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Title: High-Dose Inhaled Formoterol Associated With Serious Asthma Exacerbation

URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
Retrieve&db=PubMed&dopt=Abstract&list_uids=12853504

Chest 2003;124:1:70-74. "Serious asthma exacerbations in asthmatics treated with high-dose formoterol"
08/01/2003 10:22:29 AM
By Emma Hitt, PhD

Regular use of high-dose inhaled formoterol may be associated with episodes of serious asthma exacerbation, according to an analysis of data by the US Food and Drug Administration (FDA). Because of the findings, "Novartis Pharmaceuticals will perform a large placebo-controlled postmarketing study of Foradil Aerolizer, (24 micrograms bid), to better understand whether the safety concern raised in these trials is a real finding," the FDA researchers note. Long-acting inhaled beta2-agonists are indicated for patients who require long-term control of asthma symptoms. Formoterol (Foradil Aerolizer; Novartis Pharmaceuticals; Basel, Switzerland) and salmeterol (Serevent Diskus and Serevent Inhalation Aerosol; GlaxoSmithKline; Research Triangle Park, NC) are approved for use in the United States. However, concern has been expressed about the effect of long-acting beta2-agonists on the development of airway sensitivity. Marianne Mann, MD, with the Center for Drug Evaluation and Research, FDA, Rockville, Maryland, United States, and colleagues conducted a post-hoc analysis of data from 3 prospective randomised trials comparing treatment with formoterol, 12 micrograms bid, and formoterol, 24 micrograms bid, with placebo: two 12-week studies performed in patients 12 to 75 years of age and a 12-month safety study in children 5 to 12 years of age. More patients treated regularly with formoterol, 24 micrograms bid, had a serious asthma exacerbation than did patients who had been treated with placebo, they found. In one study, 4 of 135 adult patients (3%) who had been treated with formoterol, 24 micrograms bid, had a serious asthma exacerbation compared to none of 136 placebo-treated patients. In another study, 5 of 136 patients (3.7%) treated with formoterol, 24 micrograms 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 ľg bid, had a serious asthma exacerbation compared to none of 176 placebo-treated patients. According to the researchers, several mechanisms may be responsible for an increased risk of serious asthma exacerbation. "Chief among these is the development of desensitisation of the beta-receptor," they suggest. Dr. Mann and colleagues conclude that the added benefit of formoterol, 24 micrograms bid, over formoterol, 12 micrograms bid, was marginal. "Based on our review of the new drug application for Foradil Aerolizer, we concluded that this product has been shown to be safe and effective as a 12-micrograms bid dose," the authors note. "However, our review of the clinical data presented showed a subtle signal for concern in those patients taking a dose of 24 micrograms bid in that a higher incidence of serious asthma exacerbations was noted."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
Retrieve&db=PubMed&dopt=Abstract&list_uids=12853504

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