Review of therapeutically equivalent alternatives to short acting β₂ adrenoceptor agonists delivered via chlorofluorocarbon-containing inhalers

Abstract

BACKGROUND To study the transition from metered dose inhalers using chlorofluorocarbons as propellants (CFC-MDIs) to non-CFC containing devices, a systematic review was conducted of clinical trials which compared the delivery of salbutamol and terbutaline via CFC-MDIs and non-CFC devices.

METHODS Papers were selected by searching electronic databases (Medline, Cochrane, and BIDS) and further information and studies were sought from pharmaceutical companies. The studies were assessed for their methodological quality.

RESULTS Fifty three relevant trials were identified. Most were scientifically flawed in terms of study design, comparison of inappropriate doses, and insufficient power for the determination of therapeutic equivalence. Differences between inhaler devices were categorised according to efficacy and potency. Most trials claimed to show therapeutic equivalence, usually for the same doses from the different devices. Two commercially available salbutamol metered dose inhalers using a novel hydrofluorocarbon HFC-134a as propellant were equally as potent and efficacious as conventional CFC-MDIs, as were the Rotahaler and Clickhaler dry powder inhalers (DPIs). Evidence suggests that a dose of 200 μg salbutamol via CFC-MDI may be substituted with 200 μg and 400 μg of salbutamol via Accuhaler and Diskhaler DPIs, respectively. Terbutaline delivered via a Turbohaler DPI is equally as potent and efficacious as terbutaline delivered via a conventional CFC-MDI.

CONCLUSIONS When substituting non-CFC containing inhalers for CFC-MDIs, attention must be given to differences in inhaler characteristics which may result in variations in pulmonary function.