Novartis Pharmaceuticals UK Ltd

Renal and hepatic impairment

No dose adjustment is necessary for patients with mild to moderate renal or hepatic impairment. However, Ddue to increased exposure in moderate renal and mild to moderate hepatic impairment, 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 adverse reactions (see sections 4.4 and 5.2).  

Patients with severe hepaticliver impairment have not been studied (see section 4.34).

The use of this medicinal product is contraindicated in patients with

hypersensitivity to the active substance, other carbamate derivatives or to any of the excipients used in the formulation.,

-                   severe liver impairment, as it has not been studied in this population.

Gastrointestinal disorders such as nausea, and 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.

Special populations

Patients with clinically significant renal or hepatic impairment might experience more adverse reactions (see sections 4.2 and 5.2). Patients with severe hepatic impairment have not been studied. However, Exelon 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.

The following additional adverse reactions have been observed with Exelon transdermal patches: anxiety, delirium, pyrexia (common).

4.6     Fertility, pPregnancy and lactation

For rivastigmine no clinical data on exposed pregnancies are available. No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses related to maternal toxicity. In peri/postnatal studies in rats, an increased gestation time was observed. Rivastigmine should not be used during pregnancy unless clearly necessary.

In animals, rivastigmine is excreted into milk. It is not known if rivastigmine is excreted into human milk. Therefore, women on rivastigmine should not breast-feed.

4.8    Undesirable effects

The most commonly reported adverse reactions 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.

The following adverse reactions, listed below in Table 1, have been accumulated in patients with Alzheimer’s dementia treated with Exelon.

Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).

Table 1

The following additional adverse reactions have been observed with Exelon transdermal patches: anxiety, delirium, pyrexia (common).

Table 2 shows the adverse reactions reported in patients with dementia associated with Parkinson’s disease treated with Exelon.

Table 2

Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted with Exelon in patients with dementia associated with Parkinson’s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.

Table 3

10.     DATE OF REVISION OF THE TEXT

27.04.2010

Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu

The following additional adverse reactions have been observed with Exelon transdermal patches: anxiety, delirium, pyrexia (common).

SECTION 3:

·        “Capsule, hard” changed to “Hard capsule”

SECTION 4.2:

·        Paragraph 1:

“….Therapy with rivastigmine should only be started if a caregiver is available who will regularly monitor drug intake by the patients”

changed to read

“….Therapy with rivastigmine should only be started if a caregiver is available who will regularly monitor intake of the medicinal product by the patients”

·        The following sentence has also been added:

“Patients with severe liver impairment have not been studied (see section 4.3).”

SECTION 4.3:

·        “Hypersensitivity to rivastigmine”

changed to read:

“Hypersensitivity to the active substance”

SECTION 4.4:

·        “As with other cholinergic substances” has been deleted.

·        Paragraph 9:

“….and therefore use in these patient populations is not recommended” has been added.

SECTION 4.5:

·        “Caution is recommended when selecting anaesthetic agents. Possible dose adjustments or temporarily stopping treatment can be considered if needed.”

Has been added.

SECTION 4.6:

·        The separate subheadings “Pregnancy” and “Lactation” have been deleted.

SECTION 4.7:

·        “As a consequence, rivastigmine has minor or moderate influence on the ability to drive and use machines.”

has been added.

SECTION 4.8:

·   “Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).”

            Moved to before table 1, as opposed to after the table.

·   “Metabolism and nutritional disorders

            Very common: Anorexia”

            has been added to table 1.

·   Table 2 rewritten. Incidence figures removed and the following have been added:

“Insomnia, anxiety, restlessness, somnolence, headache, bradycardia,      dyskinesia, dystonia, bradycardia, atrial fibrillation, atrrioventricular block, abdominal pain and dyspepsia, salivary hypersecretion, sweating increased, muscle rigidity, dehydration, fatigue and asthenia, gait abnormality”.

SECTION 6.5:

·      “Blister with 14 capsules, of clear PVC tray with blue lidding foil.”

            Changed to:

            “Blister of clear PVC tray with blue lidding foil with 14 capsules.”

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

            Changed to:

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

• Updated in relation to vomiting associated with oesophageal rupture and elevated liver function tests