What are the dosing recommendations for pregabalin (lyrica) in patients with impaired renal function (chronic kidney disease)?

Pregabalin Dosing in Chronic Kidney Disease

Pregabalin requires mandatory dose reduction in patients with chronic kidney disease based on creatinine clearance, with specific adjustments outlined in the FDA label that should be strictly followed to prevent toxicity. 1

Dosing Algorithm Based on Renal Function

For Creatinine Clearance ≥60 mL/min

• Standard dosing applies with no adjustment needed 1
• Starting dose: 50-75 mg twice daily or three times daily 2
• Maximum dose: 600 mg/day (200 mg three times daily or 300 mg twice daily) 2

For Creatinine Clearance 30-60 mL/min

• Reduce total daily dose by approximately 50% compared to normal renal function 1, 3
• If standard dose would be 150 mg/day, adjust to 75 mg/day 1
• Administer in 2-3 divided doses 1

For Creatinine Clearance 15-30 mL/min

• Further 50% reduction from the 30-60 mL/min dose 1, 3
• Approximately 25-50% of the standard dose 1
• Maintain divided dosing schedule 1

For Creatinine Clearance <15 mL/min

• Reduce to 25 mg once daily or less 1
• Single daily dosing is appropriate at this level 1

For Patients on Hemodialysis

• Adjust daily dose based on residual renal function PLUS give supplemental dose after each dialysis session 1, 3
• Supplemental dose should be given immediately following every 4-hour hemodialysis treatment 1
• Pregabalin is highly cleared by hemodialysis, making supplementation essential 3

Critical Clinical Considerations

Calculating Creatinine Clearance

• Use the Cockcroft-Gault equation as specified in the FDA label for dose adjustment decisions 1
• Estimated GFR may not be equivalent to creatinine clearance for dosing purposes 1

Toxicity Risk in CKD

• Gabapentinoids cause dose-dependent toxicity that is significantly increased in renal impairment 2, 4
• Common toxic manifestations include encephalopathy, dizziness, sedation, falls, and fractures 4, 5
• Elderly patients with multiple comorbidities are at highest risk for toxicity 4
• Starting at higher doses (>75 mg/day pregabalin) in CKD patients increases 30-day risk of adverse events by 27% compared to lower starting doses 5

Monitoring Requirements

• Assess renal function before initiating therapy and monitor periodically 2
• In patients receiving nephrotoxic chemotherapy or with fluctuating renal function, more frequent monitoring is warranted 2
• Gabapentin toxicity is initially suspected in only 41.5% of symptomatic cases, requiring high clinical suspicion 4

Important Warnings

Abrupt Discontinuation

• Never abruptly discontinue pregabalin in CKD patients, even during acute illness 6
• Sudden cessation can precipitate withdrawal seizures, even in patients without epilepsy 6
• If temporary discontinuation is necessary during acute kidney injury, taper the dose and restart at renally-adjusted dose once stable 6

Pediatric Patients

• Pregabalin use in pediatric patients with renal impairment has not been studied 1
• No dosing recommendations can be provided for this population 1

Drug Interactions

• Pregabalin has few drug interactions, which is advantageous in CKD patients on multiple medications 2
• However, the dose-dependent adverse effects (dizziness, sedation) can be additive with other CNS depressants 2

Practical Prescribing Approach

Start low and titrate slowly in all CKD patients 2:

• Begin at the lower end of the renally-adjusted dose range 2
• Titrate cautiously every 3-7 days as tolerated 2
• Allow 4 weeks at maximum tolerated dose before assessing efficacy 2
• Doses above 450 mg/day are not recommended even in normal renal function due to increased adverse effects without additional benefit 1