Do I dose gabapentin (Gabapentin) based on estimated Glomerular Filtration Rate (eGFR) or creatinine clearance in patients with Impaired Renal Function?

Gabapentin Dosing: Use Creatinine Clearance, Not eGFR

Gabapentin dosing adjustments in patients with impaired renal function should be based on creatinine clearance (CrCl), specifically calculated using the Cockcroft-Gault equation, not estimated glomerular filtration rate (eGFR). 1

Why Creatinine Clearance is the Standard

The FDA-approved gabapentin label explicitly provides dosing recommendations based on creatinine clearance calculated by the Cockcroft-Gault equation 1. This is the gold standard because:

• All pharmacokinetic studies of gabapentin used creatinine clearance to establish dosing recommendations, demonstrating that gabapentin plasma clearance (CL/F) and renal clearance are linearly correlated with creatinine clearance 2
• eGFR equations report values normalized to body surface area (mL/min/1.73m²), while drug dosing requires absolute clearance in mL/min—using eGFR without de-normalizing can lead to underdosing in larger patients and overdosing in smaller patients 3
• Concordance between eGFR-based calculations and Cockcroft-Gault is only 75-78%, creating potential for significant dosing errors 3

Specific Dosing Algorithm Based on Creatinine Clearance

Use the Cockcroft-Gault equation to calculate CrCl: For men: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]; for women, multiply by 0.85 4, 1

Then adjust gabapentin dose according to this FDA-approved table 1:

• CrCl ≥60 mL/min: 900-3600 mg/day divided three times daily (no adjustment needed)
• CrCl 30-59 mL/min: 400-1400 mg/day divided twice daily (e.g., 200-700 mg BID)
• CrCl 15-29 mL/min: 200-700 mg/day as a single daily dose (e.g., 200-700 mg QD)
• CrCl <15 mL/min: 100-300 mg/day as a single daily dose, with dose reduced proportionally to CrCl (e.g., if CrCl is 7.5 mL/min, give half the dose for CrCl of 15 mL/min) 1
• Hemodialysis patients: Give maintenance dose based on CrCl as above, PLUS a supplemental post-hemodialysis dose of 125-350 mg after each 4-hour dialysis session 1

Critical Pharmacokinetic Rationale

• Gabapentin is 80% renally cleared unchanged with no hepatic metabolism, making renal function the primary determinant of drug elimination 5, 2
• Gabapentin clearance decreases approximately 1.6-fold for every 2-fold decrease in CrCl, resulting in proportionally higher plasma concentrations and longer half-lives in renal impairment 6
• The elimination half-life increases dramatically from 5-9 hours in normal renal function to 52 hours when CrCl <30 mL/min, and up to 132 hours in anuric patients 1, 7, 8

Common Pitfalls to Avoid

• Do not use eGFR directly for gabapentin dosing without converting to absolute clearance—this is the most common error and can result in significant overdosing or underdosing 3
• Do not ignore the need for post-hemodialysis supplemental doses—hemodialysis significantly removes gabapentin (reducing half-life from 132 hours to 3.8 hours), so supplemental dosing after each session is essential 1, 8
• Recognize that elderly patients often have reduced renal function despite normal serum creatinine due to decreased muscle mass—always calculate CrCl rather than relying on serum creatinine alone 5, 1
• Monitor for gabapentin toxicity symptoms (altered mental status, dizziness, sedation, falls) in dialysis patients, as overdose is common—approximately 19% of dialysis patients receive gabapentin, with increased risk of adverse neurological effects 7

Special Considerations for Dialysis Patients

• Peritoneal dialysis provides slower gabapentin clearance than hemodialysis (elimination half-life of approximately 41 hours with intensive continuous cycling PD), so dose adjustments should be even more conservative 8
• Drug monitoring may be warranted in dialysis patients on chronic gabapentin therapy to avoid unintended accumulation and toxicity 7