What is the recommended dosing adjustment for gabapentin (Neurontin) in patients with impaired renal function?

From the Guidelines

Gabapentin dosing in patients with impaired renal function should be adjusted to prevent drug accumulation and minimize adverse effects, with specific dosage reductions based on creatinine clearance (CrCl) levels, as the most recent and highest quality study is not provided in the given evidence, but general medical knowledge suggests that for CrCl ≥60 mL/min, the standard dosing can be used, for CrCl 30-59 mL/min, reduce to 200-700 mg twice daily, for CrCl 15-29 mL/min, give 200-700 mg once daily, and for CrCl <15 mL/min, administer 100-300 mg once daily 1.

Key Considerations for Gabapentin Dosing in Renal Impairment

• The provided evidence does not directly address renal dosing adjustments for gabapentin, but it does mention the need to "reduce if impaired renal function" when prescribing gabapentin, indicating an awareness of the necessity for dose adjustment in patients with renal impairment.
• General medical knowledge and other guidelines not included in the provided evidence suggest that gabapentin, being primarily eliminated unchanged through the kidneys, requires dose adjustments in patients with reduced renal function to avoid accumulation and increased risk of adverse effects such as dizziness, somnolence, and confusion.
• When initiating gabapentin therapy in patients with renal impairment, it is crucial to start at the lower end of the dosing range and titrate slowly based on clinical response and tolerability, closely monitoring for adverse effects, especially in elderly patients who may have age-related decreases in renal function.
• Patients on hemodialysis may require supplemental doses of gabapentin after each dialysis session to maintain therapeutic levels, though specific guidance on this is not provided in the given evidence.

Practical Approach to Gabapentin Dosing in Renal Impairment

• For patients with CrCl ≥60 mL/min, the standard dosing of 300-1200 mg three times daily can typically be used.
• For CrCl 30-59 mL/min, consider reducing the dose to 200-700 mg twice daily.
• For CrCl 15-29 mL/min, give 200-700 mg once daily.
• For CrCl <15 mL/min, administer 100-300 mg once daily, and for patients on hemodialysis, consider a supplemental dose of 125-350 mg after each 4-hour dialysis session, though this specific guidance may vary based on individual patient factors and should be adjusted according to clinical 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 recommended dosing adjustment for gabapentin in patients with impaired renal function is 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, as indicated in the table 2.

From the Research

Renal Gabapentin Dosing

The recommended dosing adjustment for gabapentin in patients with impaired renal function is crucial to prevent adverse effects.

• Gabapentin is entirely excreted through the renal system, and dose adjustment is necessary in patients with renal impairment 3.
• Although the provided studies do not directly address gabapentin dosing adjustments, a study on pregabalin, a similar medication, recommends a 50% reduction in daily dose for patients with creatinine clearance (CLcr) between 30 and 60 mL/min compared to those with CLcr > 60 mL/min 4.
• Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr 4.
• A study on gabapentinoid use in hospitalized patients with decreased kidney function found that patients with a CLcr <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids, leading to an increased risk of adverse effects 5.
• Another study found that appropriate dosing of gabapentinoids is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use 6.
• The importance of dose adjustment in patients with renal impairment is highlighted by a case report of gabapentin toxicity in renal failure, emphasizing the need for doctors to review indications for gabapentin use during periods of acute illness, especially with regard to renal impairment 3.
• General guidance on drug dosing adjustments in patients with chronic kidney disease suggests that dosages of drugs cleared renally, such as gabapentin, should be adjusted according to creatinine clearance or glomerular filtration rate 7.