Rivastigmine Sandoz · 4.8 Undesirable effects · 2

HOS-095614 · has-adverse-reaction-information · PDF-Seite 21

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. 21 Table 1 Infections and infestations Very rare Urinary infection Metabolism and nutrition disorders Very common Anorexia Common Decreased appetite Not known Dehydration Psychiatric disorders Common Agitation Common Confusion Common Anxiety Common Nightmares Uncommon Insomnia Uncommon Depression Very rare Hallucinations Not known Aggression, restlessness Nervous system disorders Very common Dizziness Common Headache Common Somnolence Common Tremor Uncommon Syncope Rare Seizures Very rare Extrapyramidal symptoms (including worsening of Parkinson’s disease) Not known Pleurothotonus (Pisa syndrome) Cardiac disorders Rare Angina pectoris Very rare

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HOS-095608 · has-adverse-reaction-information · PDF-Seite 6

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. 6 Table 1 Infections and infestations Very rare Urinary infection Metabolism and nutrition disorders Very common Anorexia Common Decreased appetite Not known Dehydration Psychiatric disorders Common Agitation Common Confusion Common Anxiety Common Nightmares Uncommon Insomnia Uncommon Depression Very rare Hallucinations Not known Aggression, restlessness Nervous system disorders Very common Dizziness Common Headache Common Somnolence Common Tremor Uncommon Syncope Rare Seizures Very rare Extrapyramidal symptoms (including worsening of Parkinson’s disease) Not known Pleurothotonus (Pisa syndrome) Cardiac disorders Rare Angina pectoris Very rare Car

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HOS-095610 · has-contraindication-information · PDF-Seite 18

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).

HOS-095604 · has-contraindication-information · PDF-Seite 3

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). 3

HOS-095603 · has-indication-information · PDF-Seite 2

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.

HOS-095609 · has-indication-information · PDF-Seite 17

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.

HOS-095606 · has-interaction-information · PDF-Seite 5

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 QT prolongation- or 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. 5 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.

HOS-095612 · has-interaction-information · PDF-Seite 20

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 QT prolongation-or 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. 20 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.

HOS-095613 · has-pregnancy-information · PDF-Seite 21

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.

HOS-095607 · has-pregnancy-information · PDF-Seite 6

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.

HOS-095611 · has-warning-information · PDF-Seite 18

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

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HOS-095605 · has-warning-information · PDF-Seite 4

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

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