Aclidinium Bromide: An Alternative Long-Acting Inhaled Anticholinergic in the Management of Chronic Obstructive Pulmonary Disease

Abstract

Aclidinium bromide is a novel, inhaled, long-acting anticholinergic that, when administered at the FDA-approved dose, safely produces clinically and statistically significant bronchodilation and improves health status in patients with moderate to severe COPD. Long-term clinical trials assessing the efficacy and safety of aclidinium are warranted.

Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?

“…With regard to the tolerability profile, it should be noted that receptor selectivity and rapid plasma hydrolysis of aclidinium to inactive metabolites can explain the low incidence of systemic adverse events observed in clinical trials; such events, including anticholinergic side effects, were also generally mild [35, 36] (Table 1). …”

Bronchodilating Drugs for Chronic Obstructive Pulmonary Disease: Current Status and Future Trends

“…34 Clinical trials have demonstrated that aclidinium bromide provides a sustained bronchodilation similar to that observed with tiotropium bromide and confirmed the positive safety profile of aclidinium bromide, particularly in terms of a very low propensity to cause antimuscarinic adverse events. 5 Aclidinium bromide, administered in a multidose DPI (Genuair), is rapidly hydrolyzed once absorbed into the plasma, 31 which enhances its safety profile. 111 However, as its duration of action at the doses employed in phase III clinical trials does not provide a clinically significant bronchodilation over 24 h, inhaled aclidinium bromide has been proposed for registration and approved with a twice daily regimen.…”

“…5 The predetermined dose of aclidinium bromide is 400 μg (equivalent to 343 μg of aclidinium), whereas each delivered dose, which is the amount of drug that leaves the inhaler, contains 375 μg of aclidinium bromide, equivalent to 322 μg of aclidinium. 5 The long-term efficacy and safety of aclidinium bromide were recently investigated in patients with moderate to severe COPD in two double-blind, placebo-controlled 52-week studies. 112 At 12 and 28 weeks, aclidinium bromide significantly improved trough FEV 1 compared with placebo, an effect which was maintained over the 52-week study period.…”

“…1,3,4 They are both available in short-acting and longacting inhaled formulations. 1,3,4 Inhaled mAcChR antagonists approved for the pharmacological maintenance treatment of stable COPD include ipratropium bromide [(1S,5R)-8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate bromide; C 20 H 30 BrNO 3 ] (Figure 2A), 3 oxitropium bromide (1R,2R, 4S,5S,7s,9s)-9-ethyl-7-{[(2S)-3-hydroxy-2-phenylpropanoyl]-oxy}-9-methyl-3-oxa-9-azoniatricyclo[3.3.1.0 2,4 ]nonane bromide; C 19 H 26 BrNO 4 ] (Figure 2B), 3 tiotropium bromide [1a,2b,4b,5a,7b)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0 2,4 ]nonane bromide; C 19 H 22 BrNO 4 S 2 ] (Figure 2C), 3 aclidinium bromide [(3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1azoniabicyclo[2.2.2]octane bromide; C 26 H 30 BrNO 4 S 2 ] (Figure 3A), 5 and glycopyrronium bromide (1,1-dimethylpyrrolidin-1-ium-3-yl) 2cyclopentyl-2-hydroxy-2-phenylacetate bromide; C 19 H 28 BrNO 3 ) (Figure 3B). 6 Ipratropium bromide, the prototype of anticholinergic bronchodilators, is short-acting.…”

“…6 Ipratropium bromide, the prototype of anticholinergic bronchodilators, is short-acting. 3 Tiotropium bromide and glycopyrronium bromide, which are long-acting muscarinic receptor antagonists (LAMA), are administered once a day, 3,6 whereas aclidinium bromide is administered every 12 h. 5 Umeclidinium bromide (4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide) (Figure 3C) has recently been approved for the maintenance treatment of COPD. 7 C 19 H 24 N 2 O 4 ] (Figure 5B).…”