From the FDA Drug Label
Renal Disease In a study of 11 patients with moderate to severe renal impairment (Cl C< 18 mL/min/1. 73 m 2) the clearance of donepezil hydrochloride did not differ from 11 age- and sex-matched healthy subjects.
The patient has Acute Kidney Injury (AKI) with a creatinine level of 1.39 and a GFR of 38. According to the drug label, there is no significant difference in the clearance of donepezil hydrochloride in patients with moderate to severe renal impairment compared to healthy subjects. However, the label does not provide specific guidance for patients with AKI and a GFR of 38. No conclusion can be drawn regarding the use of donepezil in this patient. 1
From the Research
Donepezil can be continued at the standard dose despite the patient's acute kidney injury (AKI) with creatinine of 1.39 and GFR of 38, as the most recent and highest quality study 2 suggests that donepezil has minimal impact on kidney function. No dose adjustment is necessary for donepezil in renal impairment, including in patients with moderate renal dysfunction (GFR 30-59 ml/min) as seen in this case. Donepezil is primarily metabolized by the liver through the CYP450 enzyme system, with minimal renal excretion of the parent drug. Only about 17% of donepezil is excreted unchanged in the urine, so kidney function has minimal impact on drug clearance. However, it's essential to monitor the patient for potential side effects such as nausea, diarrhea, insomnia, and muscle cramps, which may be more pronounced in patients with compromised organ function. Also, consider the underlying cause of the AKI and address it appropriately, as improving kidney function should remain a priority. Regular monitoring of renal function is recommended to ensure the patient's condition doesn't deteriorate further. Some studies have evaluated the efficacy and safety of donepezil in patients with Alzheimer's disease, including those with renal impairment 3, 4, 5, but the most relevant study for this specific scenario is the one that directly assesses the impact of donepezil on liver and kidney functions 2. It's also important to note that the definition of acute kidney injury and the most appropriate metric to use are still topics of discussion in the medical community 6. In clinical practice, the serum creatinine level is commonly used to define AKI, but it's essential to consider the limitations and pitfalls of using this marker. Overall, the available evidence suggests that donepezil can be safely continued in patients with moderate renal dysfunction, but close monitoring of the patient's condition is necessary to prevent any potential adverse effects.