What are the considerations for using Pregabalin (Lyrica) in patients with Impaired renal function (Kidney Disease)?

From the Guidelines

Pregabalin dosing in patients with kidney disease should be adjusted based on creatinine clearance to prevent drug accumulation and toxicity, with a recommended dose reduction for patients with moderate to severe kidney impairment, as supported by the most recent evidence 1. When managing patients with chronic kidney disease (CKD), it is crucial to consider the renal elimination of pregabalin and adjust dosing accordingly.

• For patients with normal kidney function (CrCl ≥60 mL/min), standard dosing of 150-600 mg/day divided into 2-3 doses can be used, as seen in the initial dosing recommendations 1.
• For moderate kidney impairment (CrCl 30-60 mL/min), the dose should be reduced to 75-300 mg/day in 2-3 divided doses.
• With severe impairment (CrCl 15-30 mL/min), the dose should be limited to 25-150 mg/day in 1-2 divided doses.
• For end-stage renal disease (CrCl <15 mL/min), a dose of 25-75 mg once daily is recommended, with supplemental doses given after hemodialysis, as approximately 50-60% of pregabalin is removed during a 4-hour session. It is essential to monitor patients closely for side effects, including dizziness, somnolence, peripheral edema, and weight gain, which may be more pronounced in kidney disease, as pregabalin's elimination is directly proportional to creatinine clearance 1. Key considerations for dosing adjustments in kidney disease include:
• Reducing the dose based on creatinine clearance to prevent drug accumulation and toxicity
• Monitoring patients closely for side effects
• Adjusting the dosing regimen based on the severity of kidney impairment
• Considering the use of supplemental doses after hemodialysis for patients with end-stage renal disease.

From the FDA Drug Label

In view of dose-dependent adverse reactions and since pregabalin is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function. Base the dose adjustment in patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 2. Table 2 Pregabalin Dosage Adjustment Based on Renal Function Creatinine Clearance (CLcr)(mL/min) Total Pregabalin Daily Dose (mg/day)* Greater than or equal to 60 150 300 450 600 30–60 75 150 225 300 15–30 25–50 75 100–150 150 Less than 15 25 25–50 50–75 75 Supplementary dosage following hemodialysis (mg)†

Dosing for Adult Patients with Renal Impairment:

• The dose of pregabalin should be adjusted in adult patients with reduced renal function.
• The dose adjustment should be based on creatinine clearance (CLcr).
• The recommended total daily dose of pregabalin for patients with renal impairment is as follows:
  • CLcr ≥ 60 mL/min: 150-600 mg/day
  • CLcr 30-60 mL/min: 75-300 mg/day
  • CLcr 15-30 mL/min: 25-150 mg/day
  • CLcr < 15 mL/min: 25-75 mg/day
• A supplementary dose should be administered following hemodialysis. 2

From the Research

Pregablin in Kidney Disease

• Pregabalin is a medication that requires dosage adjustment in patients with decreased renal function, as its clearance is proportional to creatinine clearance (CLcr) 3.
• Studies have shown that pregabalin is highly cleared by hemodialysis, and supplemental doses may be required for patients on chronic hemodialysis treatment to maintain steady-state plasma concentrations 3.
• The use of pregabalin in patients with kidney disease has been associated with an increased risk of adverse outcomes, such as altered mental status, falls, and fractures, particularly in those with higher doses 4.
• A study found that patients with a creatinine clearance (CrCl) <60 mL/min were frequently prescribed inappropriately high doses of pregabalin, which can lead to adverse effects 5.
• Pregabalin has been compared to gabapentin in the treatment of uremic pruritus in patients with chronic kidney disease undergoing hemodialysis, with some studies suggesting that pregabalin is more efficacious but also has a higher risk of side effects 6, 7.
• The efficacy and safety of pregabalin versus gabapentin for the treatment of uremic pruritus in patients with chronic kidney disease on maintenance hemodialysis have been compared, with results showing that both drugs can reduce itching intensity, but gabapentin may have a higher risk of side effects such as fatigue, dizziness, and somnolence 7.
• It is essential to carefully monitor patients with kidney disease who are taking pregabalin and adjust the dosage accordingly to minimize the risk of adverse effects 3, 4, 5.