Does Aricept (donepezil) cause gastrointestinal (GI) bleeding?

Donepezil (Aricept) and Risk of GI Bleeding

Donepezil can cause gastrointestinal bleeding, particularly at higher doses or in patients with risk factors for GI bleeding. 1

Mechanism and Risk

• Donepezil, as a cholinesterase inhibitor, increases cholinergic activity which may increase gastric acid secretion, potentially leading to peptic ulcer disease and GI bleeding 1
• The FDA label specifically warns that patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers 1
• Clinical studies with donepezil at 5-10 mg/day showed no increase in peptic ulcer disease or GI bleeding relative to placebo 1
• However, higher doses (23 mg/day) showed increased incidence of peptic ulcer disease (0.4% vs 0.2%) and gastrointestinal bleeding from any site (1.1% vs 0.6%) compared to 10 mg/day dosing 1

Risk Factors for GI Bleeding with Donepezil

• History of ulcer disease or previous GI bleeding 1
• Concurrent use of NSAIDs, anticoagulants, or antiplatelet medications 1, 2
• Advanced age 2
• Use of steroids 2
• Helicobacter pylori infection 2
• Higher doses of donepezil (23 mg vs lower doses) 1

Case Reports and Clinical Evidence

• There are documented case reports of upper GI bleeding associated with donepezil use, such as an 86-year-old man who developed an acute duodenal ulcer while on donepezil, with no other risk factors for GI bleeding 3
• The most common adverse effects of donepezil are gastrointestinal, including nausea, vomiting, diarrhea, and anorexia 4, 5

Management Recommendations

• For patients at high risk of GI bleeding who require donepezil:
  • Consider prophylactic use of a proton pump inhibitor (PPI) 3
  • PPIs are more effective than H2-receptor antagonists in preventing upper GI bleeding in patients on medications that increase bleeding risk 2
  • Monitor for signs and symptoms of GI bleeding 1
• For patients who develop GI bleeding while on donepezil:
  • Evaluate for other causes and risk factors for GI bleeding 2
  • Consider dose reduction or discontinuation if appropriate 1
  • Add gastroprotective therapy (preferably a PPI) if continuing donepezil is necessary 3

Alternative Approaches

• For patients with significant GI side effects, alternative administration routes may be considered, such as transdermal delivery systems that are being developed to bypass GI effects 6
• In patients with dementia who have a history of GI bleeding or multiple risk factors, carefully weigh the benefits of cognitive improvement against the risks of GI complications 2

Important Caveats

• The risk of GI bleeding appears to be dose-dependent, with higher risk at 23 mg doses compared to standard 5-10 mg doses 1
• Patients should be informed about the signs and symptoms of GI bleeding and instructed to report these promptly 1
• When prescribing donepezil to older adults, consider it a potentially inappropriate medication that requires careful monitoring for adverse effects including GI complications 2