How should pregabalin (Lyrica) be dosed in adults with normal renal function and in those with moderate (creatinine clearance 30–60 mL/min), severe (creatinine clearance 15–30 mL/min), or end‑stage (creatinine clearance <15 mL/min) renal impairment?

Pregabalin (Lyrica) Renal Dosing Guidelines

Direct Answer

Pregabalin requires mandatory dose reduction based on creatinine clearance: for normal renal function (CLcr ≥60 mL/min), the maximum dose is 600 mg/day in 2-3 divided doses; for moderate impairment (CLcr 30-60 mL/min), reduce the total daily dose by 50%; for severe impairment (CLcr 15-30 mL/min), reduce by 75%; and for end-stage renal disease (CLcr <15 mL/min or on hemodialysis), reduce by 85-90% with supplemental dosing after each dialysis session. 1, 2, 3

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Step-by-Step Dosing Algorithm

Step 1: Calculate Creatinine Clearance Before Prescribing

• Always calculate CLcr using the Cockcroft-Gault equation before initiating pregabalin, as pregabalin is 98% eliminated unchanged by the kidneys and failure to adjust dosing causes preventable toxicity 1, 2
• Formula: CLcr (mL/min) = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL), multiply by 0.85 for females 4
• Never assume normal renal function based on serum creatinine alone, especially in elderly patients where age-related decline in renal function is often masked by reduced muscle mass 4

Step 2: Determine Maximum Allowable Dose Based on Renal Function

Normal Renal Function (CLcr ≥60 mL/min):

• Maximum dose: 600 mg/day (300 mg twice daily or 200 mg three times daily) 1, 2
• Standard starting dose: 75 mg twice daily or 50 mg three times daily (150 mg/day total) 1, 4
• Target therapeutic dose: 300 mg/day (150 mg twice daily or 100 mg three times daily) 1, 4

Moderate Renal Impairment (CLcr 30-60 mL/min):

• Reduce total daily dose by approximately 50% compared to normal renal function 5, 2, 3
• Maximum dose: 300 mg/day 1, 2
• Starting dose: 75 mg/day (25-50 mg twice daily) 4
• Administer in 2-3 divided doses 2

Severe Renal Impairment (CLcr 15-30 mL/min):

• Reduce total daily dose by approximately 75% compared to normal renal function 5, 2, 3
• Maximum dose: 150 mg/day 1, 2
• Starting dose: 25-50 mg/day 4
• Administer in 1-2 divided doses 2

End-Stage Renal Disease (CLcr <15 mL/min or on hemodialysis):

• Reduce total daily dose by 85-90% compared to normal renal function 5, 4, 3
• Maximum dose: 75 mg/day 1, 2
• Starting dose: 25 mg/day 4
• Administer as single daily dose 2
• For hemodialysis patients: Give supplemental dose immediately after each 4-hour hemodialysis treatment (25-75 mg depending on daily dose), as pregabalin is highly cleared by hemodialysis 2, 3

Step 3: Titrate Slowly and Monitor Closely

• Start at the lowest dose for the patient's renal function category 1, 4
• Increase gradually (approximately weekly) based on efficacy and tolerability 1, 2
• Never exceed the renal-adjusted maximum dose for the patient's CLcr category 1
• Monitor for dose-dependent adverse effects: dizziness (23-46%), somnolence (15-25%), peripheral edema (10%), and confusion (especially in elderly) 1, 4

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Critical Clinical Pitfalls to Avoid

Most Common Prescribing Error

Never prescribe pregabalin without first calculating creatinine clearance—this is the most common prescribing error leading to toxicity, particularly in elderly patients where normal serum creatinine masks significant renal impairment 1, 4

Abrupt Discontinuation Risk

• Never abruptly discontinue pregabalin in patients with renal impairment—taper gradually over minimum of 1 week to avoid withdrawal seizures, even when temporarily holding for acute illness 4, 6
• A case report documented a tonic-clonic seizure 4 days after abrupt cessation of pregabalin in a patient with chronic kidney disease (baseline eGFR 15 mL/min) 6

Changing Renal Function

• Renal function changes frequently in hospitalized patients—30% of patients with renal dysfunction show improvements during hospitalization, requiring dose adjustments 7
• Reassess CLcr if clinical status changes (dehydration, acute illness, new nephrotoxic medications) and adjust pregabalin dose accordingly 5, 4

Hemodialysis Timing

• Always administer pregabalin after hemodialysis, not before, to avoid premature drug removal and facilitate directly observed therapy 5, 2
• Approximately 40-50% of pregabalin is removed during a 4-hour hemodialysis session 3

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Pharmacokinetic Rationale

• Pregabalin clearance is directly proportional to creatinine clearance (56-58% correlation) 3, 8
• At CLcr 18 mL/min, the area under the curve (AUC) increases 6.3-fold compared to normal renal function, with terminal half-life doubling to 28 hours 4, 3
• Pregabalin is not metabolized by the liver (<2% metabolism) and does not undergo hepatic cytochrome P450 metabolism, making renal excretion the sole elimination pathway 8
• Linear pharmacokinetics with >90% oral bioavailability makes dose adjustments predictable once renal function is accurately assessed 1, 8

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Special Population Considerations

Elderly Patients

• Consider lower starting doses (25 mg/day) and slower titration due to increased risk of dizziness, somnolence, confusion, and falls 1, 4
• Age-related decline in renal function is often masked by reduced muscle mass, causing creatinine-based equations to misclassify kidney disease in >30% of elderly patients 4

Acute-on-Chronic Renal Impairment

• When acute illness temporarily worsens renal function, reduce or hold pregabalin dose rather than continuing at baseline dose 6
• Do not abruptly discontinue—reduce to lowest renally-adjusted dose (e.g., 25 mg/day) and taper if discontinuation is necessary 6
• Resume appropriate renally-adjusted dose once renal function returns to baseline 6