Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group.
The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy.
Kupele Strbske Pleso, Sanatorium Helios, Slovak Republic.
D
D
Salat
D
D
Popov
A P
AP
Sykes
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants / Q000009:adverse effects / Q000493:pharmacokinetics*; D000368:Aged; D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D017402:Chlorofluorocarbons / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000502:physiology; D013810:Therapeutic Equivalency; D016896:Treatment Outcome; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000420:Albuterol; D001993:Bronchodilator Agents; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons