Foster Mechanism of Action

Pharmacology: Pharmacodynamics: Beclomethasone dipropionate given by inhalation at recommended doses has a glucocorticoid antiinflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma with less adverse effects than when corticosteroids are administered systemically.
Formoterol is a selective beta₂-adrenergic agonist that produces relaxation of bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect sets in rapidly, within 1-3 minutes after inhalation, and has a duration of 12 hours after a single dose.
Clinical Results: Asthma: Clinical efficacy for maintenance therapy: In clinical trials in adults, the addition of formoterol to beclometasone dipropionate improved asthma symptoms and lung function and reduced exacerbations.
In a 24-week study the effect on lung function of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) was at least equal to that of the free combination of beclometasone dipropionate and formoterol, and exceeded that of beclometasone dipropionate alone.
Clinical efficacy for maintenance and reliever therapy: In a 48-week parallel group study involving 1701 asthma patients, the efficacy of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) administered as maintenance (1 inhalation BID) and reliever therapy (up to a total of 8 puffs per day) was compared to Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) administered as maintenance therapy (1 inhalation BID) plus as needed salbutamol, in adult patients with uncontrolled moderate to severe asthma. The results demonstrated that Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) used as maintenance and reliever therapy significantly prolonged the time to first severe exacerbation (*) when compared with Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) used as maintenance plus as needed salbutamol (p <0.001 for both ITT and PP population). The rate of severe asthma exacerbations per patients/year, was significantly reduced in the maintenance and reliever therapy group compared to salbutamol group: 0.1476 vs. 0.2239 respectively (statistically significant reduction: p <0.001). Patients in the Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) maintenance and reliever group achieved a clinically meaningful improvement in asthma control. The mean number of inhalations/day of reliever medication and the proportion of patients using reliever medication decreased similarly in both groups.
Note*: severe exacerbations were defined as deterioration in asthma resulting in hospitalisation or emergency room treatment, or resulting in the need for systemic steroids for more than 3 days.
In another clinical study, a single dose of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) 100/6 mcg provided a quick bronchodilation effect and a rapid relief from dyspnea symptoms similar to that of salbutamol 200 mcg/dose in asthmatic patients when metacholine challenge is used to induce bronchoconstriction.
COPD: In two 48-weeks studies, the effects on lung function and the rate of exacerbation (defined as courses of oral steroids and/or course of antibiotics and/or hospitalisations) in patients with severe COPD (30% FEV₁% <50%) was evaluated.
One pivotal trial showed a significant improvement in lung function (primary endpoint change in pre-dose FEV₁) compared to formoterol after 12 weeks of treatment (adjusted mean difference between Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) and formoterol: 69 mL) as well as at each clinic visit during the whole treatment period (48 weeks). The study demonstrated that the mean number of exacerbations per patient/year (exacerbation rate, co-primary endpoint) was statistically significantly reduced with Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) as compared with formoterol treatment (adjusted mean rate 0.80 compared with 1.12 in the formoterol group, adjusted ratio 0.72, p <0.001) over 48 weeks treatment period in a total of 1199 patients with severe COPD. In addition, Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) statistically significantly prolonged the time to first exacerbation compared to formoterol. The superiority of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) versus formoterol was also confirmed in terms of exacerbation rate in subgroups of patients taking (around 50% in each treatment arm) or not Tiotropium Bromide as concomitant medication.
The other pivotal study, which was a three arm, randomised, parallel group study in 718 patients, confirmed the superiority of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) versus formoterol treatment in terms of change in pre-dose FEV₁ at the end of treatment (48 weeks) and demonstrated the non-inferiority of Beclomethasone dipropionate/Formoterol fumarate dihydrate (Foster) compared to budesonide/formoterol fixed dose combination on the same parameter.
Pharmacokinetics: Beclometasone is stated to be readily absorbed from sites of local application, and rapidly distributed to all body tissues. It is metabolized principally in the liver, but also in other tissues including gastrointestinal tract and lung; enzymatic hydrolysis rapidly produces the monopropionate (which has some glucocorticoid activity), and more slowly, the free alcohol, which is virtually devoid of activity. Only a small proportion of an absorbed dose is excreted in urine, the remainder being excreted in the feces mainly as metabolites.
Inhaled formoterol is rapidly absorbed. It is largely metabolized by glucuronidation and o-demethylation, with about 10% being excreted as unchanged drug. The terminal elimination half-life after inhalation is estimated to be 8 hours.