To evaluate the tolerability of budesonide/formoterol pressurized metered-dose inhaler (pMDI) in patients ≥40 years with moderate to very severe chronic obstructive pulmonary disease (COPD).
Safety data were pooled from 2 randomized, double-blind, multicenter studies (Tashkin et al. Drugs 2008;68:1975 [study I: 6-month; NCT00206154]; Rennard et al. Drugs 2009;69:549–565 [study II: 12-month; NCT00206167]). Adverse events (AEs) are presented for treatment groups common to both studies: twice-daily budesonide/formoterol pMDI 160/4.5μg ×2 inhalations (320/9μg), budesonide/formoterol pMDI 80/4.5μg ×2 inhalations (160/9μg), formoterol DPI 4.5μg ×2 inhalations (9μg), and placebo.
Of 3668 patients, 2733 completed the studies. Study discontinuation was greater and mean treatment exposure (days) lower in the placebo (32.3% and 223.7, respectively) group versus budesonide/formoterol (22.4–23.4% and 251.6–255.2, respectively) and formoterol (28.0% and 240.3, respectively) groups. The percentage of patients with ≥1 AE was slightly higher with budesonide/formoterol (60.6–62.4%) and formoterol (59.1%) versus placebo (53.8%); however, discontinuations due to AEs were similar (9.7–11.9%). Nonfatal serious AEs were slightly more frequent in the formoterol-containing groups (12.5–14.2%) versus placebo (10.6%). Drug-related AEs were more frequent with budesonide/formoterol (9.7–11.3%) and formoterol (8.2%) versus placebo (6.1%). The incidence of candidiasis and voice effects (local ICS effects) was low but slightly more frequent in the budesonide/formoterol groups (4.8–9.1%) versus formoterol (1.5%) and placebo (2.4%), with a dose-related effect in the budesonide/formoterol groups. The incidence of pneumonia-related AEs was similar for budesonide/formoterol (3.0–3.1%), formoterol (2.8%), and placebo (3.6%). There was a slight increment in bronchitis incidence in all formoterol-containing groups (3.7–5.4%) versus placebo (3.5%). Although cardiac-related AEs, including atrial fibrillation, were slightly more frequent in the budesonide/formoterol (8.8–9.1%) and formoterol (8.3%) groups versus placebo (5.8%), electrocardiogram and 24-hour Holter findings, particularly new atrial fibrillation, were similar among groups.
In this large population of COPD patients, both budesonide/formoterol pMDI doses were well tolerated, with no evidence of an increased risk for pneumonia.
Budesonide/formoterol pMDI is well tolerated for long-term maintenance of airflow obstruction in patients with moderate to very severe COPD.
Donald Tashkin, Grant monies (from sources other than industry) NIH; Grant monies (from industry related sources) Almirall, AstraZeneca, Boehringer-Ingelheim, Dey Laboratories, GlaxoSmithKline, Novartis, Pfizer, Sepracor and Forest Laboratories; Consultant fee, speaker bureau, advisory committee, etc. AstraZeneca, Boehringer-Ingelheim, Dey Laboratories, and Schering-Plough; No Product/Research Disclosure Information