Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Ultibro 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 Ultibro Breezhaler belong (see section 4.5).

Asthma
Ultibro 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
Ultibro 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 Ultibro 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.

Paradoxical bronchospasm
Administration of Ultibro Breezhaler may result in paradoxical bronchospasm which can be life-threatening. If this occurs, treatment should be discontinued immediately and alternative therapy instituted.


ULT API MAY23 V 2.1                                                        REF EU SmPC 18Nov2020 Anticholinergic effects related to glycopyrronium

Narrow-angle glaucoma
No data are available in patients with narrow-angle glaucoma, therefore Ultibro 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 Ultibro Breezhaler should any of these signs or symptoms develop.

Urinary retention
No data are available in patients with urinary retention, therefore Ultibro 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, Ultibro Breezhaler should be used only if the expected benefit outweighs the potential risk (see section 5.2). These patients should be monitored closely for potential adverse reactions.

Cardiovascular effects

Ultibro Breezhaler should be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension).

Beta2-adrenergic agonists 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 with this medicinal product, treatment may need to be discontinued. In addition, beta-adrenergic agonists have been reported to produce electrocardiographic (ECG) changes, such as flattening of the T wave, prolongation of QT interval and ST segment depression, although the clinical significance of these observations is unknown. Therefore, long-acting beta2-adrenergic agonists (LABA) or LABA-containing combination products such as Ultibro Breezhaler should be used with caution in patients with known or suspected prolongation of the QT interval or treated with medicinal products affecting the QT interval.

Patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc (Fridericia method) was prolonged (>450 ms) were excluded from the clinical trials, and therefore there is no experience in these patient groups. Ultibro Breezhaler should be used with caution in these patient groups.

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. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility to cardiac arrhythmias (see section 4.5).

Clinically relevant effects of hypokalaemia have not been observed in clinical studies of Ultibro Breezhaler at the recommended therapeutic dose (see section 5.1).



ULT API MAY23 V 2.1                                                       REF EU SmPC 18Nov2020 Hyperglycaemia

Inhalation of high doses of beta2-adrenergic agonists may produce increases in plasma glucose. Upon initiation of treatment with Ultibro Breezhaler plasma glucose should be monitored more closely in diabetic patients.

During long-term clinical studies, more patients on Ultibro Breezhaler experienced clinically notable changes in blood glucose (4.9%) at the recommended dose than on placebo (2.7%). Ultibro Breezhaler has not been investigated in patients for whom diabetes mellitus is not well controlled, therefore caution and appropriate monitoring are advised in such patients.

General disorders

Ultibro Breezhaler should be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists.

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Effects on Driving

4.7    Effects on ability to drive and use machines

This medicinal product has no or negligible influence on the ability to drive and use machines.
However, the occurrence of dizziness may influence the ability to drive and use machines (see
section 4.8).




ULT API JAN21 V 2.0                                                        REF EU SmPC 18Nov2020