title: Safety of hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol.
abstract: Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation) was similar for both BDP and placebo formulated in either chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 micrograms day-1) or CFC-BDP (800 micrograms 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 and CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 (n = 347), and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 (n = 233). For HFA-BDP at either dose, CFC-BDP 800 micrograms day-1 and HFA-placebo, the number of patients with morning plasma cortisol concentrations below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 micrograms day-1. The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 micrograms day-1, HFA-BDP is at least as well tolerated as CFC-BDP. Other studies have found that equivalent efficacy is reached 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.
authors.affiliation: Department of Medicine, University of Western Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
authors.forename: W F
authors.initials: WF
authors.lastname: Young
authors.forename: A B
authors.initials: AB
authors.lastname: Grossman
authors.forename: D
authors.initials: D
authors.lastname: Donnell
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants / Q000009:adverse effects*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000652:urine; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use; D017402:Chlorofluorocarbons / Q000009:adverse effects; D003366:Cosyntropin; D003371:Cough / Q000139:chemically induced*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects*; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D017402:Chlorofluorocarbons; D003366:Cosyntropin; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; C094049:apaflurane; D005466:Fluorocarbons