The chemical name of BRIVIACT (brivaracetam) is (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl] butanamide. Its molecular formula is C11H20N2O2 and its molecular weight is 212.29.
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.
Indications and usage
BRIVIACT is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
As the safety of BRIVIACT injection in pediatric patients has not been established, BRIVIACT injection is indicated for the treatment of partial-onset seizures only in adult patients (16 years of age and older)
Mechanism of Action
The precise mechanism by which BRIVIACT exerts its anticonvulsant activity is not known. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A(SV2A) in the brain, which may contribute to the anticonvulsant effect.
Dosage and administration
In pediatric patients 4 years to less than 16 years of age, the recommended dosing regimen is dependent upon body weight and is only recommended to be administered orally. When initiating treatment, gradual dose escalation is not required. Dosage should be adjusted based on clinical response and tolerability.
|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 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 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)|
Hypersensitivity to brivaracetam or any of the inactive ingredients in BRIVIACT (bronchospasm and angioedema have occurred)
Warnings and precautions
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.
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.
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.
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.
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.
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. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.
Adults: Most common adverse reactions (at least 5% for BRIVIACT and at least 2% more frequently than placebo) are somnolence/sedation, dizziness, fatigue, and nausea/vomiting.
Pediatric Patients: Most common adverse reactions are similar to those seen in adult patients.
Rifampin: Co-administration with rifampin decreases BRIVIACT plasma concentrations likely because of CYP2C19 induction. Prescribers should increase the BRIVIACT 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 BRIVIACT can increase plasma concentrations of phenytoin, phenytoin levels should be monitored in patients when concomitant BRIVIACT is added to or discontinued from ongoing phenytoin therapy.
Levetiracetam: BRIVIACT provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered.
Use in specific populations
Pregnancy: There are no adequate data on the developmental risks associated with use of BRIVIACT in pregnant women. 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.
Lactation: No data are available regarding the presence of brivaracetam in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Studies in lactating rats have shown excretion of brivaracetam or metabolites in milk.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BRIVIACT and any potential adverse effects on the breastfed infant from BRIVIACT or from the underlying maternal condition.
Pediatric Use: Safety and effectiveness of BRIVIACT tablets and oral solution have been established in pediatric patients 4 years to less than 16 years of age. Use of BRIVIACT in these age groups is supported by evidence from adequate and well-controlled studies of BRIVIACT in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 149 pediatric patients 4 years to less than 16 years of age
Drug abuse and dependence
Controlled Substance: BRIVIACT contains brivaracetam and is listed as a Schedule V controlled substance.
In a human abuse potential study, single doses of BRIVIACT at therapeutic and supratherapeutic doses were compared to alprazolam (C-IV) (1.5 mg and 3 mg). BRIVIACT at the recommended single dose (50 mg) caused fewer sedative and euphoric effects than alprazolam; however, BRIVIACT at supratherapeutic single doses (200 mg and 1000 mg) was similar to alprazolam on other measures of abuse.
There was no evidence of physical dependence potential or a withdrawal syndrome with BRIVIACT in a pooled review of placebo-controlled adjunctive therapy studies.
There is limited clinical experience with BRIVIACT 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 BRIVIACT. The following adverse reactions were reported with BRIVIACT overdose: vertigo, balance disorder, fatigue, nausea, diplopia, anxiety, and bradycardia. In general, the adverse reactions associated with BRIVIACT overdose were consistent with the known adverse reactions.
There is no specific antidote for overdose with BRIVIACT. 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. Acertified poison control center should be contacted for updated information on the management of overdose with BRIVIACT. 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 BRIVIACT clearance.