What is the recommended dose of Vimpat (lacosamide) for a patient with end-stage renal disease (ESRD) on hemodialysis?

Vimpat Dosing in Hemodialysis

For patients with end-stage renal disease on hemodialysis, reduce the maximum Vimpat (lacosamide) dose by 25% and administer a supplemental dose of up to 50% of the divided daily dose immediately after each hemodialysis session.

Dose Adjustment Requirements

Standard Dosing Modifications

• Maximum daily dose reduction: Decrease the maximum recommended daily dose by 25% in patients with severe renal impairment (creatinine clearance ≤30 mL/min) or ESRD 1
• Rationale: Total body clearance decreases by approximately 20% in mild-to-moderate renal impairment, but more substantial reductions occur with severe impairment, necessitating dose adjustment 1

Hemodialysis-Specific Considerations

• Dialyzability: Approximately 50% of lacosamide is removed from systemic circulation during a standard 4-hour hemodialysis session 1
• Post-dialysis supplementation: A supplemental dose (up to 50% of the divided daily dose) should be administered immediately after completing hemodialysis to compensate for drug removal 1
• Timing principle: Administer the supplemental dose after hemodialysis sessions to prevent premature drug removal, following standard principles for medications in ESRD patients 2

Pharmacokinetic Basis

Renal vs Non-Renal Clearance

• In healthy volunteers, renal clearance accounts for approximately 30% of total body clearance (0.59 L/h vs 2.13 L/h total) 1
• With severe renal impairment, renal clearance drops to approximately 11% of total body clearance (0.14 L/h vs 1.34 L/h total) 1
• Critical point: Even in patients with essentially no renal clearance, non-renal clearance remains present at approximately 1.1 L/h, meaning the drug continues to be eliminated through hepatic metabolism 1

Impact on Drug Exposure

• Terminal half-life and systemic exposure increase with worsening renal impairment 1
• Strong positive correlations exist between creatinine clearance, renal clearance, and urinary excretion 1

Practical Dosing Algorithm

For Hemodialysis Patients:

1. Calculate reduced maintenance dose: Take the standard dose and reduce maximum daily dose by 25%
2. Divide into twice-daily dosing: Administer in split doses
3. On dialysis days: Give regular scheduled dose, then administer supplemental dose (50% of single dose) immediately after completing hemodialysis
4. On non-dialysis days: Continue regular twice-daily dosing without supplementation

Example:

• If standard dose would be 200 mg twice daily (400 mg/day total)
• Reduce to maximum 300 mg/day (25% reduction)
• Give 150 mg twice daily
• After each hemodialysis session, add supplemental dose of 75 mg (50% of 150 mg single dose)

Safety and Tolerability

• Lacosamide was well tolerated by healthy volunteers and patients with renal impairment in pharmacokinetic studies 1
• The drug has high tolerability and low drug interaction potential, making it suitable for complex patients 3
• Close monitoring remains essential, particularly during dose titration in dialysis patients 3

Important Caveats

• Peritoneal dialysis differs significantly: Drug removal is substantially lower with peritoneal dialysis compared to hemodialysis, so supplemental dosing is generally not necessary for peritoneal dialysis patients 4
• Residual renal function: If the patient has significant residual urine output, this may affect total drug clearance and should be considered in dosing decisions 4
• Therapeutic drug monitoring: Consider checking lacosamide levels (goal range 5-12 mg/L) to ensure adequate dosing, particularly given the complexity of dosing in dialysis patients 5