BRIVIACT

What it is

Briviact is brivaracetam, available as film-coated tablets and oral solution. The film-coated tablets are available in strengths of 10 mg, 25 mg, 50 mg, 75 mg, and 100 mg brivaracetam. The oral solution is available as 10 mg/mL strength. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain. Binding to SV2A is considered to be the primary mechanism for brivaracetam anticonvulsant activity, however, the precise mechanism by which brivaracetam exerts its anticonvulsant activity has not been fully elucidated.

Approved indications

— Add-on therapy in the treatment of partial onset seizures with or without secondary generalisation in patients from 4 years of age with epilepsy.

Dosing overview

Briviact at doses between 50 and 200 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures. The recommended starting dose as per clinical trials is 100 mg/day. In accordance with good prescribing practice, Briviact may be initiated at a dose of 50 mg per day. Based on individual patient response, the dose may be adjusted between 50 mg/day and 200 mg/day in steps of 50 mg per day every 2 weeks. The daily dose is administered in two equally divided doses, once in the morning and once in the evening. Briviact may be taken with or without food. In patients with hepatic impairment, a 50 mg/day starting dose should be considered in adults, or in adolescents weighing 50 kg or greater. A maximum daily dose of 150 mg administered in 2 divided doses is recommended for all stages of hepatic impairment. The dose should be monitored in any form of renal impairment. No dose reduction is necessary in elderly patients. For children from 4 years of age or adolescents weighing less than 50 kg, the recommended starting dose is 1 mg/kg/day. Brivaracetam may also be initiated at 2 mg/kg/day based on physician assessment of need for seizure control. The recommended maintenance dose is 2 mg/kg/day. Based on individual patient response, the dose may be adjusted between the effective dose range of 1 mg/kg/day and 4 mg/kg/day.

Key safety warnings

Antiepileptic drugs, including Briviact, increase the risk of suicidal thoughts or behaviour 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 behaviour, and/or any unusual changes in mood or behaviour. Pooled analyses of 199 placebo controlled clinical trials of 11 different AEDs showed that patients randomised to one of the AEDs had approximately twice the risk of suicidal thinking or behaviour compared to patients randomised to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behaviour or ideation among 27,863 AED treated patients was 0.43%, compared to 0.24% among 16,029 placebo treated patients. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for the emergence of worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about self harm. Behaviours of concern should be reported immediately to the treating doctor. 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. Patients should be advised not to drive a car or to operate other potentially hazardous machines until they are familiar with the effects of brivaracetam on their ability to perform such activities, as brivaracetam treatment has been associated with somnolence and other CNS related symptoms.

Contraindications

Briviact is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

PBS listing

Briviact film-coated tablets at strengths of 25 mg, 50 mg, 75 mg, and 100 mg are each listed on the PBS with 2 items under streamlined authority required restriction, with an ex-manufacturer price of A$131.83. The oral solution at 10 mg per mL (300 mL) is listed on the PBS with 2 items under streamlined authority required restriction, with an ex-manufacturer price of A$164.79.

Regulatory history

Briviact was approved by the TGA on 2 August 2016 as add-on therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients from 16 years of age with epilepsy. The PBAC deferred a decision on brivaracetam in November 2014 to allow the sponsor to provide further information regarding the clinical place in therapy and a revised economic analysis. In November 2017, the PBAC recommended brivaracetam for listing for intractable partial epileptic seizures on a cost-minimisation basis against lacosamide, with positioning as a third-line adjunctive therapy adequately supported. The PBAC also recommended listing in November 2017 for adjunctive treatment of partial-onset seizures with or without secondary generalisation in patients aged 16 years and older with epilepsy. In November 2019, the PBAC recommended changes to the Authority Required (Streamlined) listings to include patients aged 4 to 15 years and remove continuation criteria requiring treatment to be in combination with two or more anti-epileptic drugs.