Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary disease: a review.

The inhaled, long-acting muscarinic antagonist, aclidinium bromide, was indicated in July 2012 in Europe and the USA for the maintenance of bronchodilator treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults. Although initially investigated as a once-daily agent, a lower than expected improvement in trough forced expiratory volume over 1 s prompted re-evaluation as a twice-daily (b.i.d.) regimen. The dose approved for use in Europe, 400 μg b.i.d., achieved statistically significant improvements in lung function, reductions in breathlessness, and improved health-related quality of life (HRQoL) for up to 24 weeks of treatment in the pivotal phase 3 trials (AClidinium in Chronic Obstructive Respiratory Disease I [ACCORD COPD I] [12 weeks] and Aclidinium To Treat Airway obstruction In COPD patieNts [ATTAIN] [24 weeks]). These improvements were sustained during maintenance therapy of up to 52 weeks. Pooled data from the ATTAIN and ACCORD studies (both included a placebo arm) showed that exacerbation frequency was significantly reduced, although neither study was prospectively designed to evaluate this endpoint. Pharmacological and preclinical studies demonstrated the low systemic bioavailability of aclidinium and the low propensity to induce cardiac arrhythmias. The good tolerability of aclidinium was confirmed in the phase 3 program up to 52 weeks of treatment. The adverse event (AE) profile of the approved dose, 400 μg b.i.d., was similar to that of placebo, with a low incidence of anticholinergic and cardiac AEs. Aclidinium is delivered via the Genuair(®) multidose dry powder inhaler (Almirall Sofotec GmBH, Bad Homburg, Germany). The device is simple to use with multiple feedback mechanisms ensuring consistent dose delivery. In summary, aclidinium 400 μg b.i.d. is effective for the treatment of patients with COPD, offering improvements in lung function, breathlessness, and HRQoL, with a good safety profile and a low incidence of anticholinergic and cardiac AEs.