From the Guidelines
Pregabalin is not directly nephrotoxic, but its dosage needs to be adjusted in patients with impaired renal function to prevent potential toxicity due to decreased clearance 1.
Key Considerations
- Pregabalin is primarily eliminated unchanged through the kidneys, and patients with reduced renal function will have decreased clearance, leading to higher blood levels if standard doses are used.
- Dosage adjustment is necessary based on creatinine clearance to avoid adverse effects such as dizziness, somnolence, peripheral edema, and confusion.
- For patients with impaired renal function, the recommended dosage adjustments are:
- Creatinine clearance 30-60 mL/min: 75-300 mg/day divided into 2-3 doses
- Creatinine clearance 15-30 mL/min: 25-150 mg/day in 1-2 doses
- Creatinine clearance <15 mL/min: 25-75 mg once daily
Clinical Implications
- Pregabalin can be removed by hemodialysis, so supplemental doses may be needed after dialysis sessions.
- Regular monitoring of renal function and observation for side effects is crucial when using pregabalin in patients with kidney impairment.
- The efficacy and tolerability of pregabalin are similar to those of gabapentin, but pregabalin has linear pharmacokinetics, making dosing more straightforward 1.
From the FDA Drug Label
Pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function. Pregabalin is eliminated primarily by renal excretion, and dose adjustment is recommended for adult patients with renal impairment [see DOSAGE AND ADMINISTRATION (2.7) and CLINICAL PHARMACOLOGY (12.3)].
Pregabalin Nephrotoxicity: Pregabalin is not directly nephrotoxic, but its elimination is primarily through renal excretion. Therefore, patients with impaired renal function are at a higher risk of toxic reactions due to accumulation of the drug.
- Key Points:
From the Research
Pregabalin Nephrotoxicity
- Pregabalin is primarily cleared by the kidney, and its clearance is proportional to creatinine clearance (CLcr) 3.
- Patients with impaired renal function may be at risk of adverse effects due to decreased pregabalin clearance, and dosage adjustment is recommended for patients with CLcr < 60 mL/min 3, 4.
- A study found that patients with a CrCl <60 mL/min were frequently prescribed inappropriately high doses of pregabalin, which may increase the risk of adverse effects such as falls 4.
- Pregabalin has been associated with a higher risk of altered mental status, falls, and fractures in patients on hemodialysis, particularly at higher doses 5.
- In patients with chronic kidney injury undergoing hemodialysis, pregabalin was found to be more efficacious than gabapentin in reducing uremic pruritus, but was also associated with more side effects such as sedation, nausea, and blurred vision 6.
Dosage Recommendations
- Pregabalin dosage adjustment should be considered for patients with CLcr < 60 mL/min, with a 50% reduction in daily dose recommended for patients with CLcr between 30 and 60 mL/min compared to those with CLcr > 60 mL/min 3.
- Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr 3.
- Supplemental pregabalin doses may be required for patients on chronic hemodialysis treatment after each hemodialysis treatment to maintain steady-state plasma pregabalin concentrations within desired ranges 3.
Adverse Effects
- Pregabalin has been associated with adverse effects such as altered mental status, falls, and fractures, particularly in patients with impaired renal function 4, 5.
- Common side effects of pregabalin include sedation, nausea, and blurred vision, which were found to be more frequent in patients taking pregabalin compared to gabapentin 6.