Does gabapentin (Gabapentin) exacerbate Impaired renal function?

From the Guidelines

Gabapentin generally does not worsen renal function in patients with normal kidney function, but it requires dose adjustment in those with existing kidney impairment. The medication is primarily eliminated unchanged through the kidneys, which means it can accumulate to potentially toxic levels in patients with reduced renal function if not properly dosed 1. For patients with normal kidney function, standard dosing (typically 300-600 mg three times daily for most indications) is appropriate. However, for those with reduced kidney function, dosing should be decreased based on creatinine clearance: for mild impairment (50-79 mL/min), moderate reduction is needed; for moderate impairment (30-49 mL/min), doses should be significantly reduced; and for severe impairment (<30 mL/min), minimal doses are recommended 1. Patients on hemodialysis require supplemental doses after dialysis sessions. While gabapentin itself doesn't directly damage the kidneys, it can cause side effects like dizziness, somnolence, and peripheral edema that may be more pronounced in those with kidney disease. Regular monitoring of kidney function is advisable when using gabapentin in patients with renal impairment or other risk factors for kidney disease. Some key points to consider when prescribing gabapentin include:

• Starting with low dosages and gradual titration to minimize side effects
• Adjusting dosages based on creatinine clearance in patients with renal impairment
• Monitoring for signs of toxicity, such as dizziness and somnolence, particularly in patients with reduced renal function
• Considering alternative treatments or referral to a specialist if gabapentin is not effective or is poorly tolerated.

From the FDA Drug Label

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients [see Dosage and Administration (2. 4), Adverse Reactions (6), and Clinical Pharmacology (12.3)]. Dosage adjustment in adult patients with compromised renal function is necessary [see Dosage and Administration (2.3) and Clinical Pharmacology (12. 3)].

The FDA drug label does not directly answer whether gabapentin worsens renal function. However, it does indicate that gabapentin is substantially excreted by the kidney and that patients with impaired renal function are at a greater risk of toxic reactions.

• Key points:
  • Gabapentin is primarily renally excreted.
  • Patients with impaired renal function are at a greater risk of toxic reactions.
  • Dosage adjustment is necessary in adult patients with compromised renal function.
  • The label does not provide direct information on whether gabapentin worsens renal function. 2

From the Research

Gabapentin and Renal Function

• Gabapentin is primarily cleared by the kidney, and its elimination is reduced as kidney function declines 3, 4.
• Patients with decreased renal function may be at an increased risk of adverse effects due to higher gabapentin levels 5, 6, 4.
• Studies have shown that gabapentin toxicity can occur in patients with chronic kidney disease, particularly in those with advanced age and multiple comorbidities 3, 4.

Dose Adjustment and Renal Function

• Dose adjustment of gabapentin is crucial in patients with decreased renal function to prevent toxicity 3, 4.
• A study recommended a 50% reduction in pregabalin daily dose for patients with creatinine clearance between 30 and 60 mL/min, and further reduction for each additional 50% decrease in creatinine clearance 7.
• Another study found that patients with a creatinine clearance <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids, leading to an increased risk of adverse events 5.

Adverse Events and Renal Function

• Adverse events such as falls, encephalopathy, and respiratory depression have been reported in patients with decreased renal function taking gabapentinoids 5, 6.
• A population-based cohort study found that starting a gabapentinoid at a higher dose was associated with a slightly higher risk of hospital visits or hospitalizations due to adverse events 6.
• Concomitant opioid and psychiatric medications can contribute to a higher prevalence of adverse events in patients with decreased renal function taking gabapentinoids 5.