Brivaracetam Oral
FDA Drug Information • Also known as: Brivaracetam Oral Solution
- Brand Names
- Brivaracetam Oral Solution
- Route
- ORAL
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION The chemical name of brivaracetam is (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl] butanamide. Its molecular formula is C 11 H 20 N 2 O 2 and its molecular weight is 212.29. The chemical structure is: Brivaracetam is a white to off-white crystalline powder. It is very soluble in water, buffer (pH 1.2, 4.5, and 7.4), ethanol, methanol, and glacial acetic acid. It is freely soluble in acetonitrile and acetone and soluble in toluene. It is very slightly soluble in n-hexane. Oral Solution Brivaracetam oral solution contains 10 mg of brivaracetam per mL. The inactive ingredients are anhydrous citric acid, carboxymethylcellulose sodium, glycerine, methylparaben sodium, purified water, raspberry flavour, sodium citrate, sorbitol solution, sucralose. brivaracetam-fstructure
What Is Brivaracetam Oral Used For?
1 INDICATIONS & USAGE Brivaracetam oral solution is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. Brivaracetam oral solution is indicated for the treatment of partial-onset seizures in patients 1 month of age and older. ( 1 )
Dosage and Administration
2 DOSAGE & ADMINISTRATION 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 ) 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 2.2 Administration Instructions for Brivaracetam Oral Solution Brivaracetam oral solution can be initiated with oral administration. Brivaracetam oral solution may be taken with or without food. Brivaracetam 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 brivaracetam oral solution, no dilution is necessary. Brivaracetam oral solution may also be administered using a nasogastric tube or gastrostomy tube. Discard any unused brivaracetam oral solution remaining after 5 months of first opening the bottle. 2.4 Discontinuation of Brivaracetam Oral Solution Avoid abrupt withdrawal from brivaracetam 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...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 )] Adults: Most common adverse reactions (at least 5% for brivaracetam oral solution and at least 2% more frequently than placebo) are somnolence/sedation, dizziness, fatigue, and nausea/vomiting. ( 6.1 ) Pediatric Patients: Most common adverse reactions are similar to those seen in adult patients. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact at +1 833 856 0880 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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, brivaracetam 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 brivaracetam 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) [see Clinical Studies ( 14 )] . The adverse reactions presented in Table 4 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 brivaracetam and 62% treated with placebo. The most common adverse reactions occurring at a frequency of at least 5% in patients treated with brivaracetam 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 brivaracetam at the recommended doses of 50 mg, 100 mg, and 200 mg/day, respectively, compared to 4% in patients randomized to receive placebo. Table 4 lists adverse reactions for brivaracetam that occurred at least 2% more frequently for brivaracetam doses of at least 50 mg/day than placebo. Table 4: Adverse Reactions in Pooled Placebo-Controlled Adjunctive Therapy Studies in Adult Patients with Partial- Onset Seizures (Brivaracetam 50 mg/day, 100 mg/day, and 200 mg/day) Adverse Reactions Brivaracetam (N=803) % Placebo (N=459) % Gastrointestinal disorders Nausea/vomiting symptoms 5 3 Constipation 2 0 Nervous system disorders Somnolence and sedation 16 8 Dizziness 12 7 Fatigue 9 4 Cerebellar coordination and balance disturbances* 3 1 Psychiatric disorders Irritability 3 1 * Cerebellar coordination and balance disturbances includes ataxia, balance disorder, coordination abnormal, and nystagmus. There was no apparent dose-dependent increase in adverse reactions listed in Table 4 with the exception of somnolence and sedation. Pediatric Patients Safety of Brivaracetam was evaluated in two open-label, safety and pharmacokinetic trials in pediatric patients 2 months to less than 16 years of age. Across studies of pediatric patients with partial onset seizures, 186 patients received brivaracetam oral solution or tablet, of whom 123 received brivaracetam for at least...
Drug Interactions
7 DRUG INTERACTIONS Rifampin: Because of decreased concentrations, increasing brivaracetam oral solution 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 dosage in patients on concomitant brivaracetam oral solution. ( 7.2 ) Phenytoin: Because phenytoin concentrations can increase, phenytoin levels should be monitored in patients on concomitant brivaracetam oral solution. ( 7.3 ) Levetiracetam: Brivaracetam oral solution had no added therapeutic benefit when co-administered with levetiracetam. ( 7.4 ) 7.1 Rifampin Co-administration with rifampin decreases brivaracetam plasma concentrations likely because of CYP2C19 induction [see Clinical Pharmacology ( 12.3 )] . Prescribers should increase the brivaracetam dose by up to 100% (i.e., double the dosage) in patients while receiving concomitant treatment with rifampin [see Dosage and Administration ( 2.6 )] . 7.2 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 [see Clinical Pharmacology ( 12.3 )] . 7.3 Phenytoin Because brivaracetam can increase plasma concentrations of phenytoin, phenytoin levels should be monitored in patients when concomitant brivaracetam is added to or discontinued from ongoing phenytoin therapy [see Clinical Pharmacology ( 12.3 )] . 7.4 Levetiracetam Brivaracetam provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered [see Clinical Studies ( 14 )] .
Contraindications
4 CONTRAINDICATIONS Hypersensitivity to brivaracetam or any of the inactive ingredients in brivaracetam oral solution (bronchospasm and angioedema have occurred) [see Warnings and Precautions ( 5.4 )] . Hypersensitivity to brivaracetam or any of the inactive ingredients in brivaracetam oral solution. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series are insufficient to identify a risk of major birth defects, miscarriage or other maternal or fetal outcomes associated with brivaracetam use during pregnancy. In animal studies, brivaracetam produced evidence of developmental toxicity (increased embryofetal mortality and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, and long-term neurobehavioral changes in rat offspring) at maternal plasma exposures greater than clinical exposures [see Data] . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of brivaracetam (0, 150, 300, or 600 mg/kg/day) to pregnant rats during the period of organogenesis did not produce any significant maternal or embryofetal toxicity. The highest dose tested was associated with maternal plasma exposures (AUC) approximately 30 times exposures in humans at the maximum recommended dose (MRD) of 200 mg/day. Oral administration of brivaracetam (0, 30, 60, 120, or 240 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal mortality and decreased fetal body weights at the highest dose tested, which was also maternally toxic. The highest no-effect dose (120 mg/kg/day) was associated with maternal plasma exposures approximately 4 times human exposures at the MRD. When brivaracetam (0, 150, 300, or 600 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, decreased growth, delayed sexual maturation (female), and long-term neurobehavioral changes...
Overdosage
10 OVERDOSAGE There is limited clinical experience with brivaracetam 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 brivaracetam. The following adverse reactions were reported with brivaracetam overdose: vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia. In general, the adverse reactions associated with brivaracetam overdose were consistent with the known adverse reactions. There is no specific antidote for overdose with brivaracetam. 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 rate and rhythm and vital signs is recommended. A certified poison control center should be contacted for updated information on the management of overdose with brivaracetam. There are no data on the removal of brivaracetam using hemodialysis, but because less than 10% of brivaracetam is excreted in urine, hemodialysis is not expected to enhance brivaracetam clearance.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Brivaracetam Oral Solution 10 mg/mL is a slightly viscous, clear, colorless to yellowish, raspberry-flavored liquid. It is supplied in amber glass bottles: 300 mL bottles NDC 71921-410-72 16.2 Storage and Handling Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Do not freeze brivaracetam oral solution. Discard any unused brivaracetam oral solution remaining after 5 months of first opening the bottle.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.