Does Aricept (donepezil) cause side effects?

Aricept (donepezil) is a cholinesterase inhibitor used to treat mild, moderate, or severe dementia associated with Alzheimer's disease. 

Scientists believe Alzheimer's disease may result from a deficiency in chemicals (neurotransmitters) used by nerves in the brain to communicate with one another. 

Aricept inhibits acetylcholinesterase, an enzyme responsible for the destruction of one neurotransmitter, acetylcholine. This leads to increased concentrations of acetylcholine in the brain, and the increased concentrations are believed to be responsible for the improvement seen during treatment with Aricept. 

Aricept improves the symptoms but does not slow the progression of Alzheimer's disease. 

Common side effects of Aricept include

Serious side effects of Aricept include

Drug interactions of Aricept include drugs with anti-cholinergic properties that can cross into the brain, such as atropine, benztropine, and trihexyphenidyl that can counteract the effects of Aricept.

  • Aricept is metabolized (eliminated) by enzymes in the liver.
  • The rate of metabolism of Aricept may be increased by medications that increase the amounts of these enzymes, such as carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampin.
  • By increasing elimination, these drugs may reduce the effects of Aricept.
  • Ketoconazole has been shown to block the enzymes in the liver that metabolize Aricept.
  • Concurrent use of ketoconazole and Aricept may result in increased concentrations of Aricept in the body and possibly lead to Aricept side effects.
  • Quinidine also has been shown to inhibit the enzymes that metabolize Aricept and may cause Aricept side effects. 

It is unknown if Aricept is harmful to a fetus. Safe use of Aricept during pregnancy has not been established. 

It is unknown if Aricept is secreted into breast milk or if breastfeeding while taking Aricept is safe for the nursing infant. Consult your doctor before breastfeeding.

What are the important side effects of Aricept (donepezil)?

The most common side effects associated with donepezil are:

Other important side effects include:

Aricept (donepezil) side effects list for healthcare professionals

The following serious adverse reactions are described below and elsewhere in the labeling:

  • Cardiovascular Conditions
  • Nausea and Vomiting
  • Peptic Ulcer Disease and GI Bleeding
  • Weight Loss
  • Genitourinary Conditions
  • Neurological Conditions: Seizures .
  • Pulmonary Conditions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Aricept has been administered to over 1,700 individuals during clinical trials worldwide. Approximately 1200 of these patients have been treated for at least 3 months and more than 1,000 patients have been treated for at least 6 months. Controlled and uncontrolled trials in the United States included approximately 900 patients. 

 In regards to the highest dose of 10 mg/day, this population includes 650 patients treated for 3 months, 475 patients treated for 6 months, and 116 patients treated for over 1 year. The range of patient exposure is from 1 to 1,214 days.

Mild To Moderate Alzheimer's Disease

Adverse Reactions Leading To Discontinuation

The rates of discontinuation from controlled clinical trials of Aricept due to adverse reactions for the Aricept 5 mg/day treatment groups were comparable to those of placebo treatment groups at approximately 5%. The rate of discontinuation of patients who received 7-day escalations from 5 mg/day to 10 mg/day was higher at 13%.

The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice or more the incidence seen in placebo patients, are shown in Table 1.

Table 1: Most Common Adverse Reactions Leading to Discontinuation in Patients with Mild to Moderate Alzheimer's Disease

Adverse ReactionPlacebo
(n=355) %
5 mg/day Aricept
(n=350) %
10 mg/day Aricept
(n=315) %
Nausea113
Diarrhea0<13
Vomiting<1<12

Most Common Adverse Reactions

The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving 10 mg/day and twice the placebo rate, are largely predicted by Aricept's cholinomimetic effects.

These include

These adverse reactions were often transient, resolving during continued Aricept treatment without the need for dose modification.

There is evidence to suggest that the frequency of these common adverse reactions may be affected by the rate of titration. An open-label study was conducted with 269 patients who received placebo in the 15- and 30-week studies.

These patients were titrated to a dose of 10 mg/day over a 6-week period. The rates of common adverse reactions were lower than those seen in patients titrated to 10 mg/day over one week in the controlled clinical trials and were comparable to those seen in patients on 5 mg/day.

See Table 2 for a comparison of the most common adverse reactions following one and six-week titration regimens.

Table 2: Comparison of Rates of Adverse Reactions in Mild to Moderate Patients Titrated to 10 mg/day over 1 and 6 Weeks

Adverse ReactionNo titrationOne week titrationSix week titration
Placebo
(n=315) %
5 mg/day
(n=311) %
10 mg/day
(n=315) %
10 mg/day
(n=269) %
Nausea65196
Diarrhea58159
Insomnia66146
Fatigue3483
Vomiting3385
Muscle cramps2683
Anorexia2373

Table 3 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received either Aricept 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with Aricept than with placebo. In general, adverse reactions occurred more frequently in female patients and with advancing age.

Table 3: Adverse Reactions in Pooled Placebo-Controlled Clinical Trials in Mild to Moderate Alzheimer's Disease

Adverse ReactionPlacebo
(n=355) %
Aricept
(n=747) %
Percent of Patients with any Adverse Reaction7274
Nausea611
Diarrhea510
Headache910
Insomnia69
Pain, various locations89
Dizziness68
Accident67
Muscle Cramps26
Fatigue35
Vomiting35
Anorexia24
Ecchymosis34
Abnormal Dreams03
Depression<13
Weight Loss13
Arthritis12
Frequent Urination12
Somnolence<12
Syncope12

Severe Alzheimer's Disease (Aricept 5 mg/day And 10 mg/day)

Aricept has been administered to over 600 patients with severe Alzheimer's disease during clinical trials of at least 6 months duration, including three double-blind, placebo-controlled trials, two of which had an open-label extension.

Adverse Reactions Leading To Discontinuation

The rates of discontinuation from controlled clinical trials of Aricept due to adverse reactions for the Aricept patients were approximately 12% compared to 7% for placebo patients. The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of Aricept patients and at twice or more the incidence seen in placebo, were

Most Common Adverse Reactions

The most common adverse reactions, defined as those occurring at a frequency of at least 5% in patients receiving Aricept and at twice or more the placebo rate, are largely predicted by Aricept's cholinomimetic effects.

These include

  • diarrhea,
  • anorexia,
  • vomiting,
  • nausea, and
  • ecchymosis.

These adverse reactions were often transient, resolving during continued Aricept treatment without the need for dose modification.

Table 4 lists adverse reactions that occurred in at least 2% of patients in pooled placebo-controlled trials who received Aricept 5 mg or 10 mg and for which the rate of occurrence was greater for patients treated with Aricept than with placebo.

Table 4: Adverse Reactions in Pooled Controlled Clinical Trials in Severe Alzheimer's Disease

Body System/Adverse ReactionPlacebo
(n=392) %
Aricept
(n=501) %
Percent of Patients with any Adverse Reaction7381
Accident1213
Infection911
Diarrhea410
Anorexia48
Vomiting48
Nausea26
Insomnia45
Ecchymosis25
Headache34
Hypertension23
Pain23
Back Pain23
Eczema23
Hallucinations13
Hostility23
Increase in Creatine Phosphokinase13
Nervousness23
Fever12
Chest Pain<12
Confusion12
Dehydration12
Depression12
Dizziness12
Emotional Lability12
Hemorrhage12
Hyperlipemia<12
Personality Disorder12
Somnolence12
Syncope12
Urinary Incontinence12

Moderate To Severe Alzheimer's Disease (Aricept 23 mg/day)

  • Aricept 23 mg/day has been administered to over 1300 individuals globally in clinical trials.
  • Approximately 1050 of these patients have been treated for at least three months and more than 950 patients have been treated for at least six months.
  • The range of patient exposure was from 1 to over 500 days.
Adverse Reactions Leading To Discontinuation
  • The rate of discontinuation from a controlled clinical trial of Aricept 23 mg/day due to adverse reactions was higher (19%) than for the 10 mg/day treatment group (8%).
  •  The most common adverse reactions leading to discontinuation, defined as those occurring in at least 1% of patients and greater than those occurring with 10 mg/day are shown in Table 5.

Table 5: Most Common Adverse Reactions Leading to Discontinuation in Patients with Moderate to Severe Alzheimer's Disease

Adverse Reaction23 mg/day Aricept
(n=963)%
10 mg/day Aricept
(n=471)%
Vomiting30
Diarrhea20
Nausea20
Dizziness10

The majority of discontinuations due to adverse reactions in the 23 mg group occurred during the first month of treatment.

Most Common Adverse Reactions With Aricept 23 mg/day

The most common adverse reactions, defined as those occurring at a frequency of at least 5%, include

  • nausea,
  • diarrhea,
  • vomiting, and
  • anorexia.

Table 6 lists adverse reactions that occurred in at least 2% of patients who received 23 mg/day of Aricept and at a higher frequency than those receiving 10 mg/day of Aricept in a controlled clinical trial that compared the two doses. In this study, there were no important differences in the type of adverse reactions in patients taking Aricept with or without memantine.

Table 6: Adverse Reactions in a Controlled Clinical Trial in Moderate to Severe Alzheimer's Disease

Adverse Reaction23 mg/day Aricept
(n=963)%
10 mg/day Aricept
(n=471)%
Percent of Patients with any Adverse Reaction7464
Nausea123
Vomiting93
Diarrhea85
Anorexia52
Dizziness53
Weight Loss53
Headache43
Insomnia32
Urinary Incontinence31
Asthenia21
Contusion20
Fatigue21
Somnolence21

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Aricept. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These reactions include

What drugs interact with Aricept (donepezil)?

Use With Anticholinergics

  • Because of their mechanism of action, cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications.

Use With Cholinomimetics And Other Cholinesterase Inhibitors

  • A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 12/7/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.