Dosing & Uses
Dosage Forms & Strengths
tablet: Schedule V
- 10mg
- 25mg
- 50mg
- 75mg
- 100mg
oral solution: Schedule V
- 10mg/mL
injection, solution: Schedule V
- 50mg/5mL single-dose vial
Partial-Onset Seizures
Indicated for partial-onset seizures
50 mg PO/IV q12hr initially; based on individual patient tolerability and therapeutic response, adjust dose between to 25-100 mg PO/IV BID (50-200 mg/day)
Injection may be used for patients when oral administration is temporarily not feasible; clinical study experience with injection is limited to 4 consecutive days of treatment
Dosage Modifications
Hepatic impairment
- All stages: Decrease starting dose to 25 mg BID and do not exceed 75 mg BID (150 mg/day)
Renal impairment
- Mild-to-moderate: No dose adjustment required
- ESRD undergoing dialysis: Not studied
Coadministration with rifampin
- Increase dose by 100% (ie, double dose)
Dosing Considerations
IV injection may be used when PO administration is temporarily not feasible; injection should be administered at the same dosage and same frequency as tablets or oral solution; clinical trials limited IV administration to 4 consecutive days
Dosage Forms & Strengths
tablet: Schedule V
- 10mg
- 25mg
- 50mg
- 75mg
- 100mg
oral solution: Schedule V
- 10mg/mL
injection, solution: Schedule V
- 50mg/5mL
Partial Onset Seizures
Tablets or oral solution
- Indicated for partial-onset seizures in children and adolescents ≥4 years
- <4 years: Safety and efficacy not established
-
4 to <16 years
- 11 to <20 kg: 0.5-1.25 mg/kg PO BID (1-2.5 mg/kg/day) initially; based on individual patient tolerability and therapeutic response, adjust dose between to 0.5-2.5 mg/kg PO BID (1-5 mg/kg/day)
- 20 to <50 kg: 0.5-1 mg/kg PO BID (1-2 mg/kg/day) initially; based on individual patient tolerability and therapeutic response, adjust dose between to 0.5-2 mg/kg PO BID (1-4 mg/kg/day)
- ≥50 kg: 25-50 mg PO BID (50-100 mg/day) initially; based on individual patient tolerability and therapeutic response, adjust dose between to 25-100 mg PO BID (50-200 mg/day)
-
≥16 years
- 50 mg PO BID (100 mg/day) initially; based on individual patient tolerability and therapeutic response, adjust dose between to 25-100 mg PO BID (50-200 mg/day)
Injection
- Indicated for partial-onset seizures in adolescents ≥16 years with epilepsy
- Injection may be used for patients when oral administration is temporarily not feasible
- <16 years: Safety and efficacy not established
- ≥16 years: 50 mg IV q12hr initially; based on individual patient tolerability and therapeutic response, adjust dose between to 25-100 mg IV BID (50-200 mg/day)
- Clinical study experience with injection is limited to 4 consecutive days of treatment
Dosage Modifications
Hepatic impairment
-
Starting dose adjustments
- 11 to <50 kg: Start at 0.5 mg/kg PO BID (1 mg/kg/day)
- 20 to <50 kg: Start at 1.5 mg/kg PO BID (3 mg/kg/day)
- ≥50 kg: Start at 25 mg PO BID (50 mg/day)
-
Maximum dose with hepatic impairment
- 11 to <20 kg: Not to exceed 2 mg/kg PO BID (4 mg/kg/day)
- 20 to <50 kg: 1.5 mg/kg PO BID (3 mg/kg/day)
- ≥50 kg: Not to exceed 75 mg PO BID (150 mg/day)
Renal impairment
- Mild-to-moderate: No dose adjustment required
- ESRD undergoing dialysis: Not studied
Coadministration with rifampin
- Increase dose by 100% (ie, double dose)
Dosing Considerations
IV injection may be used when PO administration is temporarily not feasible; injection should be administered at the same dosage and same frequency as tablets or oral solution; clinical trials limited IV administration to 4 consecutive days
Absence Epilepsy (Orphan)
Orphan designation for treatment of juvenile or childhood absence epilepsy
Sponsor
- UCB, Inc; 1950 Lake Park Drive, Building 2100; Smyrna, Georgia
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
Refer to Adult Dosing
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Somnolence and sedation (16%)
Dizziness (12%)
1-10%
Fatigue (9%)
Nausea and vomiting (5%)
Cerebellar coordination and balance disturbances (3%)
Irritability (3%)
Constipation (2%)
Warnings
Contraindications
Hypersensitivity; bronchospasms and angioedema have occurred
Cautions
Antiepileptic drugs increase the risk of suicidal behavior and ideation; monitor for the emergence or worsening of depression, unusual changes in mood or behavior, or suicidal thoughts, behavior, or self-harm; advise patients and caregivers/families to be alert for these behavioral changes and report them to their physician immediately
May cause psychiatric adverse reactions, including nonpsychotic and psychotic symptoms; advise patients and caregivers/families to be alert for these behavioral changes and report them to their physician immediately
May cause somnolence and fatigue (dose-dependent), dizziness, and disturbance in gait or coordination
Hypersensitivity reactions reported, including bronchospasm and angioedema
If discontinued, withdraw drug gradually because of the risk of increased seizure frequency and status epilepticus; if withdrawal is needed because of a serious adverse event, consider rapid discontinuation
Drug interactions overview
- CYP2C19 poor metabolizers and patients using inhibitors of CYP2C19 may require dose reduction
- Strong CYP2C19 inducers (eg, rifampin) require dose increase (see Dosage Modifications)
- Coadministration with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine; though data did not reveal any safety concerns, if tolerability issues arise when coadministered, consider carbamazepine reducing the dose
- Because brivaracetam can increase plasma concentrations of phenytoin, monitor phenytoin levels in patients when concomitant brivaracetam is added to or discontinued from ongoing phenytoin therapy
- No added therapeutic benefit to levetiracetam when the two drugs were coadministered
Pregnancy & Lactation
Pregnancy
No adequate and well-controlled studies in pregnant women
In animal studies, brivaracetam produced evidence of developmental toxicity at plasma exposures greater than clinical exposure
Pregnancy Registry
- Recommend that pregnant patients enroll in the North American Antiepileptic Drug Pregnancy Registry; this can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves
- Information on the registry can also be found at the Web site http://www.aedpregnancyregistry.org/
Lactation
Unknown if distributed in human breast milk
Studies in rats have shown excretion in milk
Because many drugs are excreted into human milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Exact mechanism unknown
Displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect
Absorption
Highly permeable and is rapidly and almost completely absorbed after PO administration
Peak plasma time: 1 hr (without food); slower absorption with a high-fat meal
Distribution
Protein bound: ≤20%
Vd: 0.5 L/kg
Metabolism
Primarily metabolized by hydrolysis of the amide moiety to form the corresponding carboxylic acid metabolite and is mediated by hepatic and extra-hepatic amidase
Secondarily metabolized by hydroxylation on the propyl side chain to form the hydroxy metabolite that is mediated primarily by CYP2C19
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)
The 3 metabolites are not pharmacologically active
Elimination
Half-life: 9 hr
Excretion
- Urine (>95%); feces (<1%)
- <10% of the dose is excreted unchanged in the urine
- 34% of the dose is excreted as the carboxylic acid metabolite in urine
Pharmacogenomics
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
Administration
Oral Administration
May take with or without food
Tablet
- Swallow whole; do not chew or crush
Oral solution
- Use a calibrated measuring device to measure and deliver the prescribed dose accurately
- No dilution is necessary
- May also be administered using an NT-tube or G-tube
IV Compatibilities
0.9% NaCl
Dextrose 5%
Lactated Ringer injection
IV Preparation
Inspect visually for particulate matter and discoloration prior to administration; product with particulate matter or discoloration should not be used
Vial is for single dose only
IV Administration
Can be administered IV without further dilution or may be mixed with diluents (see IV Compatibilities)
Infuse IV over 2-15 minutes
Discontinuation
Avoid abrupt withdrawal in order to minimize the risk of increased seizure frequency and status epilepticus
Storage
Oral
- Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F)
- Oral solution: Do not freeze; discard any unused oral solution remaining after 5 months of first opening the bottle
IV
- Unopened vials: Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F); do not freeze
- Diluted solution: Store at room temperature in PVC bag for up to 4 hr
- Discard any unused portion
Images
Patient Handout
Formulary
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