Common Side Effects of Donepezil
The most common side effects of donepezil are gastrointestinal symptoms including nausea, vomiting, and diarrhea, which are consistent with the expected cholinergic effects of cholinesterase inhibitors. 1, 2
Gastrointestinal Side Effects
- Nausea, vomiting, and diarrhea are the most frequently reported adverse effects 1, 2
- Diarrhea (relative risk 2.57) and nausea (relative risk 2.54) occur significantly more often than with placebo 1
- Anorexia has the largest effect size among gastrointestinal symptoms (relative risk 3.21) 1
- These side effects are typically mild and can be reduced when the medication is taken with food 1, 2
- Gastrointestinal effects are dose-related, with higher incidence at 10mg compared to 5mg dosing 1
Other Common Side Effects
- Insomnia and sleep disturbances 2, 3
- Muscle cramps, particularly leg cramps (very high relative risk in vascular dementia patients) 1, 2
- Dizziness (relative risk 1.47) 1, 2
- Headache 2, 4
- Fatigue/asthenia 2, 4
- Initial increase in agitation that typically subsides after the first few weeks of therapy 1, 5
Cardiovascular Effects
- Slow heartbeat and fainting, particularly in patients with pre-existing heart problems 2
- Caution is advised in patients with bradycardia 6
- Syncope has been reported 2, 6
Other Significant Adverse Effects
- Increased stomach acid production, raising the risk of ulcers and bleeding, especially at higher doses (23mg) 2
- Worsening of lung problems in people with asthma or other respiratory disease 2
- Seizures in susceptible individuals 2
- Difficulty passing urine 2
Monitoring and Management
- Side effects are most likely to occur during dose initiation or adjustment 2, 7
- Adverse effects can be minimized by starting at 5mg daily and gradually increasing to 10mg after 4 weeks 1, 5
- Taking donepezil with food can help reduce gastrointestinal side effects 2
- Unlike tacrine (another cholinesterase inhibitor), donepezil does not cause hepatotoxicity and does not require liver function monitoring 1, 7, 4
Drug Interactions
- Potential interactions with cimetidine, theophylline, warfarin, and digoxin should be considered 5, 7
- NSAIDs taken with donepezil may increase the risk of stomach ulcers 2
- Ketoconazole and quinidine may inhibit the metabolism of donepezil 7
Withdrawal Rates
- In clinical trials, 11% of patients on donepezil withdrew due to adverse events compared to 7% on placebo 4
- Withdrawal rates due to adverse events ranged from 0% to 57% in treatment groups compared to 0% to 20% in placebo groups 1
Donepezil is generally well-tolerated, with most side effects being mild to moderate and transient. The benefits of cognitive improvement in Alzheimer's disease patients often outweigh these adverse effects for many patients 1, 4.