Formoterol and Aclidinium bromide

Patients with a myocardial infarction during the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, QTc (Bazett’s method) above 470 msec, or hospitalisation within the previous 12 months for heart failure functional classes III and IV as per the “New York Heart Association” were excluded from the clinical studies, therefore aclidinium/formoterol combination should be used with caution in these patients groups.

There are no data available on the use of aclidinium/formoterol in pregnant women.

Studies in animals have shown foetotoxicity only at dose levels much higher than the maximum human exposure to aclidinium and adverse effects in reproduction studies with formoterol at very high systemic exposure levels.

Aclidinium/formoterol should only be used during pregnancy if the expected benefits outweigh the potential risks.

It is unknown whether aclidinium (and/or its metabolites) or formoterol are excreted in human milk. As studies in rats have shown excretion of small amounts of aclidinium (and/or its metabolites) and formoterol into milk, the use of aclidinium/formoterol by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant.

Fertility

Studies in rats have shown slight reductions in fertility only at dose levels much higher than the maximum human exposure to aclidinium and formoterol. Nevertheless, it is considered unlikely that aclidinium/formoterol administered at the recommended dose will affect fertility in humans.

Aclidinium bromide/formoterol combination has no or negligible influence on the ability to drive and use machines. The occurrence of blurred vision or dizziness may influence the ability to drive or to use machines.

The presentation of the safety profile is based on the experience with aclidinium/formoterol fixed dose combination and the individual components.

Summary of the safety profile

The safety experience withaclidinium/formoterol comprised exposure in clinical trials at the recommended therapeutic dose for up to 12 months, and in post-marketing experience.

Adverse reactions associated with aclidinium/formoterol fixed dose combination were similar to those of the individual components. As the combination contains aclidinium and formoterol, the type and severity of adverse reactions associated with each of the components may be expected with aclidinium/formoterol.

The most frequently reported adverse reactions with aclidinium/formoterol were nasopharyngitis (7.9%) and headache (6.8%).

Tabulated summary of adverse reactions

The aclidinium/formoterol clinical development programme was conducted in patients with moderate or severe COPD. A total of 1222 patients were treated with aclidinium/formoterol 340 micrograms/12 micrograms. The frequencies assigned to the adverse reactions are based on crude incidence rates observed with 340 micrograms aclidinium/12 microgram formoterol s in the pooled analysis of randomised, placebo-controlled Phase III clinical studies of at least six months duration, or on experience with individual components.

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).