Exelon Patch

Exelon Patch (rivastigmine transdermal system) is indicated for the treatment of mild to moderate dementia of the Alzheimer’s type.

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.

      See Dosage and Administration (2.1).

      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”

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 ul of excipients, see Description (11).

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)].

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 reason, patients administered Exelon Patch should always be started at a dose of 4.6 mg/24 hours and titrated to the maintenance dose of 9.5 mg/24 hours. If treatment is interrupted for longer than several days, treatment should be reinitiated 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, caregivers 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.

Exelon, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.

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.

Although this was not observed in clinical trials of Exelon, drugs that increase cholinergic activity may cause urinary obstruction.

Like other drugs that increase cholinergic activity, Exelon should be used with care in patients with a history of asthma or obstructive pulmonary disease.

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.

Significant gastrointestinal adverse reactions including nausea, vomiting, anorexia, and weight loss have been reported with the Exelon Patch at higher than recommended doses [see Warnings and Precautions (5.1)].

Exelon Patch has been administered to 1071 patients with Alzheimer’s disease during clinical trials worldwide. Of these, 869 patients have been treated for at least 3 months, 706 patients have been treated for at least 6 months, and 212 patients have been treated for 1 year.

Treatment-emergent signs and symptoms that occurred during 1 controlled and 4 open-label trials in North America, Europe, Latin America, Asia 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 the MedDRA dictionary, and event frequencies were calculated across all studies. These categories are used in the uling below. The frequencies represent the proportion of 1071 patients from these trials who experienced that event while receiving Exelon Patch. All patch doses are pooled.

All adverse events occurring in at least 1 patient (approximately 0.1%) are included, except for those already uled elsewhere in labeling, too general to be informative, or relatively minor events.

Events are classified by system organ class and uled using the following definitions: Frequent – those occurring in at least 1/100 patients; Infrequent – those occurring in 1/100 to 1/1,000 patients. These adverse events are not necessarily related to Exelon Patch treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies.

Blood and Lymphatic System Disorders: Frequent: Anemia.

Cardiac Disorders: Infrequent: Angina pectoris, cardiac failure, bradycardia, atrial fibrillation, supraventricular extrasystoles, myocardial infarction, tachycardia, arrhythmia, atrioventricular block.

Ear and Labyrinth Disorders: Infrequent: Tinnitus.

Eye Disorders: Infrequent: Cataract, glaucoma, vision blurred.

Gastrointestinal System: Frequent: Constipation, gastritis. Infrequent: Gastroesophageal reflux disease, hematochezia, peptic ulcer, hematemesis, pancreatitis, salivary hypersecretion.

General Disorders and Administration Site Conditions: Infrequent: Application site dermatitis, application site irritation, peripheral edema, chest pain, application site eczema, hyperpyrexia.

Hepatobiliary Disorders: Infrequent: Cholecystitis.

Infections and Infestations: Frequent: Nasopharyngitis, pneumonia. Infrequent: Diverticulitis.

Injury, Poisoning and Procedural Complications: Frequent: Fall. Infrequent: Hip fracture, subdural hematoma.

Investigations: Infrequent: Blood creatine phosphokinase increased, lipase increased, blood amylase increased, electrocardiogram QT prolonged.

Metabolic and Nutritional Disorders: Frequent: Dehydration Infrequent: Hyperlipidemia, hypokalemia, hyponatremia.

Musculoskeletal and Connective Tissue Disorders: Infrequent: Arthralgia, muscle spasms, myalgia.

Nervous System Disorders: Frequent: Tremor. Infrequent: Migraine, parkinsonism, epilepsy.

Psychiatric Disorders: Infrequent: Delusion.

Renal and Urinary Disorders: Frequent: Urinary incontinence. Infrequent: Pollakiuria, hematuria, nocturia, renal failure.

Reproductive System and Breast Disorders: Infrequent: Benign prostatic hyperplasia.

Respiratory, Thoracic, and Mediastinal Disorders: Infrequent: Dyspnea, bronchospasm, chronic obstructive pulmonary disease.

Skin and Subcutaneous Tissue Disorders: Frequent: Pruritus. Infrequent: Erythema, eczema, dermatitis, rash erythematous, skin ulcer.

Vascular Disorders: Infrequent: Hypotension.

No specific interaction studies have been conducted with Exelon Patch (rivastigmine transdermal system).

Rivastigmine is primarily metabolized through hydrolysis by esterases. Minimal metabolism occurs via the major cytochrome P450 isoenzymes. Based on in-vitro studies, no pharmacokinetic drug interactions with drugs metabolized by the following isoenzyme systems are expected: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, CYP2C9, CYP2C8, or CYP2C19.

No pharmacokinetic interaction was observed between rivastigmine taken orally and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine.

Drugs that induce or inhibit CYP450 metabolism are not expected to alter the metabolism of rivastigmine.

Population PK analysis with a database of 625 patients showed that the pharmacokinetics of rivastigmine taken orally were not influenced by commonly prescribed medications such as antacids (n=77), antihypertensives (n=72), ß-blockers (n=42), calcium channel blockers (n=75), antidiabetics (n=21), nonsteroidal anti-inflammatory drugs (n=79), estrogens (n=70), salicylate analgesics (n=177), antianginals (n=35) and antihistamines (n=15).

In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other cholinomimetic drugs and might interfere with the activity of anticholinergic medications. A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol.

Milk transfer studies in animals have not been conducted with dermal rivastigmine. In rats given rivastigmine orally, concentrations of rivastigmine plus metabolites were approximately two times higher in milk than in plasma. It is not known whether rivastigmine is excreted in human breast milk. Exelon Patch (rivastigmine transdermal system) has no indication for use in nursing mothers.

There are no adequate and well-controlled trials documenting the safety and efficacy of Exelon in any illness occurring in children.

Age had no impact on the exposure to rivastigmine in Alzheimer’s disease patients treated with Exelon Patch.

No pharmacokinetic study was conducted with Exelon Patch in subjects with hepatic impairment. Following a single 3-mg dose, mean oral clearance of rivastigmine was 60% lower in hepatically impaired patients (n=10, biopsy proven) than in healthy subjects (n=10). After multiple 6-mg BID oral dosing, the mean clearance of rivastigmine was 65% lower in mild (n=7, Child-Pugh score 5-6) and moderate (n=3, Child-Pugh score 7-9) hepatically impaired patients (biopsy proven, liver cirrhosis) than in healthy subjects (n=10). Dosage adjustment is not necessary in hepatically impaired patients as the dose of drug is individually titrated to tolerability.

No study was conducted with Exelon Patch in subjects with renal impairment. Following a single 3-mg dose, mean oral clearance of rivastigmine is 64% lower in moderately impaired renal patients (n=8, GFR=10-50 mL/min) than in healthy subjects (n=10, GFR≥60 mL/min); Cl/F=1.7 L/min (cv=45%) and 4.8 L/min (cv=80%), respectively. In severely impaired renal patients (n=8, GFR<10 mL/min), mean oral clearance of rivastigmine is 43% higher than in healthy subjects (n=10, GFR≥60 mL/min); Cl/F=6.9 L/min and 4.8 L/min, respectively. For unexplained reasons, the severely impaired renal patients had a higher clearance of rivastigmine than moderately impaired patients. However, dosage adjustment may not be necessary in renally impaired patients as the dose of the drug is individually titrated to tolerability.

Rivastigmine exposure is higher in subjects with low body weight. Compared to a patient with a body weight of 65 kg, the rivastigmine steady-state concentrations in a patient with a body weight of 35 kg would be approximately doubled, while for a patient with a body weight of 100 kg the concentrations would be approximately halved. This suggests special attention should be given to patients with very low body weight during up-titration [see Dosage and Administration (2)].

No specific pharmacokinetic study was conducted to investigate the effect of gender and race on the disposition of Exelon, but a population pharmacokinetic analysis indicates that gender (n=277 males and 348 females) and race (n=575 White, 34 Black, 4 Asian, and 12 Other) did not affect the clearance of Exelon administered orally. Similar results were seen with analyses of pharmacokinetic data obtained after the administration of Exelon Patch.

Population pharmacokinetic analysis showed that nicotine use increases the oral clearance of rivastigmine by 23% (n=75 Smokers and 549 Nonsmokers). No dose adjustment is necessary as the dose of the drug is individually titrated to tolerability.

Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug. As in any case of overdose, general supportive measures should be utilized.

As rivastigmine has a plasma half-life of about 3.4 hours after patch administration and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose the patch should be immediately removed and no further patch should be applied for the next 24 hours.

As in any case of overdose, general supportive measures should be utilized. Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Atypical responses in blood pressure and heart rate have been reported with other drugs that increase cholinergic activity when coadministered with quaternary anticholinergics such as glycopyrrolate. Due to the short plasma elimination half-life of rivastigmine after patch administration, dialysis (hemodialysis, peritoneal dialysis, or hemofiltration) would not be clinically indicated in the event of an overdose.

In overdose accompanied by severe nausea and vomiting, the use of antiemetics should be considered. In a documented case of an oral 46-mg overdose with Exelon, the patient experienced vomiting, incontinence, hypertension, psychomotor retardation, and loss of consciousness. The patient fully recovered within 24 hours and conservative management was all that was required for treatment.

There are currently no data on overdose with Exelon Patch (rivastigmine transdermal system).

Exelon Patch (rivastigmine transdermal system) is a reversible cholinesterase inhibitor and is known chemically as (S)- 3-[1-(dimethylamino) ethyl]phenyl ethylmethylcarbamate. It has an empirical formula of C₁₄H₂₂N₂O₂ as the base and a molecular weight of 250.34 (as the base). Rivastigmine is a viscous, clear, and colorless to yellow to very slightly brown liquid that is sparingly soluble in water and very soluble in ethanol, acetonitrile, n-octanol and ethyl acetate.

The distribution coefficient at 37°C in n-octanol/phosphate buffer solution pH 7 is 4.27.

Exelon Patch is for transdermal administration. The patch comprises a four-layer laminate containing the backing layer, drug matrix, adhesive matrix and overlapping release liner. The release liner is removed and discarded prior to use. See Figure 1 for a detailed illustration.

Excipients within the formulation include acrylic copolymer, poly(butylmethacrylate, methylmethacrylate), silicone adhesive applied to a flexible polymer backing film, silicone oil, and vitamin E.

Pathological changes in dementia of the Alzheimer’s type and dementia associated with Parkinson’s disease involve cholinergic neuronal pathways that project from the basal forebrain to the cerebral cortex and hippocampus. These pathways are thought to be intricately involved in memory, attention, learning, and other cognitive processes. While the precise mechanism of action for rivastigmine is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this proposed mechanism is correct, the effect of rivastigmine may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that rivastigmine alters the course of the underlying dementing process.

After a 6-mg oral dose of rivastigmine in humans, anticholinesterase activity is present in CSF for about 10 hours, with a maximum inhibition of about 60% 5 hours after dosing.

In-vitro and in-vivo studies demonstrate that the inhibition of cholinesterase by rivastigmine is not affected by the concomitant administration of memantine, an N-methyl-D-aspartate receptor antagonist.

In oral carcinogenicity studies conducted at doses up to 1.1 mg base/kg/day in rats and 1.6 mg base/kg/day in mice, rivastigmine was not carcinogenic.

In a dermal carcinogenicity study conducted at doses up to 0.75 mg base/kg/day in mice, rivastigmine was not carcinogenic. The mean rivastigmine plasma exposure (AUC) at this dose was 0.3-0.4 times that observed in Alzheimer’s disease patients at the recommended clinical dose (one Exelon Patch 9.5 mg/24 hours).

Rivastigmine was clastogenic in two in-vitro assays in the presence, but not the absence, of metabolic activation. It caused structural chromosomal aberrations in V79 Chinese hamster lung cells and both structural and numerical (polyploidy) chromosomal aberrations in human peripheral blood lymphocytes. Rivastigmine was not genotoxic in three in-vitro assays: the Ames test, the unscheduled DNA synthesis (UDS) test in rat hepatocytes (a test for induction of DNA repair synthesis), and the HGPRT test in V79 Chinese hamster cells. Rivastigmine was not clastogenic in the in-vivo mouse micronucleus test.

No fertility or reproduction studies have been conducted in animals treated with dermal rivastigmine. Rivastigmine had no effect on fertility or reproductive performance in rats at oral doses up to 1.1 mg base/kg/day.

The effectiveness of the Exelon Patch (rivastigmine transdermal system) in Alzheimer’s disease and dementia associated with Parkinson’s disease was based on the results of a single controlled trial in patients with Alzheimer’s disease (see below) as well as on three controlled trials of the immediate-release capsule in Alzheimer’s disease and one controlled trial in dementia associated with Parkinson’s disease (see package insert for the Exelon capsules and oral solution for details).

This was a randomized double-blind clinical investigation in patients with Alzheimer’s disease [diagnosed by NINCDS-ADRDA and DSM-IV criteria, Mini-Mental Status Examination (MMSE) score ≥10 and ≤20]. The mean age of patients participating in this trial was 74 years with a range of 50-90 years. Approximately 67% of patients were women and 33% were men. The racial distribution was Caucasian 75%, Black 1%, Oriental 9% and Other Races 15%.

The effectiveness of the Exelon Patch (rivastigmine transdermal system) was evaluated in this study using a dual outcome assessment strategy.

The ability of the Exelon Patch to improve cognitive performance was assessed with the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog), a multi-li instrument that has been extensively validated in longitudinal cohorts of Alzheimer’s disease patients. The ADAS-Cog examines selected aspects of cognitive performance including elements of memory, orientation, attention, reasoning, language and praxis. The ADAS-Cog scoring range is from 0-70, with higher scores indicating greater cognitive impairment. Elderly normal adults may score as low as 0 or 1, but it is not unusual for non-demented adults to score slightly higher.

The ability of the Exelon Patch to produce an overall clinical effect was assessed using the Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC). The ADCS-CGIC is a more standardized form of CIBIC-Plus and is also scored as a seven-point categorical rating, ranging from a score of 1, indicating “markedly improved”, to a score of 4, indicating “no change” to a score of 7, indicating “marked worsening”.

In this study, 1195 patients were randomized to one of the following 4 treatments: Exelon Patch 9.5 mg/24 hours, Exelon Patch 17.4 mg/24 hours, Exelon capsules in a dose of 6 mg BID, or placebo. This 24-week study was divided into a 16-week titration phase followed by an 8-week maintenance phase. In the active treatment arms of this study, doses below the target dose were permitted during the maintenance phase in the event of poor tolerability.

     Patch 4.6 mg/24 hours

Each patch of 5 cm² contains 9 mg rivastigmine base with in-vivo release rate of 4.6 mg/24 hours.

      Carton of 30………………………NDC 0078-0501-15

     Patch 9.5 mg/24 hours

Each patch of 10 cm² contains 18 mg rivastigmine base with in-vivo release rate of 9.5 mg/24 hours.

Carton of 30………………………..NDC 0078-0502-15

Store at 25°C (77°F); excursions permitted to 15-30°C
(59-86°F) [see USP Controlled Room Temperature].

Keep Exelon Patch (rivastigmine transdermal system) in the individual sealed pouch until use.

Used systems should be folded, with the adhesive surfaces pressed together, and discarded safely.

Each pouch contains one patch.

Patient information is printed in section 17.8. To assure safe and effective use of Exelon Patch, this information and instructions provided in the patient information section should be discussed with patients.

Patients or caregivers should be informed of the importance of applying the correct dose on the correct part of their body. They should be instructed to rotate the application site in order to minimize skin irritation. The same site should not be used within 14 days. Exelon Patch should be replaced every 24 hours and the time of day should be consistent. It may be helpful for this to be part of a daily routine, such as the daily bath or shower.

Patients or caregivers should be told to avoid exposure of the patch to external heat sources (excess sunlight, saunas, solariums) for long periods of time.

Patients or caregivers should be instructed to fold the patch in half after use. Return the used patch to its original pouch and discard it out of the reach and sight of children and pets. They should also be informed that drug still remains in the patch after 24-hour usage. They should be instructed to avoid eye contact and to wash their hands after handling the patch.

Patients or caregivers should be told that while wearing Exelon Patch they should not be taking Exelon capsules or Exelon oral solution or other drugs with cholinergic effects.

Patients or caregivers should be informed of the potential gastrointestinal adverse events such as nausea, vomiting and diarrhea. Patients and caregivers should be instructed to observe for these adverse reactions at all times, in particular when treatment is initiated or the dose is increased. Patients and caregivers should be instructed to inform their physician if these adverse events persist as a dose adjustment/
reduction may be required.

Patients or caregivers should be informed that Exelon Patch may affect the patient’s appetite and/or the patient’s weight. Any loss of appetite or weight reduction needs to be monitored.

If the patient has missed a dose, he/she should be instructed to apply a new patch immediately. They may apply the next patch at the usual time the next day. Patients should not apply two patches to make up for one missed.

If treatment has been missed for several days, the patient or caregiver should be informed to restart treatment with the starting patch dose of 4.6 mg/24 hours. Titration to the next patch dose should proceed after 4 weeks [see Dosage and Administration (2.1)].

     What is Exelon Patch and what it is used for?

Exelon belongs to a class of substances called cholinesterase inhibitors. It is used for the treatment of memory disorders in patients with Alzheimer’s disease or with Parkinson’s disease.

     Before you apply Exelon Patch:

Carefully follow all instructions given to you by your doctor, even if they differ from the information contained in this leaflet.

Read the following information before you apply Exelon Patch.

     Do not apply Exelon Patch in the following cases:

If you know that you are allergic (hypersensitive) to rivastigmine (the active substance in Exelon Patch) or to any of the other ingredients of Exelon Patch [see Description (11)].

If you have ever had an allergic reaction to a similar type of medicine.

If this applies to you, tell your doctor without applying Exelon Patch.

Take special care with Exelon Patch if:

• You have, or ever had an irregular heartbeat.
  
• You have, or ever had an active stomach ulcer.
  
• You have, or ever had difficulties in passing urine.
  
• You have, or ever had seizures.
  
• You have, or ever had asthma or a severe respiratory disease.
  
• You suffer from trembling.
  
• You have a low body weight.
  
• You have impaired liver function.

If any of these apply to you, your doctor may need to monitor you more closely while you are on this medicine.

If you have not been applying Exelon Patch for several days do not apply the next patch until you have talked to your doctor.

Exelon Patch with food and drink:

Food or drink does not affect Exelon Patch because rivastigmine enters your bloodstream through your skin.

Exelon Patch and older people:

Exelon Patch can be used by patients over the age of 65.

Exelon Patch and children:

The use of Exelon Patch in children is not recommended.

Pregnant women:

Tell your doctor if you are pregnant or planning to become pregnant. In the event of pregnancy, the benefits of Exelon Patch must be assessed against the possible effects on your unborn child. Ask your doctor or pharmacist for advice before taking any medicine during pregnancy.

     Breast-feeding mothers:

You should not breast-feed during treatment with Exelon Patch. Ask your doctor or pharmacist for advice before taking any medicine while you are breast-feeding.

     Driving and using machines:

Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. Exelon Patch may cause dizziness and drowsiness, mainly at the start of treatment or when increasing the dose. If you feel dizzy or drowsy, do not drive, use machines or perform any other tasks that require your attention.

     Taking other medicines:

Tell your doctor or pharmacist about any other medicines you are taking or have recently taken, including any you get without a prescription.

Exelon Patch should not be given together with other medicines with similar effects (cholinomimetic agents) or with anticholinergic medicines.

If you need to have surgery while using Exelon Patch, you should inform your doctor because Exelon Patch may exaggerate the effects of some muscle relaxants during anesthesia.

     How to use Exelon Patch:

Follow all instructions given to you by your doctor carefully, even if they differ from the ones given in this leaflet.

This medicine must not be given to children.

Do not eat Exelon Patch.

You must remove Exelon Patch from the previous day before applying a new one. Do not cut the patch into pieces.

     How to start treatment:

Your doctor will tell you which Exelon Patch is suitable for you. Treatment usually starts with Exelon Patch 4.6 mg/24 hours, and after several weeks many patients move to Exelon Patch 9.5 mg/24 hours as the usual daily dose. Apply the correct dose as directed by your doctor. The patch should be replaced by a new one after 24 hours.

During the course of treatment, your doctor may adjust the dose to suit your individual needs.

If you have not been applying Exelon Patch for several days, do not apply the next patch before you have talked to your doctor.

     Where to apply Exelon Patch:

Apply the patch to the upper or lower back if it is likely that the patient will remove it. If this is not a concern, the patch can be applied instead to the upper arm or chest. Avoid places where the patch can be rubbed off by tight clothing.

Before you apply Exelon Patch, make sure that your skin is:

• clean, dry and hairless
  
• free of any powder, oil, moisturizer, or lotion (that could keep the patch from sticking to your skin properly)
  
• free of cuts, rashes and/or irritations

When changing the patch, apply a new patch to a different spot of skin (for example on the right side of the body one day, then on the left side the next day). Do not apply a new patch to that same spot for at least 14 days. Apply the correct dose as directed by your doctor. The patch should be replaced by a new one after 24 hours.

How to apply Exelon Patch:

The patch is a thin, opaque, plastic patch that sticks to the skin. Each patch is sealed in a pouch that protects it until you are ready to put it on. Do not open the pouch or remove a patch until just before you apply it.

Cut the pouch along the dotted line and remove the patch.

The patch should not be cut or folded sharply.

A protective liner covers the adhesive side of the patch. Peel off one side of the protective liner and do not touch the sticky part of the patch with the fingers.

Put the sticky side of the patch on the upper or lower back, upper arm or chest and then peel off the second side of the protective liner.

Press the patch firmly in place with the hand to make sure that the edges stick well.

You may write (e.g., the day of the week) on Exelon Patch with a thin ball point pen.

Exelon Patch should be worn continuously until it is time to replace it with a new patch. Avoid placing the patch where it could be rubbed off by clothing.

     How to remove Exelon Patch:

Gently pull at one edge of Exelon Patch to remove it completely from the skin.

How to dispose of Exelon Patch:

After the patch has been removed, fold it in half with the adhesive sides on the inside and press them together. Return the used patch to its original pouch and discard safely out of the reach and sight of children and pets as there may be medicine left over in the patch. Wash your hands with soap and water after removing the patch.

Can Exelon Patch be worn when bathing, swimming, or in the sun?

Bathing, swimming, or showering should not affect the patch. When swimming, you can wear the patch under your swimsuit. Make sure the patch does not loosen during these activities.

The patch should not be exposed to any external heat sources (excessive sunlight, saunas, solariums) for long periods of time.

What to do if Exelon Patch falls off:

If the patch falls off, a new patch should be applied for the rest of the day and then replaced the next day at the same time as usual.

When and how long to apply Exelon Patch:

To benefit from your medicine you must apply a new patch every day.

Tell your caregiver that you are applying Exelon Patch. Also tell your caregiver if you have not been applying Exelon Patch for several days.

What to do if you apply more Exelon patches than you should:

If you accidentally apply more Exelon patches than you should, remove all Exelon patches from your skin, and then inform your doctor that you have accidentally applied more Exelon patches than you should have. You may require medical attention. Some people who have accidentally taken too much Exelon have experienced nausea, vomiting, diarrhea, high blood pressure and hallucinations. Slow heartbeat and fainting may also occur.

If you forget to apply Exelon Patch:

If you have forgotten to apply Exelon Patch, apply a new patch immediately. You may apply the next patch at the usual time the next day. Do not apply two Exelon patches to make up for the one that you missed.

If you have not been applying Exelon Patch for several days do not apply the next patch before you have talked to your doctor.

     Possible side effects:

Like all medicines, Exelon Patch can cause side effects, although not everybody gets them.

Do not be alarmed by this ul of possible side effects. You may not experience any of them.

You may tend to see side effects more frequently when you start your medication or increase to a higher dose. In most cases, side effects will gradually disappear as your body becomes used to the medicine. Gastrointestinal reactions such as nausea (feeling sick) and vomiting (being sick) are the most common side effects. The other common side effects are: loss of appetite, anxiety, difficulty sleeping, dizziness, headache, diarrhea, stomach discomfort after meals, stomach pain, skin reactions at the application site (redness, itching, irritation, swelling), fatigue, weakness, and weight loss.

Some side effects could become serious:

Common: depression.

Uncommon: severe confusion, hallucinations, vascular accident involving the brain (loss of coordination, difficulty in speaking or breathing and signs of brain disorder), fainting, problems with heart rhythm (irregular or fast or slow heartbeat), gastric ulcer and gastrointestinal hemorrhage (blood in stools or when vomiting).

If you experience any of these, remove Exelon Patch and tell your doctor right away.

     Other side effects:

Uncommon: agitation, drowsiness, sweating and a general feeling of being unwell.

      If any of these affect you severely, tell your doctor.

Additional side effects have been reported with Exelon capsules or oral solution:

Common: confusion and trembling.

Uncommon: changes in liver function tests and accidental falls.

Rare: convulsions, chest pain, duodenal ulcer and rash.

Very rare: urinary tract infection, high blood pressure, inflammation of the pancreas (severe upper stomach pain, often with nausea and vomiting) and severe vomiting that can lead to a rupture of the esophagus.

In addition, you should contact your doctor or pharmacist if you experience any other possible side effects not mentioned in this leaflet.

     How to store Exelon Patch:

Do not use Exelon Patch after the expiration date shown on the carton and pouch.

Store at room temperature, 59-86°F (15-30°C).

Do not use any Exelon Patch that is damaged or shows signs of tampering.

Keep Exelon Patch out of the reach and sight of children and pets.

      Manufactured by:

      LTS Lohmann Therapie-Systeme AG

      Andernach, Germany

      Distributed by:

      Novartis Pharmaceuticals Corporation

      East Hanover, New Jersey 07936

      T2007-68 / JULY 2007

     ©Novartis