Bivara Oral Solution

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

This is a preparation of Brivaracetam which is an anticonvulsant. The precise mechanism by which Brivaracetam 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.

Brivaracetam tablet or oral solution is taken in oral route. It may be taken with or without food. The recommended dose for patients 1 month of age and older is included below. 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. Dose should be adjusted based on clinical response and tolerability.

Adults (16 years and older)-

• Initial dose: 50 mg twice daily (100 mg per day)
• Minimum and maximum maintenance dose: 25 mg to 100 mg twice daily (50 mg to 200 mg per day)

Pediatric patients weighing 50 kg or more-

• Initial dose: 25 mg to 50 mg twice daily (50 mg to 100 mg per day)
• Minimum and maximum maintenance dose: 25 mg to 100 mg twice daily (50 mg to 200 mg per day)

Pediatric patients weighing 20 kg to less than 50 kg-

• Initial dose: 0.5 mg/kg to 1 mg/kg twice daily (1 mg/kg to 2 mg/kg per day)
• Minimum and maximum maintenance dose: 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-

• Initial dose: 0.5 mg/kg to 1.25 mg/kg twice daily (1 mg/kg to 2.5 mg/kg per day)
• Minimum and maximum maintenance dose: 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-

• Initial dose: 0.75 mg/kg to 1.5 mg/kg twice daily (1.5 mg/kg to 3 mg/kg per day)
• Minimum and maximum maintenance dose: 0.75 mg/kg to 3 mg/kg twice daily (1.5 mg/kg to 6 mg/kg per day)

Geriatric use: Dose selection for an elderly patient should be judicious, usually starting at the low end of the dosing range.

Renal impairment: Dose adjustments are not required for patients with impaired renal function. Use of brivaracetam is not recommended in patients with end stage renal disease undergoing dialysis.

Use in children and adolescents: Safety and effectiveness in pediatric patients below the age of 1 month have not been established.

Administration instruction of Brivaracetam injection: Brivaracetam injection may be used for adult patients when oral administration is temporarily not feasible. It can be administered intravenously without further dilution or may be mixed with diluents e.g. 0.9% Sodium Chloride injection/Lactated Ringer’s injection/5% Dextrose injection. It should be administered intravenously over 2 to 15 minutes.

Co-administration with rifampin decreases Bivara plasma concentrations likely because of CYP2C19 induction. Prescribers should increase the Bivara dose by up to 100% (i.e., double the dose) in patients while receiving concomitant treatment with rifampin. Co-administration with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine. If tolerability issues arise when co-administered, carbamazepine dose reduction should be considered. Because Bivara can increase plasma concentrations of phenytoin, phenytoin levels should be monitored in patients when concomitant Bivara is added to or discontinued from ongoing phenytoin therapy. Bivara provided no added therapeutic benefit to levetiracetam when the two drugs were co-administered.

Brivaracetam is contraindicated in patients with known hypersensitivity to brivaracetam or any other components of this product.

The most common side effects are nausea/vomiting, constipation, somnolence and sedation, dizziness, fatigue, cerebellar coordination and balance disturbances and irritability.

Pregnancy: Brivaracetam should not be used during pregnancy unless clinically necessary i.e. (if the benefit to the mother clearly outweighs the potential risk to the fetus).

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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for brivaracetam and any potential adverse effects on the breastfed infant from brivaracetam or from the underlying maternal condition.

Antiepileptic drugs (AEDs), including Bivara, increase the risk of suicidal thoughts or behavior. Patients treated with any AED should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior and/or any unusual changes in mood or behavior. Bivara 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. Bivara causes psychiatric adverse reactions which included both non-psychotic symptoms (irritability, anxiety, nervousness, aggression, belligerence, anger, agitation, restlessness, depression, depressed mood, tearfulness, apathy, mood swings, psychomotor hyperactivity, abnormal behavior and adjustment disorder) and psychotic symptoms (psychotic disorder along with hallucination, paranoia, acute psychosis and psychotic behavior). As with most antiepileptic drugs, Bivara should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus.

The adverse reactions with Bivara overdose are vertigo, balance disorder, fatigue, nausea, diplopia, anxiety and bradycardia. There is no specific antidote for overdose with Bivara. 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.

Adjunct anti-epileptic drugs

Store in a cool (below 30°C) and dry place protected from light. Keep away from the reach of children.