From the Guidelines
Gabapentin dosing should be adjusted in patients with acute kidney injury (AKI) to prevent toxicity, with dose reductions based on the severity of AKI, as evidenced by studies such as 1 and 1.
Key Considerations for Gabapentin Dosing in AKI
- For mild AKI (GFR 60-89 mL/min), reduce the daily dose to 900-1800 mg divided three times daily.
- For moderate AKI (GFR 30-59 mL/min), limit to 400-700 mg twice daily.
- In severe AKI (GFR 15-29 mL/min), use 200-300 mg once daily.
- For patients with GFR <15 mL/min or on dialysis, 100-300 mg after each dialysis session is appropriate. Gabapentin is primarily eliminated unchanged through the kidneys, so impaired renal function leads to drug accumulation, as discussed in 1. Without proper dose adjustment, patients may experience enhanced side effects including dizziness, somnolence, confusion, and in severe cases, neurotoxicity with myoclonus or altered mental status.
Monitoring and Adjustments
Monitor patients closely for signs of toxicity, especially when AKI develops in patients already taking gabapentin. Serum drug levels are not routinely measured, so clinical assessment is essential. As kidney function improves, gabapentin dosing can be gradually increased while monitoring for efficacy and side effects, considering the principles outlined in 1.
Clinical Decision Making
The selection and dosing of drugs in patients with AKI requires multiple and dynamic assessments, including understanding of the phases of AKI and the likelihood of recovery or progression to chronic kidney disease, as emphasized in 1. Factors such as the mode of drug excretion, potential for nephrotoxicity, and availability of suitable alternatives must be considered, highlighting the importance of personalized treatment plans in the context of AKI.
From the FDA Drug Label
Apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in those under 30 years of age to about 125 mL/min in those over 70 years of age. Renal clearance (CLr) and CLr adjusted for body surface area also declined with age; however, the decline in the renal clearance of gabapentin with age can largely be explained by the decline in renal function. 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).
The relationship between gabapentin and Acute Kidney Injury (AKI) is not directly addressed in the provided drug label. However, it is mentioned that renal clearance of gabapentin declines with age, which can be explained by the decline in renal function. Additionally, in adult patients with renal impairment, the mean gabapentin half-life increases as creatinine clearance decreases, indicating that gabapentin clearance is affected by renal function 2.
- Key points:
- Gabapentin clearance decreases with declining renal function.
- The half-life of gabapentin increases in patients with renal impairment. It is essential to consider these factors when administering gabapentin to patients with renal impairment or at risk of developing AKI.
From the Research
Gabapentin and AKI
- There is no direct evidence in the provided studies that links gabapentin to Acute Kidney Injury (AKI).
- However, the studies suggest that AKI can be caused by various factors, including systemic illness, toxic exposure, and nephrotoxic drugs 3, 4, 5.
- The management of AKI includes control of the underlying cause, achievement and maintenance of euvolemia, nutritional optimization, blood glucose control, and pharmacotherapy 5.
- Nephrotoxic drugs can contribute to the development of AKI, and it is essential to identify and adjust medications that may be harmful to the kidneys 4, 5.
- While gabapentin is not explicitly mentioned as a nephrotoxic drug in the provided studies, it is crucial to consider the potential risks of any medication when managing patients with AKI or those at risk of developing AKI 6, 7.