Salmeterol HFA is as effective as salmeterol CFC in children and adults with persistent asthma

Abstract

In accordance with the Montreal Protocol 1987, initiatives to phase out and replace ozone-depleting chlorofluorocarbon (CFC) propellants with non-ozone-depleting propellants in metered-dose inhalers (MDIs) in the treatment of asthma and chronic obstructive pulmonary disease are underway. In view of this, two multi-centre, randomised, parallel-group, double-blind studies were conducted to compare the safety and efficacy of salmeterol xinafoate delivered by an MDI using the hydrofluoroalkane (HFA) 134a propellant with the licensed CFC formulation (Serevent) in asthmatic populations of children (4-11 years) and adults (12 years). Patients on a stable dose of inhaled corticosteroids with a scope for improvement based on mean morning peak expiratory flow (PEF) and symptoms were randomised to receive salmeterol HFA MDI 50 microg twice daily or salmeterol CFC MDI 50 microg twice daily for 12 weeks. The primary efficacy variable was mean morning PEF and secondary variables included other lung function parameters, symptom scores, use of relief medication and safety assessments. The difference between the treatments in adjusted mean morning PEF (salmeterol HFA-salmeterol CFC) were 2.5 and -3.2 L/min for per-protocol populations of children and adults, respectively. The lower limit of 95% confidence intervals for both populations was within the pre-defined limit (-15 L/min) set for non-inferiority. Similar results were observed in intent-to-treat (ITT) populations. In children, the two formulations resulted in a lack of any statistically significant difference in secondary efficacy parameters. A significant difference at endpoint in clinic forced expiratory volume in 1s was reported in favour of the HFA formulation in the adult population, although the magnitude of this effect was not considered clinically significant. The incidences of adverse events (AEs) were similar for both formulations and populations, and no safety concerns were generated. Together these data demonstrate salmeterol HFA MDI to be as effective as salmeterol CFC MDI in adults and children.

Comparison of the systemic pharmacodynamic effects and pharmacokinetics of salmeterol delivered by CFC propellant and non-CFC propellant metered dose inhalers in healthy subjects

“…However, for topically active inhaled drugs such as salmeterol these minor differences in systemic exposure appear not to be clinically significant as there were no differences in either the efficacy or safety of CFC and HFA salmeterol in children or adults. 21 Whatever the underlying reason(s) for the lower systemic exposure seen with the salmeterol HFA MDI in this study, at the therapeutic dose the HFA MDI was associated with similar or less systemic effects and similar efficacy 21 to the CFC MDI. This is comparable to the findings with a number of other compounds, including salbutamol, 26 fluticasone propionate 27 and formoterol 28 where CFC to HFA transition resulted in little or no pharmacokinetic differences and dosage adjustments were not required.…”

“…The present study demonstrates that salmeterol delivered via the HFA-propelled MDI is not asso-ciated with a higher systemic exposure or increased systemic pharmacodynamic effects compared with salmeterol delivered by the CFC-propelled MDI. These data, together with the in vitro pharmaceutical performance 18 and demonstration of noninferiority for clinical efficacy in both adult and paediatric asthma patients, 21 suggest that the salmeterol HFA MDI represents an acceptable replacement for the salmeterol CFC MDI. At the therapeutic dose of salmeterol (50 mg), the systemic pharmacodynamic effects (heart rate, serum potassium, plasma glucose, QTc interval or blood pressure) of salmeterol via HFA and CFC MDIs were equivalent or comparable.…”

“…The purpose of this study was to determine the effect of reformulation of salmeterol in HFA-134a on the systemic pharmacodynamics and pharmacokinetics of salmeterol in man. The results of this study, together with data for in vitro performance 18 and clinical efficacy, 21 can be used to demonstrate the suitability of the salmeterol HFA MDI as a replacement for the existing CFC containing MDI.…”

One hundred years of chronic obstructive pulmonary disease (COPD)

“…More recently, the interest of researches has been focused on inhaled long-acting bronchodilators [161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176] , although some interesting new observations on short-acting bronchodilators have also been published, [177][178][179][180][181][182] particularly the documentation that prescription of ipratropium was associated with increased mortality in both COPD and asthmatic patients. 180 Moreover, there have been two interesting papers on the use of theophylline, now considered a third line agent in the therapy of COPD.…”

Development and performance of a new hydrofluoroalkane (HFA 134a)-based metered dose inhaler (MDI) of salmeterol

“…This is confirmed by the results of the clinical studies demonstrating that salmeterol HFA MDI is as effective as salmeterol CFC MDI. 10 Comparison of particle size distribution data with and without a Volumatic TM spacer…”