Is Breviracetam (nootropic agent) dialysable in patients with impaired renal function?

Brivaracetam Dialyzability in Patients with Impaired Renal Function

Brivaracetam is not significantly removed by hemodialysis and is not recommended for use in patients with end-stage renal disease undergoing dialysis due to lack of clinical data. 1

Pharmacokinetic Properties and Renal Clearance

• Brivaracetam is primarily metabolized via hydrolysis of the acetamide group and CYP2C8-mediated hydroxylation, with renal excretion playing a minor role in its clearance 2, 3
• Less than 10% of brivaracetam is excreted unchanged in urine, making hemodialysis unlikely to significantly enhance brivaracetam clearance 1
• While brivaracetam and its metabolites (which are not pharmacologically active) are excreted renally (>95% within 72 hours), the parent compound's low renal excretion means dialysis would have minimal impact 2, 3

Clinical Recommendations for Renal Impairment

• According to the FDA label, dose adjustments are not required for patients with impaired renal function 1
• However, the FDA specifically states: "There are no data in patients with end-stage renal disease undergoing dialysis, and use of BRIVIACT is not recommended in this patient population" 1
• This recommendation is based on the lack of clinical studies in dialysis patients rather than concerns about dialyzability 1

Comparison with Other Antiepileptic Drugs

• Unlike some other medications that require specific post-dialysis dosing (such as cefepime 4), brivaracetam's pharmacokinetic profile suggests minimal removal during dialysis procedures 2
• This contrasts with other drugs like lenalidomide, which is dialyzable and requires post-dialysis administration in patients on dialysis 5
• The EXTRIP workgroup has established recommendations for various medications regarding dialyzability, but brivaracetam is not specifically mentioned in their guidelines 5

Metabolite Considerations

• While brivaracetam itself is minimally affected by renal impairment (AUC increased by only 21% in severe renal impairment), its metabolites show significantly increased exposure in renal impairment 2
• Exposure to brivaracetam's three main metabolites (acid, hydroxy, and hydroxyacid) is markedly increased in severe renal impairment, but these metabolites are pharmacologically inactive and nonclinical toxicology studies have not identified safety issues related to their increased levels 2

Clinical Implications

• Brivaracetam has a favorable pharmacokinetic profile with few clinically relevant drug-drug interactions, making it potentially suitable for patients with complex medication regimens 6, 7
• Despite the increased exposure to metabolites in renal impairment, dose adjustment is not required at any stage of renal dysfunction based on available pharmacokinetic data 2
• The decision not to recommend brivaracetam in dialysis patients appears to be based on lack of clinical data rather than specific safety concerns 1

In summary, while brivaracetam is technically not significantly dialyzable due to its pharmacokinetic properties, the FDA does not recommend its use in dialysis patients due to insufficient clinical data in this population.