Azilect · 4.4 Special warnings and precautions for use · 1

HOS-093916 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile In clinical studies in Parkinson's disease patients the most commonly reported adverse reactions were: headache, depression, vertigo, and flu (influenza and rhinitis) in monotherapy; dyskinesia, orthostatic hypotension, fall, abdominal pain, nausea and vomiting, and dry mouth in adjunct to levodopa therapy; musculoskeletal pain, as back and neck pain, and arthralgia in both regimens. These adverse reactions were not associated with an elevated rate of drug discontinuation. Tabulated list of adverse reactions Adverse reactions are listed below in Tables 1 and 2 by system organ class and frequency using the following conventions: 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). Monotherapy The tabulated list below includes adverse reactions which were reported with a higher incidence in placebo-controlled studies, in patients receiving 1 mg/day rasagiline. System Organ Very common Common Uncommon Not known Class Infections and Influenza infestations Neoplasms Skin carcinoma benign, malignant and unspecified (including cysts and polyps) Blood and Leucopenia lymphatic system disorders Immune system Allergy disorders Metabolism and Decreased appetite nutrition disorders 6  System Organ Very common Common Uncommon Not known Class Psychiatric Depression, Impulse control disorders Hallucinations* disorders* Nervous system Headache Cerebrovascular Serotonin disorders accident syndrome*, Excessive daytime sleepiness (EDS) and sudden sleep

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HOS-093912 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Concomitant treatment with other monoamine oxidase (MAO) inhibitors (including medicinal and natural products without prescription e.g. St. John's Wort) or pethidine (see section 4.5). At least 14 days must elapse between discontinuation of rasagiline and initiation of treatment with MAO inhibitors or pethidine. Severe hepatic impairment.

HOS-093911 · has-indication-information · PDF-Seite 2

AZILECT is indicated in adults for the treatment of idiopathic Parkinson’s disease as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations.

HOS-093914 · has-interaction-information · PDF-Seite 4

MAO Inhibitors Rasagiline is contraindicated along with other MAO inhibitors (including medicinal and natural products without prescription e.g. St. John's Wort) as there may be a risk of non-selective MAO inhibition that may lead to hypertensive crises (see section 4.3). Pethidine Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors including another selective MAO-B inhibitor. The concomitant administration of rasagiline and pethidine is contraindicated (see section 4.3). Sympathomimetics With MAO inhibitors there have been reports of medicinal product interactions with the concomitant use of sympathomimetic medicinal products. Therefore, in view of the MAO inhibitory activity of rasagiline, concomitant administration of rasagiline and sympathomimetics such as those present in nasal and oral decongestants or cold medicinal products, containing ephedrine or pseudoephedrine, is not recommended (see section 4.4). Dextromethorphan There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. Therefore, in view of the MAO inhibitory activity of rasagiline, the concomitant administration of rasagiline and dextromethorphan is not recommended (see section 4.4). SNRI/SSRI/tri- and tetracyclic antidepressants The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided (see section 4.4). For concomitant use of rasagiline with selective serotonin reuptake inhibitors (SSRIs)/selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in clinical trials, see section 4.8. Serious adverse reactions have been reported with the concomitant use of SSRIs, SNRIs, tricyclic/tetracyclic antidepressants and MAO inhibitors. Therefore, in view of the MAO inhibitory activity of rasagiline, antidepressants should be administered with caution. Agents that affect CYP1A2 activity In vitro metabolism studies have indicated that cytochrome P450 1A2 (CYP1A2) is the major enzyme responsible for the metabolism of rasagiline. CYP1A2 inhibitors Co-administration of rasagiline and ciprofloxacin (an inhibitor of CYP1A2) increased the AUC of rasagiline by 83%. Co-administration of rasagiline and theophylline (a substrate of CYP1A2) did not affect the pharmacokinetics of either product. Thus, potent CYP1A2 inhibitors may alter rasagiline plasma levels and should be administered with caution.

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HOS-093915 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data from the use of rasagiline in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of rasagiline during pregnancy. Breast-feeding Non-clinical data indicate that rasagiline inhibits prolactin secretion and thus, may inhibit lactation. It is not known whether rasagiline is excreted in human milk. Caution should be exercised when rasagiline is administered to a breast-feeding mother. Fertility No human data on the effect of rasagiline on fertility are available. Non-clinical data indicate that rasagiline has no effect on fertility.

HOS-093913 · has-warning-information · PDF-Seite 3

Concomitant use of rasagiline with other medicinal products The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided (see section 4.5). At least five weeks should elapse between discontinuation of fluoxetine and initiation of treatment with rasagiline. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with fluoxetine or fluvoxamine. The concomitant use of rasagiline and dextromethorphan or sympathomimetics such as those present in nasal and oral decongestants or cold medicinal product containing ephedrine or pseudoephedrine is not recommended (see section 4.5). Concomitant use of rasagiline and levodopa Since rasagiline potentiates the effects of levodopa, the adverse reactions of levodopa may be increased and pre-existing dyskinesia exacerbated. Decreasing the dose of levodopa may ameliorate this adverse reaction. There have been reports of hypotensive effects when rasagiline is taken concomitantly with levodopa. Patients with Parkinson’s disease are particularly vulnerable to the adverse reactions of hypotension due to existing gait issues. Dopaminergic effects Excessive daytime sleepiness (EDS) and sudden sleep onset (SOS) episodes Rasagiline may cause daytime drowsiness, somnolence, and, occasionally, especially if used with other dopaminergic medicinal products - falling asleep during activities of daily living. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with rasagiline. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines (see section 4.7). Impulse control disorders (ICDs) ICDs can occur in patients treated with dopamine agonists and/or dopaminergic treatments. Similar reports of ICDs have also been received post-marketing with rasagiline. Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware of the behavioural symptoms of impulse control disorders that were observed in patients treated with rasagiline, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido, hypersexuality, impulsive behaviour and compulsive spending or buying. Melanoma A retrospective cohort study suggested a possibly increased risk of melanoma with the use of rasagiline, especially in patients with longer duration of rasagiline exposure and/

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