INCRUSE ELLIPTA Inhalation powder, pre-dispensed Ref.[8306] Active ingredients: Umeclidinium

Asthma

Umeclidinium bromide should not be used in patients with asthma since it has not been studied in this patient population.

Paradoxical bronchospasm

Administration of umeclidinium bromide may produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs treatment should be discontinued immediately and alternative therapy instituted if necessary.

Deterioration of disease

Umeclidinium bromide is intended for the maintenance treatment of COPD. It should not be used for the relief of acute symptoms, i.e. as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting bronchodilator. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control. In the event of deterioration of COPD during treatment with umeclidinium bromide, 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 including umeclidinium bromide (see section 4.8). In addition, patients with clinically significant uncontrolled cardiovascular disease were excluded from clinical studies. Therefore, umeclidinium bromide should be used with caution in patients with severe cardiovascular disorders, particularly cardiac arrhythmias.

Antimuscarinic activity

Due to its antimuscarinic activity, umeclidinium bromide should be used with caution in patients with urinary retention or with narrow-angle glaucoma.

Lactose contents

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

Clinically significant interactions mediated by umeclidinium bromide at clinical doses are considered unlikely due to the low plasma concentrations achieved after inhaled dosing.

Other antimuscarinics

Co-administration of umeclidinium bromide with other long-acting muscarinic antagonists or medicinal products containing this active substance has not been studied and is not recommended as it may potentiate known inhaled muscarinic antagonist adverse reactions.

Metabolic and transporter based interactions

Umeclidinium bromide is a substrate of cytochrome P450 2D6 (CYP2D6). The steady-state pharmacokinetics of umeclidinium bromide were assessed in healthy volunteers lacking CYP2D6 (poor metabolisers). No effect on umeclidinium AUC or C_max was observed at a dose 4-fold higher than the therapeutic dose. An approximately 1.3-fold increase in umeclidinium bromide AUC was observed at an 8-fold higher dose with no effect on umeclidinium bromide C_max. Based on the magnitude of these changes, no clinically relevant interaction is expected when umeclidinium is co-administered with CYP2D6 inhibitors or when administered to subjects genetically deficient in CYP2D6 activity (poor metabolisers).

Umeclidinium bromide is a substrate of P-glycoprotein (P-gp) transporter. The effect of the moderate P-gp inhibitor verapamil (240 mg once daily) on the steady-state pharmacokinetics of umeclidinium bromide was assessed in healthy volunteers. No effect of verapamil was observed on umeclidinium bromide C_max. An approximately 1.4-fold increase in umeclidinium bromide AUC was observed. Based on the magnitude of these changes, no clinically relevant interaction is expected when umeclidinium bromide is co-administered with P-gp inhibitors.

Other medicinal products for COPD

Although no formal in vivo interaction studies have been performed, inhaled umeclidinium bromide has been used concomitantly with other COPD medicinal products including short and long acting sympathomimetic bronchodilators and inhaled corticosteroids without clinical evidence of interactions.

Pregnancy

There are no data from the use of umeclidinium bromide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Umeclidinium bromide 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 bromide is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue medicinal product taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effects of umeclidinium bromide on human fertility. Animal studies indicate no effects of umeclidinium bromide on fertility.

Umeclidinium bromide has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequently reported adverse reactions are nasopharyngitis (6%) and upper respiratory tract infection (5%).

Tabulated list of adverse reactions

The safety profile of umeclidinium bromide was evaluated in patients with COPD who received doses of 55 micrograms or greater for up to one year. This includes patients who received the recommended dose of 55 micrograms once daily.

The frequencies assigned to the adverse reactions identified in the table below include crude incidence rates observed from efficacy studies, the long-term safety study (which involved patients who received umeclidinium bromide), post-marketing studies and spontaneous reporting.

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).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.