Brivaracetam- Briviact -@- (Feb 2016) - Anticonvulsant
Drug Name:Brivaracetam- Briviact -@- (Feb 2016) - Anticonvulsant
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
Rifampin-
Because of decreased BRIVIACT concentrations, increasing
BRIVIACT dosage in patients on concomitant rifampin is recommended.
Carbamazepine-
Because of increased exposure to carbamazepine metabolite,
if tolerability issues arise, consider reducing carbamazepine
dosage in patients on concomitant BRIVIACT.
Phenytoin-
Because phenytoin concentrations can increase, phenytoin
levels should be monitored in patients on concomitant BRIVIACT.
Levetiracetam-
BRIVIACT had no added therapeutic benefit when coadministered
with levetiracetam.
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
2. Briviact Brvaracetam 2/18/2016 To treat partial onset seizures in
patients age 16 years and older with epilepsy
Press Release
Drug trials Snapshot
Approved by FDA on 2/18/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
BRIVIACTR safely and effectively. See full prescribing information for
BRIVIACT.
BRIVIACTR (brivaracetam) tablets, for oral use
BRIVIACTR (brivaracetam) oral solution
BRIVIACTR (brivaracetam) injection, for intravenous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
BRIVIACT is indicated as adjunctive therapy in the treatment of partial-onset
seizures in patients 16 years of age and older with epilepsy.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (at least 5% for BRIVIACT and at least 2%
more frequently than placebo) are somnolence/sedation, dizziness, fatigue,
and nausea/vomiting.
Contra-Indications:
CONTRAINDICATIONS
Hypersensitivity to brivaracetam or any of the inactive ingredients in
BRIVIACT.
WARNINGS AND PRECAUTIONS
Suicidal Behavior and Ideation:
Monitor patients for suicidal behavior and ideation.
Neurological Adverse Reactions:
Monitor for somnolence and fatigue, and advise patients not to drive or
operate machinery until they have gained sufficient experience on BRIVIACT.
Psychiatric Adverse Reactions:
Behavioral reactions including psychotic symptoms, irritability, depression,
aggressive behavior, and anxiety; monitor patients for symptoms.
Hypersensitivity Bronchospasm and Angioedema:
Advise patients to seek immediate medical care.
Discontinue and do not restart BRIVIACT if hypersensitivity occurs.
Withdrawal of Antiepileptic Drugs:
BRIVIACT should be gradually withdrawn.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
BRIVIACT is indicated as adjunctive therapy in the treatment of partial-onset
seizures in patients 16 years of age and older with epilepsy.
DOSAGE AND ADMINISTRATION
The recommended starting dosage is 50 mg twice daily. Based on
individual patient tolerability and therapeutic response, the dosage may be
adjusted down to 25 mg twice daily (50 mg per day) or up to 100 mg twice
daily (200 mg per day).
BRIVIACT injection may be used when oral administration is temporarily
not feasible.
Hepatic Impairment For all stages of hepatic impairment, the
recommended starting dosage is 25 mg twice daily; maximum dosage is 75
mg twice daily.
DOSAGE FORMS AND STRENGTHS
Tablets: 10 mg, 25 mg, 50 mg, 75 mg, and 100 mg
Oral solution: 10 mg/mL
Injection: 50 mg/5 mL single-dose vial
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.
Patient Information:
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 .
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.
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
.
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 .
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.
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.
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.
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
BRIVIACT Tablets, BRIVIACT Oral Solution,
and BRIVIACT Injection manufactured for
UCB, Inc.
Smyrna, GA 30080
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
The precise mechanism by which BRIVIACT exerts its anticonvulsant activity
is not known. Brivaracetam displays a high and selective affinity for synaptic
vesicle protein 2A (SV2A) in the brain, which may contribute to the
anticonvulsant effect
2.Pharmacokinetics
BRIVIACT tablets, oral solution, and injection can be used interchangeably.
Brivaracetam exhibits linear and time-independent pharmacokinetics at the
approved doses.
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.
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.
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.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women.
In animal studies, brivaracetam produced evidence of developmental toxicity
at plasma exposures greater than clinical exposures.
BRIVIACT should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Labor and Delivery
The effect of BRIVIACT on labor and delivery in humans is unknown.
3. Nursing Mothers
It is not known whether BRIVIACT is excreted in human milk.
Studies in rats have shown excretion of brivaracetam in milk. Because
many drugs are excreted into human milk, a decision should be made
whether to discontinue nursing or to discontinue BRIVIACT, taking into
account the importance of the drug to the mother.
4. Pediatric Use
Safety and effectiveness of BRIVIACT in adolescents 16 years of age have
been established. Safety and effectiveness of BRIVIACT in patients less
than 16 years of age 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.
5. 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
6. 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
7. Hepatic Impairment
Because of increases in BRIVIACT exposure, dosage adjustment is recommended
for all stages of hepatic impairment .
8 DRUG ABUSE AND DEPENDENCE
8.1. Controlled Substance
BRIVIACT contains brivaracetam (schedule to be determined after DEA review).
8.2. 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.
8.3. 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 .
9. 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.
