Side Effects of Donepezil (Aricept)
Donepezil commonly causes gastrointestinal side effects including nausea, vomiting, and diarrhea, with diarrhea (relative risk 2.57) and nausea (relative risk 2.54) occurring significantly more often than with placebo. 1
Common Side Effects
Gastrointestinal Effects
- Nausea and vomiting (relative risk 2.54) are among the most frequently reported adverse effects 1
- Diarrhea (relative risk 2.57) is significantly more common than with placebo 1
- Anorexia has the largest effect size among gastrointestinal symptoms (relative risk 3.21) 1
- These gastrointestinal effects are dose-related, with higher incidence at 10mg compared to 5mg dosing 1, 2
Neurological Effects
- Initial increase in agitation that typically subsides after the first few weeks of therapy 1, 3
- Dizziness (relative risk 1.47) is a common side effect 1
- Sleep disturbances, particularly when taken at bedtime 4, 5
- Muscle cramps, particularly leg cramps, occur with a very high relative risk in vascular dementia patients 1, 5
Cardiovascular Effects
- Slow heartbeat and fainting, especially in patients with pre-existing heart problems 6
- Risk of bradyarrhythmia 7
Other Significant Side Effects
- Increased stomach acid production, raising the chance of ulcers and bleeding, especially at higher doses 6
- Worsening of lung problems in people with asthma or other lung disease 6
- Seizures in susceptible individuals 6
- Difficulty passing urine 6
Side Effect Management
Minimizing Adverse Effects
- Start at 5mg daily and gradually increase to 10mg after 4 weeks to minimize side effects 1
- Taking donepezil in the morning rather than at bedtime may minimize sleep disturbances 2
- Unlike some other cholinesterase inhibitors, donepezil does not cause hepatotoxicity and does not require liver function monitoring 1
When to Contact Healthcare Provider
- For fainting or feeling lightheaded 6
- New or persistent heartburn or stomach pain 6
- Nausea or vomiting, especially if blood is present 6
- Dark stools that look like black tar 6
- New or worsening asthma or breathing problems 6
- Seizures 6
- Difficulty passing urine 6
Drug Interactions
- Potential interactions with cimetidine, theophylline, warfarin, and digoxin 1
- Increased risk of stomach ulcers when taken with NSAIDs or aspirin 6
- Interactions with certain anesthesia medications, requiring disclosure before surgery or dental procedures 6
Withdrawal Rates and Discontinuation
- Withdrawal rates due to adverse events ranged from 0% to 57% in treatment groups compared to 0% to 20% in placebo groups 1
- If donepezil is missed for 7 days or more, consultation with a doctor is needed before restarting 6
- Side effects may improve after taking donepezil for a while as the body adjusts to the medication 6
Special Considerations
- Patients with pre-existing heart problems should be monitored for slow heartbeat and fainting 6
- Those with history of stomach ulcers or taking NSAIDs should be monitored for GI bleeding 6
- Patients with asthma or lung disease may experience worsening of respiratory symptoms 6
- Caution is advised in patients with seizure disorders 6
- Patients with urinary retention issues may experience worsening symptoms 6