A. FDA is announcing its recommendations to change how long-acting inhaled medications called Long-Acting Beta-Agonists (or "LABAs" for short) are used in the treatment of asthma. These changes are based on FDA’s analyses of studies showing an increased risk of severe exacerbation (worsening) of asthma symptoms, leading to hospitalization in pediatric and adult patients as well as death in some patients using LABAs for the treatment of asthma. FDA is also requiring a risk management program called a risk evaluation and mitigation strategy (REMS) to help ensure the safe use of these products.
A. LABAs are used to help people with asthma or a lung condition called chronic obstructive pulmonary disease (COPD) breathe easier. LABAs are also used for exercise-induced bronchospasm. LABAs improve breathing by relaxing the muscles of the airways to allow more air to flow into and out of the lungs. LABAs are inhaled through the mouth into the lungs using an inhaler or nebulizer device. LABAs are available as single ingredient products, or in combination with a corticosteroid medication. For asthma, LABAs are available by prescription in dry powder inhalers or metered-dose inhalers. LABAs are called long-acting because their effects last for at least 12-hours.
A. Despite the benefits of LABAs in helping people with asthma and COPD breathe easier, FDA's analyses indicate there is an increase in the risk of severe exacerbation of asthma symptoms in some patients with asthma that use a LABA compared to patients with asthma that do not use a LABA. Because of this risk, FDA wants to make sure LABAs are used appropriately in patients with asthma. Even though LABAs are approved for use in asthma and COPD, FDA's new recommendations only apply to the use of LABAs in the treatment of asthma. In order to ensure the safe use of these medicines, FDA is requiring the manufacturers of LABAs to develop this risk management program for healthcare professionals and patients.
A. The risk management program for LABAs requires the manufacturers to better inform healthcare professionals and patients about the risk of LABAs for patients with asthma and ways to decrease that risk while maintaining the benefits of the drug. Under the program, patients who have a prescription filled for a LABA will receive a revised Medication Guide that explains the risks and benefits of the medicine. In addition manufacturers of LABAs will update the prescribing information they provide to healthcare professionals to include the latest recommendations for safe use of these important medicines.
A.The key points are:
- The use of LABAs is contraindicated without the use of an asthma controller medication such as inhaled corticosteroid. Single-ingredient LABAs should only be used in combination with an asthma controller medication; they should not be used alone.
- LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications.
- LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication.
- Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA to ensure compliance with both medications.
A. Below are the names of the LABA-containing medicines approved by FDA to treat asthma:
|Brand Name(s)||Generic Name(s)||Description|
|Advair Diskus, Advair HFA||salmeterol and fluticasone||salmeterol is a LABA and fluticasone is a corticosteroid asthma controller|
|Symbicort Inhalation Aerosol||formoterol and budesonide||formoterol is a LABA and budesonide is a corticosteroid asthma controller|
|Serevent Diskus||salmeterol||single ingredient LABA with no corticosteroid asthma controller|
|Foradil Aerolizer||formoterol||single ingredient LABA with no corticosteroid asthma controller|
Q7. Why should LABAs only be used with an asthma controller medication, are they safer when used this way?
A. At this time, there is no conclusive evidence that the combination of an asthma controller medicine with a LABA decreases or eliminates the risk of a LABA. More study and analysis is required in this area. However, because of the risks of LABAs, FDA recommends that a LABA should not be used for a patient whose asthma can be controlled with an asthma controller medicine, such as an inhaled corticosteroid. If a LABA needs to be added to that medicine, it should only be used until the patient's healthcare professional determines their asthma is under control, and then the LABA should be stopped if possible. This means it is always necessary for a patient to use a LABA in combination with an asthma controller medication.
As part of today's announcement, FDA is requiring the manufacturers of LABAs to conduct studies evaluating the safety of LABAs when used with an inhaled corticosteroid to better understand this issue.
Q8. If LABAs are to be used with an asthma controller medicine, why aren't all LABA products required by FDA to be in a combination product with an asthma controller medicine?
A. There are several kinds of asthma controller medicines patients may use in combination with a LABA, but not all are able to be made into a combination product. For example, there are many different inhaled corticosteroids available and some pills, such as Singulair (montelukast) or prednisone, which patients may take with a LABA. This means that some single ingredient LABA products need to be available for patients whose other asthma controller medicine cannot be combined in the same inhaled dose. Additionally, single ingredient LABA products are used in the treatment of COPD.
Q9. Is the use of LABAs without the use of an asthma controller medication a big problem in the treatment of asthma?
A. No, currently, about 95% of patients using a LABA use an inhaled combination product that contains a LABA and a corticosteroid. However, discontinuation of the LABA once control of asthma is achieved is not currently a widespread practice; therefore, many patients who are using a combination LABA product may be unnecessarily exposed to the risks of LABAs. FDA is emphasizing its recommendation that when LABAs are needed that they be used for the shortest time possible to achieve asthma control and then be discontinued, if possible, to limit the long-term use.
Q10. Why is the new risk management program designed for patients with asthma and not for patients with COPD, aren't LABAs used to treat both conditions?
A. LABAs are used to treat both asthma and COPD, however, the studies reviewed by FDA included patients using LABAs for the treatment of asthma. These studies indicated an increased risk of severe exacerbation of asthma symptoms leading to hospitalization and death in these patients. There is no evidence to conclude that people with COPD who use LABAs are at any greater risk compared to people with COPD who do not use LABAs. FDA does not recommend any change in the use of LABAs for COPD.
Q11. What information did FDA review to help the Agency decide to require a risk management program?
A. FDA used a variety of studies and research in patients with asthma using a LABA. Two specific studies that provided valuable information were 1) the Salmeterol Multi-center Asthma Research Trial (SMART) and 2), the Serevent Nationwide Surveillance study (SNS). Salmeterol is the LABA in Serevent. Each of these studies showed a higher risk of death for patients with asthma that used a LABA (salmeterol) compared to patients with asthma that did not use a LABA. In addition, FDA used a research method called a meta-analysis to further understand the risks associated with the use of LABAs in patients with asthma. A meta-analysis uses data from multiple studies on a particular topic to enable scientists to combine information from those studies to make scientific conclusions or recommendations in that area. For more information on these specific studies please see the Drug Safety Communication on New Safety Requirements for LABAs.