Aclidinium (Bretaris Genuair) for chronic obstructive pulmonary disease

Aclidinium is indicated for long-term maintenance treatment and is not indicated for acute exacerbations of COPD.²

Do not prescribe aclidinium concomitantly with other anticholinergics.² If treating with aclidinium, prescribe a short-acting beta-2 agonist (SABA) as a reliever instead of the anticholinergic ipratropium.

Current clinical management guidelines support regular use of an inhaled long-acting bronchodilator, in conjunction with short-acting reliever bronchodilators, for relief of symptoms in patients with mild to severe COPD.^{5, 6}

Use a long-acting anticholinergic inhaled bronchodilator as an alternative to, or in conjunction with, a long-acting beta-2 agonist inhaled bronchodilator (LABA) for maintenance treatment of COPD.⁵

Both these classes of long-acting bronchodilator appear to be of similar effectiveness.⁷ Therefore select a long-acting bronchodilator that is effective for the individual patient.⁸

The fixed-dose combinations of fluticasone–salmeterol and budesonide–eformoterol are combinations of glucocorticoids with LABAs, used as long-acting bronchodilators in severe COPD, and either may be used concurrently with aclidinium for severe COPD.⁵

In a randomised double-blind trial (ATTAIN) 272 patients with moderate to severe COPD assigned to 400 microgram aclidinium inhaled twice daily were compared with 276 on placebo over 24 weeks.⁹

Improvement in trough FEV₁ was 128 mL ± 22 mL compared with placebo (p < 0.0001) and there were statistically and clinically significant improvements in the St George’s Respiratory Questionnaire (SGRQ) and the Transitional Dyspnoea Index (TDI).⁹

The level of improvement in FEV₁ is comparable to that seen in trials against placebo for tiotropium³ and glycopyrronium.⁴

An active comparator 6-week clinical trial comparing aclidinium with placebo and tiotropium with placebo found the medicines performed with comparable efficacy.¹⁰

No studies have been conducted comparing aclidinium and glycopyrronium. However, glycopyrronium performs similarly to tiotropium¹¹ and a systematic review and network meta-analysis*¹² of these long-acting anticholinergics suggests they have similar therapeutic effects.¹³

In the pivotal trials, rates of adverse events common with anticholinergics, such as dry mouth and constipation, were low overall (< 2%) and similar in the treatment and placebo arms.^{9, 14} A longer (52 week) study found rates of anticholinergic events of < 3%.¹⁵

In the ATTAIN study UTI was more common in the 400 microgram aclidinium arm (2.2%) compared with placebo (0.7%).⁹

The 6-week trial comparing aclidinium with tiotropium found the two medicines to have similar safety profiles.¹⁰

No studies of efficacy or safety have been carried out for longer than 52 weeks.²

* A network meta-analysis is a comparison of three or more trials that includes indirect comparisons across trials based on a common comparator such as placebo. It is usually less reliable than a traditional meta-analysis.¹²

A network meta-analysis comparing seven long-acting bronchodilator treatments (not including aclidinium) scored indacaterol highest in efficacy, followed by glycopyrronium and tiotropium (18 micrograms), in terms of trough FEV₁ and SGRQ score at 6 months.⁷

Given the similarity in efficacy and safety of the currently listed long-acting anticholinergics, choice is guided by individual effectiveness and the most appropriate inhaler for each patient.⁸

Conduct a therapeutic trial of several weeks for any long-acting bronchodilator to determine effectiveness in improving symptoms in the individual.⁶

Do not prescribe aclidinium for patients with asthma.²

As with other inhaled medicines, aclidinium may cause paradoxical bronchospasm. If this occurs, advise patients to stop aclidinium immediately, use a SABA for relief and institute an alternative therapy.²

Because of its anticholinergic activity, clinical trials of aclidinium did not include patients with certain cardiac disorders.^{9, 14} Use with caution in patients who:²

• have had an MI in the previous 6 months
• have unstable angina
• have arrhythmia diagnosed in the previous 3 months
• have been hospitalised for heart failure (classes III or IV as per the New York Heart Association classification) in the preceding year.

As with all anticholinergics, use with caution in patients with symptomatic prostatic hyperplasia, bladder-neck obstruction or angle-closure glaucoma.²

The medicine contains lactose.²

For further information

For further information on the use of long-acting anticholinergics in COPD refer to the April 2014 full RADAR review on glycopyrronium.¹¹