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Donepezil Can Be Toxic if Too Much Is Taken

The Bottom Line

Donepezil is frequently prescribed to help treat Alzheimer's dementia. It raises levels of acetylcholine in the brain. That can modestly improve symptoms but also cause numerous adverse reactions and drug interactions. Toxic exposures can occur when Alzheimer's dementia patients inadvertently take extra doses and when young children access family members' medications.

The Full Story

Do you know someone with dementia? Chances are, most of us do. With the aging of the American population, Alzheimer’s disease (AD) is the leading cause of dementia. According to the Alzheimer's Association, one in 10 people aged 65 years and over currently have Alzheimer's disease. That's about 5.3 million Americans. Adults younger than 65 are sometimes diagnosed with AD as well and account for another 200,000 cases. Nearly a half million new cases are projected for 2017. The chances of developing Alzheimer's dementia increase with age, and about one-third of Americans 85 years of age and older currently have this condition. More than 15 million Americans care for family members or friends with dementia.

If you're wondering whether forgetting where you left your keys or what you ate for lunch yesterday might be symptoms of Alzheimer's, relax. Alzheimer's dementia involves memory loss severe enough to interfere with daily life, such as not remembering how to do things you have always done or forgetting things that you would normally know. More on Alzheimer's disease and its treatment appeared in the March 2017 edition of The Poison Post®.

Is donepezil an effective treatment for AD?

Donepezil (Aricept) is commonly prescribed for Alzheimer's and some other forms of dementia. It was one of the first medicines developed for AD and is approved by the FDA to treat the mild, moderate, and severe stages of AD. It works by preventing the breakdown of acetylcholine (ACh), a chemical in the brain involved with learning and memory that becomes depleted in AD. Clinical studies have shown that donepezil can raise ACh concentrations in the brain and modestly improve thinking and daily functioning, although dementia's progress is not reversed by any medicine currently available. In many cases, donepezil and medications like it often lose their effectiveness after about a year of treatment.

Donepezil works best in people with mild to moderate AD because once AD becomes severe, the nerves that once produced ACh can no longer function. Most patients take 5 or 10 milligrams (mg) once a day in the form of either oral tablets or tablets that will dissolve in the mouth. For those who need a higher dose, there is also a 23-mg tablet that should not be crushed or chewed. Generic versions are available for all of these dosage forms.

What else should patients and caregivers know about donepezil?

People who take donepezil can experience adverse effects such as nausea, vomiting, diarrhea, urine leakage (incontinence), vivid dreams, slowed heart rate, drowsiness, and weakness. These can pose health hazards for patients who already might not be eating well, have cardiovascular problems, or are at risk for falls. The occurrence of adverse effects doubles in patients over the age of 85 years. To complicate things further, interactions can occur between donepezil and some common medications including antihistamines, medicines for overactive bladder, and antidepressants.

People with AD are at risk for medication errors involving donepezil. A patient might forget what their dose is, or whether they already took their dose, and then unintentionally take more than they should. As little as one donepezil tablet taken by a child, or a few extra doses in adults, have caused symptoms requiring hospitalization lasting several days.

  • A review of 189 patients under 19 years of age reported to poison centers after taking dementia drugs found that 2 year olds were most commonly involved, and 99% of the exposures were unintentional.
  • A review of 1026 adults (19+ years) found that the majority were between 70 and 89 years old and had unintentionally overdosed when taking their own dementia medications.
  • Children and adults most often experienced vomiting, diarrhea, and drowsiness.
  • About half of the people in both age groups were referred for evaluation at a health care facility.

If you have questions about an adverse reaction or possible overdose of donepezil, immediately check the webPOISONCONTROL® online tool or call Poison Control at 1-800-222-1222 for help 24 hours a day, every day.

Leslie A. McCament-Mann, PhD, RPh
Clinical Toxicologist

For More Information

Alzheimer's Association [internet]. Chicago IL [accessed Oct 13, 2017].

Alzheimer's disease fact sheet [Internet]. Bethesda MD: National Institute on Aging; 2017. [accessed Nov 6, 2017]

MedLine Plus: donepezil [internet]. Bethesda MD: National Library of Medicine; 2017. [accessed Nov 6, 2017]


Alzheimer's Association. 2017 Alzheimer's disease facts and figures. Alzheimers Dement 2017;13:325-73.

Buckley JS, Salpeter SR. A risk-benefit assessment of dementia medications: systematic review of the evidence. Drugs Aging 2015;32:453-67.

Garlich FM, Balakrishnan K, Shah SK, Howland MA, Fong J, Nelson LS. Prolonged altered mental status and bradycardia following pediatric donepezil ingestion. Clin Toxicol (Phila) 2014;52:291-4.

Karlawish J, Jack CR Jr, Rocca WA, Snyder HM, Carrillo MC. Alzheimer's Disease: the next frontier – Special Report 2017. Alzheimers Dement 2017;13:374-380.

McCain KR, Sawyer TS, Spiller HA. Evaluation of centrally acting cholinesterase inhibitor exposures in adults. Ann Pharmacother 2007;41:1632-7.

Pourmand A, Shay C, Redha W, Aalam A, Mazer-Amirshahi M. Cholinergic symptoms and QTc prolongation following donepezil overdose. Am J Emerg Med 2017;35:1386 e1- e3.

Shepherd G, Klein-Schwartz W, Edwards R. Donepezil overdose: a tenfold dosing error. Ann Pharmacother 1999;33:812-5.

Thornton SL, Clark RF. Encephalopathy from unintentional donepezil and memantine ingestion. Pediatr Emerg Care 2014;30:649-50.

Thornton SL, Pchelnikova JL, Cantrell FL. Characteristics of pediatric exposures to antidementia drugs reported to a poison control system. J Pediatr 2016;172:147-50.


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Prevention Tips

  • Keep prescription and over-the-counter medications in child-resistant containers, away from children and pets.
  • Grandparents and older relatives often have medications that are especially hazardous if taken incorrectly or swallowed by a child. Extra precautions are needed to reduce dosing errors and unintentional poisonings.
  • If you or a family member take donepezil, ask your doctor and pharmacist to review your medication list for possible drug interactions. Be sure to mention herbals and dietary supplements in addition to all over-the-counter and prescription medicines.

This Really Happened

Case 1. A 14-month-old boy was brought to an ER 3 hours after swallowing one of his grandfather's 10-mg donepezil tablets. He was sleepy and drooling and experienced several episodes of vomiting and diarrhea. These symptoms slowly improved, but he had recurrent episodes of slow heart rate. This eventually resolved and he was sent home on the 5th day.

Case 2. A 2-year-old girl swallowed up to 20 mg of donepezil and 10 mg of memantine (also used to treat dementia) belonging to a family member. When she became agitated and seemed to be hallucinating at home, her family took her to an ER. She became lethargic and developed deviation of one eye. These neurologic symptoms cleared slowly over 3 days in the hospital. Blood tests showed that the amount of donepezil in her system was 10 times greater than a therapeutic dose, while memantine was in the therapeutic range, suggesting that her symptoms were likely due to donepezil.

Case 3. A 79-year-old nursing home patient was given 10 times her normal dose of donepezil (50 mg instead of 5 mg). In the ER, she had nausea, vomiting, and a slow heart rate (less than 50 beats per minute) that required multiple doses of medication to speed up her heart. Her symptoms resolved over 2 days.

Case 4. An 84-year-old Alzheimer's patient unintentionally took seven of his 5-mg donepezil tablets instead of just one. When he arrived at an ER 6-7 hours later, he had nausea, vomiting, diarrhea, fatigue, drooling, and excessive sweating. His heart rate was low (50 beats per minute), and an electrocardiogram (EKG) showed an abnormal heart rhythm. His symptoms gradually cleared during 2 days in the hospital.