Long-term safety of nebulized formoterol: results of a twelve-month open-label clinical trial.
Formoterol fumarate is a long-acting beta2-agonist that is an effective bronchodilator for the maintenance management of patients with chronic obstructive pulmonary disease. The safety profile of the newly developed nebulized formoterol was evaluated over a twelve-month period in an open-label, active-control study. After completing a twelve-week double-blind double-dummy period, 569 subjects with chronic obstructive pulmonary disease entered an open-label extension study and received twice-daily 20 microg formoterol fumarate inhalation solution for nebulization (FFIS) or 12 microg formoterol fumarate dry powder inhalation (FA) for 52 weeks. Most of the FFIS-treated subjects (86%) completed at least six months of open-label treatment with over 90% compliance, comparable to the FA group (88%).


RESULTS
of safety monitoring for adverse events, laboratory values, and cardiac changes were similar between treatment groups. Three hundred forty (73%) of FFIS-treated subjects and 83 (78%) of FA-treated subjects experienced an adverse event over the course of the study, the majority of which were mild to moderate and considered unrelated to treatment. COPD exacerbation occurred in 15.8% of FFIS-treated and 17.9% of FA-treated subjects. Deaths, serious adverse events, and discontinuations for adverse events occurred in 1.3, 16.2, and 5.4% of the nebulized group versus 1.9, 17.9, and 7.5% of the inhaled group, respectively. There were no clinically important changes from baseline in laboratory tests, including serum potassium and glucose, or vital signs and no treatment-related increases in cardiac arrhythmias, heart rate, or QTc prolongation. We conclude that nebulized formoterol fumarate twice daily is well tolerated over long-term treatment in moderate-to-severe COPD subjects and has a similar safety profile to the DPI formulation.
Donohue
James F
JF
University of North Carolina, 4125 BioInformatics Building, 130 Mason Farm Road, CB 7020, Chapel Hill, NC, 27599, USA. james_donohue@med.unc.edu
Hanania
N A
NA
Fogarty
C
C
Campbell
S C
SC
Rinehart
M
M
Denis-Mize
K
K
D000280:Administration, Inhalation; D001794:Blood Pressure; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000068759:Formoterol Fumarate; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012720:Severity of Illness Index
D001993:Bronchodilator Agents; D004983:Ethanolamines; D011208:Powders; D000068759:Formoterol Fumarate