Onbrez Breezhaler · 4.8 Undesirable effects · 1

HOS-095494 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most common adverse reactions at the recommended doses were nasopharyngitis (14.3%), upper respiratory tract infection (14.2%), cough (8.2%), headache (3.7%) and muscle spasms (3.5%). These were in the vast majority mild or moderate and became less frequent if treatment was continued. At the recommended doses, the adverse reaction profile of Onbrez Breezhaler in patients with COPD shows clinically insignificant systemic effects of beta2-adrenergic stimulation. Mean heart rate changes were less than one beat per minute, and tachycardia was infrequent and reported at a similar rate as under placebo treatment. Relevant prolongations of QTcF were not detectable in comparison to placebo. The frequency of notable QTcF intervals [i.e. >450 ms (males) and >470 ms (females)] and reports of hypokalaemia were similar to placebo. The mean of the maximum changes in blood glucose were similar between Onbrez Breezhaler and placebo. Tabulated summary of adverse reactions The Onbrez Breezhaler Phase III clinical development programme involved patients with a clinical diagnosis of moderate to severe COPD. 4 764 patients were exposed to indacaterol up to one year at doses up to twice the maximum recommended dose. Of these patients, 2 611 were on treatment with 150 microgram once daily and 1 157 on treatment with 300 microgram once daily. Approximately 41% of patients had severe COPD. The mean age of patients was 64 years, with 48% of patients aged 65 years or older, and the majority (80%) was Caucasian. Adverse reactions in Table 1 are listed according to MedDRA system organ class in the COPD safety database. Within each system organ class, adverse reactions are ranked by frequency in descending order according to 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). 6 Table 1 Adverse reactions Adverse reactions Frequency category Infections and infestations Nasopharyngitis Very common Upper respiratory tract infection Very common Sinusitis Co

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HOS-095490 · has-contraindication-information · PDF-Seite 3

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

HOS-095489 · has-indication-information · PDF-Seite 2

Onbrez Breezhaler is indicated for maintenance bronchodilator treatment of airflow obstruction in adult patients with chronic obstructive pulmonary disease (COPD). 2

HOS-095492 · has-interaction-information · PDF-Seite 5

Sympathomimetic medicinal products Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) may potentiate adverse reactions to Onbrez Breezhaler. Onbrez Breezhaler should not be used in conjunction with other long-acting beta2-adrenergic agonists or medicinal products containing long-acting beta2-adrenergic agonists. Hypokalaemic treatment Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium- sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists, therefore caution is required (see section 4.4). Beta-adrenergic blockers Beta-adrenergic blockers and beta2-adrenergic agonists may weaken or antagonise the effect of each other when administered concurrently. Therefore indacaterol should not be given together with beta- adrenergic blockers (including eye drops) unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution. Metabolic and transporter based interactions Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp) raises the systemic exposure of indacaterol by up to two-fold. The magnitude of exposure increases due to interactions does not raise any safety concerns given the safety experience of treatment with Onbrez Breezhaler in clinical studies of up to one year at doses up to twice the maximum recommended therapeutic dose. Indacaterol has not been shown to cause interactions with medicinal products administered concomitantly. In vitro investigations have indicated that indacaterol has negligible potential to cause metabolic interactions with medicinal products at the systemic exposure levels achieved in clinical practice.

HOS-095493 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no data from the use of indacaterol in pregnant women available. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant exposures (see section 5.3). Like other beta2-adrenergic agonists, indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle. Onbrez Breezhaler should only be used during pregnancy if the expected benefits outweigh the potential risks. 5 Breast-feeding It is not known whether indacaterol/metabolites are excreted in human milk. Available pharmacokinetic/toxicological data in animals have shown excretion of indacaterol/metabolites in milk (see section 5.3). A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Onbrez Breezhaler therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility A decreased pregnancy rate has been observed in rats. Nevertheless, it is considered unlikely that indacaterol will affect reproductive or fertility performance in humans following inhalation of the maximum recommended dose (see section 5.3).

HOS-095491 · has-warning-information · PDF-Seite 3

Asthma Onbrez Breezhaler is a long-acting beta2-adrenergic agonist, which is only indicated for COPD and should not be used in asthma due to the absence of long-term outcome data in asthma. 3 Long-acting beta2-adrenergic agonists may increase the risk of asthma-related serious adverse events, including asthma-related deaths, when used for the treatment of asthma. Hypersensitivity Immediate hypersensitivity reactions have been reported after administration of Onbrez Breezhaler. If signs suggesting allergic reactions (in particular, difficulties in breathing or swallowing, swelling of tongue, lips and face, urticaria, skin rash) occur, Onbrez Breezhaler should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm As with other inhalation therapy, administration of Onbrez Breezhaler may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs Onbrez Breezhaler should be discontinued immediately and alternative therapy substituted. Deterioration of disease Onbrez Breezhaler is not indicated for the treatment of acute episodes of bronchospasm, i.e. as rescue therapy. In the event of deterioration of COPD during treatment with Onbrez Breezhaler, a re- evaluation of the patient and of the COPD treatment regimen should be undertaken. An increase in the daily dose of Onbrez Breezhaler beyond the maximum dose of 300 microgram is not appropriate. Systemic effects Although no clinically relevant effect on the cardiovascular system is usually seen after the administration of Onbrez Breezhaler at the recommended doses, as with other beta2-adrenergic agonists, indacaterol should be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to beta2- adrenergic agonists. Cardiovascular effects Like other beta2-adrenergic agonists, indacaterol may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. In case such effects occur, treatment may need to be discontinued. In addition, beta-adrenergic agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of QT interval and ST segment depression

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