A Comparison of Fluticasone Propionate
Objective: This study was designed to demonstrate equivalent efficacy and similar tolerability of a fluticasone propionate (FP) 50µg hydrofluoroalkane HFA 134a formulation with that of the established chlorofluorocarbon (CFC) 50µg formulation in adult patients with asthma.
Design and Setting: The study was a multicentre, randomised, double-blind, parallel-group design conducted in general practice centres in the UK.
Patients: Adult patients with mild asthma who were receiving inhaled ß2-agonists as required and up to 400µg of inhaled corticosteroid.
Interventions: 178 patients were randomised to receive FP 100µg twice daily via a pressurised metered-dose inhaler (pMDI) propelled by HFA 134a and 173 patients to FP administered via a CFC pMDI for 4 weeks.
Results: Fluticasone propionate significantly improved lung function in both groups. Mean morning peak expiratory flow (PEF) increased by 17 L/min in the HFA134a group and 19 L/min in the CFC group, with a mean treatment difference between the two formulations (HFA-CFC) of -2 L/min, with a 90% confidence interval of (-8; +4 L/min), well within the pre-set equivalence limit of ±15L/min. A comparable increase in evening PEF, symptom-free days and nights, days and nights with no rescue medication and clinic lung function was seen between the groups. The frequency of adverse events was low and equally distributed. Neither treatment had any significant effect on morning serum cortisol levels and there were no reported incidences of bronchospasm.
Conclusions: The FP 50µg HFA134a pMDI is as effective and well tolerated as the CFC product. It is a suitable replacement for the 50µg CFC pMDI product at a microgram equivalent dose.
The pressurised metered-dose inhaler (pMDI) remains the most widely prescribed device for the delivery of asthma medications. Experienced users are well satisfied with many features of the device. Some patients do, however, have difficulties in coordinating inhalation with actuation, but this can be overcome by use of a spacer device that also serves to reduce the oropharyngeal impact of a high velocity aerosol spray and hence minimises the risk of local adverse effects observed with inhaled corticosteroids, such as candidiasis and hoarseness. Historically, chlorofluorocarbons (CFCs) 11and 12 have been used as propellants in the pMDI. In recent years, CFCs have been shown to reduce stratospheric ozone, and although the contribution from medicinal aerosols has been minimal, the pharmaceutical industry, consistent with environmental legislation, has been searching for an alternative, environmentally friendly replacement propellant that is well tolerated in patients. HFA134a, a hydrofluoroalkane, has been chosen as an alternative propellant for the pMDI. Extensive preclinical and clinical testing has demonstrated that HFA 134a behaves like an inert gas and has a similar tolerability profile in humans to CFC propellants 11 and 12.
Fluticasone propionate (FP) is a topically active corticosteroid that shows little or no systemic activity after oral administration. Fluticasone propionate is available in the pMDI, nebulised and dry powder formulations (Diskhaler and Diskus/Accuhaler Glaxo Wellcome). The pMDI formulation includes the 50, 125 and 250µg per actuation strength products recognising the need to treat different severities of asthma with different doses of inhaled corticosteroid. Previous studies have demonstrated clinical equivalence between the CFC-containing pMDI and powder formulations for FP at a microgram equal dose. Fluticasone propionate has recently been reformulated in an HFA 134a-containing pMDI without added excipients at the same strengths. The pharmaceutical and pharmacokinetic performance characteristics of the FP HFA 134a pMDI have been shown to be similar to their CFC-containing counterparts. Furthermore, clinical equivalence has also been shown for both the 125 and 250µg strength FPHFA 134a formulations compared with their CFC counterparts in patients with moderate to severe asthma.
This study was designed to demonstrate equivalent efficacy and similar tolerability of the lower strength FP 50µg HFA134a formulation, delivered as a 100µg twice-daily dose, with that of the established CFC 50µg formulation in patients with mild asthma.
Objective: This study was designed to demonstrate equivalent efficacy and similar tolerability of a fluticasone propionate (FP) 50µg hydrofluoroalkane HFA 134a formulation with that of the established chlorofluorocarbon (CFC) 50µg formulation in adult patients with asthma.
Design and Setting: The study was a multicentre, randomised, double-blind, parallel-group design conducted in general practice centres in the UK.
Patients: Adult patients with mild asthma who were receiving inhaled ß2-agonists as required and up to 400µg of inhaled corticosteroid.
Interventions: 178 patients were randomised to receive FP 100µg twice daily via a pressurised metered-dose inhaler (pMDI) propelled by HFA 134a and 173 patients to FP administered via a CFC pMDI for 4 weeks.
Results: Fluticasone propionate significantly improved lung function in both groups. Mean morning peak expiratory flow (PEF) increased by 17 L/min in the HFA134a group and 19 L/min in the CFC group, with a mean treatment difference between the two formulations (HFA-CFC) of -2 L/min, with a 90% confidence interval of (-8; +4 L/min), well within the pre-set equivalence limit of ±15L/min. A comparable increase in evening PEF, symptom-free days and nights, days and nights with no rescue medication and clinic lung function was seen between the groups. The frequency of adverse events was low and equally distributed. Neither treatment had any significant effect on morning serum cortisol levels and there were no reported incidences of bronchospasm.
Conclusions: The FP 50µg HFA134a pMDI is as effective and well tolerated as the CFC product. It is a suitable replacement for the 50µg CFC pMDI product at a microgram equivalent dose.
The pressurised metered-dose inhaler (pMDI) remains the most widely prescribed device for the delivery of asthma medications. Experienced users are well satisfied with many features of the device. Some patients do, however, have difficulties in coordinating inhalation with actuation, but this can be overcome by use of a spacer device that also serves to reduce the oropharyngeal impact of a high velocity aerosol spray and hence minimises the risk of local adverse effects observed with inhaled corticosteroids, such as candidiasis and hoarseness. Historically, chlorofluorocarbons (CFCs) 11and 12 have been used as propellants in the pMDI. In recent years, CFCs have been shown to reduce stratospheric ozone, and although the contribution from medicinal aerosols has been minimal, the pharmaceutical industry, consistent with environmental legislation, has been searching for an alternative, environmentally friendly replacement propellant that is well tolerated in patients. HFA134a, a hydrofluoroalkane, has been chosen as an alternative propellant for the pMDI. Extensive preclinical and clinical testing has demonstrated that HFA 134a behaves like an inert gas and has a similar tolerability profile in humans to CFC propellants 11 and 12.
Fluticasone propionate (FP) is a topically active corticosteroid that shows little or no systemic activity after oral administration. Fluticasone propionate is available in the pMDI, nebulised and dry powder formulations (Diskhaler and Diskus/Accuhaler Glaxo Wellcome). The pMDI formulation includes the 50, 125 and 250µg per actuation strength products recognising the need to treat different severities of asthma with different doses of inhaled corticosteroid. Previous studies have demonstrated clinical equivalence between the CFC-containing pMDI and powder formulations for FP at a microgram equal dose. Fluticasone propionate has recently been reformulated in an HFA 134a-containing pMDI without added excipients at the same strengths. The pharmaceutical and pharmacokinetic performance characteristics of the FP HFA 134a pMDI have been shown to be similar to their CFC-containing counterparts. Furthermore, clinical equivalence has also been shown for both the 125 and 250µg strength FPHFA 134a formulations compared with their CFC counterparts in patients with moderate to severe asthma.
This study was designed to demonstrate equivalent efficacy and similar tolerability of the lower strength FP 50µg HFA134a formulation, delivered as a 100µg twice-daily dose, with that of the established CFC 50µg formulation in patients with mild asthma.