What is the clearance of Pregabalin (Lyrica) in patients with Impaired renal function?

From the Guidelines

Pregabalin clearance is primarily dependent on renal excretion, with approximately 90% of the drug eliminated unchanged in the urine, and its clearance is directly affected by creatinine clearance 1.

Key Points

• The typical elimination half-life of pregabalin is about 6 hours in patients with normal renal function.
• Dosage adjustments are necessary for patients with impaired kidney function, as creatinine clearance directly affects pregabalin clearance.
• For patients with creatinine clearance less than 60 mL/min, dose reductions are recommended, with specific reductions based on the level of renal impairment.

Renal Impairment Considerations

• When creatinine clearance is 30-60 mL/min, the dose should be reduced by about 50%.
• For clearance 15-30 mL/min, a 75% reduction is needed.
• For clearance less than 15 mL/min, the dose should be reduced by approximately 85%.

Additional Considerations

• Pregabalin is effectively removed by hemodialysis, with about 50-60% cleared during a 4-hour session, so supplemental doses may be required after dialysis.
• Age-related decreases in renal function may also necessitate dose adjustments in elderly patients.
• The drug does not undergo significant hepatic metabolism, making liver impairment less relevant to its clearance profile compared to kidney function 1.

From the FDA Drug Label

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80. 9 mL/min in young healthy subjects. Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Pregabalin CL/F is nearly proportional to CLcr (mL/min).

Pregabalin Clearance: Pregabalin is primarily eliminated by renal excretion, with a mean renal clearance of 67.0 to 80.9 mL/min in young healthy subjects.

• The clearance of pregabalin is nearly proportional to creatinine clearance (CLcr).
• Dose adjustment is necessary in patients with renal dysfunction 2, 2.

From the Research

Pregabalin Clearance

• Pregabalin clearance is proportional to creatinine clearance (CLcr) 3
• Total and renal pregabalin clearance were found to be 56% and 58% proportional to CLcr, respectively 3
• The area under the plasma concentration-time profile (AUC) and terminal elimination half-life (t1/2) values increase with decreasing renal function 3
• Pregabalin dosage adjustment is recommended for patients with CLcr < 60 mL/min, with a 50% reduction in daily dose for patients with CLcr between 30 and 60 mL/min 3
• Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr 3
• Pregabalin is highly cleared by hemodialysis, and supplemental doses may be required for patients on chronic hemodialysis treatment after each hemodialysis treatment 3

Renal Impairment and Pregabalin Dosing

• Patients with decreased renal function may be at an increased risk of adverse effects due to higher gabapentinoid doses 4
• A study found that patients with a CrCl <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids, including pregabalin 4
• The relationship between gabapentinoid dosing, kidney function, and the incidence of gabapentinoid-related adverse effects requires larger, multicentre studies 4

Pregabalin in Uremic Pruritus

• Pregabalin has been compared to gabapentin in the treatment of uremic pruritus in patients with chronic kidney disease on maintenance haemodialysis 5, 6
• Both pregabalin and gabapentin were found to be effective in reducing itching intensity, but pregabalin was associated with more adverse effects, such as fatigue, dizziness, and somnolence 5
• A study found that pregabalin was more efficacious than gabapentin in reducing pruritus, but patients who took gabapentin experienced significantly fewer side effects 6