Exelon (rivastigmine, Exelon Patch)

Exelon and Exelon Patch (rivastigmine) are a reversible cholinesterase inhibitor used to treat mild to moderate dementia of the Alzheimer's type or mild to moderate dementia associated with Parkinson's disease.

Common side effects of Exelon and Exelon Patch

• include dizziness,
• diarrhea,
• headache,
• stomach pain,
• vomiting,
• nausea,
• weight loss, and
• loss of appetite.

Serious side effects of Exelon and Exelon Patch include

• seizures,
• decreased heart rate,
• low blood pressure,
• fainting, and
• depression.

Drug interactions of Exelon and Exelon Patch include drugs with anticholinergic effects and which cross into the brain, such as atropine, benztropine, and trihexyphenidyl because they oppose the effects of Exelon and should be avoided during therapy with Exelon and Exelon Patch.

Unlike donepezil, Exelon and Exelon Patch do not cause the blood levels of other medications to rise and increase their risk for side effects.

No studies have been performed with Exelon and Exelon Patch use in pregnant women. Physicians must weigh the potential benefit of prescribing Exelon to pregnant women against the potential risks to the fetus.

It is unknown if Exelon and Exelon Patch are secreted in breast milk. Consult your doctor before breastfeeding. 

• The most common side effects Exelon and Exelon Patch are:
  • Dizziness
  • Diarrhea
  • Headache
  • Stomach pain
  • Vomiting
  • Nausea
  • Weight loss
  • About one-half of patients who take Exelon and Exelon Patch develop symptoms of nausea, and about one-third vomit at least once, most commonly during the first few weeks of treatment as the dose is slowly increased.
  • Between one in five and one in four patients lose weight during rivastigmine therapy (about 7 to 10 pounds, on average).
  • One in six patients experiences a loss of appetite.
  • About one in fifty patients develops dizziness. Overall, 15% of patients (between one in seven and one in six) discontinue therapy due to side effects.
• Serious side effects include:
  • Seizures
  • Decreased heart rate
  • Low blood pressure
  • Fainting
  • Depression

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

• Gastrointestinal Adverse Reactions
• Allergic Dermatitis
• Other Adverse Reactions from Increased Cholinergic Activity

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 Common 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.

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

Adverse Reactions Observed at an Incidence of at Least 2%

• Table 2 lists adverse reactions that occurred 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.
• 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 reactions 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 Greater Than or Equal to 2% and at a Rate Greater than Placebo in Clinical Trials

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 Common 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,
  • tremor,
  • anorexia, and
  • dizziness.

Discontinuation Rates

• The rate of discontinuation due to adverse events in the single placebo-controlled trial of Exelon was 18% for patients receiving 3 mg to 12 mg per day compared to 11% for patients on placebo during the 24-week study.
• The most frequent adverse reactions 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 adverse reactions that occurred 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.
• In general, adverse reactions were less frequent later in the course of treatment.

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

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Exelon Capsules, Exelon Oral Solution, or Exelon Patch. 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.

• Cardiac Disorders: Tachycardia
• Hepatobiliary Disorders: Abnormal liver function tests, hepatitis
• Nervous System Disorders: seizure
• Psychiatric Disorders: Aggression, nightmares
• Skin and Subcutaneous Tissue Disorders: Allergic dermatitis, application site hypersensitivity (patch), blister, disseminated allergic dermatitis, Stevens-Johnson syndrome, urticaria

Metoclopramide

• Due to the risk of additive extrapyramidal adverse reactions, the concomitant use of metoclopramide and Exelon is not recommended.

Cholinomimetic And Anticholinergic Medications

• Exelon may increase the cholinergic effects of other cholinomimetic medications and may also interfere with the activity of anticholinergic medications (e.g., oxybutynin, tolterodine).
• Concomitant use of Exelon with medications having these pharmacologic effects is not recommended unless deemed clinically necessary.

Beta-Blockers

• Additive bradycardic effects resulting in syncope may occur when Exelon is used concomitantly with beta-blockers, especially cardioselective beta-blockers (including atenolol).
• Concomitant use of Exelon with beta-blockers is not recommended.