What Is Briviact Tablet, Film Coated Used For?

Uses and indications

BRIVIACT is indicated for the treatment of partial-onset seizures in patients 1 month of age and older.

Contraindications

Hypersensitivity to brivaracetam or any of the inactive ingredients in BRIVIACT (bronchospasm and angioedema have occurred) [see Warnings and Precautions (5.4)] .

Side effects

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…

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.

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.

Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults [see Adverse Reactions (6.1)and Use in Specific Populations (8.4)].

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)]
Serious Dermatologic Reactions [see Warnings and Precautions (5.5)]
Withdrawal of Antiepileptic Drugs [see Warnings and Precautions (5.6)]

Precautions

• Suicidal Behavior and Ideation : Monitor patients for suicidal behavior and ideation. (5.1) • 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…

• Suicidal Behavior and Ideation

: Monitor patients for suicidal behavior and ideation. (5.1)

• 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. (5.2)

• Psychiatric Adverse Reactions

: Behavioral reactions including psychotic symptoms, irritability, depression, aggressive behavior, and anxiety; monitor patients for symptoms. (5.3)

• Hypersensitivity: Bronchospasm and Angioedema

: Advise patients to seek immediate medical care. Discontinue and do not restart BRIVIACT if hypersensitivity occurs. (5.4)

• Serious Dermatologic Reactions

: Discontinue BRIVIACT unless an alternative etiology is established (5.5)

• Withdrawal of Antiepileptic Drugs

: BRIVIACT should be gradually withdrawn. (5.6) 5.1 Suicidal 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 3 shows absolute and relative risk by indication for all evaluated AEDs.

Table 3: 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. 5.2 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. 5.3 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.

Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults

[see

Adverse Reactions (6.1)and

Use in Specific Populations (8.4)]. 5.4 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)]. 5.5 Serious Dermatologic Reactions

Serious dermatologic reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with BRIVIACT. Time to onset of the serious dermatologic reaction ranged from 3 to 45 days after BRIVIACT initiation in reported cases. BRIVIACT should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest a serious dermatologic reaction, use of BRIVIACT should not be resumed and alternative therapy should be considered. 5.6 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.

Dosage

• Adults (16 Years and Older): The recommended starting dosage for monotherapy or adjunctive therapy 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…

• Adults (16 Years and Older): The recommended starting dosage for monotherapy or adjunctive therapy 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). (2.1) • Pediatric Patients (1 Month to less than 16 Years): The recommended dosage is based on body weight and is administered orally twice daily (2.1) • Injection: for intravenous use only when oral administration is temporarily not feasible; dosing is the same as oral regimen. (2.1, 2.3) • Hepatic Impairment: Dose adjustment is recommended for all stages of hepatic impairment. (2.5) 2.1 Dosage Information Monotherapy or Adjunctive Therapy The recommended dosage for patients 1 month of age and older is included in Table 1. In pediatric patients weighing less than 50 kg, the recommended dosing regimen is dependent upon body weight. When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability. Table 1: Recommended Dosage for Patients 1 Month of Age and Older Age and Body Weight Initial Dosage Minimum and Maximum Maintenance Dosage Adults (16 years and older) 50 mg twice daily (100 mg per day) 25 mg to 100 mg twice daily (50 mg to 200 mg per day) Pediatric patients weighing 50 kg or more 25 mg to 50 mg twice daily (50 mg to 100 mg per day) 25 mg to 100 mg twice daily (50 mg to 200 mg per day) Pediatric patients weighing 20 kg to less than 50 kg 0.5 mg/kg to 1 mg/kg twice daily (1 mg/kg to 2 mg/kg per day) 0.5 mg/kg to 2 mg/kg twice daily (1 mg/kg to 4 mg/kg per day) Pediatric patients weighing 11 kg to less than 20 kg 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 2.5 mg/kg twice daily (1 mg/kg to 5 mg/kg per day) Pediatric patients weighing less than 11 kg 0.75 mg/kg to 1.5 mg/kg twice daily (1.5 mg/kg to 3 mg/kg per day) 0.75 mg/kg to 3 mg/kg twice daily (1.5 mg/kg to 6 mg/kg per day) BRIVIACT Injection Dosage BRIVIACT injection may be used when oral administration is temporarily not feasible [see Dosage and Administration (2.3)]. BRIVIACT injection should be administered intravenously at the same dosage and same frequency as BRIVIACT tablets and oral solution. The clinical study experience with BRIVIACT injection is up to 4 consecutive days of treatment. 2.2 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. 2.3 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. 2.4 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 (5.6)and Clinical Studies (14)]. 2.5 Patients with Hepatic Impairment The recommended dosage for patients with hepatic impairment is included in Table 2 [see Use in Specific Populations (8.7)and Clinical Pharmacology (12.3)]. Table 2: Recommended Dosage for Patients with Hepatic Impairment Age and Body Weight Initial Dosage Maximum Maintenance Dosage Adults (16 years and older) 25 mg twice daily (50 mg per day) 75 mg twice daily (150 mg per day) Pediatric patients weighing 50 kg or more Pediatric patients weighing 20 kg to less than 50 kg 0.5 mg/kg twice daily (1 mg/kg per day) 1.5 mg/kg twice daily (3 mg/kg per day) Pediatric patients weighing 11 kg to less than 20 kg 0.5 mg/kg twice daily (1 mg/kg per day) 2 mg/kg twice daily (4 mg/kg per day) Pediatric patients weighing less than 11 kg 0.75 mg/kg twice daily (1.5 mg/kg per day) 2.25 mg/kg twice daily (4.5 mg/kg per day) 2.6 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)].

Monotherapy or Adjunctive Therapy

The recommended dosage for patients 1 month of age and older is included in Table 1. In pediatric patients weighing less than 50 kg, the recommended dosing regimen is dependent upon body weight. When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability.

Table 1: Recommended Dosage for Patients 1 Month of Age and Older
Age and Body Weight	Initial Dosage	Minimum and Maximum Maintenance Dosage
Adults (16 years and older)	50 mg twice daily (100 mg per day)	25 mg to 100 mg twice daily (50 mg to 200 mg per day)
Pediatric patients weighing 50 kg or more	25 mg to 50 mg twice daily (50 mg to 100 mg per day)	25 mg to 100 mg twice daily (50 mg to 200 mg per day)
Pediatric patients weighing 20 kg to less than 50 kg	0.5 mg/kg to 1 mg/kg twice daily (1 mg/kg to 2 mg/kg per day)	0.5 mg/kg to 2 mg/kg twice daily (1 mg/kg to 4 mg/kg per day)
Pediatric patients weighing 11 kg to less than 20 kg	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 2.5 mg/kg twice daily (1 mg/kg to 5 mg/kg per day)
Pediatric patients weighing less than 11 kg	0.75 mg/kg to 1.5 mg/kg twice daily (1.5 mg/kg to 3 mg/kg per day)	0.75 mg/kg to 3 mg/kg twice daily (1.5 mg/kg to 6 mg/kg per day)

BRIVIACT Injection Dosage

BRIVIACT injection may be used when oral administration is temporarily not feasible [see Dosage and Administration (2.3)]. BRIVIACT injection should be administered intravenously at the same dosage and same frequency as BRIVIACT tablets and oral solution.

The clinical study experience with BRIVIACT injection is up to 4 consecutive days of treatment.

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 .

Drug interactions

• Rifampin: Because of decreased concentrations, increasing BRIVIACT dosage in patients on concomitant rifampin is recommended. (2.6, 7.1) • Carbamazepine: Because of increased exposure to carbamazepine metabolite, if tolerability issues arise, consider reducing carbamazepine…

References

Source: DailyMed, U.S. National Library of Medicine. Additional information compiled from online sources.

Uses and indications

Contraindications

Side effects

Precautions

Dosage

Drug interactions

References

Medicine rating