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Aricept (Donepezil Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

ADVERSE EVENTS LEADING TO DISCONTINUATION

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%.

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.

Table 1. Most Frequent Adverse Events Leading to Withdrawal from Controlled Clinical Trials by Dose Group
Dose Group Placebo 5 mg/day ARICEPT® 10 mg/day ARICEPT®
Patients Randomized 355 350 315
Event/% Discontinuing
    Nausea   1%   1% 3%
    Diarrhea   0% <1% 3%
    Vomiting <1% <1% 2%

MOST FREQUENT ADVERSE CLINICAL EVENTS SEEN IN ASSOCIATION WITH THE USE OF ARICEPT®

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 ARICEPT®'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 con-tinued ARICEPT® 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.

Table 2. Comparison of rates of adverse events in patients titrated to 10 mg/day over 1 and 6 weeks
  No titration One week titration Six week titration
Adverse Event Placebo (n=315) 5 mg/day (n=311) 10 mg/day (n=315) 10 mg/day (n=269)
Nausea 6% 5% 19% 6%
Diarrhea 5% 8% 15% 9%
Insomnia 6% 6% 14% 6%
Fatigue 3% 4% 8% 3%
Vomiting 3% 3% 8% 5%
Muscle
cramps
2% 6% 8% 3%
Anorexia 2% 3% 7% 3%

ADVERSE EVENTS REPORTED IN CONTROLLED TRIALS

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 ARICEPT® and for which the rate of occurrence was greater for ARICEPT® assigned than placebo assigned patients. In general, adverse events occurred more frequently in female patients and with advancing age.

Table 3. Adverse Events Reported in Controlled Clinical
Trials in at Least 2% of Patients Receiving ARICEPT® and at a Higher Frequency than Placebo-treated Patients
Body System/Adverse Event Placebo (n=355) ARICEPT® (n=747)
Percent of Patients with any Adverse Event 72 74
Body as a Whole
    Headache 9 10
    Pain, various locations 8 9
    Accident 6 7
    Fatigue 3 5
Cardiovascular System
    Syncope 1 2
Digestive System
    Nausea 6 11
    Diarrhea 5 10
    Vomiting 3 5
    Anorexia 2 4
Hemic and Lymphatic System
    Ecchymosis 3 4
Metabolic and Nutritional Systems
    Weight Decrease 1 3
Musculoskeletal System
    Muscle Cramps 2 6
    Arthritis 1 2
Nervous System
    Insomnia 6 9
    Dizziness 6 8
    Depression <1   3
    Abnormal Dreams 0 3
    Somnolence <1   2
Urogenital System
    Frequent Urination 1 2

OTHER ADVERSE EVENTS OBSERVED DURING CLINICAL TRIALS

ARICEPT® 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 ARICEPT®. 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 ARICEPT® 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.



REPORTS OF SUSPECTED ARICEPT SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Aricept. The information is not vetted and should not be considered as verified clinical evidence.

Possible Aricept side effects / adverse reactions in 74 year old male

Reported by a health professional (non-physician/pharmacist) from Germany on 2011-10-05

Patient: 74 year old male

Reactions: Refusal of Treatment by Patient, Rhabdomyolysis

Suspect drug(s):
Memantine
    Dosage: 20 mg (20 mg, 1 in 1 d), oral
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-07-12
    End date: 2011-08-11

Memantine
    Dosage: 5 mg (5 mg, 1 in 1 d), oral; increased dose, oral
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-06-21
    End date: 2011-06-01

Memantine
    Dosage: 5 mg (5 mg, 1 in 1 d), oral; increased dose, oral
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-06-01
    End date: 2011-07-11

Lyrica
    Dosage: 300 mg (150 mg, 2 in 1 d), oral
    Administration route: Oral
    Indication: Pain
    Start date: 2011-08-01
    End date: 2011-08-11

Gramalil (Tiapride Hydrochloride)
    Dosage: 25 mg (25 mg, 1 in 1 d),oral
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-04-25
    End date: 2011-08-12

Aricept
    Dosage: 5 mg (5 mg, 1 in 1 d), oral
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-01-31
    End date: 2011-08-11

Other drugs received by patient: Yoku-KAN-SAN (Herbal Extract Nos) (Herbal Extract Nos); Methycobal (Mecobalamin) (Mecobalamin)



Possible Aricept side effects / adverse reactions in 85 year old female

Reported by a physician from Japan on 2011-10-05

Patient: 85 year old female

Reactions: Epilepsy, Tremor

Adverse event resulted in: hospitalization

Suspect drug(s):
Aromasin
    Dosage: 25 mg, 1x/day
    Administration route: Oral
    Indication: Breast Cancer

Aricept
    Dosage: 10 mg, 1x/day
    Administration route: Oral
    Start date: 2011-08-04
    End date: 2011-09-08

Aricept
    Dosage: 5 mg, 1x/day
    Administration route: Oral
    Start date: 2011-06-16
    End date: 2011-08-03

Lansoprazole
    Dosage: 15 mg, 1x/day
    Administration route: Oral
    Indication: Gastrooesophageal Reflux Disease
    End date: 2011-09-08

Aricept
    Dosage: 3 mg, 1x/day
    Administration route: Oral
    Indication: Dementia Alzheimer's Type
    Start date: 2011-06-02
    End date: 2011-06-15

Other drugs received by patient: Candesartan Cilexetil; Depas



Possible Aricept side effects / adverse reactions in 64 year old female

Reported by a physician from Germany on 2011-10-10

Patient: 64 year old female weighing 60.0 kg (132.0 pounds)

Reactions: Hyperchromic Anaemia

Suspect drug(s):
Aricept
    Dosage: unk

Venlafaxine HCL
    Dosage: 300 mg daily
    Administration route: Oral
    Indication: Depression
    Start date: 2006-01-01



See index of all Aricept side effect reports >>

Drug label data at the top of this Page last updated: 2006-11-23

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