Rivastigmine 3M Health Care Ltd

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each transdermal patch releases 4.6 mg of rivastigmine per 24 hours. Each transdermal patch of 
4.15 cm2 contains 7.17 mg of rivastigmine. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Transdermal patch 
 
Rectangular patches, approximately 2.5 cm by 1.8 cm with rounded corners. Each patch consists of a 
combination of a removable, transparent, split release liner, a functional layer containing drug-in-
adhesive (DIA) matrix, and a protective backing layer. The backing layer is transparent to translucent, 
labelled with “R5”  in a repeated pattern. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment 
of Alzheimer’s dementia. Diagnosis should be made according to current guidelines. Similar to any 
treatment initiated in patients with dementia, therapy with rivastigmine should only be started if a 
caregiver is available to regularly administer and monitor the treatment. 
 
Posology 
 
Transdermal patches Rivastigmine in vivo release 

rates per 24 h
Rivastigmine 4.6 mg/24 h 4.6 mg 
Rivastigmine 9.5 mg/24 h 9.5 mg 
Rivastigmine 13.3 mg/24 h* 13.3 mg 
 
*A marketing authorisation for Rivastigmine 3M Health Care Ltd. 13.3 mg/24 h transdermal patch is 
currently not available, this presentation may although be available from other marketing authorisation 
holders. 
 
Initial dose 
Treatment is started with 4.6 mg/24 h. 
 
Maintenance dose 
After a minimum of four weeks of treatment and if well tolerated according to the treating physician, the 
dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, the daily recommended effective dose, which 
should be continued for as long as the patient continues to demonstrate therapeutic benefit. 
 

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Dose escalation 
9.5 mg/24 h is the recommended daily effective dose which should be continued for as long as the patient 
continues to demonstrate therapeutic benefit. If well tolerated and only after a minimum of six months 
of treatment at 9.5 mg/24 h, the treating physician may consider increasing the dose to 13.3 mg/24 h in 
patients who have demonstrated a meaningful cognitive deterioration (e.g. decrease in the MMSE) 
and/or functional decline (based on physician judgement) while on the recommended daily effective 
dose of 9.5 mg/24 h (see section 5.1). 
 
The clinical benefit of rivastigmine should be reassessed on a regular basis. Discontinuation should also 
be considered when evidence of a therapeutic effect at the optimal dose is no longer present. 
 
Treatment should be temporarily interrupted if gastrointestinal adverse reactions are observed until 
these adverse reactions resolve. Transdermal patch treatment can be resumed at the same dose if 
treatment is not interrupted for more than three days. Otherwise treatment should be re-initiated with 
4.6 mg/24 h. 
 
Switching from capsules or oral solution to transdermal patches 
Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients 
treated with rivastigmine capsules or oral solution can be switched to Rivastigmine 3M Health Care 
Ltd. transdermal patches as follows: 
- A patient on a dose of 3 mg/day oral rivastigmine can be switched to 4.6 mg/24 h transdermal 

patches. 
- A patient on a dose of 6 mg/day oral rivastigmine can be switched to 4.6 mg/24 h transdermal 

patches. 
- A patient on a stable and well tolerated dose of 9 mg/day oral rivastigmine can be switched to 

9.5 mg/24 h transdermal patches. If the oral dose of 9 mg/day has not been stable and well 
tolerated, a switch to 4.6 mg/24 h transdermal patches is recommended. 

- A patient on a dose of 12 mg/day oral rivastigmine can be switched to 9.5 mg/24 h transdermal 
patches. 

 
After switching to 4.6 mg/24 h transdermal patches, provided these are well tolerated after a minimum of 
four weeks of treatment, the dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, which is the 
recommended effective dose. 
 
It is recommended to apply the first transdermal patch on the day following the last oral dose. 
 
Special populations 
- Paediatric population: There is no relevant use of Rivastigmine 3M Health Care Ltd. in the 

paediatric population in the treatment of Alzheimer’s disease. 
- Patients with body weight below 50 kg: Particular caution should be exercised in titrating 

patients with body weight below 50 kg above the recommended effective dose of 9.5 mg/24 h 
(see section 4.4). They may experience more adverse reactions and may be more likely to 
discontinue due to adverse reactions. 

- Hepatic impairment: No dose adjustment is necessary for patients with hepatic impairment. 
However, due to increased exposure in these populations as observed with the oral forms, dosing 
recommendations to titrate according to individual tolerability should be closely followed as 
patients with clinically significant hepatic impairment might experience more adverse reactions. 
Patients with severe hepatic impairment have not been studied (see sections 4.4 and 5.2). 

- Renal impairment: No dose adjustment is necessary for patients with renal impairment. 
However, due to increased exposure in these populations as observed with the oral forms, dosing 
recommendations to titrate according to individual tolerability should be closely followed as 
patients with clinically significant renal impairment might experience more adverse reactions 
(see sections 4.4 and 5.2). 

 
Method of administration 
Transdermal patches should be applied once a day to clean, dry, hairless, intact healthy skin on the upper 
or lower back, upper arm or chest, in a place which will not be rubbed by tight clothing. It is not 

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recommended to apply the transdermal patch to the thigh or to the abdomen due to decreased 
bioavailability of rivastigmine observed when the transdermal patch is applied to these areas of the body. 
 
The transdermal patch should not be applied to skin that is red, irritated or cut. Reapplication to the exact 
same skin location within 14 days should be avoided to minimise the potential risk of skin irritation. 
 
Patients and caregivers should be instructed on important administration instructions: 
- The previous day’s patch must be removed before applying a new one every day (see section 4.9). 
- The patch should be replaced by a new one after 24 hours. Only one patch should be worn at a 

time (see section 4.9). 
- The patch should be pressed down firmly for at least 30 seconds using the palm of the hand until 

the edges stick well. 
- If the patch falls off, a new one should be applied for the rest of the day, then it should be replaced 

at the same time as usual the next day. 
- The patch can be used in everyday situations, including bathing and during hot weather. 
- The patch should not be exposed to any external heat sources (e.g. excessive sunlight, saunas, 

solarium) for long periods of time. 
- The patch should not be cut into pieces. 
 
4.3 Contraindications 
 
The use of this medicinal product is contraindicated in patients with known hypersensitivity to the active 
substance rivastigmine, to other carbamate derivatives or to any of the excipients listed in section 6.1. 
 
Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine 
patch (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
The incidence and severity of adverse reactions generally increase with increasing doses, particularly 
at dose changes. If treatment is interrupted for more than three days, it should be re-initiated with 
4.6 mg/24 h. 
 
Misuse of the medicinal product and dosing errors resulting in overdose 
Misuse of the medicinal product and dosing errors with rivastigmine transdermal patches have resulted 
in serious adverse reactions; some cases have required hospitalisation, and rarely led to death (see 
section 4.9). Most cases of misuse of the medicinal product and dosing errors have involved not 
removing the old patch when putting on a new one and the use of multiple patches at the same time. 
Patients and their caregivers must be instructed on important administration instructions for 
Rivastigmine 3M Health Care Ltd. transdermal patch (see section 4.2). 
 
Gastrointestinal disorders 
Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose-related, and may occur 
when initiating treatment and/or increasing the dose (see section 4.8). These adverse reactions occur 
more commonly in women. Patients who show signs or symptoms of dehydration resulting from 
prolonged vomiting or diarrhoea can be managed with intravenous fluids and dose reduction or 
discontinuation if recognised and treated promptly. Dehydration can be associated with serious 
outcomes. 
 
Weight loss 
Patients with Alzheimer’s disease may lose weight whilst taking cholinesterase inhibitors, including 
rivastigmine. The patient’s weight should be monitored during therapy with Rivastigmine 3M Health 
Care Ltd. transdermal patches. 
 
Other adverse reactions 
Care must be taken when prescribing Rivastigmine 3M Health Care Ltd. transdermal patches: 
- to patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular 

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block) (see section 4.8) 
- to patients with active gastric or duodenal ulcers or patients predisposed to these conditions 

because rivastigmine may cause increased gastric secretions (see section 4.8) 
- to patients predisposed to urinary obstruction and seizures because cholinomimetics may induce 

or exacerbate these diseases. 
- to patients with a history of asthma or obstructive pulmonary disease. 
 
Skin application site reactions 
Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in 
intensity. Patients and caregivers should be instructed accordingly. 
 
These reactions are not in themselves an indication of sensitisation. 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, oedema, papules, vesicles) 
and if symptoms do not significantly improve within 48 hours after patch removal. In these cases, 
treatment should be discontinued (see section 4.3). 
 
Patients who develop application site reactions suggestive of allergic contact dermatitis to rivastigmine 
patch and who still require rivastigmine treatment should only be switched to oral rivastigmine after 
negative allergy testing and under close medical supervision. It is possible that some patients sensitised to 
rivastigmine by exposure to rivastigmine patch may not be able to take rivastigmine in any form. 
 
There have been rare post-marketing reports of patients experiencing disseminated skin hypersensitivity 
reactions when administered rivastigmine irrespective of the route of administration (oral, transdermal). 
In these cases, treatment should be discontinued (see section 4.3). 
 
Other warnings and precautions 
 
Rivastigmine may exacerbate or induce extrapyramidal symptoms. 
 
Contact with the eyes should be avoided after handling Rivastigmine 3M Health Care Ltd. transdermal 
patches (see section 5.3). Hands should be washed 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. 
 
Special populations: 
- Patients with body weight below 50 kg may experience more adverse reactions and may be 

more likely to discontinue due to adverse reactions (see section 4.2). Carefully titrate and 
monitor these patients for adverse reactions (e.g. excessive nausea or vomiting) and consider 
reducing the maintenance dose to the 4.6 mg/24 h transdermal patch if such adverse reactions 
develop. 

- Hepatic impairment: Patients with clinically significant hepatic impairment might experience 
more adverse reactions (see sections 4.2 and 5.2). Consider using the 4.6 mg/24 h transdermal 
patch both as initial and maximum dose in these patients. 

- Renal impairment: Patients with clinically significant renal impairment might experience more 
adverse reactions (see sections 4.2 and 5.2). Consider using the 4.6 mg/24 h transdermal patch 
both as initial and maximum dose in these patients. 

 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No specific interaction studies have been performed with Rivastigmine 3M Health Care Ltd. transdermal 
patches. 
 
As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle 

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relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible dose 
adjustments or temporarily stopping treatment can be considered if needed. 
 
In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other 
cholinomimetic substances and might interfere with the activity of anticholinergic medicinal products. 
 
No pharmacokinetic interaction was observed between oral rivastigmine 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 oral rivastigmine. No untoward effects on cardiac conduction were 
observed following concomitant administration of digoxin and oral rivastigmine. 
 
Concomitant administration of rivastigmine with commonly prescribed medicinal products, such as 
antacids, antiemetics, antidiabetics, centrally acting antihypertensives, beta blockers, calcium channel 
blockers, inotropic agents, antianginals, non-steroidal anti-inflammatory agents, oestrogens, analgesics, 
benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine 
or an increased risk of clinically relevant untoward effects. 
 
According to its metabolism, metabolic interactions with other medicinal products appear unlikely, 
although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
No clinical data on exposed pregnancies are available. In peri/postnatal studies in rats, an increased 
gestation time was observed. Rivastigmine should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
In animals, rivastigmine is excreted into milk. It is not known if rivastigmine is excreted into human 
milk. Therefore, women on rivastigmine should not breast-feed. 
 
Fertility 
No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses 
related to maternal toxicity. 
 
4.7 Effects on ability to drive and use machines 
 
Alzheimer’s disease may cause gradual impairment of driving performance or compromise the ability to 
use machines. Furthermore, rivastigmine may induce syncope or delirium. As a consequence, 
rivastigmine has minor or moderate influence on the ability to drive and use machines. Therefore, in 
patients with dementia treated with rivastigmine, the ability to continue driving or operating complex 
machines should be routinely evaluated by the treating physician. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Application site skin reactions (usually mild to moderate application site erythema), are the most 
frequent adverse reactions observed with the use of rivastigmine transdermal patch. The next most 
common adverse reactions are gastrointestinal in nature including nausea and vomiting. 
 
Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency 
category. Frequency categories are defined using the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000); not known (cannot be estimated from the available data). 
 
Tabulated list of adverse reactions 

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Table 1 displays the adverse reactions reported in 854 patients with Alzheimer’s dementia treated in 
randomised, double-blind, placebo and active-controlled clinical studies with rivastigmine transdermal 
patches for a duration of 24-48 weeks and from post-marketing data. 
 
Table 1 
 
Infections and infestations 
 Common Urinary tract infection 
Metabolism and nutrition disorders 
 Common Anorexia, decreased appetite 
 Uncommon Dehydration 
Psychiatric disorders
 Common Anxiety, depression, delirium, agitation 
 Uncommon Aggression 
 Not known Hallucinations, restlessness 
Nervous system disorders 
 Common Headache, syncope, dizziness 
 Uncommon Psychomotor hyperactivity 
 Very rare Extrapyramidal symptoms 
 Not known Worsening of Parkinson’s disease, seizure 
Cardiac disorders 
 Uncommon Bradycardia 
 Not known Atrioventricular block, atrial fibrillation, tachycardia, sick sinus 

syndrome 
Vascular disorders 
 Not known Hypertension 
Gastrointestinal disorders 
 Common Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain 
 Uncommon Gastric ulcer 
 Not known Pancreatitis 
Hepatobiliary disorders 
 Not known Hepatitis, elevated liver function tests 
Skin and subcutaneous tissue disorders
 Common Rash 
 Not known Pruritus, erythema, urticaria, vesicles, allergic dermatitis, disseminated 

cutaneous hypersensitivity reactions 
Renal and urinary disorders 
 Common Urinary incontinence 
General disorders and administration site conditions
 Common Application site skin reactions (e.g. application site erythema, 

application site pruritus, application site oedema, application site 
dermatitis, application site irritation), asthenic conditions (e.g. fatigue, 
asthenia), pyrexia, weight decreased 

 Rare Fall 
 
Description of selected adverse reactions 
When doses higher than 13.3 mg/24 h were used in the above-mentioned placebo-controlled study, 
insomnia and cardiac failure were observed more frequently than with 13.3 mg/24 h or placebo, 
suggesting a dose effect relationship. However, these events did not occur at a higher frequency with 
rivastigmine 13.3 mg/24 h transdermal patches than with placebo. 
 
The following adverse reactions have only been observed with rivastigmine capsules and oral solution 
and not in clinical studies with rivastigmine transdermal patches: somnolence, malaise, tremor, 
confusion, sweating increased (common); duodenal ulcers, angina pectoris (rare); gastrointestinal 
haemorrhage (very rare); and some cases of severe vomiting were associated with oesophageal rupture 
(not known). 
 

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Skin irritation 
In a 24-week double-blind, placebo-controlled clinical trial, skin reactions were measured at each visit 
using a skin irritation rating scale that rated the degree of erythema, oedema, scaling, fissures, pruritus 
and pain/stinging/burning at the application site. The most commonly observed symptom was 
erythema which disappeared within 24 hours in the vast majority of patients. In the 24-week double-
blind study, the most commonly observed symptoms (skin irritation rating scale) with rivastigmine 
9.5 mg/24 h transdermal patches were very slight (21.8%), mild (12.5%) or moderate (6.5%) erythema 
or very slight (11.9%), mild (7.3%) or moderate (5.0%) pruritus. The most commonly observed severe 
symptoms with rivastigmine 9.5 mg/24 h transdermal patches were pruritus (1.7%) and erythema 
(1.1%). Most skin reactions were limited to the application site and resulted in discontinuation in only 
2.4% of the patients in the rivastigmine 9.5 mg/24 h transdermal patch group. 
 
In a 48-week active-controlled clinical trial, cases of skin irritation were captured as patient or 
caregiver reported adverse reactions. The most commonly reported skin irritation events during the 
first 24 weeks of the double-blind period with rivastigmine 13.3 mg/24 h transdermal patches and 
rivastigmine 9.5 mg/24 h transdermal patches, respectively were application site erythema (5.7% vs 
4.6%) and application site pruritus (3.6% vs 2.8%). The percentages decreased in both rivastigmine 
13.3 mg/24 h transdermal patch and rivastigmine 9.5 mg/24 h transdermal patch treatment groups over 
time (>24 weeks): application site erythema (0.8% vs. 1.6%) and application site pruritus (0.4% vs. 
1.2%), respectively. Application site pruritus led to discontinuation in 1.1% of the patients from each 
of the treatment groups during the total 48-week double-blind treatment phase. Application site 
reactions were mostly mild to moderate in severity and were rated as severe in less than 2% of 
patients. 
 
A direct comparison of the rate of skin irritation events reported in each of these studies cannot be 
made due to the difference in data collection methods employed. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
Most cases of accidental overdose of oral rivastigmine have not been associated with any clinical signs or 
symptoms and almost all of the patients concerned continued rivastigmine treatment. Where symptoms 
have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations. Due to 
the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may 
also occur. Ingestion of 46 mg of oral rivastigmine occurred in one case; following conservative 
management the patient fully recovered within 24 hours. Overdose with rivastigmine transdermal patches 
resulting from misuse/dosing errors (application of multiple patches at a time) has been reported in the 
post-marketing setting. The typical symptoms reported among these cases are similar to those seen with 
cases of overdose associated with rivastigmine oral formulations. 
 
Treatment 
As rivastigmine has a plasma half-life of about 3.4 hours and a duration of acetylcholinesterase inhibition 
of about 9 hours, it is recommended that in cases of asymptomatic overdose all Rivastigmine 3M Health 
Care Ltd. transdermal patches should be removed immediately and no further transdermal patch should 
be applied for the next 24 hours. In overdose accompanied by severe nausea and vomiting, the use of 
antiemetics should be considered. Symptomatic treatment for other adverse reactions should be given as 
necessary. 
 
In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine sulphate is 
recommended, with subsequent doses based on clinical response. Use of scopolamine as an antidote is 
not recommended. 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: psychoanaleptics, anticholinesterases, ATC code: N06DA03 
 
Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to 
facilitate cholinergic neurotransmission by slowing the degradation of acetylcholine released by 
functionally intact cholinergic neurones. Thus, rivastigmine may have an ameliorative effect on 
cholinergic-mediated cognitive deficits in dementia associated with Alzheimer’s disease. 
 
Rivastigmine interacts with its target enzymes by forming a covalently bound complex that 
temporarily inactivates the enzymes. In healthy young men, an oral 3 mg dose decreases 
acetylcholinesterase (AChE) activity in CSF by approximately 40% within the first 1.5 hours after 
administration. Activity of the enzyme returns to baseline levels about 9 hours after the maximum 
inhibitory effect has been achieved. In patients with Alzheimer’s disease, inhibition of AChE in CSF 
by oral rivastigmine was dose-dependent up to 6 mg given twice daily, the highest dose tested. 
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by oral 
rivastigmine was similar to the inhibition of AChE activity. 
 
Clinical studies in Alzheimer’s dementia 
The efficacy of rivastigmine transdermal patches in patients with Alzheimer’s dementia has been 
demonstrated in a 24-week double-blind, placebo-controlled core study and its open-label extension 
phase and in a 48-week double-blind comparator study.  
 
24-week placebo-controlled study 
Patients involved in the placebo-controlled study had an MMSE (Mini-Mental State Examination) 
score of 10–20. Efficacy was established by the use of independent, domain-specific assessment tools 
which were applied at regular intervals during the 24-week treatment period. These include the 
ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a performance-based 
measure of cognition) and the ADCS-CGIC (Alzheimer’s Disease Cooperative Study – Clinician’s 
Global Impression of Change, a comprehensive global assessment of the patient  by the physician 
incorporating caregiver input), and the ADCS-ADL (Alzheimer’s Disease Cooperative Study – 
Activities of Daily Living, a caregiver-rated assessment of the activities of daily living including 
personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient 
oneself to surroundings as well as involvement in activities related to finances). The 24-week results 
for the three assessment tools are summarised in Table 2. 
 
Table 2 
 
 Rivastigmine 

transdermal patches 
9.5 mg/24 h 

Rivastigmine 
capsules 

12 mg/day 

Placebo 

ITT-LOCF population N = 251 N = 256 N = 282 
ADAS-Cog    
 (n=248) (n=253) (n=281) 
Mean baseline  SD 27.0  10.3 27.9  9.4 28.6  9.9 
Mean change at week 24  SD -0.6  6.4 -0.6  6.2 1.0  6.8 
p-value versus placebo 0.005*1 0.003*1  
ADCS-CGIC    
 (n=248) (n=253) (n=278) 
Mean score  SD 3.9  1.20 3.9  1.25 4.2  1.26 
p-value versus placebo 0.010*2 0.009*2  
ADCS-ADL    

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 (n=247) (n=254) (n=281) 
Mean baseline  SD 50.1  16.3 49.3  15.8 49.2  16.0 
Mean change at week 24  SD -0.1  9.1 -0.5  9.5 -2.3  9.4 
p-value versus placebo 0.013*1 0.039*1  
* p≤0.05 versus placebo 
ITT: Intent-To-Treat; LOCF: Last Observation Carried Forward 
1 Based on ANCOVA with treatment and country as factors and baseline value as a covariate. 
Negative ADAS-Cog changes indicate improvement. Positive ADCS-ADL changes indicate 
improvement. 
2 Based on CMH test (van Elteren test) blocking for country. ADCS-CGIC scores <4 indicate 
improvement. 
 
The results for clinically relevant responders from the 24-week placebo-controlled study are provided 
in Table 3. Clinically relevant improvement was defined a priori as at least 4-point improvement on 
the ADAS-Cog, no worsening on the ADCS-CGIC, and no worsening on the ADCS-ADL. 
 
Table 3 
 

 Patients with clinically significant response (%) 
 
 
 
ITT-LOCF population 

Rivastigmine 
transdermal patches 

9.5 mg/24 h 
N = 251 

Rivastigmine 
capsules 

12 mg/day 
N = 256 

Placebo 
 

 
N = 282 

At least 4 points 
improvement on ADAS-Cog 
with no worsening on ADCS-
CGIC and ADCS-ADL 
 

17.4 19.0 10.5 

p-value versus placebo 0.037* 0.004*  
*p<0.05 versus placebo 

 
As suggested by compartmental modelling, 9.5 mg/24 h transdermal patches exhibited exposure 
similar to that provided by an oral dose of 12 mg/day. 
 
48-week active comparator controlled study 
Patients involved in the active comparator controlled study had an initial baseline MMSE score of 
10-24. The study was designed to compare the efficacy of the 13.3 mg/24 h transdermal patch against 
the 9.5 mg/24 h transdermal patch during a 48-week double-blind treatment phase in Alzheimer’s 
disease patients who demonstrated functional and cognitive decline after an initial 24-48 week open-
label treatment phase while on a maintenance dose of 9.5 mg/24 h transdermal patch. Functional 
decline was assessed by the investigator and cognitive decline was defined as a decrease in the MMSE 
score of >2 points from the previous visit or a decrease of >3 points from baseline. Efficacy was 
established by the use of ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a 
performance-based measure of cognition) and the ADCS-IADL (Alzheimer’s Disease Cooperative 
Study – Instrumental Activities of Daily Living) assessing instrumental activities which include 
maintaining finances, meal preparation, shopping, ability to orient oneself to surroundings, ability to 
be left unattended. The 48-week results for the two assessment tools are summarised in Table 4. 
 
Table 4 
 
 
Population/Visit 

Rivastigmine 
13.3 mg/24 h 
N = 265 

Rivastigmine 
9.5 mg/24 h 
N = 271 

Rivastigmine 
13.3 mg/24 h 

Rivastigmine 
9.5 mg/24 h 

n Mean n Mean DLSM 95% CI p-value 
ADAS-Cog         
LOCF Baseline 264 34.4 268 34.9    

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 DB-week 48 Value 264 38.5 268 39.7    
  Change 264 4.1 268 4.9 -0.8 (-2.1, 

0.5) 
0.227 

ADCS-IADL         
LOCF Baseline 265 27.5 271 25.8    
 Week 48 Value 265 23.1 271 19.6    
  Change 265 -4.4 271 -6.2 2.2 (0.8, 

3.6) 
0.002* 

CI – confidence interval. 
DLSM – difference in least square means. 
LOCF – Last Observation Carried Forward. 
ADAS-cog scores: A negative difference in DLSM indicates greater improvement in Rivastigmine 
13.3 mg/24 h as compared to Rivastigmine 9.5 mg/24 h. 
ADCS-IADL scores: A positive difference in DLSM indicates greater improvement in Rivastigmine 
13.3 mg/24 h as compared to Rivastigmine 9.5 mg/24 h. 
N is the number of patients with an assessment at baseline (last assessment in the initial open-label 
phase) and with at least 1 post-baseline assessment (for the LOCF). 
The DLSM, 95% CI, and p-value are based on an ANCOVA (analysis of covariance) model adjusted 
for country and baseline ADAS-cog score. 
* p<0.05 
 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
rivastigmine in all subsets of the paediatric population in the treatment of Alzheimer’s dementia (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Absorption of rivastigmine from rivastigmine transdermal patches is slow. After the first dose, 
detectable plasma concentrations are observed after a lag time of 0.5-1 hour. Cmax is reached after 
10-16 hours. After the peak, plasma concentrations slowly decrease over the remainder of the 24-hour 
period of application. With multiple dosing (such as at steady state), after the previous transdermal 
patch is replaced with a new one, plasma concentrations initially decrease slowly for about 40 minutes 
on average, until absorption from the newly applied transdermal patch becomes faster than 
elimination, and plasma levels begin to rise again to reach a new peak at approximately 8 hours. At 
steady state, trough levels are approximately 50% of peak levels, in contrast to oral administration, 
with which concentrations fall off to virtually zero between doses. Although less pronounced than 
with the oral formulation, exposure to rivastigmine (Cmax and AUC) increased over-proportionally by a 
factor of 2.6 and 4.9 when escalating from 4.6 mg/24 h to 9.5 mg/24 h and to 13.3 mg/24 h, 
respectively. The fluctuation index (FI), a measure of the relative difference between peak and trough 
concentrations ((Cmax-Cmin)/Cavg), was 0.58 for rivastigmine 4.6 mg/24 h transdermal patches, 0.77 for 
rivastigmine 9.5 mg/24 h transdermal patches and 0.72 for rivastigmine 13.3 mg/24 h transdermal 
patches, thus demonstrating a much smaller fluctuation between trough and peak concentrations than 
for the oral formulation (FI = 3.96 (6 mg/day) and 4.15 (12 mg/day)). 
 
The dose of rivastigmine released from the transdermal patch over 24 hours (mg/24 h) cannot be 
directly equated to the amount (mg) of rivastigmine contained in a capsule with respect to plasma 
concentration produced over 24 hours. 
 
The single-dose inter-subject variability in rivastigmine pharmacokinetic parameters (normalised to 
dose/kg bodyweight) was 43% (Cmax) and 49% (AUC0-24h) after transdermal administration versus 
74% and 103%, respectively, after the oral form. The inter-patient variability in a steady-state study in 
Alzheimer’s dementia was at most 45% (Cmax) and 43% (AUC0-24h) after use of the transdermal patch, 
and 71% and 73%, respectively, after administration of the oral form. 
 
A relationship between active substance exposure at steady state (rivastigmine and metabolite 

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NAP226-90) and bodyweight was observed in Alzheimer’s dementia patients. 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. The effect of bodyweight on active substance 
exposure suggests special attention to patients with very low body weight during up-titration (see 
section 4.4). 
 
Exposure (AUC∞) to rivastigmine (and metabolite NAP266-90) was highest when the transdermal 
patch was applied to the upper back, chest, or upper arm and approximately 20–30% lower when 
applied to the abdomen or thigh. 
 
There was no relevant accumulation of rivastigmine or the metabolite NAP226-90 in plasma in patients 
with Alzheimer’s disease, except that plasma levels were higher on the second day of transdermal patch 
therapy than on the first. 
 
Distribution 
Rivastigmine is weakly bound to plasma proteins (approximately 40%). It readily crosses the blood-brain 
barrier and has an apparent volume of distribution in the range of 1.8-2.7 l/kg. 
 
Biotransformation 
Rivastigmine is rapidly and extensively metabolised with an apparent elimination half-life in plasma of 
approximately 3.4 hours after removal of the transdermal patch. Elimination was absorption rate limited 
(flip-flop kinetics), which explains the longer t½ after transdermal patch (3.4 h) versus oral or intravenous 
administrations (1.4 to 1.7 h). Metabolism is primarily via cholinesterase-mediated hydrolysis to the 
metabolite NAP226-90. In vitro, this metabolite shows minimal inhibition of acetylcholinesterase 
(<10%). Based on evidence from in vitro and animal studies, the major cytochrome P450 isoenzymes are 
minimally involved in rivastigmine metabolism. Total plasma clearance of rivastigmine was 
approximately 130 litres/h after a 0.2 mg intravenous dose and decreased to 70 litres/h after a 2.7 mg 
intravenous dose, which is consistent with the non-linear, over-proportional pharmacokinetics of 
rivastigmine due to saturation of its elimination. 
 
The metabolite-to-parent AUC∞ ratio was around 0.7 after transdermal patch administration versus 3.5 
after oral administration, indicating that much less metabolism occurred after dermal compared to oral 
treatment. Less NAP226-90 is formed following application of the transdermal patch, presumably 
because of the lack of presystemic (hepatic first pass) metabolism, in contrast to oral administration. 
 
Elimination 
Unchanged rivastigmine is found in trace amounts in the urine; renal excretion of the metabolites is the 
major route of elimination after transdermal patch administration. Following administration of oral 14C-
rivastigmine, renal elimination was rapid and essentially complete (>90%) within 24 hours. Less than 1% 
of the administered dose is excreted in the faeces. 
 
Elderly population 
Age had no impact on the exposure to rivastigmine in Alzheimer’s disease patients treated with 
rivastigmine transdermal patches. 
 
Hepatic impairment 
No study was conducted with rivastigmine transdermal patches in subjects with hepatic impairment. 
After oral administration, the Cmax of rivastigmine was approximately 60% higher and the AUC of 
rivastigmine was more than twice as high in subjects with mild to moderate hepatic impairment than in 
healthy subjects. 
 
Renal impairment 
No study was conducted with rivastigmine transdermal patches in subjects with renal impairment. After 
oral administration, Cmax and AUC of rivastigmine were more than twice as high in Alzheimer patients 
with moderate renal impairment compared with healthy subjects; however there were no changes in Cmax 
and AUC of rivastigmine in Alzheimer patients with severe renal impairment. 

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5.3 Preclinical safety data 
 
Oral and topical repeated-dose toxicity studies in mice, rats, rabbits, dogs and minipigs revealed only 
effects associated with an exaggerated pharmacological action. No target organ toxicity was observed. 
Oral and topical dosing in animal studies was limited due to the sensitivity of the animal models used. 
 
Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a 
chromosomal aberration test in human peripheral lymphocytes at a dose exceeding 104 times the foreseen 
clinical exposure. The in vivo micronucleus test was negative. 
 
No evidence of carcinogenicity was found in oral and topical studies in mice and in an oral study in 
rats at the maximum tolerated dose. The exposure to rivastigmine and its metabolites was 
approximately equivalent to human exposure with highest doses of rivastigmine capsules and 
transdermal patches. 
 
In animals, rivastigmine crosses the placenta and is excreted into milk. Oral studies in pregnant rats and 
rabbits gave no indication of teratogenic potential on the part of rivastigmine. Specific dermal studies in 
pregnant animals have not been conducted. 
 
Rivastigmine transdermal patches were not phototoxic. In some other dermal toxicity studies, a mild 
irritant effect on the skin of laboratory animals, including controls, was observed. This may indicate a 
potential for rivastigmine transdermal patches to induce mild erythema in patients. When administered to 
rabbit eyes in primary eye irritation studies, rivastigmine caused reddening and swelling of the 
conjunctiva, corneal opacities and miosis which persisted for 7 days. Therefore, the patient/caregiver 
should avoid contact with the eyes after handling of the patch (see section 4.4). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Backing layer 
Polyester and ethyl vinyl acetate 
 
Drug-in-adhesive (DIA) matrix 
Acrylate copolymer adhesive 
Isopropyl myristate 
 
Release liner 
Polyester 
 
6.2 Incompatibilities 
 
To prevent interference with the adhesive properties of the transdermal patch, no cream, lotion or 
powder should be applied to the skin area where the medicinal product is to be applied. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container 
 

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Heat-sealed pouches made of paper/aluminium/acrylonitrile-methacrylate copolymer laminate. One 
pouch contains one transdermal patch.  
 
Available in packs containing 7, 30, 60 and 90 pouches. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Used transdermal patches should be folded in half, with the adhesive side inwards, placed in the original 
pouch and discarded safely and out of the sight and reach of children. 
Any used or unused transdermal patches should be disposed of in accordance with local requirements or 
returned to the pharmacy. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/14/911/001 
EU/1/14/911/002 
EU/1/14/911/003 
EU/1/14/911/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
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1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patch 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each transdermal patch releases 9.5 mg of rivastigmine per 24 hours. Each transdermal patch of 
8.3 cm2 contains 14.33 mg of rivastigmine. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Transdermal patch 
 
Rectangular patches, approximately 3.5 cm by 2.6 cm with rounded corners. Each patch consists of a 
combination of a removable, transparent, split release liner, a functional layer containing drug-in-
adhesive (DIA) matrix, and a protective backing layer. The backing layer is transparent to translucent, 
labelled with “R10” in a repeated pattern. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment 
of Alzheimer’s dementia. Diagnosis should be made according to current guidelines. Similar to any 
treatment initiated in patients with dementia, therapy with rivastigmine should only be started if a 
caregiver is available to regularly administer and monitor the treatment. 
 
Posology 
 
Transdermal patches Rivastigmine in vivo release 

rates per 24 h
Rivastigmine 4.6 mg/24 h 4.6 mg 
Rivastigmine 9.5 mg/24 h 9.5 mg 
Rivastigmine 13.3 mg/24 h* 13.3 mg 
 
*A marketing authorisation for Rivastigmine 3M Health Care Ltd. 13.3 mg/24 h transdermal patch is 
currently not available, this presentation may although be available from other marketing authorisation 
holders.  
 
Initial dose 
Treatment is started with 4.6 mg/24 h. 
 
Maintenance dose 
After a minimum of four weeks of treatment and if well tolerated according to the treating physician, the 
dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, the daily recommended effective dose, which 
should be continued for as long as the patient continues to demonstrate therapeutic benefit. 

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Dose escalation 
9.5 mg/24 h is the recommended daily effective dose which should be continued for as long as the patient 
continues to demonstrate therapeutic benefit. If well tolerated and only after a minimum of six months 
of treatment at 9.5 mg/24 h, the treating physician may consider increasing the dose to 13.3 mg/24 h in 
patients who have demonstrated a meaningful cognitive deterioration (e.g. decrease in the MMSE) 
and/or functional decline (based on physician judgement) while on the recommended daily effective 
dose of 9.5 mg/24 h (see section 5.1). 
 
The clinical benefit of rivastigmine should be reassessed on a regular basis. Discontinuation should also 
be considered when evidence of a therapeutic effect at the optimal dose is no longer present. 
 
Treatment should be temporarily interrupted if gastrointestinal adverse reactions are observed until 
these adverse reactions resolve. Transdermal patch treatment can be resumed at the same dose if 
treatment is not interrupted for more than three days. Otherwise treatment should be re-initiated with 
4.6 mg/24 h. 
 
Switching from capsules or oral solution to transdermal patches 
Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients 
treated with rivastigmine capsules or oral solution can be switched to Rivastigmine 3M Health Care 
Ltd. transdermal patches as follows: 
- A patient on a dose of 3 mg/day oral rivastigmine can be switched to 4.6 mg/24 h transdermal 

patches. 
- A patient on a dose of 6 mg/day oral rivastigmine can be switched to 4.6 mg/24 h transdermal 

patches. 
- A patient on a stable and well tolerated dose of 9 mg/day oral rivastigmine can be switched to 

9.5 mg/24 h transdermal patches. If the oral dose of 9 mg/day has not been stable and well 
tolerated, a switch to 4.6 mg/24 h transdermal patches is recommended. 

- A patient on a dose of 12 mg/day oral rivastigmine can be switched to 9.5 mg/24 h transdermal 
patches. 

 
After switching to 4.6 mg/24 h transdermal patches, provided these are well tolerated after a minimum of 
four weeks of treatment, the dose of 4.6 mg/24 h should be increased to 9.5 mg/24 h, which is the 
recommended effective dose. 
 
It is recommended to apply the first transdermal patch on the day following the last oral dose. 
 
Special populations 
- Paediatric population: There is no relevant use of Rivastigmine 3M Health Care Ltd. in the 

paediatric population in the treatment of Alzheimer’s disease. 
- Patients with body weight below 50 kg: Particular caution should be exercised in titrating 

patients with body weight below 50 kg above the recommended effective dose of 9.5 mg/24 h 
(see section 4.4). They may experience more adverse reactions and may be more likely to 
discontinue due to adverse reactions. 

- Hepatic impairment: No dose adjustment is necessary for patients with hepatic impairment. 
However, due to increased exposure in these populations as observed with the oral forms, dosing 
recommendations to titrate according to individual tolerability should be closely followed as 
patients with clinically significant hepatic impairment might experience more adverse reactions. 
Patients with severe hepatic impairment have not been studied (see sections 4.4 and 5.2). 

- Renal impairment: No dose adjustment is necessary for patients with renal impairment. 
However, due to increased exposure in these populations as observed with the oral forms, dosing 
recommendations to titrate according to individual tolerability should be closely followed as 
patients with clinically significant renal impairment might experience more adverse reactions 
(see sections 4.4 and 5.2). 

 
Method of administration 
Transdermal patches should be applied once a day to clean, dry, hairless, intact healthy skin on the upper 

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or lower back, upper arm or chest, in a place which will not be rubbed by tight clothing. It is not 
recommended to apply the transdermal patch to the thigh or to the abdomen due to decreased 
bioavailability of rivastigmine observed when the transdermal patch is applied to these areas of the body. 
 
The transdermal patch should not be applied to skin that is red, irritated or cut. Reapplication to the exact 
same skin location within 14 days should be avoided to minimise the potential risk of skin irritation. 
 
Patients and caregivers should be instructed on important administration instructions: 
- The previous day’s patch must be removed before applying a new one every day (see section 4.9). 
- The patch should be replaced by a new one after 24 hours. Only one patch should be worn at a 

time (see section 4.9). 
- The patch should be pressed down firmly for at least 30 seconds using the palm of the hand until 

the edges stick well. 
- If the patch falls off, a new one should be applied for the rest of the day, then it should be replaced 

at the same time as usual the next day. 
- The patch can be used in everyday situations, including bathing and during hot weather. 
- The patch should not be exposed to any external heat sources (e.g. excessive sunlight, saunas, 

solarium) for long periods of time. 
- The patch should not be cut into pieces. 
 
4.3 Contraindications 
 
The use of this medicinal product is contraindicated in patients with known hypersensitivity to the active 
substance rivastigmine, to other carbamate derivatives or to any of the excipients listed in section 6.1. 
 
Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine 
patch (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
The incidence and severity of adverse reactions generally increase with increasing doses, particularly 
at dose changes. If treatment is interrupted for more than three days, it should be re-initiated with 
4.6 mg/24 h. 
 
Misuse of the medicinal product and dosing errors resulting in overdose 
Misuse of the medicinal product and dosing errors with rivastigmine transdermal patches have resulted 
in serious adverse reactions; some cases have required hospitalisation, and rarely led to death (see 
section 4.9). Most cases of misuse of the medicinal product and dosing errors have involved not 
removing the old patch when putting on a new one and the use of multiple patches at the same time. 
Patients and their caregivers must be instructed on important administration instructions for 
Rivastigmine 3M Health Care Ltd. transdermal patch (see section 4.2). 
 
Gastrointestinal disorders 
Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose-related, and may occur 
when initiating treatment and/or increasing the dose (see section 4.8). These adverse reactions occur 
more commonly in women. Patients who show signs or symptoms of dehydration resulting from 
prolonged vomiting or diarrhoea can be managed with intravenous fluids and dose reduction or 
discontinuation if recognised and treated promptly. Dehydration can be associated with serious 
outcomes. 
 
Weight loss 
Patients with Alzheimer’s disease may lose weight whilst taking cholinesterase inhibitors, including 
rivastigmine. The patient’s weight should be monitored during therapy with Rivastigmine 3M Health 
Care Ltd. transdermal patches. 
 
Other adverse reactions 
Care must be taken when prescribing Rivastigmine 3M Health Care Ltd. transdermal patches: 

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- to patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular 
block) (see section 4.8) 

- to patients with active gastric or duodenal ulcers or patients predisposed to these conditions 
because rivastigmine may cause increased gastric secretions (see section 4.8) 

- to patients predisposed to urinary obstruction and seizures because cholinomimetics may induce 
or exacerbate these diseases. 

- to patients with a history of asthma or obstructive pulmonary disease. 
 
Skin application site reactions 
Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in 
intensity. Patients and caregivers should be instructed accordingly. 
 
These reactions are not in themselves an indication of sensitisation. 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, oedema, papules, vesicles) 
and if symptoms do not significantly improve within 48 hours after patch removal. In these cases, 
treatment should be discontinued (see section 4.3). 
 
Patients who develop application site reactions suggestive of allergic contact dermatitis to rivastigmine 
patch and who still require rivastigmine treatment should only be switched to oral rivastigmine after 
negative allergy testing and under close medical supervision. It is possible that some patients sensitised to 
rivastigmine by exposure to rivastigmine patch may not be able to take rivastigmine in any form. 
 
There have been rare post-marketing reports of patients experiencing disseminated skin hypersensitivity 
reactions when administered rivastigmine irrespective of the route of administration (oral, transdermal). 
In these cases, treatment should be discontinued (see section 4.3). 
 
Other warnings and precautions 
 
Rivastigmine may exacerbate or induce extrapyramidal symptoms. 
 
Contact with the eyes should be avoided after handling Rivastigmine 3M Health Care Ltd. transdermal 
patches (see section 5.3). Hands should be washed 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. 
 
Special populations: 
- Patients with body weight below 50 kg may experience more adverse reactions and may be 

more likely to discontinue due to adverse reactions (see section 4.2). Carefully titrate and 
monitor these patients for adverse reactions (e.g. excessive nausea or vomiting) and consider 
reducing the maintenance dose to the 4.6 mg/24 h transdermal patch if such adverse reactions 
develop. 

- Hepatic impairment: Patients with clinically significant hepatic impairment might experience 
more adverse reactions (see sections 4.2 and 5.2). Consider using the 4.6 mg/24 h transdermal 
patch both as initial and maximum dose in these patients. 

- Renal impairment: Patients with clinically significant renal impairment might experience more 
adverse reactions (see sections 4.2 and 5.2). Consider using the 4.6 mg/24 h transdermal patch 
both as initial and maximum dose in these patients. 

 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No specific interaction studies have been performed with Rivastigmine 3M Health Care Ltd. transdermal 
patches. 
 
As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle 

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relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible dose 
adjustments or temporarily stopping treatment can be considered if needed. 
 
In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other 
cholinomimetic substances and might interfere with the activity of anticholinergic medicinal products. 
 
No pharmacokinetic interaction was observed between oral rivastigmine 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 oral rivastigmine. No untoward effects on cardiac conduction were 
observed following concomitant administration of digoxin and oral rivastigmine. 
 
Concomitant administration of rivastigmine with commonly prescribed medicinal products, such as 
antacids, antiemetics, antidiabetics, centrally acting antihypertensives, beta blockers, calcium channel 
blockers, inotropic agents, antianginals, non-steroidal anti-inflammatory agents, oestrogens, analgesics, 
benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine 
or an increased risk of clinically relevant untoward effects. 
 
According to its metabolism, metabolic interactions with other medicinal products appear unlikely, 
although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
No clinical data on exposed pregnancies are available. In peri/postnatal studies in rats, an increased 
gestation time was observed. Rivastigmine should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
In animals, rivastigmine is excreted into milk. It is not known if rivastigmine is excreted into human 
milk. Therefore, women on rivastigmine should not breast-feed. 
 
Fertility 
No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses 
related to maternal toxicity. 
 
4.7 Effects on ability to drive and use machines 
 
Alzheimer’s disease may cause gradual impairment of driving performance or compromise the ability to 
use machines. Furthermore, rivastigmine may induce syncope or delirium. As a consequence, 
rivastigmine has minor or moderate influence on the ability to drive and use machines. Therefore, in 
patients with dementia treated with rivastigmine, the ability to continue driving or operating complex 
machines should be routinely evaluated by the treating physician. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Application site skin reactions (usually mild to moderate application site erythema), are the most 
frequent adverse reactions observed with the use of rivastigmine transdermal patch. The next most 
common adverse reactions are gastrointestinal in nature including nausea and vomiting. 
 
Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency 
category. Frequency categories are defined using the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000); not known (cannot be estimated from the available data). 
 
Tabulated list of adverse reactions 

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Table 1 displays the adverse reactions reported in 854 patients with Alzheimer’s dementia treated in 
randomised, double-blind, placebo and active-controlled clinical studies with rivastigmine transdermal 
patches for a duration of 24-48 weeks and from post-marketing data. 
 
Table 1 
 
Infections and infestations 
 Common Urinary tract infection 
Metabolism and nutrition disorders 
 Common Anorexia, decreased appetite 
 Uncommon Dehydration 
Psychiatric disorders
 Common Anxiety, depression, delirium, agitation 
 Uncommon Aggression 
 Not known Hallucinations, restlessness 
Nervous system disorders 
 Common Headache, syncope, dizziness 
 Uncommon Psychomotor hyperactivity 
 Very rare Extrapyramidal symptoms 
 Not known Worsening of Parkinson’s disease, seizure 
Cardiac disorders 
 Uncommon Bradycardia 
 Not known Atrioventricular block, atrial fibrillation, tachycardia, sick sinus 

syndrome 
Vascular disorders 
 Not known Hypertension 
Gastrointestinal disorders 
 Common Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain 
 Uncommon Gastric ulcer 
 Not known Pancreatitis 
Hepatobiliary disorders 
 Not known Hepatitis, elevated liver function tests 
Skin and subcutaneous tissue disorders
 Common Rash 
 Not known Pruritus, erythema, urticaria, vesicles, allergic dermatitis, disseminated 

cutaneous hypersensitivity reactions 
Renal and urinary disorders 
 Common Urinary incontinence 
General disorders and administration site conditions
 Common Application site skin reactions (e.g. application site erythema, 

application site pruritus, application site oedema, application site 
dermatitis, application site irritation), asthenic conditions (e.g. fatigue, 
asthenia), pyrexia, weight decreased 

 Rare Fall 
 
Description of selected adverse reactions 
When doses higher than 13.3 mg/24 h were used in the above-mentioned placebo-controlled study, 
insomnia and cardiac failure were observed more frequently than with 13.3 mg/24 h or placebo, 
suggesting a dose effect relationship. However, these events did not occur at a higher frequency with 
rivastigmine 13.3 mg/24 h transdermal patches than with placebo. 
 
The following adverse reactions have only been observed with rivastigmine capsules and oral solution 
and not in clinical studies with rivastigmine transdermal patches: somnolence, malaise, tremor, 
confusion, sweating increased (common); duodenal ulcers, angina pectoris (rare); gastrointestinal 
haemorrhage (very rare); and some cases of severe vomiting were associated with oesophageal rupture 
(not known). 
 

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Skin irritation 
In a 24-week double-blind, placebo-controlled clinical trial, skin reactions were measured at each visit 
using a skin irritation rating scale that rated the degree of erythema, oedema, scaling, fissures, pruritus 
and pain/stinging/burning at the application site. The most commonly observed symptom was 
erythema which disappeared within 24 hours in the vast majority of patients. In the 24-week double-
blind study, the most commonly observed symptoms (skin irritation rating scale) with rivastigmine 
9.5 mg/24 h transdermal patches were very slight (21.8%), mild (12.5%) or moderate (6.5%) erythema 
or very slight (11.9%), mild (7.3%) or moderate (5.0%) pruritus. The most commonly observed severe 
symptoms with rivastigmine 9.5 mg/24 h transdermal patches were pruritus (1.7%) and erythema 
(1.1%). Most skin reactions were limited to the application site and resulted in discontinuation in only 
2.4% of the patients in the rivastigmine 9.5 mg/24 h transdermal patch group. 
 
In a 48-week active-controlled clinical trial, cases of skin irritation were captured as patient or 
caregiver reported adverse reactions. The most commonly reported skin irritation events during the 
first 24 weeks of the double-blind period with rivastigmine 13.3 mg/24 h transdermal patches and 
rivastigmine 9.5 mg/24 h transdermal patches, respectively were application site erythema (5.7% vs 
4.6%) and application site pruritus (3.6% vs 2.8%). The percentages decreased in both rivastigmine 
13.3 mg/24 h transdermal patch and rivastigmine 9.5 mg/24 h transdermal patch treatment groups over 
time (>24 weeks): application site erythema (0.8% vs. 1.6%) and application site pruritus (0.4% vs. 
1.2%), respectively. Application site pruritus led to discontinuation in 1.1% of the patients from each 
of the treatment groups during the total 48-week double-blind treatment phase. Application site 
reactions were mostly mild to moderate in severity and were rated as severe in less than 2% of 
patients. 
 
A direct comparison of the rate of skin irritation events reported in each of these studies cannot be 
made due to the difference in data collection methods employed. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
Most cases of accidental overdose of oral rivastigmine have not been associated with any clinical signs or 
symptoms and almost all of the patients concerned continued rivastigmine treatment. Where symptoms 
have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations. Due to 
the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may 
also occur. Ingestion of 46 mg of oral rivastigmine occurred in one case; following conservative 
management the patient fully recovered within 24 hours. Overdose with rivastigmine transdermal patches 
resulting from misuse/dosing errors (application of multiple patches at a time) has been reported in the 
post-marketing setting. The typical symptoms reported among these cases are similar to those seen with 
cases of overdose associated with rivastigmine oral formulations. 
 
Treatment 
As rivastigmine has a plasma half-life of about 3.4 hours and a duration of acetylcholinesterase inhibition 
of about 9 hours, it is recommended that in cases of asymptomatic overdose all Rivastigmine 3M Health 
Care Ltd. transdermal patches should be removed immediately and no further transdermal patch should 
be applied for the next 24 hours. In overdose accompanied by severe nausea and vomiting, the use of 
antiemetics should be considered. Symptomatic treatment for other adverse reactions should be given as 
necessary. 
 
In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine sulphate is 
recommended, with subsequent doses based on clinical response. Use of scopolamine as an antidote is 
not recommended. 

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22 

 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: psychoanaleptics, anticholinesterases, ATC code: N06DA03 
 
Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to 
facilitate cholinergic neurotransmission by slowing the degradation of acetylcholine released by 
functionally intact cholinergic neurones. Thus, rivastigmine may have an ameliorative effect on 
cholinergic-mediated cognitive deficits in dementia associated with Alzheimer’s disease. 
 
Rivastigmine interacts with its target enzymes by forming a covalently bound complex that 
temporarily inactivates the enzymes. In healthy young men, an oral 3 mg dose decreases 
acetylcholinesterase (AChE) activity in CSF by approximately 40% within the first 1.5 hours after 
administration. Activity of the enzyme returns to baseline levels about 9 hours after the maximum 
inhibitory effect has been achieved. In patients with Alzheimer’s disease, inhibition of AChE in CSF 
by oral rivastigmine was dose-dependent up to 6 mg given twice daily, the highest dose tested. 
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by oral 
rivastigmine was similar to the inhibition of AChE activity. 
 
Clinical studies in Alzheimer’s dementia 
The efficacy of rivastigmine transdermal patches in patients with Alzheimer’s dementia has been 
demonstrated in a 24-week double-blind, placebo-controlled core study and its open-label extension 
phase and in a 48-week double-blind comparator study.  
 
24-week placebo-controlled study 
Patients involved in the placebo-controlled study had an MMSE (Mini-Mental State Examination) 
score of 10–20. Efficacy was established by the use of independent, domain-specific assessment tools 
which were applied at regular intervals during the 24-week treatment period. These include the 
ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a performance-based 
measure of cognition) and the ADCS-CGIC (Alzheimer’s Disease Cooperative Study – Clinician’s 
Global Impression of Change, a comprehensive global assessment of the patient  by the physician 
incorporating caregiver input), and the ADCS-ADL (Alzheimer’s Disease Cooperative Study – 
Activities of Daily Living, a caregiver-rated assessment of the activities of daily living including 
personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient 
oneself to surroundings as well as involvement in activities related to finances). The 24-week results 
for the three assessment tools are summarised in Table 2. 
 
Table 2 
 
 Rivastigmine 

transdermal patches 
9.5 mg/24 h 

Rivastigmine 
capsules 

12 mg/day 

Placebo 

ITT-LOCF population N = 251 N = 256 N = 282 
ADAS-Cog    
 (n=248) (n=253) (n=281) 
Mean baseline  SD 27.0  10.3 27.9  9.4 28.6  9.9 
Mean change at week 24  SD -0.6  6.4 -0.6  6.2 1.0  6.8 
p-value versus placebo 0.005*1 0.003*1  
ADCS-CGIC    
 (n=248) (n=253) (n=278) 
Mean score  SD 3.9  1.20 3.9  1.25 4.2  1.26 
p-value versus placebo 0.010*2 0.009*2  
ADCS-ADL    

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23 

 (n=247) (n=254) (n=281) 
Mean baseline  SD 50.1  16.3 49.3  15.8 49.2  16.0 
Mean change at week 24  SD -0.1  9.1 -0.5  9.5 -2.3  9.4 
p-value versus placebo 0.013*1 0.039*1  
* p≤0.05 versus placebo 
ITT: Intent-To-Treat; LOCF: Last Observation Carried Forward 
1 Based on ANCOVA with treatment and country as factors and baseline value as a covariate. 
Negative ADAS-Cog changes indicate improvement. Positive ADCS-ADL changes indicate 
improvement. 
2 Based on CMH test (van Elteren test) blocking for country. ADCS-CGIC scores <4 indicate 
improvement. 
 
The results for clinically relevant responders from the 24-week placebo-controlled study are provided 
in Table 3. Clinically relevant improvement was defined a priori as at least 4-point improvement on 
the ADAS-Cog, no worsening on the ADCS-CGIC, and no worsening on the ADCS-ADL. 
 
Table 3 
 

 Patients with clinically significant response (%) 
 
 
 
ITT-LOCF population 

Rivastigmine 
transdermal patches 

9.5 mg/24 h 
N = 251 

Rivastigmine 
capsules 

12 mg/day 
N = 256 

Placebo 
 

 
N = 282 

At least 4 points 
improvement on ADAS-Cog 
with no worsening on ADCS-
CGIC and ADCS-ADL 
 

17.4 19.0 10.5 

p-value versus placebo 0.037* 0.004*  
*p<0.05 versus placebo 

 
As suggested by compartmental modelling, 9.5 mg/24 h transdermal patches exhibited exposure 
similar to that provided by an oral dose of 12 mg/day. 
 
48-week active comparator controlled study 
Patients involved in the active comparator controlled study had an initial baseline MMSE score of 
10-24. The study was designed to compare the efficacy of the 13.3 mg/24 h transdermal patch against 
the 9.5 mg/24 h transdermal patch during a 48-week double-blind treatment phase in Alzheimer’s 
disease patients who demonstrated functional and cognitive decline after an initial 24-48 week open-
label treatment phase while on a maintenance dose of 9.5 mg/24 h transdermal patch. Functional 
decline was assessed by the investigator and cognitive decline was defined as a decrease in the MMSE 
score of >2 points from the previous visit or a decrease of >3 points from baseline. Efficacy was 
established by the use of ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a 
performance-based measure of cognition) and the ADCS-IADL (Alzheimer’s Disease Cooperative 
Study – Instrumental Activities of Daily Living) assessing instrumental activities which include 
maintaining finances, meal preparation, shopping, ability to orient oneself to surroundings, ability to 
be left unattended. The 48-week results for the two assessment tools are summarised in Table 4. 
 
Table 4 
 
 
Population/Visit 

Rivastigmine 
13.3 mg/24 h 
N = 265 

Rivastigmine 
9.5 mg/24 h 
N = 271 

Rivastigmine 
13.3 mg/24 h 

Rivastigmine 
9.5 mg/24 h 

n Mean n Mean DLSM 95% CI p-value 
ADAS-Cog         
LOCF Baseline 264 34.4 268 34.9    

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 DB-week 48 Value 264 38.5 268 39.7    
  Change 264 4.1 268 4.9 -0.8 (-2.1, 

0.5) 
0.227 

ADCS-IADL         
LOCF Baseline 265 27.5 271 25.8    
 Week 48 Value 265 23.1 271 19.6    
  Change 265 -4.4 271 -6.2 2.2 (0.8, 

3.6) 
0.002* 

CI – confidence interval. 
DLSM – difference in least square means. 
LOCF – Last Observation Carried Forward. 
ADAS-cog scores: A negative difference in DLSM indicates greater improvement in Rivastigmine 
13.3 mg/24 h as compared to Rivastigmine 9.5 mg/24 h. 
ADCS-IADL scores: A positive difference in DLSM indicates greater improvement in Rivastigmine 
13.3 mg/24 h as compared to Rivastigmine 9.5 mg/24 h. 
N is the number of patients with an assessment at baseline (last assessment in the initial open-label 
phase) and with at least 1 post-baseline assessment (for the LOCF). 
The DLSM, 95% CI, and p-value are based on an ANCOVA (analysis of covariance) model adjusted 
for country and baseline ADAS-cog score. 
* p<0.05 
 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
rivastigmine in all subsets of the paediatric population in the treatment of Alzheimer’s dementia (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Absorption of rivastigmine from rivastigmine transdermal patches is slow. After the first dose, 
detectable plasma concentrations are observed after a lag time of 0.5-1 hour. Cmax is reached after 
10-16 hours. After the peak, plasma concentrations slowly decrease over the remainder of the 24-hour 
period of application. With multiple dosing (such as at steady state), after the previous transdermal 
patch is replaced with a new one, plasma concentrations initially decrease slowly for about 40 minutes 
on average, until absorption from the newly applied transdermal patch becomes faster than 
elimination, and plasma levels begin to rise again to reach a new peak at approximately 8 hours. At 
steady state, trough levels are approximately 50% of peak levels, in contrast to oral administration, 
with which concentrations fall off to virtually zero between doses. Although less pronounced than 
with the oral formulation, exposure to rivastigmine (Cmax and AUC) increased over-proportionally by a 
factor of 2.6 and 4.9 when escalating from 4.6 mg/24 h to 9.5 mg/24 h and to 13.3 mg/24 h, 
respectively. The fluctuation index (FI), a measure of the relative difference between peak and trough 
concentrations ((Cmax-Cmin)/Cavg), was 0.58 for rivastigmine 4.6 mg/24 h transdermal patches, 0.77 for 
rivastigmine 9.5 mg/24 h transdermal patches and 0.72 for rivastigmine 13.3 mg/24 h transdermal 
patches, thus demonstrating a much smaller fluctuation between trough and peak concentrations than 
for the oral formulation (FI = 3.96 (6 mg/day) and 4.15 (12 mg/day)). 
 
The dose of rivastigmine released from the transdermal patch over 24 hours (mg/24 h) cannot be 
directly equated to the amount (mg) of rivastigmine contained in a capsule with respect to plasma 
concentration produced over 24 hours. 
 
The single-dose inter-subject variability in rivastigmine pharmacokinetic parameters (normalised to 
dose/kg bodyweight) was 43% (Cmax) and 49% (AUC0-24h) after transdermal administration versus 
74% and 103%, respectively, after the oral form. The inter-patient variability in a steady-state study in 
Alzheimer’s dementia was at most 45% (Cmax) and 43% (AUC0-24h) after use of the transdermal patch, 
and 71% and 73%, respectively, after administration of the oral form. 
 
A relationship between active substance exposure at steady state (rivastigmine and metabolite 

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NAP226-90) and bodyweight was observed in Alzheimer’s dementia patients. 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. The effect of bodyweight on active substance 
exposure suggests special attention to patients with very low body weight during up-titration (see 
section 4.4). 
 
Exposure (AUC∞) to rivastigmine (and metabolite NAP266-90) was highest when the transdermal 
patch was applied to the upper back, chest, or upper arm and approximately 20–30% lower when 
applied to the abdomen or thigh. 
 
There was no relevant accumulation of rivastigmine or the metabolite NAP226-90 in plasma in patients 
with Alzheimer’s disease, except that plasma levels were higher on the second day of transdermal patch 
therapy than on the first. 
 
Distribution 
Rivastigmine is weakly bound to plasma proteins (approximately 40%). It readily crosses the blood-brain 
barrier and has an apparent volume of distribution in the range of 1.8-2.7 l/kg. 
 
Biotransformation 
Rivastigmine is rapidly and extensively metabolised with an apparent elimination half-life in plasma of 
approximately 3.4 hours after removal of the transdermal patch. Elimination was absorption rate limited 
(flip-flop kinetics), which explains the longer t½ after transdermal patch (3.4 h) versus oral or intravenous 
administrations (1.4 to 1.7 h). Metabolism is primarily via cholinesterase-mediated hydrolysis to the 
metabolite NAP226-90. In vitro, this metabolite shows minimal inhibition of acetylcholinesterase 
(<10%). Based on evidence from in vitro and animal studies, the major cytochrome P450 isoenzymes are 
minimally involved in rivastigmine metabolism. Total plasma clearance of rivastigmine was 
approximately 130 litres/h after a 0.2 mg intravenous dose and decreased to 70 litres/h after a 2.7 mg 
intravenous dose, which is consistent with the non-linear, over-proportional pharmacokinetics of 
rivastigmine due to saturation of its elimination. 
 
The metabolite-to-parent AUC∞ ratio was around 0.7 after transdermal patch administration versus 3.5 
after oral administration, indicating that much less metabolism occurred after dermal compared to oral 
treatment. Less NAP226-90 is formed following application of the transdermal patch, presumably 
because of the lack of presystemic (hepatic first pass) metabolism, in contrast to oral administration. 
 
Elimination 
Unchanged rivastigmine is found in trace amounts in the urine; renal excretion of the metabolites is the 
major route of elimination after transdermal patch administration. Following administration of oral 14C-
rivastigmine, renal elimination was rapid and essentially complete (>90%) within 24 hours. Less than 1% 
of the administered dose is excreted in the faeces. 
 
Elderly population 
Age had no impact on the exposure to rivastigmine in Alzheimer’s disease patients treated with 
rivastigmine transdermal patches. 
 
Hepatic impairment 
No study was conducted with rivastigmine transdermal patches in subjects with hepatic impairment. 
After oral administration, the Cmax of rivastigmine was approximately 60% higher and the AUC of 
rivastigmine was more than twice as high in subjects with mild to moderate hepatic impairment than in 
healthy subjects. 
 
Renal impairment 
No study was conducted with rivastigmine transdermal patches in subjects with renal impairment. After 
oral administration, Cmax and AUC of rivastigmine were more than twice as high in Alzheimer patients 
with moderate renal impairment compared with healthy subjects; however there were no changes in Cmax 
and AUC of rivastigmine in Alzheimer patients with severe renal impairment. 

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5.3 Preclinical safety data 
 
Oral and topical repeated-dose toxicity studies in mice, rats, rabbits, dogs and minipigs revealed only 
effects associated with an exaggerated pharmacological action. No target organ toxicity was observed. 
Oral and topical dosing in animal studies was limited due to the sensitivity of the animal models used. 
 
Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a 
chromosomal aberration test in human peripheral lymphocytes at a dose exceeding 104 times the foreseen 
clinical exposure. The in vivo micronucleus test was negative. 
 
No evidence of carcinogenicity was found in oral and topical studies in mice and in an oral study in 
rats at the maximum tolerated dose. The exposure to rivastigmine and its metabolites was 
approximately equivalent to human exposure with highest doses of rivastigmine capsules and 
transdermal patches. 
 
In animals, rivastigmine crosses the placenta and is excreted into milk. Oral studies in pregnant rats and 
rabbits gave no indication of teratogenic potential on the part of rivastigmine. Specific dermal studies in 
pregnant animals have not been conducted. 
 
Rivastigmine transdermal patches were not phototoxic. In some other dermal toxicity studies, a mild 
irritant effect on the skin of laboratory animals, including controls, was observed. This may indicate a 
potential for rivastigmine transdermal patches to induce mild erythema in patients. When administered to 
rabbit eyes in primary eye irritation studies, rivastigmine caused reddening and swelling of the 
conjunctiva, corneal opacities and miosis which persisted for 7 days. Therefore, the patient/caregiver 
should avoid contact with the eyes after handling of the patch (see section 4.4). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Backing layer 
Polyester and ethyl vinyl acetate 
 
Drug-in-adhesive (DIA) matrix 
Acrylate copolymer adhesive 
Isopropyl myristate 
 
Release liner 
Polyester 
 
6.2 Incompatibilities 
 
To prevent interference with the adhesive properties of the transdermal patch, no cream, lotion or 
powder should be applied to the skin area where the medicinal product is to be applied. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container 
 

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Heat-sealed pouches made of paper/aluminium/acrylonitrile-methacrylate copolymer laminate. One 
pouch contains one transdermal patch.  
 
Available in packs containing 7, 30, 60 and 90 pouches. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Used transdermal patches should be folded in half, with the adhesive side inwards, placed in the original 
pouch and discarded safely and out of the sight and reach of children. 
Any used or unused transdermal patches should be disposed of in accordance with local requirements or 
returned to the pharmacy. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/14/911/005 
EU/1/14/911/006 
EU/1/14/911/007 
EU/1/14/911/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
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ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
Name and address of the manufacturer responsible for batch release 
 
Enestia 
Klöcknerstraat 1, 3930 Hamont-Achel 
Belgium 
 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 

 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 

 Periodic Safety Update Reports 
 
At the time of granting the marketing authorisation, the submission of periodic safety update reports is 
not required for this medicinal product. However, the marketing authorisation holder shall submit 
periodic safety update reports for this medicinal product if the product is included in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83 and published on 
the European medicines web-portal 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency;  

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 

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30 

 
 Additional risk minimisation measures 

 
The MAH shall ensure that, following discussions and agreement with the National Competent 
Authorities in each Member State where Rivastigmine 3M Health Care Ltd. is marketed, at launch and 
after launch of the transdermal patch all physicians who are expected to prescribe Rivastigmine 3M 
Health Care Ltd. are provided with an information pack containing the following elements: 

 Summary of Product Characteristics 

 Patient reminder card 

 Instructions to provide patients and caregivers with the patient reminder card 

The patient reminder card should contain the following key messages: 

 Take off the previous patch before putting ONE new patch on. 

 Only one patch per day. 

 Do not cut the patch into pieces. 

 Press the patch firmly in place for at least 30 seconds using the palm of the hand. 

 How to use the reminder card to record patch application and removal. 

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31 

 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch 
rivastigmine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 transdermal patch of 4.15 cm2 contains 7.17 mg rivastigmine and delivers 4.6 mg/24 h. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains polyester, ethyl vinyl acetate, acrylate copolymer adhesive and isopropyl myristate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 transdermal patches 
30 transdermal patches 
60 transdermal patches 
90 transdermal patches 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Transdermal use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light. 
 

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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/14/911/001 [7 pouches] 
EU/1/14/911/002 [30 pouches] 
EU/1/14/911/003 [60 pouches] 
EU/1/14/911/004 [90 pouches] 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POUCH 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch 
rivastigmine 
Transdermal use 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 transdermal patch per pouch. 
 
 
6. OTHER 
 
Apply one patch per day. Take off the previous patch before putting ONE new patch on. 
 

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36 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patch 
rivastigmine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 transdermal patch of 8.3 cm2 contains 14.33 mg rivastigmine and delivers 9.5 mg/24 h. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains polyester, ethyl vinyl acetate, acrylate copolymer adhesive and isopropyl myristate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 transdermal patches 
30 transdermal patches 
60 transdermal patches 
90 transdermal patches 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Transdermal use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light. 
 

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37 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/14/911/005 [7 pouches] 
EU/1/14/911/006 [30 pouches] 
EU/1/14/911/007 [60 pouches] 
EU/1/14/911/008 [90 pouches] 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h 

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38 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POUCH 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patch 
rivastigmine 
Transdermal use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 transdermal patch per pouch. 
 
 
6. OTHER 
 
Apply one patch per day. Take off the previous patch before putting ONE new patch on. 
 

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39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

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Package Leaflet: Information for the user 
 

Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch 
Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patch 

rivastigmine 
 
 

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Rivastigmine 3M Health Care Ltd. is and what it is used for 
2. What you need to know before you use Rivastigmine 3M Health Care Ltd. 
3. How to use Rivastigmine 3M Health Care Ltd. 
4. Possible side effects 
5. How to store Rivastigmine 3M Health Care Ltd. 
6. Contents of the pack and other information 
 
 
1. What Rivastigmine 3M Health Care Ltd. is and what it is used for 
 
The active substance of Rivastigmine 3M Health Care Ltd. is rivastigmine. 
 
Rivastigmine belongs to a class of substances called cholinesterase inhibitors. In patients with 
Alzheimer’s dementia, certain nerve cells die in the brain, resulting in low levels of the 
neurotransmitter acetylcholine (a substance that allows nerve cells to communicate with each other). 
Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and 
butyrylcholinesterase. By blocking these enzymes, Rivastigmine 3M Health Care Ltd. allows levels of 
acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer’s disease. 
 
Rivastigmine 3M Health Care Ltd. is used for the treatment of adult patients with mild to moderately 
severe Alzheimer’s dementia, a progressive brain disorder that gradually affects memory, intellectual 
ability and behaviour. 
 
 
2. What you need to know before you use Rivastigmine 3M Health Care Ltd. 
 
Do not use Rivastigmine 3M Health Care Ltd. 
- if you are allergic to rivastigmine or any of the other ingredients of this medicine (listed in 

section 6). 
- if you have ever had an allergic reaction to a similar type of medicine (carbamate derivatives). 
- if you have a skin reaction spreading beyond the patch size, if there is a more intense local 

reaction (such as blisters, increasing skin inflammation, swelling) and if it does not improve 
within 48 hours after removal of the transdermal patch. 

If this applies to you, tell your doctor and do not apply Rivastigmine 3M Health Care Ltd. transdermal 
patches. 
 
Warnings and precautions 
Talk to your doctor before using Rivastigmine 3M Health Care Ltd.: 
- if you have, or have ever had, an irregular heartbeat. 
- if you have, or have ever had, an active stomach ulcer. 

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41 

- if you have, or have ever had, difficulties in passing urine. 
- if you have, or have ever had, seizures. 
- if you have, or have ever had, asthma or a severe respiratory disease. 
- if you suffer from trembling. 
- if you have a low body weight. 
- if you have gastrointestinal reactions such as feeling sick (nausea), being sick (vomiting) and 

diarrhoea. You may become dehydrated (losing too much fluid) if vomiting or diarrhoea are 
prolonged. 

- if 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 applied a patch for several days, do not apply the next one before you have talked to 
your doctor. 
 
Use in children and adolescents 
There is no relevant use of Rivastigmine 3M Health Care Ltd. in the paediatric population in the 
treatment of Alzheimer’s disease. 
 
Other medicines and Rivastigmine 3M Health Care Ltd. 
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Rivastigmine 3M Health Care Ltd. might interfere with anticholinergic medicines some of which are 
medicines used to relieve stomach cramps or spasms (e.g. dicyclomine), to treat Parkinson’s disease 
(e.g. amantadine) or to prevent motion sickness (e.g. diphenhydramine, scopolamine or meclizine). 
 
If you have to undergo surgery whilst using Rivastigmine 3M Health Care Ltd. transdermal patches, 
tell your doctor that you are using them because they may exaggerate the effects of some muscle 
relaxants during anaesthesia. 
 
Pregnancy, breast feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.  
 
If you are pregnant, the benefits of using Rivastigmine 3M Health Care Ltd. transdermal patches must 
be assessed against the possible effects on your unborn child. Rivastigmine 3M Health Care Ltd. 
should not be used during pregnancy unless clearly necessary. 
 
You should not breast-feed during treatment with Rivastigmine 3M Health Care Ltd. transdermal 
patches. 
 
Driving and using machines 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. 
Rivastigmine 3M Health Care Ltd. transdermal patches may cause fainting or severe confusion. If you 
feel faint or confused do not drive, use machines or perform any other tasks that require your attention. 
 
 
3. How to use Rivastigmine 3M Health Care Ltd. 
 
Always use this medicine exactly as described in this leaflet and as your doctor has told you. Check 
with your doctor, pharmacist or nurse if you are not sure. 
 
IMPORTANT: 
- Take off the previous patch before putting ONE new patch on. 
- Only one patch per day. 
- Do not cut the patch into pieces. 

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- Press the patch firmly in place for at least 30 seconds using the palm of the hand. 
 
How to start treatment 
Your doctor will tell you which Rivastigmine 3M Health Care Ltd. transdermal patch is most suitable 
for you. 
- Treatment usually starts with Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h. 
- The recommended daily dose is Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h. If well 

tolerated, the treating physician may consider increasing the dose to 13.3 mg/24 h (this high 
strength is currently not available from 3M but may be available from other Marketing 
Authorisation Holders). 

- Only wear one Rivastigmine 3M Health Care Ltd. patch at a time and replace the patch with a 
new one after 24 hours. 

 
During the course of the treatment your doctor may adjust the dose to suit your individual needs. 
 
If you have not applied a patch for three days, do not apply the next one before you have talked to 
your doctor. Transdermal patch treatment can be resumed at the same dose if treatment is not 
interrupted for more than three days. Otherwise your doctor will restart your treatment on 
Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h. 
 
Rivastigmine 3M Health Care Ltd. can be used with food, drink and alcohol. 
 
Where to apply your Rivastigmine 3M Health Care Ltd. transdermal patch 
- Before you apply a patch, make sure that your skin is clean, dry and hairless, free of any 

powder, oil, moisturiser or lotion that could keep the patch from sticking to your skin properly, 
 free of cuts, rashes and/or irritations. 

- Carefully remove any existing patch before putting on a new one. Having multiple patches 
on your body could expose you to an excessive amount of this medicine which could be 
potentially dangerous. 

- Apply ONE patch per day to ONLY ONE of the possible locations shown in the following 
diagrams: 

 
Every 24 hours take off the previous patch before putting 
ONE new patch on to ONLY ONE of the following possible 
locations. 

 
 • left upper arm or right upper arm 

 
 

 • left upper chest or right upper chest (avoid breast) 

 

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43 

 
 • left upper back or right upper back 

 
 

 • left lower back or right lower back 

 
 
When changing the patch, you must remove the previous day’s patch before you apply the new one to 
a different location of skin each time (for example on the right side of your body one day, then on the 
left side the next day, and on your upper body one day, then on your lower body the next day). Do not 
apply a new patch to the same skin area twice within 14 days. 
 
How to apply your Rivastigmine 3M Health Care Ltd. transdermal patch 
Rivastigmine 3M Health Care Ltd. patches are transparent to translucent, plastic patches that stick 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. 
 
Carefully remove the existing patch before putting on a new one. 
 
 
For patients starting treatment for the first time and for patients 
restarting Rivastigmine 3M Health Care Ltd. after treatment 
interruption, please begin with the second picture. 

 
 
 
- Each patch is sealed in its own protective pouch. 

You should only open the pouch when you are ready to 
apply the patch. 
Tear the pouch open where indicated and remove the patch 
from the pouch. The pouch can be torn open in two places. 

 
 

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- A protective liner covers the sticky side of the patch. 
Peel off one half 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 half of the 
protective liner. 

 
 
- Then press the patch firmly in place for at least 30 seconds 

using the palm of the hand to make sure that the edges stick 
well. 

 
If it helps you, you may write, for example, the day of the week, 
on the patch with a thin ball point pen. 
 

 
 
The patch should be worn continuously until it is time to replace it with a new one. You may wish to 
experiment with different locations when applying a new patch, to find ones that are most comfortable 
for you and where clothing will not rub on the patch. 
 
How to remove your Rivastigmine 3M Health Care Ltd. transdermal patch 
Gently pull at one edge of the patch to remove it slowly from the skin. In case the adhesive residue is 
left over on your skin, gently soak the area with warm water and mild soap or use baby oil to remove 
it. Alcohol or other dissolving liquids (nail polish remover or other solvents) should not be used. 
 
You should wash your 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. 
 
Can you wear your Rivastigmine 3M Health Care Ltd. transdermal patch when you are bathing, 
swimming, or in the sun? 
- Bathing, swimming or showering should not affect the patch. Make sure the patch does not 

loosen during these activities. 
- Do not expose the patch to any external heat sources (e.g. excessive sunlight, saunas, solarium) 

for long periods of time. 
 
What to do if a patch falls off 
If a patch falls off, apply a new one for the rest of the day, then replace it at the same time as usual the 
next day. 
 
When and for how long to apply your Rivastigmine 3M Health Care Ltd. transdermal patch 
- To benefit from treatment, you must apply a new patch every day, preferably at the same time 

of day. 

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- Only wear one Rivastigmine 3M Health Care Ltd. patch at a time and replace the patch with a 
new one after 24 hours. 

 
If you use more Rivastigmine 3M Health Care Ltd. than you should 
If you accidentally apply more than one patch, remove all the patches from your skin, then inform 
your doctor that you have accidentally applied more than one patch. You may require medical 
attention. Some people who have accidentally taken too much Rivastigmine 3M Health Care Ltd. have 
experienced feeling sick (nausea), being sick (vomiting), diarrhoea, high blood pressure and 
hallucinations. Slow heartbeat and fainting may also occur. 
 
If you forget to use Rivastigmine 3M Health Care Ltd. 
If you find you have forgotten to apply a patch, apply one immediately. You may apply the next patch 
at the usual time the next day. Do not apply two patches to make up for the one that you missed. 
 
If you stop using Rivastigmine 3M Health Care Ltd. 
Tell your doctor or pharmacist if you stop using the patch. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
You may have side effects more often when you start your medicine or when your dose is increased. 
Usually, the side effects will slowly go away as your body gets used to the medicine. 
 
Take off your patch and tell your doctor straight away, if you notice any of the following side 
effects which could become serious: 
 
Common (may affect up to 1 in 10 people) 
- Loss of appetite 
- Feeling dizzy 
- Feeling agitated or sleepy 
- Urinary incontinence (inability to retain adequate urine) 
 
Uncommon (may affect up to 1 in 100 people) 
- Problems with your heartbeat such as slow heartbeat 
- Seeing things that are not really there (hallucinations) 
- Stomach ulcer 
- Dehydration (losing too much fluid) 
- Hyperactivity (high level of activity, restlessness) 
- Aggression 
 
Rare (may affect up to 1 in 1,000 people) 
- Falling 
 
Very rare (may affect up to 1 in 10,000 people) 
- Stiff arms or legs 
- Trembling hands 
 
Not known (frequency cannot be estimated from the available data) 
- Allergic reaction where the patch was used, such as blisters or inflamed skin 
- The signs of Parkinson’s disease get worse – such as tremor, stiffness and shuffling 
- Inflammation of the pancreas – signs include serious upper stomach pain, often with feeling sick 

(nausea) or being sick (vomiting) 

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- Fast or uneven heartbeat 
- High blood pressure 
- Fits (seizures) 
- Liver disorders (yellow skin, yellowing of the whites of the eyes, abnormal darkening of the 

urine or unexplained nausea, vomiting, tiredness and loss of appetite) 
- Changes in tests which show how well the liver is working 
- Feeling restless 
Take off your patch and tell your doctor straight away, if you notice any of the side effects above. 
 
Other side effects seen with Rivastigmine 3M Health Care Ltd. capsules or oral solution and 
which may occur with the patch: 
 
Common (may affect up to 1 in 10 people) 
- Too much saliva 
- Loss of appetite 
- Feeling restless 
- Generally feeling unwell 
- Trembling or feeling confused 
- Increased sweating 
 
Uncommon (may affect up to 1 in 100 people) 
- Uneven heart rate (e.g. fast heart rate) 
- Difficulty sleeping 
- Accidental falls 
 
Rare (may affect up to 1 in 1,000 people) 
- Fits (seizures) 
- Ulcer in the intestine 
- Chest pain – this may be caused by heart spasm 
 
Very rare (may affect up to 1 in 10,000 people) 
- High blood pressure 
- Inflammation of the pancreas – the signs include serious upper stomach pain, often with feeling 

sick (nausea) or being sick (vomiting) 
- Bleeding in the gut – shows as blood in stools or when being sick 
- Seeing things that are not there (hallucinations) 
- Some people who have been violently sick have had tearing of the tube that connects your 

mouth with your stomach (oesophagus) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Rivastigmine 3M Health Care Ltd. 
 
- Keep this medicine out of the sight and reach of children. 
- Do not use this medicine after the expiry date, which is stated on the carton and pouch after 

EXP. The expiry date refers to the last day of that month. 
- Store in the original package in order to protect from light. 
- Do not use this medicine if you see that the patch is damaged or shows signs of tampering. 
- After removing a patch, fold it in half with the sticky sides on the inside and press them 

together. Return the used patch to its sachet and dispose of it in such a way that children cannot 
handle it. Do not touch your eyes with your fingers and wash your hands with soap and water 

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47 

after removing the patch. If your community burns domestic rubbish, you can dispose of the 
patch with your domestic rubbish. Otherwise, return used patches to a pharmacy, preferably in 
the original packaging. 

 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Rivastigmine 3M Health Care Ltd. contains 
- The active substance is rivastigmine. 

- Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patches: Each patch releases 
4.6 mg of rivastigmine per 24 hours, is 4.15 cm2 and contains 7.17 mg of rivastigmine. 

- Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patches: Each patch releases 
9.5 mg of rivastigmine per 24 hours, is 8.3 cm2 and contains 14.33 mg of rivastigmine. 

 
- The other ingredients are polyester, ethyl vinyl acetate, acrylate copolymer adhesive and 

isopropyl myristate. 
 
What Rivastigmine 3M Health Care Ltd. looks like and contents of the pack 
The transdermal patches are rectangular with rounded corners, approximately 2.5 cm by 1.8 cm 
(Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch) or 3.5 cm by 2.6 cm (Rivastigmine 
3M Health Care Ltd. 9.5 mg/24 h transdermal patch). 
Each transdermal patch consists of three layers; a backing layer, an adhesive layer containing the 
medicine and a transparent, split release liner. The backing layer is transparent to translucent and 
labelled with “R5” (Rivastigmine 3M Health Care Ltd. 4.6 mg/24 h transdermal patch) or “R10” 
(Rivastigmine 3M Health Care Ltd. 9.5 mg/24 h transdermal patch). 
 
One transdermal patch is sealed in one pouch. The patches are available in packs containing 7, 30, 60 
and 90 pouches. Not all pack sizes may be marketed in your country. 
 
Marketing Authorisation Holder 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
 
Manufacturer 
Enestia 
Klöcknerstraat 1 
3930 Hamont-Achel 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
3M Health Care Limited,  
1 Morley Street,  
Loughborough,  
Leicestershire,  
LE11 1EP  
United Kingdom 
Tel: +44 (0)1509 611611 

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This leaflet was last revised in {month YYYY} 
 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET