Should gabapentin or risperidone be held in a patient with Acute Kidney Injury (AKI)?

From the Guidelines

In an acute kidney injury (AKI), it is recommended to adjust the dose of gabapentin but risperidone can likely be continued at its usual dose, considering the individualized approach for medication management in AKI as suggested by the consensus report of the acute disease quality initiative (ADQI) 16 workgroup 1. When managing medications in the context of AKI, several factors need to be considered, including renal versus non-renal excretion, potential for nephrotoxicity, and the effect of AKI on drug metabolites or non-renal metabolism, as outlined in the consensus statement 1. Key considerations for gabapentin include:

• Its primary elimination pathway is through the kidneys, which means its clearance is significantly decreased in AKI, potentially leading to accumulation and increased side effects.
• The degree of dose reduction should be based on the severity of AKI and the patient's estimated glomerular filtration rate (eGFR), with possible reductions ranging from 25-50% for mild to moderate AKI to 75% or temporary discontinuation for severe AKI. For risperidone:
• It is extensively metabolized by the liver, with only a small portion excreted unchanged by the kidneys, suggesting that dose adjustment in AKI may not be necessary.
• However, closer monitoring for side effects is advised, especially in elderly patients or those with hepatic impairment alongside AKI. Regular reassessment of kidney function during the AKI episode is crucial to adjust medications accordingly as renal function improves or worsens, aligning with the principle of individualizing medication management in AKI patients 1.

From the FDA Drug Label

In patients with moderate to severe (Clcr 59 to 15 mL/min) renal disease, clearance of the sum of risperidone and its active metabolite decreased by 60%, compared to young healthy subjects. RISPERIDONE doses should be reduced in patients with renal disease [see DOSAGE AND ADMINISTRATION ( 2.4)].

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).

Key Points:

• Risperidone doses should be reduced in patients with renal disease.
• Gabapentin half-life increases significantly in patients with renal impairment.

Clinical Decision: It is recommended to reduce the dose of both gabapentin and risperidone in a patient with Acute Kidney Injury (AKI), as both drugs are substantially excreted by the kidneys and their clearance is decreased in renal impairment. However, the decision to hold these medications should be based on the severity of the AKI, the patient's overall clinical condition, and the potential benefits and risks of continuing or withholding the medications. In general, it is prudent to err on the side of caution and consider reducing or holding these medications in patients with significant renal impairment. 2 3

From the Research

Medication Management in Acute Kidney Injury (AKI)

• In the context of AKI, medication management is crucial, particularly for drugs that may be nephrotoxic or require dose adjustment based on renal function 4, 5.
• The decision to hold or continue medications such as gabapentin or risperidone in a patient with AKI should be based on the potential benefits and risks of the medication, as well as the patient's overall clinical condition.

Gabapentin and Risperidone in AKI

• There is limited direct evidence in the provided studies regarding the specific management of gabapentin or risperidone in AKI.
• However, it is known that gabapentin is primarily excreted by the kidneys, and its dose should be adjusted in patients with renal impairment to avoid toxicity 6.
• Risperidone, an atypical antipsychotic, has been associated with an increased risk of AKI, particularly in older adults, due to its potential to cause hypotension, acute urinary retention, and other adverse outcomes 7.

General Principles for Medication Adjustment in AKI

• The general principle in managing patients with AKI involves discontinuing nephrotoxic medications and adjusting the doses of other medications that are renally cleared 4, 5.
• Given the potential risks associated with risperidone, particularly in vulnerable populations like older adults, careful consideration should be given to its use in the context of AKI 7.
• For gabapentin, dose adjustment according to renal function is recommended to prevent accumulation and potential toxicity, but there is no clear indication to necessarily "hold" the medication unless the patient's renal function is severely impaired or the medication is deemed unnecessary 6.