Is lacosamide renally safe in patients with impaired renal function?

Lacosamide Renal Safety

Lacosamide can be used safely in patients with mild-to-moderate renal impairment without dose adjustment, but requires dose reduction in severe renal dysfunction (CrCl <30 mL/min) and supplementation after hemodialysis. 1

Pharmacokinetic Profile in Renal Impairment

Lacosamide undergoes significant renal elimination, making renal function a critical consideration for dosing:

• In healthy individuals, renal clearance accounts for approximately 30% of total body clearance 1
• With severe renal impairment, renal clearance drops to only 11% of total body clearance, while terminal half-life and systemic exposure increase 1
• Nonrenal clearance remains preserved at approximately 1.1 L/h even in patients with essentially no renal function, providing a safety margin 1

Specific Dosing Recommendations by Renal Function

Mild-to-Moderate Renal Impairment

• No dose adjustment necessary, as total body clearance decreases by only approximately 20% 1
• Standard dosing can be maintained safely 1

Severe Renal Impairment (CrCl <30 mL/min)

• Dose reduction is required due to significantly decreased clearance and increased drug exposure 1, 2
• Therapeutic drug monitoring (TDM) may be particularly useful in this population to optimize dosing 2

End-Stage Renal Disease (ESRD) and Hemodialysis

• Hemodialysis removes approximately 50% of lacosamide from plasma during a 4-hour session 1, 3
• Dose supplementation following hemodialysis should be considered to maintain therapeutic levels 1
• Lacosamide is classified as high risk for extraction by hemodialysis 3

Peritoneal Dialysis

• Lower removal efficacy compared to hemodialysis, requiring close attention to possible drug accumulation 4
• Blood levels increase linearly but more slowly than in patients without renal impairment 4
• Close monitoring is essential due to limited pharmacokinetic data in this population 4

Safety and Tolerability

• Lacosamide was well tolerated by both healthy volunteers and patients with varying degrees of renal impairment in clinical studies 1
• The drug has few clinically relevant drug-drug interactions, making it advantageous in patients with renal disease who often take multiple medications 2, 4
• Linear pharmacokinetics allow for predictable dose-concentration relationships, even in renal impairment 2

Clinical Monitoring Recommendations

Therapeutic drug monitoring is particularly valuable in:

• Patients with severe renal dysfunction 2
• Patients on dialysis (both hemodialysis and peritoneal dialysis) 2, 4
• Older adults with declining renal function 2

Common Pitfalls to Avoid

• Do not assume standard dosing is safe in severe renal impairment (CrCl <30 mL/min) - dose reduction is mandatory 1
• Do not forget supplemental dosing after hemodialysis - approximately half the drug is removed during dialysis 1, 3
• Do not rely solely on total body clearance estimates - strong positive correlations exist between creatinine clearance, renal clearance, and urinary excretion that must be considered 1
• Exercise greater caution with peritoneal dialysis than hemodialysis due to lower drug removal and risk of accumulation 4