We’re at the U.S. Food and Drug Administration with the Division of Drug Information pharmacists. Today they are discussing important new recommendations for long-acting beta-agonists or LABAs. This is FDA Drug Info Rounds, a program by pharmacists for pharmacists.
I saw that the updated prescribing information with the new recommendations for the safe use of LABAs in the treatment of asthma was approved. Have you had a chance to read it yet?
Yes, I read it the other day. The new recommendations are very important because they are based on FDA’s review of data that found that LABAs increased the risk of severe exacerbation of asthma symptoms, leading to hospitalizations in pediatric and adult patients, as well as death in some patients using LABAs to treat asthma.
Right. FDA’s decision to require changes to how these drugs are used in the treatment of asthma is based on analyses from the Salmeterol Multi-center Asthma Research Trial, or SMART, the Salmeterol Nationwide Surveillance study, or SNS, and a meta-analysis conducted by FDA in 2008.
These data were discussed at the joint Pulmonary Allergy Drugs, Drug Safety and Risk Management, and Pediatric Advisory Committees, held in December 2008.
Let’s look more closely at the data FDA reviewed.
SMART was a large, randomized, placebo-controlled trial that evaluated 26,355 patients 12 years of age and older receiving standard asthma therapy and the addition of either salmeterol or placebo. Results showed that patients receiving salmeterol were at an increased risk of asthma-related death compared to patients receiving placebo.
The SNS was a 16-week, double-blind study that compared the addition of salmeterol or albuterol to standard asthma therapy in 25,180 asthma patients who were 12 years of age and older. In this study, there was an increase in the number of respiratory and asthma-related deaths in the salmeterol group, with 12 deaths out of 16,787 patients, compared to the albuterol group, with 2 deaths out of the 8,393 patients.
In addition to the SMART and SNS studies, FDA conducted a meta-analysis of 110 studies evaluating the use of LABAs in 60,954 patients with asthma. The meta-analysis used a composite endpoint to measure severe exacerbation of asthma symptoms, including asthma-related death, intubation, and hospitalization. The results of the meta-analysis suggested an increased risk for severe exacerbation of asthma symptoms in patients using LABAs compared to those not using LABAs. The largest risk difference per thousand treated patients was seen in children 4 to 11 years of age. The results of the meta-analysis were primarily driven by asthma-related hospitalizations. Other meta-analyses, not conducted by FDA, evaluating the safety of LABAs in the treatment of asthma have not shown a significant increase in the risk for severe asthma exacerbations.
Based on the findings from FDA’s review, there was sufficient data to support a decision to require new recommendations in the prescribing information.
It's clear that the new recommendations reiterate some of the important points for pharmacists and patients, such as:
LABAs should only be used as additional therapy for patients with asthma who are currently taking but are not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, and that LABAs should not be used in patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
Use of a LABA alone without use of a long-term asthma control medication, such as an inhaled corticosteroid, is now contraindicated in the treatment of asthma.
Plus, the new recommendations also state that:
Once asthma control is achieved and maintained, patients should be assessed at regular intervals and step down therapy, including discontinuation of the LABA, should begin if possible,. This should be done without loss of asthma control, and the patient should continue to be treated with a long-term asthma control medication, such as an inhaled corticosteroid.
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 adherence with both medications.
These new recommendations are important for pharmacists since they can review their patients’ medication profile to be certain that all patients being treated for asthma with a LABA are also receiving an asthma control medication, such as an inhaled corticosteroid.
You are absolutely right, Brenda, pharmacists should also review their patients’ profiles to ensure they have a rescue inhaler, such as an albuterol inhaler, and know how to use it.
They should discuss with patients, families, and care-givers the warning signs of worsening asthma and advise them to seek immediate medical attention if their condition deteriorates.
In addition, pharmacists should encourage patients, families, and caregivers to read the Medication Guide that accompanies LABA prescriptions. This will help them understand the benefits and potential risks of LABAs.
FDA believes that when LABAs are used according to the recommendations outlined above and in the approved drug labels, the benefits of LABAs in improving asthma symptoms outweigh their risks of increasing severe asthma exacerbations and deaths from asthma.
Thanks for joining the FDA pharmacists at their Drug Info Rounds. This is our FDA program of pharmacists helping pharmacists educate consumers, so they can make better medication choices.
To report medication adverse events call 1-800-332-1088 or go online to www.fda.gov/medwatch. If you have any questions, you may reach FDA’s Division of Drug Information by calling 1-888-463-6332 or email us at email@example.com.