Adult and Adolescent Patients 12 Years of Age and Older

The overall safety data in adults and adolescents are based upon 10 active- and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated with budesonide and formoterol fumarate dihydrate 80/4.5 or 160/4.5 taken 2 inhalations once or twice daily for 12 to 52 weeks. In these trials, the patients on budesonide and formoterol fumarate dihydrate had a mean age of 38 years and were predominantly Caucasian (82%).

The incidence of common adverse events in Table 2 below is based upon pooled data from three 12-week, double-blind, placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years and older were treated with 2 inhalations of budesonide and formoterol fumarate dihydrate 80/4.5 or budesonide and formoterol fumarate dihydrate 160/4.5 twice daily. The budesonide and formoterol fumarate dihydrate group was composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV1 at baseline of 76 and 68 for the 80/4.5 mcg and 160/4.5 mcg treatment groups, respectively. Control arms for comparison included 2 inhalations of budesonide HFA metered dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI) 4.5 mcg, or placebo (MDI and DPI) twice daily. Table 2 includes all adverse events that occurred at an incidence of >3% in any one budesonide and formoterol fumarate dihydrate group and more commonly than in the placebo group with twice-daily dosing. In considering these data, the increased average duration of patient exposure for budesonide and formoterol fumarate dihydrate patients should be taken into account, as incidences are not adjusted for an imbalance of treatment duration. 

Long-term safety - asthma clinical trials in patients 12 years and older

Long-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year at doses up to 1280/36 mcg/day (640/18 mcg twice daily), revealed neither clinically important changes in the incidence nor new types of adverse events emerging after longer periods of treatment. Similarly, no significant or unexpected patterns of abnormalities were observed for up to 1 year in safety measures including chemistry, hematology, ECG, Holter monitor, and HPA-axis assessments.

Pediatric Patients 6 to Less than 12 Years of Age

The safety data for pediatric patients aged 6 to less than 12 years is based on 1 trial of 12 weeks treatment duration. Patients (79 female and 105 male) receiving inhaled corticosteroid at trial entry were randomized to budesonide and formoterol fumarate dihydrate 80/4.5 (n=92) or budesonide pMDI 80 mcg (n=92), 2 inhalations twice daily. The overall safety profile of these patients was similar to that observed in patients 12 years of age and older who received budesonide and formoterol fumarate dihydrate 80/4.5 twice daily in studies of similar design. Common adverse reactions that occurred in patients treated with budesonide and formoterol fumarate dihydrate 80/4.5 with a frequency of ≥3% and more frequently than patients treated only with budesonide pMDI 80 mcg included upper respiratory tract infection, pharyngitis, headache, and rhinitis.