Safety of long-term treatment with HFA albuterol

Background: Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public healt h concerns. Albuterol has been reformulated in the non-ozone-depleting prop ellant, hydrofluoroalkane-134a (HFA albuterol), Objectives: The primary objective was to compare the safety of HFA albutero l to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics, Bronchodilator effica cy of the two products was assessed as a secondary objective. Methods: The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom contr ol were combined. Patients took two puffs bid of either HFA albuterol or CF C albuterol for 1 year, Additional puffs of study drug were allowed as need ed to control asthma symptoms. Adverse events were recorded at clinic visit s. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy var iables, based on FEV1 response to study drug, were proportion of responders , time to onset of effect, peak percent change, time to peak effect, durati on of effect, and area under the curve. Differences between products and ch anges over time in efficacy variables were assessed using an analysis of va riance model. Regression analyses with FEV1 as a covariate were performed p ost-hoc to analyze changes in bronchodilator efficacy over time. Results: Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total repor ted adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reporte d more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration, Adverse events attributed to study drug use w ere infrequent, No serious adverse events were related to study drug use. P redose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12, The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inh aled corticosteroids, nasal corticosteroids, or theophylline did not explai n the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12, The change in predo se FEV1 did not entirely account for the reduced bronchodilator efficacy ov er time. Conclusions: HFA albuterol has a safety profile similar to that of CFC albu terol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, b ut bronchodilator efficacy decreased for both products with 1 year of use.