Pharmacological Class:
Anticholinergic.

Active Ingredient(s):
Aclidinium bromide 400mcg/actuation; dry powder for oral inhalation.

Company
Forest Laboratories

Indication(s):

Long-term, maintenance treatment of bronchospasm associated with COPD, ­including chronic bronchitis and emphysema.

Pharmacology:

Aclidinium bromide is a long-acting antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharma­cological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The bronchodilation following inhalation of aclidinium bromide is predominantly a site-specific effect.

Clinical Trials:

The Tudorza Pressair clinical ­development program included a dose-ranging trial (Trial A) for nominal dose selection and three confirmatory trials (Trials B, C, and D). Trial A was a randomized, double-blind, placebo-controlled, active-controlled, cross-over trial with 7-day treatment periods separated by 5-day washout periods. Trial A enrolled 79 patients who had a clinical diagnosis of COPD, were ≥40 years of age, had a history of smoking at least 10 pack-years, had a forced expiratory ­volume in one second (FEV1) of at least 30% and less than 80% of predicted normal value, and a ratio of FEV1 over forced vital capacity (FEV1/FVC) of less than 0.7. Trial A included Tudorza Pressair doses of 400mcg, 200mcg and 100mcg twice daily, formoterol active control, and placebo. Trial A demonstrated that the effect on trough FEV1 and serial FEV1 in patients treated with the Tudorza Pressair 100mcg twice daily and 200mcg twice daily doses was lower compared to patients treated with the Tudorza Pressair 400mcg twice daily dose.

Trials B, C, and D were three randomized, double-blind, placebo-controlled trials in patients with COPD. Trials B and C were 3 months in duration, and Trial D was 6 months in duration. These trials enrolled 1,276 patients who had a clinical diagnosis of COPD, were ≥40 years of age, had a history of smoking at least 10 pack-years, had an FEV1 of at least 30% and less than 80% of predicted normal value, and a ratio of FEV1/FVC of less than 0.7. These clinical trials eva luated Tudorza Pressair 400mcg twice daily (636 patients) and placebo (640 patients). Tudorza Pressair 400mcg resulted in statistically significantly greater bronchodilation as measured by change from baseline in morning pre-dose FEV1 at 12 weeks (the primary efficacy endpoint) compared to placebo in all three trials.
 
Serial spirometric eva luations were performed throughout daytime hours in a subset of patients in the three trials. Improvement of lung function was maintained for 12 hours after a single dose and was consistent over the 3- or 6-month treatment period. Mean peak improvements in FEV1, for Tudorza Pressair relative to baseline were ­assessed in all patients in trials B, C and D after the first dose on day 1 and were similar at week 12. In Trials B and D but not in Trial C, patients treated with Tudorza Pressair used less daily ­rescue albuterol during the trial compared to patients treated with placebo.

Legal Classification:

Rx

Adults:

400mcg twice daily.

Children:

Not established.

Warnings/Precautions:

Not for initial treatment of acute episodes of bronchospasm. Narrow-angle glaucoma. Urinary retention. Milk ­protein sensitivity. Labor & delivery. Pregnancy (Cat. C). Nursing mothers.

Interaction(s)

Avoid concomitant anticholinergic agents.

Adverse Reaction(s)

Headache, nasopharyngitis, cough; hypersensitivity reactions (discontinue if occurs), paradoxical bronchospasm possible.

How Supplied:

Dry powder inhaler—60 doses

LAST UPDATED:

12/10/2012