BRETARIS GENUAIR Inhalation powder Ref.[6076] Active ingredients: Aclidinium

Paradoxical bronchospasm

Administration of Bretaris Genuair may cause paradoxical bronchospasm. If this occurs, treatment with Bretaris Genuair should be stopped and other treatments considered.

Deterioration of disease

Aclidinium bromide is a maintenance bronchodilator and should not be used for the relief of acute episodes of bronchospasm, i.e. as a rescue therapy. In the event of a change in COPD intensity while the patient is being treated with aclidinium bromide so that the patient considers additional rescue medication is required, a re-evaluation of the patient and the patients' treatment regimen should be conducted.

Cardiovascular effects

Bretaris Genuair should be used with caution in patients who had a myocardial infarction during the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalisation within the previous 12 months for heart failure functional classes III and IV as per the “New York Heart Association”. Experience in patients with cardiovascular comorbidities in clinical trials is limited (see section 5.1). These conditions may be affected by the anticholinergic mechanism of action.

Anticholinergic activity

Dry mouth, which has been observed with anticholinergic treatment, may in the long term be associated with dental caries.

Consistent with its anticholinergic activity, aclidinium bromide should be used with caution in patients with symptomatic prostatic hyperplasia or bladder-neck obstruction or with narrow-angle glaucoma (even though direct contact of the product with the eyes is very unlikely).

Excipients

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

Co-administration of aclidinium bromide with other anticholinergic-containing medicinal products has not been studied and is not recommended.

Although no formal in vivo drug interaction studies have been performed, inhaled aclidinium bromide has been used concomitantly with other COPD medicinal products including sympathomimetic bronchodilators, methylxanthines, and oral and inhaled steroids without clinical evidence of drug interactions.

In vitro studies have shown that aclidinium bromide or the metabolites of aclidinium bromide at the therapeutic dose are not expected to cause interactions with active substances that are substrates of Pglycoprotein (P-gp) or active substances metabolised by cytochrome P450 (CYP450) enzymes and esterases (see section 5.2).

Pregnancy

There are no data available on the use of aclidinium bromide in pregnant women. Studies in animals have shown fetotoxicity only at dose levels much higher than the maximum human exposure to aclidinium bromide (see section 5.3). Aclidinium bromide should only be used during pregnancy if the expected benefits outweigh the potential risks.

Breast-feeding

It is unknown whether aclidinium bromide/metabolites are excreted in human milk. Animal studies have shown excretion of small amounts of aclidinium bromide and/or metabolites into milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Bretaris Genuair therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Studies in rats have shown slight reductions in fertility only at dose levels much higher than the maximum human exposure to aclidinium bromide (see section 5.3). It is considered unlikely that aclidinium bromide administered at the recommended dose will affect fertility in humans.

Aclidinium bromide may have minor influence on the ability to drive and use machines. The occurrence of headache, dizziness or blurred vision following administration of aclidinium bromide (see section 4.8) may influence the ability to drive or to use machinery.

Summary of the safety profile

The most frequently reported adverse reactions with Bretaris Genuair were headache (6.6%) and nasopharyngitis (5.5%).

Tabulated summary of adverse reactions

The frequencies assigned to the undesirable effects listed below are based on crude incidence rates of adverse reactions (i.e. events attributed to Bretaris Genuair) observed with Bretaris Genuair 322 µg (636 patients) in the pooled analysis of one 6-month and two 3-month randomised, placebo-controlled clinical trials.

A placebo-controlled trial in 1791 patients with moderate to very severe COPD treated with Bretaris Genuair up to 36 months did not identify other adverse reactions.

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 the available data). System organ class Preferred term Frequency.

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.