Donepezil side effects

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Contents

* 1 List of side effects
* 1.1 Mild to moderate Alzheimer's disease
* 1.1.1 Adverse events leading to discontinuation (moderate Alzheimer's disease)
* 1.1.2 Most frequent adverse clinical events seen in association with the use of Aricept® (moderate Alzheimer's disease)
* 1.1.2.1 Effect of rate of titration
* 1.1.3 Adverse events reported in controlled trials (moderate Alzheimer's disease)
* 1.1.4 Other adverse events observed during clinical trials (moderate Alzheimer's disease)
* 1.1.4.1 Body as a whole (moderate Alzheimer's disease)
* 1.1.4.2 Cardiovascular system (moderate Alzheimer's disease)
* 1.1.4.3 Digestive system (moderate Alzheimer's disease)
* 1.1.4.4 Endocrine system (moderate Alzheimer's disease)
* 1.1.4.5 Hemic and lymphatic system (moderate Alzheimer's disease)
* 1.1.4.6 Metabolic and nutritional disorders (moderate Alzheimer's disease)
* 1.1.4.7 Musculoskeletal system (moderate Alzheimer's disease)
* 1.1.4.8 Nervous system (moderate Alzheimer's disease)
* 1.1.4.9 Respiratory system (moderate Alzheimer's disease)
* 1.1.4.10 Skin and appendages (moderate Alzheimer's disease)
* 1.1.4.11 Special senses (moderate Alzheimer's disease)
* 1.1.4.12 Urogenital system (moderate Alzheimer's disease)
* 1.2 Severe Alzheimer's disease
* 1.2.1 Adverse events leading to discontinuation (severe Alzheimer's disease)
* 1.2.2 Most frequent adverse clinical events seen in association with the use of Aricept® (severe Alzheimer's disease)
* 1.2.3 Other adverse events observed during clinical trials (severe Alzheimer's disease)
* 1.2.3.1 Body as a whole (severe Alzheimer's disease)
* 1.2.3.2 Cardiovascular system (severe Alzheimer's disease)
* 1.2.3.3 Digestive system (severe Alzheimer's disease)
* 1.2.3.4 Endocrine system (severe Alzheimer's disease)
* 1.2.3.5 Hemic and lymphatic system (severe Alzheimer's disease)
* 1.2.3.6 Metabolic and nutritional disorders (severe Alzheimer's disease)
* 1.2.3.7 Musculoskeletal system (severe Alzheimer's disease)
* 1.2.3.8 Nervous system (severe Alzheimer's disease)
* 1.2.3.9 Respiratory system (severe Alzheimer's disease)
* 1.2.3.10 Skin and appendages (severe Alzheimer's disease)
* 1.2.3.11 Special senses (severe Alzheimer's disease)
* 1.2.3.12 Urogenital system (severe Alzheimer's disease)
* 1.3 Postintroduction reports

## List of side effects

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Mild to moderate Alzheimer's disease

* Adverse events leading to discontinuation (moderate Alzheimer's disease)
* Effect of rate of titration
* Adverse events reported in controlled trials (moderate Alzheimer's disease)
* Other adverse events observed during clinical trials (moderate Alzheimer's disease)
* Body as a whole (moderate Alzheimer's disease)
* Cardiovascular system (moderate Alzheimer's disease)
* Digestive system (moderate Alzheimer's disease)
* Endocrine system (moderate Alzheimer's disease)
* Hemic and lymphatic system (moderate Alzheimer's disease)
* Metabolic and nutritional disorders (moderate Alzheimer's disease)
* Musculoskeletal system (moderate Alzheimer's disease)
* Nervous system (moderate Alzheimer's disease)
* Respiratory system (moderate Alzheimer's disease)
* Skin and appendages (moderate Alzheimer's disease)
* Special senses (moderate Alzheimer's disease)
* Urogenital system (moderate Alzheimer's disease)

Severe Alzheimer's disease

* Adverse events leading to discontinuation (severe Alzheimer's disease)
* Most frequent adverse clinical events seen in association with the use of Aricept® (severe Alzheimer's disease)
* Other adverse events observed during clinical trials (severe Alzheimer's disease)
* Body as a whole (severe Alzheimer's disease)
* Cardiovascular system (severe Alzheimer's disease)
* Digestive system (severe Alzheimer's disease)
* Endocrine system (severe Alzheimer's disease)
* Hemic and lymphatic system (severe Alzheimer's disease)
* Metabolic and nutritional disorders (severe Alzheimer's disease)
* Musculoskeletal system (severe Alzheimer's disease)
* Nervous system (severe Alzheimer's disease)
* Respiratory system (severe Alzheimer's disease)
* Skin and appendages (severe Alzheimer's disease)
* Special senses (severe Alzheimer's disease)
* Urogenital system (severe Alzheimer's disease)

Postintroduction reports

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### Mild to moderate Alzheimer's disease

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#### Adverse events leading to discontinuation (moderate Alzheimer's disease)

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The rates of discontinuation from controlled clinical trials of Aricept® due to adverse events 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%. Return to top

#### Most frequent adverse clinical events seen in association with the use of Aricept® (moderate Alzheimer's disease)

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The most common adverse events, defined as those occurring at a in patifrequency of at least 5%ents receiving 10 mg/day and twice the placebo rate, are largely predicted by Aricept®'s cholinomimetic effects. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia. These adverse events were often of mild intensity and trancontinuesient, resolving during d Aricept® treatment without the need for dose modification. Return to top

##### Effect of rate of titration

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There is evidence to suggest that the frequency of these common adverse events 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 events 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. Return to top

#### Adverse events reported in controlled trials (moderate Alzheimer's disease)

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The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. In general, adverse events occurred more frequently in female patients and with advancing age. Return to top

#### Other adverse events observed during clinical trials (moderate Alzheimer's disease)

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##### Body as a whole (moderate Alzheimer's disease)

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Frequent: influenza, chest pain, toothache;
Infrequent: fever, edema face, periorbital edema, hernia hiatal, abscess, cellulitis, chills, generalized coldness, head fullness, listlessness. Return to top

##### Cardiovascular system (moderate Alzheimer's disease)

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Frequent: hypertension, vasodilation, atrial fibrillation, hot flashes, hypotension;
Infrequent: angina pectoris, postural hypotension, myocardial infarction, AV block (first degree), congestive heart failure, arteritis, bradycardia, peripheral vascular disease, supraventricular tachycardia, deep vein thrombosis. Return to top

##### Digestive system (moderate Alzheimer's disease)

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Frequent: fecal incontinence, gastrointestinal bleeding, bloating, epigastric pain;
Infrequent: eructation, gingivitis, increased appetite, flatulence, periodontal abscess, cholelithiasis, diverticulitis, drooling, dry mouth, fever sore, gastritis, irritable colon, tongue edema, epigastric distress, gastroenteritis, increased transaminases, hemorrhoids, ileus, increased thirst, jaundice, melena, polydipsia, duodenal ulcer, stomach ulcer. Return to top

##### Endocrine system (moderate Alzheimer's disease)

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Infrequent: diabetes mellitus, goiter. Return to top

##### Hemic and lymphatic system (moderate Alzheimer's disease)

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Infrequent: anemia, thrombocythemia, thrombocytopenia, eosinophilia, erythrocytopenia. Return to top

##### Metabolic and nutritional disorders (moderate Alzheimer's disease)

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Frequent: dehydration;
Infrequent: gout, hypokalemia, increased creatine kinase, hyperglycemia, weight increase, increased lactate dehydrogenase. Return to top

##### Musculoskeletal system (moderate Alzheimer's disease)

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Frequent: bone fracture;
Infrequent: muscle weakness, muscle fasciculation. Return to top

##### Nervous system (moderate Alzheimer's disease)

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Frequent: delusions, tremor, irritability, paresthesia, aggression, vertigo, ataxia, increased libido, restlessness, abnormal crying, nervousness, aphasia;
Infrequent: cerebrovascular accident, intracranial hemorrhage, transient ischemic attack, emotional lability, neuralgia, coldness (localized), muscle spasm, dysphoria, gait abnormality, hypertonia, hypokinesia, neurodermatitis, numbness (localized), paranoia, dysarthria, dysphasia, hostility, decreased libido, melancholia, emotional withdrawal, nystagmus, pacing. Return to top

##### Respiratory system (moderate Alzheimer's disease)

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Frequent: dyspnea, sore throat, bronchitis;
Infrequent: epistaxis, post nasal drip, pneumonia, hyperventilation, pulmonary congestion, wheezing, hypoxia, pharyngitis, pleurisy, pulmonary collapse, sleep apnea, snoring. Return to top

##### Skin and appendages (moderate Alzheimer's disease)

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Frequent: pruritus, diaphoresis, urticaria;
Infrequent: dermatitis, erythema, skin discoloration, hyperkeratosis, alopecia, fungal dermatitis, herpes zoster, hirsutism, skin striae, night sweats, skin ulcer. Return to top

##### Special senses (moderate Alzheimer's disease)

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Frequent: cataract, eye irritation, vision blurred;
Infrequent: dry eyes, glaucoma, earache, tinnitus, blepharitis, decreased hearing, retinal hemorrhage, otitis externa, otitis media, bad taste, conjunctival hemorrhage, ear buzzing, motion sickness, spots before eyes. Return to top

##### Urogenital system (moderate Alzheimer's disease)

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Frequent: urinary incontinence, nocturia;
Infrequent: dysuria, hematuria, urinary urgency, metrorrhagia, cystitis, enuresis, prostate hypertrophy, pyelonephritis, inability to empty bladder, breast fibroadenosis, fibrocystic breast, mastitis, pyuria, renal failure, vaginitis. Return to top

### Severe Alzheimer's disease

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#### Adverse events leading to discontinuation (severe Alzheimer's disease)

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The rates of discontinuation from controlled clinical trials of Aricept® due to adverse events for the Aricept® patients were approximately 12% compared to 7% for placebo patients.
The most common adverse events leading to discontinuation, defined as those occurring in at least 2% of Aricept® patients and at twice the incidence seen in placebo patients, were anorexia (2% vs 1% placebo), nausea (2% vs <1% placebo), diarrhea (2% vs 0% placebo) and urinary tract infection (2% vs 1% placebo). Return to top

#### Most frequent adverse clinical events seen in association with the use of Aricept® (severe Alzheimer's disease)

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The most common adverse events, defined as those occurring at a frequency of at least 5% in patients receiving Aricept® and twice the placebo rate, are largely predicted by Aricept®'s cholinomimetic effects. These include diarrhea, anorexia, vomiting, nausea, and ecchymosis. These adverse events were often of mild intensity and transient, resolving during continued Aricept® treatment without the need for dose modification. Return to top

#### Other adverse events observed during clinical trials (severe Alzheimer's disease)

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These adverse events are not necessarily related to Aricept® treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies.

##### Body as a whole (severe Alzheimer's disease)

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Frequent: abdominal pain, asthenia, fungal infection, flu syndrome;
Infrequent: allergic reaction, cellulitis, malaise, sepsis, face edema, hernia. Return to top

##### Cardiovascular system (severe Alzheimer's disease)

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Frequent: hypotension, bradycardia, ECG abnormal, heart failure;
Infrequent: myocardial infarction, angina pectoris, atrial fibrillation, congestive heart failure, peripheral vascular disorder, supraventricular extrasystoles, ventricular extrasystoles, cardiomegaly. Return to top

##### Digestive system (severe Alzheimer's disease)

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Frequent: constipation, gastroenteritis, fecal incontinence, dyspepsia;
Infrequent: gamma glutamyl transpeptidase increase, gastritis, dysphagia, periodontitis, stomach ulcer, periodontal abscess, flatulence, liver function tests abnormal, eructation, esophagitis, rectal hemorrhage. Return to top

##### Endocrine system (severe Alzheimer's disease)

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Infrequent: diabetes mellitus. Return to top

##### Hemic and lymphatic system (severe Alzheimer's disease)

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Frequent: anemia;
Infrequent: leukocytosis. Return to top

##### Metabolic and nutritional disorders (severe Alzheimer's disease)

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Frequent: weight loss, peripheral edema, edema, lactic dehydrogenase increased, alkaline phosphatase increased;
Infrequent: hypercholesteremia, hypokalemia, hypoglycemia, weight gain, bilirubinemia, BUN increased, B12 deficiency anemia, cachexia, creatinine increased, gout, hyponatremia, hypoproteinemia, iron deficiency anemia, SGOT increased, SGPT increased. Return to top

##### Musculoskeletal system (severe Alzheimer's disease)

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Frequent: arthritis;
Infrequent: arthrosis, bone fracture, arthralgia, leg cramps, osteoporosis, myalgia. Return to top

##### Nervous system (severe Alzheimer's disease)

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Frequent: agitation, anxiety, tremor, convulsion, wandering, abnormal gait;
Infrequent: apathy, vertigo, delusions, abnormal dreams, cerebrovascular accident, increased salivation, ataxia, euphoria, vasodilatation, cerebral hemorrhage, cerebral infarction, cerebral ischemia, dementia, extrapyramidal syndrome, grand mal convulsion, hemiplegia, hypertonia, hypokinesia. Return to top

##### Respiratory system (severe Alzheimer's disease)

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Frequent: pharyngitis, pneumonia, cough increased, bronchitis;
Infrequent: dyspnea, rhinitis, asthma. Return to top

##### Skin and appendages (severe Alzheimer's disease)

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Frequent: rash, skin ulcer, pruritus;
Infrequent: psoriasis, skin discoloration, herpes zoster, dry skin, sweating, urticaria, vesiculobullous rash Return to top

##### Special senses (severe Alzheimer's disease)

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Infrequent: conjunctivitis, glaucoma, abnormal vision, ear pain, lacrimation disorder. Return to top

##### Urogenital system (severe Alzheimer's disease)

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Frequent: urinary tract infection, cystitis, hematuria, glycosuria;
Infrequent: vaginitis, dysuria, urinary frequency, albuminuria. Return to top

### Postintroduction reports

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Voluntary reports of adverse events temporally associated with Aricept® that have been received since market introduction that are not listed above, and that there is inadequate data to determine the causal relationship with the drug include the following: abdominal pain, agitation, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, and rash. Return to top

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Adapted from the FDA Package Insert.