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Aclidinium Bromide Inhalation Powder (Tudorza™ Pressair™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
A NEW LONG-ACTING INHALED MUSCARINIC ANTAGONIST (LAMA) has been approved for treating chronic obstructive pulmonary disease (COPD). The product is marketed by Forest Laboratories as Tudorza™ Pressair™.
Aclidinium is indicated for the long-term maintenance treatment of bronchospasm associated with COPD and emphysema.1
The recommended dose is one inhalation (400 mcg) twice daily.1
Aclidinium is supplied as a multi-dose powder with 60 metered doses. Each actuation provides 400 mcg.
Aclidinium is rapidly metabolized into active metabolites, therefore, it has very low systemic exposure.
Aclidinium is dosed twice daily in contrast to tiotropium, which is dosed once daily.
Similar to tiotropium, aclidinium bromide exerts its pharmacologic effect by inhibition of the M3 receptor, resulting in bronchodilation. The efficacy and safety of aclidinium in COPD was evaluated in a dose-ranging study and three confirmation studies. A dose of 400 mcg twice daily is the optimal and FDA-approved dose. In the three randomized, double-blind, placebo-controlled, confirmatory studies, COPD subjects were randomized to aclidinium 400 mcg twice daily (n = 636) or placebo (n = 640). These subjects were 40 years of age or older, with a history of smoking at least 10 pack-years, and had an FEV1 between 30% and 80% of predicted normal value and an FEV1/FVC of less than 0.7. Two studies were for 12 weeks and one for 24 weeks. Baseline FEV1 values for aclidinium ranged from 1.25 L to 1.51 L and 1.38 to 1.50 L for placebo. Least square mean differences (95% CI) from baseline at week 12 were 0.12 L (0.08, 0.16), 0.07 L (0.03, 0.12), and 0.11 L (0.07, 0.14) for the three studies. In the 24-week study, treatment difference was maintained, 0.11 L (0.07, 0.14) at week 12 and 0.13 (0.09, 0.17) at week 24.1 A difference of 0.1 L or greater is considered as clinically significant.
Aclidinium appears to be well tolerated. Common adverse events (< 7%) were headache, nasopharyngitis, and cough. The adverse events reported were similar during the long-term (40-52 weeks) safety trials.1 Aclidinium has also been reported to improve health status (St. George’s Respiratory Questionnaire) and dyspnea (Transitional Dyspnea Index).2 Data from the preclinical evaluation indicated that at equipotent doses, aclidinium was less effective than tiotropium.3 These data suggest that more than a once-daily dosing would be required. In a small (n = 30) Phase 2a study, aclidinium (400 mcg twice daily) was reported to be comparable to tiotropium (18 mcg once daily), but with evidence of favorable benefit for aclidinium during the nighttime period.4
Aclidinium is the second LAMA to be approved and is an alternative to tiotropium. These agents are indicated for COPD patients with moderate-to-severe disease.5
1. Tudorza Pressair Prescribing Information. St. Louis, MO: Forest Pharmaceuticals, Inc.; July 2012.
2. Jones PW, et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: The ATTAIN study. Eur Respir J 2012; Mar 22. [Epub ahead of print.]
3. Casarosa P, et al. Preclinical evaluation of long-acting muscarinic antagonists: Comparison of tiotropium and investigational drugs. J Pharmacol Exp Ther 2009; 330:660-668.
4. Fuhr R, et al. Efficacy of aclidinium bromide 400 mcg twice daily compared with placebo and tiotropium in patients with moderate to severe COPD. Chest 2012; 141:745-752.
5. Gobal Initiative for Chronic Obstructive Lung Disease: Management Reference for Chronic Obstructive Pulmonary Disease. www.goldcopd.org. Accessed August 4, 2012.