Xadago · 4.1 Therapeutic indications · 1

HOS-096146 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Dyskinesia was the most common adverse reaction reported in safinamide patients when used in combination with L-dopa alone or in combination with other PD treatments. Serious adverse reactions are known to occur with the concomitant use of SSRIs, SNRIs, tricyclic/tetracyclic antidepressants and MAO inhibitors, such as hypertensive crisis (high blood pressure, collapse), neuroleptic malignant syndrome (confusion, sweating, muscle rigidity, hyperthermia, CPK increase), serotonin syndrome (confusion, hypertension, muscle stiffness, hallucinations), and hypotension. With MAO-inhibitors there have been reports of drug interactions with concomitant use of sympathomimetic medicinal products. Impulse control disorders; pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments. Tabulated list of adverse reactions The tabulation below includes all adverse reactions in clinical trials where adverse reactions were considered related. Adverse reactions are ranked under headings of frequency using the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data). System Organ Very Common Uncommon Rare Class common Infections and Urinary tract infection Bronchopneumonia, infestations furuncle, nasopharyngitis, pyoderma, rhinitis, tooth infection, viral infection Neoplasms Basal cell carcinoma Acrochordon, benign, melanocytic naevus, malignant and seborrhoeic keratosis, unspecified (incl skin pa

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HOS-096142 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients (see section 6.1). Concomitant treatment with other monoamine oxidase (MAO) inhibitors (see sections 4.4 and 4.5). Concomitant treatment with pethidine (see sections 4.4 and 4.5). Use in patients with severe hepatic impairment (see section 4.2). Use in patients with albinism, retinal degeneration, uveitis, inherited retinopathy or severe progressive diabetic retinopathy (see sections 4.4 and 5.3).

HOS-096141 · has-indication-information · PDF-Seite 2

Xadago is indicated for the treatment of adult patients with idiopathic Parkinson’s disease (PD) as add- on therapy to a stable dose of levodopa (L-dopa) alone or in combination with other PD medicinal products in mid-to late-stage fluctuating patients.

HOS-096144 · has-interaction-information · PDF-Seite 4

In vivo and in vitro pharmacodynamic drug interactions MAO inhibitors and pethidine Safinamide must not be administered along with other MAO inhibitors (including moclobemide) as there may be a risk of non-selective MAO inhibition that may lead to a hypertensive crisis (see section 4.3). Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors. As this may be a class-effect, the concomitant administration of safinamide and pethidine is contraindicated (see section 4.3). There have been reports of medicinal product interactions with the concomitant use of MAO inhibitors and sympathomimetic medicinal products. In view of the MAO inhibitory activity of safinamide, concomitant administration of safinamide and sympathomimetics, such as those present in nasal and oral decongestants or cold medicinal products containing ephedrine or pseudoephedrine, requires caution (see section 4.4). Dextromethorphan There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. In view of the MAO inhibitory activity of safinamide, the concomitant administration of safinamide and dextromethorphan is not recommended, or if concomitant treatment is necessary, it should be used with caution (see section 4.4). Antidepressants The concomitant use of safinamide and fluoxetine or fluvoxamine should be avoided (see section 4.4), this precaution is based on the occurrence of serious adverse reactions (e.g. serotonin syndrome), although rare, that have occurred when SSRIs and dextromethorphan have been used with MAO inhibitors. If necessary, the concomitant use of these medicinal products should be at the lowest effective dose. A washout period corresponding to 5 half-lives of the SSRI used previously should be considered prior to initiating treatment with safinamide. 4 Serious adverse reactions have been reported with the concomitant use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic/tetracyclic antidepressants and MAO inhibitors (see section 4.4). In view of the selective and reversible MAO-B inhibitory activity of safinamide, antidepressants may be administered but used at the lowest doses necessary. In vivo and in vitro pharmacokinetic drug interactions Safinamide may transiently inhibit BCRP in vitro. In drug-drug-interaction studies i

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HOS-096145 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential Safinamide should not be given to women of childbearing potential unless adequate contraception is practiced. Pregnancy There are no or limited amount of data from the use of safinamide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Xadago is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of safinamide in milk (for details see 5.3). A risk for the breast-fed child cannot be excluded. Xadago should not be used during breast-feeding. 5 Fertility Animal studies indicate that safinamide treatment is associated with adverse reactions on female rat reproductive performance and sperm quality. Male rat fertility is not affected (see section 5.3).

HOS-096143 · has-warning-information · PDF-Seite 3

General warning In general, safinamide may be used with selective serotonin re-uptake inhibitors (SSRIs) at the lowest effective dose, with caution for serotoninergic symptoms. In particular, the concomitant use of safinamide and fluoxetine or fluvoxamine should be avoided, or if concomitant treatment is necessary these medicinal products should be used at low doses (see section 4.5). A washout period corresponding to 5 half-lives of the SSRI used previously should be considered prior to initiating treatment with safinamide. At least 7 days must elapse between discontinuation of safinamide and initiation of treatment with MAO inhibitors or pethidine (see section 4.3 and 4.5). When safinamide is co-administered with products that are BCRP substrates, please refer to the SmPC for that particular medicinal product. Hepatic impairment Caution should be exercised when initiating treatment with safinamide in patients with moderate hepatic impairment. In case patients progress from moderate to severe hepatic impairment, treatment with safinamide should be stopped (see sections 4.2, 4.3 and 5.2). Potential for retinal degeneration in patients with prior history of retinal disease 3 Safinamide should not be administered to patients with ophthalmological history that would put them at increased risk for potential retinal effects (e.g., family history of hereditary retinal disease, or history of uveitis) see sections 4.3 and 5.3. Impulse control disorders (ICDs) Impulse control disorders can occur in patients treated with dopamine agonists and/or dopaminergic treatments. Some reports of ICDs have also been observed with other MAO-inhibitors. Safinamide treatment has not been associated with any increase in the appearance of ICDs. Patients and carers should be made aware of the behavioural symptoms of ICDs that were observed in patients treated with MAO-inhibitors, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido, hypersexuality, impulsive behaviour and compulsive spending or buying. Dopaminergic side effects Safinamide used as an adjunct to levodopa may potentiate the side effects of levodopa, and pre- existing dyskinesia may be exacerbated, requiring a decrease of levodopa. This effect was not seen when safinamide was used as an adjunct to dopamine agonists in early stage PD patients.