Chest
Volume 124, Issue 1, July 2003, Pages 70-74
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Clinical Investigations
Asthma
Serious Asthma Exacerbations in Asthmatics Treated With High-Dose Formoterol

https://doi.org/10.1378/chest.124.1.70Get rights and content

Objective

To review three prospective, randomized, placebo-controlled, double-blind clinical studies of formoterol (Foradil Aerolizer; Novartis Pharmaceuticals; Basel, Switzerland) at dosages of 12 μg and 24 μg bid for the treatment of patients with asthma.

Data sources

Clinical studies submitted to the US Food and Drug Administration in support of the approval of Foradil Aerolizer for marketing in the United States.

Results

More patients treated regularly with formoterol, 24 μg bid, had a serious asthma exacerbation than did patients who had been treated with placebo. In the first study, 4 of 135 adult patients (3%) who had been treated with formoterol, 24 μg bid, had a serious asthma exacerbation compared to none of 136 placebo-treated patients. In the second study, 5 of 136 patients (3.7%) treated with formoterol, 24 μg bid, had a serious asthma exacerbation compared to 2 of 141 placebo-treated patients (1.4%). In the third study, 11 of 171 pediatric patients (6.4%) treated with formoterol, 24 μg bid, had a serious asthma exacerbation compared to none of 176 placebo-treated patients.

Conclusion

Regular use of high-dose inhaled formoterol (24 μg bid) may be associated with more frequent serious asthma exacerbations.

Section snippets

Materials and Methods

Novartis Pharmaceuticals submitted data from clinical studies to support the use of orally inhaled formoterol (Foradil Aerolizer) twice daily for the long-term maintenance treatment of asthma. Three of the studies were placebo-controlled randomized clinical studies evaluating multiple doses of formoterol. Two of these trials have been reported in the literature.45

There were two 12-week, double-blind, randomized, placebo-controlled, parallel-group studies performed in patients 12 to 75 years of

Results

The two adult/adolescent studies randomized 541 patients and 554 patients. Each study showed that both formoterol doses were statistically significantly better than placebo for the primary end point of FEV1 measurement taken at the 12th hour posttreatment (ie, FEV1 at trough) at the week 12 visit. The pediatric study randomized 518 patients. In children, both formoterol doses were also statistically significantly better than placebo for the primary end point of FEV1 area under the curve

Discussion and Conclusions

The three clinical studies reported on herein demonstrated that twice daily formoterol (at a dose of either 12 μg or 24 μg) was statistically superior to placebo in terms of improving FEV1, which is an accepted end point for asthma control. The added benefit of formoterol, 24 μg bid, over formoterol, 12 μg bid, was considered to be marginal, and more patients who were randomized to receive formoterol, 24 μg bid, experienced serious asthma exacerbations compared to placebo, albuterol, 180 μg

ACKNOWLEDGMENT

The authors would thank Drs. Craig Ostroff, Virgil Whitehurst, and Laurence Sancilio for their helpful comments in preparing this manuscript.

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The opinions expressed in this article are those of the authors and do not reflect the official opinions of the US Food and Drug Administration.

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