What are the contraindications to donepezil (Aricept)?

Contraindications to Donepezil (Aricept)

Donepezil is contraindicated in patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives. 1

Primary Contraindications

• Known hypersensitivity to donepezil hydrochloride or piperidine derivatives is the only absolute contraindication listed in the FDA label 1

Cautions and Relative Contraindications

Cardiovascular Concerns

• Use with caution in patients with cardiac conduction abnormalities due to potential vagotonic effects on sinoatrial and atrioventricular nodes, which may manifest as bradycardia or heart block 1
• Syncopal episodes have been reported with donepezil use 1

Gastrointestinal Concerns

• Use with caution in patients with active or history of peptic ulcer disease, as cholinesterase inhibitors may increase gastric acid secretion 1
• Use with caution in patients on concurrent NSAIDs due to increased risk of gastrointestinal bleeding 1
• Higher doses (23 mg) show increased incidence of peptic ulcer disease (0.4% vs 0.2%) and gastrointestinal bleeding (1.1% vs 0.6%) compared to 10 mg dosing 1

Anesthesia Considerations

• Donepezil may exaggerate succinylcholine-type muscle relaxation during anesthesia due to its cholinesterase inhibitor properties 1

Special Populations

• While not contraindicated, donepezil should be used with caution in advanced dementia as cholinesterase inhibitors may lack long-term benefit in this population 2
• Adverse effects including nausea, vomiting, diarrhea, nightmares, and bradyarrhythmia may outweigh benefits in advanced dementia 2

Common Adverse Effects to Monitor

• Gastrointestinal effects: nausea, vomiting, diarrhea (more common with higher doses) 2, 1
• Initial increase in agitation that typically subsides after a few weeks 2
• Weight loss (reported in 4.7% of patients on 23 mg/day vs 2.5% on 10 mg/day) 1
• Neurological effects: headache, dizziness, sleep disturbance 3

Drug Interactions

• Conflicting evidence about interactions with cimetidine, theophylline, warfarin, and digoxin 2
• May have additive effects with other cholinergic agents 1
• Use caution when combining with medications that can cause bradycardia due to potential additive effects 1

Clinical Decision-Making Algorithm

1. Assess for absolute contraindication:

   • Known hypersensitivity to donepezil or piperidine derivatives 1

2. Evaluate for relative contraindications:

   • Cardiac conduction abnormalities (risk of bradycardia/heart block) 1
   • Active peptic ulcer disease or concurrent NSAID use 1
   • Upcoming surgical procedures requiring anesthesia 1
   • Advanced dementia where benefits may not outweigh risks 2

3. Consider starting at lower dose (5 mg) if patient has:

   • History of GI sensitivity 2
   • Low body weight 1
   • Concurrent medications with potential interactions 2

4. Monitor for adverse effects, particularly during initiation and dose increases, with special attention to:

   • Gastrointestinal symptoms 2, 1
   • Cardiac effects (heart rate, syncope) 1
   • Weight loss 1
   • Behavioral changes 2