Fluticasone propionate/formoterol: A fixed-combination therapy with flexible dosage

Abstract

International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β 2 -agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studies demonstrate that the fixed combination of fluticasone propionate/formoterol in a single inhaler is effective in terms of lung function and symptom control. These studies highlight the dose flexibility, safety and tolerability of this new inhaled combination. These characteristics meet the recommendations of international guidelines, and the preferences of respiratory physicians who identified these aspects as critical components of a successful asthma therapy. Combination of fluticasone propionate/formoterol in a single inhaler provides potent anti-inflammatory activity of fluticasone propionate and rapid onset of action of the β 2 -agonist formoterol making this association a viable treatment option both in terms of effectiveness and compliance.

Therapeutic novelties of inhaled corticosteroids and bronchodilators in asthma

“…Anti-inflammatory power of ICS and rapid bronchodilator activity of LABA are mentioned by physicians as two of the most important properties for asthma treatment [71].…”

“…formoterol) cause more phosphorylation and internalization of the receptor than low efficacy agonists (e.g. salmeterol) [71]. However, high-efficacy agonists do not necessarily cause desensitization, as once assumed [101].…”

“…Moreover, lowefficacy ligands have a reduced capability of receptor activation, which may not be sufficient to generate a full response, even at full occupancy of available receptors. High efficacy agonists instead allow even a small percentage of receptors to generate a full response, thus leaving a sufficient amount of spare receptors available [71].…”

“…The relative receptor-binding affinity (versus dexamethasone) of fluticasone is second only to mometasone however, the inhalation halflife of mometasone is much lower than that of fluticasone [71].…”

“…Between the two available inhaled LABA, formoterol demonstrates higher intrinsic efficacy than salmeterol when stimulating cAMP synthesis. Having salmeterol a far lower intrinsic efficacy, it appears as a partial agonist [71]. Highefficacy agonists (e.g.…”