What are the side effects of donepezil?

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From the Guidelines

Donepezil can cause several side effects, ranging from mild to severe, including nausea, diarrhea, vomiting, loss of appetite, weight loss, muscle cramps, fatigue, and insomnia, as reported in studies such as 1 and 1. To manage these side effects:

  • Take donepezil with food to reduce gastrointestinal issues.
  • Start with a low dose (typically 5 mg daily) and gradually increase as tolerated.
  • Take the medication in the evening to minimize daytime fatigue.
  • Stay hydrated and maintain a balanced diet to counteract potential weight loss.
  • Monitor for any severe symptoms and report them to your healthcare provider immediately. Donepezil works by increasing acetylcholine levels in the brain, which can improve cognitive function in Alzheimer's disease. However, this mechanism also affects other body systems, leading to the observed side effects. Most side effects are due to cholinergic stimulation throughout the body and tend to diminish over time as the body adjusts to the medication, as noted in 1 and 1.

The most common side effects of donepezil include:

  • Nausea
  • Diarrhea
  • Vomiting
  • Loss of appetite
  • Weight loss
  • Muscle cramps
  • Fatigue
  • Insomnia These side effects are generally mild to moderate in severity, but can be more severe in some cases, as reported in 1 and 1.

It's essential to note that the risk of side effects can be minimized by:

  • Starting with a low dose and gradually increasing as tolerated
  • Taking the medication with food
  • Monitoring for any severe symptoms and reporting them to your healthcare provider immediately
  • Maintaining a balanced diet and staying hydrated to counteract potential weight loss and other side effects, as recommended in 1 and 1.

From the FDA Drug Label

Donepezil hydrochloride tablets may cause the following serious side effects: slow heartbeat and fainting. more stomach acid. 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, fainting, increased stomach acid, worsening of lung problems, seizures, and difficulty passing urine.
  • Common side effects: nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and decreased appetite 2.

From the Research

Side Effects of Donepezil

The side effects of donepezil have been reported in several studies, including:

  • Nausea and/or vomiting 3, 4
  • Diarrhoea 3, 4
  • Dizziness 3, 4
  • Headache 3
  • Hypertension 3
  • Malaise 4
  • Insomnia 4
  • Aggression, agitation, and abnormal dreams (uncommonly associated) 4
  • Muscle-related symptoms, such as muscle weakness and cramps 5

Adverse Events

Adverse events reported in the studies included:

  • Donepezil 10 mg was associated with more adverse events than placebo, including nausea, diarrhoea, and dizziness 3
  • Galantamine 16 to 24 mg was probably associated with a slight excess of adverse events over placebo 3
  • Rivastigmine 3 to 12 mg had a very uncertain effect on adverse events 3
  • High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with N-acetylcysteine (NAC) 5

Cardiac Effects

Cardiac effects of donepezil overdose have been reported, including:

  • QTc prolongation 6
  • Cardiac dysrhythmias 6

Management of Adverse Effects

The management of adverse effects of donepezil is crucial to improve patient compliance and quality of life. Studies suggest that:

  • Co-treatment with NAC may attenuate the adverse effects of donepezil by regulating ROS and [Ca2+]i levels in the skeletal muscle 5
  • Supportive care with particular attention to the management of cardiac dysrhythmias is essential in patients displaying signs of toxicity due to donepezil overdose 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adverse effects associated with the use of donepezil in general practice in England.

Journal of psychopharmacology (Oxford, England), 2000

Research

Cholinergic symptoms and QTc prolongation following donepezil overdose.

The American journal of emergency medicine, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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