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February 19, 2010


FDA Announces Label Changes for LABA Asthma Use

Yesterday, the Food and Drug Administration (FDA) announced long-awaited revisions to the labeling indications for long-acting beta-agonists (LABAs) in the treatment of asthma. There are four key changes that will now be required in the labeling of LABAs:

The use of LABAs is contraindicated without the use of an asthma controller medication such as an 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.

The full text of the FDA announcement can be found at:

Asthma experts generally agree that the FDA's announcement is consistent with current treatment guides. The point that will likely generate the most interest is FDA's recommendation that LABAs should be "discontinued, if possible" after control of asthma has been established.

On a conference call about the announcement with FDA staff yesterday, ATS leadership asked for clarification on how to interpret the recommendation that LABA use should be "discontinued, if possible." In the ensuing discussion, a more nuanced interpretation emerged than what had appeared to be a flat recommendation to discontinue LABA use as soon as asthma control has been established. The FDA's intention is to encourage patients and provides to seek to reduce LABA use as much as possible if symptom control can be maintained without it. However, the FDA recognizes in some cases, discontinuation of LABA use, or even reduction of LABA use, may not be possible.

The FDA has been considering labeling revisions for LABA products since December 2008, when the FDA Pulmonary Allergy Drug Advisory Committee held a two-day public meeting to discuss the available safety data on LABAs for the treatment of asthma. The focus of the meetings centered on studies and meta-analysis that suggests increases in severe adverse outcomes associated, including increases in asthma-related hospitalizations and deaths with LABA use. FDA staff was divided on how to respond to the safety concerns. Staff in the FDA Office of Surveillance and Epidemiology recommended:

Withdrawing the asthma indication form all LABAs for individuals younger than 18 years of age;
Removing the asthma indication and contraindicating the use of single entity LABA for all ages;
Considering removal of the asthma indication for combined inhaled corticosteroids/LABAs (Advair and Symbicort).

Staff at the FDA Center for Drug Evaluation and Research - Pulmonary Allergy Products Division recommended:

Continuing to market products containing LABA for asthma (both single agent LABA and LABA/ICS products);
Labeling these products to manage the safety risk.

Alfred Munzer, M.D., Chair of the ATS International Lung Health Committee, presented the comments of the ATS, drafted by a panel of asthma experts, to the FDA advisory committee. The ATS recommended the following:

Keeping LABAs in combination with inhaled corticosteroids on the market for the treatment of asthma;
Keeping single agent LABA products on the market for asthma, but for use in combination with ICS;
Ensuring that further changes or enhancements to the existing black box warning for LABAs are consistent with the NAEPP EPR 3 recommendations, and making any changes to the label indications for LABA for asthma only;
Conducting further safety and efficacy research on LABAs

Several other physician organizations submitted comments in line with the ATS position.

In related news, the FDA's Pulmonary Allergy Drug Advisory Committee is scheduled to hold a public meeting next month to solicit public input for the development of clinical trials regarding the safety of LABA use for the treatment of asthma in children and adults. The ATS will provide comment at the FDA meeting.

Clean Air

ATS Comments on SO2 Proposed Rule

This week the ATS submitted written comments to the Environmental Protection Agency (EPA) regarding the proposed revision to the National Ambient Air Quality Standard (NAAQS) for sulfur dioxide (SO2). In the written comments, the ATS suggested the following actions:

1) Creation of an hourly short-term standard of 50 ppb at the 99th percentile;

2) Enhancement of the EPA's regional monitoring network to better measure SO2 and other pollutant emissions;

3) Establishing an EPA requirement for the reporting of SO2 emissions on all 12 five-minute periods for every hour. The provision of such time series data will allow EPA staff and other researchers to analyze the impact "upset conditions" may have on human health and may provide useful data for future standard setting.

EPA is expected to issue a final rule for SO2.in June of 2010.

                 Points of Contact

Gary Ewart Senior Director, Government Relations
Nuala Moore Senior Legislative Representative
Joe Kirby DC Office Administrator