Anoro Ellipta (previously Anoro) · 4.6 Fertility, pregnancy and lactation · 1

HOS-096688 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most frequently reported adverse reaction is nasopharyngitis (9%). Tabulated list of adverse reactions The safety profile of ANORO ELLIPTA is based on safety experience with umeclidinium/vilanterol and the individual components from the clinical development program comprising of 6 855 patients with COPD and 6 from spontaneous reporting. The clinical development programme included 2 354 patients who received umeclidinium/vilanterol once daily in the Phase III clinical studies of 24 weeks or more, of whom 1 296 patients received the recommended dose of 55/22 micrograms in 24-week studies, 832 patients received a higher dose of 113/22 micrograms in 24-week studies and 226 patients received 113/22 micrograms in a 12-month study. The frequencies assigned to the adverse reactions identified in the table below include crude incidence rates observed in the integration of five 24-week studies and in the 12-month safety study. The frequency of adverse reactions is 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) and not known (cannot be estimated from available data). System Organ Class Adverse reactions Frequency Infections and infestations Urinary tract infection Common Sinusitis Common Nasopharyngitis Common Pharyngitis Common Upper respiratory tract infection Common Immune system disorders Hypersensitivity reactions including: Rash Uncommon Anaphylaxis, angioedema, and urticaria Rare Nervous system disorders Headache Common Tremor Uncommon Dysgeusia Uncommon Dizziness Not known Eye disorders Vision blurred

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HOS-096684 · has-contraindication-information · PDF-Seite 4

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

HOS-096683 · has-indication-information · PDF-Seite 2

ANORO ELLIPTA is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

HOS-096686 · has-interaction-information · PDF-Seite 5

Clinically significant interactions mediated by umeclidinium/vilanterol at clinical doses are considered unlikely due to the low plasma concentrations achieved after inhaled dosing. Beta-adrenergic blockers Beta2-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists, such as vilanterol. Concurrent use of either non-selective or selective beta-adrenergic blockers should be avoided unless there are compelling reasons for their use. Metabolic and transporter based interactions Vilanterol is a substrate of cytochrome P450 3A4 (CYP3A4). Concomitant administration of strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole, ritonavir, telithromycin) may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Co-administration with ketoconazole (400 mg) in healthy volunteers increased mean vilanterol AUC(0-t) and Cmax, 65% and 22% respectively. The increase in vilanterol exposure was not associated with an increase in beta-adrenergic agonist related systemic effects on heart rate, blood potassium or QT interval (corrected using the Fridericia method). Care is advised when co-administering umeclidinium/vilanterol with ketoconazole and other known strong CYP3A4 inhibitors as there is potential for an increased systemic exposure to vilanterol, which could lead to an increase in the potential for adverse reactions. Verapamil, a moderate CYP3A4 inhibitor, did not significantly affect the pharmacokinetics of vilanterol. Umeclidinium is a substrate of cytochrome P450 2D6 (CYP2D6). The steady-state pharmacokinetics of umeclidinium was assessed in healthy volunteers lacking CYP2D6 (poor metabolisers). No effect on umeclidinium AUC or Cmax was observed at a 8-fold higher dose. An approximately 1.3-fold increase in umeclidinium AUC was observed at 16-fold higher dose with no effect on umeclidinium Cmax. Based on the magnitude of these changes, no clinically relevant interaction is expected when umeclidinium/vilanterol is co-administered with CYP2D6 inhibitors or when administered to patients genetically deficient in CYP2D6 activity (poor metabolisers). Both umeclidinium and vilanterol are substrates of the P-glycoprotein transporter (P-gp). The effect of the moderate P-gp inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of umeclidinium and vilanterol was assessed in healthy volunteers. No effect of verapamil was observed on umeclidinium or vilanterol Cmax. An approximatel

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HOS-096687 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are no data from the use of umeclidinium/vilanterol in pregnant women. Studies in animals have shown reproductive toxicity at exposures which are not clinically relevant after administration of vilanterol (see section 5.3). Umeclidinium/vilanterol should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the foetus. Breast-feeding It is unknown whether umeclidinium or vilanterol are excreted in human milk. However, other beta2-adrenergic agonists are detected in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue umeclidinium/vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the effects of umeclidinium/vilanterol on human fertility. Animal studies indicate no effects of umeclidinium or vilanterol on fertility.

HOS-096685 · has-warning-information · PDF-Seite 4

Asthma This medicinal product should not be used in patients with asthma since it has not been studied in this patient population. Paradoxical bronchospasm Administration of umeclidinium/vilanterol may produce paradoxical bronchospasm that may be life- threatening. If paradoxical bronchospasm occurs, treatment should be discontinued immediately and alternative therapy instituted if necessary. Not for acute use Umeclidinium/vilanterol is not indicated for the treatment of acute episodes of bronchospasm. Deterioration of disease Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control. In the event of deterioration of COPD during treatment with umeclidinium/vilanterol, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Cardiovascular effects Cardiovascular effects, such as cardiac arrhythmias e.g. atrial fibrillation and tachycardia, may be seen after the administration of muscarinic receptor antagonists and sympathomimetics, including umeclidinium/vilanterol (see section 4.8). Patients with clinically significant uncontrolled cardiovascular disease were excluded from clinical studies. Therefore, umeclidinium/vilanterol should be used with caution in patients with severe cardiovascular disease. Antimuscarinic activity Due to its antimuscarinic activity, umeclidinium/vilanterol should be used with caution in patients with urinary retention or with narrow-angle glaucoma. Hypokalaemia Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. No clinically relevant effects of hypokalaemia were observed in clinical studies with umeclidinium/vilanterol at the recommended therapeutic dose. Caution should be exercised when umeclidinium/vilanterol is used with other medicinal products that also have the potential to cause hypokalaemia (see section 4.5). Hyperglycaemia Beta2-adrenergic agonists may produce transient hyperglycemia in some patients. 4 No clinically relevant effects on plasma glucose were observed in clinical studies with umeclidinium/vilanterol at the recommended therapeutic dose. Upon initiation of treatment with umeclidinium/vilanterol plasma glucose should be monitored more closely in diabetic patients. Coexisting conditions

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