Exelon
EXELON- rivastigmine patch, extended release
Rebel Distributors Corp
1 INDICATIONS AND USAGE
1.1 Alzheimer’s Disease
Exelon Patch (rivastigmine transdermal system) is indicated for the treatment of mild to moderate dementia of the Alzheimer’s type.
1.2 Parkinson’s Disease Dementia
Exelon Patch (rivastigmine transdermal system) is indicated for the treatment of mild to moderate dementia associated with Parkinson’s disease.
The dementia of Parkinson’s disease is purportedly characterized by impairments in executive function, memory retrieval, and attention in patients with an established diagnosis of Parkinson’s disease. The diagnosis of dementia of Parkinson’s disease can be made reliably in patients in whom a progressive dementia syndrome occurs (without the necessity to document the specific deficits described above) at least 2 years after a diagnosis of Parkinson’s disease has been made, and in whom other causes of dementia have been ruled out.
2 DOSAGE AND ADMINISTRATION
2.1 Alzheimer’s Disease
| Rivastigmine Nominal Dose | Rivastigmine Content per Exelon Patch | Exelon Patch Size |
| 4.6 mg/24 hours | 9 mg | 5 cm2 |
| 9.5 mg/24 hours | 18 mg | 10 cm2 |
2.1.1
Initial Dose
Treatment is started with Exelon Patch 4.6 mg/24 hours.
After a minimum of four weeks of treatment and if well tolerated, this dose should be increased to Exelon Patch 9.5 mg/24 hours, which is the recommended effective dose.
2.1.2
Maintenance Dose
Dose increases should occur only after a minimum of 4 weeks at the previous dose, and only if the previous dose has been well tolerated. The maximum recommended dose is 9.5 mg/24 hours. Higher doses confer no appreciable additional benefit, and are associated with significant increase in the incidence of adverse events [see Adverse Reactions (6) ].
If adverse effects (e.g., nausea, vomiting, diarrhea, loss of appetite) cause intolerance during treatment, the patient should be instructed to discontinue treatment for several days and then restart at the same or next lower dose level. If treatment is interrupted for longer than several days, treatment should be reinitiated with the lowest daily dose and titrated as described above [also see Warnings and Precautions (5) ].
2.1.3
Switching from Capsules or Oral S
olution
Patients treated with Exelon capsules or oral solution may be switched to Exelon Patch as follows:
A patient who is on a total daily dose of less than 6 mg of oral rivastigmine can be switched to Exelon Patch 4.6 mg/24 hours.
A patient who is on a total daily dose of 6-12 mg of oral rivastigmine may be directly switched to Exelon Patch 9.5 mg/24 hours.
It is recommended to apply the first patch on the day following the last oral dose.
2.1.4
Method of Administration
Exelon Patch should be applied once a day to clean, dry, hairless, intact healthy skin in a place that will not be rubbed against by tight clothing. The upper or lower back is recommended as the site of application because the patch is less likely to be removed by the patient; however, when sites on the back are not accessible the patch can be applied to the upper arm or chest. The patch should not be applied to skin that is red, irritated, or cut. It is recommended that the site of patch application be changed daily to avoid potential irritation, although consecutive patches can be applied to the same anatomic site (e.g., another spot on the upper back).
The patch should be pressed down firmly until the edges stick well. The patch can be used in situations that include bathing and hot weather.
The patch should be replaced with a new one every 24 hours. Do not apply a new patch to that same spot for at least 14 days. Patients and caregivers should be instructed accordingly [see Patient Counseling Information (17) ].
2.1.5
Incompatibilities
To prevent interference with the adhesive properties of the patch, the patch should not be applied to a skin area where cream, lotion or powder has recently been applied.
2.1.6
Special Populations
2.1.6.1 Hepatic Impairment
Dosage adjustment is not necessary in hepatically impaired patients, as the dose of drug is individually titrated to tolerability.
2.1.6.2 Renal Impairment
No dose adjustment is necessary for patients with renal impairment.
2.1.6.3 Low Body Weight
Patients with body weight below 50 kg may experience more adverse events and may be more likely to discontinue due to adverse events. Particular caution should be exercised in titrating these patients above the recommended maintenance dose of Exelon Patch 9.5 mg/24 hours.
2.2 Parkinson’s Disease Dementia
See Dosage and Administration (2.1).
3 DOSAGE FORMS AND STRENGTHS
3.1 Dosage Form
Patch.
Each patch is a thin, matrix-type transdermal system consisting of three layers when worn by the patient. A fourth layer, the release liner, covers the adhesive layer prior to use and is removed at the time the system is applied to the skin.
The outside of the backing layer is beige and labeled for each dose as follows:
— “EXELON ® PATCH “4.6 mg/24 hours” and “AMCX”
— “EXELON ® PATCH “9.5 mg/24 hours” and “BHDI”
3.2 Dosage Strengths
Table 1 summarizes the available strengths and quantity of rivastigmine provided in each patch:
- Each 5 cm2 patch contains 9 mg rivastigmine base, with
in vivo release rate of 4.6 mg/24 hours. - Each 10 cm2 patch contains 18 mg rivastigmine base, with in vivo release rate of 9.5 mg/24 hours.
For a full list of excipients, see Description (11).
4 CONTRAINDICATIONS
4.1 Hypersensitivity
Exelon Patch (rivastigmine transdermal system) is contraindicated in patients with known hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation [see Description (11) ].
5 WARNINGS AND PRECAUTIONS
5.1 Gastrointestinal Adverse Reactions
At higher than recommended doses , Exelon Patch (rivastigmine transdermal system) use is associated with significant gastrointestinal adverse reactions, including nausea , vomiting, diarrhea, anorexia/decreased appetite and weight loss. For this re ason, patients administered Exelon Patch should always be started at a dose of 4.6 mg/24 hours and titrated to th e maintenance dose of 9.5 mg/24 hours . If treatment is interrupted for longer than several days, treatment should be reinitia ted with the lowest daily dose [ see Dosage and Administration (2) ] to reduce the possibility of severe vomiting and its potentially serious sequelae (e.g., there has been one post-marketing report of severe vomiting with esophageal rupture following inappropriate reinitiation of treatment with a 4.5 –mg dose of an oral formulation after 8 weeks of treatment interruption).
At higher than recommended doses , c aregivers should be advised of the high incidence of nausea and vomiting associated with the use of Exelon Patch along with the possibility of anorexia and weight loss . Caregivers should be encouraged to monitor for these adverse events and inform the physician if they occur. It is critical to inform caregivers that if therapy has been interrupted for more than several days, the next dose should not be administered until they have discussed this with the physician.
5.1.1
Nausea and Vomiting
In the controlled clinical trial, 7% of patients treated with Exelon Patch 9.5 mg/24 hours developed nausea, as compared to 23% of patients who received the Exelon capsule at doses up to 6 mg BID and 5% of those who received placebo. In the same clinical trial, 6% of patients treated with Exelon Patch 9.5 mg/24 hours developed vomiting, as compared with 17% of patients who received the Exelon capsule at doses up to 6 mg BID and 3% of those who received placebo. The proportion of patients who discontinued treatment on account of vomiting was 0% of the patients who received Exelon Patch 9.5 mg/24 hours as well as 2% of patients who received the Exelon capsule at doses up to 6 mg BID and 0% of those who received placebo. Vomiting was severe in 0% of patients who received Exelon Patch 9.5 mg/24 hours and 1% of patients who received the Exelon capsule at doses up to 6 mg BID and 0% of those who received placebo.
In the same clinical trial, 21% of patients treated with the higher dose of Exelon Patch 17.4 mg/24 hours developed nausea, 19% developed vomiting, and the proportion of these patients who discontinued treatment on account of vomiting was 2%. Vomiting was severe in 1% of patients treated with Exelon Patch 17.4 mg/24 hours.
5.1.2
Weight Loss
In the controlled clinical trial, the proportion of patients who had weight loss equal to or greater than 7% of their baseline weight was 8% of those treated with Exelon Patch 9.5 mg/24 hours, 11% of patients who received the Exelon capsule at doses up to 6 mg BID and 6% of those who received placebo.
In the same clinical trial, 12% of those treated with 17.4 mg/24 hours had weight loss equal to or greater than 7% of their baseline weight. It is not clear how much of the weight loss was associated with anorexia, nausea, vomiting, and the diarrhea associated with the drug.
5.1.3
Diarrhea
In the controlled clinical trial, 6% of patients treated with Exelon Patch 9.5 mg/24 hours developed diarrhea, as compared with 5% of patients who received the Exelon capsule at doses up to 6 mg BID, 10% of those treated with 17.4 mg/24 hours and 3% of those who received placebo.
5.1.4
Anorexia/Decreased Appetite
In the controlled clinical trial, 3% of patients treated with Exelon Patch 9.5 mg/24 hours were recorded as developing decreased appetite or anorexia, as compared with 9% of patients who received the Exelon capsule at doses up to 6 mg BID, 9% of those treated with Exelon Patch 17.4 mg/24 hours and 2% of those who received placebo.
5.1.5
Peptic Ulcers/Gastrointestinal Bleeding
Because of their pharmacological action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of Exelon have shown no significant increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
5.2
Anesthesia
Exelon, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
5.3
Cardiovascular Conditions
Drugs that increase cholinergic activity may have vagotonic effects on heart rate (e.g., bradycardia). The potential for this action may be particularly important to patients with sick sinus syndrome or other supraventricular cardiac conduction conditions. In clinical trials, Exelon was not associated with any increased incidence of cardiovascular adverse events, heart rate or blood pressure changes, or ECG abnormalities.
5.
4
Genitourinary Conditions
Although this was not observed in clinical trials of Exelon, drugs that increase cholinergic activity may cause urinary obstruction.
5.
5
Neurological Conditions
5.5.1
Seizures
Drugs that increase cholinergic activity are believed to have some potential for causing seizures. However, seizure activity also may be a manifestation of Alzheimer’s disease.
5.5.2
Extrapyramidal Symptoms
Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms. Worsening of parkinsonian symptoms, particularly tremor, has been observed in patients with dementia associated with Parkinson’s disease who were treated with Exelon capsules.
5.
6
Pulmonary Conditions
Like other drugs that increase cholinergic activity, Exelon should be used with care in patients with a history of asthma or obstructive pulmonary disease.
5.
7
Effects on Ability to Drive and Use Machines
Dementia may cause gradual impairment of driving performance or compromise the ability to use machinery. The administration of rivastigmine may also result in adverse events that are detrimental to these functions. Thus, the ability to continue driving or operating machinery should be routinely evaluated by the treating physician.
5.
8
Special Populations
5.8.1
Low Body Weight
Patients with body weight below 50 kg may experience more adverse events and may be more likely to discontinue due to adverse events. Particular caution should be exercised in titrating these patients above the recommended maintenance dose of the Exelon Patch 9.5 mg/24 hours.
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