What is the benefit of Keppra (Levetiracetam) in patients with End-Stage Renal Disease (ESRD) on dialysis?

From the FDA Drug Label

The disposition of levetiracetam was studied in adult subjects with varying degrees of renal function Total body clearance of levetiracetam is reduced in patients with impaired renal function by 40% in the mild group (CLcr = 50 to 80 mL/min), 50% in the moderate group (CLcr = 30 to 50 mL/min) and 60% in the severe renal impairment group (CLcr <30 mL/min). Clearance of levetiracetam is correlated with creatinine clearance In anuric (end stage renal disease) patients, the total body clearance decreased 70% compared to normal subjects (CLcr >80mL/min). Approximately 50% of the pool of levetiracetam in the body is removed during a standard 4-hour hemodialysis procedure Dosage should be reduced in patients with impaired renal function receiving levetiracetam, and supplemental doses should be given to patients after dialysis

The benefit of Keppra (Levetiracetam) in patients with End-Stage Renal Disease (ESRD) on dialysis is that it can still be used, but with reduced dosage and supplemental doses given after dialysis, as approximately 50% of the pool of levetiracetam is removed during a standard 4-hour hemodialysis procedure 1. Key points to consider include:

• Reduced total body clearance of levetiracetam in patients with impaired renal function
• Correlation between clearance of levetiracetam and creatinine clearance
• Need for reduced dosage and supplemental doses after dialysis in patients with ESRD on dialysis

From the Research

Levetiracetam is a beneficial treatment option for patients with End-Stage Renal Disease (ESRD) on dialysis, with a recommended dose of 750-1000 mg twice daily, and an initial loading dose of 60 mg/kg, to achieve therapeutic drug concentrations. This recommendation is based on the most recent and highest quality study available, which suggests that this dosing strategy can help achieve therapeutic drug concentrations in a high percentage of patients 2.

Key Considerations

• Levetiracetam is primarily eliminated by the kidneys, with approximately 66% of the unchanged drug being eliminated through this route 3, 4.
• In patients with ESRD on dialysis, the elimination half-life of levetiracetam is increased, and the drug is eliminated by dialysis at a rate of approximately 50% 5, 2.
• The use of a reduced loading dose or twice daily doses of 500 mg or less without loading may result in prolonged sub-therapeutic drug concentrations 2.
• Therapeutic drug monitoring is essential to ensure that patients with ESRD on dialysis achieve therapeutic drug concentrations and minimize the risk of adverse effects.

Benefits and Risks

• Levetiracetam has a favorable pharmacokinetic profile, with a low protein binding rate, minimal hepatic metabolism, and a low potential for drug interactions 4.
• However, levetiracetam can cause adverse effects such as somnolence, irritability, and fatigue, which may be more pronounced in patients with ESRD on dialysis 3, 6.
• The risk of acute kidney injury induced by levetiracetam poisoning is also a concern, and hemodialysis may be required in severe cases 6.

Clinical Implications

• Clinicians should be aware of the potential for levetiracetam to cause adverse effects in patients with ESRD on dialysis and monitor patients closely for signs of toxicity.
• The use of therapeutic drug monitoring can help ensure that patients achieve therapeutic drug concentrations and minimize the risk of adverse effects.
• In cases of acute renal failure in levetiracetam poisoning, induction of dialysis is beneficial, and clinicians should be prepared to initiate dialysis as needed 6.