Can gabapentin be used in patients with impaired renal function?

From the Guidelines

Gabapentin can be used in renal failure, but it requires careful dose adjustment based on the patient's kidney function to prevent toxicity and ensure efficacy. The dosage adjustment is crucial because gabapentin is primarily eliminated unchanged through the kidneys, and its accumulation can lead to increased side effects such as dizziness, somnolence, confusion, and ataxia 1. For patients with renal impairment, the standard dosing must be reduced. According to the guidelines, for mild renal impairment (creatinine clearance 60-89 mL/min), the dose may be adjusted, for moderate impairment (30-59 mL/min), a further reduction is recommended, and for severe impairment (15-29 mL/min), an even lower dose is appropriate 1. In end-stage renal disease (less than 15 mL/min), the dose should be significantly reduced, typically to 100-300 mg daily after hemodialysis.

Key Considerations

• Gabapentin pharmacokinetics are nonlinear due to saturable absorption, requiring careful titration 1.
• Dosage reduction in patients with renal insufficiency is necessary, with adjustments made in relation to creatinine clearance 1.
• Regular monitoring of renal function and clinical response is essential when using gabapentin in patients with kidney disease to ensure both safety and efficacy.

Dosing Adjustments

• Mild renal impairment (creatinine clearance 60-89 mL/min): dose adjustment may be necessary.
• Moderate renal impairment (30-59 mL/min): reduce dose to 200-700 mg twice daily.
• Severe renal impairment (15-29 mL/min): reduce dose to 200-300 mg once daily.
• End-stage renal disease (less than 15 mL/min): 100-300 mg daily after hemodialysis. It is critical to follow these guidelines and adjust the dose according to the patient's renal function to minimize the risk of adverse effects while maintaining therapeutic efficacy 1.

From the FDA Drug Label

1. 3 Dosage Adjustment in Patients with Renal Impairment 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

Gabapentin can be used in patients with renal failure, but the dose needs to be adjusted based on the patient's creatinine clearance.

• The dosage adjustment is recommended for patients 12 years of age and older with compromised renal function or undergoing hemodialysis.
• The dose regimen is provided in Table 1, which takes into account the patient's renal function, as measured by creatinine clearance.
• For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance.
• Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis 2.

From the Research

Gabapentin Use in Renal Failure

• Gabapentin is entirely excreted through the renal system, making dose adjustment crucial in patients with renal impairment 3.
• The risk of gabapentin toxicity increases in renal failure, and significant morbidity can occur due to continued use without dose adjustment 3.
• Studies have shown that patients with chronic kidney disease (CKD) are frequently prescribed inappropriately high doses of gabapentinoids, which can lead to adverse events 4, 5.

Dose Adjustment Recommendations

• The manufacturer's recommendation for gabapentin dose adjustment in patients with decreased renal function should be considered 4.
• A 50% reduction in gabapentin daily dose is recommended for patients with creatinine clearance (CLcr) between 30 and 60 mL/min compared to those with CLcr > 60 mL/min 6.
• Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr 6.

Adverse Events Associated with Gabapentinoid Use

• Adverse events related to gabapentinoids, such as falls, encephalopathy, and respiratory depression, are more common in patients with CKD 4, 5, 7.
• Concomitant use of opioids and psychiatric medications can contribute to a higher prevalence of adverse events regardless of renal function 4, 5.
• Older age, history of seizures, and concomitant antipsychotic use are associated with an increased risk of gabapentinoid-related adverse events 5.