10 Common Side Effects of Combination Inhalers

Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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Combination inhalers prescribed for asthma, smoking lung disease (COPD), or persistent cough after an upper respiratory infection are some of the top selling drugs in the United States. Several steroid + long acting bronchodilator combinations are currently available: the older Advair and Symbicort and the newer Dulera and Breo Ellipta.

While Advair and Symbicort are recommended for treatment of both moderate persistent asthma and COPD, Breo has been introduced with the indication for COPD treatment only. Which combo inhaler you are prescribed is often based on your insurance coverage because while they differ in delivery mechanism, they generally work just as well.

If you have similar insurance coverage for Advair, Symbicort, Dulera, or Breo, you may want to consider the commonly reported side effects:

  1. Voice changes. Hoarseness or huskiness are common symptoms, related to the steroid component of the inhaler. Voice changes occur in 5 to 10% of people and are more common with frequent use and with fluticasone (in the Advair) compared to other steroids. Rinsing your mouth by gargling with water will help remove the locally deposited steroid in the mouth (not where you want it, you want it in the lungs). It has been shown that 56% of the dose from your inhaler is deposited in the mouth/throat and a mouth rinse promptly can remove 60% of this residue.
  2. Yeast infections of the mouth/thrush. The steroid in your combo inhaler may cause candidiasis (yeast) infection in the mouth as a potential side effect. This will look like white, soft plaques that leave a painful red, eroded, or ulcerated surface. The sides of the tongue, back of throat and inside the cheek are common sites where you may notice tenderness, burning, and pain with swallowing. The antifungal mouthwash Nystatin can be used to treat this.
  3. Cavities (dental caries) from dry mouth. Dry mouth and increased thirst is reported with the combination inhalers. The bronchodilator part of the inhaler (beta-2 agonist) is associated with the increased frequency of cavities. Long term use of beta-2 agonists is associated with diminished saliva production and secretion.
  4. Pneumonia. This may be the case only with the steroid in Advair (fluticasone) and not with Symbicort (budesonide). The use of Advair has been associated with a higher prevalence of pneumonia in the major long-term studies, but no similar increased risk of pneumonia has been reported in patients with COPD treated with Symbicort. This difference may be explained by the longer retention of fluticasone in the airways.
  5. Headache. 7% to 11% of folks using these combination inhalers report headaches.
  6. Cough. While we don’t know exactly why this occurs, cough may be a result of throat irritation from the inhaler.
  7. Throat pain. Even without thrush, pain and soreness in the throat is reported in 6 to 9% of folks using these combination inhalers.
  8. Adrenocortical suppression. Side effects like this are unlikely to occur at prescribed doses of the newer inhalers unless you are using them long term. With long term use of inhaled steroids at high doses you can suppress your own production of certain hormones (cortisol). Abruptly discontinuing your inhaler may lead to serious symptoms like extreme fatigue and low blood pressure.
  9. Osteoporosis and bone fractures. Steroids stimulate the process of bone turnover but at doses lower than 800 mcg a day this is unlikely to occur. Long term use of inhaled steroids (half of the contents of your combination inhaler) may lead to brittle bones and increased risk of spine and hip fractures. For reassurance you can look at your inhaler for the dose of steroid it contains: for example Advair 250 mcg/50 mcg contains 250 mcg of the steroid fluticasone.
  10. Skin thinning and purpura (purple spots on the skin, most commonly arms). Long term use of the steroid in your combo inhaler leads to loss of subcutaneous fat. Skin bruising and purple spots may happen with long term combination inhaler use.

One last note on weaning off and discontinuing Advair, Symbicort, Dulera or Breo:

An interesting fact—inhaled corticosteroids, particularly fluticasone, are absorbed more (meaning more chance for unwanted systemic side effects) in folks with normal lung function. This is a reminder that you should step down the inhaled steroid dose/combo inhaler once your breathing from asthma or COPD is adequately controlled.

Dr O.

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