What is the recommended dosing of gabapentin (Gabapentin) for patients with End-Stage Renal Disease (ESRD)?

Gabapentin Dosing in End-Stage Renal Disease

For patients with ESRD, gabapentin should be dosed at 100-300 mg once daily, with a supplemental dose of 125-350 mg administered after each 4-hour hemodialysis session. 1

Dosing Recommendations for ESRD

For Patients with CrCl <15 mL/min (Not on Dialysis)

• Starting dose: 100 mg once daily 1
• Dose range: 100-300 mg once daily 1
• The daily dose should be reduced 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

For Patients on Hemodialysis

• Maintenance dose: 100-300 mg once daily on non-dialysis days, based on creatinine clearance 1
• Post-hemodialysis supplemental dose: 125-350 mg after each 4-hour hemodialysis session 1
• An initial loading dose of 300-400 mg may be considered for treatment initiation 2

The FDA label provides specific supplemental dosing based on the maintenance dose: if the maintenance dose is 100 mg daily, give 125 mg post-dialysis; if 300 mg daily, give 350 mg post-dialysis 1

Pharmacokinetic Rationale

Gabapentin elimination is dramatically prolonged in ESRD, making dose reduction critical to avoid toxicity:

• The elimination half-life increases from 5-9 hours in normal renal function to approximately 132 hours in anuric patients on non-dialysis days 2, 3
• During hemodialysis, the half-life decreases to approximately 4 hours 2
• Hemodialysis clearance of gabapentin averages 142 mL/min, which is approximately 93% of dialyzer creatinine clearance 2
• Approximately 35% of the gabapentin dose is recovered in dialysate during a hemodialysis session 2
• Plasma concentrations may increase approximately 30% during the first 2 hours after hemodialysis due to drug redistribution 2

Special Considerations for Peritoneal Dialysis

For patients on peritoneal dialysis, gabapentin clearance is significantly slower than hemodialysis:

• The elimination half-life with continuous automated cycling peritoneal dialysis is approximately 41 hours 4
• Gabapentin clearance by peritoneal dialysis is estimated at 94% of urea clearance 4
• Intensive peritoneal dialysis can effectively treat gabapentin toxicity, though more slowly than hemodialysis, with symptom resolution occurring after approximately 36 hours 4

Critical Safety Warnings

Gabapentin toxicity is a significant risk in ESRD patients and presents with characteristic neurological symptoms:

• Common manifestations include myoclonus, altered mental status, dizziness, and encephalopathy 3, 5
• Epidemiological data show that 19% of dialysis patients receive gabapentin, and its use is associated with increased risk of altered mental status, falls, and fractures 3
• Toxicity symptoms typically resolve with drug discontinuation and dialysis treatment 5
• Drug level monitoring should be considered to avoid unintended overdose, particularly given the narrow therapeutic window in this population 3

Dose Titration and Monitoring

When initiating or adjusting gabapentin in ESRD:

• Start at the lower end of the dosing range (100 mg daily) 1
• Titrate gradually based on clinical response and tolerability 1
• The maximum time between doses should not exceed 12 hours for patients on divided dosing regimens 1
• If discontinuing gabapentin, taper gradually over a minimum of 1 week to avoid withdrawal symptoms 1
• Monitor closely for signs of neurotoxicity, particularly myoclonus and altered mental status 3, 5