Leitlinien & Arzneimittelsicherheit

HOS-216767 · has-adverse-reaction-information · PDF-Seite 7

The presentation of the safety profile is based on the experience with Ulunar Breezhaler and the individual active substances. Summary of the safety profile The safety experience with Ulunar Breezhaler was comprised of exposure of up to 15 months at the recommended therapeutic dose. Ulunar Breezhaler showed similar adverse reactions to the individual components. As it contains indacaterol and glycopyrronium, the type and severity of adverse reactions associated with each of these components may be expected in the combination. The safety profile is characterised by typical anticholinergic and beta-adrenergic symptoms related to the individual components of the combination. Other most common adverse reactions related to the medicinal product (at least 3% of patients for Ulunar Breezhaler and also greater than placebo) were cough, nasopharyngitis and headache. Tabulated summary of adverse reactions Adverse reactions detected during clinical trials and from post-marketing sources are listed by MedDRA system organ class (Table 1). 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: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Table 1 Adverse reactions Adverse reactions Frequency category Infections and infestations Upper respiratory tract infection Very common Nasopharyngitis Common Urinary tract infection Common Sinusitis Common Rhinitis Common Immune system disorders Hypersensitivity Common Angioedema2 Uncommon Metabolism and nutrition disorders Hyperglycaemia and diabetes mellitus Common Psychiatric disorders Insomnia Uncommon Nervous system disorders Dizziness

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216763 · has-contraindication-information · PDF-Seite 3

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

HOS-216762 · has-indication-information · PDF-Seite 2

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

HOS-216765 · has-interaction-information · PDF-Seite 5

Concomitant administration of orally inhaled indacaterol and glycopyrronium, under steady-state conditions of both active substances, did not affect the pharmacokinetics of either active substance. No specific interaction studies were conducted with Ulunar Breezhaler. Information on the potential for interactions is based on the potential for each of its two active substances. Concomitant use not recommended Beta-adrenergic blockers Beta-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Therefore Ulunar Breezhaler 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. Anticholinergics The co-administration of Ulunar Breezhaler with other anticholinergic-containing medicinal products has not been studied and is therefore not recommended (see section 4.4). Sympathomimetics Concomitant administration of other sympathomimetics (alone or as part of combination therapy) may potentiate the adverse events of indacaterol (see section 4.4). 5 Caution required with concomitant use 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 use with caution (see section 4.4). To be taken into account with concomitant use 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 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 indacaterol in clinical studies of up to one year at doses up to twice the maximum recommended indacaterol dose. 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 expected when glycopyrronium is co-administer

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216766 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are no data from the use of Ulunar Breezhaler 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). Indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle. Therefore, Ulunar Breezhaler should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. Breast-feeding It is not known whether indacaterol, glycopyrronium and their metabolites are excreted in human milk. Available pharmacokinetic/toxicological data have shown excretion of indacaterol, glycopyrronium and their metabolites in the milk of lactating rats. The use of Ulunar Breezhaler by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant (see section 5.3). Fertility Reproduction studies and other data in animals do not indicate a concern regarding fertility in either males or females.

HOS-216764 · has-warning-information · PDF-Seite 3

Ulunar Breezhaler should not be administered concomitantly with medicinal products containing other long-acting beta-adrenergic agonists or long-acting muscarinic antagonists, the pharmacotherapeutic groups to which the components of Ulunar Breezhaler belong (see section 4.5). Asthma Ulunar Breezhaler should not be used for the treatment of asthma due to the absence of data in this indication. 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. Not for acute use Ulunar Breezhaler is not indicated for the treatment of acute episodes of bronchospasm. Hypersensitivity Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrronium, which are the active substances of Ulunar Breezhaler. If signs suggesting allergic reactions occur, in particular, angioedema (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. 3 Paradoxical bronchospasm Administration of Ulunar Breezhaler may result in paradoxical bronchospasm which can be life-threatening. If this occurs, treatment should be discontinued immediately and alternative therapy instituted. Anticholinergic effects related to glycopyrronium Narrow-angle glaucoma No data are available in patients with narrow-angle glaucoma, therefore Ulunar Breezhaler should be used with caution in these patients. Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and should be informed to stop using Ulunar Breezhaler should any of these signs or symptoms develop. Urinary retention No data are available in patients with urinary retention, therefore Ulunar Breezhaler should be used with caution in these patients. Patients with severe renal impairment A moderate mean increase in total system exposure (AUClast) to glycopyrronium of up to 1.4-fold was seen in subjects with mild and moderate renal impairment and up to 2.2-fold in subjects with severe renal impairment and end-stage renal disease. In patients with severe renal impairment (estimated glomerular filtration rate below 30 ml/min/1.73 m2), including those with end-stage renal disease requiring dialysis, Ulunar Breezhaler should be used only if the expected benefit outweighs the pote

Auszug; vollständigen Abschnitt im Original lesen.