Exelon
rivastigmine · Patch, Extended Release · Transdermal
Uses
1 INDICATIONS AND USAGE EXELON PATCH is an acetylcholinesterase inhibitor indicated for treatment of:
• Mild, moderate, and severe dementia of the Alzheimer’s type (AD). ( 1.1 )
• Mild-to-moderate dementia associated with Parkinson’s disease (PD). ( 1.2 ) 1.1 Alzheimer’s Disease EXELON PATCH is indicated for the treatment of dementia of the Alzheimer’s type (AD). Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer’s disease. 1.2 Parkinson’s Disease Dementia EXELON PATCH is indicated for the treatment of mild-to-moderate dementia associated with Parkinson’s disease (PDD).
Dosage and administration
• Apply patch on intact skin for a 24-hour period; replace with a new patch every 24 hours. ( 2.1 , 2.4 )
• Initial Dose: Initiate treatment with 4.6 mg/24 hours EXELON PATCH. ( 2.1 )
• Dose Titration: After a minimum of 4 weeks, if tolerated, increase dose to 9.5 mg/24 hours, which is the minimum effective dose. Following a minimum additional 4 weeks, may increase dosage to maximum dosage of 13.3 mg/24 hours. ( 2.1 )
• Mild-to-Moderate Alzheimer’s Disease and Parkinson’s Disease Dementia: EXELON PATCH 9.5 mg/24 hours or 13.3 mg/24 hours once daily. ( 2.1 )
• Severe Alzheimer’s Disease: EXELON PATCH 13.3 mg/24 hours once daily. ( 2.1 )
• For treatment interruption longer than 3 days, retitrate dosage starting at 4.6 mg per 24 hours. ( 2.1 )
• Consider dose adjustments in patients with ( 2.2 ): o Mild-to-moderate hepatic impairment ( 8.6 ) o Low (less than 50 kg) body weight ( 8.7 ) 2.1 Recommended Dosing Initial Dose Initiate treatment with one 4.6 mg/24 hours EXELON PATCH applied to the skin once daily [see Dosage and Administration (2.4)] . Dose Titration Increase the dose only after a minimum of 4 weeks at the previous dose, and only if the previous dose has been tolerated. For mild-to-moderate AD and PDD patients, continue the effective dose of 9.5 mg/24 hours for as long as therapeutic benefit persists. Patients can then be increased to the maximum effective dose of 13.3 mg/24 hours dose. For patients with severe AD, 13.3 mg/24 hours is the effective dose. Doses higher than 13.3 mg/24 hours confer no appreciable additional benefit, and are associated with an increase in the incidence of adverse reactions [see Warnings and Precautions (5.2), Adverse Reactions (6.1)] . Mild-to-Moderate Alzheimer’s Disease and Mild-to-Moderate Parkinson’s Disease Dementia The effective dosage of EXELON PATCH is 9.5 mg/24 hours or 13.3 mg/24 hours administered once per day; replace with a new patch every 24 hours. Severe Alzheimer’s Disease The effective dosage of EXELON PATCH in patients with severe Alzheimer’s disease is 13.3 mg/24 hours administered once per day; replace with a new patch every 24 hours. Interruption of Treatment If dosing is interrupted for 3 days or fewer, restart treatment with the same or lower strength EXELON PATCH. If dosing is interrupted for more than 3 days, restart treatment with the 4.6 mg/24 hours EXELON PATCH and titrate as described above. 2.2 Dosing in Specific Populations Dosing Modifications in Patients with Hepatic Impairment Consider using the 4.6 mg/24 hours EXELON PATCH as both the initial and maintenance dose in patients with mild (Child-Pugh score 5 to 6) to moderate (Child-Pugh score 7 to 9) hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] . Dosing Modifications in Patients with Low Body Weight Carefully titrate and monitor patients with low body weight (less than 50 kg) for toxicities (e.g., excessive nausea, vomiting), and consider reducing the maintenance dose to the 4.6 mg/24 hours EXELON PATCH if such toxicities develop. 2.3 Switching to EXELON PATCH from EXELON Capsules or EXELON Oral Solution 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 the 4.6 mg/24 hours EXELON PATCH.
• A patient who is on a total daily dose of 6 mg to 12 mg of oral rivastigmine can be switched to the 9.5 mg/24 hours EXELON PATCH. Instruct patients or caregivers to apply the first patch on the day following the last oral dose. 2.4 Important Administration Instructions EXELON PATCH is for transdermal use on intact skin. (a) Do not use the patch if the pouch seal is broken or the patch is cut, damaged, or changed in any way. (b) Apply the EXELON PATCH once a day.
• Press down firmly for 30 seconds until the edges stick well when applying to clean, dry, hairless, intact healthy skin in a place that will not be rubbed against by tight clothing.
• Use the upper or lower back as the site of application because the patch is less likely to be removed by the patient. If sites on the back are not accessible, apply the patch to the upper arm or chest.
• Do not apply to a skin area where cream, lotion, or powder has recently been applied. (c) Do not apply to skin that is red, irritated, or cut. (d) Replace the EXELON PATCH with a new patch every 24 hours. Instruct patients to only wear 1 patch at a time (remove the previous day’s patch before applying a new patch) [see Warnings and Precautions (5.1), Overdosage (10)] . If a patch falls off or if a dose is missed, apply a new patch immediately, and then replace this patch the following day at the usual application time. (e) Change the site of patch application daily to minimize potential irritation, although a new patch can be applied to the same general anatomic site (e.g., another spot on the upper back) on consecutive days. Do not apply a new patch to the same location for at least 14 days. (f) May wear the patch during bathing and in hot weather. Avoid long exposure to external heat sources (excessive sunlight, saunas, solariums). (g) Place used patches in the previously saved pouch and discard in the trash, away from pets or children. (h) Wash hands with soap and water after removing the patch. In case of contact with eyes or if the eyes become red after handling the patch, rinse immediately with plenty of water, and seek medical advice if symptoms do not resolve.
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS EXELON PATCH is available in 3 strengths. Each patch has a beige backing layer labeled as either:
• EXELON ® PATCH 4.6 mg/24 hours, AMCX
• EXELON ® PATCH 9.5 mg/24 hours, BHDI
• EXELON ® PATCH 13.3 mg/24 hours, CNFU Patch: 4.6 mg/24 hours or 9.5 mg/24 hours or 13.3 mg/24 hours ( 3 )
Contraindications
4 CONTRAINDICATIONS EXELON PATCH is contraindicated in patients with:
• known hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation [see Description (11)]
• previous history of application-site reactions with rivastigmine transdermal patch suggestive of allergic contact dermatitis [see Warnings and Precautions (5.3)] . Isolated cases of generalized skin reactions have been described in postmarketing experience [see Adverse Reactions (6.2)] .
• Known hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation. ( 4 )
• History of application-site reactions with rivastigmine transdermal patch suggestive of allergic contact dermatitis. ( 4 , 6.2 )
Warnings and precautions
• Hospitalization and, rarely, death have been reported due to application of multiple patches at same time. Ensure patients or caregivers receive instruction on proper dosing and administration. ( 5.1 )
• Gastrointestinal Adverse Reactions: May include significant nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss, and may necessitate treatment interruption. Dehydration may result from prolonged vomiting or diarrhea and can be associated with serious outcomes. ( 5.2 )
• Application-site reactions may occur with the patch form of rivastigmine. Discontinue treatment if application-site reactions spread beyond the patch size, if there is evidence of a more intense local reaction (e.g., increasing erythema, edema, papules, vesicles), and if symptoms do not significantly improve within 48 hours after patch removal. ( 5.3 ) 5.1 Medication Errors Resulting in Overdose Medication errors with EXELON PATCH have resulted in serious adverse reactions; some cases have required hospitalization, and rarely, led to death. The majority of medication errors have involved not removing the old patch when putting on a new one and the use of multiple patches at one time. Instruct patients and their caregivers on important administration instructions for EXELON PATCH [see Dosage and Administration (2.4)] . 5.2 Gastrointestinal Adverse Reactions EXELON PATCH can cause gastrointestinal adverse reactions, including significant nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss. Dehydration may result from prolonged vomiting or diarrhea and can be associated with serious outcomes. The incidence and severity of these reactions are dose-related [see Adverse Reactions (6.1)] . For this reason, initiate treatment with EXELON PATCH at a dose of 4.6 mg/24 hours, and titrate to a dose of 9.5 mg/24 hours and then to a dose of 13.3 mg/24 hours, if appropriate [see Dosage and Administration (2.1)] . If treatment is interrupted for more than 3 days because of intolerance, reinitiate EXELON PATCH with the 4.6 mg/24 hours dose to reduce the possibility of severe vomiting and its potentially serious sequelae. A postmarketing report described a case of severe vomiting with esophageal rupture following inappropriate reinitiation of treatment of an oral formulation of rivastigmine without retitration after 8 weeks of treatment interruption. Inform caregivers to monitor for gastrointestinal adverse reactions and to inform the physician if they occur. It is critical to inform caregivers that if therapy has been interrupted for more than 3 days because of intolerance, the next dose should not be administered without contacting the physician regarding proper retitration. 5.3 Skin Reactions Skin application-site reactions may occur with EXELON PATCH. These reactions are not in themselves an indication of sensitization. However, use of rivastigmine patch may lead to allergic contact dermatitis. Allergic contact dermatitis should be suspected if application-site reactions spread beyond the patch size, if there is evidence of a more intense local reaction (e.g., increasing erythema, edema, papules, vesicles), and if symptoms do not significantly improve within 48 hours after patch removal. In these cases, treatment should be discontinued [see Contraindications (4)] . In patients who develop application-site reactions to EXELON PATCH, suggestive of allergic contact dermatitis and who still require rivastigmine, treatment should be switched to oral rivastigmine only after negative allergy testing and under close medical supervision. It is possible that some patients sensitized to rivastigmine by exposure to rivastigmine patch may not be able to take rivastigmine in any form. There have been isolated postmarketing reports of patients experiencing disseminated allergic dermatitis when administered rivastigmine irrespective of the route of administration (oral or transdermal). In these cases, treatment should be discontinued [see Contraindications (4)] . Patients and caregivers should be instructed accordingly. 5.4 Other Adverse Reactions From Increased Cholinergic Activity Neurologic Effects Extrapyramidal Symptoms : Cholinomimetics, including 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. 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. Peptic Ulcers/Gastrointestinal Bleeding Cholinesterase inhibitors, including rivastigmine, may increase gastric acid secretion due to increased cholinergic activity. Monitor patients using EXELON PATCH 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 rivastigmine have shown no significant increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Use with Anesthesia Rivastigmine, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. Cardiac Conduction Effects Because rivastigmine increases cholinergic activity, use of the EXELON PATCH may have vagotonic effects on heart rate (e.g., bradycardia). The potential for this action may be particularly important in patients with sick sinus syndrome or other supraventricular cardiac conduction conditions. Genitourinary Effects Although not observed in clinical trials of rivastigmine, drugs that increase cholinergic activity may cause urinary obstruction.
Side effects
The following clinically significant adverse reactions are described below and elsewhere in the labeling:
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2)]
• Skin Reactions [see Warnings and Precautions (5.3)]
• Other Adverse Reactions from Increased Cholinergic Activity [see Warnings and Precautions (5.4)] Most common adverse reactions (less than 5% and higher than with placebo): Nausea, vomiting, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 PATCH has been administered to 4516 patients with Alzheimer’s disease during clinical trials worldwide. Of these, 3005 patients have been treated for at least 26 weeks, 1771 patients have been treated for at least 52 weeks, 974 patients have been treated for at least 78 weeks, and 24 patients have been treated for at least 104 weeks. Mild-to-Moderate Alzheimer’s Disease 24-Week International Placebo-Controlled Trial (Study 1) Most Common Adverse Reactions The most common adverse reactions in patients administered EXELON PATCH in Study 1 [see Clinical Studies (14)] , defined as those occurring at a frequency of at least 5% in the 9.5 mg/24 hours EXELON PATCH arm and at a frequency at higher than in the placebo group, were nausea, vomiting, and diarrhea. These reactions were dose-related, with each being more common in patients using the unapproved 17.4 mg/24 hours EXELON PATCH than in those using the 9.5 mg/24 hours EXELON PATCH. Discontinuation Rates In Study 1, which randomized a total of 1195 patients, the proportions of patients in the EXELON PATCH 9.5 mg/24 hours, EXELON Capsules 6 mg twice daily, and placebo groups who discontinued treatment due to adverse events were 10%, 8%, and 5%, respectively. The most common adverse reactions in the EXELON PATCH-treated groups that led to treatment discontinuation in this study were nausea and vomiting. The proportions of patients who discontinued treatment due to nausea were 0.7%, 1.7%, and 1.3% in the EXELON PATCH 9.5 mg/24 hours, EXELON Capsules 6 mg twice daily, and placebo groups, respectively. The proportions of patients who discontinued treatment due to vomiting were 0%, 2.0%, and 0.3% in the EXELON PATCH 9.5 mg/24 hours, EXELON Capsules 6 mg twice daily, and placebo groups, respectively. Adverse Reactions Observed at an Incidence of Greater than or Equal to 2% Table 1 lists adverse reactions seen at an incidence of greater than or equal to 2% in either EXELON PATCH-treated group in Study 1, and for which the rate of occurrence was greater for patients treated with that dose of EXELON PATCH than for those treated with placebo. The unapproved 17.4 mg/24 hours EXELON PATCH arm is included to demonstrate the increased rates of gastrointestinal adverse reactions over those seen with the 9.5 mg/24 hours EXELON PATCH. Table 1: Proportion of Adverse Reactions Observed With a Frequency of Greater Than or Equal to 2% and Occurring at a Rate Greater Than Placebo in Study 1 Abbreviation: ARs, adverse reactions. *Vomiting was severe in 0% of patients who received EXELON PATCH 9.5 mg/24 hours, 1% of patients who received EXELON PATCH 17.4 mg/24 hours, 1% of patients who received the EXELON Capsule at doses up to 6 mg twice daily, and 0% of those who received placebo. **Weight Decreased as presented in Table 1 is based upon clinical observations and/or adverse events reported by patients or caregivers. Body weight was also monitored at prespecified time points throughout the course of the clinical study. 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, 12% of those treated with EXELON PATCH 17.4 mg/24 hours, 11% of patients who received the EXELON Capsule at doses up to 6 mg twice daily and 6% of those who received placebo. It is not clear how much of the weight loss was associated with anorexia, nausea, vomiting, and the diarrhea associated with the drug. Adverse reaction EXELON PATCH 9.5 mg/24 hours EXELON PATCH 17.4 mg/24 hours EXELON Capsule 6 mg twice daily Placebo Total patients studied 291 303 294 302 Total percentage of patients with ARs (%) 51 66 63 46 Nausea 7 21 23 5 Vomiting* 6 19 17 3 Diarrhea 6 10 5 3 Depression 4 4 4 1 Headache 3 4 6 2 Anxiety 3 3 2 1 Anorexia/Decreased appetite 3 9 9 2 Weight decreased** 3 8 5 1 Dizziness 2 7 7 2 Abdominal pain 2 4 1 1 Urinary tract infection 2 2 1 1 Asthenia 2 3 6 1 Fatigue 2 2 1 1 Insomnia 1 4 2 2 Abdominal pain upper 1 3 2 2 Vertigo 0 2 1 1 48-Week International Active Comparator-Controlled Trial (Study 2) Most Common Adverse Reactions In Study 2 [see Clinical Studies (14)] of the commonly observed adverse reactions (greater than or equal to 3% in any treatment group), the most frequent event in the EXELON PATCH 13.3 mg/24 hours group was nausea, followed by vomiting, fall, weight decreased, application-site erythema, decreased appetite, diarrhea and urinary tract infection (Table 3). The percentage of patients with these events was higher in the EXELON PATCH 13.3 mg/24 hours group than in the EXELON PATCH 9.5 mg/24 hours group. Patients with nausea, vomiting, diarrhea and decreased appetite experienced these reactions more often during the first 4 weeks of the double-blind treatment phase. These reactions decreased over time in each treatment group. Weight decreased was reported to have increased over time in each treatment group. Discontinuation Rates Table 2 displays the most common adverse reactions leading to discontinuation during the 48-week, double-blind treatment phase in Study 2.
Drug interactions
Concomitant use with metoclopramide, beta-blockers, or cholinomimetics and anticholinergic medications is not recommended. ( 7.1 , 7.2 , 7.3 ) 7.1 Metoclopramide Due to the risk of additive extra-pyramidal adverse reactions, the concomitant use of metoclopramide and EXELON PATCH is not recommended. 7.2 Cholinomimetic and Anticholinergic Medications EXELON PATCH 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 PATCH with medications having these pharmacologic effects is not recommended unless deemed clinically necessary [see Warnings and Precautions ( 5.5 )] . 7.3 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 is not recommended when signs of bradycardia, including syncope are present.
Use in specific populations
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of EXELON in pregnant women. In animals, no adverse effects on embryo-fetal development were observed at oral doses 2-4 times the maximum recommended human dose (MRHD) (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Oral administration of rivastigmine to pregnant rats and rabbits throughout organogenesis produced no adverse effects on embryo-fetal development up to the highest dose tested (2.3 mg/kg/day), which is 2 and 4 times, respectively, the MRHD of 12 mg per day on a body surface area (mg/m 2 ) basis. 8.2 Lactation Risk Summary There are no data on the presence of rivastigmine in human milk, the effects on the breastfed infant, or the effects of rivastigmine on milk production. Rivastigmine and its metabolites are excreted in rat milk following oral administration of rivastigmine; levels of rivastigmine plus metabolites in rat milk are approximately 2 times that in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EXELON and any potential adverse effects on the breastfed infant from EXELON or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. The use of EXELON PATCH in pediatric patients (below 18 years of age) is not recommended. 8.5 Geriatric Use Of the total number of patients in clinical studies of EXELON PATCH, 88% were 65 years and over, while 55% were 75 years. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment Increased exposure to rivastigmine was observed in patients with mild or moderate hepatic impairment with oral rivastigmine. Patients with mild or moderate hepatic impairment may be able to only tolerate lower doses [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] . No data are available on the use of rivastigmine in patients with severe hepatic impairment. 8.7 Low or High Body Weight Because rivastigmine blood levels vary with weight, careful titration and monitoring should be performed in patients with low or high body weights [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] .
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of EXELON in pregnant women. In animals, no adverse effects on embryo-fetal development were observed at oral doses 2-4 times the maximum recommended human dose (MRHD) (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data Oral administration of rivastigmine to pregnant rats and rabbits throughout organogenesis produced no adverse effects on embryo-fetal development up to the highest dose tested (2.3 mg/kg/day), which is 2 and 4 times, respectively, the MRHD of 12 mg per day on a body surface area (mg/m 2 ) basis.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. The use of EXELON PATCH in pediatric patients (below 18 years of age) is not recommended.
Geriatric use
8.5 Geriatric Use Of the total number of patients in clinical studies of EXELON PATCH, 88% were 65 years and over, while 55% were 75 years. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
Overdose with EXELON PATCH has been reported in the postmarketing setting [see Warnings and Precautions (5.1)] . Overdoses have occurred from application of more than one patch at one time and not removing the previous day’s patch before applying a new patch. The symptoms reported in these overdose cases are similar to those seen in cases of overdose associated with rivastigmine oral formulations. 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 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, 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. Additional symptoms associated with rivastigmine overdose are diarrhea, abdominal pain, dizziness, tremor, headache, somnolence, confusional state, hyperhidrosis, hypertension, hallucinations and malaise. 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. A fatal outcome has rarely been reported with rivastigmine overdose.
Description
(rivastigmine transdermal system) contains rivastigmine, a reversible cholinesterase inhibitor known chemically as (S)-3-[1-(dimethylamino) ethyl]phenyl ethylmethylcarbamate. It has an empirical formula of C 14 H 22 N 2 O 2 as the base and a molecular weight of 250.34 g/mol (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 is a 4-layer laminate containing the backing layer, drug matrix, adhesive matrix and overlapping release liner (see Figure 1). The release liner is removed and discarded prior to use. Figure 1: Cross Section of the EXELON PATCH Layer 1: Backing Film Layer 2: Drug Product (Acrylic) Matrix Layer 3: Adhesive (Silicone) Matrix Layer 4: Release Liner (removed at time of use) Excipients within the formulation include acrylic copolymer, poly (butylmethacrylate, methylmethacrylate), silicone adhesive applied to a flexible polymer backing film, silicone oil, and vitamin E. rivastigmine chemical structure Figure 1: Cross Section of the EXELON PATCH
Mechanism of action
12.1 Mechanism of Action Although the precise mechanism of action of rivastigmine is unknown, it is thought 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. 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.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING EXELON PATCH: 4.6 mg/24 hours Each patch of 5 cm 2 contains 9 mg rivastigmine base with in vivo release rate of 4.6 mg/24 hours. Carton of 30………………………NDC 0078-0501-15 EXELON PATCH: 9.5 mg/24 hours Each patch of 10 cm 2 contains 18 mg rivastigmine base with in vivo release rate of 9.5 mg/24 hours. Carton of 30………………………..NDC 0078-0502-15 EXELON PATCH: 13.3 mg/24 hours Each patch of 15 cm 2 contains 27 mg rivastigmine base with in vivo release rate of 13.3 mg/24 hours. Carton of 30………………………NDC 0078-0503-15 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep EXELON PATCH in the individual sealed pouch until use. Each pouch contains 1 patch. Used systems should be folded, with the adhesive surfaces pressed together, and discarded safely.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Importance of Correct Usage Inform patients or caregivers of the importance of applying the correct dose on the correct part of the 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. The previous day’s patch must be removed before applying a new patch to a different skin location. 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. Only 1 patch should be worn at a time [see Dosage and Administration (2.4), Warnings and Precautions (5.1)] . Instruct patients or caregivers to avoid exposure of the patch to external heat sources (excessive sunlight, saunas, solariums) for long periods of time. Instruct patients who have missed a dose to apply a new patch immediately. They may apply the next patch at the usual time the next day. Instruct patients to not apply 2 patches to make up for 1 missed. Inform the patient or caregiver to contact the physician for retitration instructions if treatment has been interrupted. Discarding Used Patches Instruct patients or caregivers 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. In case of accidental contact with the eyes, or if their eyes become red after handling the patch, they should be instructed to rinse immediately with plenty of water and to seek medical advice if symptoms do not resolve [see Dosage and Administration (2.4)] . Gastrointestinal Adverse Reactions Inform patients or caregivers of the potential gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, including the possibility of dehydration due to these symptoms. Explain that EXELON PATCH may affect the patient’s appetite and/or the patient’s weight. Patients and caregivers should be instructed to look for these adverse reactions, in particular when treatment is initiated or the dose is increased. Instruct patients and caregivers to inform a physician if these adverse reactions persist [see Warnings and Precautions (5.2)] . Skin Reactions Inform patients or caregivers about the potential for allergic contact dermatitis reactions to occur. Patients or caregivers should be instructed to inform a physician if application-site reactions spread beyond the patch size, if there is evidence of a more intense local reaction (e.g., increasing erythema, edema, papules, vesicles) and if symptoms do not significantly improve within 48 hours after patch removal [see Warnings and Precautions (5.3)] . Concomitant Use of Drugs With Cholinergic Action Inform patients or caregivers that while wearing EXELON PATCH, patients should not be taking EXELON Capsules or EXELON Oral Solution or other drugs with cholinergic effects [see Warnings and Precautions (5.4)] . Pregnancy Advise patients to notify their healthcare provider if they are pregnant or plan to become pregnant. Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936
Label text from the FDA structured product label by Novartis Pharmaceuticals Corporation (revised May 8, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Rivastigmine in 6 products
Exelon NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0078-0501 | Rivastigmine 4.6 mg/24h Patch, Extended Release | Novartis Pharmaceuticals Corporation | NDA |
| 0078-0502 | Rivastigmine 9.5 mg/24h Patch, Extended Release | Novartis Pharmaceuticals Corporation | NDA |
| 0078-0503 | Rivastigmine 13.3 mg/24h Patch, Extended Release | Novartis Pharmaceuticals Corporation | NDA |
| 66758-142 | Rivastigmine 4.6 mg/24h Patch, Extended Release | Sandoz Inc | NDA |
| 66758-143 | Rivastigmine 9.5 mg/24h Patch, Extended Release | Sandoz Inc | NDA |
| 66758-144 | Rivastigmine 13.3 mg/24h Patch, Extended Release | Sandoz Inc | NDA |
Frequently asked questions
What is Exelon used for?
1 INDICATIONS AND USAGE EXELON PATCH is an acetylcholinesterase inhibitor indicated for treatment of: • Mild, moderate, and severe dementia of the Alzheimer’s type (AD). ( 1.1 ) • Mild-to-moderate dementia associated with Parkinson’s disease (PD). ( 1.2 ) 1.1 Alzheimer’s Disease EXELON PATCH is indicated for the treatment of dementia of the Alzheimer’s type (AD). Efficacy has been demonstrated in…
What are the side effects of Exelon?
The following clinically significant adverse reactions are described below and elsewhere in the labeling: • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2)] • Skin Reactions [see Warnings and Precautions (5.3)] • Other Adverse Reactions from Increased Cholinergic Activity [see Warnings and Precautions (5.4)] Most common adverse reactions (less than 5% and higher than with… See the full label for the complete list.
Who makes Exelon?
Exelon is listed by 2 labelers in the FDA NDC directory, including Novartis Pharmaceuticals Corporation, Sandoz Inc.