What is the recommended dosing of Keppra (levetiracetam) for patients with impaired renal function undergoing dialysis?

Levetiracetam Dosing in Dialysis Patients

For patients on dialysis, levetiracetam should be dosed at 500-1000 mg every 12 hours with a supplemental dose after hemodialysis sessions. This dosing regimen helps maintain therapeutic levels while accounting for significant drug removal during dialysis procedures.

Pharmacokinetics in Renal Impairment

Levetiracetam is primarily eliminated through the kidneys, with approximately 66% excreted unchanged in the urine and 24% as an inactive metabolite 1. The FDA label clearly indicates that dosage adjustments are necessary in patients with impaired renal function 2:

• Total body clearance of levetiracetam is reduced by:
  • 40% in mild renal impairment (CrCl 50-80 mL/min)
  • 50% in moderate renal impairment (CrCl 30-50 mL/min)
  • 60% in severe renal impairment (CrCl <30 mL/min)
  • 70% in anuric (end-stage renal disease) patients

Specific Dosing Recommendations for Dialysis Patients

Hemodialysis Patients

• Approximately 50% of levetiracetam is removed during a standard 4-hour hemodialysis procedure 2
• Research shows that hemodialysis can significantly reduce serum levetiracetam levels, potentially leading to breakthrough seizures 3
• A twice-daily (BID) dosing regimen achieves significantly higher levels and better recovery to pre-dialysis levels compared to daily dosing 4
• Supplemental doses should be given after dialysis sessions to maintain therapeutic levels 2

Peritoneal Dialysis Patients

• Limited data exists for peritoneal dialysis patients
• One case report showed an increased half-life of 18.4 hours (compared to normal 7 hours) in a peritoneal dialysis patient 1
• The cumulative removal of renally excretable drugs is higher in CAPD patients than in hemodialysis patients between sessions 5

Practical Dosing Algorithm

1. Initial Dosing:

   • Start with 500 mg twice daily for most dialysis patients
   • For elderly patients or those with lower body weight, consider starting at 250 mg twice daily

2. Hemodialysis Patients:

   • Administer 250-500 mg supplemental dose after each hemodialysis session
   • Monitor for clinical response and adverse effects

3. Peritoneal Dialysis Patients:

   • Use similar dosing as for severe renal impairment (500-1000 mg every 12 hours)
   • Consider therapeutic drug monitoring due to limited pharmacokinetic data

Monitoring and Adjustments

• Regular monitoring of levetiracetam levels is recommended, especially in peritoneal dialysis patients 1
• Target therapeutic range: 12-46 mg/L 1
• Watch for signs of toxicity: fatigue, somnolence, and depression 1, 6
• Elderly patients with renal impairment may be particularly susceptible to adverse effects 6

Important Considerations

• Depression has been reported as a probable adverse effect of levetiracetam in elderly patients with kidney disease 6
• Breakthrough seizures during dialysis sessions have been reported due to significant drug removal 3
• The twice-daily regimen provides more stable drug levels compared to daily dosing in hemodialysis patients 4

By following these dosing recommendations and monitoring parameters, clinicians can optimize levetiracetam therapy in dialysis patients while minimizing the risk of both toxicity and breakthrough seizures.