Leitlinien & Arzneimittelsicherheit

HOS-288199 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most common adverse reactions over 52 weeks were asthma (exacerbation) (41.8%), nasopharyngitis (10.9%), upper respiratory tract infection (5.6%) and headache (4.2%). Tabulated list of adverse reactions Adverse reactions are listed by MedDRA system organ class (Table 1). The frequency of the adverse reactions is based on the IRIDIUM study. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention (CIOMS III): 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). 7 Table 1 Adverse reactions System organ class Adverse reactions Frequency category Nasopharyngitis Very common Upper respiratory tract Common Infections and infestations infection Candidiasis*1 Common Urinary tract infection*2 Common Immune system disorders Hypersensitivity*3 Common Metabolism and nutrition disorders Hyperglycaemia*4 Uncommon Nervous system disorders Headache*5 Common Eye disorders Cataract Uncommon Cardiac disorders Tachycardia*6 Common Asthma (exacerbation) Very common Oropharyngeal pain*7 Common Respiratory, thoracic and mediastinal disorders

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HOS-288195 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

HOS-288194 · has-indication-information · PDF-Seite 2

Zimbus Breezhaler is indicated as a maintenance treatment of asthma in adult patients not adequately controlled with a maintenance combination of a long-acting beta2-agonist and a high dose of an inhaled corticosteroid who experienced one or more asthma exacerbations in the previous year.

HOS-288197 · has-interaction-information · PDF-Seite 6

No specific interaction studies were conducted with indacaterol/glycopyrronium/mometasone furoate. Information on the potential for interactions is based on the potential for each of the monotherapy components. Medicinal products known to prolong the QTc interval Like other medicinal products containing a beta2-adrenergic agonist, this medicinal product should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or medicinal products known to prolong the QT interval, as any effect of these on the QT interval may be potentiated. Medicinal products known to prolong the QT interval may increase the risk of ventricular arrhythmia (see sections 4.4 and 5.1). Hypokalaemic treatment Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium- sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists (see section 4.4). Beta-adrenergic blockers Beta-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Therefore, this medicinal product should not be given together with beta-adrenergic blockers unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution. Interaction with CYP3A4 and P-glycoprotein inhibitors Inhibition of CYP3A4 and P-glycoprotein (P-gp) has no impact on the safety of therapeutic doses of Zimbus Breezhaler. Inhibition of the key contributors of indacaterol clearance (CYP3A4 and P-gp) or mometasone furoate clearance (CYP3A4) raises the systemic exposure of indacaterol or mometasone furoate up to two- fold. Due to the very low plasma concentration achieved after inhaled dosing, clinically significant interactions with mometasone furoate are unlikely. However, there may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered. Cimetidine or other inhibitors of organic cation transport In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is thought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) to glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these changes, no clinically relevant drug interaction is expect

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HOS-288198 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are insufficient data from the use of Zimbus Breezhaler or its individual components (indacaterol, glycopyrronium and mometasone furoate) in pregnant women to determine whether there is a risk. Indacaterol and glycopyrronium were not teratogenic in rats and rabbits following subcutaneous or inhalation administration, respectively (see section 5.3). In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate caused increased foetal malformations and decreased foetal survival and growth. Like other medicinal products containing beta2-adrenergic agonists, indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle. This medicinal product should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. Breast-feeding There is no information available on the presence of indacaterol, glycopyrronium or mometasone furoate in human milk, on the effects on a breast-fed infant, or on the effects on milk production. Other inhaled corticosteroids similar to mometasone furoate are transferred into human milk. Indacaterol, glycopyrronium and mometasone furoate have been detected in the milk of lactating rats. Glycopyrronium reached up to 10-fold higher concentrations in the milk of lactating rats than in the blood of the dam after intravenous administration. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility Reproduction studies and other data in animals did not indicate a concern regarding fertility in either males or females.

HOS-288196 · has-warning-information · PDF-Seite 3

Deterioration of disease This medicinal product should not be used to treat acute asthma symptoms, including acute episodes of bronchospasm, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician. Patients should not stop treatment without physician supervision since symptoms may recur after discontinuation. It is recommended that treatment with this medicinal product should not be stopped abruptly. If patients find the treatment ineffective, they should continue treatment but must seek medical attention. Increasing use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Sudden and progressive deterioration in the symptoms of asthma is potentially life-threatening and the patient should undergo urgent medical assessment. 3 Hypersensitivity Immediate hypersensitivity reactions have been observed after administration of this medicinal product. If signs suggesting allergic reactions occur, in particular angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm As with other inhalation therapy, administration of this medicinal product may result in paradoxical bronchospasm, which can be life-threatening. If this occurs, treatment should be discontinued immediately and alternative therapy instituted. Cardiovascular effects Like other medicinal products containing beta2-adrenergic agonists, this medicinal product may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. If such effects occur, treatment may need to be discontinued. This medicinal product should be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists. Patients with unstable ischaemic heart disease, a history of myocardial infarction in last 12 months, New York Heart Association (NYHA) class III/IV left ventricular failure, arrhythmia, uncontrolled hy

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