Brivlera

Brivlera is indicated as adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy.

Brivlera is an anti-epileptic drug, also called an anticonvulsant.

Brivlera is used to treat partial onset seizures in people with epilepsy.

Brivlera oral is for use in adults and children who are at least 4 years old. Brivlera injection is for use in people who are at least 16 years old.

Brivlera may also be used for purposes not listed in this medication guide.

Dosage 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).

Brivlera injection may be used when oral administration is temporarily not feasible. Brivlera injection should be administered at the same dosage and same frequency as Brivlera tablets and oral solution.

The clinical study experience with Brivlera injection is limited to 4 consecutive days of treatment.

Administration Instructions for Brivlera Tablets and Brivlera

Oral Solution

Brivlera can be initiated with either intravenous or oral administration.

Brivlera tablets and oral solution may be taken with or without food.

Brivlera Tablets

Brivlera tablets should be swallowed whole with liquid. Brivlera tablets should not be chewed or crushed.

Brivlera

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 Brivlera oral solution, no dilution is necessary. Brivlera oral solution may also be administered using a nasogastric tube or gastrostomy tube.

Discard any unused Brivlera oral solution remaining after 5 months of first opening the bottle.

Preparation and Administration Instructions for Brivlera Injection

Brivlera injection is for intravenous use only.

Preparation

Brivlera injection can be administered intravenously without further dilution or may be mixed with diluents listed below.

Administration

Brivlera 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. Brivlera 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 Brivlera injection vial contents.

Discontinuation of Brivlera

Avoid abrupt withdrawal from Brivlera in order to minimize the risk of increased seizure frequency and status epilepticus.

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).

Co-administration with Rifampin

Increase the Brivlera dosage in patients on concomitant rifampin by up to 100% (i.e., double the dosage).

See also:
What is the most important information I should know about Brivlera?

Hypersensitivity to Brivlera or any of the inactive ingredients in Brivlera (bronchospasm and angioedema have occurred).

Use: Labeled Indications

Partial-onset seizures: Treatment of partial-onset seizures in patients with epilepsy as monotherapy or adjunctive therapy.

See also:
What other drugs will affect Brivlera?

Rifampin

Co-administration with rifampin decreases Brivlera plasma concentrations likely because of CYP2C19 induction. Prescribers should increase the Brivlera dose by up to 100% (i.e., double the dosage) in patients while receiving concomitant treatment with rifampin.

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.

Phenytoin

Because Brivlera can increase plasma concentrations of phenytoin, phenytoin levels should be monitored in patients when concomitant Brivlera is added to or discontinued from ongoing phenytoin therapy.

Levetiracetam

Brivlera provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered.

Drug Abuse And Dependence

Controlled Substance

Brivlera contains brivaracetam and is listed as a Schedule V controlled substance.

Abuse

In a human abuse potential study, single doses of Brivlera at therapeutic and supratherapeutic doses were compared to alprazolam (C-IV) (1.5 mg and 3 mg). Brivlera at the recommended single dose (50 mg) caused fewer sedative and euphoric effects than alprazolam; however, Brivlera 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 Brivlera in a pooled review of placebo-controlled adjunctive therapy studies.

See also:
What are the possible side effects of Brivlera?

The following serious adverse reactions are described elsewhere in labeling:

• Suicidal Behavior and Ideation
• Neurological Adverse Reactions
• Psychiatric Adverse Reactions
• Hypersensitivity: Bronchospasm and Angioedema
• Withdrawal of Antiepileptic Drugs

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, Brivlera 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 Brivlera 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). 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 Brivlera and 62% treated with placebo. The most common adverse reactions occurring at a frequency of at least 5% in patients treated with Brivlera 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 Brivlera 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 Brivlera that occurred at least 2% more frequently for Brivlera 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 (Brivlera 50 mg/day, 100 mg/day, and 200 mg/day)

There was no apparent dose-dependent increase in adverse reactions listed in Table 2 with the exception of somnolence and sedation.

Hematologic Abnormalities

Brivlera can cause hematologic abnormalities. In the Phase 3 controlled adjunctive epilepsy studies, a total of 1.8% of Brivlera-treated patients and 1.1% of placebo-treated patients had at least one clinically significant decreased white blood cell count ( < 3.0 x 10/L).

Adverse Reactions With Brivlera Injection

Adverse reactions with Brivlera injection were generally similar to those observed with Brivlera tablets. Other adverse events that occurred in at least 3% of patients who received Brivlera 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.