Gabapentin Dosing in Renal Insufficiency
Gabapentin requires mandatory dose reduction in patients with renal impairment based on creatinine clearance, with specific adjustments ranging from twice-daily dosing for moderate impairment to once-daily dosing for severe impairment, plus supplemental post-hemodialysis doses for dialysis patients. 1
Calculate Creatinine Clearance First
Before initiating gabapentin therapy, you must calculate creatinine clearance using the Cockcroft-Gault equation—never rely on serum creatinine alone, as this significantly underestimates renal impairment, particularly in elderly patients with reduced muscle mass. 2, 3 This is the most common preventable error leading to gabapentin toxicity. 2
Specific Dosing Adjustments by Renal Function
The FDA-approved dosing adjustments are structured as follows 1:
CrCl ≥60 mL/min (Normal Function)
- Total daily dose: 900-3600 mg/day
- Dosing frequency: Three times daily (TID)
- Individual doses: 300-1200 mg per dose
- No adjustment needed 1
CrCl 30-59 mL/min (Moderate Impairment)
- Total daily dose: 400-1400 mg/day (at least 50% reduction)
- Dosing frequency: Twice daily (BID)
- Individual doses: 200-700 mg per dose
- Starting dose: 100-300 mg at bedtime or three times daily, titrating slowly by 100-300 mg every 1-7 days 2, 3
CrCl 15-29 mL/min (Severe Impairment)
- Total daily dose: 200-700 mg/day
- Dosing frequency: Once daily (QD)
- Individual doses: 200-700 mg per dose 4, 1
CrCl <15 mL/min (End-Stage Renal Disease)
- Total daily dose: 100-300 mg/day
- Dosing frequency: Once daily (QD)
- Individual doses: 100-300 mg per dose
- For CrCl <15 mL/min, reduce the daily dose in proportion to creatinine clearance (e.g., patients with CrCl of 7.5 mL/min should receive one-half the daily dose that patients with CrCl of 15 mL/min receive) 1
Hemodialysis Patients
- Maintenance dose: Based on residual CrCl as above
- Supplemental post-hemodialysis dose: 125-350 mg administered after each 4-hour hemodialysis session 4, 1
- The elimination half-life increases from 5-9 hours in normal function to 132 hours in dialysis patients 5
Pharmacokinetic Rationale
Gabapentin is eliminated entirely by renal excretion without metabolism, making dose adjustment critical. 6 Gabapentin oral clearance (CL/F) decreases approximately 1.6-fold for every 2-fold decrease in creatinine clearance, with plasma concentrations and elimination half-life increasing proportionally as renal function declines. 7, 6 In elderly patients, apparent oral clearance decreases from approximately 225 mL/min in patients <30 years to 125 mL/min in patients >70 years, primarily due to decreased renal function. 4
Critical Monitoring During Titration
Monitor closely for dose-dependent adverse effects, particularly dizziness and sedation, which are the most common toxicities. 2, 3 Titrate cautiously over weeks rather than days due to gabapentin's nonlinear pharmacokinetics in renal impairment. 2 Gabapentin toxicity in renal impairment can manifest as altered mental status, myoclonus, tremulousness, confusion with hallucinations, hearing loss, or even coma. 8, 5
Common Pitfalls to Avoid
- Never use serum creatinine alone to assess renal function—always calculate CrCl using Cockcroft-Gault, especially in elderly patients where normal serum creatinine can mask significant renal impairment. 2, 4
- Temporarily discontinue gabapentin during acute illness that increases risk of acute kidney injury in patients with baseline CrCl <60 mL/min. 3
- Reassess renal function regularly, as chronic kidney disease is progressive and dosing requirements will change over time. 9
- When discontinuing or reducing gabapentin, taper gradually over a minimum of 1 week to avoid withdrawal effects. 1
Special Population Considerations
In elderly patients, care should be taken in dose selection, and dose must be adjusted based on creatinine clearance values, as this population is more likely to have decreased renal function. 1 The use of gabapentin in patients less than 12 years of age with compromised renal function has not been studied. 1