Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 22 November 2019

Indication(s)

1 INDICATIONS AND USAGE Rivastigmine transdermal system 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 Rivastigmine transdermal system 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 Rivastigmine transdermal system is indicated for the treatment of mild-to-moderate dementia associated with Parkinson's disease (PDD).

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Advisory information

contraindications
4 CONTRAINDICATIONS Known hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation. (4) History of application site reactions with rivastigmine transdermal system suggestive of allergic contact dermatitis (4, 6.2) Rivastigmine transdermal system 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 system 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)].
Adverse reactions
6 ADVERSE REACTIONS Most common adverse reactions (less than 5% and higher than with placebo): Nausea, vomiting, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following 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)]. 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. Rivastigmine transdermal system 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 rivastigmine transdermal system 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 rivastigmine transdermal system 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 rivastigmine transdermal system than in those using the 9.5 mg/24 hours rivastigmine transdermal system. Discontinuation Rates In Study 1, which randomized a total of 1195 patients, the proportions of patients in the rivastigmine transdermal system 9.5 mg/24 hours, rivastigmine 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 rivastigmine transdermal system-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 rivastigmine transdermal system 9.5 mg/24 hours, rivastigmine 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 rivastigmine transdermal system 9.5 mg/24 hours, rivastigmine 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 rivastigmine transdermal system-treated group in Study 1 and for which the rate of occurrence was greater for patients treated with that dose of rivastigmine transdermal system than for those treated with placebo. The unapproved 17.4 mg/24 hours rivastigmine transdermal system arm is included to demonstrate the increased rates of gastrointestinal adverse reactions over those seen with the 9.5 mg/24 hours rivastigmine transdermal system. Table 1 Proportion of Adverse Reactions (ARs) Observed with a Frequency of Greater Than or Equal to 2% and Occurring at a Rate Greater Than Placebo in Study 1 Rivastigmine Transdermal System 9.5 mg/24 hours Rivastigmine Transdermal System 17.4 mg/24 hours Rivastigmine 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 *Vomiting was severe in 0% of patients who received rivastigmine transdermal system 9.5 mg/24 hours, 1% of patients who received rivastigmine transdermal system 17.4 mg/24 hours, 1% of patients who received the rivastigmine 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 rivastigmine transdermal system 9.5 mg/24 hours, 12% of those treated with rivastigmine transdermal system 17.4 mg/24 hours, 11% of patients who received the rivastigmine 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. 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 rivastigmine transdermal system 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 rivastigmine transdermal system 13.3 mg/24 hours group than in the rivastigmine transdermal system 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. Table 2 Proportion of Most Common ARs (Greater Than 1% at any dose) Leading to Discontinuation During 48-week Double-Blind (DB) Treatment Phase in Study 2 Rivastigmine Transdermal System 13.3 mg/24 hours Rivastigmine Transdermal System 9.5 mg/24 hours Total Total Patients Studied 280 283 563 Total Percentage of Patients with ARs Leading to Discontinuation (%) 9.6 12.7 11.2 Vomiting 1.4 0.4 0.9 Application site pruritus 1.1 1.1 1.1 Aggression 0.4 1.1 0.7 Most Common Adverse Reactions Greater Than or Equal to 3% Other adverse reactions of interest which occurred less frequently, but which were observed in a markedly higher percentage of patients in the rivastigmine transdermal system 13.3 mg/24 hours group than in the rivastigmine transdermal system 9.5 mg/24 hours group in Study 2, included dizziness and upper abdominal pain. The percentage of patients with these reactions decreased over time in each treatment group (Table 3). The adverse reaction severity profile was generally similar for both the rivastigmine transdermal system 13.3 mg/24 hours and 9.5 mg/24 hours groups. Table 3 Proportion of ARs Over Time in the 48-week DB-Treatment Phase (at Least 3% in any Treatment Group) in Study 2 Cumulative Week 0 to 48 (DB Phase) Week 0 to 24 (DB Phase) Week > 24 to 48 (DB Phase) Preferred Term Rivastigmine Transdermal System 13.3 mg/24 hours Rivastigmine Transdermal System 9.5 mg/24 hours Rivastigmine Transdermal System 13.3 mg/24 hours Rivastigmine Transdermal System 9.5 mg/24 hours Rivastigmine Transdermal System 13.3 mg/24 hours Rivastigmine Transdermal System 9.5 mg/24 hours Total Patients Studied 280 283 280 283 241 246 Total Percentage of Patients with ARs (%) 75 68 65 55 42 40 Nausea 12 5 10 4 4 2 Vomiting 10 5 9 3 3 2 Fall 8 6 4 4 4 3 Weight decreased* 7 3 3 1 5 2 Application site erythema 6 6 6 5 1 2 Decreased appetite 6 3 5 2 2 <1 Diarrhea 6 5 5 4 2 <1 Urinary tract infection 5 4 3 3 3 2 Agitation 5 5 4 3 1 2 Depression 5 5 3 3 3 2 Dizziness 4 1 3 <1 2 <1 Application site pruritus 4 4 4 3 <1 1 Headache 4 4 4 4 <1 <1 Insomnia 4 3 2 1 3 2 Abdominal pain upper 4 1 3 1 1 <1 Anxiety 4 3 2 2 2 1 Hypertension 3 3 3 2 1 1 Urinary incontinence 3 2 2 1 1 <1 Psychomotor hyperactivity 3 3 2 3 2 1 Aggression 2 3 1 3 1 1 *Decreased Weight as presented in Table 3 is based upon clinical observations and/or adverse events reported by patients or caregivers. Body weight was monitored as a vital sign at pre-specified 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 15.2% of those treated with rivastigmine transdermal system 9.5 mg/24 hours and 18.6% of those treated with rivastigmine transdermal system 13.3 mg/24 hours during the 48-week double-blind treatment period Severe Alzheimer's Disease 24-Week US Controlled Trial (Study 3) Most Commonly Observed Adverse Reactions The most common adverse reactions in patients administered rivastigmine transdermal system in the controlled clinical trial, defined as those occurring at a frequency of at least 5% in the 13.3 mg/24 hours rivastigmine transdermal system arm and at a frequency higher than in the 4.6 mg/24 hours rivastigmine transdermal system were application site erythema, fall, insomnia, vomiting, diarrhea, weight decreased, and nausea (Table 4). Patients in the lower dose group reported more events of agitation, urinary tract infection, and hallucinations than patients in the higher dose group. Discontinuation Rates In Study 3 [see Clinical Studies (14)], the proportions of patients in the rivastigmine transdermal system 13.3 mg/24 hours (n=355) and rivastigmine transdermal system 4.6 mg/24 hours (n=359), who discontinued treatment due to adverse reactions were 21% and 14%, respectively. The most frequent adverse reaction leading to discontinuation in the 13.3 mg/24 hours treatment group versus the 4.6 mg/24 hours treatment group was agitation (2.8% versus 2.2%), followed by vomiting (2.5% and 1.1%), nausea (1.7% and 1.1%), decreased appetite (1.7% and 0%), aggression (1.1% and 0.3%), fall (1.1% and 0.3%) and syncope (1.1% and 0.3%). Otherwise, all AEs leading to discontinuation were reported in less than 1% of patients. Most Commonly Observed Adverse Reactions Greater than or Equal to 5% Other adverse reactions of interest, which were observed in a higher percentage of patients in the rivastigmine transdermal system 13.3 mg/24 hours group than in the rivastigmine transdermal system 4.6 mg/24 hours group, included application site erythema, fall, insomnia, vomiting, diarrhea, weight decreased, and nausea (Table 4). Overall, the majority of patients in this study experienced adverse reactions that were mild (30.7%) or moderate (32.1%) in severity. Slightly more patients in the 4.6 mg/24 hours transdermal system group reported mild events than in the 13.3 mg/24 hours transdermal system group, while the numbers of patients reporting moderate events were comparable between groups. Severe adverse reactions were reported at a slightly higher percentage at the higher dose (12.4%) than at the lower dose (10%) treatment groups. With the exception of severe adverse reactions of agitation (13.3 mg: 1.1%; 4.6 mg: 1.4%), fall (13.3 mg: 1.1%) and urinary tract infection (4.6 mg: 1.1%), all adverse reactions reported as severe occurred in less than 1% of patients in either treatment group. Table 4 Proportion of ARs in the 24-week DB-Treatment Phase (at Least 5% in any Treatment Group) in Study 3 Preferred term Rivastigmine Transdermal System 13.3 mg/24 hours Rivastigmine Transdermal System 4.6 mg/24 hours Total number of patients studied 355 359 Total percentage of patients with ARs (%) 75 73 Application site erythema 13 12 Agitation 12 14 Urinary tract infection 8 10 Fall 8 6 Insomnia 7 4 Vomiting 7 3 Diarrhea 7 5 Weight decreased* 7 3 Nausea 6 3 Depression 5 4 Decreased appetite 5 1 Anxiety 5 5 Hallucination 2 5 *Weight Decreased as presented in Table 4 is based upon clinical observations and/or adverse events reported by patients or caregivers. Body weight was monitored as a vital sign 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 11% of those treated with rivastigmine transdermal system 4.6 mg/24 hours and 14.1% of those treated with rivastigmine transdermal system 13.3 mg/24 hours during the 24-week double-blind treatment. Application Site Reactions Application site skin reactions leading to discontinuation were observed in less than or equal to 2.3% of rivastigmine transdermal system patients. This number was 4.9% and 8.4% in the Chinese population and Japanese population, respectively. Cases of skin irritation were captured separately on an investigator-rated skin irritation scale. Skin irritation, when observed, was mostly slight or mild in severity and was rated as severe in less than or equal to 2.2% of rivastigmine transdermal system patients in a double-blind controlled study and in less than or equal to 3.7% of rivastigmine transdermal system patients in a double-blind controlled study in Japanese patients. Parkinson's Disease Dementia 76-week International Open-Label Trial (Study 4) Rivastigmine transdermal system has been administered to 288 patients with mild-to-moderate Parkinson's Disease Dementia in a single, 76-week, open-label, active-comparator safety study. Of these, 256 have been treated for at least 12 weeks, 232 for at least 24 weeks, and 196 for at least 52 weeks. Treatment with rivastigmine transdermal system was initiated at 4.6 mg/24 hours and if tolerated the dose was increased after 4 weeks to 9.5 mg/24 hours. Rivastigmine capsule (target maintenance dose of 12 mg/day) served as the active comparator and was administered to 294 patients. Adverse reactions are presented in Table 5. Table 5 Proportion of ARs Reported at a Rate Greater Than or Equal to 2% During the Initial 24-Week Period in Study 4 Adverse Drug Reactions Rivastigmine Transdermal System Total patients studied 288 Percentage (%) Psychiatric Disorders Insomnia 6 Depression 6 Anxiety 5 Agitation 3 Nervous System Disorders Tremor 7 Dizziness 6 Somnolence 4 Hypokinesia 4 Bradykinesia 4 Cogwheel rigidity 3 Dyskinesia 3 Gastrointestinal Disorders Abdominal pain 2 Vascular Disorders Hypertension 3 General Disorders and Administration-site Conditions Fall 12 Application site erythema 11 Application site irritation, pruritus, rash 3,5,2 Fatigue 4 Asthenia 2 Gait disturbance 4 Additional adverse reactions observed during the 76-week prospective, open-label study in patients with dementia associated with Parkinson's disease treated with rivastigmine transdermal system: Frequent (those occurring in at least 1/100 patients): dehydration, weight decreased, aggression, hallucination visual. In patients with dementia associated with Parkinson's disease, the following adverse drug reactions have only been observed in clinical trials with rivastigmine capsules: Frequent: nausea, vomiting, decreased appetite, restlessness, worsening of Parkinson's disease, bradycardia, diarrhea, dyspepsia, salivary hypersecretion, sweating increased; Infrequent (those occurring between 1/100 to 1/1000 patients): dystonia, atrial fibrillation, atrioventricular block. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of rivastigmine capsules, rivastigmine oral solution, or rivastigmine transdermal system. 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: Parkinson's disease (worsening), seizure, tremor. Psychiatric Disorders: nightmares. Skin and Subcutaneous Tissue Disorders: Allergic dermatitis, application site hypersensitivity, blister, disseminated allergic dermatitis, Stevens-Johnson syndrome, urticaria. Vascular Disorders: Hypertension.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Apply transdermal system 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 rivastigmine transdermal system. (2.1) Dose Titration (2.1): 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. Mild-to-Moderate Alzheimer's Disease and Parkinson's Disease Dementia : Rivastigmine transdermal system 9.5 mg/24 hours or 13.3 mg/24 hours once daily. (2.1) Severe Alzheimer's Disease : Rivastigmine transdermal system 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): ○ Mild-to-moderate hepatic impairment (8.6) ○ Low (less than 50 kg) body weight (8.7) 2.1 Recommended Dosing Initial Dose Initiate treatment with one 4.6 mg/24 hours rivastigmine transdermal system 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 rivastigmine transdermal system is 9.5 mg/24 hours or 13.3 mg/24 hours administered once per day; replace with a new transdermal system every 24 hours. Severe Alzheimer's Disease The effective dosage of rivastigmine transdermal system in patients with severe Alzheimer's disease is 13.3 mg/24 hours administered once per day; replace with a new transdermal system every 24 hours. Interruption of Treatment If dosing is interrupted for 3 days or fewer, restart treatment with the same or lower strength rivastigmine transdermal system. If dosing is interrupted for more than 3 days, restart treatment with the 4.6 mg/24 hours rivastigmine transdermal system 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 rivastigmine transdermal system 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 rivastigmine transdermal system if such toxicities develop. 2.3 Switching to Rivastigmine Transdermal System from Rivastigmine Capsules or Rivastigmine Oral Solution Patients treated with rivastigmine capsules or oral solution may be switched to rivastigmine transdermal system 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 rivastigmine transdermal system. 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 rivastigmine transdermal system. Instruct patients or caregivers to apply the first transdermal system on the day following the last oral dose. 2.4 Important Administration Instructions Rivastigmine transdermal system is for transdermal use on intact skin. a) Do not use the transdermal system if the pouch seal is broken or the transdermal system is cut, damaged, or changed in any way. b) Apply the rivastigmine transdermal system 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 transdermal system is less likely to be removed by the patient. If sites on the back are not accessible, apply the transdermal system 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 rivastigmine transdermal system with a new transdermal system every 24 hours. Instruct patients to only wear 1 transdermal system at a time (remove the previous day's transdermal system before applying a new transdermal system) [see Warnings and Precautions (5.1), Overdosage (10)]. If a transdermal system falls off or if a dose is missed, apply a new transdermal system immediately and then replace this transdermal system the following day at the usual application time. e) Change the site of transdermal system application daily to minimize potential irritation, although a new transdermal system 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 transdermal system to the same location for at least 14 days. f) May wear the transdermal system during bathing and in hot weather. But avoid long exposure to external heat sources (excessive sunlight, saunas, solariums). g) Place used transdermal systems 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 transdermal system. In case of contact with eyes or if the eyes become red after handling the transdermal system, rinse immediately with plenty of water, and seek medical advice if symptoms do not resolve.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of rivastigmine 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/m2) 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 rivastigmine and any potential adverse effects on the breastfed infant from rivastigmine or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. The use of rivastigmine transdermal system 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 rivastigmine transdermal system, 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 and lactation
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 rivastigmine and any potential adverse effects on the breastfed infant from rivastigmine or from the underlying maternal condition.

Interactions

7 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 rivastigmine transdermal system is not recommended. 7.2 Cholinomimetic and Anticholinergic Medications Rivastigmine transdermal system 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 rivastigmine transdermal system with medications having these pharmacologic effects is not recommended unless deemed clinically necessary [see Warnings and Precautions (5.4)]. 7.3 Beta-blockers Additive bradycardic effects resulting in syncope may occur when rivastigmine 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.

More information

Category Value
Authorisation number ANDA206318
Agency product number PKI06M3IW0
Orphan designation No
Product NDC 16714-117,16714-116,16714-115
Date Last Revised 06-07-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 725021
Marketing authorisation holder Northstar Rx LLC.