Can I resume gabapentin (Neurontin) in a patient with Acute Kidney Injury (AKI)?

From the Guidelines

Gabapentin should be used with caution in patients with acute kidney injury (AKI) and typically requires dose adjustment or temporary discontinuation depending on the severity of kidney dysfunction. For mild AKI, consider reducing the gabapentin dose by 50-75% while monitoring renal function 1. In moderate to severe AKI, it's often best to temporarily discontinue gabapentin until renal function improves, as the drug is primarily eliminated unchanged through the kidneys. When renal function begins to recover, gabapentin can be reintroduced at a lower dose (such as 100-300 mg daily or every other day) with gradual titration based on symptom control and kidney function. Close monitoring of the patient for signs of gabapentin toxicity is essential, including excessive sedation, dizziness, ataxia, and confusion. The reason for these precautions is that gabapentin accumulates in patients with impaired kidney function, potentially leading to neurotoxicity. Once the patient's renal function stabilizes, establish a maintenance dose based on the new estimated glomerular filtration rate (eGFR), typically following dosing guidelines for chronic kidney disease patients. Some key considerations for managing AKI include:

• Using isotonic crystalloids rather than colloids for initial management of intravascular volume expansion in patients at risk for AKI or with AKI 1
• Avoiding the use of diuretics to prevent or treat AKI, except in the management of volume overload 1
• Not using low-dose dopamine to prevent or treat AKI 1
• Considering the use of protocol-based management of hemodynamic and oxygenation parameters to prevent the development or worsening of AKI in high-risk patients 1 It is crucial to prioritize the patient's renal function and adjust the gabapentin dose accordingly to minimize the risk of toxicity and ensure optimal management of the patient's condition. In the context of AKI, the primary goal is to prevent further kidney damage and manage the patient's symptoms effectively, which may involve temporarily discontinuing or adjusting the dose of medications like gabapentin that are primarily eliminated through the kidneys. By carefully monitoring the patient's renal function and adjusting the gabapentin dose as needed, healthcare providers can help minimize the risk of adverse effects and ensure the best possible outcomes for patients with AKI. The management of AKI requires a comprehensive approach that takes into account the patient's overall clinical condition, including their renal function, and adjusts treatment strategies accordingly. Healthcare providers should be aware of the potential risks and benefits of using gabapentin in patients with AKI and take a cautious approach to minimize the risk of toxicity and ensure optimal patient outcomes. In addition to adjusting the gabapentin dose, healthcare providers should also consider other strategies for managing AKI, such as using renal replacement therapy (RRT) and managing fluid and electrolyte balance 1. By taking a comprehensive and cautious approach to managing AKI, healthcare providers can help minimize the risk of adverse effects and ensure the best possible outcomes for patients.

From the FDA Drug Label

Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance. In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced.

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).

Resuming Gabapentin in a Patient with Acute Kidney Injury (AKI)

• The patient's renal function should be closely monitored, as gabapentin is primarily renally excreted.
• The dosage of gabapentin may need to be adjusted based on the patient's creatinine clearance.
• Given the potential for reduced gabapentin clearance in patients with impaired renal function, it is recommended to exercise caution when resuming gabapentin in a patient with AKI.
• Consider consulting the dosage guidelines for patients with renal impairment, as provided in the drug label 2 and 2.
• It is recommended to start with a lower dose and gradually increase as needed and as tolerated, while closely monitoring the patient's renal function and for any signs of gabapentin toxicity.

From the Research

Resuming Gabapentin in Patients with Acute Kidney Injury (AKI)

• Gabapentin is excreted unchanged in urine, and its plasma clearance is directly proportional to creatinine clearance 3.
• Renal impairment reduces gabapentin excretion and increases plasma gabapentin concentrations in a linear fashion, which can lead to toxicity 3, 4.
• The elimination half-life of gabapentin increases significantly in patients with renal impairment, from 5-9 hours in patients with normal renal function to 132 hours in patients on dialysis 3.
• Gabapentin toxicity can occur in patients with AKI, and it is often underrecognized 5.
• The risk of gabapentin toxicity is higher in patients with chronic kidney disease, especially in those with advanced age and multiple comorbidities 5.

Considerations for Resuming Gabapentin

• Gabapentin dose should be tightly controlled in patients with renal impairment, and drug monitoring should be used to avoid unintended overdose 3.
• The use of gabapentin in patients with AKI should be carefully evaluated, and alternative treatments should be considered if possible 4.
• Peritoneal dialysis can provide significant clearance of gabapentin, but it is a slow process 6.
• Preventive strategies, such as avoiding nephrotoxic medications and using preventive measures, can help reduce the risk of drug-induced AKI 7.