What are the contraindications or precautions for starting donepezil (Aricept) in a geriatric patient with dementia?

Contraindications and Precautions for Starting Donepezil

Donepezil has only one absolute contraindication: known hypersensitivity to donepezil or piperidine derivatives. 1 Beyond this, there are several important clinical situations requiring caution rather than complete avoidance.

Absolute Contraindication

• Known hypersensitivity to donepezil hydrochloride or piperidine derivatives is the only FDA-labeled contraindication 1

Cardiovascular Precautions

Exercise caution in patients with cardiac conduction abnormalities, as donepezil can cause vagotonic effects on the sinoatrial and atrioventricular nodes. 1

• Bradycardia and heart block can occur in patients both with and without underlying cardiac conduction disease 1
• Syncopal episodes have been reported with donepezil use 1
• Screen for sick sinus syndrome, significant AV block, or symptomatic bradycardia before initiating therapy

Gastrointestinal Concerns

Patients with active peptic ulcer disease or those at high risk for GI bleeding require close monitoring, though this is not an absolute contraindication. 1

• Cholinesterase inhibitors increase gastric acid secretion through increased cholinergic activity 1
• Particular caution is needed in patients with:
  • History of ulcer disease 1
  • Concurrent NSAID use 1
  • History of GI bleeding 1
• The 23 mg dose shows increased risk of peptic ulcer disease (0.4% vs 0.2%) and GI bleeding (1.1% vs 0.6%) compared to 10 mg 1

Anesthesia Planning

Inform anesthesiologists that the patient is taking donepezil, as it will exaggerate succinylcholine-type muscle relaxation during anesthesia. 1

• This is a predictable pharmacological effect of cholinesterase inhibition 1

Expected Adverse Effects (Not Contraindications)

Gastrointestinal side effects are common and predictable but should not prevent initiation in most patients. 1

• Nausea, vomiting, and diarrhea occur more frequently with 10 mg than 5 mg doses 1
• The American Geriatrics Society recommends taking donepezil with food to reduce these effects 2
• Most GI effects are transient, lasting 1-3 weeks, and resolve with continued use 1
• Only 2.9% of patients discontinued the 23 mg dose due to vomiting 1

Weight Loss Monitoring

Monitor weight in all patients, particularly those on higher doses, but this is not a reason to avoid starting therapy. 1

• Weight loss occurred in 4.7% on 23 mg versus 2.5% on 10 mg 1
• 8.4% of patients on 23 mg experienced ≥7% weight loss by study end 1

When NOT to Start Donepezil

Do not initiate donepezil in patients with mild cognitive impairment (MCI) without dementia. 3

• Donepezil does not prevent progression to Alzheimer's disease in MCI patients after 3 years of treatment 3
• Benefits are minor, short-lived, and associated with significant side effects in this population 3
• After one year, fewer MCI patients on donepezil progressed to dementia, but this difference disappeared by 3 years 3

Common Pitfall to Avoid

The most important pitfall is withholding donepezil due to minor, manageable side effects rather than true contraindications. The drug is generally well-tolerated, with serious adverse event rates similar to placebo (4-10% vs 5-9%) in short-term trials 4. Unlike tacrine, donepezil shows no evidence of hepatotoxicity 2, making it safer than older cholinesterase inhibitors.