What is the recommended titration schedule for gabapentin (Neurontin) in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Gabapentin titration in patients with Chronic Kidney Disease (CKD) should start with 100-300 mg at bedtime or 100-300 mg 3 times daily, with increases by 100-300 mg 1-7 days as tolerated, and reduced if impaired renal function is present. According to the study published in the Mayo Clinic Proceedings 1, the recommended titration schedule for gabapentin in patients with CKD is crucial to avoid drug accumulation and minimize adverse effects.

Key Considerations

• The dosing should be adjusted based on the patient's renal function, with careful monitoring for increased side effects such as dizziness, somnolence, and peripheral edema.
• For patients with impaired renal function, the dose should be reduced to prevent accumulation of the drug.
• The study suggests that gabapentin can be increased by 100-300 mg 1-7 days as tolerated, but it is essential to consider the patient's individual response and adjust the dose accordingly.

Titration Schedule

• Start with 100-300 mg at bedtime or 100-300 mg 3 times daily.
• Increase by 100-300 mg 1-7 days as tolerated.
• Reduce the dose if impaired renal function is present.

Monitoring and Adjustments

• Monitor patients for increased side effects, including dizziness, somnolence, and peripheral edema.
• Adjust the dose gradually to minimize adverse effects while maintaining efficacy.
• Consider evening dosing initially to minimize daytime sedation.
• Elderly CKD patients may require even lower starting doses and more gradual titration due to increased sensitivity to side effects.

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

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).

The recommended titration schedule for gabapentin in patients with Chronic Kidney Disease (CKD) is to adjust the dosage based on renal function as indicated in Table 1.

• 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 2.

From the Research

Gabapentin Titration in Patients with CKD

The recommended titration schedule for gabapentin in patients with Chronic Kidney Disease (CKD) is crucial to ensure safe and effective treatment.

• Gabapentin is cleared via renal excretion, and its elimination is proportional to creatinine clearance (CrCL) 3, 4.
• The pharmacokinetics of gabapentin are affected by renal function, and dosage adjustments are necessary in patients with impaired renal function 3, 4.
• Apparent oral plasma clearance (CL/F) and renal clearance (CLR) of gabapentin decrease as renal function diminishes, resulting in higher plasma gabapentin concentrations and longer elimination half-lives 4.
• Gabapentin CL/F and CLR are linearly correlated with creatinine clearance, allowing for dosage adjustments based on CrCL 4.

Dosage Adjustments

• The dosing regimen of gabapentin in subjects with renal impairment may be adjusted on the basis of creatinine clearance 4.
• Genetic variation in the organic cation transporter OCTN1 can affect gabapentin renal clearance, with the OCTN1-L503F variant resulting in reduced net secretion of gabapentin in the kidney 5.
• Creatinine clearance and OCTN1 genotype can account for a significant portion of the variation in gabapentin renal clearance 5.

Clinical Considerations

• The timing of dialysis initiation and the choice of dialysis modality can impact patient outcomes, with peritoneal dialysis potentially providing better initial outcomes and preserving renal function 6.
• Estimating equations, such as the Cockcroft-Gault and MDRD equations, may not accurately estimate glomerular filtration rate (GFR) in critically ill patients with acute kidney injury, highlighting the need for alternative methods 7.