From the Guidelines
Donepezil can cause several side effects, including nausea, vomiting, diarrhea, and muscle cramps, with diarrhea and nausea being the most frequently reported, as shown in studies 1. The most common side effects of donepezil include:
- Nausea
- Vomiting
- Diarrhea
- Loss of appetite
- Weight loss
- Muscle cramps
- Fatigue
- Insomnia These side effects occur because donepezil increases acetylcholine levels in the brain by inhibiting the enzyme acetylcholinesterase, which breaks down acetylcholine, as reported in studies 1.
Management of Side Effects
Patients should take donepezil in the evening before bedtime to minimize daytime side effects, start with a lower dose (typically 5mg daily) before potentially increasing to 10mg after 4-6 weeks, and always take it with food if gastrointestinal symptoms occur, as suggested by the evidence 1. If severe side effects develop, patients should contact their healthcare provider immediately rather than discontinuing the medication abruptly. The quality of reporting harms in the studies was generally low to moderate, with some studies not specifying the mode of recording harms, as noted in 1. However, the evidence suggests that donepezil can cause significant side effects, and patients should be closely monitored for these adverse events.
Dose-Response Effect
Six studies reported a dose–response effect, with increasing frequency of adverse events as dose increased, as shown in 1. This suggests that higher doses of donepezil may be associated with a greater risk of side effects. Therefore, patients should be started on a lower dose and gradually increased as needed and tolerated.
Serious Side Effects
More serious but less common side effects of donepezil include slow heart rate, fainting, difficulty urinating, seizures, and gastrointestinal bleeding, as reported in 1. These side effects can be life-threatening and require immediate medical attention. Patients should be closely monitored for these adverse events, and healthcare providers should be notified immediately if they occur.
From the FDA Drug Label
Donepezil hydrochloride tablets may cause the following serious side effects: slow heartbeat and fainting. This happens more often in people with heart problems. more stomach acid. This raises the chance of ulcers and bleeding, especially when taking donepezil hydrochloride tablets 23 mg The risk is higher for people who have had ulcers, or take aspirin or other NSAIDs. worsening of lung problems in people with asthma or other lung disease. seizures. difficulty passing urine. The most common side effects of donepezil hydrochloride tablets are: nausea diarrhea not sleeping well vomiting muscle cramps feeling tired not wanting to eat
The side effects of donepezil include:
- Serious side effects:
- Slow heartbeat and fainting
- Increased stomach acid, which can lead to ulcers and bleeding
- Worsening of lung problems in people with asthma or other lung disease
- Seizures
- Difficulty passing urine
- Common side effects:
- Nausea
- Diarrhea
- Not sleeping well
- Vomiting
- Muscle cramps
- Feeling tired
- Not wanting to eat 2
From the Research
Side Effects of Donepezil
- The most common side effects of donepezil are cholinergic in nature and generally related to the gastrointestinal and nervous systems 3.
- Adverse events associated with donepezil include nausea, vomiting, diarrhea, and anorexia, with more incidents reported in the 10 mg/day group compared to placebo and the 5 mg/day group 3, 4, 5, 6.
- The incidence of serious adverse events was generally similar between donepezil 5 and 10 mg and placebo in short-term trials 3.
- There was no evidence of hepatotoxicity with donepezil 3, 4, 5.
- Participants receiving donepezil were more likely to withdraw from studies before the end of treatment or to experience an adverse event during the studies 6.
Comparison of Donepezil Doses
- The 10 mg/day dose of donepezil was associated with better cognitive function and global clinical state compared to the 5 mg/day dose, but also with more adverse events and withdrawals from treatment 6.
- There were no differences in efficacy outcomes between donepezil 10 mg/day and 23 mg/day, but fewer participants on 10 mg/day experienced adverse events or withdrew from treatment 6.