How is Lyrica (pregabalin) elimination affected in a patient with impaired renal function on dialysis but with normal, non-toxin clearing urine output?

Pregabalin Elimination in Dialysis Patients with Normal Urine Output

Pregabalin is primarily eliminated by renal excretion and requires significant dose adjustment in dialysis patients, regardless of their urine output status, as approximately 98% of pregabalin is excreted unchanged in the urine. 1

Pharmacokinetics of Pregabalin in Renal Impairment

• Pregabalin is rapidly absorbed in all patients but its clearance is directly proportional to creatinine clearance (CLcr), with total and renal pregabalin clearance reduced by approximately 56-58% in patients with impaired renal function 2
• The elimination half-life of pregabalin increases significantly as renal function declines, leading to drug accumulation if doses are not adjusted 2
• Despite normal urine output, dialysis patients still have severely impaired ability to clear toxins, including medications like pregabalin that are primarily eliminated by glomerular filtration 3

Dosing Recommendations for Dialysis Patients

• According to the FDA label, pregabalin dosing in hemodialysis patients should be based on creatinine clearance, not urine output volume 1
• For patients on hemodialysis, the recommended starting total daily dose is 25-75 mg/day given as a single daily dose 1
• A supplemental dose should be administered immediately following every 4-hour hemodialysis treatment to maintain therapeutic levels 1, 2
• Hemodialysis efficiently removes pregabalin from circulation, with approximately 50-60% of the drug removed during a 4-hour hemodialysis session 2

Clinical Implications

• Even with preserved urine output, the non-toxin clearing nature of the urine in dialysis patients means that pregabalin will still accumulate without proper dose adjustment 3
• Failure to adjust pregabalin dosing in renal impairment can lead to serious adverse effects including myoclonic encephalopathy, even when plasma levels appear to be within therapeutic range 4
• The presence of normal urine volume does not indicate normal drug clearance capacity, as the quality of filtration (glomerular filtration rate) is more important than the quantity of urine produced 5

Monitoring Recommendations

• Regular monitoring for adverse effects is essential in dialysis patients taking pregabalin, including assessment for CNS symptoms such as dizziness, somnolence, and confusion 6
• Dose adjustments should be based on creatinine clearance measurements rather than urine output volume 1
• Patients with residual kidney function on dialysis may still require dose adjustments similar to those with severe renal impairment (CLcr <30 mL/min) 2

Common Pitfalls to Avoid

• Do not assume that normal urine output indicates normal drug clearance capacity in dialysis patients 3
• Avoid standard dosing of pregabalin in dialysis patients even if they have preserved urine output, as this can lead to drug accumulation and toxicity 2, 4
• Remember that successful removal of a drug by dialysis requires that it possesses polar characteristics, low protein binding, and a small to moderate volume of distribution - all properties that pregabalin exhibits 3