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Important Label Changes ICS/LABA

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Dec. 20, 2017 A U.S. Food and Drug Administration review of four large clinical safety trials shows that treating asthma with long-acting beta agonists (LABAs) in combination with inhaled corticosteroids (ICS) does not result in significantly more serious asthma-related side effects than treatment with ICS alone. In 2011, the FDA required the drug companies that market LABAs to conduct these trials to evaluate the safety of LABAs when used in combination with ICS, and it reviewed the results of these recently completed trials.

Based on the review, the Boxed Warning, the most prominent warning, about asthma-related death has been removed from the drug labels of medicines that contain both an ICS and LABA. A description of the four trials is now also included in the Warnings and Precautions section of the drug labels. These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone.

Using LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death. Therefore, the Boxed Warning stating this will remain in the labels of all single-ingredient LABA medicines, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and wheezing caused by exercise. The labels of medicines that contain both an ICS and LABA also retain a Warning and Precaution related to the increased risk of asthma-related death when LABAs are used without an ICS to treat asthma.

Medicines that contain both an ICS and LABA are FDA-approved to treat both asthma and COPD. ICS medicines help decrease inflammation in the lungs. This inflammation can lead to breathing problems. LABAs help the muscles around the airways in the lungs stay relaxed to prevent symptoms such as wheezing, coughing, chest tightness, and shortness of breath. ICS/LABA medicines are marketed under several brand names, including Advair, Airduo, Breo, Dulera, and Symbicort (see Table 1).

Health care professionals should refer to the most recently approved drug labels for recommendations on using ICS/LABA medicines (see links in Table 1). Patients and parents/caregivers should talk to their health care professional regarding any questions or concerns. They should not stop taking their asthma medicines without first talking to a health care professional. Patients are advised to read the information leaflets that come with every prescription.

Four recently completed clinical trials involving 41,297 patients were evaluated. Three trails were conducted in patients 12 years and older, and one in children 4 to 11 years. Patients in all the trials were treated for six months to evaluate serious asthma outcomes including asthma-related death, intubation, or hospitalization. The results of all trials showed that the use of LABA with ICS does not significantly increase the risk of serious asthma outcomes compared to ICS alone. The trials also showed that ICS/LABA combination medicines were more effective in decreasing asthma attacks (e.g., the need to use oral corticosteroids) compared to ICS alone. This additional information has been added to the ICS/LABA labels.

To ensure the ongoing evaluation of the safety of all medicines, including LABAs and ICS, patients and health care professionals are urged to report side effects involving LABAs, ICS, or other medicines to the FDA MedWatch program. Refer to the FDA Safety Alert webpage and use the contact box.

Table 1. List of Approved ICS/LABA Combination Medicines

Brand Name

Generic Names

Advair Diskus

fluticasone (ICS), salmeterol (LABA)

Advair HFA

fluticasone (ICS), salmeterol (LABA)

Airduo Respiclick

fluticasone (ICS), salmeterol (LABA)

Breo Ellipta

fluticasone (ICS), vilanterol (LABA)


mometasone (ICS), formoterol (LABA)


budesonide (ICS), formoterol (LABA)

Read more in the Safety Alert 
"Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed Warning About Asthma-Related Death Removed"

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