What is the dosage of Keppra (Levetiracetam) in a patient with impaired renal function undergoing dialysis?

From the Guidelines

Keppra dosing in dialysis patients should be adjusted to 500-1000 mg once daily, with supplemental doses of 250-500 mg after each dialysis session, due to reduced renal clearance and significant removal of the drug during dialysis 1.

Key Considerations

• The dosage adjustment is necessary because levetiracetam is primarily eliminated unchanged through the kidneys, and renal dysfunction significantly affects its clearance.
• For patients with severe renal impairment (creatinine clearance <30 mL/min) not on dialysis, a dose reduction of 50-75% is recommended, typically 500-1000 mg once or twice daily.
• Continuous renal replacement therapy patients may require doses similar to those with severe renal impairment, with potential supplementation based on the intensity of the therapy.

Monitoring and Safety

• Monitoring for side effects such as somnolence, dizziness, and behavioral changes is crucial, as these may be more pronounced in patients with renal impairment.
• Serum drug levels can be checked if there are concerns about efficacy or toxicity, though routine monitoring is not typically required.

Evidence Basis

• The recommended dosing adjustments are based on the pharmacokinetics of levetiracetam and the impact of renal dysfunction on its clearance, as well as clinical guidelines for managing patients with chronic kidney disease 1.

From the FDA Drug Label

Dosage should be reduced in patients with impaired renal function receiving levetiracetam, and supplemental doses should be given to patients after dialysis Approximately 50% of the pool of levetiracetam in the body is removed during a standard 4-hour hemodialysis procedure

• Dosage adjustment is needed for patients with impaired renal function, including those on dialysis.
• Supplemental doses should be given to patients after dialysis.
• The extent of dosage reduction is not explicitly stated in the label, but it is mentioned that total body clearance of levetiracetam is reduced in patients with impaired renal function by 40% in the mild group, 50% in the moderate group, and 60% in the severe renal impairment group 2.

From the Research

Keppra Dosage in Dialysis Patients

• The recommended dosage of Keppra (levetiracetam) in patients with chronic kidney disease stage 5 D, i.e., patients undergoing dialysis treatment, is a dose reduction by 50% 3.
• This means that patients should receive 250-750 mg every 12 hours 3.
• However, the pharmacokinetics of levetiracetam can vary depending on the modality and intensity of dialysis 3, 4, 5.
• In patients undergoing intermittent hemodialysis, a twice-daily dosing regimen may be more effective than a daily dosing regimen in achieving therapeutic levels of levetiracetam 4.
• Haemodialysis can significantly reduce serum levetiracetam levels, leading to subtherapeutic levels and potentially inducing epileptic seizures 6.
• Continuous renal replacement therapy (CRRT) and sustained low efficiency dialysis (SLED) can also substantially clear levetiracetam, with potential for subtherapeutic concentrations with current recommended dosing strategies 5.

Factors Affecting Keppra Dosage

• Renal function: Levetiracetam is primarily renally eliminated, and dose adjustments are needed in patients with chronic kidney disease stage 5 D 3, 7.
• Dialysis modality: Different dialysis modalities, such as peritoneal dialysis, hemodialysis, CRRT, and SLED, can affect levetiracetam pharmacokinetics 3, 4, 6, 5.
• Treatment intensity: The intensity of dialysis, such as blood flow rate and dialysate flow rate, can impact levetiracetam clearance 5.

Monitoring and Dosing Recommendations

• Close monitoring of serum levetiracetam levels is necessary in patients undergoing dialysis to avoid subtherapeutic or supratherapeutic levels 3, 7, 6.
• Dosing regimens should be individualized based on the patient's renal function, dialysis modality, and treatment intensity 4, 5.