Symbicort, Advair, and Safety

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Both Symbicort and Advair contain drugs called long acting beta-agonists, or LABAs for short.  Symbicort contains formoterol and Advair contains salmeterol.  Advair and Symbicort also contain inhaled corticosteroids(ICS), fluticasone and budesonide, respectively.  This combination of medications has been repeatedly shown in multiple prospective, randomized placebo-controlled trials to improve symptoms, lung function, and quality of life in asthmatics.  More importantly, combination ICS/LABA medications have been shown to reduce asthma exacerbations.  So what’s the problem?

The problem is, there are now two large meta-analyses which have shown an increased risk of adverse events in patients receiving LABAs.  A meta-analysis pools data from multiple trials in order to achieve higher statistical power.  These meta analyses have serious limitations, however.  

The first meta analysis was published by Dr. Shelley Salpeter, a primary care physician, in June, 2006.  It examined the use of salmeterol.  Among the co-authors were her father, an astrophysicist, and her son, then a high-school student.  Remarkably, and somewhat disconcertingly, the study was published in the Annals of Internal Medicine, one of the most rigorous and respected journals in the field.  It set off a firestorm of controversy in the asthma community and was roundly panned.  The primary flaw in the Salpeter paper was the large number of patients who came from the inaptly named SMART trial, where subjects were not required to utilize ICS along with their salmeterol.  That is a big no-no.  Not surprisingly, the majority of serious adverse events in the meta-analysis came from the SMART trial.  A follow-up meta-analysis published by respected asthma physicians Hal Nelson and Jean Bousquet, among others, confirmed what previous trials had shown- patients receiving combination ICS/LABA medications have fewer exacerbations and no increased risk for serious adverse events.

Now, a new meta-analysis has come out examining formoterol.  Apparently, the authors have not boned up on their recent history, because they repeat the same fatal flaw of the Salpeter paper- they included subjects who were not required to utilize ICS concomitantly with their LABA.  Predictably, the results are similar.  The shock value headline will read, “57% increase in serious non-fatal events!”, but the reality is that for every 1000 asthma patients in the analysis, 16 formoterol patients had a serious event and 10 placebo patients had a serious event, so the absolute risk increase is only 0.6%.  Additionally, the meta-analysis does not tell us whether those 6 extra patients were on formoterol alone or in combination or what dose of formoterol was used.  

The take home message is this: if your asthma is bad enough to require combination ICS/LABA therapy, then you can be reassured that there a wealth of data and experience supporting their effectiveness and safety.

Disclaimer:  I have no financial ties to either GlaxoSmithKline(Advair) or AstraZeneca(Symbicort), or to any other pharmaceutical company for that matter. On occasion,  I eat a grilled chicken salad at lunch with a GSK rep.

5 Comments

  1. I was put on Symbicort and it made me cough endlessly, vomit, and my peak flow dropped from 430 to at worst 320. I couldn´t last as long playing tennis, and I finally looked it up myself online to see if it could be the cause of all my problems. I´m now back on Pulmicort and getting better. Peak flow now 410 after 3 weeks of being off Symbicort.

    Message to take home- it doesn´t help everyone and is not safe for all. Trial period must be given and check for signs of worsening.

  2. There are no medications that work in everybody without any side effects, but reactions such as yours are very unusual. I’ve seen a few people have similar experiences, though with a diskus device, not an MDI. As usual, YMMV.

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  4. i M JUST READING AND RESEARCHING AT THIS TIME ….I AM ON SPIRIVA AND ADVAIR CURRENTLY BUT HAVE COMPLAINED OF PAINS GOING FROM MY CHETS TO MY BACK……DR HAS NOW PRESCRIBED AS OF TODAY DULCERA AND SPIRIVA….I HAVE ALSO TRIED SYMBICORT,ALSO WITH SPIRIVA…..I WILL BE STARTING THAT MONDAY…ANY SUGGESTIONS OR ADVICE IS WELCOMED AS THIS IS ALL FAIRLY NEW TO ME. I STARTED MEDICATIONS 8 MONTHS AGO,FOR SHORTNESS OF BREATH,SINCE THEN I HAVE HAD TO GO TO THE HOSPITAL ONE TIME,IT ALMOST SEEMS TO ME ,MEDICINES ARE MAKING ME WORSE IN THE LONG RUN.

    • This sounds like a pretty complex problem. In general, when good medications like Dulera, Symbicort, and Advair aren’t working you might need to make sure you’re using them properly or maybe even rethink the diagnosis. If it really is asthma, other options include omalizumab or bronchial thermoplasty.

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