Salmeterol/Fluticasone Propionate

Abstract

Salmeterol/fluticasone propionate (Seretide/Advair Diskus® [dry powder inhaler] or Seretide/Advair® inhalation aerosol [metered-dose inhaler]) is a fixed-dose combination inhalation agent containing a long-acting β₂-adrenoceptor agonist (LABA) plus a corticosteroid. In patients with symptomatic asthma, twice-daily salmeterol/fluticasone propionate maintenance therapy improves lung function and asthma symptoms to a greater extent than monotherapy with inhaled corticosteroids (ICS), such as fluticasone propionate, oral montelukast with or without fluticasone propionate, or sustained-release theophylline plus fluticasone propionate. The greater efficacy achieved with salmeterol/fluticasone propionate versus fluticasone propionate alone was sustained for 1 year in a well designed trial. Salmeterol/fluticasone propionate is also associated with a corticosteroid-sparing effect. Results of studies comparing fixed dosages of salmeterol/fluticasone propionate with formoterol/budesonide in adults and adolescents are equivocal. Twice-daily salmeterol/fluticasone propionate is associated with clinically meaningful improvements from baseline in health-related quality of life (HR-QOL), and improvements were greater than those reported with fluticasone propionate alone. Salmeterol/fluticasone propionate is generally well tolerated in adults, adolescents and children aged 4–11 years, and the fixed-combination inhaler ensures the appropriate use of a LABA in combination with an ICS. In cost-utility analyses in patients with uncontrolled asthma, salmeterol/fluticasone propionate compares favourably with fluticasone propionate alone or oral montelukast. Thus, salmeterol/fluticasone propionate provides an effective, well tolerated and cost-effective option for maintenance treatment in patients with asthma. Salmeterol is a selective LABA, which causes bronchodilation and inhibition of the release of hypersensitivity mediators from mast cells. The corticosteroid fluticasone propionate inhibits eosinophil activation and the subsequent release of inflammatory mediators. Coadministration of inhaled salmeterol and fluticasone propionate produce similar effects to those observed when the two agents are administered separately, and in vitro studies suggest beneficial additive or synergistic effects. The pharmacokinetics of concomitant salmeterol and fluticasone propionate are generally similar to those recorded following individual administration, with no systemic pharmacokinetic interaction. The action of inhaled salmeterol or fluticasone propionate is local to the lung, so plasma levels are not an indication of therapeutic effect. Salmeterol is extensively metabolized via hydroxylation, and fluticasone propionate is principally metabolized to an inactive metabolite by the cytochrome P450 (CYP) isoenzyme CYP3A4. Salmeterol/fluticasone propionate maintenance therapy improves lung function and asthma symptoms to a greater extent than monotherapy with ICS or montelukast in adults, adolescents and children aged 4–11 years with symptomatic asthma. In well designed, long-term studies of up to 1 year, twice-daily salmeterol/fluticasone propionate achieved better asthma control than twice-daily fluticasone propionate alone. The combination of salmeterol/fluticasone propionate has a corticosteroid-sparing effect, with twice-daily salmeterol/fluticasone propionate 50 μg/100 μg maintaining a level of control that was not significantly different to that achieved with twice-daily fluticasone propionate 250 μg. Twice-daily salmeterol/fluticasone propionate in a single inhaler was as effective as the same dosages of twice-daily salmeterol plus fluticasone propionate administered concurrently in separate inhalers. Results of studies comparing salmeterol/fluticasone propionate with formoterol/budesonide maintenance therapy in adults and adolescents have been mixed, with some showing similar efficacy and others demonstrating greater efficacy with either agent. Twice-daily salmeterol/fluticasone propionate provided more effective control of asthma symptoms than twice-daily sustained-release theophylline plus fluticasone propionate. Clinically meaningful improvements from baseline in HR-QOL have been observed in asthmatics treated with twice-daily salmeterol/fluticasone propionate. Asthma quality-of-life questionnaire scores were improved more with salmeterol/fluticasone propionate than with fluticasone propionate alone or oral montelukast, but results from HR-QOL studies comparing salmeterol/fluticasone propionate with formoterol/budesonide were mixed. In patients with uncontrolled asthma, salmeterol/fluticasone propionate was cost effective compared with monotherapy with fluticasone propionate or oral montelukast, with regard to the incremental cost per quality-adjusted life-year gained, per symptom- or rescue-free day, or cost per 12% improvement in forced expiratory volume in 1 second, but results of studies comparing salmeterol/fluticasone propionate with formoterol/budesonide were mixed. Salmeterol/fluticasone propionate is generally well tolerated in adults, adolescents and children and, overall, the most frequent treatment-related adverse effects include upper respiratory tract infection, pharyngitis, headaches and throat irritation/cough. In clinical trials, the incidence of treatment-related effects was generally similar to that of comparators, including fluticasone propionate alone, montelukast or formoterol/budesonide. In a well designed, 12-week study in asthmatic children aged 6–14 years, the most common adverse event associated with salmeterol/fluticasone propionate or oral motelukast was headache. The incidence of treatment-related adverse effects was 2% in each treatment group, with serious events reported in zero and three patients, respectively. Urinary cortisol excretion over 24 hours remained within normal limits after 12 weeks of treatment with...