Rivastigmine Hexal

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

 1 



1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 1.5 mg hard capsules 
Rivastigmine HEXAL 3 mg hard capsules 
Rivastigmine HEXAL 4.5 mg hard capsules 
Rivastigmine HEXAL 6 mg hard capsules 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each capsule contains rivastigmine hydrogen tartrate corresponding to 1,5mg rivastigmine.  
Each capsule contains rivastigmine hydrogen tartrate corresponding to 3 mg rivastigmine.  
Each capsule contains rivastigmine hydrogen tartrate corresponding to 4,5 mg rivastigmine.  
Each capsule contains rivastigmine hydrogen tartrate corresponding to 6 mg rivastigmine.  
 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule  
 
Off-white to slightly yellow powder in a capsule with yellow cap and yellow body, with red imprint 
“RIV 1.5 mg” on the body. 
 
Off-white to slightly yellow powder in a capsule with orange cap and orange body, with red imprint 
“RIV 3 mg” on the body. 
 
Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint “RIV 
4.5 mg” on the body. 
 
Off-white to slightly yellow powder in a capsule with red cap and orange body, with red imprint “RIV 
6 mg” on the body. 
 
 
 
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. 

 2 



 
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.  
 
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, rivastigmine 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 rivastigmine in the paediatric population in the treatment of Alzheimer’s 
disease. 
 
4.3  Contraindications 
 
The use of this medicinal product is contraindicated in patients with known hypersensitivity to the 
active substance rivastigmine, to other carbamate derivatives or to any of the excipients listed in 
section 6.1. 
 
Previous history of application site reactions suggestive of allergic contact dermatitis with 
rivastigmine patch (see section 4.4). 
 
4.4  Special warnings and precautions for use 

 3 



 
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, rivastigmine 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.  
 
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 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). 
 

 4 



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, rivastigmine 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. 
 
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 

 5 



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. 
 
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 rivastigmine. 
 
Table 1  
 
Infections and infestations  

Very rare 
 
Urinary infection  

Metabolism and nutrition disorders  
Very common 
Common 
Not known 

 
Anorexia  
Decreased appetite 
Dehydration 

Psychiatric disorders  
Common  

 
Agitation  

 6 



Common  
Common 
Common 
Uncommon  
Uncommon  
Very rare  
Not known 

Confusion  
Anxiety 
Nightmares 
Insomnia  
Depression  
Hallucinations  
Aggression, restlessness 

Nervous system disorders  
Very common  
Common  
Common  
Common  
Uncommon  
Rare  
Very rare  
 

 
Dizziness  
Headache  
Somnolence  
Tremor  
Syncope  
Seizures  
Extrapyramidal symptoms (including 
worsening of Parkinson’s disease)  
 

Cardiac disorders  
Rare  
Very rare  

 
 

Not known 
 

 
Angina pectoris  
Cardiac arrhythmia (e.g. bradycardia, atrio-
ventricular block, atrial fibrillation and 
tachycardia)  
Sick sinus syndrome 

Vascular disorders  
Very rare 

 

 
Hypertension  
 

Gastrointestinal disorders  
Very common  
Very common  
Very common  
Common  
Rare 
Very rare  
Very rare  
Not known  

 

 
Nausea  
Vomiting  
Diarrhoea  
Abdominal pain and dyspepsia 
Gastric and duodenal ulcers  
Gastrointestinal haemorrhage  
Pancreatitis  
Some cases of severe vomiting were 
associated with oesophageal rupture (see 
section 4.4).  

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Hepatobiliary disorders  
Uncommon 
Not known 
 

 
Elevated liver function tests  
Hepatitis 

Skin and subcutaneous tissue disorders  
Common  
Rare  
Not known 

 
Hyperhydrosis 
Rash  
Pruritus, allergic dermatitis (disseminated)  

General disorders and administration site 
conditions  

Common  
Common  
Uncommon  

 
 
Fatigue and asthenia  
Malaise  
Fall  

Investigations  
Common 

 
Weight loss  

 
The following additional adverse reactions have been observed with rivastigmine 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 rivastigmine capsules.  
 
Table 2  
 
Metabolism and nutrition disorders  

Common 
Common 

 
Decreased appetite 
Dehydration 

Psychiatric disorders  
Common  
Common  
Common  
Common 
Common 
Not known 

 
Insomnia 
Anxiety 
Restlessness  
Hallucination, visual 
Depression 
Aggression 

Nervous system disorders  
Very common  
Common  
Common  
Common  
Common 
 
Common 
Common 
Common 
Common 
Uncommon  

 
Tremor  
Dizziness  
Somnolence  
Headache  
Parkinson’s disease (worsening) 
Bradykinesia  
Dyskinesia 
Hypokinesia 
Cogwheel rigidity 
Dystonia  

Cardiac disorders  
Common  
Uncommon 
Uncommon  
Not known 

 
Bradycardia  
Arial fibrillation 
Atrioventricular block  
Sick sinus syndrome 

Vascular disorders 
             Common 
             Uncommon 

 
Hypertension 
Hypotension 

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Gastrointestinal disorders  
Very common  
Very common  
Common  
Common 
Common  

 
Nausea  
Vomiting  
Diarrhoea  
Abdominal pain and dyspepsia 
Salivary hypersecretion  

Hepatobiliary disorders 
Not known 

 
Hepatitis 

Skin and subcutaneous tissue disorders  
Common 
Not known  

 
Hyperhydrosis  
Allergic dermatitis (disseminated) 

General disorders and administration site 
conditions  

Very common 
Common  
Common  
Common 

 
 
Fall 
Fatigue and asthenia  
Gait disturbance 
Parkinson gait 

 
The following additional adverse reaction has been observed in a study of patients with dementia 
associated with Parkinson’s disease treated with rivastigmine transdermal patches: agitation 
(common). 
 
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 
with rivastigmine 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  

Rivastigmine 
n (%) 

 

Placebo 
n (%) 

 

Total patients studied  
Total patients with pre-defined AE(s)  

362 (100) 
99 (27.3) 

179 (100) 
28 (15.6) 

Tremor  
Fall  
Parkinson’s disease (worsening)  
Salivary hypersecretion  
Dyskinesia  
Parkinsonism  
Hypokinesia  
Movement disorder  
Bradykinesia  
Dystonia  
Gait abnormality  
Muscle rigidity  
Balance disorder  
Musculoskeletal stiffness  
Rigors  
Motor dysfunction  

37 (10.2) 
21 (5.8) 
12 (3.3) 
5 (1.4) 
5 (1.4) 
8 (2.2) 
1 (0.3) 
1 (0.3) 
9 (2.5) 
3 (0.8) 
5 (1.4) 
1 (0.3) 
3 (0.8) 
3 (0.8) 
1 (0.3) 
1 (0.3) 

7 (3.9) 
11 (6.1) 
2 (1.1) 

0 
1 (0.6) 
1 (0.6) 

0 
0 

3 (1.7) 
1 (0.6) 

0 
0 

2 (1.1) 
0 
0 
0 

 
 
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. 

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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.  
 
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 

 10 



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  
 
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 
Rivastigmine 

ADAS-Cog 
Placebo 

 

ADCS-CGIC 
Rivastigmine 

 

ADCS-CGIC 
Placebo 

 
ITT + RDO population  
Mean baseline ± SD  
Mean change at  
24 weeks ± SD  

(n=329) 
23.8 ± 10.2 

 
2.1 ± 8.2 

(n=161) 
24.3 ± 10.5 

 
-0.7 ± 7.5 

(n=329) 
n/a 

 
3.8 ± 1.4 

(n=165) 
n/a 

 
4.3 ± 1.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
2.881 

<0.0011 

 
n/a 

0.0072 

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ITT - LOCF population 
Mean baseline ± SD  
Mean change at  
24 weeks ± SD 

(n=287) 
24.0 ± 10.3 

 
2.5 ± 8.4 

(n=154) 
24.5 ± 10.6 

 
-0.8 ± 7.5 

(n=289) 
n/a 

 
3.7 ± 1.4 

(n=158) 
n/a 

 
4.3 ± 1.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
3.541 

<0.0011 

 
n/a 

<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  
 
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 
Rivastigmine 

ADAS-Cog 
Placebo 

 

ADAS-Cog 
Rivastigmine 

 

ADAS-Cog 
Placebo 

 
 Patients with visual 

hallucinations 
Patients without visual 

hallucinations 
ITT + RDO population  
Mean baseline ± SD  
Mean change at  
24 weeks ± SD  

(n=107) 
25.4 ± 9.9 

 
1.0 ± 9.2 

(n=60) 
27.4 ± 10.4 

 
-2.1 ± 8.3 

(n=220) 
23.1 ± 10.4 

 
2.6 ± 7.6 

(n=101) 
22.5 ± 10.1 

 
0.1 ± 6.9 

Adjusted treatment  
difference  
p-value versus placebo  

 
4.271 
0.0021 

 
2.091 
0.0151 

 Patients with moderate 
dementia (MMSE 10-17) 

Patients with mild dementia 
(MMSE 18-24) 

ITT + RDO population 
Mean baseline ± SD  
Mean change at  
24 weeks ± SD 

(n=87) 
32.6 ± 10.4 

 
2.6 ± 9.4 

(n=44) 
33.7 ± 10.3 

 
-1.8 ± 7.2 

(n=237) 
20.6 ± 7.9 

 
1.9 ± 7.7 

(n=115) 
20.7 ± 7.9 

 
-0.2 ± 7.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
4.731 
0.0021 

 
2.141 
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 
rivastigmine 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%.  

 12 



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.  
 
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. 
 
Elderly population  
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.  
 

 13 



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 
 
Rivastigmine HEXAL 1.5 mg hard capsules: 
 
- Capsule shell:  
- Gelatin 
- Titanium dioxide (E171) 
- Yellow iron oxide (E172) 

 
- Capsule fill: 
- Microcrystaline cellulose  
- Magnesium stearate  
- Hypromellose 
- Silica, colloidal anhydrous  

 
- Printing ink: 
- Shellac 
- Red iron oxide (E172) 
 
Rivastigmine HEXAL 3 mg and 6 mg hard capsules: 
 
- Capsule shell:  
- Gelatin 
- Titanium dioxide (E171) 
- Yellow iron oxide (E172) 
- Red iron oxide (E172) 

 
- Capsule fill: 
- Microcrystaline cellulose  
- Magnesium stearate  
- Hypromellose 
- Silica, colloidal anhydrous  

 
- Printing ink: 
- Shellac 
- Red iron oxide (E172) 
 
Rivastigmine HEXAL 4.5 mg hard capsules: 
 
- Capsule shell:  
- Gelatin 
- Titanium dioxide (E171) 
- Yellow iron oxide (E172) 
- Red iron oxide (E172) 

 
- Capsule fill: 
- Microcrystaline cellulose  

 14 



- Magnesium stearate  
- Hypromellose 
- Silica, colloidal anhydrous  

 
- Printing ink: 
- Shellac 
- Titanium dioxide (E171) 
 
 
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 2, 4 or 8 

blisters.  
- HDPE bottles with plastic closure with induction inner seal. 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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
Rivastigmine HEXAL 1.5 mg hard capsules: 
 
EU/1/09/589/001 
EU/1/09/589/002 
EU/1/09/589/003 
EU/1/09/589/004 
 
Rivastigmine HEXAL 3 mg hard capsules: 
 
EU/1/09/589/005 
EU/1/09/589/006 
EU/1/09/589/007 
EU/1/09/589/008 

 15 



 
Rivastigmine HEXAL 4.5 mg hard capsules: 
 
EU/1/09/589/009 
EU/1/09/589/010 
EU/1/09/589/011 
EU/1/09/589/012 
 
Rivastigmine HEXAL 6 mg hard capsules: 
 
EU/1/09/589/013 
EU/1/09/589/014 
EU/1/09/589/015 
EU/1/09/589/016 
 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 11/12/2009 
Date of first renewal: 11/07/2014 
 
 
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 
 

 16 



 
1.  NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 2 mg/ml oral solution 
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml contains rivastigmine hydrogen tartrate corresponding to 2g rivastigmine.  
 
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.  
 
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.  
 

 17 



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.  
 
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, rivastigmine 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 rivastigmine in the paediatric population in the treatment of Alzheimer’s 
disease. 
 
4.3  Contraindications 
 
The use of this medicinal product is contraindicated in patients with known hypersensitivity to the 
active substance rivastigmine, to other carbamate derivatives or to any of the excipients listed in 
section 6.1. 
 
Previous history of application site reactions suggestive of allergic contact dermatitis with 
rivastigmine patch (see section 4.4). 
 
4.4  Special warnings and precautions for use 
 
The incidence and severity of adverse reactions generally increase with 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.  
 

 18 



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, rivastigmine 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.  
 
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 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). 
 
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.  
 

 19 



One of the excipients in Rivastigmine HEXAL oral solution is sodium benzoate. Benzoic acid is a 
mild irritant to the skin, eyes and mucous membrane.  
 
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, rivastigmine 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. 
 
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 

 20 



 
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. 
 
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 rivastigmine. 
Table 1  
 
Infections and infestations  

Very rare 
 
Urinary infection  

Metabolism and nutrition disorders  
Very common 
Common  
Not known 

 
Anorexia 
Decreased appetite 
Dehydration  

Psychiatric disorders  
Common  
Common 
Common  
Common 
Uncommon  
Uncommon  
Very rare  
Not known 

 
Agitation  
Confusion  
Anxiety 
Nightmares 
Insomnia  
Depression  
Hallucinations  
Aggression, restlessness 

Nervous system disorders   

 21 



Very common  
Common  
Common  
Common  
Uncommon  
Rare  
Very rare  
 

Dizziness  
Headache  
Somnolence  
Tremor  
Syncope  
Seizures  
Extrapyramidal symptoms (including 
worsening of Parkinson’s disease)  

Cardiac disorders  
Rare  
Very rare  
 
 
Not known 

 

 
Angina pectoris  
Cardiac arrhythmia (e.g. bradycardia, atrio-
ventricular block, atrial fibrillation and 
tachycardia) 
Sick sinus syndrome  

Vascular disorders  
Very rare 

 
Hypertension  

Gastrointestinal disorders  
Very common  
Very common  
Very common  
Common  
Rare 
Very rare  
Very rare  
Not known  

 

 
Nausea  
Vomiting  
Diarrhoea  
Abdominal pain and dyspepsia 
Gastric and duodenal ulcers  
Gastrointestinal haemorrhage  
Pancreatitis  
Some cases of severe vomiting were 
associated with oesophageal rupture (see 
section 4.4).  

Hepatobiliary disorders  
Uncommon 
Not known 

 
Elevated liver function tests  
Hepatitis 

Skin and subcutaneous tissue disorders  
Common  
Rare 
Not known  

 
Hyperhydrosis  
Rash 
Pruritus, allergic dermatitis (disseminated)  

General disorders and administration site 
conditions  

Common  
Common  
Uncommon  

 
 
Fatigue and asthenia  
Malaise  
Fall  

Investigations  
Common 

 
Weight loss  

 
The following additional adverse reactions have been observed with rivastigmine 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 rivastigmine capsules.  
 
Table 2  
 
Metabolism and nutrition disorders  

Common 
Common 

 
 Decreased appetite 
Dehydration 

Psychiatric disorders  
Common  

 
Insomnia 

 22 



Common  
Common  
Common 
Common 
Not known 

Anxiety 
Restlessness  
Hallucination, visual 
Depression 
Aggression 

Nervous system disorders  
Very common  
Common  
Common  
Common  
Common 
 
Common 
Common 
Common 
Common 
Uncommon  

 
Tremor  
Dizziness  
Somnolence  
Headache  
Parkinson’s disease (worsening) 
Bradykinesia  
Dyskinesia 
Hypokinesia 
Cogwheel rigidity 
Dystonia  

Cardiac disorders  
Common  
Uncommon 
Uncommon  
Not known 

 
Bradycardia  
Arial fibrillation 
Atrioventricular block  
Sick sinus syndrome 

Vascular disorders 
             Common 
            Uncommon 

 
Hypertension 
Hypotension 

 23 



Gastrointestinal disorders  
Very common  
Very common  
Common  
Common 
Common  

 
Nausea  
Vomiting  
Diarrhoea  
Abdominal pain and dyspepsia 
Salivary hypersecretion  

Hepatobiliary disorders 
Not known 

 
Hepatitis 

Skin and subcutaneous tissue disorders  
Common  
Not known 

 
Hyperhydrosis 
Allergic dermatitis (disseminated)  

General disorders and administration site 
conditions  

Very common 
Common  
Common  
Common 

 
 
Fall 
Fatigue and asthenia  
Gait disturbance 
Parkinson gait 

 
The following additional adverse reaction has been observed in a study of patients with dementia 
associated with Parkinson’s disease treated with rivastigmine transdermal patches: agitation 
(common). 
 
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 
with rivastigmine 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  

Rivastigmine 
n (%) 

 

Placebo 
n (%) 

 

Total patients studied  
Total patients with pre-defined AE(s)  

362 (100) 
99 (27.3) 

179 (100) 
28 (15.6) 

Tremor  
Fall  
Parkinson’s disease (worsening)  
Salivary hypersecretion  
Dyskinesia  
Parkinsonism  
Hypokinesia  
Movement disorder  
Bradykinesia  
Dystonia  
Gait abnormality  
Muscle rigidity  
Balance disorder  
Musculoskeletal stiffness  
Rigors  
Motor dysfunction  

37 (10.2) 
21 (5.8) 
12 (3.3) 
5 (1.4) 
5 (1.4) 
8 (2.2) 
1 (0.3) 
1 (0.3) 
9 (2.5) 
3 (0.8) 
5 (1.4) 
1 (0.3) 
3 (0.8) 
3 (0.8) 
1 (0.3) 
1 (0.3) 

7 (3.9) 
11 (6.1) 
2 (1.1) 

0 
1 (0.6) 
1 (0.6) 

0 
0 

3 (1.7) 
1 (0.6) 

0 
0 

2 (1.1) 
0 
0 
0 

 
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. 
 

 24 



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.  
 
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 

 25 



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  
 
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 
Rivastigmine 

ADAS-Cog 
Placebo 

 

ADCS-CGIC 
Rivastigmine 

 

ADCS-CGIC 
Placebo 

 
ITT + RDO population  
Mean baseline ± SD  
Mean change at  
24 weeks ± SD  

(n=329) 
23.8 ± 10.2 

 
2.1 ± 8.2 

(n=161) 
24.3 ± 10.5 

 
-0.7 ± 7.5 

(n=329) 
n/a 

 
3.8 ± 1.4 

(n=165) 
n/a 

 
4.3 ± 1.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
2.881 

<0.0011 

 
n/a 

0.0072 

 26 



ITT - LOCF population 
Mean baseline ± SD  
Mean change at  
24 weeks ± SD 

(n=287) 
24.0 ± 10.3 

 
2.5 ± 8.4 

(n=154) 
24.5 ± 10.6 

 
-0.8 ± 7.5 

(n=289) 
n/a 

 
3.7 ± 1.4 

(n=158) 
n/a 

 
4.3 ± 1.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
3.541 

<0.0011 

 
n/a 

<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  
 
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 
Rivastigmine 

ADAS-Cog 
Placebo 

ADAS-Cog 
Rivastigmine 

ADAS-Cog 
Placebo 

 Patients with visual 
hallucinations 

Patients without visual 
hallucinations 

ITT + RDO population  
Mean baseline ± SD  
Mean change at  
24 weeks ± SD  

(n=107) 
25.4 ± 9.9 

 
1.0 ± 9.2 

(n=60) 
27.4 ± 10.4 

 
-2.1 ± 8.3 

(n=220) 
23.1 ± 10.4 

 
2.6 ± 7.6 

(n=101) 
22.5 ± 10.1 

 
0.1 ± 6.9 

Adjusted treatment  
difference  
p-value versus placebo  

 
4.271 
0.0021 

 
2.091 
0.0151 

 Patients with moderate 
dementia (MMSE 10-17) 

Patients with mild dementia 
(MMSE 18-24) 

ITT + RDO population 
Mean baseline ± SD  
Mean change at  
24 weeks ± SD 

(n=87) 
32.6 ± 10.4 

 
2.6 ± 9.4 

(n=44) 
33.7 ± 10.3 

 
-1.8 ± 7.2 

(n=237) 
20.6 ± 7.9 

 
1.9 ± 7.7 

(n=115) 
20.7 ± 7.9 

 
-0.2 ± 7.5 

Adjusted treatment  
difference  
p-value versus placebo  

 
4.731 
0.0021 

 
2.141 
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 
rivastigmine 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%.  

 27 



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.  
 
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. 
 
Elderly population  
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.  
 

 28 



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 
Rivastigmine HEXAL 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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/017 
EU/1/09/589/018 
 

 29 



 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 11/12/2009 
Date of first renewal: 11/07/2014 
 
 
10.  DATE OF REVISION OF THE TEXT 
 
Detailed information of this medicinal product  is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu/ 
 

 30 

http://www.emea.europa.eu/


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS  OR RESTRICTION REGARDING SUPPLY 

AND USE 
 
C.         OTHER CODDITIONS AND REQUIREMENT OF THE 

MARKETING AUTHORISATION 
 
D.         CONDITIONS OR RESTRICTIONS WITH REGARDS TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 

 31 



A. MANUFACTURER(S)  RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Hard gelatine capsules 
Novartis Farmacéutica S.A. 
Ronda Santa Maria 158 
ES-08210 Barberà del Vallès 
Barcelona 
Spain 
 
Oral solution 
Novartis Pharma GmbH 
Roonstrasse 25 
D-90429 Nuremberg 
Germany 
 
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 on  “restricted” medical prescription, reserved for use in certain specialised area 
(See Annex I: Summary of Product Characteristics, Section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance, as  presented in Module 1.8.1. of the 
Marketing Authorisation Application, is in place and functioning before and whilst the product is on 
the market. 
 
PSURs 
 
The PSUR cycle of Rivastigmine Hexal is aligned with the cross-referred product, Exelon, until 
otherwise specified. 
 
  

D.      CONDITIONS OR RESTRICTIONS WITH REGARDS TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
Not applicable. 
 
Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and intervention detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 

 32 



An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk 
profile or as the result of an important (pharmacovigilance or risk minimisation) 
milestone being reached. 

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

 33 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

 34 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

 35 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 1.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 1.5 mg of rivastigmine (as 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 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 36 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/001  
EU/1/09/589/002 
EU/1/09/589/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine HEXAL 1.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 

 37 



MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 1.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
HEXAL  AG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Monday  
Tuesday  
Wednesday  
Thursday  
Friday  
Saturday  
Sunday 

 38 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON FOR HDPE BOTTLE 
LABEL FOR HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 1.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains1.5 mg of rivastigmine (as hydrogen tartrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
250 hard capsules  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 39 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Only for carton box: 
Rivastigmine HEXAL 1.5 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Only for carton box: 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Only for carton box: 
 
PC:  
SN:  
NN:  
 

 40 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 3 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 3 mg of rivastigmine (as 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 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 41 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/005  
EU/1/09/589/006 
EU/1/09/589/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine HEXAL 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 

 42 



MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 3 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
HEXAL  AG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Monday  
Tuesday  
Wednesday  
Thursday  
Friday  
Saturday  
Sunday 
 

 43 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON FOR HDPE BOTTLE 
LABEL FOR HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 3 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 3 mg of rivastigmine (as hydrogen tartrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
250 hard capsules  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 44 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Only for carton box: 
Rivastigmine HEXAL 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Only for carton box: 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Only for carton box: 
 
PC:  
SN:  
NN:  
 
 

 45 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 4.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 4.5 mg of rivastigmine (as 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 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 46 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/009 
EU/1/09/589/010 
EU/1/09/589/011 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine HEXAL 4.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 

 47 



MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 4.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
HEXAL  AG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Monday  
Tuesday  
Wednesday  
Thursday  
Friday  
Saturday  
Sunday 

 48 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON FOR HDPE BOTTLE 
LABEL FOR HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 4.5 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 4.5 mg of rivastigmine (as hydrogen tartrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
250 hard capsules  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 49 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/012 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Only for carton box: 
Rivastigmine HEXAL 4.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Only for carton box: 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Only for carton box: 
 
PC:  
SN:  
NN:  
 
 

 50 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 6 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains  6 mg of rivastigmine (as 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 
 
To be swallowed whole without crushing or opening. 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

 51 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/013 
EU/1/09/589/014 
EU/1/09/589/015 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Rivastigmine HEXAL 6 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 

 52 



MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
ALU/PVC BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Rivastigmine HEXAL 6 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
HEXAL  AG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
5. OTHER 
 
Monday  
Tuesday  
Wednesday  
Thursday  
Friday  
Saturday  
Sunday 

 53 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON FOR HDPE BOTTLE 
LABEL FOR HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 6 mg hard capsules  
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 6 mg of rivastigmine (as hydrogen tartrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
250 hard capsules  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be swallowed whole without crushing or opening. 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 
 
 
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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/016 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Only for carton box: 
Rivastigmine HEXAL 6 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Only for carton box: 
 
2D barcode carrying the unique identifier included. 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Only for carton box: 
 
PC:  
SN:  
NN:  
 

 55 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON FOR GLASS BOTTLE 
LABEL FOR GLASS BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Rivastigmine HEXAL 2 mg/ml oral solution 
 
rivastigmine (as hydrogen tartrate) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml contains 2.0 mg of rivastigmine (as hydrogen tartrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium benzoate (E 211). See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
50 ml oral solution 
120 ml oral solution 
 
 
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 
 
After opening: 1 month 
 
 

 56 



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 
 
HEXAL  AG 
Industriestraße 25 
83607 Holzkirchen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/589/017 
EU/1/09/589/018 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Only for carton box: 
Rivastigmine HEXAL 2 mg/ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Only for carton box: 
 
2D barcode carrying the unique identifier included. 
 
 

 57 



18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Only for carton box: 
 
PC:  
SN:  
NN:  
 
 
 
 
 

 58 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

 59 



 
Package leaflet: Information for the patient 

 
Rivastigmine HEXAL 1.5 mg hard capsules  
Rivastigmine HEXAL 3 mg hard capsules  

Rivastigmine HEXAL 4.5 mg hard capsules  
Rivastigmine HEXAL 6 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 or pharmacist. 
- 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 or pharmacist. This includes  any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in  this leaflet:  
 
1. What Rivastigmine HEXAL is and what it is used for 
2. What you need to know before you take Rivastigmine HEXAL 
3. How to take Rivastigmine HEXAL 
4. Possible side effects 
5. How to store Rivastigmine HEXAL 
6. Contents of the pack and other  information 
 
 
1. What Rivastigmine HEXAL is and what it is used for 
 
The active substance of Rivastigmine HEXAL 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, 
Rivastigmine 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.  
 
Rivastigmine HEXAL 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 Rivastigmine HEXAL 
 
Do not take Rivastigmine HEXAL 
 
- if you are allergic to rivastigmine (the active substance in Rivastigmine HEXAL) or any of the 

other ingredients of this medicine (listed in section 6).  
- if you have had a previous skin reaction suggestive of allergic contact dermatitis with 

rivastigmine. 
 

 60 



If this applies to you, tell your doctor and do not take Rivastigmine HEXAL. 
 
Warnings and precautions 
Talk to your doctor before taking Rivastigmine HEXAL 
- 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 Rivastigmine HEXAL 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 Rivastigmine HEXAL in the paediatric population in the treatment of 
Alzheimer’s disease. 
 
Other medicines and Rivastigmine HEXAL 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Rivastigmine Hexal should not be given at the same time as other medicines with similar effects to 
Rivastigmine HEXAL. Rivastigmine HEXAL might interfere with anticholinergic medicines 
(medicines used to relieve stomach cramps or spasms, to treat Parkinson’s disease or to prevent travel 
sickness). 
 
Rivastigmine Hexal 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 Rivastigmine HEXAL, tell your doctor before you are 
given any anaesthetics, because Rivastigmine HEXAL may exaggerate the effects of some muscle 
relaxants during anaesthesia.  
 
Caution when Rivastigmine HEXAL 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 Rivastigmine HEXAL must be assessed against the possible 
effects on your unborn child. Rivastigmine HEXAL should not be used during pregnancy unless 
clearly necessary.  
 

 61 



You should not breast-feed during treatment with Rivastigmine HEXAL.  
 
Driving and using machines 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely.  
Rivastigmine HEXAL 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.   
 
 
3. How to take Rivastigmine HEXAL 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
How to start treatment 
 
Your doctor will tell you what dose of Rivastigmine HEXAL 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 Rivastigmine HEXAL 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 Rivastigmine HEXAL. 
• To benefit from your medicine, take it every day. 
• Take Rivastigmine HEXAL 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 Rivastigmine HEXAL than you should 
 
If you accidentally take more Rivastigmine HEXAL than you should, inform your doctor. You may 
require medical attention. Some people who have accidentally taken too much Rivastigmine HEXAL 
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 Rivastigmine HEXAL 
 
If you find you have forgotten to take your dose of Rivastigmine HEXAL, 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.  
 

 62 



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 
 
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) 

 63 



• 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 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 or pharmacist. This includes any possible side effects 
not listed in this leaflet.  
 
You can also report side effects directly via the national reporting system listed in Appendix V. By 
reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Rivastigmine Hexal 
 
Keep this medicine  out of the sight  and reach of children.  
 
Do not use Rivastigmine HEXAL after the expiry date which is stated on the carton. 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. 
 
 
6. Content of the pack and other information 
 
What Rivastigmine HEXAL contains 

 64 



 
- The active substance is rivastigmine hydrogen tartrate.  
- The other ingredients are:  hypromellose, magnesium stearate, microcrystalline cellulose, colloidal 

anhydrous silica, gelatin, yellow iron oxide red iron oxide, titanium dioxide, and shellac.  
 
Each Rivastigmine HEXAL 1.5 mg capsule contains 1.5 mg of rivastigmine.  
Each Rivastigmine HEXAL 3 mg capsule contains 3 mg of rivastigmine.  
Each Rivastigmine HEXAL 4.5 mg capsule contains 4.5 mg of rivastigmine.  
Each Rivastigmine HEXAL 6 mg capsule contains 6 mg of rivastigmine. 
 
What Rivastigmine HEXAL looks like and contents of the pack 
 
- Rivastigmine HEXAL 1.5 mg hard capsules, which contain an off-white to slightly yellow 

powder, have a yellow cap and yellow body, with a red imprint “RIV 1.5 mg” on the body.  
 
- Rivastigmine HEXAL 3 mg hard capsules, which contain an off-white to slightly yellow powder, 

have an orange cap and orange body, with a red imprint “RIV 3 mg” on the body.  
 
- Rivastigmine HEXAL 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 “RIV 4.5 mg” on the body.  
 
- Rivastigmine HEXAL 6 mg hard capsules, which contain an off-white to slightly yellow powder, 

have a red cap and orange body, with a red imprint “RIV 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 
 
HEXAL  AG 
Industriestraße 25 
D-83607 Holzkirchen 
Germany 
 
Manufacturer 
 
Novartis Farmacéutica, S.A.  
Planta de Producción  
Ronda de Santa Maria 158  
E-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 
Sandoz N.V. 
Telecom Gardens 
Medialaan 40 
B-1800 Vilvoorde 
Tel: +32 (0)2 722  97 98 
 

Luxembourg/Luxemburg 
HEXAL AG 
Industriestraße 25 
D-83607 Holzkirchen 
Tél/Tel: + 49 8024 908 0 
E-mail: service@hexal.com 
 

България 
Representative office Sandoz d.d. 
BG-1766 Sofia  
 
Business Park Sofia, buil. 7B, fl. 3  

Magyarország 
Sandoz Hungária Kft. 
Bartók Béla út 43-47 
H-1114 Budapest 
Phone: +36 1 430 2890 

 65 

mailto:service@hexal.com


Teл.: + 359 2 970 47 47 E-mail: info.hungary@sandoz.com 
 

Česká republika 
Sandoz s.r.o. 
U Nákladového nádraží 10 
CZ-13000 Praha 3 
E-mail: office.cz@sandoz.com 
Tel: +420 221 421 612 
 

Malta 
Cherubino LTD 
DELF Building 
Sliema Road 
Gzira  
MALTA 
Tel: 00356 21343270 
Email: care@cherubino.com.mt 
  

Danmark 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Nederland 
Sandoz B.V. 
Veluwezoom 22  
NL-1327 AH Almere 
Tel: +31 36 5241600 
E-mail: info.sandoz-nl@sandoz.com 
 

Deutschland 
HEXAL AG 
Industriestraße 25 
D-83607 Holzkirchen 
Tel: + 49 8024 908 0 
E-mail: service@hexal.com 
 

Norge 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Eesti 
Sandoz d.d. Eesti filiaal,  
Pärnu mnt 105,  
EE-11312 Tallinn,  
Tel: +372 6652401 
 

Österreich 
HEXAL Pharma GmbH 
Stella-Klein-Löw-Weg 17 
1020 WienTel: + 43 (0)1 486 96 22  
 

Ελλάδα 
Sandoz dd 
Κηφισίας 18 & Γκύζη 
GR - 151 25 Μαρούσι 
Τηλ: +30 216 600 500 0 
 

Polska 
Sandoz Polska Sp.z o.o. 
ul. Domaniewska 50 C 
PL - 02-672 Warszawa 
Phone: +48 22 549 15 00 

España 
Sandoz Farmacéutica, S.A. / BEXAL 
FARMACÉUTICA, S.A.  
Centro Empresarial Osa Mayor 
Avda. Osa Mayor, nº 4 
28023 (Aravaca) Madrid 
España 
Tel: +34 91 548 84 04 
Registros.spain@sandoz.com 
 

Portugal 
Sandoz Farmacêutica Lda. 
Avenida Professor Doutor Cavaco Silva, n.º 10E 
Taguspark 
P-2740-255 Porto Salvo 
Tel: +351 219 241 911 
 

France 
Sandoz SAS 
49, avenue Georges Pompidou 
F-92593 Levallois-Perret Cedex 
Tel: +33 1 4964 4801 

România 
SC Sandoz S.R.L. 
Str Livezeni nr. 7A,  
Targu Mures, 540472 - RO 
Romania 
Phone: +40 265 208 120 
 

Ireland 
Rowex Ltd. 
Newtown 

Slovenija 
Lek Pharmaceuticals d.d. 
Verovśkova 57 

 66 

mailto:info.hungary@sandoz.com
mailto:info.sandoz-nl@sandoz.com


IE - Bantry  Co. Cork 
Tel: + 353 27 50077 
 

SI-1526 Ljubljana 
Tel: +386 1 5802111 
E-mail: info.lek@sandoz.com 
 

Ísland 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Slovenská republika 
Sandoz d.d. - organizačná zložka 
Galvaniho 15/C 
SK-821 04 Bratislava 
Tel: +421 2 48 200 601  
 

Italia 
Hexal S.p.A. c/o Sandoz S.p.A. 
Largo Umberto Boccioni 1 
I-21040 Origgio / VA  
Tel: + 39-02-96 541 
 

Suomi/Finland 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 Kööpenhamina S/Köpenhamn S 
E-mail: info.sandoz-dk@sandoz.com 

Κύπρος 
Π.T.Χατζηγeωργίου εταιρεία Ltd 
Γιλντίζ 31-3042 Λεμεσός 
Τηλέφωνο: 00357 25372425 
Φαξ: 00357 25376400 
e-mail: hapanicos@cytanet.com.cy 
 

Sverige 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 Köpenhamn S 
E-mail: info.sandoz-dk@sandoz.com 

Latvija 
Sandoz d.d. Representative Office in Latvia 
K.Valdemāra Str. 33 – 30 
LV-1010 Riga 
Phone: +371 67892007 

United Kingdom 
Sandoz Ltd 
Frimley Business Park 
Frimley Camberley Surrey GU16 7SR 
Tel: +44 1276 69 8020 
E-mail: uk.drugsafety@sandoz.com 
 

Lietuva 
Sandoz Pharmaceuticals d.d., 
Branch Office Lithuania 
Seimyniskiu Str. 3A 
LT-09312 Vilnius 
Phone: +370 5 2636038 

Hrvatska 
Sandoz d.o.o. 
Maksimirska 120 
HR – 10000 Zagreb 

 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency (EMA) web 
site: http://www.ema.europa.eu/ 
 

 67 

mailto:info.lek@sandoz.com
mailto:uk.drugsafety@sandoz.com
http://www.ema.europa.eu/


Package leaflet: Information for the patient 
 

Rivastigmine HEXAL 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 or pharmacist. 
- 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 or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4 
 
What is in  this leaflet:  
 
1. What Rivastigmine HEXAL is and what it is used for 
2. What you need to know before you take Rivastigmine HEXAL 
3. How to take Rivastigmine HEXAL 
4. Possible side effects 
5. How to store Rivastigmine HEXAL 
6. Contents of the pack and other  information 
 
 
1. What Rivastigmine HEXAL is and what it is used for  
 
The active substance of Rivastigmine HEXAL 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, 
Rivastigmine HEXAL 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.  
 
Rivastigmine HEXAL 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 Rivastigmine HEXAL 
 
Do not take Rivastigmine HEXAL 
 
- if you are allergic to rivastigmine (the active substance in Rivastigmine HEXAL) 

or any of the other ingredients of this medicine (listed in section 6).  
- if you have had a previous skin reaction suggestive of allergic contact dermatitis with 

rivastigmine. 
 
If this applies to you, tell your doctor and do not take Rivastigmine HEXAL. 
 

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Warnings and precautions 
 
Talk to your doctor before taking Rivastigmine HEXAL 
 
- 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 Rivastigmine HEXAL 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 Rivastigmine HEXAL in the paediatric population in the treatment of 
Alzheimer’s disease. 
 
Other medicines and Rivastigmine HEXAL 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Rivastigmine HEXAL should not be given at the same time as other medicines with similar effects to 
Rivastigmine HEXAL. Rivastigmine HEXAL might interfere with anticholinergic medicines 
(medicines used to relieve stomach cramps or spasms, to treat Parkinson’s disease or to prevent travel 
sickness). 
 
Rivastigmine HEXAL 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 Rivastigmine HEXAL, tell your doctor before you are 
given any anaesthetics, because Rivastigmine HEXAL may exaggerate the effects of some muscle 
relaxants during anaesthesia.  
 
Caution when Rivastigmine HEXAL 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.  
 

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If you are pregnant, the benefits of using Rivastigmine HEXAL must be assessed against the possible 
effects on your unborn child. Rivastigmine HEXAL should not be used during pregnancy unless 
clearly necessary  
 
You should not breast-feed during treatment with Rivastigmine HEXAL.  
 
Driving and using machines 
 
Your doctor will tell you whether your illness allows you to drive vehicles and use machines safely.  
Rivastigmine HEXAL 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. 
 
Important information about some of the ingredients of Rivastigmine HEXAL 
 
One of the inactive ingredients in Rivastigmine HEXAL oral solution is sodium benzoate. Benzoic 
acid is a mild irritant to the skin, eyes and mucous membranes. 
 
 
3. How to take Rivastigmine HEXAL 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
How to start treatment 
 
Your doctor will tell you what dose of Rivastigmine HEXAL 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 (corresponding to 3 ml) 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 Rivastigmine HEXAL 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 Rivastigmine HEXAL. 
• To benefit from your medicine, take it every day. 
• Take Rivastigmine HEXAL twice a day, in the morning and evening, with food. 
 
How to use this medicine 
 

 70 



 
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. 
 
 

 71 



 
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. 
 
 

 72 



 
 
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 Rivastigmine HEXAL than you should 
 
If you accidentally take more Rivastigmine HEXAL than you should, inform your doctor. You may 
require medical attention. Some people who have accidentally taken too much Rivastigmine HEXAL 
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 Rivastigmine HEXAL 
 
If you find you have forgotten to take your dose of Rivastigmine HEXAL, 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. 
 
 

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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 
 
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) 

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• 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 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 or pharmacist. This includes any possible side effects 
not listed in this leaflet.  
 
You can also report side effects directly via the national reporting system listed in Appendix V. By 
reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. HOW TO STORE RIVASTIGMINE HEXAL 
 
Keep this medicine  out of the sight  and reach of children.  
 
Do not use Rivastigmine HEXAL after the expiry date which is stated on the carton. The expiry date 
refers to the last day of that month.  
 
Do not store above 30°C. Do not refrigerate or freeze. 

 75 



 
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. 
 
Store in an upright position. 
 
Use Rivastigmine HEXAL oral solution within 1 month of opening the bottle. 
 
 
6. Content of the pack and other information 
 
What Rivastigmine HEXAL 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 Rivastigmine HEXAL looks like and contents of the pack 
 
Rivastigmine HEXAL 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 
 
HEXAL  AG 
Industriestraße 25 
D-83607 Holzkirchen 
Germany 
 
Manufacturer 
 
Novartis Pharma GmbH 
Roonstrasse 25 
D-90429 Nuremberg 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sandoz N.V. 
Telecom Gardens 
Medialaan 40 
B-1800 Vilvoorde 
Tel: +32 (0)2 722  97 98 
 

Luxembourg/Luxemburg 
HEXAL AG 
Industriestraße 25 
D-83607 Holzkirchen 
Tél/Tel: + 49 8024 908 0 
E-mail: service@hexal.com 

България 
Representative office Sandoz d.d. 
Business Park Sofia, buil. 7B, fl. 3 
BG-1766 Sofia  
Tel.: + 359 2 970 47 47  
 

Magyarország 
Sandoz Hungária Kft. 
Bartók Béla út 43-47 
H-1114 Budapest 
Phone: +36 1 430 2890 
E-mail: info.hungary@sandoz.com 
 

 76 

mailto:info.hungary@sandoz.com


Česká republika 
Sandoz s.r.o. 
U Nákladového nádraží 10 
CZ-13000 Praha 3 
E-mail: office.cz@sandoz.com 
Tel: +420 221 421 612 

Malta 
Cherubino LTD 
DELF Building 
Sliema Road 
Gzira  
MALTA 
Tel: 00356 21343270 
Email: care@cherubino.com.mt  
 

Danmark 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Nederland 
Sandoz B.V. 
Veluwezoom 22  
NL-1327 AH Almere 
Tel: +31 36 5241600 
info.sandoz-nl@sandoz.com 
 

Deutschland 
HEXAL AG 
Industriestraße 25 
D-83607 Holzkirchen 
Tel: + 49 8024 908 0 
E-mail:  service@hexal.com 
 

Norge 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Eesti 
Sandoz d.d. Eesti filiaal,  
Pärnu mnt 105,  
EE-11312 Tallinn,  
Tel: +372 6652401 

Österreich 
HEXAL Pharma GmbH 
Stella-Klein-Löw-Weg 171020 Wien 
Tel: + 43 (0)1 486 96 22 
 

 
Ελλάδα 
Sandoz dd 
Κηφισίας 18 & Γκύζη 
GR - 151 25 Μαρούσι 
Τηλ: +30 216 600 500 0 
 

 
Polska 
Sandoz Polska Sp.z o.o. 
ul. Domaniewska 50 C 
PL - 02-672 Warszawa 
Phone: +48 22 549 15 00 

España 
Sandoz Farmacéutica, S.A. / BEXAL 
FARMACÉUTICA, S.A.  
Centro Empresarial Osa Mayor 
Avda. Osa Mayor, nº 4 
28023 (Aravaca) Madrid 
España 
Tel: +34 91 548 84 04 
Registros.spain@sandoz.com 
 

Portugal 
Sandoz Farmacêutica Lda. 
Avenida Professor Doutor Cavaco Silva, n.º 10E 
Taguspark 
P-2740-255 Porto Salvo 
Tel: +351 219 241 911 
 

France 
Sandoz SAS 
49, avenue Georges Pompidou 
F-92593 Levallois-Perret Cedex 
Tel: +33 1 4964 4801 

România 
SC Sandoz S.R.L. 
Str Livezeni nr. 7A,  
Targu Mures, 540472 - RO 
Romania 
Phone: +40 265 208 120 
 

Ireland 
Rowex Ltd. 
Newtown 
IE - Bantry  Co. Cork 
Tel: + 353 27 50077 

Slovenija 
Lek Pharmaceuticals d.d. 
Verovśkova 57 
SI-1526 Ljubljana 
Tel: +386 1 5802111 

 77 

mailto:info.sandoz-nl@sandoz.com


 E-mail: info.lek@sandoz.com 
 

Ísland 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 København S 
E-mail: info.sandoz-dk@sandoz.com 

Slovenská republika 
Sandoz d.d. - organizačná zložka 
Galvaniho 15/C 
SK-821 04 Bratislava 
Tel: +421 2 48 200 601  
 

Italia 
Hexal S.p.A. c/o Sandoz S.p.A. 
Largo Umberto Boccioni 1 
I-21040 Origgio / VA  
Tel: + 39-02-96 541 
 

Suomi/Finland 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 Kööpenhamina S/Köpenhamn S 
E-mail: info.sandoz-dk@sandoz.com 

Κύπρος 
Π.T.Χατζηγeωργίου εταιρεία Ltd 
Γιλντίζ 31-3042 Λεμεσός  
Τηλέφωνο: 00357 25372425 
Φαξ: 00357 25376400 
e-mail: hapanicos@cytanet.com.cy 
 

 
Sverige 
Sandoz A/S 
Edvard Thomsens Vej 14 
DK-2300 Köpenhamn S  
E-mail: info.sandoz-dk@sandoz.com 

Latvija 
Sandoz d.d. Representative Office in Latvia 
K.Valdemāra Str. 33 – 30 
LV-1010 Riga 
Phone: +371 67892007 

United Kingdom 
Sandoz Ltd 
Frimley Business Park 
Frimley Camberley Surrey GU16 7SR 
Tel: +44 1276 69 8020 
E-mail: uk.drugsafety@sandoz.com 
 

Lietuva 
Sandoz Pharmaceuticals d.d., 
Branch Office Lithuania 
Seimyniskiu Str. 3A 
LT-09312 Vilnius 
Phone: +370 5 2636038 

Hrvatska 
Sandoz d.o.o. 
Maksimirska 120 
HR – 10 000 Zagreb 

 

 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency (EMA) web 
site: http://www.ema.europa.eu/ 
 

  
 

 78 

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mailto:uk.drugsafety@sandoz.com
http://www.emea.europa.eu/

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