What are the renal adjustment guidelines for gabapentin (Neurontin) in patients with impaired renal function?

From the Guidelines

Gabapentin dosing should be adjusted in patients with impaired renal function to minimize the risk of adverse effects, with specific dose reductions recommended for patients with creatinine clearance (CrCl) less than 60 mL/min. The dosing adjustments are crucial because gabapentin is primarily eliminated unchanged through the kidneys, and reduced kidney function can lead to decreased clearance and higher blood levels, increasing the risk of side effects such as dizziness, somnolence, and peripheral edema 1.

Key Considerations for Renal Adjustment

• For patients with CrCl greater than 60 mL/min, the standard dosing of 300-1200 mg three times daily can be used.
• For those with CrCl between 30-59 mL/min, the dose should be reduced to 200-700 mg twice daily.
• Patients with CrCl between 15-29 mL/min should receive 100-300 mg once daily.
• For patients with CrCl less than 15 mL/min, the recommended dose is 100-300 mg once daily, with supplemental doses after each hemodialysis session for those on dialysis.

Monitoring and Titration

Monitoring for adverse effects is particularly important when initiating therapy or adjusting doses in renally impaired patients. Gabapentin levels do not need to be routinely monitored, but clinical response and tolerability should guide treatment. Increases in dosage should be made until pain relief is achieved, dose-limiting adverse effects occur, or the maximum dosage is reached, which for gabapentin can be up to 3600 mg/d in 3 divided doses, though this may need to be adjusted based on renal function 1.

Comparison with Other Medications

It's worth noting that while gabapentin requires careful dose adjustment in patients with renal impairment, other medications like pregabalin have linear pharmacokinetics and more straightforward dosing, which may be advantageous in certain clinical scenarios 1. However, the choice of medication should be based on individual patient needs, response, and tolerability.

From the FDA Drug Label

Dosage adjustment in patients 12 years of age and older with compromised renal function or undergoing hemodialysis is recommended, as follows:

TABLE 1 Gabapentin Tablets Dosage Based on Renal Function

Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg)

≥60 900-3600 300 TID 400 TID 600 TID 800 TID 1200 TID

30-59 400-1400 200 BID 300 BID 400 BID 500 BID 700 BID

15-29 200-700 200 QD 300 QD 400 QD 500 QD 700 QD

15a 100-300 100 QD 125 QD 150 QD 200 QD 300 QD

Post-Hemodialysis Supplemental Dose (mg)b

Hemodialysis 125b 150b 200b 250b 350b

TID = Three times a day; BID = Two times a day; QD = Single daily dose

a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7. 5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table

The renal adjustment guidelines for gabapentin in patients with impaired renal function are as follows:

• For patients with creatinine clearance ≥60 mL/min, the total daily dose range is 900-3600 mg/day, with a dose regimen of 300-1200 mg three times a day.
• For patients with creatinine clearance >30-59 mL/min, the total daily dose range is 400-1400 mg/day, with a dose regimen of 200-700 mg two times a day.
• For patients with creatinine clearance >15-29 mL/min, the total daily dose range is 200-700 mg/day, with a dose regimen of 200-700 mg once daily.
• For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance.
• For patients on hemodialysis, a supplemental post-hemodialysis dose should be administered after each 4 hours of hemodialysis, with doses ranging from 125-350 mg 2.

From the Research

Renal Adjustment Guidelines for Gabapentin

The renal adjustment guidelines for gabapentin in patients with impaired renal function are crucial to prevent toxicity and ensure effective treatment.

• Gabapentin is cleared via renal excretion, and its elimination is proportional to creatinine clearance (CrCL) 3, 4, 5.
• The pharmacokinetics of gabapentin are affected by renal function, and dosage adjustments are necessary in patients with impaired renal function 3, 5.
• Gabapentin clearance is directly proportional to creatinine clearance, and renal impairment reduces gabapentin excretion and increases plasma gabapentin concentrations in a linear fashion 4, 5.

Dosage Adjustments

• The dosing regimen of gabapentin in subjects with renal impairment may be adjusted on the basis of creatinine clearance 5.
• Gabapentin enacarbil, a prodrug of gabapentin, requires dosage adjustment in patients with impaired renal function, with an approximately 1.6-fold decrease in clearance for every 2-fold decrease in CrCL 3.
• Indication and drug dose of gabapentin in dialysis patients should be tightly controlled, and drug monitoring used to avoid unintended overdose 4.

Treatment of Gabapentin Toxicity

• Gabapentin toxicity can be treated with hemodialysis, which provides effective clearance of the drug 6, 7.
• Peritoneal dialysis can also be used to treat gabapentin toxicity, with an apparent elimination half-life of 41.33 hours 6.
• Symptoms of gabapentin toxicity, such as hearing loss, myoclonus, and confusion, can improve rapidly after dialysis and discontinuation of the drug 7.