brivaracetam produced evidence of developmental toxicity
(increased embryofetal mortality and decreased fetal body weights in rabbits;
decreased growth, delayed sexual maturation, and long-term neurobehavioral
changes in rat offspring) at maternal plasma exposures greater than clinical
exposures [see Data].
In the U.S. general
population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively. The background risk of major birth defects and miscarriage for
the indicated population is unknown.
Data
Animal Data
Oral administration of
brivaracetam (0, 150, 300, or 600 mg/kg/day) to pregnant rats during the period
of organogenesis did not produce any significant maternal or embryofetal
toxicity. The highest dose tested was associated with maternal plasma exposures
(AUC) approximately 30 times exposures in humans at the maximum recommended
dose (MRD) of 200 mg/day.
Oral administration of
brivaracetam (0, 30, 60, 120, or 240 mg/kg/day) to pregnant rabbits during the
period of organogenesis resulted in embryofetal mortality and decreased fetal
body weights at the highest dose tested, which was also maternally toxic. The
highest no-effect dose (120 mg/kg/day) was associated with maternal plasma
exposures approximately 4 times human exposures at the MRD.
When brivaracetam (0, 150,
300, or 600 mg/kg/day) was orally administered to rats throughout pregnancy and
lactation, decreased growth, delayed sexual maturation (female), and long-term
neurobehavioral changes were observed in the offspring at the highest dose. The
highest no-effect dose (300 mg/kg/day) was associated with maternal plasma
exposures approximately 7 times human exposures at the MRD.
Brivaracetam was shown to
readily cross the placenta in pregnant rats after a single oral (5 mg/kg) dose
of 14C-brivaracetam. From 1 hour post dose, radioactivity levels in
fetuses, amniotic fluid, and placenta were similar to those measured in
maternal blood.
Lactation
Risk Summary
No data are available
regarding the presence of brivaracetam in human milk, the effects on the breastfed
infant, or the effects of the drug on milk production. Studies in lactating
rats have shown excretion of brivaracetam or metabolites in milk [see Data].
The developmental and health
benefits of breastfeeding should be considered along with the mother's clinical
need for Briviact and any potential adverse effects on the breastfed infant
from Briviact or from the underlying maternal condition.
Data
Animal Data
Following a single oral (5 mg/kg)
dose of 14C-brivaracetam to lactating rats, radioactivity was secreted in
milk and rapidly reached levels similar to those in plasma.
Pediatric Use
Safety and effectiveness of
Briviact in adolescents 16 years of age have been established [see Clinical Studies (14)].
Safety and effectiveness in
pediatric patients below the age of 16 years have not been established.
The potential adverse effects
of brivaracetam on postnatal growth and development were investigated in
juvenile rats and dogs. Oral administration (0, 150, 300, or 600 mg/kg/day) to
rats during the neonatal and juvenile periods of development resulted in
increased mortality, decreased body weight gain, delayed male sexual maturation,
and adverse neurobehavioral effects at the highest dose tested and decreased
brain size and weight at all doses. Therefore, a no-effect dose was not
established; the lowest dose tested in juvenile rats was associated with plasma
exposures (AUC) approximately 2 times those in adult humans at the maximum
recommended dose (MRD) of 200 mg/day. In dogs, oral administration (0, 15, 30,
or 100 mg/kg/day) throughout the neonatal and juvenile periods of development
induced liver changes similar to those observed in adult animals at the highest
dose but produced no adverse effects on growth, bone density or strength,
neurological testing, or neuropathology evaluation. The overall no-effect dose
(30 mg/kg/day) and the no-effect dose for adverse effects on developmental
parameters (100 mg/kg/day) were associated with plasma exposures approximately
equal to and 4 times, respectively, adult human exposures at the MRD.
Geriatric Use
There were insufficient
numbers of patients 65 years of age and older in the double-blind,
placebo-controlled epilepsy trials (n=38) to allow adequate assessment of the
effectiveness of Briviact in this population. In general, dose selection for an
elderly patient should be judicious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology
(12.3)].
Renal
Impairment
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 [see Clinical
Pharmacology (12.3)].
Hepatic
Impairment
Because of increases in
Briviact exposure, dosage adjustment is recommended for all stages of hepatic
impairment [see Dosage
and Administration (2.5) and Clinical Pharmacology
(12.3)].
Drug Abuse and DependenceControlled
Substance
Briviact contains brivaracetam
and is listed as a Schedule V controlled substance.
Abuse
In a human abuse potential
study, single doses of Briviact at therapeutic and supratherapeutic doses were
compared to alprazolam (C-IV) (1.5 mg and 3 mg). Briviact at the recommended
single dose (50 mg) caused fewer sedative and euphoric effects than alprazolam;
however, Briviact at supratherapeutic single doses (200 mg and 1000 mg) was
similar to alprazolam on other measures of abuse.
Dependence
There was no evidence of
physical dependence potential or a withdrawal syndrome with Briviact in a
pooled review of placebo-controlled adjunctive therapy studies [see Warnings and
Precautions (5.5)].
Overdosage
There is limited clinical
experience with Briviact overdose in humans. Somnolence and dizziness were
reported in a patient taking a single dose of 1400 mg (14 times the highest
recommended single dose) of Briviact. The following adverse reactions were
reported with Briviact overdose: vertigo, balance disorder, fatigue, nausea,
diplopia, anxiety, and bradycardia. In general, the adverse reactions
associated with Briviact overdose were consistent with the known adverse
reactions.
There is no specific antidote
for overdose with Briviact. In the event of overdose, standard medical practice
for the management of any overdose should be used. An adequate airway,
oxygenation, and ventilation should be ensured; monitoring of cardiac rate and
rhythm and vital signs is recommended. A certified poison control center should
be contacted for updated information on the management of overdose with
Briviact. There are no data on the removal of brivaracetam using hemodialysis,
but because less than 10% of brivaracetam is excreted in urine, hemodialysis is
not expected to enhance Briviact clearance.
Briviact 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:
Brivaracetam is a white to
off-white crystalline powder. It is very soluble in water, buffer (pH 1.2, 4.5,
and 7.4), ethanol, methanol, and glacial acetic acid. It is freely soluble in
acetonitrile and acetone and soluble in toluene. It is very slightly soluble in
n-hexane.
Tablets
Briviact tablets are for oral
administration and contain the following inactive ingredients: croscarmellose
sodium, lactose monohydrate, betadex (β-cyclodextrin), anhydrous lactose,
magnesium stearate, and film coating agents specified below:
10 mg tablets: polyvinyl
alcohol, talc, polyethylene glycol 3350, titanium dioxide
25 mg and 100 mg tablets:
polyvinyl alcohol, talc, polyethylene glycol 3350, titanium dioxide, yellow
iron oxide, black iron oxide
50 mg tablets: polyvinyl
alcohol, talc, polyethylene glycol 3350, titanium dioxide, yellow iron oxide,
red iron oxide
75 mg tablets: polyvinyl
alcohol, talc, polyethylene glycol 3350, titanium dioxide, yellow iron oxide,
red iron oxide, black iron oxide
Oral Solution
Briviact oral solution
contains 10 mg of brivaracetam per mL. The inactive ingredients are sodium
citrate, anhydrous citric acid, methylparaben, sodium carboxymethylcellulose,
sucralose, sorbitol solution, glycerin, raspberry flavor, and purified water.
Injection
Briviact injection is a clear,
colorless liquid provided as a sterile, preservative-free solution. Briviact
injection contains 10 mg brivaracetam per mL for intravenous administration.
One vial contains 50 mg of brivaracetam drug substance. It contains the
following inactive ingredients: sodium acetate (trihydrate), glacial acetic
acid (for pH adjustment to 5.5), sodium chloride, and water for injection.
Briviact - Clinical PharmacologyMechanism 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.
Pharmacodynamics
Interactions with Alcohol
In a pharmacokinetic and
pharmacodynamic interaction study in healthy subjects, co-administration of
Briviact (single dose 200 mg [2 times greater than the highest recommended
single dose]) and ethanol (continuous intravenous infusion to achieve a blood alcohol
concentration of 60 mg/100 mL during 5 hours) increased the effects of alcohol
on psychomotor function, attention, and memory. Co-administration of Briviact
and ethanol caused a larger decrease from baseline in saccadic peak velocity,
smooth pursuit, adaptive tracking performance, and Visual Analog Scale (VAS)
alertness, and a larger increase from baseline in body sway and in saccadic
reaction time compared with Briviact alone or ethanol alone. The immediate word
recall scores were generally lower for Briviact when co-administered with
ethanol.
Cardiac Electrophysiology
At a dose 4 times the maximum
recommended dose, Briviact did not prolong the QT interval to a clinically
relevant extent.
Pharmacokinetics
Briviact tablets, oral
solution, and injection can be used interchangeably. Brivaracetam exhibits
linear and time-independent pharmacokinetics at the approved doses.
The pharmacokinetics of
brivaracetam are similar when used as monotherapy or as adjunctive therapy for
the treatment of partial-onset seizures.
Absorption
Brivaracetam is highly
permeable and is rapidly and almost completely absorbed after oral
administration. Pharmacokinetics is dose-proportional from 10 to 600 mg (a
range that extends beyond the minimum and maximum single-administration dose
levels described in Dosage and Administration [see Dosage
and Administration (2.1)]). The median Tmax for tablets taken
without food is 1 hour (range 0.25 to 3 hours). Co-administration with a
high-fat meal slowed absorption, but the extent of absorption remained
unchanged. Specifically, when a 50 mg tablet was administered with a high-fat
meal, Cmax (maximum brivaracetam plasma concentration during a dose
interval, an exposure metric) was decreased by 37% and Tmax was delayed by 3 hours,
but AUC (area under the brivaracetam plasma concentration versus time curve, an
exposure metric) was essentially unchanged (decreased by 5%).
Distribution
Brivaracetam is weakly bound
to plasma proteins (≤20%). The volume of distribution is 0.5 L/kg, a value
close to that of the total body water. Brivaracetam is rapidly and evenly
distributed in most tissues.
Elimination
Metabolism
Brivaracetam is primarily
metabolized by hydrolysis of the amide moiety to form the corresponding
carboxylic acid metabolite, and secondarily by hydroxylation on the propyl side
chain to form the hydroxy metabolite. The hydrolysis reaction is mediated by
hepatic and extra-hepatic amidase. The hydroxylation pathway is mediated
primarily by CYP2C19. In human subjects possessing genetic variations in
CYP2C19, production of the hydroxy metabolite is decreased 2-fold or 10-fold,
while the blood level of brivaracetam itself is increased by 22% or 42%,
respectively, in individuals with one or both mutated alleles. CYP2C19 poor
metabolizers and patients using inhibitors of CYP2C19 may require dose
reduction. An additional hydroxy acid metabolite is created by hydrolysis of
the amide moiety on the hydroxy metabolite or hydroxylation of the propyl side
chain on the carboxylic acid metabolite (mainly by CYP2C9). None of the 3
metabolites are pharmacologically active.
Excretion
Brivaracetam is eliminated
primarily by metabolism and by excretion in the urine. More than 95% of the
dose, including metabolites, is excreted in the urine within 72 hours after
intake. Fecal excretion accounts for less than 1% of the dose. Less than 10% of
the dose is excreted unchanged in the urine. Thirty-four percent of the dose is
excreted as the carboxylic acid metabolite in urine. The terminal plasma
half-life (t1/2) is approximately 9 hours.
Specific Populations
Age
Geriatric Population: In a
study in elderly subjects (65 to 79 years old; creatinine clearance 53 to 98
mL/min/1.73 m2) receiving Briviact 200 mg twice daily (2 times the highest
recommended dosage), the plasma half-life of brivaracetam was 7.9 hours and 9.3
hours in the 65 to 75 and >75 years groups, respectively. The steady-state
plasma clearance of brivaracetam was slightly lower (0.76 mL/min/kg) than in
young healthy controls (0.83 mL/min/kg).
Sex
There were no differences
observed in the pharmacokinetics of brivaracetam between male and female
subjects.
Race/Ethnicity
A population pharmacokinetic
analysis comparing Caucasian and non-Caucasian patients showed no significant
pharmacokinetic difference.
Renal Impairment
A study in subjects with
severe renal impairment (creatinine clearance <30 mL/min/1.73m2 and not requiring
dialysis) revealed that the plasma AUC of brivaracetam was moderately increased
(21%) relative to healthy controls, while the AUCs of the acid, hydroxy, and
hydroxyacid metabolites were increased 3-fold, 4-fold, and 21-fold, respectively.
The renal clearance of these inactive metabolites was decreased 10-fold.
Brivaracetam has not been studied in patients undergoing hemodialysis [see Use in Specific
Populations (8.6)].
Hepatic Impairment
A pharmacokinetic study in
subjects with hepatic cirrhosis, Child-Pugh grades A, B, and C, showed 50%,
57%, and 59% increases in brivaracetam exposure, respectively, compared to
matched healthy controls [see Dosage
and Administration (2.5) and Use in Specific
Populations (8.7)].
Drug Interaction Studies
In Vitro Assessment of Drug Interactions
Drug-Metabolizing Enzyme Inhibition
Brivaracetam did not inhibit
CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, or 3A4. Brivaracetam weakly inhibited CYP2C19
and would not be expected to cause significant inhibition of CYP2C19 in humans.
Brivaracetam was an inhibitor of epoxide hydrolase, (IC50 = 8.2 μM), suggesting
that brivaracetam can inhibit the enzyme in vivo.
Drug-Metabolizing Enzyme Induction
Brivaracetam at concentrations
up to 10 μM caused little or no change of mRNA expression of CYP1A2, 2B6, 2C9,
2C19, 3A4, and epoxide hydrolase. It is unlikely that brivaracetam will induce
these enzymes in vivo.
Transporters
Brivaracetam was not a
substrate of P-gp, MRP1, or MRP2. Brivaracetam did not inhibit or weakly
inhibit BCRP, BSEP, MATE1, MATE2/K, MRP2, OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3,
or P-gp, suggesting that brivaracetam is unlikely to inhibit these
transporters in vivo.
In Vivo Assessment of Drug Interactions
Drug Interaction Studies with Antiepileptic Drugs (AEDs)
Potential interactions between
Briviact (25 mg twice daily to 100 mg twice daily) and other AEDs were
investigated in a pooled analysis of plasma drug concentrations from all Phase
2 and 3 studies and in a population exposure-response analysis of
placebo-controlled, Phase 3 studies in adjunctive therapy in the treatment of
partial-onset seizures. None of the interactions require changes in the dose of
Briviact. Interactions with carbamazepine and phenytoin can be clinically
important [see Drug
Interactions (7.2)and (7.3)]. The interactions are
summarized in Table 3.
Table 3: Drug Interactions Between Briviact and Concomitant
Antiepileptic Drugs
|
|
Concomitant AED
|
Influence of AED on Briviact
|
Influence of Briviact on AED
|
|
*
Brivaracetam is
a reversible inhibitor of epoxide hydrolase resulting in an increased
concentration of carbamazepine epoxide, an active metabolite of
carbamazepine. The carbamazepine epoxide plasma concentration increased up to
198% at a Briviact dose of 100 mg twice daily.
†
At a supratherapeutic dose of 400 mg/day
brivaracetam, there was a 20% increase in phenytoin plasma concentration.
|
|
Carbamazepine
|
26% decrease in
plasma concentration
|
None for
carbamazepine
|
|
|
|
Increase of
carbamazepine-epoxide metabolite*
[see Drug Interactions (7.2)]
|
|
Lacosamide
|
No data
|
None
|
|
Lamotrigine
|
None
|
None
|
|
Levetiracetam
|
None
|
None
|
|
Oxcarbazepine
|
None
|
None on the
active monohydroxy metabolite derivative (MHD)
|
|
Phenobarbital
|
19% decrease in
plasma concentration
|
None
|
|
Phenytoin
|
21% decrease in
plasma concentration
|
Up to 20%
increase in plasma concentration
[see Drug Interactions (7.3)]†
|
|
Pregabalin
|
No data
|
None
|
|
Topiramate
|
None
|
None
|
|
Valproic acid
|
None
|
None
|
|
Zonisamide
|
No data
|
None
|
Drug Interaction Studies with Other Drugs
Effect of Other Drugs on Briviact
Co-administration with CYP
inhibitors or transporter inhibitors is unlikely to significantly affect
brivaracetam exposure.
Co-administration with
rifampin decreases brivaracetam plasma concentrations by 45%, an effect that is
probably the result of CYP2C19 induction [see Dosage
and Administration (2.6) and Drug Interactions (7.1)].
Oral Contraceptives
Co-administration of Briviact
200 mg twice daily (twice the recommended maximum daily dosage) with an oral
contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15
mg) reduced estrogen and progestin AUCs by 27% and 23%, respectively, without
impact on suppression of ovulation. However, co-administration of Briviact 50
mg twice daily with an oral contraceptive containing ethinylestradiol (0.03 mg)
and levonorgestrel (0.15 mg) did not significantly influence the pharmacokinetics
of either substance. The interaction is not expected to be of clinical
significance.
Nonclinical ToxicologyCarcinogenesis,
Mutagenesis, Impairment of Fertility
Carcinogenesis
In a carcinogenicity study in
mice, oral administration of brivaracetam (0, 400, 550, or 700 mg/kg/day) for
104 weeks increased the incidence of liver tumors (hepatocellular adenoma and
carcinoma) in male mice at the two highest doses tested. At the dose (400
mg/kg) not associated with an increase in liver tumors, plasma exposures (AUC)
were approximately equal to those in humans at the maximum recommended dose
(MRD) of 200 mg/day. Oral administration (0, 150, 230, 450, or 700 mg/kg/day)
to rats for 104 weeks resulted in an increased incidence of thymus tumors (benign
thymoma) in female rats at the highest dose tested. At the highest dose not
associated with an increase in thymus tumors, plasma exposures were
approximately 9 times those in humans at the MRD.
Mutagenesis
Brivaracetam was negative for
genotoxicity in in vitro (Ames,
mouse lymphoma, and CHO chromosomal aberration) and in
vivo (rat bone marrow micronucleus) assays.
Impairment of Fertility
Oral administration of
brivaracetam (0, 100, 200, or 400 mg/kg/day) to male and female rats prior to
and throughout mating and early gestation produced no adverse effects on
fertility. The highest dose tested was associated with plasma exposures
approximately 6 (males) and 13 (females) times those in humans at the MRD.
Clinical Studies
The effectiveness of Briviact
in partial-onset seizures with or without secondary generalization was
established in 3 fixed-dose, randomized, double-blind, placebo-controlled,
multicenter studies (Studies 1, 2, and 3), which included 1550 patients.
Patients enrolled had partial-onset seizures that were not adequately
controlled with 1 to 2 concomitant antiepileptic drugs (AEDs). In each of these
studies, 72% to 86% of patients were taking 2 or more concomitant AEDs with or
without vagal nerve stimulation. The median baseline seizure frequency across
the 3 studies was 9 seizures per 28 days. Patients had a mean duration of
epilepsy of approximately 23 years.
All trials had an 8-week
baseline period, during which patients were required to have at least 8
partial-onset seizures. The baseline period was followed by a 12-week treatment
period. There was no titration period in these studies. Study 1 compared doses
of Briviact 50 mg/day and 100 mg/day with placebo. Study 2 compared a dose of
Briviact 50 mg/day with placebo. Study 3 compared doses of Briviact 100 mg/day
and 200 mg/day with placebo. Briviact was administered in equally divided twice
daily doses. Upon termination of Briviact treatment, patients were
down-titrated over a 1-, 2-, and 4-week duration for patients receiving 25, 50,
and 100 mg twice daily Briviact, respectively.
The primary efficacy outcome
in Study 1 and Study 2 was the percent reduction in 7-day partial-onset seizure
frequency over placebo, while the primary outcome for Study 3 was the percent
reduction in 28-day partial-onset seizure frequency over placebo. The criteria
for statistical significance for all 3 studies was p<0.05. Table 4 presents
the primary efficacy outcome of the percent change in seizure frequency over
placebo, based upon each study's protocol-defined 7- and 28-day seizure
frequency efficacy outcome.
Table 4: Percent Reduction in Partial-Onset Seizure Frequency over
Placebo (Studies 1, 2, and 3)
|
|
|
Percent Reduction Over Placebo
(%)
|
|
*
Based upon 7-day
seizure frequency
†
Statistically
significant based on testing procedure with alpha = 0.05
‡
Based upon 28-day seizure frequency
|
|
STUDY 1*
|
|
Placebo
(n=100)
|
-------
|
|
50 mg/day
(n=99)
|
9.5
|
|
100 mg/day
(n=100)
|
17.0
|
|
STUDY 2*
|
|
Placebo
(n=96)
|
-------
|
|
50 mg/day
(n=101)
|
16.9†
|
|
STUDY 3‡
|
|
Placebo
(n=259)
|
------
|
|
100 mg/day
(n=252)
|
25.2†
|
|
200 mg/day
(n= 249)
|
25.7†
|
Figure 1 presents the
percentage of patients by category of reduction from baseline in partial-onset
seizure frequency per 28 days for all pooled patients in the 3 pivotal studies.
Patients in whom the seizure frequency increased are shown at left as
"worse." Patients with an improvement in percent reduction from
baseline partial-onset seizure frequency are shown in the 4 right-most
categories.
Figure
1: Proportion of Patients by Category of Seizure Response for Briviact and
Placebo Across all Three Double-Blind Trials
Treatment with Levetiracetam
In Studies 1 and 2, which
evaluated Briviact dosages of 50 mg and 100 mg daily, approximately 20% of the
patients were on concomitant levetiracetam. Although the numbers of patients
were limited, Briviact provided no added benefit when it was added to
levetiracetam.
Although patients on
concomitant levetiracetam were excluded from Study 3, which evaluated 100 and
200 mg daily, approximately 54% of patients in this study had prior exposure to
levetiracetam.
How Supplied/Storage and Handling
How Supplied
Briviact Tablets
10 mg are white to off-white, round, film-coated,
and debossed with "u10" on one side. They are supplied as
follows:
|
|
Bottles of 60
tablets
|
NDC 50474-370-66
|
25 mg are grey, oval, film-coated, and debossed
with "u25" on one side. They are supplied as follows:
|
|
Bottles of 60
tablets
|
NDC 50474-470-66
|
|
|
Unit dose
cartons of 100 tablets
|
NDC 50474-470-09
|
50 mg are yellow, oval, film-coated, and debossed
with "u50" on one side. They are supplied as follows:
|
|
Bottles of 60
tablets
|
NDC 50474-570-66
|
|
|
Unit dose
cartons of 100 tablets
|
NDC 50474-570-09
|
75 mg are purple, oval, film-coated, and debossed
with "u75" on one side. They are supplied as follows:
|
|
Bottles of 60
tablets
|
NDC 50474-670-66
|
100 mg are green-grey, oval, film-coated, and
debossed with "u100" on one side. They are supplied as follows:
|
|
Bottles of 60
tablets
|
NDC 50474-770-66
|
|
|
Unit dose
cartons of 100 tablets
|
NDC 50474-770-09
|
Briviact Oral Solution
10 mg/mL is a slightly viscous, clear, colorless to
yellowish, raspberry-flavored liquid. It is supplied in amber glass
bottles:
|
|
300 mL bottles
|
NDC 50474-870-15
|
Briviact Injection
50 mg/5 mL is a clear, colorless, sterile solution
supplied in colorless single-dose glass vials.
|
|
Carton of 10
vials
|
NDC 50474-970-75
|
Storage and
Handling
Store at 25°C (77°F);
excursions permitted between 15°C to 30°C (59°F to 86°F). See USP Controlled
Room Temperature. Do not freeze Briviact injection or oral solution.
Discard any unused Briviact
oral solution remaining after 5 months of first opening the bottle.
Briviact injection vials are
single-dose only [see Dosage
and Administration (2.3)].
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide).
Suicidal Behavior and Ideation
Counsel patients, their
caregivers, and/or families that antiepileptic drugs, including Briviact, may
increase the risk of suicidal thoughts and behavior, and advise patients to be
alert for the emergence or worsening of symptoms of depression; unusual changes
in mood or behavior; or suicidal thoughts, behavior, or thoughts about
self-harm. Advise patients, their caregivers, and/or families to report
behaviors of concern immediately to a healthcare provider [see Warnings and
Precautions (5.1)].
Neurological Adverse Reactions
Counsel patients that Briviact
causes somnolence, fatigue, dizziness, and gait disturbance. These adverse
reactions, if observed, are more likely to occur early in treatment but can
occur at any time. Advise patients not to drive or operate machinery until they
have gained sufficient experience on Briviact to gauge whether it adversely
affects their ability to drive or operate machinery [see Warnings
and Precautions (5.2)].
Psychiatric Adverse Reactions
Advise patients that Briviact
causes changes in behavior (e.g., aggression, agitation, anger, anxiety, and
irritability) and psychotic symptoms. Instruct patients to report these
symptoms immediately to their healthcare provider [see Warnings
and Precautions (5.3)].
Hypersensitivity: Bronchospasm and Angioedema
Advise patients that symptoms
of hypersensitivity including bronchospasm and angioedema can occur with
Briviact. Instruct them to seek immediate medical care should they experience
signs and symptoms of hypersensitivity [see Warnings
and Precautions (5.4)].
Withdrawal of Antiepileptic Drugs
Advise patients not to
discontinue use of Briviact without consulting with their healthcare provider.
Briviact should normally be gradually withdrawn to reduce the potential for
increased seizure frequency and status epilepticus [see Warnings
and Precautions (5.5)].
Pregnancy
Advise patients to notify
their healthcare provider if they become pregnant or intend to become pregnant
during Briviact therapy. Encourage patients to enroll in the North American
Antiepileptic Drug Pregnancy Registry if they become pregnant. This registry is
collecting information about the safety of antiepileptic drugs during
pregnancy [see Use in
Specific Populations (8.1)].
Dosing Instructions
Counsel patients that Briviact
may be taken with or without food. Instruct patients that Briviact tablets
should be swallowed whole with liquid and not chewed or crushed [see Dosage and
Administration (2.2)].
Advise patients that the
dosage of Briviact oral solution should be measured using a calibrated
measuring device and not a household teaspoon. Instruct patients to discard any
unused Briviact oral solution after 5 months of first opening the bottle [see Dosage and
Administration (2.2)].
Briviact Tablets, Briviact
Oral Solution, and Briviact Injection manufactured for
UCB, Inc.
Smyrna, GA 30080
Briviact® is a registered
trademark of the UCB Group of Companies.
©2017, UCB, Inc., Smyrna, GA 30080
All rights reserved.
MEDICATION GUIDE
Briviact® (briv
ee akt) CV
(brivaracetam)
tablets, oral solution, and injection for intravenous use
What
is the most important information I should know about Briviact?
Briviact
is a federally controlled substance (CV) because it can be abused or lead to
dependence. Keep Briviact in a safe place to prevent misuse and abuse. Selling
or giving away Briviact may harm others and is against the law.
Like
other antiepileptic drugs, Briviact may cause suicidal thoughts or actions in a
very small number of people, about 1 in 500 people taking it.
Call a
healthcare provider right away if you have any of these symptoms, especially if
they are new, worse, or worry you:
|
· thoughts
about suicide or dying
· new
or worse depression
· feeling
agitated or restless
· trouble
sleeping (insomnia)
· acting
aggressive, feeling angry, or being violent
· an
extreme increase in activity and talking (mania)
|
· attempts
to commit suicide
· new
or worse anxiety
· panic
attacks
· new
or worse irritability
· acting
on dangerous impulses
· other
unusual changes in behavior or mood
|
Suicidal thoughts or actions
can be caused by things other than medicines. If you have suicidal thoughts or
actions, your healthcare provider may check for other causes.
How
can I watch for early symptoms of suicidal thoughts and actions?
Pay attention to any changes, especially sudden
changes, in mood, behaviors, thoughts, or feelings.Keep all follow-up visits with your healthcare provider
as scheduled.
Call your healthcare provider
between visits as needed, especially if you are worried about symptoms.
Do not
stop Briviact without first talking to a healthcare provider.
Stopping Briviact suddenly can cause serious
problems.Stopping a seizure medicine suddenly can cause
seizures that will not stop (status epilepticus).
What
is Briviact?
Briviact is a prescription medicine that can be
used to treat partial-onset seizures in people 16 years of age and older
with epilepsy. Briviact may be given in the vein (intravenously) when
Briviact is not able to be taken by mouth.
It is not known if Briviact is
safe and effective in children younger than 16 years of age.
Who
should not take Briviact?
Do not take Briviact if you
are allergic to brivaracetam or any of the inactive ingredients in Briviact.
See the end of this Medication Guide for a complete list of ingredients in
Briviact.
What
should I tell my healthcare provider before starting Briviact?
Before taking Briviact, tell
your healthcare provider about all of your medical conditions, including if
you:
·
have or had depression, mood
problems, or suicidal thoughts or behavior
·
have liver problems
·
have abused or been dependent
on prescription medicines, street drugs, or alcohol
·
have any other medical
problems
·
are pregnant or plan to become
pregnant. It is not known if Briviact will harm your unborn baby. Tell your
healthcare provider right away if you become pregnant while taking Briviact.
You and your healthcare provider will have to decide if you should take
Briviact while you are pregnant. If you become pregnant while taking Briviact,
talk to your healthcare provider about registering with the North American
Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by
calling 1-888-233-2334. The purpose of this registry is to collect information
about the safety of Briviact and other antiepileptic medicines during
pregnancy.
·
are breastfeeding or plan to
breastfeed. It is not known if Briviact passes into your breast milk. Talk to
your healthcare provider about the best way to feed your baby if you take
Briviact.
Tell
your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. Briviact may affect the way other medicines
work, and other medicines may affect how Briviact works. Do not start a new
medicine without first talking with your healthcare provider. Know the
medicines you take. Keep a list of them to show your healthcare provider and
pharmacist each time you get a new medicine.
How
should I take Briviact?
·
Take Briviact exactly as your
healthcare provider tells you.
·
Your healthcare provider will
tell you how much Briviact to take and when to take it.
·
Your healthcare provider may
change your dose if needed. Do not change your dose without talking to your
healthcare provider.
·
Take Briviact with or without
food.
·
Swallow Briviact tablets whole
with a liquid. Do not chew or crush Briviact tablets before swallowing.
·
If your healthcare provider
has prescribed Briviact oral solution, be sure to ask your pharmacist for a
medicine dropper or medicine cup to help you measure the correct amount of
Briviact oral solution. Do not use a household teaspoon. Ask your pharmacist for
instructions on how to use the measuring device the right way.
·
Briviact injection can be
given to you by intravenous (IV) infusion into your vein, as prescribed by your
healthcare provider.
What should I
avoid while taking Briviact?
Do not drive or
operate machinery until you know how Briviact affects you. Briviact may cause
drowsiness, tiredness, dizziness, and problems with your balance and
coordination.
What are the
possible side effects of Briviact?
Briviact may
cause serious side effects, including:
·
See "What
is the most important information I should know about Briviact?"
·
Nervous system problems. Drowsiness,
tiredness, and dizziness are common with Briviact, but can be severe. See
"What
should I avoid while taking Briviact?" Briviact can also cause problems
with balance and coordination.
·
Mental (psychiatric) symptoms. Briviact
can cause mood and behavior changes such as aggression, agitation, anger,
anxiety, apathy, mood swings, depression, hostility, and irritability.
Irritability and anxiety are common with Briviact, and can be severe. People
who take Briviact can also get psychotic symptoms such as hallucinations (seeing
or hearing things that are really not there), delusions (false or strange
thoughts or beliefs), and unusual behavior.
The most common
side effects of Briviact include:
sleepinessdizzinessfeeling
tirednausea
and vomiting
These are not
all the possible side effects of Briviact. For more information, ask your
healthcare provider or pharmacist. Tell your healthcare provider about any side
effect that bothers you or that does not go away. Call your doctor for medical
advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.
How should I
store Briviact?
·
Store Briviact at room temperature between 59°F to 86°F
(15°C to 30°C).
·
Do not freeze Briviact oral solution.
·
Safely throw away any opened bottle of Briviact oral
solution after 5 months of first opening the bottle, even if there is medicine
left in the bottle.
·
Keep Briviact and all medicines out of
the reach of children.
General
information about the safe and effective use of Briviact.
Medicines are
sometimes prescribed for purposes other than those listed in a Medication
Guide. Do not use Briviact for a condition for which it was not prescribed. Do
not give Briviact to other people, even if they have the same symptoms that you
have. It may harm them.
This Medication
Guide summarizes the most important information about Briviact. If you would
like more information, talk with your healthcare provider. You can ask your
pharmacist or healthcare provider for information about Briviact that is
written for health professionals.
What are the
ingredients in Briviact?
Active
ingredient: brivaracetam
Tablet inactive
ingredients: croscarmellose sodium, lactose monohydrate, betadex
(β-cyclodextrin), anhydrous lactose, and magnesium stearate. The tablet film
coating contains the inactive ingredients listed below:
·
10 mg tablets: polyvinyl alcohol, talc,
polyethylene glycol 3350, titanium dioxide
·
25 mg and 100 mg tablets: polyvinyl
alcohol, talc, polyethylene glycol 3350, titanium dioxide, yellow iron oxide,
black iron oxide
·
50 mg tablets: polyvinyl alcohol, talc,
polyethylene glycol 3350, titanium dioxide, yellow iron oxide, red iron oxide
·
75 mg tablets: polyvinyl alcohol, talc,
polyethylene glycol 3350, titanium dioxide, yellow iron oxide, red iron oxide,
black iron oxide
Oral solution
inactive ingredients: sodium citrate, anhydrous citric acid,
methylparaben, sodium carboxymethylcellulose, sucralose, sorbitol solution,
glycerin, raspberry flavor, and purified water.
Injection
inactive ingredients: sodium acetate (trihydrate), glacial acetic acid,
sodium chloride, and water for injection.
Manufactured for
UCB, Inc., Smyrna, GA 30080.
Briviact® is a
registered trademark of the UCB Group of Companies. ©2017, UCB, Inc., Smyrna,
GA 30080. All rights reserved.
For more
information, go to www.Briviact.com or call 1-844-599-2273.
This Medication
Guide has been approved by the U.S. Food and Drug Administration.
Issued: 9/2017
PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton
Briviact®
(brivaracetam)
tablets
CV
10 mg
ucb
Manufactured for
UCB, Inc.
Smyrna, GA 30080
Made in Belgium
PRINCIPAL DISPLAY PANEL - 25 mg Tablet Bottle Carton
Briviact®
(brivaracetam)
tablets
CV
25 mg
ucb
Manufactured for
UCB, Inc.
Smyrna, GA 30080
Made in Belgium
PRINCIPAL DISPLAY PANEL - 50 mg Tablet Bottle Carton
Briviact®
(brivaracetam)
tablets
CV
50 mg
ucb
Manufactured for
UCB, Inc.
Smyrna, GA 30080
Made in Belgium
PRINCIPAL DISPLAY PANEL - 75 mg Tablet Bottle Carton
Briviact®
(brivaracetam)
tablets
CV
75 mg
ucb
Manufactured for
UCB, Inc.
Smyrna, GA 30080
Made in Belgium
PRINCIPAL DISPLAY PANEL - 100 mg Tablet Bottle Carton
Briviact®
(brivaracetam)
tablets
CV
100 mg
ucb
Manufactured for
UCB, Inc.
Smyrna, GA 30080
Made in Belgium
PRINCIPAL DISPLAY PANEL - 10 mg/mL Bottle Carton
NDC 50474-870-15
Rx only
Briviact®
(brivaracetam)
oral solution
CV
10
mg/mL
ATTENTION
PHARMACIST:
Dispense accompanying
medication guide to
each patient
300 mL
PRINCIPAL DISPLAY PANEL - 50 mg/5 mL Vial Carton
NDC 50474-970-75
Rx only
Briviact®
(brivaracetam) injection CV
50 mg/5 mL
(10 mg/mL)
For
Intravenous Use Only
10
vials
|
Briviact brivaracetam tablet, film
coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-370
|
|
Route of Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
10 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
croscarmellose sodium
|
|
|
lactose monohydrate
|
|
|
betadex
|
|
|
anhydrous lactose
|
|
|
magnesium stearate
|
|
|
polyvinyl alcohol, unspecified
|
|
|
talc
|
|
|
polyethylene glycol 3350
|
|
|
titanium dioxide
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
no score
|
|
Shape
|
ROUND
|
Size
|
7mm
|
|
Flavor
|
|
Imprint Code
|
u10
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-370-66
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
60 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205836
|
05/12/2016
|
|
|
|
Briviact brivaracetam tablet, film
coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-470
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active Ingredient/Active
Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
25 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
croscarmellose sodium
|
|
|
lactose monohydrate
|
|
|
betadex
|
|
|
anhydrous lactose
|
|
|
magnesium stearate
|
|
|
polyvinyl alcohol, unspecified
|
|
|
talc
|
|
|
polyethylene glycol 3350
|
|
|
titanium dioxide
|
|
|
ferric oxide yellow
|
|
|
ferrosoferric oxide
|
|
|
|
Product
Characteristics
|
|
Color
|
GRAY
|
Score
|
no score
|
|
Shape
|
OVAL
|
Size
|
9mm
|
|
Flavor
|
|
Imprint Code
|
u25
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-470-66
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
60 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
2
|
NDC:50474-470-09
|
100 BLISTER
PACK in 1 CARTON
|
|
|
2
|
|
1 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
3
|
NDC:50474-470-12
|
5 CARTON in 1
CARTON
|
|
|
3
|
|
2 BLISTER PACK
in 1 CARTON
|
|
|
3
|
|
14 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205836
|
05/12/2016
|
|
|
|
Briviact brivaracetam tablet, film
coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-570
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
50 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
croscarmellose sodium
|
|
|
lactose monohydrate
|
|
|
betadex
|
|
|
anhydrous lactose
|
|
|
magnesium stearate
|
|
|
polyvinyl alcohol, unspecified
|
|
|
talc
|
|
|
polyethylene glycol 3350
|
|
|
titanium dioxide
|
|
|
ferric oxide yellow
|
|
|
ferric oxide red
|
|
|
|
Product
Characteristics
|
|
Color
|
YELLOW
|
Score
|
no score
|
|
Shape
|
OVAL
|
Size
|
12mm
|
|
Flavor
|
|
Imprint Code
|
u50
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-570-66
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
60 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
2
|
NDC:50474-570-09
|
100 BLISTER
PACK in 1 CARTON
|
|
|
2
|
|
1 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
3
|
NDC:50474-570-12
|
5 CARTON in 1
CARTON
|
|
|
3
|
|
2 BLISTER PACK
in 1 CARTON
|
|
|
3
|
|
14 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205836
|
05/12/2016
|
|
|
|
Briviact brivaracetam tablet, film
coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-670
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
75 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
croscarmellose sodium
|
|
|
lactose monohydrate
|
|
|
betadex
|
|
|
anhydrous lactose
|
|
|
magnesium stearate
|
|
|
polyvinyl alcohol, unspecified
|
|
|
talc
|
|
|
polyethylene glycol 3350
|
|
|
titanium dioxide
|
|
|
ferric oxide yellow
|
|
|
ferric oxide red
|
|
|
ferrosoferric oxide
|
|
|
|
Product
Characteristics
|
|
Color
|
PURPLE
|
Score
|
no score
|
|
Shape
|
OVAL
|
Size
|
13mm
|
|
Flavor
|
|
Imprint Code
|
u75
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:50474-670-66
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
60 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205836
|
05/12/2016
|
|
|
|
Briviact brivaracetam tablet, film
coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-770
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
100 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
croscarmellose sodium
|
|
|
lactose monohydrate
|
|
|
betadex
|
|
|
anhydrous lactose
|
|
|
magnesium stearate
|
|
|
polyvinyl alcohol, unspecified
|
|
|
talc
|
|
|
polyethylene glycol 3350
|
|
|
titanium dioxide
|
|
|
ferric oxide yellow
|
|
|
ferrosoferric oxide
|
|
|
|
Product
Characteristics
|
|
Color
|
GREEN
(green-grey)
|
Score
|
no score
|
|
Shape
|
OVAL
|
Size
|
15mm
|
|
Flavor
|
|
Imprint Code
|
u100
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-770-66
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
60 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
2
|
NDC:50474-770-09
|
100 BLISTER
PACK in 1 CARTON
|
|
|
2
|
|
1 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
3
|
NDC:50474-770-12
|
5 CARTON in 1
CARTON
|
|
|
3
|
|
2 BLISTER PACK
in 1 CARTON
|
|
|
3
|
|
14 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205836
|
05/12/2016
|
|
|
|
Briviact brivaracetam solution
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-870
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
10 mg
in 1 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
sodium citrate, unspecified form
|
|
|
anhydrous citric acid
|
|
|
methylparaben
|
|
|
carboxymethylcellulose sodium, unspecified
form
|
|
|
sucralose
|
|
|
sorbitol
|
|
|
glycerin
|
|
|
water
|
|
|
|
Product
Characteristics
|
|
Color
|
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
RASPBERRY
|
Imprint Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-870-15
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
300 mL in 1
BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205838
|
05/12/2016
|
|
|
|
Briviact brivaracetam injection,
suspension
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50474-970
|
|
Route of
Administration
|
INTRAVENOUS
|
DEA Schedule
|
CV
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
brivaracetam (brivaracetam)
|
brivaracetam
|
50 mg
in 5 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
sodium acetate
|
|
|
acetic acid
|
|
|
sodium chloride
|
|
|
water
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50474-970-75
|
10 VIAL, GLASS
in 1 CARTON
|
|
|
1
|
NDC:50474-970-63
|
5 mL in 1 VIAL,
GLASS
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205837
|
05/12/2016
|
|
|
|
Labeler - UCB, Inc. (028526403)
|
Revised:
09/2017
UCB, Inc.
