From the Guidelines
Gabapentin use in patients with Chronic Kidney Disease (CKD) should be restricted and dosages adjusted according to the patient's creatinine clearance to minimize the risk of adverse effects. The most recent and highest quality study, 1, suggests that gabapentin can be used in adults with Restless Legs Syndrome (RLS) and end-stage renal disease (ESRD), but with caution.
Key Considerations
- Gabapentin is primarily eliminated by renal excretion, and impaired kidney function can lead to drug accumulation, increasing the risk of side effects such as dizziness, somnolence, and confusion.
- For patients with a creatinine clearance of 30-59 mL/min, the recommended dosage is 400-1,400 mg/day divided into two or three doses.
- For those with a creatinine clearance of 15-29 mL/min, the dose should be reduced to 200-700 mg once daily.
- In severe CKD with creatinine clearance <15 mL/min, the dose should not exceed 300 mg once daily.
Monitoring and Adjustments
- Regular monitoring of kidney function and adjustment of the gabapentin dose is crucial for safe use in CKD patients.
- Despite these restrictions, gabapentin can still be an effective treatment option for neuropathic pain or epilepsy in CKD patients when used cautiously and at appropriate doses, as suggested by 1.
Important Notes
- The study 1 provides conditional recommendations for the use of gabapentin in adults with RLS and ESRD, but the certainty of evidence is very low.
- However, in the context of real-life clinical medicine, it is essential to prioritize caution and adjust dosages according to kidney function to minimize the risk of adverse effects.
From the FDA Drug Label
Adult Patients with Renal Impairment Subjects (N=60) with renal impairment (mean creatinine clearance ranging from 13 to 114 mL/min) were administered single 400 mg oral doses of gabapentin. The mean gabapentin half-life ranged from about 6. 5 hours (patients with creatinine clearance >60 mL/min) to 52 hours (creatinine clearance <30 mL/min) and gabapentin renal clearance from about 90 mL/min (>60 mL/min group) to about 10 mL/min (<30 mL/min). Mean plasma clearance (CL/F) decreased from approximately 190 mL/min to 20 mL/min [see Dosage and Administration (2.3) and Use in Specific Populations (8. 6)].
The restrictions on taking gabapentin with Chronic Kidney Disease (CKD) are related to the decreased renal clearance of gabapentin in patients with renal impairment.
- Dose adjustment is necessary in patients with renal impairment, as the mean gabapentin half-life increases significantly with decreasing creatinine clearance.
- Patients with creatinine clearance <30 mL/min may require more significant dose adjustments due to the substantial decrease in gabapentin renal clearance.
- The specific dose adjustments for patients with CKD can be found in the Dosage and Administration (2.3) section of the drug label 2.
From the Research
Restrictions on Taking Gabapentin with Chronic Kidney Disease (CKD)
- Gabapentin is exclusively eliminated renally, and patients with CKD are at risk for toxicity 3
- Patients with CKD often receive inappropriately high gabapentin dosage for their kidney function, occasioning overt toxicity 3, 4
- Gabapentin toxicity in patients with CKD is underrecognized, and advanced age and comorbidity predispose these patients to toxicity 3
- Appropriate dosing of gabapentinoids is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use 4
Dosing Considerations
- Higher-dose gabapentinoids are associated with a slightly higher risk of adverse events, including hospital visits with encephalopathy, falls, or fractures, or hospitalizations with respiratory depression 5
- Starting a gabapentinoid at a higher versus a lower dose is associated with a higher 30-day risk of serious adverse events 5
- The dosage of gabapentin should be adjusted in patients with renal insufficiency to avoid severe adverse effects 6