August 28, 2015
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Aricept

"The costs of caring for people with dementia in the United States in 2010 were between $159 billion to $215 billion, and those costs could rise dramatically with the increase in the numbers of older people in coming decades, according to estimate"...

Aricept




Side Effects
Interactions

SIDE EFFECTS

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

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 Reaction Placebo
(n=355) %
5 mg/day ARICEPT
(n=350) %
10 mg/day ARICEPT
(n=315) %
Nausea 1 1 3
Diarrhea 0 < 1 3
Vomiting < 1 < 1 2

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 nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue, and anorexia. 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 Reaction No titration One week titration Six week titration
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

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 Reaction Placebo
(n=355)%
ARICEPT
(n=747)%
Percent of Patients with any Adverse Reaction 72 74
  Nausea 6 11
  Diarrhea 5 10
  Headache 9 10
  Insomnia 6 9
  Pain, various locations 8 9
  Dizziness 6 8
  Accident 6 7
  Muscle Cramps 2 6
  Fatigue 3 5
  Vomiting 3 5
  Anorexia 2 4
  Ecchymosis 3 4
  Abnormal Dreams 0 3
  Depression < 1 3
  Weight Loss 1 3
  Arthritis 1 2
  Frequent Urination 1 2
  Somnolence < 1 2
  Syncope 1 2

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 anorexia (2% vs. 1% placebo), nausea (2% vs. < 1% placebo), diarrhea (2% vs. 0% placebo), and urinary tract infection (2% vs. 1% placebo).

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 Reaction Placebo
(n=392) %
ARICEPT
(n=501) %
Percent of Patients with any Adverse Reaction 73 81
  Accident 12 13
  Infection 9 11
  Diarrhea 4 10
  Anorexia 4 8
  Vomiting 4 8
  Nausea 2 6
  Insomnia 4 5
  Ecchymosis 2 5
  Headache 3 4
  Hypertension 2 3
  Pain 2 3
  Back Pain 2 3
  Eczema 2 3
  Hallucinations 1 3
  Hostility 2 3
  Increase in Creatine Phosphokinase 1 3
  Nervousness 2 3
  Fever 1 2
  Chest Pain < 1 2
  Confusion 1 2
  Dehydration 1 2
  Depression 1 2
  Dizziness 1 2
  Emotional Lability 1 2
  Hemorrhage 1 2
  Hyperlipemia < 1 2
  Personality Disorder 1 2
  Somnolence 1 2
  Syncope 1 2
  Urinary Incontinence 1 2

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 Reaction 23 mg/day ARICEPT
(n=963) %
10 mg/day ARICEPT
(n=471) %
Vomiting 3 0
Diarrhea 2 0
Nausea 2 0
Dizziness 1 0

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 Reaction 23 mg/day ARICEPT
(n=963)%
10 mg/day ARICEPT
(n=471)%
Percent of Patients with any Adverse Reaction 74 64
  Nausea 12 3
  Vomiting 9 3
  Diarrhea 8 5
  Anorexia 5 2

Postmarketing Experience

The following adverse reactions have been identified during post-approval use 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.

Abdominal pain, agitation, aggression, cholecystitis, confusion, convulsions, hallucinations, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash, rhabdomyolysis, QTc prolongation, and torsade de pointes.

Read the Aricept (donepezil hydrochloride) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

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.

Read the Aricept Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 8/5/2015
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions

Aricept - User Reviews

Aricept User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Aricept sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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