How to dose gabapentin (Neurontin) in patients with impaired renal function?

Gabapentin Dosing in Renal Insufficiency

Gabapentin requires mandatory dose reduction in patients with renal impairment based on creatinine clearance, with dosing frequency decreasing from three times daily to once daily as renal function declines. 1

Calculate Creatinine Clearance First

• Always calculate creatinine clearance using the Cockcroft-Gault equation before initiating gabapentin therapy—do not rely on serum creatinine alone, as it significantly underestimates renal impairment in elderly patients with reduced muscle mass. 2, 1
• Apparent oral clearance of gabapentin decreases from approximately 225 mL/min in patients under 30 years to 125 mL/min in those over 70 years, primarily due to declining renal function. 3, 1
• The elimination half-life increases dramatically from 5-9 hours in normal renal function to 52 hours when creatinine clearance is below 30 mL/min, and up to 132 hours in anuric patients. 4, 5

Specific Dosing Algorithm by Creatinine Clearance

For CrCl ≥60 mL/min:

• Start with 300 mg three times daily (TID) and titrate up to 900-3600 mg/day divided TID. 1
• Maximum time between doses should not exceed 12 hours. 1

For CrCl 30-59 mL/min (moderate impairment):

• Reduce to twice daily (BID) dosing with total daily dose of 400-1400 mg/day. 1
• Start with 200-300 mg BID and titrate slowly by 100-300 mg every 1-7 days as tolerated. 6, 7
• This represents at least a 50% reduction from standard dosing. 2

For CrCl 15-29 mL/min (severe impairment):

• Reduce to once daily (QD) dosing with total daily dose of 200-700 mg/day. 1
• Dosing options: 200 mg, 300 mg, 400 mg, 500 mg, or 700 mg once daily. 1

For CrCl <15 mL/min:

• Reduce to once daily dosing with total daily dose of 100-300 mg/day. 1
• Reduce daily dose in proportion to creatinine clearance (e.g., patients with CrCl of 7.5 mL/min should receive one-half the daily dose of patients with CrCl of 15 mL/min). 1

Hemodialysis Patients

• Patients on hemodialysis require both maintenance dosing based on residual renal function AND supplemental post-dialysis doses. 3, 1
• Give an initial loading dose of 300-400 mg. 5
• Maintenance doses should be based on residual creatinine clearance as outlined above. 1
• Administer supplemental post-hemodialysis doses of 125-350 mg after each 4-hour hemodialysis session. 1
• Hemodialysis removes approximately 35% of gabapentin, with a dialysis clearance of approximately 142 mL/min and elimination half-life during dialysis of approximately 4 hours. 5
• Plasma concentrations may increase approximately 30% during the first 2 hours after hemodialysis due to drug redistribution. 5

Critical Monitoring and Safety Considerations

• Monitor closely for dose-dependent adverse effects during titration, particularly dizziness and sedation, which are the most common toxicities. 6, 7
• Failing to calculate creatinine clearance accurately is the most common preventable error leading to gabapentin toxicity, especially in elderly patients. 2, 3
• Epidemiological data show that approximately 19% of dialysis patients receive gabapentin, and its use is associated with increased risk of altered mental status, falls, and fractures when dosed inappropriately. 4
• Temporarily discontinue gabapentin during acute illness that increases risk of acute kidney injury in patients with baseline CrCl <60 mL/min. 7

Titration Strategy

• Start with lower initial doses (100-300 mg at bedtime or three times daily for moderate impairment) and titrate cautiously over weeks rather than days. 6, 2
• Gabapentin has nonlinear pharmacokinetics due to saturable absorption, requiring careful titration. 6
• When discontinuing or reducing gabapentin, taper gradually over a minimum of 1 week to avoid withdrawal symptoms. 1