Prometax

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 

Prometax 1.5 mg hard capsules 

Prometax 3.0 mg hard capsules 

Prometax 4.5 mg hard capsules 

Prometax 6.0 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Prometax 1.5 mg hard capsules 

 

Each capsule contains rivastigmine hydrogen tartrate corresponding to 1.5 mg rivastigmine. 

 

Prometax 3.0 mg hard capsules 

 

Each capsule contains rivastigmine hydrogen tartrate corresponding to 3.0 mg rivastigmine. 

 

Prometax 4.5 mg hard capsules 

 

Each capsule contains rivastigmine hydrogen tartrate corresponding to 4.5 mg rivastigmine. 

 

Prometax 6.0 mg hard capsules 

 

Each capsule contains rivastigmine hydrogen tartrate corresponding to 6.0 mg rivastigmine. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsules 

 

Prometax 1.5 mg hard capsules 

 

Off-white to slightly yellow powder in a capsule with yellow cap and yellow body, with red imprint 

“ENA 713 1,5 mg” on body. 

 

Prometax 3.0 mg hard capsules 

 

Off-white to slightly yellow powder in a capsule with orange cap and orange body, with red imprint 

“ENA 713 3 mg” on body. 

 

Prometax 4.5 mg hard capsules 

 

Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint 

“ENA 713 4,5 mg” on body. 

 

Prometax 6.0 mg hard capsules 

 

Off-white to slightly yellow powder in a capsule with red cap and orange body, with red imprint 

“ENA 713 6 mg” on body. 

 

 



 

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4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. 

Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson’s 

disease. 

 

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 or dementia associated with Parkinson’s disease. Diagnosis should be made 

according to current guidelines. Therapy with rivastigmine should only be started if a caregiver is 

available who will regularly monitor intake of the medicinal product by the patient. 

 

Posology 

 

Rivastigmine should be administered twice a day, with morning and evening meals. The capsules should 

be swallowed whole. 

 

Initial dose 

1.5 mg twice a day. 

 

Dose titration 

The starting dose is 1.5 mg twice a day. If this dose is well tolerated after a minimum of two weeks of 

treatment, the dose may be increased to 3 mg twice a day. Subsequent increases to 4.5 mg and then 6 mg 

twice a day should also be based on good tolerability of the current dose and may be considered after a 

minimum of two weeks of treatment at that dose level. 

 

If adverse reactions (e.g. nausea, vomiting, abdominal pain or loss of appetite), weight decrease or 

worsening of extrapyramidal symptoms (e.g. tremor) in patients with dementia associated with 

Parkinson’s disease are observed during treatment, these may respond to omitting one or more doses. If 

adverse reactions persist, the daily dose should be temporarily reduced to the previous well-tolerated 

dose or the treatment may be discontinued. 

 

Maintenance dose 

The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be 

maintained on their highest well tolerated dose. The recommended maximum daily dose is 6 mg twice a 

day. 

 

Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. 

Therefore, the clinical benefit of rivastigmine should be reassessed on a regular basis, especially for 

patients treated at doses less than 3 mg twice a day. If after 3 months of maintenance dose treatment the 

patient’s rate of decline in dementia symptoms is not altered favourably, the treatment should be 

discontinued. Discontinuation should also be considered when evidence of a therapeutic effect is no 

longer present. 

 

Individual response to rivastigmine cannot be predicted. However, a greater treatment effect was seen in 

Parkinson’s disease patients with moderate dementia. Similarly a larger effect was observed in 

Parkinson’s disease patients with visual hallucinations (see section 5.1). 

 

Treatment effect has not been studied in placebo-controlled trials beyond 6 months. 

 

Re-initiation of therapy 

If treatment is interrupted for more than three days, it should be re-initiated at 1.5 mg twice daily. 

Dose titration should then be carried out as described above. 

 



 

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Special populations 

 

Renal and hepatic impairment 

No dose adjustment is necessary for patients with mild to moderate renal or hepatic impairment. 

However, due to increased exposure in these populations dosing recommendations to titrate according to 

individual tolerability should be closely followed as patients with clinically significant renal or hepatic 

impairment might experience more dose-dependent adverse reactions. Patients with severe hepatic 

impairment have not been studied, however, Prometax capsules may be used in this patient population 

provided close monitoring is exercised (see sections 4.4 and 5.2). 

 

Paediatric population 

There is no relevant use of Prometax in the paediatric population in the treatment of Alzheimer’s 

disease. 

 

4.3 Contraindications 
 

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 higher doses. If treatment is 

interrupted for more than three days, it should be re-initiated at 1.5 mg twice daily to reduce the 

possibility of adverse reactions (e.g. vomiting). 

 

Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in 

intensity. 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 allergic dermatitis 

(disseminated) when administered rivastigmine irrespective of the route of administration (oral, 

transdermal). In these cases, treatment should be discontinued (see section 4.3). 

 

Patients and caregivers should be instructed accordingly. 

 

Dose titration: Adverse reactions (e.g. hypertension and hallucinations in patients with Alzheimer’s 

dementia and worsening of extrapyramidal symptoms, in particular tremor, in patients with dementia 

associated with Parkinson’s disease) have been observed shortly after dose increase. They may 

respond to a dose reduction. In other cases, Prometax has been discontinued (see section 4.8). 

 



 

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Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose-related, and may occur 

particularly 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. 

 

Patients with Alzheimer’s disease may lose weight. Cholinesterase inhibitors, including rivastigmine, 

have been associated with weight loss in these patients. During therapy patient’s weight should be 

monitored. 

 

In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as 

recommended in section 4.2 must be made. Some cases of severe vomiting were associated with 

oesophageal rupture (see section 4.8). Such events appeared to occur particularly after dose increments 

or high doses of rivastigmine. 

 

Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de 

pointes, predominantly in patients with risk factors. Caution is advised in patients at higher risk of 

developing torsade de pointes; for example, those with uncompensated heart failure, recent myocardial 

infarction, bradyarrhythmias, a predisposition to hypokalaemia or hypomagnesaemia, or concomitant 

use with medicinal products known to induce QT prolongation and/or torsade de pointes (see sections 

4.5 and 4.8). 

 

Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects 

(sino-atrial block, atrio-ventricular block) (see section 4.8). 

 

Rivastigmine may cause increased gastric acid secretions. Care should be exercised in treating patients 

with active gastric or duodenal ulcers or patients predisposed to these conditions. 

 

Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or 

obstructive pulmonary disease. 

 

Cholinomimetics may induce or exacerbate urinary obstruction and seizures. Caution is recommended in 

treating patients predisposed to such diseases. 

 

The use of rivastigmine in patients with severe dementia of Alzheimer’s disease or associated with 

Parkinson’s disease, other types of dementia or other types of memory impairment (e.g. age-related 

cognitive decline) has not been investigated and therefore use in these patient populations is not 

recommended. 

 

Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms. 

Worsening (including bradykinesia, dyskinesia, gait abnormality) and an increased incidence or severity 

of tremor have been observed in patients with dementia associated with Parkinson’s disease (see section 

4.8). These events led to the discontinuation of rivastigmine in some cases (e.g. discontinuations due to 

tremor 1.7% on rivastigmine vs 0% on placebo). Clinical monitoring is recommended for these adverse 

reactions. 

 

Special populations 

 

Patients with clinically significant renal or hepatic impairment might experience more adverse reactions 

(see sections 4.2 and 5.2). Dosing recommendations to titrate according to individual tolerability must be 

closely followed. Patients with severe hepatic impairment have not been studied. However, Prometax 

may be used in this patient population and close monitoring is necessary. 

 

Patients with body weight below 50 kg may experience more adverse reactions and may be more likely 

to discontinue due to adverse reactions. 

 



 

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4.5 Interaction with other medicinal products and other forms of interaction 
 

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle 

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 and possible additive effects, rivastigmine should not be given 

concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of 

anticholinergic medicinal products (e.g oxybutynin, tolterodine). 

 

Additive effects leading to bradycardia (which may result in syncope) have been reported with the 

combined use of various beta-blockers (including atenolol) and rivastigmine. Cardiovascular beta- 

blockers are expected to be associated with the greatest risk, but reports have also been received in 

patients using other beta-blockers. Therefore, caution should be exercised when rivastigmine is 

combined with beta-blockers and also other bradycardia agents (e.g.class III antiarrhythmic agents, 

calcium channel antagonists, digitalis glycoside, pilocarpin). 

 

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of 

rivastigmine with torsades de pointes-inducing medicinal products such as antipsychotics i.e. some 

phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, sultopride, amisulpride, 

tiapride, veralipride), pimozide, haloperidol, droperidol, cisapride, citalopram, diphemanil, 

erythromycin IV, halofantrin, mizolastin, methadone, pentamidine and moxifloxacine should be 

observed with caution and clinical monitoring (ECG) may also be required. 

 

No pharmacokinetic interaction was observed between 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 rivastigmine. No untoward effects on cardiac conduction were observed 

following concomitant administration of digoxin and rivastigmine. 

 

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 

 

In pregnant animals, rivastigmine and/or metabolites crossed the placenta. It is not known if this occurs 

in humans. 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 in milk. It is not known if rivastigmine is excreted into human milk. 

Therefore, women on rivastigmine should not breast-feed. 

 

Fertility 

 

No adverse effects of rivastigmine were observed on fertility or reproductive performance in rats (see 

section 5.3). Effects of rivastigmine on human fertility are not known. 

 



 

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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 machinery. Furthermore, rivastigmine can induce dizziness and somnolence, mainly when initiating 

treatment or increasing the dose. As a consequence, rivastigmine has minor or moderate influence on the 

ability to drive and use machines. Therefore, the ability of patients with dementia on rivastigmine to 

continue driving or operating complex machines should be routinely evaluated by the treating physician. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

 

The most commonly reported adverse reactions (ADRs) are gastrointestinal, including nausea (38%) and 

vomiting (23%), especially during titration. Female patients in clinical studies were found to be more 

susceptible than male patients to gastrointestinal adverse reactions and weight loss. 

 

Tabulated list of adverse reactions 

 

Adverse reactions in Table 1 and Table 2 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). 

 

The following adverse reactions, listed below in Table 1, have been accumulated in patients with 

Alzheimer’s dementia treated with Prometax. 

 

Table 1 

 

Infections and infestations 

 Very rare Urinary infection 

Metabolism and nutrition disorders 
 Very common Anorexia 

 Common Decreased appetite 

 Not known Dehydration 

Psychiatric disorders 

 Common Nightmares 

 Common Agitation 

 Common Confusion 

 Common Anxiety 

 Uncommon Insomnia 

 Uncommon Depression 

 Very rare Hallucinations 

 Not known Aggression, restlessness 

Nervous system disorders 

 Very common Dizziness 

 Common Headache 

 Common Somnolence 

 Common Tremor 

 Uncommon Syncope 

 Rare Seizures 

 Very rare Extrapyramidal symptoms (including worsening of 

Parkinson’s disease) 

Cardiac disorders 

 Rare Angina pectoris 

 Very rare Cardiac arrhythmia (e.g. bradycardia, atrio-ventricular block, 

atrial fibrillation and tachycardia) 

 Not known Sick sinus syndrome 



 

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Vascular disorders 

 Very rare Hypertension 

Gastrointestinal disorders 

 Very common Nausea 

 Very common Vomiting 

 Very common Diarrhoea 

 Common Abdominal pain and dyspepsia 

 Rare Gastric and duodenal ulcers 

 Very rare Gastrointestinal haemorrhage 

 Very rare Pancreatitis 

 Not known Some cases of severe vomiting were associated with 

oesophageal rupture (see section 4.4). 

Hepatobiliary disorders 

 Uncommon Elevated liver function tests 

 Not known Hepatitis 

Skin and subcutaneous tissue disorders 

 Common Hyperhydrosis 

 Rare Rash 

 Not known Pruritus, allergic dermatitis (disseminated) 

General disorders and administration site conditions 

 Common Fatigue and asthenia 

 Common Malaise 

 Uncommon Fall 

Investigations 

 Common Weight loss 

 

The following additional adverse reactions have been observed with Prometax transdermal patches: 

delirium, pyrexia, decreased appetite, urinary incontinence (common), psychomotor hyperactivity 

(uncommon), erythema, urticaria, vesicles, allergic dermatitis (not known). 

 

Table 2 shows the adverse reactions reported during clinical studies conducted in patients with dementia 

associated with Parkinson’s disease treated with Prometax capsules. 

 

Table 2 

 

Metabolism and nutrition disorders 

 Common Decreased appetite 

 Common Dehydration 

Psychiatric disorders 

 Common Insomnia 

 Common Anxiety 

 Common Restlessness 

 Common Hallucination, visual 

 Common Depression 

 Not known Aggression 

Nervous system disorders 

 Very common Tremor 

 Common Dizziness 

 Common Somnolence 

 Common Headache 

 Common Parkinson’s disease (worsening) 

 Common Bradykinesia 

 Common Dyskinesia 

 Common Hypokinesia 

 Common Cogwheel rigidity 

 Uncommon Dystonia 



 

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Cardiac disorders 

 Common Bradycardia 

 Uncommon Atrial Fibrillation 

 Uncommon Atrioventricular block 

 Not known Sick sinus syndrome 

Vascular disorders 

 Common Hypertension 

 Uncommon Hypotension 

Gastrointestinal disorders 

 Very common Nausea 

 Very common Vomiting 

 Common Diarrhoea 

 Common Abdominal pain and dyspepsia 

 Common Salivary hypersecretion 

Hepatobiliary disorders 

 Not known Hepatitis 

Skin and subcutaneous tissue disorders 

 Common Hyperhydrosis 

 Not known Allergic dermatitis (disseminated) 

General disorders and administration site conditions 

 Very common Fall 

 Common Fatigue and asthenia 

 Common Gait disturbance 

 Common Parkinson gait 

 

The following additional adverse reaction has been observed in a study of patients with dementia 

associated with Parkinson’s disease treated with Prometax transdermal patches: agitation (common). 

 

Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 

with Prometax in patients with dementia associated with Parkinson’s disease with pre-defined adverse 

events that may reflect worsening of parkinsonian symptoms. 

 

Table 3 

 

Pre-defined adverse events that may reflect worsening 

of parkinsonian symptoms in patients with dementia 

associated with Parkinson’s disease 

Prometax 

n (%) 

Placebo 

n (%) 

Total patients studied 362 (100) 179 (100) 

Total patients with pre-defined AE(s) 99 (27.3) 28 (15.6) 

Tremor 37 (10.2) 7 (3.9) 

Fall 21 (5.8) 11 (6.1) 

Parkinson’s disease (worsening) 12 (3.3) 2 (1.1) 

Salivary hypersecretion 5 (1.4) 0 

Dyskinesia 5 (1.4) 1 (0.6) 

Parkinsonism 8 (2.2) 1 (0.6) 

Hypokinesia 1 (0.3) 0 

Movement disorder 1 (0.3) 0 

Bradykinesia 9 (2.5) 3 (1.7) 

Dystonia 3 (0.8) 1 (0.6) 

Gait abnormality 5 (1.4) 0 

Muscle rigidity 1 (0.3) 0 

Balance disorder 3 (0.8) 2 (1.1) 

Musculoskeletal stiffness 3 (0.8) 0 

Rigors 1 (0.3) 0 

Motor dysfunction 1 (0.3) 0 

 



 

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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 have not been associated with any clinical signs or symptoms and 

almost all of the patients concerned continued rivastigmine treatment 24 hours after the overdose. 

 

Cholinergic toxicity has been reported with muscarinic symptoms that are observed with moderate 

poisonings such as miosis, flushing, digestive disorders including abdominal pain, nausea, vomiting and 

diarrhoea, bradycardia, bronchospasm and increased bronchial secretions, hyperhidrosis, involuntary 

urination and/or defecation, lacrimation, hypotension and salivary hypersecretion. 

 

In more severe cases nicotinic effects might develop such as muscular weakness, fasciculations, seizures 

and respiratory arrest with possible fatal outcome. 

 

Additionally there have been post-marketing cases of dizziness, tremor, headache, somnolence, 

confusional state, hypertension, hallucinations and malaise. 

 

Management 

 

As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of 

about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine 

should be administered 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. 

 

 

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 and 

Parkinson’s disease. 

 



 

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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 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 rivastigmine was similar 

to that of AChE. 

 

Clinical studies in Alzheimer’s dementia 

 

The efficacy of rivastigmine has been established through the use of three independent, domain 

specific, assessment tools which were assessed at periodic intervals during 6 month treatment periods. 

These include the ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a 

performance based measure of cognition), the CIBIC-Plus (Clinician’s Interview Based Impression of 

Change-Plus, a comprehensive global assessment of the patient by the physician incorporating 

caregiver input), and the PDS (Progressive Deterioration Scale, 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 

relating to finances, etc.). 

 

The patients studied had an MMSE (Mini-Mental State Examination) score of 10–24. 

 

The results for clinically relevant responders pooled from two flexible dose studies out of the three 

pivotal 26-week multicentre studies in patients with mild-to-moderately severe Alzheimer’s Dementia, 

are provided in Table 4 below. Clinically relevant improvement in these studies was defined a priori as 

at least 4-point improvement on the ADAS-Cog, improvement on the CIBIC-Plus, or at least a 10% 

improvement on the PDS. 

 

In addition, a post-hoc definition of response is provided in the same table. The secondary definition 

of response required a 4-point or greater improvement on the ADAS-Cog, no worsening on the 

CIBIC-Plus, and no worsening on the PDS. The mean actual daily dose for responders in the 6–12 mg 

group, corresponding to this definition, was 9.3 mg. It is important to note that the scales used in this 

indication vary and direct comparisons of results for different therapeutic agents are not valid. 

 

Table 4 

 

 Patients with Clinically Significant Response (%) 

 Intent to Treat Last Observation Carried 

Forward 

Response Measure Rivastigmine 

6–12 mg 

N=473 

Placebo 

 

N=472 

Rivastigmine 

6–12 mg 

N=379 

Placebo 

 

N=444 

ADAS-Cog: improvement 

of at least 4 points 

21*** 

 

12 

 

25*** 

 

12 

CIBIC-Plus: improvement 29*** 18 32*** 19 

PDS: improvement of at 

least 10% 

26*** 17 30*** 18 

At least 4 points 

improvement on ADAS-

Cog with no worsening on 

CIBIC-Plus and PDS 

10* 

 

6 

 

12** 

 

6 

*p<0.05, **p<0.01, ***p<0.001 

 



 

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Clinical studies in dementia associated with Parkinson’s disease 

 

The efficacy of rivastigmine in dementia associated with Parkinson’s disease has been demonstrated in 

a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label 

extension phase. Patients involved in this study had an MMSE (Mini-Mental State Examination) score 

of 10–24. Efficacy has been established by the use of two independent scales which were assessed at 

regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a 

measure of cognition, and the global measure ADCS-CGIC (Alzheimer’s Disease Cooperative Study-

Clinician’s Global Impression of Change). 

 

Table 5 

 

Dementia associated with 

Parkinson’s Disease 

ADAS-Cog 

Prometax 

 

ADAS-Cog 

Placebo 

 

ADCS-

CGIC 

Prometax 

 

ADCS-CGIC 

Placebo 

 

ITT + RDO population (n=329) (n=161) (n=329) (n=165) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

23.8 ± 10.2 

2.1 ± 8.2 

24.3 ± 10.5 

-0.7 ± 7.5 

n/a 

3.8 ± 1.4 

n/a 

4.3 ± 1.5 

Adjusted treatment 

difference 

 

2.881 

 

n/a 

p-value versus placebo <0.0011 0.0072 

     

ITT - LOCF population (n=287) (n=154) (n=289) (n=158) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

24.0 ± 10.3 

2.5 ± 8.4 

24.5 ± 10.6 

-0.8 ± 7.5 

n/a 

3.7 ± 1.4 

n/a 

4.3 ± 1.5 

Adjusted treatment 

difference 

 

3.541 

 

n/a 

p-value versus placebo <0.0011 <0.0012 

     
1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A 

positive change indicates improvement. 
2 Mean data shown for convenience, categorical analysis performed using van Elteren test 

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward 

 

  



 

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Although a treatment effect was demonstrated in the overall study population, the data suggested that a 

larger treatment effect relative to placebo was seen in the subgroup of patients with moderate dementia 

associated with Parkinson’s disease. Similarly a larger treatment effect was observed in those patients 

with visual hallucinations (see Table 6). 

 

Table 6 

 

Dementia associated with 

Parkinson’s Disease 

ADAS-Cog 

Prometax 

 

ADAS-Cog 

Placebo 

 

ADAS-Cog 

Prometax 

 

ADAS-Cog 

Placebo 

 

 Patients with visual 

hallucinations 

Patients without visual 

hallucinations 

     

ITT + RDO population (n=107) (n=60) (n=220) (n=101) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

25.4 ± 9.9 

1.0 ± 9.2 

27.4 ± 10.4 

-2.1 ± 8.3 

23.1 ± 10.4 

2.6 ± 7.6 

22.5 ± 10.1 

0.1 ± 6.9 

Adjusted treatment 

difference 

 

4.271 

 

2.091 

p-value versus placebo 0.0021 0.0151 

 Patients with moderate 

dementia (MMSE 10-17) 

Patients with mild dementia 

(MMSE 18-24) 

     

ITT + RDO population (n=87) (n=44) (n=237) (n=115) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

32.6 ± 10.4 

2.6 ± 9.4 

33.7 ± 10.3 

-1.8 ± 7.2 

20.6 ± 7.9 

1.9 ± 7.7 

20.7 ± 7.9 

-0.2 ± 7.5 

Adjusted treatment 

difference 

 

4.731 

 

2.141 

p-value versus placebo 0.0021 0.0101 

     
1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A 

positive change indicates improvement. 

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Prometax in all subsets of the paediatric population in the treatment of Alzheimer’s dementia and in 

the treatment of dementia in patients with idiopathic Parkinson’s disease (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 
 

Absorption 

 

Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in 

approximately 1 hour. As a consequence of rivastigmine’s interaction with its target enzyme, the 

increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose. Absolute 

bioavailability after a 3 mg dose is about 36%13%. Administration of rivastigmine with food delays 

absorption (tmax) by 90 min and lowers Cmax and increases AUC by approximately 30%. 

 

Distribution 

 

Protein binding of rivastigmine is 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. 

 



14 

Biotransformation 

Rivastigmine is rapidly and extensively metabolised (half-life in plasma approximately 1 hour), 

primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. In vitro, this 

metabolite shows minimal inhibition of acetylcholinesterase (<10%). 

Based on in vitro studies, no pharmacokinetic interaction is expected with medicinal products 

metabolised by the following cytochromes isoemzymes: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, 

CYP2C9, CYP2C8, CYP2C19, or CYP2B6. Based on evidence from animal studies the major 

cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism. Total plasma 

clearance of rivastigmine was approximately 130 l/h after a 0.2 mg intravenous dose and decreased to 

70 l/h after a 2.7 mg intravenous dose. 

Elimination 

Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route of 

elimination. Following administration of 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. There 

is no accumulation of rivastigmine or the decarbamylated metabolite in patients with Alzheimer’s 

disease. 

A population pharmacokinetic analysis showed that nicotine use increases the oral clearance of 

rivastigmine by 23% in patients with Alzheimer’s disease (n=75 smokers and 549 non-smokers) 

following rivastigmine oral capsule doses of up to 12 mg/day. 

Special populations 

Elderly 

While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in 

Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age. 

Hepatic impairment 

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 

Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment 

compared with healthy subjects; however there were no changes in Cmax and AUC of rivastigmine in 

subjects with severe renal impairment. 

5.3 Preclinical safety data 

Repeated-dose toxicity studies in rats, mice and dogs revealed only effects associated with an 

exaggerated pharmacological action. No target organ toxicity was observed. No safety margins to human 

exposure were achieved in the animal studies 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 104 times the maximum clinical 

exposure. The in vivo micronucleus test was negative. The major metabolite NAP226-90 also did not 

show a genotoxic potential. 

No evidence of carcinogenicity was found in studies in mice and rats at the maximum tolerated dose, 

although the exposure to rivastigmine and its metabolites was lower than the human exposure. When 

normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately 

equivalent to the maximum recommended human dose of 12 mg/day; however, when compared to the 

maximum human dose, a multiple of approximately 6-fold was achieved in animals. 



 

15 

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. In oral studies with male 

and female rats, no adverse effects of rivastigmine were observed on fertility or reproductive 

performance of either the parent generation or the offspring of the parents. 

 

A mild eye/mucosal irritation potential of rivastigmine was identified in a rabbit study. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Gelatin 

Magnesium stearate 

Hypromellose 

Microcrystalline cellulose 

Silica, colloidal anhydrous 

Yellow iron oxide (E172) 

Red iron oxide (E172) 

Titanium dioxide (E171) 

Shellac 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

5 years 

 

6.4 Special precautions for storage 
 

Do not store above 30°C. 

 

6.5 Nature and contents of container 
 

- Blister of clear PVC tray with blue lidding foil with 14 capsules. Each box contains 28, 56 or 

112 capsules. 

- HDPE bottles with plastic closure with induction innerseal. Each bottle contains 250 capsules. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 



 

16 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Prometax 1.5 mg hard capsules 

 

EU/1/98/092/001-3 

EU/1/98/092/014 

 

Prometax 3.0 mg hard capsules 

 

EU/1/98/092/004-6 

EU/1/98/092/015 

 

Prometax 4.5 mg hard capsules 

 

EU/1/98/092/007-9 

EU/1/98/092/016 

 

Prometax 6.0 mg hard capsules 

 

EU/1/98/092/010-12 

EU/1/98/092/017 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 04 December 1998 

Date of latest renewal: 21 May 2008 

 

 

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 



 

17 

1. NAME OF THE MEDICINAL PRODUCT 
 

Prometax 2 mg/ml oral solution 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml contains rivastigmine hydrogen tartrate corresponding to 2 mg rivastigmine. 

 

Excipient(s) with known effect 

 
Each 3 ml oral solution contains 3 mg of sodium benzoate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Oral solution 

 

Clear, yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. 

Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson’s 

disease. 

 

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 or dementia associated with Parkinson’s disease. Diagnosis should be made 

according to current guidelines. Therapy with rivastigmine should only be started if a caregiver is 

available who will regularly monitor intake of the medicinal product by the patient. 

 

Posology 

 

Rivastigmine oral solution should be administered twice a day, with morning and evening meals. The 

prescribed amount of solution should be withdrawn from the container using the oral dosing syringe 

supplied. Rivastigmine oral solution may be swallowed directly from the syringe. Rivastigmine oral 

solution and rivastigmine capsules may be interchanged at equal doses. 

 

Initial dose 

1.5 mg twice a day. 

 

Dose titration 

The starting dose is 1.5 mg twice a day. If this dose is well tolerated after a minimum of two weeks of 

treatment, the dose may be increased to 3 mg twice a day. Subsequent increases to 4.5 mg and then 6 mg 

twice a day should also be based on good tolerability of the current dose and may be considered after a 

minimum of two weeks of treatment at that dose level. 

 



18 

If adverse reactions (e.g. nausea, vomiting, abdominal pain or loss of appetite), weight decrease or 

worsening of extrapyramidal symptoms (e.g. tremor) in patients with dementia associated with 

Parkinson’s disease are observed during treatment, these may respond to omitting one or more doses. If 

adverse reactions persist, the daily dose should be temporarily reduced to the previous well-tolerated 

dose or the treatment may be discontinued. 

Maintenance dose 

The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be 

maintained on their highest well tolerated dose. The recommended maximum daily dose is 6 mg twice a 

day. 

Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. 

Therefore, the clinical benefit of rivastigmine should be reassessed on a regular basis, especially for 

patients treated at doses less than 3 mg twice a day. If after 3 months of maintenance dose treatment the 

patient’s rate of decline in dementia symptoms is not altered favourably, the treatment should be 

discontinued. Discontinuation should also be considered when evidence of a therapeutic effect is no 

longer present. 

Individual response to rivastigmine cannot be predicted. However, a greater treatment effect was seen in 

Parkinson’s disease patients with moderate dementia. Similarly a larger effect was observed in 

Parkinson’s disease patients with visual hallucinations (see section 5.1). 

Treatment effect has not been studied in placebo-controlled trials beyond 6 months. 

Re-initiation of therapy 

If treatment is interrupted for more than three days, it should be re-initiated at 1.5 mg twice daily. 

Dose titration should then be carried out as described above. 

Special populations 

Renal and hepatic impairment 

No dose adjustment is necessary for patients with mild to moderate renal or hepatic impairment. 

However, due to increased exposure in these populations dosing recommendations to titrate according to 

individual tolerability should be closely followed as patients with clinically significant renal or hepatic 

impairment might experience more dose-dependent adverse reactions. Patients with severe hepatic 

impairment have not been studied, however, Prometax oral solution may be used in this patient 

population provided close monitoring is exercised (see sections 4.4 and 5.2). 

Paediatric population 

There is no relevant use of Prometax in the paediatric population in the treatment of Alzheimer’s 

disease. 

4.3 Contraindications 

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). 



 

19 

4.4 Special warnings and precautions for use 
 

The incidence and severity of adverse reactions generally increase with higher doses. If treatment is 

interrupted for more than three days, it should be re-initiated at 1.5 mg twice daily to reduce the 

possibility of adverse reactions (e.g. vomiting). 

 

Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in 

intensity. 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 allergic dermatitis 

(disseminated) when administered rivastigmine irrespective of the route of administration (oral, 

transdermal). In these cases, treatment should be discontinued (see section 4.3). 

 

Patients and caregivers should be instructed accordingly. 

 

Dose titration: Adverse reactions (e.g. hypertension and hallucinations in patients with Alzheimer’s 

dementia and worsening of extrapyramidal symptoms, in particular tremor, in patients with dementia 

associated with Parkinson’s disease) have been observed shortly after dose increase. They may 

respond to a dose reduction. In other cases, Prometax has been discontinued (see section 4.8). 

 

Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose-related, and may occur 

particularly 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. 

 

Patients with Alzheimer’s disease may lose weight. Cholinesterase inhibitors, including rivastigmine, 

have been associated with weight loss in these patients. During therapy patient’s weight should be 

monitored. 

 

In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as 

recommended in section 4.2 must be made. Some cases of severe vomiting were associated with 

oesophageal rupture (see section 4.8). Such events appeared to occur particularly after dose increments 

or high doses of rivastigmine. 

 

Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de 

pointes, predominantly in patients with risk factors. Caution is advised in patients at higher risk of 

developing torsade de pointes; for example, those with uncompensated heart failure, recent myocardial 

infarction, bradyarrhythmias, a predisposition to hypokalaemia or hypomagnesaemia, or concomitant 

use with medicinal products known to induce QT prolongation and/or torsade de pointes (see sections 

4.5 and 4.8). 

 

Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects 

(sino-atrial block, atrio-ventricular block) (see section 4.8). 



 

20 

 

Rivastigmine may cause increased gastric acid secretions. Care should be exercised in treating patients 

with active gastric or duodenal ulcers or patients predisposed to these conditions. 

 

Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or 

obstructive pulmonary disease. 

 

Cholinomimetics may induce or exacerbate urinary obstruction and seizures. Caution is recommended in 

treating patients predisposed to such diseases. 

 

The use of rivastigmine in patients with severe dementia of Alzheimer’s disease or associated with 

Parkinson’s disease, other types of dementia or other types of memory impairment (e.g. age-related 

cognitive decline) has not been investigated and therefore use in these patient populations is not 

recommended. 

 

Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms. 

Worsening (including bradykinesia, dyskinesia, gait abnormality) and an increased incidence or severity 

of tremor have been observed in patients with dementia associated with Parkinson’s disease (see section 

4.8). These events led to the discontinuation of rivastigmine in some cases (e.g. discontinuations due to 

tremor 1.7% on rivastigmine vs 0% on placebo). Clinical monitoring is recommended for these adverse 

reactions. 

 

Special populations 

 

Patients with clinically significant renal or hepatic impairment might experience more adverse reactions 

(see sections 4.2 and 5.2). Dosing recommendations to titrate according to individual tolerability must be 

closely followed. Patients with severe hepatic impairment have not been studied. However, Prometax 

may be used in this patient population and close monitoring is necessary. 

 

Patients with body weight below 50 kg may experience more adverse reactions and may be more likely 

to discontinue due to adverse reactions. 

 

Excipients with known effects 

 

One of the excipients in Prometx oral solution is sodium benzoate. Benzoic acid is a mild irritant to the 

skin, eyes and mucous membrane. 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially 

'sodium-free'. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle 

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 and possible additive effects, rivastigmine should not be given 

concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of 

anticholinergic medicinal products (e.g oxybutynin, tolterodine). 

 

Additive effects leading to bradycardia (which may result in syncope) have been reported with the 

combined use of various beta-blockers (including atenolol) and rivastigmine. Cardiovascular beta- 

blockers are expected to be associated with the greatest risk, but reports have also been received in 

patients using other beta- blockers. Therefore, caution should be exercised when rivastigmine is 

combined with beta-blockers and also other bradycardia agents (e.g.class III antiarrhythmic agents, 

calcium channel antagonists, digitalis glycoside, pilocarpin). 

 



 

21 

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of 

rivastigmine with torsades de pointes-inducing medicinal products such as antipsychotics i.e. some 

phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, sultopride, amisulpride, 

tiapride, veralipride), pimozide, haloperidol, droperidol, cisapride, citalopram, diphemanil, 

erythromycin IV, halofantrin, mizolastin, methadone, pentamidine and moxifloxacine should be 

observed with caution and clinical monitoring (ECG) may also be required. 

 

No pharmacokinetic interaction was observed between 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 rivastigmine. No untoward effects on cardiac conduction were observed 

following concomitant administration of digoxin and rivastigmine. 

 

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 

 

In pregnant animals, rivastigmine and/or metabolites crossed the placenta. It is not known if this occurs 

in humans. 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 in milk. It is not known if rivastigmine is excreted into human milk. 

Therefore, women on rivastigmine should not breast-feed. 

 

Fertility 

 

No adverse effects of rivastigmine were observed on fertility or reproductive performance in rats (see 

section 5.3). Effects of rivastigmine on human fertility are not known. 

 

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 machinery. Furthermore, rivastigmine can induce dizziness and somnolence, mainly when initiating 

treatment or increasing the dose. As a consequence, rivastigmine has minor or moderate influence on the 

ability to drive and use machines. Therefore, the ability of patients with dementia on rivastigmine to 

continue driving or operating complex machines should be routinely evaluated by the treating physician. 

 

  



22 

4.8 Undesirable effects 

Summary of the safety profile 

The most commonly reported adverse reactions (ADRs) are gastrointestinal, including nausea (38%) and 

vomiting (23%), especially during titration. Female patients in clinical studies were found to be more 

susceptible than male patients to gastrointestinal adverse reactions and weight loss. 

Tabulated list of adverse reactions 

Adverse reactions in Table 1 and Table 2 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). 

The following adverse reactions, listed below in Table 1, have been accumulated in patients with 

Alzheimer’s dementia treated with Prometax. 

Table 1 

Infections and infestations 

Very rare Urinary infection 

Metabolism and nutrition disorders 
Very common Anorexia 

Common Decreased appetite 

Not known Dehydration 

Psychiatric disorders 

Common Nightmares 

Common Agitation 

Common Confusion 

Common Anxiety 

Uncommon Insomnia 

Uncommon Depression 

Very rare Hallucinations 

Not known Aggression, restlessness 

Nervous system disorders 

Very common Dizziness 

Common Headache 

Common Somnolence 

Common Tremor 

Uncommon Syncope 

Rare Seizures 

Very rare Extrapyramidal symptoms (including worsening of 

Parkinson’s disease) 

Cardiac disorders 

Rare Angina pectoris 

Very rare Cardiac arrhythmia (e.g. bradycardia, atrio-ventricular block, 

atrial fibrillation and tachycardia) 

Not known Sick sinus syndrome 

Vascular disorders 

Very rare Hypertension 



 

23 

Gastrointestinal disorders 

 Very common Nausea 

 Very common Vomiting 

 Very common Diarrhoea 

 Common Abdominal pain and dyspepsia 

 Rare Gastric and duodenal ulcers 

 Very rare Gastrointestinal haemorrhage 

 Very rare Pancreatitis 

 Not known Some cases of severe vomiting were associated with 

oesophageal rupture (see section 4.4). 

Hepatobiliary disorders 

 Uncommon Elevated liver function tests 

 Not known Hepatitis 

Skin and subcutaneous tissue disorders 

 Common Hyperhydrosis 

 Rare Rash 

 Not known Pruritus, allergic dermatitis (disseminated) 

General disorders and administration site conditions 

 Common Fatigue and asthenia 

 Common Malaise 

 Uncommon Fall 

Investigations 

 Common Weight loss 

 

The following additional adverse reactions have been observed with Prometax transdermal patches: 

delirium, pyrexia, decreased appetite, urinary incontinence (common), psychomotor hyperactivity 

(uncommon), erythema, urticaria, vesicles, allergic dermatitis (not known). 

 

Table 2 shows the adverse reactions reported during clinical studies conducted in patients with dementia 

associated with Parkinson’s disease treated with Prometax capsules. 

 

Table 2 

 

Metabolism and nutrition disorders 

 Common Decreased appetite 

 Common Dehydration 

Psychiatric disorders 

 Common Insomnia 

 Common Anxiety 

 Common Restlessness 

 Common Hallucination, visual 

 Common Depression 

 Not known Aggression 

Nervous system disorders 

 Very common Tremor 

 Common Dizziness 

 Common Somnolence 

 Common Headache 

 Common Parkinson’s disease (worsening) 

 Common Bradykinesia 

 Common Dyskinesia 

 Common Hypokinesia 

 Common Cogwheel rigidity 

 Uncommon Dystonia 



 

24 

Cardiac disorders 

 Common Bradycardia 

 Uncommon Atrial Fibrillation 

 Uncommon Atrioventricular block 

 Not known Sick sinus syndrome 

Vascular disorders 

 Common Hypertension 

 Uncommon Hypotension 

Gastrointestinal disorders 

 Very common Nausea 

 Very common Vomiting 

 Common Diarrhoea 

 Common Abdominal pain and dyspepsia 

 Common Salivary hypersecretion 

Hepatobiliary disorders 

 Not known Hepatitis 

Skin and subcutaneous tissue disorders 

 Common Hyperhydrosis 

 Not known Allergic dermatitis (disseminated) 

General disorders and administration site conditions 

 Very common Fall 

 Common Fatigue and asthenia 

 Common Gait disturbance 

 Common Parkinson gait 

 

The following additional adverse reaction has been observed in a study of patients with dementia 

associated with Parkinson’s disease treated with Prometax transdermal patches: agitation (common). 

 

Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 

with Prometax in patients with dementia associated with Parkinson’s disease with pre-defined adverse 

events that may reflect worsening of parkinsonian symptoms. 

 

Table 3 

 

Pre-defined adverse events that may reflect worsening 

of parkinsonian symptoms in patients with dementia 

associated with Parkinson’s disease 

Prometax 

n (%) 

Placebo 

n (%) 

Total patients studied 362 (100) 179 (100) 

Total patients with pre-defined AE(s) 99 (27.3) 28 (15.6) 

Tremor 37 (10.2) 7 (3.9) 

Fall 21 (5.8) 11 (6.1) 

Parkinson’s disease (worsening) 12 (3.3) 2 (1.1) 

Salivary hypersecretion 5 (1.4) 0 

Dyskinesia 5 (1.4) 1 (0.6) 

Parkinsonism 8 (2.2) 1 (0.6) 

Hypokinesia 1 (0.3) 0 

Movement disorder 1 (0.3) 0 

Bradykinesia 9 (2.5) 3 (1.7) 

Dystonia 3 (0.8) 1 (0.6) 

Gait abnormality 5 (1.4) 0 

Muscle rigidity 1 (0.3) 0 

Balance disorder 3 (0.8) 2 (1.1) 

Musculoskeletal stiffness 3 (0.8) 0 

Rigors 1 (0.3) 0 

Motor dysfunction 1 (0.3) 0 

 



25 

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 have not been associated with any clinical signs or symptoms and 

almost all of the patients concerned continued rivastigmine treatment 24 hours after the overdose. 

Cholinergic toxicity has been reported with muscarinic symptoms that are observed with moderate 

poisonings such as miosis, flushing, digestive disorders including abdominal pain, nausea, vomiting and 

diarrhoea, bradycardia, bronchospasm and increased bronchial secretions, hyperhidrosis, involuntary 

urination and/or defecation, lacrimation, hypotension and salivary hypersecretion. 

In more severe cases nicotinic effects might develop such as muscular weakness, fasciculations, seizures 

and respiratory arrest with possible fatal outcome. 

Additionaly there have been post-marketing cases of dizziness, tremor, headache, somnolence, 

confusional state, hypertension, hallucinations and malaise. 

Management 

As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of 

about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine 

should be administered 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. 

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 and 

Parkinson’s disease. 



 

26 

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 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 rivastigmine was similar 

to that of AChE. 

 

Clinical studies in Alzheimer’s dementia 

 

The efficacy of rivastigmine has been established through the use of three independent, domain 

specific, assessment tools which were assessed at periodic intervals during 6 month treatment periods. 

These include the ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale, a 

performance based measure of cognition), the CIBIC-Plus (Clinician’s Interview Based Impression of 

Change-Plus, a comprehensive global assessment of the patient by the physician incorporating 

caregiver input), and the PDS (Progressive Deterioration Scale, 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 

relating to finances, etc.). 

 

The patients studied had an MMSE (Mini-Mental State Examination) score of 10–24. 

 

The results for clinically relevant responders pooled from two flexible dose studies out of the three 

pivotal 26-week multicentre studies in patients with mild-to-moderately severe Alzheimer’s Dementia, 

are provided in Table 4 below. Clinically relevant improvement in these studies was defined a priori as 

at least 4-point improvement on the ADAS-Cog, improvement on the CIBIC-Plus, or at least a 10% 

improvement on the PDS. 

 

In addition, a post-hoc definition of response is provided in the same table. The secondary definition 

of response required a 4-point or greater improvement on the ADAS-Cog, no worsening on the 

CIBIC-Plus, and no worsening on the PDS. The mean actual daily dose for responders in the 6–12 mg 

group, corresponding to this definition, was 9.3 mg. It is important to note that the scales used in this 

indication vary and direct comparisons of results for different therapeutic agents are not valid. 

 

Table 4 

 

 Patients with Clinically Significant Response (%) 

 Intent to Treat Last Observation Carried 

Forward 

Response Measure Rivastigmine 

6–12 mg 

N=473 

Placebo 

 

N=472 

Rivastigmine 

6–12 mg 

N=379 

Placebo 

 

N=444 

ADAS-Cog: improvement 

of at least 4 points 

21*** 

 

12 

 

25*** 

 

12 

CIBIC-Plus: improvement 29*** 18 32*** 19 

PDS: improvement of at 

least 10% 

26*** 17 30*** 18 

At least 4 points 

improvement on ADAS-

Cog with no worsening on 

CIBIC-Plus and PDS 

10* 

 

6 

 

12** 

 

6 

*p<0.05, **p<0.01, ***p<0.001 

 



27 

Clinical studies in dementia associated with Parkinson’s disease 

The efficacy of rivastigmine in dementia associated with Parkinson’s disease has been demonstrated in 

a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label 

extension phase. Patients involved in this study had an MMSE (Mini-Mental State Examination) score 

of 10–24. Efficacy has been established by the use of two independent scales which were assessed at 

regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a 

measure of cognition, and the global measure ADCS-CGIC (Alzheimer’s Disease Cooperative Study-

Clinician’s Global Impression of Change). 

Table 5 

Dementia associated with 

Parkinson’s Disease 

ADAS-Cog 

Prometax 

ADAS-Cog 

Placebo 

ADCS-

CGIC 

Prometax 

ADCS-CGIC 

Placebo 

ITT + RDO population (n=329) (n=161) (n=329) (n=165) 

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

23.8 ± 10.2 

2.1 ± 8.2 

24.3 ± 10.5 

-0.7 ± 7.5

n/a 

3.8 ± 1.4 

n/a 

4.3 ± 1.5 

Adjusted treatment 

difference 2.881 n/a 

p-value versus placebo <0.0011 0.0072 

ITT - LOCF population (n=287) (n=154) (n=289) (n=158) 

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

24.0 ± 10.3 

2.5 ± 8.4 

24.5 ± 10.6 

-0.8 ± 7.5

n/a 

3.7 ± 1.4 

n/a 

4.3 ± 1.5 

Adjusted treatment 

difference 3.541 n/a 

p-value versus placebo <0.0011 <0.0012 

1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A 

positive change indicates improvement. 
2 Mean data shown for convenience, categorical analysis performed using van Elteren test 

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward 



 

28 

Although a treatment effect was demonstrated in the overall study population, the data suggested that a 

larger treatment effect relative to placebo was seen in the subgroup of patients with moderate dementia 

associated with Parkinson’s disease. Similarly a larger treatment effect was observed in those patients 

with visual hallucinations (see Table 6). 

 

Table 6 

 

Dementia associated with 

Parkinson’s Disease 

ADAS-Cog 

Prometax 

 

ADAS-Cog 

Placebo 

 

ADAS-Cog 

Prometax 

 

ADAS-Cog 

Placebo 

 

 Patients with visual 

hallucinations 

Patients without visual 

hallucinations 

     

ITT + RDO population (n=107) (n=60) (n=220) (n=101) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

25.4 ± 9.9 

1.0 ± 9.2 

27.4 ± 10.4 

-2.1 ± 8.3 

23.1 ± 10.4 

2.6 ± 7.6 

22.5 ± 10.1 

0.1 ± 6.9 

Adjusted treatment 

difference 

 

4.271 

 

2.091 

p-value versus placebo 0.0021 0.0151 

 Patients with moderate 

dementia (MMSE 10-17) 

Patients with mild dementia 

(MMSE 18-24) 

     

ITT + RDO population (n=87) (n=44) (n=237) (n=115) 

     

Mean baseline ± SD 

Mean change at 24 weeks 

± SD 

32.6 ± 10.4 

2.6 ± 9.4 

33.7 ± 10.3 

-1.8 ± 7.2 

20.6 ± 7.9 

1.9 ± 7.7 

20.7 ± 7.9 

-0.2 ± 7.5 

Adjusted treatment 

difference 

 

4.731 

 

2.141 

p-value versus placebo 0.0021 0.0101 

     
1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A 

positive change indicates improvement. 

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Prometax in all subsets of the paediatric population in the treatment of Alzheimer’s dementia and in 

the treatment of dementia in patients with idiopathic Parkinson’s disease (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 
 

Absorption 

 

Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in 

approximately 1 hour. As a consequence of rivastigmine’s interaction with its target enzyme, the 

increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose. Absolute 

bioavailability after a 3 mg dose is about 36%  13%. Administration of rivastigmine oral solution with 

food delays absorption (tmax) by 74 min and lowers Cmax by 43% and increases AUC by approximately 

9%. 

 

Distribution 

 

Protein binding of rivastigmine is 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. 



29 

Biotransformation 

Rivastigmine is rapidly and extensively metabolised (half-life in plasma approximately 1 hour), 

primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. In vitro, this 

metabolite shows minimal inhibition of acetylcholinesterase (<10%). 

Based on in vitro studies, no pharmacokinetic interaction is expected with medicinal products 

metabolised by the following cytochromes isoemzymes: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, 

CYP2C9, CYP2C8, CYP2C19, or CYP2B6. Based on evidence from animal studies the major 

cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism. Total plasma 

clearance of rivastigmine was approximately 130 l/h after a 0.2 mg intravenous dose and decreased to 

70 l/h after a 2.7 mg intravenous dose. 

Elimination 

Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route of 

elimination. Following administration of 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. There 

is no accumulation of rivastigmine or the decarbamylated metabolite in patients with Alzheimer’s 

disease. 

A population pharmacokinetic analysis showed that nicotine use increases the oral clearance of 

rivastigmine by 23% in patients with Alzheimer’s disease (n=75 smokers and 549 non-smokers) 

following rivastigmine oral capsule doses of up to 12 mg/day. 

Special populations 

Elderly 

While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in 

Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age. 

Hepatic impairment 

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 

Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment 

compared with healthy subjects; however there were no changes in Cmax and AUC of rivastigmine in 

subjects with severe renal impairment. 

5.3 Preclinical safety data 

Repeated-dose toxicity studies in rats, mice and dogs revealed only effects associated with an 

exaggerated pharmacological action. No target organ toxicity was observed. No safety margins to human 

exposure were achieved in the animal studies 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 104 times the maximum clinical 

exposure. The in vivo micronucleus test was negative. The major metabolite NAP226-90 also did not 

show a genotoxic potential. 

No evidence of carcinogenicity was found in studies in mice and rats at the maximum tolerated dose, 

although the exposure to rivastigmine and its metabolites was lower than the human exposure. When 

normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately 

equivalent to the maximum recommended human dose of 12 mg/day; however, when compared to the 

maximum human dose, a multiple of approximately 6-fold was achieved in animals. 



30 

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. In oral studies with male 

and female rats, no adverse effects of rivastigmine were observed on fertility or reproductive 

performance of either the parent generation or the offspring of the parents. 

A mild eye/mucosal irritation potential of rivastigmine was identified in a rabbit study. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium benzoate 

Citric acid 

Sodium citrate 

Quinoline yellow WS dye (E104) 

Purified water 

6.2 Incompatibilities 

Not applicable. 

6.3 Shelf life 

3 years 

Prometax oral solution should be used within 1 month of opening the bottle. 

6.4 Special precautions for storage 

Do not store above 30°C. Do not refrigerate or freeze. 

Store in an upright position. 

6.5 Nature and contents of container 

Type III amber glass bottle with a child-resistant cap, dip tube and self aligning plug. 50 ml or 120 ml 

bottle. The oral solution is packaged with an oral dosing syringe in a plastic tube container. 

6.6 Special precautions for disposal and other handling 

The prescribed amount of solution should be withdrawn from the bottle using the oral dosing syringe 

supplied. 

7. MARKETING AUTHORISATION HOLDER

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 



 

31 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/013 

EU/1/98/092/018 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 04 December 1998 

Date of latest renewal: 21 May 2008 

 

 

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 



 

32 

1. NAME OF THE MEDICINAL PRODUCT 
 

Prometax 4.6 mg/24 h transdermal patch 

Prometax 9.5 mg/24 h transdermal patch 

Prometax 13.3 mg/24 h transdermal patch 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Prometax 4.6 mg/24 h transdermal patch 

 

Each transdermal patch releases 4.6 mg of rivastigmine per 24 hours. Each transdermal patch of 5 cm2 

contains 9 mg of rivastigmine. 

 

Prometax 9.5 mg/24 h transdermal patch 

 

Each transdermal patch releases 9.5 mg of rivastigmine per 24 hours. Each transdermal patch of 10 cm2 

contains 18 mg of rivastigmine. 

 

Prometax 13.3 mg/24 h transdermal patch 

 

Each transdermal patch releases 13.3 mg of rivastigmine per 24 hours. Each transdermal patch of 15 cm2 

contains 27 mg of rivastigmine. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Transdermal patch 

 

Prometax 4.6 mg/24 h transdermal patch 

 

Each transdermal patch is a thin, matrix-type transdermal patch consisting of three layers. The outside of 

the backing layer is beige and labelled with “Prometax”, “4.6 mg/24 h” and “AMCX”. 

 

Prometax 9.5 mg/24 h transdermal patch 

 

Each transdermal patch is a thin, matrix-type transdermal patch consisting of three layers. The outside of 

the backing layer is beige and labelled with “Prometax”, “9.5 mg/24 h” and “BHDI”. 

 

Prometax 13.3 mg/24 h transdermal patch 

 

Each transdermal patch is a thin, matrix-type transdermal patch consisting of three layers. The outside of 

the backing layer is beige and labelled with “Prometax”, “13.3 mg/24 h” and “CNFU”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Symptomatic treatment of mild to moderately severe Alzheimer’s dementia. 

 



33 

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 

Prometax 4.6 mg/24 h 4.6 mg 

Prometax 9.5 mg/24 h 9.5 mg 

Prometax 13.3 mg/24 h 13.3 mg 

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. 

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 Prometax capsules or oral solution can be switched to Prometax 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. 



 

34 

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 Prometax 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: Due to increased exposure in mild to moderate hepatic impairment as 

observed with the oral formulation, dosing recommendations to titrate according to individual 

tolerability should be closely followed. Patients with clinically significant hepatic impairment 

may experience more dose-dependent adverse reactions. Patients with severe hepatic impairment 

have not been studied. Particular caution should be exercised in titrating these patients (see 

sections 4.4 and 5.2). 

 Renal impairment: No dose adjustment is necessary for patients with renal impairment (see 

section 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 

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 
 

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. 

 



35 

Misuse of the medicinal product and dosing errors resulting in overdose 

Misuse of the medicinal product and dosing errors with Prometax transdermal patch 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 Prometax 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 Prometax transdermal 

patches. 

Bradycardia 

Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de 

pointes, predominantly in patients with risk factors. Caution is advised in patients at higher risk of 

developing torsade de pointes; for example, those with uncompensated heart failure, recent myocardial 

infarction, bradyarrhythmias, a predisposition to hypokalaemia or hypomagnesaemia, or concomitant 

use with medicinal products known to induce QT prolongation and/or torsade de pointes (see sections 

4.5 and 4.8). 

Other adverse reactions 

Care must be taken when prescribing Prometax transdermal patches: 

 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). 



36 

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 allergic dermatitis 

(disseminated) 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 Prometax 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 may experience

more adverse reactions. Dosing recommendations to titrate according to individual tolerability

must be closely followed. Patients with severe hepatic impairment have not been studied.

Particular caution must be exercised in titrating these patients (see sections 4.2 and 5.2).

4.5 Interaction with other medicinal products and other forms of interaction

No specific interaction studies have been performed with Prometax transdermal patches. 

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle 

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 and possible additive effects, rivastigmine should not be given 

concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of 

anticholinergic medicinal products (e.g. oxybutynin, tolterodine). 

Additive effects leading to bradycardia (which may result in syncope) have been reported with the 

combined use of various beta-blockers (including atenolol) and rivastigmine. Cardiovascular beta-

blockers are expected to be associated with the greatest risk, but reports have also been received in 

patients using other beta-blockers. Therefore, caution should be exercised when rivastigmine is 

combined with beta-blockers and also other bradycardia agents (e.g.class III antiarrhythmic agents, 

calcium channel antagonists, digitalis glycoside, pilocarpin). 

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of 

rivastigmine with torsades de pointes-inducing medicinal products such as antipsychotics i.e. some 

phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, sultopride, amisulpride, 

tiapride, veralipride), pimozide, haloperidol, droperidol, cisapride, citalopram, diphemanil, 

erythromycin IV, halofantrin, mizolastin, methadone, pentamidine and moxifloxacine should be 

observed with caution and clinical monitoring (ECG) may also be required. 



 

37 

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, 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 

 

In pregnant animals, rivastigmine and /or metabolites crossed the placenta. It is not known if this occurs 

in humans. 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 in milk. It is not known if rivastigmine is excreted into human milk. 

Therefore, women on rivastigmine should not breast-feed. 

 

Fertility 

 

No adverse effects of rivastigmine were observed on fertility or reproductive performance in rats (see 

section 5.3). Effects of rivastigmine on human fertility are not known. 

 

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 Prometax 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). 

 



 

38 

Tabulated list of adverse reactions 

 

Table 1 displays the adverse reactions reported in 1,670 patients with Alzheimer’s dementia treated in 

randomised, double-blind, placebo and active-controlled clinical studies with Prometax 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, nightmares 

Nervous system disorders 
 Common Headache, syncope, dizziness 

 Uncommon Psychomotor hyperactivity 

 Very rare Extrapyramidal symptoms 

 Not known Worsening of Parkinson’s disease, seizure, tremor, somnolence 

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) 

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 

*In a 24-week controlled study in Japanese patients, application site erythema, application site oedema 

and application site pruritus were reported as “very common”. 

 

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 

Prometax 13.3 mg/24 h transdermal patches than with placebo. 

 



 

39 

The following adverse reactions have only been observed with Prometax capsules and oral solution and 

not in clinical studies with Prometax transdermal patches: malaise, 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). 

 

Skin irritation 

In double-blind controlled clinical trials, application site reactions were mostly mild to moderate in 

severity. The incidence of application site skin reactions leading to discontinuation was ≤2.3% in patients 

treated with Prometax transdermal patches. The incidence of application site skin reactions leading to 

discontinuation was higher in the Asian population with 4.9% and 8.4% in the Chinese and Japanese 

population respectively. 

 

In two 24-week double-blind, placebo-controlled clinical trials, skin reactions were measured at each 

visit using a skin irritation rating scale. When observed in patients treated with Prometax transdermal 

patches, skin irritation was mostly slight or mild in severity. It was rated as severe in ≤2.2% of patients 

in these studies and in ≤3.7% of patients treated with Prometax transdermal patches in a Japanese study. 

 

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 24 hours after the 

overdose. 

 

Cholinergic toxicity has been reported with muscarinic symptoms that are observed with moderate 

poisonings such as miosis, flushing, digestive disorders including abdominal pain, nausea, vomiting and 

diarrhoea, bradycardia, bronchospasm and increased bronchial secretions, hyperhidrosis, involuntary 

urination and/or defecation, lacrimation, hypotension and salivary hypersecretion. 

 

In more severe cases nicotinic effects might develop such as muscular weakness, fasciculations, seizures 

and respiratory arrest with possible fatal outcome. 

 

Additionaly there have been post-marketing cases of dizziness, tremor, headache, somnolence, 

confusional state, hypertension, hallucinations and malaise. Overdose with Prometax transdermal patch 

resulting from misuse/dosing errors (application of multiple patches at a time) has been reported in the 

post-marketing setting and rarely in clinical trials. 

 

Management 

 

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 Prometax 

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. 

 



40 

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 Prometax 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. 



 

41 

Table 2 

 

 Prometax 

transdermal patches 

9.5 mg/24 h 

Prometax 

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    

 (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 

Prometax 

transdermal patches 

9.5 mg/24 h 

N = 251 

Prometax 

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. 

 



 

42 

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 

Prometax 

15 cm2 

N = 265 

Prometax 

10 cm2 

N = 271 

Prometax 15 cm2 Prometax 

10 cm2 

n Mean n Mean DLS

M 

95% CI p-value 

ADAS-Cog         

LOCF Baseline 264 34.4 268 34.9    

 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 Prometax 

15 cm2 as compared to Prometax 10 cm2. 

ADCS-IADL scores: A positive difference in DLSM indicates greater improvement in Prometax 

15 cm2 as compared to Prometax 10 cm2. 

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 

Source: Study D2340-Table 11-6 and Table 11-7  

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Prometax in all subsets of the paediatric population in the treatment of Alzheimer’s dementia (see 

section 4.2 for information on paediatric use). 

 



43 

5.2 Pharmacokinetic properties 

Absorption 

Absorption of rivastigmine from Prometax 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 Prometax 4.6 mg/24 h transdermal patches, 0.77 for Prometax 

9.5 mg/24 h transdermal patches and 0.72 for Prometax 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 

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. 



44 

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 in vitro studies, no pharmacokinetic interaction is expected with medicinal products 

metabolised by the following cytochrome isoenzymes: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, 

CYP2C9, CYP2C8, CYP2C19, or CYP2B6. Based on evidence from 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. 

A population pharmacokinetic analysis showed that nicotine use increases the oral clearance of 

rivastigmine by 23% in patients with Alzheimer’s disease (n=75 smokers and 549 non-smokers) 

following rivastigmine oral capsule doses for up to 12 mg/day. 

Special populations 

Elderly 

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

Prometax transdermal patches. 

Hepatic impairment 

No study was conducted with Prometax 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. 

Following a single 3 mg or 6 mg oral dose, the mean oral clearance of rivastigmine was approximately 

46-63% lower in patients with mild to moderate hepatic impairment (n=10, Child-Pugh score 5-12, 

biopsy proven) than in healthy subjects (n=10). 

Renal impairment 

No study was conducted with Prometax transdermal patches in subjects with renal impairment. Based on 

population analysis, creatinine clearance did not show any clear effect on steady state concentrations of 

rivastigmine or its metabolite. No dose adjustment is necessary in patients with renal impairment (see 

section 4.2). 



 

45 

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. The major metabolite NAP226-

90 also did not show a genotoxic potential. 

 

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. In oral studies with male 

and female rats, no adverse effects of rivastigmine were observed on fertility or reproductive 

performance of either the parent generation or the offspring of the parents. Specific dermal studies in 

pregnant animals have not been conducted. 

 

Rivastigmine transdermal patches were not phototoxic and considered to be a non-sensitiser. 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 Prometax transdermal patches to induce mild erythema 

in patients. 

 

A mild eye/mucosal irritation potential of rivastigmine was identified in a rabbit study. 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 

 

Polyethylene terephthalate film, lacquered 

 

Medicinal product matrix 

 

Alpha-tocopherol 

Poly(butylmethacrylate, methylmethacrylate) 

Acrylic copolymer 

 

Adhesive matrix 

 

Alpha-tocopherol 

Silicone oil 

Dimethicone 

 

Release liner 

 

Polyester film, fluoropolymer-coated 

 



 

46 

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 
 

Do not store above 25°C. 

Keep the transdermal patch in the sachet until use. 

 

6.5 Nature and contents of container 
 

Prometax 9 mg/5 cm2, 18 mg/10 cm2 and 27 mg/15 cm2 transdermal patches are individually packaged 

in child-resistant, heat-sealed sachets made of a 

paper/polyethyleneterephthalate/aluminum/polyacrylnitrile (PAN) multi-laminated material 

(paper/PET/alu/PAN) or in heat-sealed, child-resistant sachets made of multi-layer composite laminate 

consisting of paper/polyethylene terephthalate/polyethylene/aluminum/polyamide 

(paper/PET/PE/alu/PA). 

 

Available in packs containing 7 or 30 sachets and in multipacks containing 60 or 90 sachets. 

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 

sachet and discarded safely and out of the reach and sight 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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

  



 

47 

8. MARKETING AUTHORISATION NUMBERS 

 

Prometax 4.6 mg/24 h transdermal patch 

 

EU/1/98/092/019-022 

EU/1/98/092/031-034 

 

Prometax 9.5 mg/24 h transdermal patch 

 

EU/1/98/092/023-026 

EU/1/98/092/035-038 

 

Prometax 13.3 mg/24 h transdermal patch 

 

EU/1/98/092/027-030 

EU/1/98/092/039-042 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 04 December 1998 

Date of latest renewal: 21 May 2008 

 

 

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 

  



 

48 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURERS 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 

 



 

49 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturers responsible for batch release 

 

Capsule, hard 

Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Oral solution 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Transdermal patch 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

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 (PSURs) 

 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 



 

50 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk management plan (RMP) 

 

The marketing authorisation holder (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. 
 

 Additional risk minimisation measures 

 

Prior to launch in each Member State the Marketing Authorisation Holder (MAH) shall agree the final 

educational material with the National Competent Authority. 

 

The MAH shall ensure that, following discussions and agreement with the National Competent 

Authorities in each Member State where Prometax patch is marketed, all physicians who are expected 

to prescribe Prometax patch are provided with an information pack containing the following elements: 

 The 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. 

 

  



 

51 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

 

  



 

52 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

53 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 1.5 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 1.5 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

56 hard capsules 

112 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

54 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/001 28 hard capsules 

EU/1/98/092/002 56 hard capsules 

EU/1/98/092/003 112 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 1.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



 

55 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 1.5 mg hard capsules 

rivastigmine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

  



 

56 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 1.5 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 1.5 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

57 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/014 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 1.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 
 

  



 

58 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 3.0 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 3.0 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

56 hard capsules 

112 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

59 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/004 28 hard capsules 

EU/1/98/092/005 56 hard capsules 

EU/1/98/092/006 112 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 3.0 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



 

60 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 3.0 mg hard capsules 

rivastigmine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

  



 

61 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 3.0 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 3.0 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

62 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/015 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 3.0 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 
 

  



 

63 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.5 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 4.5 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

56 hard capsules 

112 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

64 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/007 28 hard capsules 

EU/1/98/092/008 56 hard capsules 

EU/1/98/092/009 112 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 4.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



 

65 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.5 mg hard capsules 

rivastigmine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

  



 

66 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.5 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 4.5 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

67 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/016 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 4.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 
 

  



 

68 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 6.0 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 6.0 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

56 hard capsules 

112 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

69 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/010 28 hard capsules 

EU/1/98/092/011 56 hard capsules 

EU/1/98/092/012 112 hard capsules 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 6.0 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



 

70 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 6.0 mg hard capsules 

rivastigmine 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

  



 

71 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 6.0 mg hard capsules 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 capsule contains 6.0 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

250 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

 

To be swallowed whole without crushing or opening. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

 

 



 

72 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/017 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 6.0 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 
 

  



 

73 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

FOLDING BOX AND BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 2 mg/ml oral solution 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 2 mg rivastigmine present as rivastigmine hydrogen tartrate. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sodium benzoate, citric acid, sodium citrate, quinoline yellow dye (E104) and purified 

water. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Oral solution 

 

50 ml 

120 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral 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 

Use Prometax oral solution within 1 month of opening the bottle. 

 

 



 

74 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. Do not refrigerate or freeze. 

Store in an upright position. 

 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/018 50 ml 

EU/1/98/092/013 120 ml 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 2 mg/ml [folding box only] 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. [folding box only] 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC [folding box only] 

SN [folding box only] 

NN [folding box only] 

 

  



 

75 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.6 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 5 cm2 contains 9 mg rivastigmine and delivers 4.6 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 transdermal patches 

30 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

76 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/019 7 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/020 30 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/031 7 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/032 30 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 4.6 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

77 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.6 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 5 cm2 contains 9 mg rivastigmine and delivers 4.6 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 transdermal patches. Component of a multipack. Not to be sold separately. 

 

 

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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 

 



 

78 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/021 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/022 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/033 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/034 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 4.6 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



 

79 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 4.6 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 5 cm2 contains 9 mg rivastigmine and delivers 4.6 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 60 (2 packs of 30) transdermal patches 

Multipack: 90 (3 packs of 30) 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

80 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/021 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/022 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/033 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/034 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 4.6 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

81 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SACHET 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Prometax 4.6 mg/24 h transdermal patch 

rivastigmine 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Transdermal use 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 transdermal patch per sachet 

 

 

6. OTHER 

 

Apply one patch per day. Take off the previous patch before putting ONE new patch on. 

  



 

82 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 9.5 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 10 cm2 contains 18 mg rivastigmine and delivers 9.5 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 transdermal patches 

30 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

83 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/023 7 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/024 30 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/035 7 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/036 30 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 9.5 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

84 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 9.5 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 10 cm2 contains 18 mg rivastigmine and delivers 9.5 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 transdermal patches. Component of a multipack. Not to be sold separately. 

 

 

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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 

 



 

85 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/025 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/026 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/037 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/038 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 9.5 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



 

86 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 9.5 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 10 cm2 contains 18 mg rivastigmine and delivers 9.5 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 60 (2 packs of 30) transdermal patches 

Multipack: 90 (3 packs of 30) 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

87 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/025 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/026 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/037 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/038 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 9.5 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

88 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SACHET 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Prometax 9.5 mg/24 h transdermal patch 

rivastigmine 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Transdermal use 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 transdermal patch per sachet 

 

 

6. OTHER 

 

Apply one patch per day. Take off the previous patch before putting ONE new patch on. 

  



 

89 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 13.3 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 15 cm2 contains 27 mg rivastigmine and delivers 13.3 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 transdermal patches 

30 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

90 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/027 7 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/028 30 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/039 7 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/040 30 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 13.3 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

91 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 13.3 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 15 cm2 contains 27 mg rivastigmine and delivers 13.3 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 transdermal patches. Component of a multipack. Not to be sold separately. 

 

 

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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 

 



 

92 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/029 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/030 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/041 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/042 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 13.3 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

  



 

93 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Prometax 13.3 mg/24 h transdermal patch 

rivastigmine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 transdermal patch of 15 cm2 contains 27 mg rivastigmine and delivers 13.3 mg/24 h. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: polyethylene terephthalate film lacquered, alpha-tocopherol, poly(butylmethacrylate, 

methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, polyester film fluoropolymer-

coated. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 60 (2 packs of 30) transdermal patches 

Multipack: 90 (3 packs of 30) 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 

 

Do not store above 25°C. 

Keep the patch in the sachet until use. 

 



 

94 

 

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 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/98/092/029 60 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/030 90 transdermal patches (sachet: paper/PET/alu/PAN) 

EU/1/98/092/041 60 transdermal patches (sachet: paper/PET/PE/alu/PA) 

EU/1/98/092/042 90 transdermal patches (sachet: paper/PET/PE/alu/PA) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Prometax 13.3 mg/24 h 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



 

95 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SACHET 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Prometax 13.3 mg/24 h transdermal patch 

rivastigmine 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Transdermal use 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 transdermal patch per sachet 

 

 

6. OTHER 

 

Apply one patch per day. Take off the previous patch before putting ONE new patch on. 

  



 

96 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

97 

Package leaflet: Information for the user 
 

Prometax 1.5 mg hard capsules 

Prometax 3.0 mg hard capsules 

Prometax 4.5 mg hard capsules 

Prometax 6.0 mg hard capsules 

rivastigmine 

 

 

Read all of this leaflet carefully before you start taking 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 Prometax is and what it is used for 

2. What you need to know before you take Prometax 

3. How to take Prometax 

4. Possible side effects 

5. How to store Prometax 

6. Contents of the pack and other information 

 

 

 

1. What Prometax is and what it is used for 
 

The active substance of Prometax is rivastigmine. 

 

Rivastigmine belongs to a class of substances called cholinesterase inhibitors. In patients with 

Alzheimer’s dementia or dementia due to Parkinson’s disease, 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, Prometax 

allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of 

Alzheimer’s disease and dementia associated with Parkinson’s disease. 

 

Prometax 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. The capsules and oral solution can also be used for the treatment of dementia in adult 

patients with Parkinson’s disease. 

 

 

2. What you need to know before you take Prometax 

 

Do not take Prometax 
- if you are allergic to rivastigmine (the active substance in Prometax) or any of the other 

ingredients of this medicine (listed in section 6). 

- 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 take Prometax. 

 



 

98 

Warnings and precautions 

Talk to your doctor before taking Prometax: 

- if you have, or have ever had, irregular or slow heartbeat. 

- if you have, or have ever had, an active stomach ulcer. 

- 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 severe respiratory disease. 

- if you have, or have ever had impaired kidney function. 

- if you have, or have ever had, impaired liver function. 

- 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 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 taken Prometax for more than three days, do not take the next dose until you have 

talked to your doctor. 

 

Children and adolescents 

There is no relevant use of Prometax in the paediatric population in the treatment of Alzheimer’s disease. 

 

Other medicines and Prometax 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Prometax should not be given at the same time as other medicines with similar effects to Prometax. 

Prometax might interfere with anticholinergic medicines (medicines used to relieve stomach cramps or 

spasms, to treat Parkinson’s disease or to prevent travel sickness). 

 

Prometax should not be given at the same time as metoclopramide (a medicine used to relieve or 

prevent nausea and vomiting). Taking the two medicines together could cause problems such as stiff 

limbs and trembling hands. 

 

If you have to undergo surgery whilst taking Prometax, tell your doctor before you are given any 

anaesthetics, because Prometax may exaggerate the effects of some muscle relaxants during 

anaesthesia. 

 

Caution when Prometax is taken together with beta-blockers (medicines such as atenolol used to treat 

hypertension, angina and other heart conditions). Taking the two medicines together could cause 

problems such as slowing of the heartbeat (bradycardia) leading to fainting or loss of consciousness. 

 

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 Prometax must be assessed against the possible effects on 

your unborn child. Prometax should not be used during pregnancy unless clearly necessary. 

 

You should not breast-feed during treatment with Prometax. 

 

Driving and using machines 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. 

Prometax may cause dizziness and somnolence, mainly at the start of treatment or when increasing the 

dose. If you feel dizzy or sleepy, do not drive, use machines or perform any tasks that require your 

attention. 



 

99 

 

 

3. How to take Prometax 
 

Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 

nurse if you are not sure. 

 

How to start treatment 

Your doctor will tell you what dose of Prometax to take. 

 Treatment usually starts with a low dose. 

 Your doctor will slowly increase your dose depending on how you respond to treatment. 

 The highest dose that should be taken is 6.0 mg twice a day. 

 

Your doctor will regularly check if the medicine is working for you. Your doctor will also monitor 

your weight whilst you are taking this medicine. 

 

If you have not taken Prometax for more than three days, do not take the next dose until you have 

talked to your doctor. 

 

Taking this medicine 

 Tell your caregiver that you are taking Prometax. 

 To benefit from your medicine, take it every day. 

 Take Prometax twice a day, in the morning and evening, with food. 

 Swallow the capsules whole with a drink. 

 Do not open or crush the capsules. 

 

If you take more Prometax than you should 
If you accidentally take more Prometax than you should, inform your doctor. You may require 

medical attention. Some people who have accidentally taken too much Prometax 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 take Prometax 
If you find you have forgotten to take your dose of Prometax, wait and take the next dose at the usual 

time. Do not take a double dose to make up for a forgotten dose. 

 

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. 

 

Very common (may affect more than 1 in 10 people) 

 Feeling dizzy 

 Loss of appetite 

 Stomach problems such as feeling sick (nausea) or being sick (vomiting), diarrhoea 

 

  



 

100 

Common (may affect up to 1 in 10 people) 

 Anxiety 

 Sweating 

 Headache 

 Heartburn 

 Weight loss 

 Stomach pain 

 Feeling agitated 

 Feeling tired or weak 

 Generally feeling unwell 

 Trembling or feeling confused 

 Decreased appetite 

 Nightmares 

 

Uncommon (may affect up to 1 in 100 people) 

 Depression 

 Difficulty in sleeping 

 Fainting or accidentally falling 

 Changes in how well your liver is working 

 

Rare (may affect up to 1 in 1,000 people) 

 Chest pain 

 Rash, itching 

 Fits (seizures) 

 Ulcers in your stomach or intestine 

 

Very rare (may affect up to 1 in 10,000 people) 

 High blood pressure 

 Urinary tract infection 

 Seeing things that are not there (hallucinations) 

 Problems with your heartbeat such as fast or slow heartbeat 

 Bleeding in the gut – shows as blood in stools or when being sick 

 Inflammation of the pancreas – the signs include serious upper stomach pain, often with feeling 

sick (nausea) or being sick (vomiting) 

 The signs of Parkinson’s disease get worse or getting similar signs – such as stiff muscles, 

difficulty in carrying out movements 

 

Not known (frequency cannot be estimated from the available data) 

 Being violently sick (vomiting) that can cause tearing of the tube that connects your mouth with 

your stomach (oesophagus) 

 Dehydration (losing too much fluid) 

 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) 

 Aggression, feeling restless 

 Uneven heartbeat 

 

  



 

101 

Patients with dementia and Parkinson’s disease 

These patients have some side effects more often. They also have some additional side effects: 

 

Very common (may affect more than 1 in 10 people) 

 Trembling 

 Fainting 

 Accidentally falling 

 

Common (may affect up to 1 in 10 people) 

 Anxiety 

 Feeling restless 

 Slow and fast heartbeat 

 Difficulty in sleeping 

 Too much saliva and dehydration 

 Unusually slow movements or movements you cannot control 

 The signs of Parkinson’s disease get worse or getting similar signs – such as stiff muscles, 

difficulty in carrying out movements and muscle weakness 

 

Uncommon (may affect up to 1 in 100 people) 

 Uneven heartbeat and poor control of movements 

 

Other side effects seen with Prometax transdermal patches and which may occur with the hard 

capsules: 

 

Common (may affect up to 1 in 10 people) 

 Fever 

 Severe confusion 

 Urinary incontinence (inability to retain adequate urine) 

 

Uncommon (may affect up to 1 in 100 people) 

 Hyperactivity (high level of activity, restlessness) 

 

Not known (frequency cannot be estimated from the available data) 

 Allergic reaction where the patch was used, such as blisters or skin inflammation 

If you get any of these side effects, contact your doctor as you may need medical assistance. 

 

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 Prometax 

 

 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 after EXP. The 

expiry date refers to the last day of that month. 

 Do not store above 30°C. 

 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. 

 

 



 

102 

6. Contents of the pack and other information 

 

What Prometax contains 

- The active substance is rivastigmine hydrogen tartrate. 

- The other ingredients are hypromellose, magnesium stearate, microcrystalline cellulose, 

colloidal anhydrous silica, gelatin, yellow iron oxide (E172), red iron oxide (E172), titanium 

dioxide (E171) and shellac. 

 

Each Prometax 1.5 mg capsule contains 1.5 mg of rivastigmine. 

Each Prometax 3.0 mg capsule contains 3.0 mg of rivastigmine. 

Each Prometax 4.5 mg capsule contains 4.5 mg of rivastigmine. 

Each Prometax 6.0 mg capsule contains 6.0 mg of rivastigmine. 

 

What Prometax looks like and contents of the pack 

- Prometax 1.5 mg hard capsules, which contain an off-white to slightly yellow powder, have a 

yellow cap and yellow body, with red imprint “ENA 713 1,5 mg” on the body. 

- Prometax 3.0 mg hard capsules, which contain an off-white to slightly yellow powder, have an 

orange cap and orange body, with a red imprint “ENA 713 3 mg” on the body. 

- Prometax 4.5 mg hard capsules, which contain an off-white to slightly yellow powder, have a 

red cap and red body, with a white imprint “ENA 713 4,5 mg” on the body. 

- Prometax 6.0 mg hard capsules, which contain an off-white to slightly yellow powder, have a 

red cap and orange body, with a red imprint “ENA 713 6 mg” on the body. 

They are packed in blisters available in three different pack sizes (28, 56 or 112 capsules) and plastic 

bottles of 250 capsules, but these may not all be available in your country. 

 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 



 

103 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Sandoz Polska Sp. z o.o. 

Tel.: +48 22 549 1500 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Laboratório Normal - Produtos Farmacêuticos, 

Lda. 

Tel: +351 21 000 8600 

 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 



 

104 

Package leaflet: Information for the user 
 

Prometax 2 mg/ml oral solution 

rivastigmine 

 

 

Read all of this leaflet carefully before you start taking 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 Prometax is and what it is used for 

2. What you need to know before you take Prometax 

3. How to take Prometax 

4. Possible side effects 

5. How to store Prometax 

6. Contents of the pack and other information 

 

 

 

1. What Prometax is and what it is used for 
 

The active substance of Prometax is rivastigmine. 

 

Rivastigmine belongs to a class of substances called cholinesterase inhibitors. In patients with 

Alzheimer’s dementia or dementia due to Parkinson’s disease, 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, Prometax 

allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of 

Alzheimer’s disease and dementia associated with Parkinson’s disease. 

 

Prometax 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. The capsules and oral solution can also be used for the treatment of dementia in adult 

patients with Parkinson’s disease. 

 

 

2. What you need to know before you take Prometax 

 

Do not take Prometax 
- if you are allergic to rivastigmine (the active substance in Prometax) or any of the other 

ingredients of this medicine (listed in section 6). 

- 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 take Prometax. 

 

  



 

105 

Warnings and precautions 

Talk to your doctor before taking Prometax: 

- if you have, or have ever had, irregular or slow heartbeat. 

- if you have, or have ever had, an active stomach ulcer. 

- 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 severe respiratory disease. 

- if you have, or have ever had impaired kidney function. 

- if you have, or have ever had, impaired liver function. 

- 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 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 taken Prometax for more than three days, do not take the next dose until you have 

talked to your doctor. 

 

Children and adolescents 

There is no relevant use of Prometax in the paediatric population in the treatment of Alzheimer’s disease. 

 

Other medicines and Prometax 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Prometax should not be given at the same time as other medicines with similar effects to Prometax. 

Prometax might interfere with anticholinergic medicines (medicines used to relieve stomach cramps or 

spasms, to treat Parkinson’s disease or to prevent travel sickness). 

 

Prometax should not be given at the same time as metoclopramide (a medicine used to relieve or 

prevent nausea and vomiting). Taking the two medicines together could cause problems such as such 

as stiff limbs and trembling hands. 

 

If you have to undergo surgery whilst taking Prometax, tell your doctor before you are given any 

anaesthetics, because Prometax may exaggerate the effects of some muscle relaxants during 

anaesthesia. 

 

Caution when Prometax is taken together with beta-blockers (medicines such as atenolol used to treat 

hypertension, angina, and other heart conditions). Taking the two medicines together could cause 

problems such as slowing of the heartbeat (bradycardia) leading to fainting or loss of consciousness. 

 

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 Prometax must be assessed against the possible effects on 

your unborn child. Prometax should not be used during pregnancy unless clearly necessary. 

 

You should not breast-feed during treatment with Prometax. 

 

Driving and using machines 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. 

Prometax may cause dizziness and somnolence, mainly at the start of treatment or when increasing the 

dose. If you feel dizzy or sleepy, do not drive, use machines or perform any tasks that require your 

attention. 



 

106 

 

Prometax contains sodium benzoate and sodium 

One of the inactive ingredients in Prometax oral solution is sodium benzoate. Benzoic acid is a mild 

irritant to the skin, eyes and mucous membranes. This medicine contains 3 mg of sodium benzoate in 

each 3 ml of oral solution. 

 

This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially 'sodium-

free'. 

 

 

3. How to take Prometax 
 

Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 

nurse if you are not sure. 

 

How to start treatment 

Your doctor will tell you what dose of Prometax to take. 

 Treatment usually starts with a low dose. 

 Your doctor will slowly increase your dose depending on how you respond to the treatment. 

 The highest dose that should be taken is 6.0 mg twice a day. 

 

Your doctor will regularly check if the medicine is working for you. Your doctor will also monitor 

your weight whilst you are taking this medicine. 

 

If you have not taken Prometax for more than three days, do not take the next dose until you have 

talked to your doctor. 

 

Taking this medicine 

 Tell your caregiver that you are taking Prometax. 

 To benefit from your medicine, take it every day. 

 Take Prometax twice a day, in the morning and evening, with food. 

 

How to use this medicine 

 

 

1. Preparing the bottle and syringe 

 Take the syringe out of its protective case. 

 Push down and turn the child resistant cap to open 

bottle. 

 

 

2. Attaching the syringe to the bottle 

 Push the nozzle of the syringe into the hole in the 

white stopper. 

 



 

107 

 

3. Filling the syringe 

 Pull the plunger upwards until it reaches the right 

mark for the dose that your doctor has prescribed. 

 

 

 

4. Removing bubbles 

 Push down and pull up the plunger a few times to 

get rid of any large bubbles. 

 A few tiny bubbles are not important and will not 

affect your dose in any way. 

 Check the dose is still correct. 

 Then, remove the syringe from the bottle. 

 

 

5. Taking your medicine 

 Swallow your medicine straight from the syringe. 

 You can also mix your medicine with water in a 

small glass. Stir and drink all of the mixture. 

 

 

6. After using the syringe 

 Wipe the outside of the syringe with a clean 

tissue. 

 Then, put the syringe back in its protective case. 

 Put the child resistant cap back on the bottle to 

close it. 

 

 

If you take more Prometax than you should 
If you accidentally take more Prometax than you should, inform your doctor. You may require 

medical attention. Some people who have accidentally taken too much Prometax 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 take Prometax 
If you find you have forgotten to take your dose of Prometax, wait and take the next dose at the usual 

time. Do not take a double dose to make up for a forgotten dose. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 



 

108 

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. 

 

Very common (may affect more than 1 in 10 people) 

 Feeling dizzy 

 Loss of appetite 

 Stomach problems such as feeling sick (nausea) or being sick (vomiting), diarrhoea 

 

Common (may affect up to 1 in 10 people) 

 Anxiety 

 Sweating 

 Headache 

 Heartburn 

 Weight loss 

 Stomach pain 

 Feeling agitated 

 Feeling tired or weak 

 Generally feeling unwell 

 Trembling or feeling confused 

 Decreased appetite 

 Nightmares 

 

Uncommon (may affect up to 1 in 100 people) 

 Depression 

 Difficulty in sleeping 

 Fainting or accidentally falling 

 Changes in how well your liver is working 

 

Rare (may affect up to 1 in 1,000 people) 

 Chest pain 

 Rash, itching 

 Fits (seizures) 

 Ulcers in your stomach or intestine 

 

Very rare (may affect up to 1 in 10,000 people) 

 High blood pressure 

 Urinary tract infection 

 Seeing things that are not there (hallucinations) 

 Problems with your heartbeat such as fast or slow heartbeat 

 Bleeding in the gut – shows as blood in stools or when being sick 

 Inflammation of the pancreas – the signs include serious upper stomach pain, often with feeling 

sick (nausea) or being sick (vomiting) 

 The signs of Parkinson’s disease get worse or getting similar signs – such as stiff muscles, 

difficulty in carrying out movements 

 

  



 

109 

Not known (frequency cannot be estimated from the available data) 

 Being violently sick (vomiting) that can cause tearing of the tube that connects your mouth with 

your stomach (oesophagus) 

 Dehydration (losing too much fluid) 

 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) 

 Aggression, feeling restless 

 Uneven heartbeat 

 

Patients with dementia and Parkinson’s disease 

These patients have some side effects more often. They also have some additional side effects: 

 

Very common (may affect more than 1 in 10 people) 

 Trembling 

 Fainting 

 Accidentally falling 

 

Common (may affect up to 1 in 10 people) 

 Anxiety 

 Feeling restless 

 Slow and fast heartbeat 

 Difficulty in sleeping 

 Too much saliva and dehydration 

 Unusually slow movements or movements you cannot control 

 The signs of Parkinson’s disease get worse or getting similar signs – such as stiff muscles, 

difficulty in carrying out movements and muscle weakness 

 

Uncommon (may affect up to 1 in 100 people) 

 Uneven heartbeat and poor control of movements 

 

Other side effects seen with Prometax transdermal patches and which may occur with the oral 

solution: 

 

Common (may affect up to 1 in 10 people) 

 Fever 

 Severe confusion 

 Urinary incontinence (inability to retain adequate urine) 

 

Uncommon (may affect up to 1 in 100 people) 

 Hyperactivity (high level of activity, restlessness) 

 

Not known (frequency cannot be estimated from the available data) 

 Allergic reaction where the patch was used, such as blisters or skin inflammation 

If you get any of these side effects, contact your doctor as you may need medical assistance. 

 

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. 

 

 

  



 

110 

5. How to store Prometax 
 

 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 after EXP. The 

expiry date refers to the last day of that month. 

 Do not store above 30°C. Do not refrigerate or freeze. 

 Store in an upright position. 

 Use Prometax oral solution within 1 month of opening the bottle. 

 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 Prometax contains 

- The active substance is rivastigmine hydrogen tartrate. Each ml contains rivastigmine hydrogen 

tartrate corresponding to rivastigmine base 2.0 mg. 

- The other ingredients are sodium benzoate, citric acid, sodium citrate, quinoline yellow WS dye 

(E104) and purified water. 

 

What Prometax looks like and contents of the pack 

Prometax oral solution is supplied as 50 ml or 120 ml of a clear, yellow solution (2.0 mg/ml base) in 

an amber glass bottle with a child-resistant cap, foam liner, dip tube and self aligning plug. The oral 

solution is packaged with an oral dosing syringe in a plastic tube container. 

 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

  



 

111 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Laboratório Normal - Produtos Farmacêuticos, 

Lda. 

Tel: +351 21 000 8600 

 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



 

112 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 



 

113 

Package leaflet: Information for the user 

 

Prometax 4.6 mg/24 h transdermal patch 

Prometax 9.5 mg/24 h transdermal patch 

Prometax 13.3 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 Prometax is and what it is used for 

2. What you need to know before you use Prometax 

3. How to use Prometax 

4. Possible side effects 

5. How to store Prometax 

6. Contents of the pack and other information 

 

 

1. What Prometax is and what it is used for 

 

The active substance of Prometax 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, Prometax allows levels of acetylcholine to be 

increased in the brain, helping to reduce the symptoms of Alzheimer’s disease. 

 

Prometax 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 Prometax 

 

Do not use Prometax 
- if you are allergic to rivastigmine (the active substance in Prometax) 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 Prometax transdermal patches. 

 

  



 

114 

Warnings and precautions 

Talk to your doctor before using Prometax: 

- if you have, or have ever had, an irregular or slow heartbeat. 

- if you have, or have ever had, an active stomach ulcer. 

- 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 more than three days, do not apply the next one before you have 

talked to your doctor. 

 

Children and adolescents 

There is no relevant use of Prometax in the paediatric population in the treatment of Alzheimer’s disease. 

 

Other medicines and Prometax 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Prometax 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). 

 

Prometax Patch should not be given at the same time as metoclopramide (a medicine used to relieve or 

prevent nausea and vomiting). Taking the two medicines together could cause problems such as stiff 

limbs and trembling hands. 

 

If you have to undergo surgery whilst using Prometax transdermal patches, tell your doctor that you 

are using them because they may exaggerate the effects of some muscle relaxants during anaesthesia. 

 

Caution when Prometax Patch is given together with beta-blockers (medicines such as atenolol used to 

treat hypertension, angina, and other heart conditions). Taking the two medicines together could cause 

problems such as slowing of the heartbeat (bradycardia) leading to fainting or loss of consciousness. 

 

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 Prometax must be assessed against the possible effects on 

your unborn child. Prometax should not be used during pregnancy unless clearly necessary. 

 

You should not breast-feed during treatment with Prometax transdermal patches. 

 

Driving and using machines 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely. 

Prometax 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. 

 

 



 

115 

3. How to use Prometax 

 

Always use Prometax transdermal patches exactly 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. 

 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 Prometax transdermal patch is most suitable for you. 

 Treatment usually starts with Prometax 4.6 mg/24 h. 

 The recommended usual daily dose is Prometax 9.5 mg/24 h. If well tolerated, the treating 

physician may consider increasing the dose to 13.3 mg/24 h. 

 Only wear one Prometax 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 more than 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 Prometax 

4.6 mg/24 h. 

 

Prometax can be used with food, drink and alcohol. 

 

Where to apply your Prometax 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: 

- left upper arm or right upper arm 

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

- left upper back or right upper back 

- left lower back or right lower back 

 



 

116 

Every 24 hours take off the previous patch before putting 

ONE new patch on to ONLY ONE of the following possible 

locations. 

 
 

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 Prometax transdermal patch 

Prometax patches are thin, opaque, plastic patches that stick to the skin. Each patch is sealed in a 

sachet that protects it until you are ready to put it on. Do not open the sachet 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 Prometax after treatment interruption, please begin with 

the second picture. 

 
 

- Each patch is sealed in its own protective sachet. 

You should only open the sachet when you are ready to 

apply the patch. 

Cut the sachet along the dotted line with scissors and 

remove the patch from the sachet. 

 
 

- A protective liner covers the sticky side of the patch. 

Peel off one side of the protective liner and do not touch the 

sticky part of the patch with the fingers. 

 
 



 

117 

- Put the sticky side of the patch on the upper or lower back, 

upper arm or chest and then peel off the second side of the 

protective liner. 

 
 

- 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 Prometax 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 Prometax 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 Prometax transdermal patch 

 To benefit from treatment, you must apply a new patch every day, preferably at the same time 

of day. 

 Only wear one Prometax patch at a time and replace the patch with a new one after 24 hours. 

 

If you use more Prometax 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 Prometax 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 Prometax 

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. 

 



 

118 

If you stop using Prometax 

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, Prometax transdermal patches 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) 

 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 

 Nightmares 

Take off your patch and tell your doctor straight away, if you notice any of the side effects above. 

 



 

119 

Other side effects seen with Prometax 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 Prometax 

 

 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 sachet after 

EXP. The expiry date refers to the last day of that month. 

 Do not store above 25°C. 

 Keep the transdermal patch in the sachet until use. 

 Do not use any patch that 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 

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. 

 

 



 

120 

6. Contents of the pack and other information 

 

What Prometax contains 

- The active substance is rivastigmine. 

- Prometax 4.6 mg/24 h transdermal patches: Each patch releasing 4.6 mg of rivastigmine 

per 24 hours is 5 cm2 and contains 9 mg of rivastigmine. 

- Prometax 9.5 mg/24 h transdermal patches: Each patch releasing 9.5 mg of rivastigmine 

per 24 hours is 10 cm2 and contains 18 mg of rivastigmine. 

- Prometax 13.3 mg/24 h transdermal patches: Each patch releasing 13.3 mg of 

rivastigmine per 24 hours is 15 cm2 and contains 27 mg of rivastigmine. 

 

- The other ingredients are polyethylene terephthalate film lacquered, alpha-tocopherol, 

poly(butylmethacrylate, methylmethacrylate), acrylic copolymer, silicone oil, dimethicone, 

polyester film fluoropolymer-coated. 

 

What Prometax looks like and contents of the pack 

Each transdermal patch is a thin patch consisting of three layers. The outer layer is beige and labelled 

with the following: 

- “Prometax”, “4.6 mg/24 h” and “AMCX”, 

- “Prometax”, “9.5 mg/24 h” and “BHDI”, 

- “Prometax”, “13.3 mg/24 h” and “CNFU”. 

 

One transdermal patch is sealed in one sachet. The patches are available in packs containing 7 or 

30 sachets and in multipacks containing 60 or 90 sachets. Not all pack sizes may be marketed in your 

country. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

Novartis Farmacéutica, S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

  



 

121 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

Česká republika 

Sandoz s.r.o. 

Tel: +420 221 421 658 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Sandoz A/S 

Tlf: +45 63 95 10 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Sandoz B.V. 

Tel: +31 36 52 41 600 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Sandoz A/S 

Tlf: +45 63 95 10 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Sandoz GmbH 

Tel: +43 5 33 8200 

 

España 

Esteve Pharmaceuticals, S.A. 

Tel: +34 93 446 60 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Laboratório Normal - Produtos Farmacêuticos, 

Lda. 

Tel: +351 21 000 8600 

 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Sandoz SRL Romania 

Tel: +40 21 40751 83 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Lek Pharmaceuticals d.d. 

Tel: +386 1 580 33 27 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Sandoz d.d. organizačná zložka 

Tel: + 421 2 4820 0600 

Italia 
Sandoz S.p.A. 

Tel: +39 02 96 54 3483 

 

Suomi/Finland 

Sandoz A/S 

Puh/Tel: +45 6 395 10 00 



 

122 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 
Sandoz A/S 

Tel: +45 6 395 10 00 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Sandoz Limited  

Tel: +44 1276 698020 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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
	A. LABELLING
	B. PACKAGE LEAFLET