Source: Health Products and Food Branch (CA) Revision Year: 2022
BRIVLERA (brivaracetam) is indicated as adjunctive therapy in the management of partialonset seizures in patients 4 years of age and older with epilepsy who are not satisfactorily controlled with conventional therapy.
BRIVLERA (brivaracetam) solution for injection for intravenous use is an alternative for adults when oral administration is temporarily not feasible.
Pediatrics (<4 years of age): The safety and efficacy of BRIVLERA in children under 4 years of age have not been established and its use in this patient population is not indicated (see 7.1.3 Pediatrics).
Geriatrics (≥65 years of age): The clinical experience with BRIVLERA in elderly patients with epilepsy is limited (29 elderly patients aged between 65 and 80 years). No dose adjustment based on age is necessary. 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 7.1.4 Geriatrics; 4 DOSAGE AND ADMINISTRATION and 10.3 Pharmacokinetics, Special Populations and Conditions, Geriatrics).
BRIVLERA (brivaracetam) may be taken with or without food.
BRIVLERA can be initiated in adults with either intravenous or oral administration. BRIVLERA solution for injection is for intravenous use in adults only.
The recommended starting dose in adults is 50 mg twice daily (100 mg per day). Based on individual patient response and tolerability, the dose may be adjusted between 25 mg twice daily (50 mg per day) and 100 mg twice daily (200 mg per day). Maximum recommended daily dose of BRIVLERA is 200 mg, administered in two equal intakes.
When switching to or from oral to intravenous administration of BRIVLERA, the total daily dose and frequency of administration should be maintained.
The physician should prescribe the most appropriate formulation and strength according to weight and dose. Dosage should be adjusted based on the clinical response and tolerability. The following table summarizes the recommended dosing for children from 4 years of age and adolescents.
Table 1. Dosing Recommendations for Pediatrics (aged 4 years and older):
| Pediatric patients (≥4 years) | |||
|---|---|---|---|
| Weighing 11 kg to <20kg | Weighing 20 kg to <50kg | weighing 50kg or more | |
| Therapeutic dose range | 0.5 mg/kg to 2.5 mg/kg twice daily (1 mg/kg to 5 mg/kg per day) | 0.5 mg/kg to 2 mg/kg twice daily (1 mg/kg to 4 mg/kg per day) | 25 mg to 100 mg twice daily (50 mg to 200 mg per day) |
| Recommended starting dose | 0.5 mg/kg to 1.25 mg/kg twice daily (1 mg/kg to 2.5 mg/kg per day) | 0.5 mg/kg to 1 mg/kg twice daily (1 mg/kg to 2 mg/kg per day) | 25 mg to 50 mg twice daily (50 mg to100 mg per day) |
| Hepatic Impairment | |||
| Recommended Starting Dose | 1 mg/kg/day | 1 mg/kg/day | 50 mg/day |
| Recommended Maximum Dose | 4 mg/kg/day | 3 mg/kg/day | 150 mg/day |
The dose per intake for each patient should be calculated using the following formula: Volume per administration (mL) = Dose per administration (mg, as per Table 1) ÷ 10 mg/mL
Patients with Renal Impairment: There are limited clinical data on the use of BRIVLERA in patients with pre-existing renal impairment as these patients were excluded from pre-market clinical studies of epilepsy. Based on a single-dose adult pharmacokinetic study, dose adjustments are not required for patients with impaired renal function. Based on data in adults, no dose adjustment is necessary in pediatric patients with impaired renal function.
There are no data in patients with end-stage renal disease undergoing dialysis. Thus, BRIVLERA is not recommended in this population (see 7 WARNINGS AND PRECAUTIONS, Renal and 10.3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency).
Patients with Hepatic Impairment: In adults, and children and adolescents weighing 50 kg or more, a reduced starting dose of 25 mg twice daily (50 mg per day) should be considered. A maximum dose of 75 mg twice daily (150 mg per day) is recommended for all stages of hepatic impairment (see 10.3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency). The recommended dosing for pediatrics with hepatic impairment is shown in Table 1.
Pediatrics (<4 years of age): The safety and efficacy of BRIVLERA in children aged less than 4 years have not been established.
Geriatrics (≥65 years of age): There was an insufficient number of patients 65 years of age and older in the double-blind placebo controlled epilepsy studies in adults (29 elderly patients aged between 65 and 80 years completed Phase 3 clinical trials) to adequately assess the safety and efficacy of BRIVLERA in this population. According to data obtained from a pharmacokinetic study that was conducted in patients ≥65 years of age, no BRIVLERA dose adjustment based on age is necessary (see 1 INDICATIONS and 10.3 Pharmacokinetics, Special Populations and Conditions, Geriatrics).
As with all antiepileptic drugs, BRIVLERA should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. When discontinuing BRIVLERA, reduce the dosage gradually (e.g., for adults and pediatrics over 50 kg: taper it gradually by 50 mg/day on a weekly basis. After 1 week of treatment at 50 mg/day, a final week of treatment at the dose of 20 mg/day is recommended).
BRIVLERA solution for injection can be administered intravenously in adults without further dilution or may be mixed with the diluents listed below. Withdraw the exact amount of BRIVLERA solution for injection required for administration.
As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discolouration and leakage prior to administration. Solution showing haziness, particulate matter, precipitate, discolouration or leakage should not be used. Discard unused portions. The clinical study experience of intravenous BRIVLERA is limited to 4 days of consecutive treatment. See 11 STORAGE, STABILITY AND DISPOSAL.
BRIVLERA tablets should be swallowed whole with liquid. BRIVLERA tablets should not be chewed or crushed.
When using BRIVLERA oral solution, no dilution is necessary. BRIVLERA oral solution may also be administered using a nasogastric tube or gastrostomy tube.
BRIVLERA Solution for Injection
It may be administered as a bolus injection or as a 15-minute IV infusion.
Should patients miss a dose, they should be instructed to take BRIVLERA as soon as they remember and take the following dose at the usual morning or evening time. This may avoid the brivaracetam plasma concentration falling below the efficacy level and prevent breakthrough seizures from occurring.
For management of a suspected drug overdose, contact your regional poison control centre.
There is limited clinical experience with BRIVLERA (brivaracetam) overdose in humans. During pre-marketing clinical trials of BRIVLERA, the types of adverse events experienced by patients exposed to acute BRIVLERA overdose were mostly similar to those observed in patients administered therapeutic doses of the drug. Somnolence and dizziness have been reported in a patient taking a single dose of 1400 mg of BRIVLERA, which is the highest known non-lethal overdose. The following additional adverse reactions were reported with BRIVLERA overdose: vertigo, balance disorder, fatigue, nausea, diplopia and anxiety.
There is no specific antidote for overdose with BRIVLERA. 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 rhythm and vital sign measurement is recommended. A certified poison control centre should be contacted for updated information on the management of overdose with BRIVLERA. There is no data on the potential removal of BRIVLERA using hemodialysis. Since less than 10% of BRIVLERA is excreted in urine, hemodialysis is not expected to significantly enhance BRIVLERA clearance.
Store at room temperature (15-30°C). Do not freeze BRIVLERA (brivaracetam) solution for injection or oral solution.
Discard any unused BRIVLERA oral solution remaining after 5 months of first opening the bottle.
BRIVLERA solution for injection should be used immediately after dilution. If not used immediately, the diluted solution should not be stored for more than 4 hours at room temperature and may be stored in polyvinyl chloride (PVC) or polyolefin bags.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
