No Specific Renal Function Cut-off for Aricept (Donepezil)
There is no renal function cut-off that contraindicates the use of Aricept (donepezil) in geriatric patients with Alzheimer's disease, as the drug's clearance is not significantly affected by renal impairment. 1
Pharmacokinetic Evidence in Renal Impairment
The FDA label for donepezil explicitly states that in a study of 11 patients with moderate to severe renal impairment (creatinine clearance < 18 mL/min/1.73 m²), the clearance of donepezil did not differ from 11 age- and sex-matched healthy subjects 1
Donepezil is primarily metabolized by hepatic CYP450 enzymes (CYP2D6 and CYP3A4) and undergoes glucuronidation, with only approximately 17% of the dose recovered in urine as unchanged drug 1
Following administration of radiolabeled donepezil, approximately 57% of total radioactivity was recovered in urine and 15% in feces over 10 days, but most urinary excretion represents metabolites rather than intact drug 1
Clinical Experience in Dialysis Patients
A case series of 5 chronic hemodialysis patients (ages 65-86 years) with moderate Alzheimer's disease successfully tolerated donepezil starting at 2.5 mg/day, with dose escalation to 5 mg/day after one month, without any episodes of drug toxicity over 6 months and maintained stable condition for up to 10 years of follow-up 2
These dialysis patients showed improvement in behavioral symptoms and slight improvement in cognitive and executive functions without adverse events, demonstrating that donepezil can be safely used even in patients with end-stage renal disease requiring dialysis 2
Practical Dosing Approach
Standard dosing of donepezil (starting at 5 mg once daily, increasing to 10 mg after 4-6 weeks) can be used in patients with any degree of renal impairment without dose adjustment 3, 1
For patients with severe renal impairment or on dialysis, consider a more conservative approach by starting at 2.5 mg/day (half tablet) and monitoring closely for the first month before escalating to standard doses 2
The once-daily dosing schedule and lack of hepatotoxicity make donepezil particularly suitable for elderly patients with multiple comorbidities, including renal disease 3, 4
Important Caveats
While renal function does not affect donepezil clearance, age does have a modest effect: 90-year-old subjects have a 17% decrease in clearance compared to 65-year-old subjects, though this is not clinically significant enough to warrant dose adjustment 1
The primary concern with donepezil in elderly patients relates to cholinergic side effects (nausea, vomiting, diarrhea) rather than renal accumulation, and these can be minimized by taking the medication with food 3, 4
Approximately 15-20% of AD patients may exhibit abnormal metabolism of donepezil due to CYP2D6 genetic polymorphisms, which is independent of renal function 5