Is brivaracetam safe for patients with chronic kidney disease, and how should the dose be adjusted according to estimated glomerular filtration rate?

Brivaracetam Safety in Chronic Kidney Disease

Brivaracetam does not require dose adjustment in patients with chronic kidney disease, including those with severe renal impairment, and is safe to use across all stages of CKD except end-stage renal disease requiring dialysis. 1

FDA-Approved Dosing Guidance

• No dose adjustments are required for patients with impaired renal function at any stage of CKD. 1
• Brivaracetam is NOT recommended in patients with end-stage renal disease undergoing dialysis due to lack of data in this specific population. 1
• Standard dosing can be maintained in patients with CKD G1-G5 (not on dialysis), as renal impairment does not significantly affect brivaracetam exposure. 1

Pharmacokinetic Evidence Supporting Safety

• In patients with severe renal impairment (creatinine clearance <30 mL/min), brivaracetam exposure (AUC) increased only minimally by 21%, which is not clinically significant. 2
• The maximum concentration (Cmax) of brivaracetam remains unchanged in severe renal impairment compared to healthy controls. 2
• While inactive metabolites (acid, hydroxy, and hydroxyacid) accumulate significantly in renal impairment (up to 21-fold for hydroxyacid metabolite), nonclinical toxicology studies confirmed these metabolites pose no safety concerns. 2

Renal Clearance Mechanism

• Brivaracetam has predominantly nonrenal clearance (approximately 90% of total clearance), which explains why renal impairment has minimal impact on drug exposure. 2
• Renal clearance of brivaracetam decreases from 4.5 mL/min/1.73 m² in healthy individuals to 1.7 mL/min/1.73 m² in severe renal impairment, but this represents only a small fraction of total drug elimination. 2

Monitoring Recommendations in CKD

• Monitor eGFR and electrolytes at baseline and periodically during treatment, as recommended for all medications in CKD patients. 3
• Assess for central nervous system adverse effects (sedation, confusion, behavioral changes), which are the primary safety concerns with brivaracetam regardless of renal function. 4
• Therapeutic drug monitoring is not routinely required for brivaracetam, as it has a wide therapeutic index. 3

Contrast with Other Antiepileptic Drugs

• Unlike gabapentin, which requires substantial dose reduction in CKD, brivaracetam's predominantly hepatic metabolism makes it uniquely advantageous in renal impairment. 4
• This represents a significant practical advantage when selecting antiepileptic therapy for patients with CKD, as dose adjustments and complex calculations are unnecessary. 5, 6

Critical Exception: End-Stage Renal Disease on Dialysis

• The only absolute contraindication is ESRD requiring dialysis, where brivaracetam use is not recommended due to absence of pharmacokinetic data. 1
• If dialysis becomes necessary in a patient already taking brivaracetam, consultation with nephrology and clinical pharmacology is warranted to determine whether continuation is appropriate. 4

Hepatic Impairment Consideration

• Dose adjustment IS required for hepatic impairment at all stages (unlike renal impairment), as brivaracetam is primarily metabolized hepatically. 1
• Do not confuse the dosing requirements: renal function does not require adjustment, but hepatic function does. 1