Denise Till

Faster onset of bronchodilation with formoterol than with salmeterol in patients with stable, moderate to severe COPD: Results of a randomized, double-blind clinical study

OBJECTIVES To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1 AUC*0-1 h). DESIGN A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study. SETTING Five centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands. PATIENTS Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV1 1.17 L (range 0.56 to 1.77 L). INTERVENTIONS Patients inhaled single doses of formoterol dry powder (12 and 24 mg), single doses of salmeterol (50 and 100 mg) and matching placebo on five separate days. MAIN RESULTS The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1 AUC*0-1 h, showed that formoterol 12 mg was statistically significantly superior to salmeterol 50 mg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol. CONCLUSIONS Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Formoterol delivered via a dry powder inhaler (Aerolizer): results from long-term clinical trials in children.

Summary Over 500 children with asthma, aged 5-12 years, have been treated with formoterol fumarate (Foradilt) delivered via the Aerolizer dry powder inhaler in clinical trials, with treatment periods of up to 15 months. In pivotal double-blind trials, two dose levels, 12 and 24 |ig taken twice daily, provided significant benefit in terms of lung function measurements and symptom control (a lower dose of 6 |ig twice daily appeared insufficient with this formulation). The higher, 24 |ig dose appeared to provide an additional margin of benefit in a subgroup of children with more unstable/severe disease when the results from long-term follow-up (12-15 months) were analysed. Formoterol was shown to have a good safety profile when taken as regular maintenance treatment and when used as rescue medication by patients already receiving formoterol as regular maintenance treatment. In this flexible regimen, with formoterol used for rescue and maintenance, the overall daily intake of formoterol was low, with 96.1% of all treatment days (n = 2452) covered by a total daily dose (regular + rescue) of 48 |ig (four doses) or less. There was no increase in the average daily intake of rescue formoterol over time. The clinical efficacy associated with this regimen was maintained over time and, in the case of morning peak expiratory flow rate, steadily improved over time. The Foradil Aerolizer inhalation system is simple to use and has a low resistance to inspiratory airflow that maximises the patients control over dosing, while minimising the risk of under- and overdosing. These features may be especially valuable in a young patient population.

Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction in children.

BACKGROUND Exercise-induced bronchoconstriction (EIB) is common, particularly in children. OBJECTIVES To compare the protective effect of single doses of formoterol fumarate via Aerolizer with placebo and albuterol in children with EIB. METHODS In this randomized, double-blind, double-dummy, crossover trial, 23 children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180 microg; or placebo at 4 separate visits. Protection against EIB was evaluated as the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) from the preexercise value after exercise challenge tests (6-minute treadmill) conducted 15 minutes and 4, 8, and 12 hours after administration of the dose. RESULTS The maximum percentage decrease in FEV1 after the 4-hour exercise test (primary efficacy variable) was significantly less for formoterol, 12 and 24 microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010, respectively); albuterol was not significantly different from placebo. Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and .001, respectively), with a smaller difference between albuterol and placebo (P = .045). Rescue medication use and a high dropout rate may have biased treatment differences at later time points. Protection against EIB (<20% maximum decrease in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of 23 children with formoterol, 12 and 24 microg, respectively, compared with 8 (35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS Single doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in children, affording a statistically significantly greater protective effect than placebo or albuterol.

FEV1 reversibility does not adequately predict effect of formoterol via Aerolizer® in chronic obstructive pulmonary disease

Evaluation of patients with chronic obstructive pulmonary disease (COPD) often includes the use of post‐bronchodilator reversibility testing to guide treatment decisions. Recommendations for reversibility testing differ and there is no universally accepted method or outcome criterion.

Inhalation devices for long-acting β2-agonists: efficiency and ease of use of dry powder formoterol inhalers for use by patients with asthma and COPD

ABSTRACT Background: Since the long-acting β2-agonist bronchodilator, formoterol, first became available for the treatment of subjects with asthma or chronic obstructive pulmonary disease (COPD), generic forms of this agent have been launched in a variety of devices. It is timely to review the characteristics of the original dry powder delivery device, the single-dose Aerolizer*, its in vitro performance and its comparability with other inhaler devices that are now available for delivery of formoterol. Scope: This review focuses on the performance of the formoterol Aerolizer inhaler in comparison with other inhalers. Publically available data (PubMed) on the device performance characteristics of the Aerolizer were reviewed and summarized, together with the results of comparative studies performed by the authors. Published studies (PubMed) on patient handling and inhaler technique that include the Aerolizer are described and studies comparing the clinical effect of formoterol in the Aerolizer with formoterol delivered via other devices were reviewed and are summarized. Findings: The Aerolizer performs consistently in dosing efficiency across a range of inspiratory flow rates, suggesting its suitability for use by patients with differing inspiratory flow abilities. The single-dose, capsule-based nature of the device provides patients with obvious feedback on whether the drug has been taken successfully and the Aerolizer has been shown to be one of the more easily used devices in comparative patient handling studies. Studies comparing the clinical effect of formoterol delivered by different inhalation devices show that formoterol via Aerolizer has an equivalent therapeutic effect. Conclusion: Judged on the basis of dosing efficiency, ease of use and clinical equivalence, formoterol Aerolizer remains a useful option in the management of patients with asthma or COPD.