What is the dosing for Gabapentin (Gabapentin) for a patient with impaired renal function, specifically a glomerular filtration rate (GFR) of 17?

From the Guidelines

For a patient with a GFR of 17 mL/min, the recommended gabapentin dosing should be significantly reduced to 100-300 mg once daily. This dosing adjustment is crucial due to gabapentin's primary elimination pathway being through the kidneys, as indicated in studies on anticonvulsant use in adult cancer pain 1. With severe renal impairment, as denoted by a GFR of 17, the clearance of gabapentin is substantially decreased, which could lead to drug accumulation and an increased risk of side effects if standard doses are administered. Key considerations in managing such patients include:

• Monitoring closely for signs of toxicity such as excessive sedation, dizziness, or confusion.
• Gradual dose titration, allowing at least 7 days between dose increases to assess tolerance and efficacy.
• Potential need for a supplemental dose after each dialysis session, given that gabapentin is removed by hemodialysis.
• Regular reassessment of renal function, as changes in GFR may necessitate further dose adjustments.

The importance of dose adjustment in renal impairment is highlighted by the fact that standard dosing regimens, such as starting at 100-300 mg nightly and increasing to 900-3600 mg daily in divided doses, are not suitable for patients with a GFR of 17 mL/min, as suggested by guidelines for the use of anticonvulsants like gabapentin in pain management 1. Therefore, a cautious and individualized approach to gabapentin dosing in patients with severe renal impairment is essential to balance efficacy with the risk of adverse effects.

From the FDA Drug Label

TABLE 1 Gabapentin Tablets Dosage Based on Renal Function Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) ... 15a 100-300 100 QD 125 QD 150 QD 200 QD 300 QD 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).

To calculate the dose for a patient with a glomerular filtration rate (GFR) of 17, which is equivalent to a creatinine clearance of 17 mL/min, we need to reduce the daily dose in proportion to creatinine clearance.

• For a creatinine clearance of 15 mL/min, the dose range is 100-300 mg/day.
• Since 17 mL/min is slightly higher than 15 mL/min, the dose should be slightly higher than the dose for 15 mL/min, but still lower than the dose for patients with a creatinine clearance of 30 mL/min.
• The dose for a patient with a creatinine clearance of 17 mL/min can be estimated as follows:
  • First, calculate the ratio of the patient's creatinine clearance to the creatinine clearance of 15 mL/min: 17 mL/min / 15 mL/min = 1.133.
  • Then, apply this ratio to the dose for a patient with a creatinine clearance of 15 mL/min:
    • For the lower end of the dose range (100 mg/day), the estimated dose would be 100 mg/day * 1.133 = 113 mg/day, which is approximately 100-125 mg/day.
    • For the upper end of the dose range (300 mg/day), the estimated dose would be 300 mg/day * 1.133 = 340 mg/day, but since the patient's creatinine clearance is still less than 30 mL/min, the dose should not exceed the upper limit of the dose range for a creatinine clearance of 30 mL/min, which is 700 mg/day, but rather be closer to the dose range of 100-300 mg/day for a creatinine clearance of 15 mL/min.
• Therefore, a conservative estimate for the dose of gabapentin for a patient with a GFR of 17 would be 100-200 mg/day, administered as a single daily dose, with close monitoring of the patient's response to the medication and adjustment of the dose as needed 2.

From the Research

Gabapentin Dosing for Impaired Renal Function

• The dosing of Gabapentin for a patient with impaired renal function, specifically a glomerular filtration rate (GFR) of 17, requires careful consideration of the patient's kidney function to avoid toxicity 3, 4.
• According to the study by 4, patients with end-stage renal disease maintained on hemodialysis should receive an initial 300-mg to 400-mg Gabapentin loading dose, and plasma Gabapentin concentrations can be maintained by giving 200 to 300 mg of Gabapentin after every 4 hours of hemodialysis.
• For patients with decreased kidney function, dosages of drugs cleared renally, such as Gabapentin, should be adjusted according to creatinine clearance or glomerular filtration rate 5.
• The study by 6 found that patients with a CrCl <60 mL/min were frequently prescribed inappropriately high doses of Gabapentinoids, highlighting the need for careful dosing adjustments in patients with impaired renal function.

Dosing Adjustments for Impaired Renal Function

• Recommended methods for maintenance dosing adjustments include dose reductions, lengthening the dosing interval, or both 5.
• Online or electronic calculators can be used to calculate the adjusted dose based on creatinine clearance or glomerular filtration rate 5.
• The study by 3 suggests that patients with chronic kidney disease often receive inappropriately high Gabapentin dosage for their kidney function, occasioning overt toxicity, and that advanced age and comorbidity predispose these patients to toxicity.

Considerations for Gabapentin Use in Impaired Renal Function

• Gabapentin is exclusively eliminated renally, and patients with chronic kidney disease are at risk for toxicity 3.
• The elimination half-life of Gabapentin is dependent on renal function, and patients with impaired renal function may experience prolonged elimination half-lives 4.
• The study by 7 suggests that Gabapentin is "dialyzable" for patients with decreased kidney function, but the clinical benefit of extracorporeal treatment is unclear.