SAFETY OF HYDROFLUOROALKANE-134A BECLOMETHASONE DIPROPIONATE EXTRAFINE AEROSOL

Herein we assess the safety of an inhaled formulation of beclomethason e dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assess ed by the incidence of cough and mean forced expiratory volume after I s inhalation) was similar for both BDP and placebo formulated in eith er chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 mu g day(-1)) or CFC-BD P (800 mu g day(-1)) for 14 days and their 24 h urinary free cortisol (UFC) excretion and response to cosyntropin stimulation were measured. There was no difference in UFC between any of the doses of HFA-BDP an d CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was norma l in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 mu g day(-1) and CFC-BDP 800 mu g day(-1) (n = 347), and HFA-BDP 800 mu g day(-1) and CFC-BDP 1500 mu g day(-1) (n = 233). For HFA-BDP at either dose, CFC-BDP 800 mu g day(-1) and HFA-p lacebo. the number of patients with morning plasma cortisol concentrat ions below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 mu g day(-1). The incidence of adverse events was lower in the HFA-BDP g roups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 mu g day(-1), HFA-BDP is at least as well tolera ted as CFC-BDP. Other studies have found that equivalent efficacy is r eached at lower doses of HFA-BDP than CFC-BDP. Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk:benefit ratio than CFC-BDP when used at the recommended lower doses.