What is the recommended dose adjustment for Gabapentin (Gabapentin) in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Gabapentin dose adjustment is crucial in patients with chronic kidney disease (CKD) to prevent toxicity and maintain efficacy, with recommended daily doses ranging from 100-300 mg in severe CKD to 400-1,400 mg in mild to moderate CKD, divided into twice daily dosing. When managing patients with CKD, it's essential to consider the renal elimination of gabapentin, as it accumulates in renal impairment due to its lack of metabolism and unchanged elimination by the kidneys 1. Key considerations for dose adjustment include:

• CKD stage 3 (GFR 30-59 ml/min): reduce the daily dose to 400-1,400 mg divided into twice daily dosing
• CKD stage 4 (GFR 15-29 ml/min): limit to 200-700 mg once daily
• Severe CKD stage 5 or dialysis patients (GFR <15 ml/min): give 100-300 mg once daily, with a supplemental dose after each hemodialysis session It's also important to start with lower doses and titrate slowly based on response and tolerability, monitoring for side effects like dizziness, somnolence, and peripheral edema, which may be more pronounced in CKD patients 1. Regular reassessment of kidney function is crucial for patients on long-term gabapentin therapy to ensure appropriate dosing and prevent potential toxicity. In the context of gabapentin dosing for CKD patients, the most recent and highest quality study available is from 2010, which provides guidance on prescribing recommendations for first-line medications, including gabapentin 1. However, it's essential to note that more recent studies may have been published since then, and clinicians should always consult the most up-to-date guidelines and research when making treatment decisions. Given the available evidence, dose adjustment of gabapentin in CKD patients is essential to balance efficacy and safety, and clinicians should carefully monitor patients and adjust doses accordingly.

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) ≥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 dosage adjustment for gabapentin in patients with chronic kidney disease (CKD) is as follows:

• For patients with creatinine clearance ≥60 mL/min, the total daily dose range is 900-3600 mg/day, administered three times a day.
• For patients with creatinine clearance >30-59 mL/min, the total daily dose range is 400-1400 mg/day, administered two times a day.
• For patients with creatinine clearance >15-29 mL/min, the total daily dose range is 200-700 mg/day, administered once daily.
• For patients with creatinine clearance <15 mL/min, the daily dose should be reduced in proportion to creatinine clearance 2.

From the Research

Gabapentin Dose Adjustment for CKD

• Gabapentin is an anticonvulsive drug that requires dose adjustment in patients with impaired kidney function 3.
• The drug's elimination is reduced as kidney function declines, and higher doses may increase the risk of adverse events in older adults with CKD 4.
• Studies suggest that gabapentin should be used with caution in patients with CKD, and the dose should be adjusted according to the patient's creatinine clearance or glomerular filtration rate 5.

Dose Adjustment Recommendations

• The recommended dose adjustment for gabapentin in patients with CKD is not explicitly stated in the provided studies, but it is suggested that the dose should be reduced or the dosing interval should be lengthened 5.
• One study found that starting a gabapentinoid at a higher dose was associated with a slightly higher risk of adverse events, including hospital visits with encephalopathy, falls, or fractures, or hospitalization with respiratory depression 4.
• Another study found that patients with a creatinine clearance <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids, which may increase the risk of adverse events 6.

Safety and Efficacy of Gabapentin in CKD Patients

• Gabapentin has been shown to be effective in reducing itching intensity in patients with CKD on maintenance hemodialysis, but it may cause adverse events such as fatigue, dizziness, and somnolence 7.
• Pregabalin, another gabapentinoid, has also been shown to be effective in reducing itching intensity in CKD patients, but it may have a better safety profile compared to gabapentin 7.
• The safety and efficacy of gabapentinoids in CKD patients require further study, particularly in terms of dosing and adverse event risk 4, 6.