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Exelon

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Exelon

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are described elsewhere in other sections of the prescribing information:

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.

Exelon has been administered to over 5,297 individuals during clinical trials worldwide. Of these, 4,326 patients have been treated for at least 3 months, 3,407 patients have been treated for at least 6 months, 2,150 patients have been treated for 1 year, 1,250 patients have been treated for 2 years, and 168 patients have been treated for over 3 years. With regard to exposure to the highest dose, 2,809 patients were exposed to doses of 10 mg to 12 mg, 2,615 patients treated for 3 months, 2,328 patients treated for 6 months, 1,378 patients treated for 1 year, 917 patients treated for 2 years, and 129 patients treated for over 3 years.

Mild to Moderate Alzheimer's Disease

Most Commonly Observed Adverse Reactions

The most common adverse reactions, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by Exelon's cholinergic effects. These include nausea, vomiting, anorexia, dyspepsia, and asthenia.

Gastrointestinal Adverse Reactions

Exelon use is associated with significant nausea, vomiting, and weight loss [see WARNINGS AND PRECAUTIONS].

Discontinuation Rates

The rate of discontinuation due to adverse events in controlled clinical trials of Exelon (rivastigmine tartrate) was 15% for patients receiving 6 mg to 12 mg per day compared to 5% for patients on placebo during forced weekly dose titration. While on a maintenance dose, the rates were 6% for patients on Exelon compared to 4% for those on placebo.

The most common adverse reactions 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 Reactions Leading to Withdrawal from Clinical Trials during Titration and Maintenance in Patients Receiving 6 mg to 12 mg per day Exelon Using a Forced-Dose Titration

Study Phase Titration Maintenance Overall
Exelon ≥ 6-12 mg/day
(n=1,189)
Placebo
(n=868)
Exelon ≥ 6-12 mg/day
(n=987)
Placebo
(n=788)
Exelon ≥ 6-12 mg/day
(n=1,189)
Placebo
(n=868)
Event/%Discontinuing
Nausea 8 < 1 1 < 1 8 1
Vomiting 4 < 1 1 < 1 5 < 1
Anorexia 2 0 1 < 1 3 < 1
Dizziness 2 < 1 1 < 1 2 < 1

Adverse Reactions Observed at an Incidence of at Least 2%

Table 2 lists treatment-emergent signs and symptoms that were reported in at least 2% of patients in placebo-controlled trials and for which the rate of occurrence was greater for patients treated with Exelon doses of 6 mg to 12 mg per day than for those treated with placebo. The prescriber should be aware that these figures cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis by which to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied.

In general, adverse reactions were less frequent later in the course of treatment.

No systematic effect of race or age could be determined from the incidence of adverse events in the controlled studies. Nausea, vomiting and weight loss were more frequent in women than men.

Table 2 : Proportion of Adverse Reactions Observed with a Frequency of ≥ 2% and at a Rate Greater than Placebo in Clinical Trials

Body System/Adverse Reaction Exelon (6-12 mg/day)
(n=1,189)
Placebo
(n=868)
Percent of Patients with any Adverse Event 92 79
Autonomic Nervous System
  Sweating Increased 4 1
  Syncope 3 2
Body as a Whole
  Fatigue 9 5
  Asthenia 6 2
  Malaise 5 2
  Weight Decrease** 3 < 1
Cardiovascular Disorders, General
  Hypertension 3 2
Central and Peripheral Nervous System
  Dizziness 21 11
  Headache 17 12
  Somnolence 5 3
  Tremor 4 1
Gastrointestinal System
  Nausea* 47 12
  Vomiting* 31 6
  Diarrhea 19 11
  Anorexia*** 17 3
  Abdominal Pain 13 6
  Dyspepsia 9 4
Psychiatric Disorders
  Insomnia 9 7
  Confusion 8 7
  Depression 6 4
  Anxiety 5 3
  Hallucination 4 3
  Aggressive Reaction 3 2
Resistance Mechanism Disorders
  Urinary Tract Infection 7 6
*Nausea and Vomiting: In the controlled clinical trials, 47% of the patients treated with an Exelon dose in the therapeutic range of 6 mg to 12 mg per day (n=1189) developed nausea (compared with 12% in placebo). A total of 31% of Exelontreated patients developed at least 1 episode of vomiting (compared with 6% for placebo). The rate of vomiting was higher during the titration phase (24% versus 3% for placebo) than in the maintenance phase (14% versus 3% for placebo). The rates were higher in women than men. Five percent of patients discontinued for vomiting, compared to less than 1% for patients on placebo. Vomiting was severe in 2% of Exelon-treated patients and was rated as mild or moderate each in 14% of patients. The rate of nausea was higher during the titration phase (43% versus 9% for placebo) than in the maintenance phase (17% versus 4% for placebo).
**Weight Decreased: In the controlled trials, approximately 26% of women on high doses of Exelon (greater than 9 mg per day) had weight loss equal to or greater than 7% of their baseline weight compared to 6% in the placebo-treated patients. About 18% of the males in the high-dose group experienced a similar degree of weight loss compared to 4% in placebo-treated patients. It is not clear how much of the weight loss was associated with anorexia, nausea, vomiting, and the diarrhea associated with the drug.
***Anorexia: In the controlled clinical trials, of the patients treated with an Exelon dose of 6 mg to 12 mg per day, 17% developed anorexia compared to 3% of the placebo patients. Neither the time course nor the severity of the anorexia is known.

Mild to Moderate Parkinson's Disease Dementia

Exelon has been administered to 779 individuals during clinical trials worldwide. Of these, 663 patients have been treated for at least 3 months, 476 patients have been treated for at least 6 months, and 313 patients have been treated for 1 year.

Most Commonly Observed Adverse Reactions

The most common adverse events, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by Exelon's cholinergic effects. These include nausea, vomiting, tremor, anorexia, and dizziness.

Discontinuation Rates

The rate of discontinuation due to adverse events in the single placebo-controlled trial of Exelon was 18.2% for patients receiving 3 mg to 12 mg per day compared to 11.2% for patients on placebo during the 24-week study.

The most frequent adverse events that led to discontinuation from this study, defined as those occurring in at least 1% of patients receiving Exelon and more frequent than those receiving placebo, were nausea (3.6% Exelon versus 0.6% placebo), vomiting (1.9% Exelon versus 0.6% placebo), and tremor (1.7% Exelon versus 0.0% placebo).

Adverse Reactions Observed at an Incidence of at Least 2%

Table 3 lists treatment-emergent signs and symptoms that were reported in at least 2% of patients in a single placebo-controlled trial and during the first 24 weeks of a 76-week open-label active-controlled trial for which the rate of occurrence was greater for patients treated with Exelon doses of 3 mg to 12 mg per day than for those treated with placebo in the placebo-controlled trial. The prescriber should be aware that these figures cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with 1 basis by which to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

In general, adverse reactions were less frequent later in the course of treatment.

Table 3 : Proportion of Adverse Reactions Observed at a Frequency ≥ 2% and Occurring at Rate Greater than Placebo in Clinical Trials

Body System/Adverse Reaction Active-Controlled Study Placebo-Controlled Study
Exelon (3-12 mg/day)
(n=294)
Exelon (3-12 mg/day)
(n=362)
Placebo
(n=179)
Percent of Patients with any Adverse Event 88 84 71
Gastrointestinal Disorders
  Nausea 38 29 11
  Vomiting 13 17 2
  Diarrhea 8 7 4
  Upper Abdominal Pain 4 4 1
  Salivary hypersecretion 2 1 0
General Disorders and Administrative Site Conditions
  Fall 10 6 6
  Fatigue 5 4 3
  Asthenia 4 2 1
Metabolism and Nutritional Disorders
  Anorexia - 6 3
  Decreased Appetite 5 8 5
  Dehydration 1 2 1
Nervous System Disorders
  Tremor 23 10 4
  Dizziness 8 6 1
  Headache 4 4 3
  Somnolence 6 4 3
  Parkinson's Disease (worsening) -* 3 1
  Bradykinesia 3 3 2
  Dyskinesia 3 1 1
  Cogwheel rigidity 3 1 0
  Hypokinesia 2 1 0
  Parkinsonism - 2 1
Psychiatric Disorders
  Anxiety 4 4 1
  Insomnia 2 3 2
  Restlessness 1 3 2
Skin and Subcutaneous Tissue Disorders
  Sweating increased 2 2 1
*Parkinson's disease (worsening) in the active-controlled study was assessed by reported pre-identified adverse events (tremor, cogwheel rigidity, fall), each of them listed with corresponding frequencies.

Other Adverse Events Observed During Clinical Trials

Mild to Moderate Alzheimer's Disease

Treatment-emergent signs and symptoms that occurred during 8 controlled clinical trials and 9 open-label trials in North America, Western Europe, Australia, South Africa, and Japan 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 WHO dictionary, and event frequencies were calculated across all studies. These categories are used in the listing below. The frequencies represent the proportion of 5,297 patients from these trials who experienced that event while receiving Exelon. All adverse events occurring in at least 6 patients (approximately 0.1%) are included, except for those already listed elsewhere in labeling, WHO terms too general to be informative, relatively minor events, or events unlikely 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 1/1,000 patients. These adverse events are not necessarily related to Exelon treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies.

Autonomic Nervous System: Infrequent: Increased saliva.

Body as a Whole: Frequent: Allergy, hot flushes.

Cardiovascular System: Frequent: Hypotension, postural hypotension.

Central and Peripheral Nervous System: Frequent: Abnormal gait, ataxia, paresthesia, convulsions. Infrequent: Dysphonia, hypoesthesia, migraine, nystagmus.

Gastrointestinal System: Frequent: Gastritis, constipation, flatulence. Infrequent: Gastric ulcer, gastroesophageal reflux, GI hemorrhage, hernia, melena, rectal hemorrhage, duodenal ulcer, hematemesis, pancreatitis.

Hearing and Vestibular Disorders: Frequent: Tinnitus.

Heart Rate and Rhythm Disorders: Frequent: Atrial fibrillation, bradycardia, palpitation. Infrequent: AV block, sick sinus syndrome, supraventricular tachycardia, extrasystoles, tachycardia.

Liver and Biliary System Disorders: Infrequent: Abnormal hepatic function tests.

Metabolic and Nutritional Disorders: Frequent: Dehydration, hypokalemia. Infrequent: Hyponatremia.

Musculoskeletal Disorders: Infrequent: Muscle weakness.

Myo-, Endo-, Pericardial and Valve Disorders: Frequent: Angina pectoris, myocardial infarction.

Psychiatric Disorders: Frequent: Confusion. Infrequent: Apathy, suicide attempt, increased libido, suicidal ideation.

Reproductive Disorders (Female and Male): Infrequent: Breast pain.

Resistance Mechanism Disorders: Infrequent: Herpes simplex, otitis media.

Respiratory System: Infrequent: Bronchospasm.

Skin and Appendages: Frequent: Rashes of various kinds (maculopapular, eczema, bullous, exfoliative, psoriaform, erythematous). Infrequent: Urticaria, contact dermatitis.

Urinary System Disorders: Frequent: Hematuria. Infrequent: Acute renal failure, dysuria.

Vascular (extracardiac) Disorders: Infrequent: Peripheral ischemia, intracranial hemorrhage.

Vision Disorders: Frequent: Cataract. Infrequent: Diplopia, glaucoma.

White Cell and Resistance Disorders: Infrequent: Lymphadenopathy.

Mild to Moderate Parkinson's Disease Dementia

Additional treatment-emergent adverse events in patients with Parkinson's disease dementia occurring in at least 1 patient (approximately 0.3%) are listed below, excluding events that are already listed above for the dementia of the Alzheimer's type or elsewhere in labeling, WHO terms too general to be informative, relatively minor events, or events unlikely 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 1/1,000 patients. These adverse events are not necessarily related to Exelon treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies.

Central and Peripheral Nervous System: Frequent: Transient ischemic attack.

Gastrointestinal System: Frequent: Dyspepsia. Infrequent: Fecaloma, dysphagia.

General Disorders and Administration Site Conditions: Frequent: Chest pain.

Liver and Biliary System Disorders: Infrequent: Elevated gamma-glutamyltransferase level.

Musculoskeletal Disorders: Frequent: Back pain. Infrequent: Muscle stiffness.

Psychiatric Disorders: Frequent: Agitation, depression.

Respiratory System: Frequent: Dyspnea. Infrequent: Cough.

Urinary System Disorders: Infrequent: Urinary incontinence.

Vision Disorders: Infrequent: Blurred vision.

Other Adverse Reactions Observed with Exelon Transdermal Patch

The following additional adverse reactions have been observed with Exelon transdermal patch:

Cerebrovascular accident, delirium, psychomotor hyperactivity, erythema, blister, dermatitis allergic.

Postmarketing Experience

Voluntary reports of adverse events temporally associated with Exelon that have been received since market introduction that are not listed above, and that may or may not be causally related to the drug include the following:

Hepatobiliary Disorders: Hepatitis.

Psychiatric Disorders: Aggression.

Skin and Appendages: Stevens-Johnson syndrome, disseminated cutaneous hypersensitivity reactions.

Read the Exelon (rivastigmine tartrate) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Cholinomimetic and Anticholinergic Drugs

Increased cholinergic effects may be expected when rivastigmine is given with other cholinomimetic drugs. Rivastigmine may also interfere with the activity of anticholinergic medications. Avoid concomitant use of rivastigmine with drugs having these pharmacologic effects unless deemed clinically necessary.

Last reviewed on RxList: 10/18/2013
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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Exelon - User Reviews

Exelon User Reviews

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