Thus, here is a draft letter to the FDA that I will soon send to request such a move. Your comments are appreciated. Below the letter is the boxed warning for Symbicort for your reference.
I am thrilled that despite a very vocal minority that seems to wave the safety banner to promote their own agendas, your advisory panel has decided to remove the asthma indication for both formterol (Foradil) and salmeterol (Serevent), and feels strongly about the efficacy and safety of ICS/LABA combinations (Advair, Symbicort) for the treatment of asthma. The problem is that all of the news headlines which state "F.D.A. Panel Votes to Ban Asthma Drugs" and "FDA Advisers: Restrict Some Asthma Drugs" still continue to scare patients. I have one patient whose previously poorly controlled asthma was improved with Advair, but stopped because of an article she read in Men's Health Magazine that implied no doctor would ever prescribe this.
Almost all the controversy regarding LABA's has come from the SMART study, which showed a problem with salmeterol taken alone, but showed no issue when taken with an inhaled corticosteroid. At the time, you decided to give a boxed warning to all products containing LABA's. However in light of the pages and pages of data you reviwed before the recent committee meeting as well as your advisor's recommendations, it seems that now would be the time to reconsider this. The only way to definitely answer this question is a randomized trial of patients on ICS, with half on LABA and half on placebo or increased ICS does, looking at serious exacerbation or asthma death. The problem is that since these events are so rare, and since ICS/LABA does not seem to cause a problem, it would likely take a study of more than 200,000 patients to show what we already know; that ICS/LABA combination is safe and effective for asthma. In addition, no drug company or even the NIH would ever fund such a study.
Though asthma mortality has gone down since the mid-90's, despite an increasing prevalence (and probably helped with the introduction of LABA's), asthma morbidity continues to be a problem. Over 5000 ER visits and 11 deaths a day are due to asthma. ICS/LABA is the most effective treatment for asthma, but some patients and even physicians are concerned about taking them because of the LABA controversy caused primarily by the SMART study. The only way reassure doctors, patients, critics and the media that Advair and Symbicort are safe and effective is to remove the boxed warning from their labels. I truly hope you will consider this.
Dr. Matthew Mintz
Boxed Warning for Symbicort (Advair's is similar)
Important Safety InformationLong acting beta2-adrenergic agonists may increase the risk of asthma-related death. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on other asthma-controller medications (e.g., low-to-medium dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with two maintenance therapies. Data from a large placebo-controlled U.S. study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to formoterol (a long-acting beta2-adrenergic agonist), one of the active ingredients in SYMBICORT.