The Therapeutic Goods Administration (TGA) has approved brivaracetam as add-on therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients aged 16 years and over. Like levetiracetam, brivaracetam exerts its anticonvulsant effect by binding to synaptic vesicle protein 2A(SV2A). SV2A is a membrane protein found on all synaptic vesicles that is thought to influence vesicle fusion and neurotransmitter exocytosis. Although structurally similar to levetiracetam, brivaracetam demonstrates a 15 to 30 fold higher affinity for SV2A.

Tolerability is a major limiting factor in the treatment of epilepsy. One study reported that 46.4% of patients treated with levetiracetam discontinued therapy after two years; behavioural adverse effects (BAEs) being the most frequently cited reason. A small open-label study of patients experiencing BEAs during levetiracetam therapy demonstrated a significant reduction in these adverse effects when patients switched to brivaracetam. Larger studies are required to confirm these results. As with other antiepileptic medications, patients should be monitored for the emergence or worsening of depression, suicidal thoughts, and mood changes.

Brivaracetam undergoes extensive hepatic metabolism. The resultant metabolites are then cleared renally. Exposure to brivaracetam is increased by 50% and 59% in patients with mild and severe hepatic impairment respectively. Severe renal impairment results in significantly increased exposure to the metabolites. Close monitoring is recommended for all patients with renal impairment, although dose adjustment may not be required as the metabolites are inactive.

An application was made for listing on the Pharmaceutical Benefits Scheme (PBS) in July 2016. The application was rejected due to a lack of clinical data in the proposed population and a lack of comparison data with a similarly listed antiepileptic medication.

References:

  1. Briviact® (brivaracetam) Australian approved product information. Malvern: UCB Pharma. Approved August 2016.
  2. Chung S, Wang N, Hank N. Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure. 2007; 16(4): 296-304.
  3. Yates SL, Fakhoury T, Liang W, Eckhardt K, Borghs S, D’Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015; 52(A): 165-8.

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