Donepezil Side Effects

Brand Names: Aricept, Aricept ODT

Please note - some side effects for Donepezil may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Donepezil - for the Consumer

Donepezil

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Donepezil:

Abnormal dreams; diarrhea; dizziness; loss of appetite; muscle cramps; nausea; tiredness; trouble sleeping; vomiting; weight loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; chest pain; decreased urination; depression; fainting; fever; seizures; severe dizziness or headache; shortness of breath; slow or irregular heartbeat; swelling of the hands, ankles, or feet; unusual bruising; tremor.

Donepezil Orally Disintegrating Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Donepezil Orally Disintegrating Tablets:

Abnormal dreams; diarrhea; dizziness; loss of appetite; muscle cramps; nausea; tiredness; trouble sleeping; vomiting; weight loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; chest pain; decreased urination; depression; fainting; fever; seizures; severe dizziness or headache; shortness of breath; slow or irregular heartbeat; swelling of the hands, ankles, or feet; unusual bruising; tremor.

Donepezil Side Effects - for the Professional

Donepezil

Mild to Moderate Alzheimer’s Disease

The rates of discontinuation from controlled clinical trials of Donepezil hydrochloride due to adverse events for the Donepezil hydrochloride 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 events leading to discontinuation, defined as those occurring in at least 2% of patients and at twice the incidence seen in placebo patients, are shown in Table 1.

The most common adverse events, 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 Donepezil hydrochloride’s cholinomimetic effects. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia. These adverse events were often of mild intensity and transient, resolving during continued Donepezil hydrochloride treatment without the need for dose modification.

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.

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

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. Table 3 lists treatment emergent signs and symptoms that were reported in at least 2% of patients in placebo-controlled trials who received Donepezil hydrochloride and for which the rate of occurrence was greater for Donepezil hydrochloride assigned than placebo assigned patients. In general, adverse events occurred more frequently in female patients and with advancing age.

Donepezil hydrochloride has been administered to over 1700 individuals during clinical trials worldwide. Approximately 1200 of these patients have been treated for at least 3 months and more than 1000 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 1214 days.

Treatment emergent signs and symptoms that occurred during 3 controlled clinical trials and two open-label trials in the United States were recorded as adverse events by the clinical investigators using terminology of their own choosing. To provide an overall estimate of the proportion of individuals having similar types of events, the events were grouped into a smaller number of standardized categories using a modified COSTART dictionary and event frequencies were calculated across all studies. These categories are used in the listing below. The frequencies represent the proportion of 900 patients from these trials who experienced that event while receiving Donepezil hydrochloride. All adverse events occurring at least twice are included, except for those already listed in Tables 2 or 3, COSTART terms too general to be informative, or events less likely to be drug caused. Events are classified by body system and listed using the following definitions: frequent adverse events - those occurring in at least 1/100 patients; infrequent adverse events - those occurring in 1/100 to 1/1000 patients. These adverse events are not necessarily related to Donepezil hydrochloride treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies. No important additional adverse events were seen in studies conducted outside the United States.

Body as a Whole:Frequent: influenza, chest pain, toothache; Infrequent: fever, edema face, periorbital edema, hernia hiatal, abscess, cellulitis, chills, generalized coldness, head fullness, listlessness.

Cardiovascular System: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.

Digestive System: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.

Endocrine System:Infrequent: diabetes mellitus, goiter.

Hemic and Lymphatic System:Infrequent: anemia, thrombocythemia, thrombocytopenia, eosinophilia, erythrocytopenia.

Metabolic and Nutritional Disorders:Frequent: dehydration; Infrequent: gout, hypokalemia, increased creatine kinase, hyperglycemia, weight increase, increased lactate dehydrogenase.

Musculoskeletal System:Frequent: bone fracture; Infrequent: muscle weakness, muscle fasciculation.

Nervous System: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.

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

Skin and Appendages:Frequent: pruritus, diaphoresis, urticaria; Infrequent: dermatitis, erythema, skin discoloration, hyperkeratosis, alopecia, fungal dermatitis, herpes zoster, hirsutism, skin striae, night sweats, skin ulcer.

Special Senses: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.

Urogenital System: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.

Postintroduction Reports

Voluntary reports of adverse events temporally associated with Donepezil hydrochloride 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.

Side Effects by Body System

Nervous system

Nervous system side effects have included headache (10%), insomnia (up to 9%), dizziness (up to 8%), hostility (3%), nervousness (3%), hallucinations (3%), somnolence (2%), depression (2%), confusion (2%), emotional lability (2%), and personality disorder (2%). Delusions, tremor, irritability, paresthesia, aggression, vertigo, ataxia, increased libido, restlessness, abnormal crying, and aphasia have been reported frequently. Cerebrovascular accident, intracranial hemorrhage, transient ischemic attack, neuralgia, coldness (localized), muscle spasm, dysphoria, gait abnormality, hypertonia, hypokinesia, neurodermatitis, numbness (localized), paranoia, dysarthria, dysphasia, decreased libido, melancholia, emotional withdrawal, nystagmus, and pacing have been reported infrequently. A case of Pisa Syndrome and a dose-related case of restless legs, mumbling, and stuttering have been reported. Two cases of worsening Parkinson's disease, a case report of convulsions, and a case report of delirium which may possibly have been associated with the use of donepezil have also been reported.

The case of restless legs, mumbling, and stuttering resolved after discontinuation of donepezil and there was a positive rechallenge.

Genitourinary

Genitourinary side effects including incontinence (7%) have been reported. Nocturia has been reported frequently. Dysuria, hematuria, urinary urgency, metrorrhagia, cystitis, enuresis, prostate hypertrophy, pyelonephritis, inability to empty bladder, breast fibroadenosis, fibrocystic breast, mastitis, pyuria, renal failure, and vaginitis have been reported infrequently.

Musculoskeletal

Musculoskeletal side effects including muscle cramps (6%) and back pain (3%) have been reported. Bone fracture has been reported frequently. Muscle weakness, and muscle fasciculation have been reported infrequently.

Gastrointestinal

Gastrointestinal side effects reported in at least 5% of patients include nausea, vomiting, diarrhea, and anorexia. Fecal incontinence, gastrointestinal bleeding, bloating, and epigastric pain have been reported frequently. 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, and stomach ulcer have been reported infrequently.

Dermatologic

Dermatologic side effects including eczema (3%) have been reported. Pruritus, diaphoresis, and urticaria have been reported frequently. Dermatitis, erythema, skin discoloration, hyperkeratosis, alopecia, fungal dermatitis, herpes zoster, hirsutism, skin striae, night sweats, and skin ulcer have been reported infrequently. A case of purpuric rash has been reported.

Cardiovascular

Cardiovascular side effects including hypertension (up to 3%), hemorrhage (up to 2%), and syncope (2%) have been reported. Hypotension and bradycardia have been reported in less than 1% of patients. Vasodilation, atrial fibrillation, hot flashes, and hypotension have been reported frequently. Angina pectoris, postural hypotension, myocardial infarction, AV block (first degree), congestive heart failure, arteritis, bradycardia, peripheral vascular disease, supraventricular tachycardia, and deep vein thrombosis have been reported infrequently.

Metabolic

Metabolic side effects including increased creatine phosphokinase (3%), dehydration (2%), and hyperlipemia (2%) have been reported. Gout, hypokalemia, increased creatine kinase, hyperglycemia, increased weight, and increased lactate dehydrogenase have been reported infrequently.

General

General side effects including fever (2%) and chest pain (2%) have been reported. Fever, facial edema, periorbital edema, hiatal hernia, abscess, cellulitis, chills, generalized coldness, head fullness, and listlessness have been reported infrequently. Side effects are generally mild in nature and well tolerated.

Frequency of common adverse effects may be influenced by the rate of titration.

Other

Other side effects including earache, tinnitus, decreased hearing, otitis externa, otitis media, bad taste, ear buzzing, and motion sickness have been reported infrequently. Cholinergic effects such as frequent urination have been reported in 2% of patients. Tremor, restlessness, hypertension, hypotension, ataxia, bradycardia, and diaphoresis have been reported in less than 1% of patients.

Ocular

Ocular side effects including cataract, eye irritation, and blurred vision have been reported frequently. Dry eyes, glaucoma, blepharitis, retinal hemorrhage, conjunctival hemorrhage, and spots before eyes have been reported infrequently.

Endocrine

Endocrine side effects including diabetes mellitus and goiter have been reported infrequently.

Hematologic

Hematologic side effects including anemia, thrombocythemia, thrombocytopenia, eosinophilia, and erythrocytopenia have been reported infrequently.

Respiratory

Respiratory side effects including dyspnea, sore throat, and bronchitis have been reported frequently. Epistaxis, post nasal drip, pneumonia, hyperventilation, pulmonary congestion, wheezing, hypoxia, pharyngitis, pleurisy, pulmonary collapse, sleep apnea, and snoring have been reported infrequently.

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