Keppra Dosing in Hemodialysis
For patients on hemodialysis, reduce the levetiracetam dose by 50-70% with supplemental dosing after each dialysis session, typically 250-750 mg every 12 hours with an additional 250-500 mg post-dialysis.
Dosing Recommendations
Standard Hemodialysis Dosing
- Patients with end-stage renal disease on hemodialysis should receive 250-750 mg every 12 hours, representing a 50% dose reduction from standard dosing 1
- An additional supplemental dose of 250-500 mg should be administered after each dialysis session 1
- Total body clearance decreases by approximately 70% in anuric patients compared to those with normal renal function 1
Timing of Administration
- All doses should be given after hemodialysis on dialysis days to avoid premature drug removal and facilitate directly observed therapy 1, 2
- Approximately 50% of levetiracetam is removed during a standard 4-hour hemodialysis procedure 1
- Administering the drug before dialysis results in significant removal and can lead to subtherapeutic levels that may precipitate seizures 3
Pharmacokinetic Considerations
Drug Clearance in Renal Impairment
- Levetiracetam is primarily renally eliminated, with 66% excreted unchanged in urine and 24% as an inactive metabolite 4
- Clearance is reduced by 40% in mild renal impairment (CrCl 50-80 mL/min), 50% in moderate impairment (CrCl 30-50 mL/min), and 60% in severe impairment (CrCl <30 mL/min) 1
- The half-life increases from approximately 7 hours in normal patients to significantly longer in dialysis patients 4
Dialysis Removal
- Hemodialysis efficiently removes levetiracetam due to its low protein binding and small molecular weight 1, 3
- The dialysis clearance is substantial enough to warrant supplemental dosing after each session 1
Monitoring Requirements
Therapeutic Drug Monitoring
- Serum levetiracetam concentrations should be monitored regularly in hemodialysis patients to avoid both subtherapeutic levels (which can precipitate seizures) and supratherapeutic levels (which can cause sedation and cognitive impairment) 4, 3
- The therapeutic range is 12-46 mg/L 4
- Monitoring is particularly important because individual pharmacokinetic variability can be substantial in dialysis patients 4
Clinical Monitoring
- Assess for signs of toxicity including fatigue, somnolence, and cognitive impairment, which may indicate excessive drug accumulation 4
- Monitor for breakthrough seizures, particularly around dialysis sessions, which may indicate inadequate supplemental dosing 3
Critical Pitfalls to Avoid
Common Dosing Errors
- Failure to provide supplemental post-dialysis dosing is a critical error that leads to subtherapeutic levels and breakthrough seizures 3
- Administering the full standard dose without renal adjustment causes drug accumulation and toxicity 4
- Giving doses before rather than after dialysis results in excessive drug removal 1, 2
Special Considerations
- In peritoneal dialysis patients, pharmacokinetics differ substantially from hemodialysis, with prolonged half-life (up to 18.4 hours) and continuous but slower drug removal 4
- Residual renal function, if present, contributes to drug clearance and may allow for slightly higher dosing 1
- No hepatic dose adjustment is needed, as levetiracetam clearance is not significantly affected by liver impairment 1