How to adjust Keppra (levetiracetam) dosage in a patient with end-stage renal disease (ESRD) on dialysis, currently on 500mg daily with a subtherapeutic level of 2.0, who was previously stable on 750mg daily?

Keppra Dosing Adjustment for ESRD Patient on Hemodialysis with Subtherapeutic Level

Increase the Keppra dose to 750 mg after each dialysis session (three times weekly), administered immediately post-dialysis, and discontinue any daily dosing schedule. 1, 2

Rationale for Dose Adjustment

Your patient's levetiracetam level of 2.0 mcg/mL is subtherapeutic (therapeutic range typically 12-46 mcg/mL), explaining why he was previously stable on 750 mg daily before developing ESRD. 2 The current 500 mg daily regimen is inadequate because:

• Hemodialysis removes approximately 50% of levetiracetam from the body during a standard 4-hour session, requiring supplemental dosing after each dialysis treatment. 1
• Total body clearance decreases by 70% in anuric ESRD patients compared to those with normal renal function, but dialysis itself becomes the primary route of drug removal. 1
• The FDA label specifically recommends 500-1000 mg every 24 hours for ESRD patients on dialysis, with a 250-500 mg supplemental dose following each dialysis session. 1

Specific Dosing Recommendation

Prescribe levetiracetam 750 mg administered immediately after each hemodialysis session (Monday, Wednesday, Friday or whatever his schedule is). 1, 2 This approach:

• Returns him to his previously effective dose of 750 mg that controlled his myoclonus before hospitalization
• Ensures the medication is given when you can directly observe administration, improving adherence 2
• Prevents drug removal during dialysis by timing administration post-dialysis 2
• Achieves significantly better recovery of plasma levels compared to daily dosing regimens 2

Evidence Supporting Post-Dialysis Dosing

A 2017 prospective study comparing dosing regimens in ESRD patients on hemodialysis demonstrated that post-dialysis supplemental dosing achieved 81.4% recovery to pre-dialysis levels, significantly better than daily dosing schedules. 2 The study found that patients receiving levetiracetam after dialysis maintained mean pre-dialysis levels of 43.1 mcg/mL compared to only 21.1 mcg/mL with daily dosing. 2

Critical Timing Consideration

Administer the dose immediately after dialysis completion, not before or during the session. 2 A case report documented breakthrough generalized tonic-clonic seizures occurring during hemodialysis in a patient on levetiracetam, demonstrating that dialysis can reduce serum levels to subtherapeutic ranges and precipitate seizures. 3

Monitoring Plan

• Recheck levetiracetam level in 1-2 weeks, drawn pre-dialysis to assess trough level 2
• Monitor for seizure activity or myoclonus recurrence as clinical endpoints
• If the level remains subtherapeutic or symptoms persist, increase to 1000 mg post-dialysis (the upper end of the FDA-recommended range for ESRD) 1

Why Not Continue Daily Dosing?

Daily dosing in ESRD patients on intermittent hemodialysis creates problematic fluctuations in drug levels. 2 Between dialysis sessions, the drug accumulates due to minimal renal clearance, but then gets rapidly removed during the 4-hour dialysis session, creating a sawtooth pattern of drug levels that may contribute to breakthrough seizures or myoclonus. 3