Background: Chlorofluorocarbons (CFCs) used as
propellants in metered-dose inhalers deplete stratospheric ozone, which
results in serious public health concerns. Albuterol has been
reformulated in the non-ozone-depleting propellant,
hydrofluoroalkane-134a (HFA albuterol).
The primary objective was to compare the safety of HFA albuterol to an
albuterol product formulated in chlorofluorocarbon propellants (CFC
albuterol) during 1 year of treatment in asthmatics. Bronchodilator
efficacy of the two products was assessed as a secondary
Methods: The results from two open-label,
parallel-group trials of similar design in asthmatics requiring
short-acting β-agonists for symptom control were combined. Patients
took two puffs bid of either HFA albuterol or CFC albuterol for 1 year.
Additional puffs of study drug were allowed as needed to control asthma
symptoms. Adverse events were recorded at clinic visits. Patients
self-administered study drug at quarterly visits and underwent serial
spirometry during a 6-h period postdose. Bronchodilator efficacy
variables, based on FEV1 response to study drug, were
proportion of responders, time to onset of effect, peak percent change,
time to peak effect, duration of effect, and area under the curve.
Differences between products and changes over time in efficacy
variables were assessed using an analysis of variance model. Regression
analyses with FEV1 as a covariate were performed post-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 reported adverse events were similar for
the two treatments. Differences in only four individual adverse events
were noted: the HFA albuterol group reported more gastroenteritis and
dizziness; the CFC albuterol group reported more epistaxis and
expectoration. Adverse events attributed to study drug use were
infrequent. No serious adverse events were related to study drug use.
Predose 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 inhaled corticosteroids, nasal
corticosteroids, or theophylline did not explain the increase in
predose FEV1 over time and did not protect patients from
developing reduced bronchodilator efficacy by month 12. The change in
predose FEV1 did not entirely account for the reduced
bronchodilator efficacy over time.
albuterol has a safety profile similar to that of CFC albuterol during
chronic, scheduled use, and both drugs are well tolerated. HFA
albuterol and CFC albuterol provided comparable bronchodilator
efficacy, but bronchodilator efficacy decreased for both products with
1 year of use.
Abbreviations: AUC = area under the
curve; CFC = chlorofluorocarbon; CFC albuterol = albuterol
formulated in chlorofluorocarbon propellants: FDA = Food and Drug
Administration; HFA = hydrofluoroalkane-134a; HFA
albuterol = albuterol formulated in propellant
hydrofluoroalkane-134a; MDI = metered-dose inhaler