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Questions and Answers

Questions about LABA safety

Why is FDA requiring LABA manufacturers to have a risk management program for these medicines?

Despite the benefits of long-acting beta2-agonists (LABAs) in helping people with asthma, FDA's analyses indicate there is an increase in the risk of severe exacerbation of asthma symptoms leading to hospitalizations in pediatric and adult patients as well as death 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. 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.

What is the goal of the new risk management program for LABAs?

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.

What are the key points people should know about the safe use of LABAs in patients with asthma?

The key points are:

  • Use of a LABA alone without use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated (absolutely advised against) in the treatment of asthma.
  • LABAs should not be used in patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
  • 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.
  • Once asthma control is achieved and maintained, patients should be assessed at regular intervals and step down therapy should begin (e.g., discontinue LABA), if possible 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.

What information did FDA review to help the Agency decide to require a risk management program?

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 Multicenter 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 February 2010 LABA Drug Safety Communication for more information.

What are the names of LABA-containing medicines used to treat asthma?

Below are the names of the LABA-containing medicines approved by FDA to treat asthma:

Table 1. LABA-Containing Medicines Approved by FDA to Treat Asthma

ADVAIR, SEREVENT and DISKUS are registered trademarks of GlaxoSmithKline, FORADIL is a registered trademark of Astellas Pharm Inc., AEROLIZER is a registered trademarks of Novartis AG., SYMBICORT is a registered trademark of the AstraZeneca group of companies, DULERA is a registered trademark of Schering Corp., a subsidiary of Merck & Co., Inc.

The brands listed are trademarks of their respective owners and are not trademarks of Dey Pharma, L.P. The makers of these brands are not affiliated with and do not endorse Dey Pharma, L.P. or its products.

Why should LABAs only be used with a long-term asthma control medication, are they safer when used this way?

At this time, there is no conclusive evidence that the combination of a long-term asthma control medication with a LABA decreases or eliminates the risk of a LABA. More study and analysis is required in this area. FDA is requiring the manufacturers' studies evaluating the safety of LABAs when used with an inhaled corticosteroid to better understand this issue. Because of the risks of LABAs, FDA recommends that a LABA should not be used for a patient whose asthma can be controlled with long-term asthma control medication, 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 a long-term asthma control medication.

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?

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.

Is the use of LABAs without the use of an asthma controller medication a big problem in the treatment of asthma?

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.

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?

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.

Questions about PERFOROMIST®

Why does PERFOROMIST have a boxed warning?

Due to an increased risk of asthma-related death, FDA has mandated that all Long-Acting Beta Agonists (LABAs) and LABA-containing products, like PERFOROMIST, carry a boxed warning. PERFOROMIST is not indicated in asthma, it is only indicated for use in COPD. The boxed warning for PERFOROMIST reads as follows:

WARNING: ASTHMA-RELATED DEATH
Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another longacting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol, the active ingredient in PERFOROMIST Inhalation Solution. The safety and efficacy of PERFOROMIST in patients with asthma have not been established. All LABA, including PERFOROMIST, are contraindicated in patients with asthma without use of a long-term asthma control medication.

What should I tell patients about the risk of asthma-related death?

Patients should be informed that formoterol, the active ingredient in PERFOROMIST, increases the risk of asthma-related death. In pediatric and adolescent patients, formoterol may increase the risk of asthma-related hospitalization. They should also be informed that data are not adequate to determine whether the concurrent use of inhaled corticosteroids or other long-term asthma-control therapy mitigates this risk. See Warnings and Precautions Section 5.1 of the full Prescribing Information.

Can PERFOROMIST be used for acute asthma symptoms or COPD?

No. The safety and efficacy of PERFOROMIST in patients with asthma have not been established. PERFOROMIST Inhalation Solution is not indicated for relief of acute symptoms of asthma or COPD, and extra doses should not be used for that purpose. Acute COPD symptoms should be treated with an inhaled, short-acting beta2-agonist (the healthcare provider should provide the patient with such medication and instruct the patient in how it should be used). Patients should be instructed to seek medical attention if their symptoms worsen despite recommended doses of PERFOROMIST Inhalation Solution, if PERFOROMIST Inhalation Solution treatment becomes less effective, or if they need more inhalations of a short-acting beta2-agonist than usual. See Warnings and Precautions Section in the full Prescribing Information.

Can additional LABAs be used with PERFOROMIST?

No. When patients are prescribed PERFOROMIST, other long-acting beta2-agonists should not be used. See Warnings and Precautions Section 5.3 of the full Prescribing Information.

What are the risks of Beta-Agonist Therapy?

Patients should be informed that treatment with beta2-agonists may lead to adverse events which include palpitations, chest pain, rapid heart rate, tremor or nervousness. See Warnings and Precautions Section 5.5 of the full Prescribing Information.

For more information: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandP roviders/ucm200776.htm

References

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  5. Rodriguez-Roisin R, Anzueto A, Bourbeau J, et al; GOLD Executive Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (updated 2009). Global Initiative for Chronic Obstructive Lung Disease website: http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Accessed March 8, 2010.
  6. National Heart Lung and Blood Institute: National Institutes of Health. When you are diagnosed with COPD. Available at: http://www.nhlbi.nih.gov/health/public/lung/copd/breathing-better/taking-action.htm. Accessed July 13, 2011.
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Please see full Prescribing Information and Medication Guide, including Boxed Warning.

Indication

PERFOROMIST (formoterol fumarate) Inhalation Solution is used for the long-term treatment of chronic obstructive pulmonary disease (COPD) including chronic inflammation of the lungs (bronchitis) and emphysema. It is only to be used with a nebulizer and is taken twice daily (morning and evening).

WARNING: ASTHMA-RELATED DEATH

PERFOROMIST Inhalation Solution belongs to a class of drugs called long-acting beta2-agonists (LABA). People with asthma who take LABA such as PERFOROMIST Inhalation Solution have an increased risk of death from asthma problems. Do not use PERFOROMIST Inhalation Solution if you have asthma without using a long-term asthma control medicine.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions
PERFOROMIST Inhalation Solution should not be used instead of rescue inhaler or nebulized medicine for the treatment of acute symptoms. Extra doses of PERFOROMIST Inhalation Solution should not be used for that purpose since overuse can cause serious heart problems, including death. Acute or sudden symptoms should be treated with an inhaled short-acting beta2-agonist. Seek immediate medical attention if:

  • your symptoms quickly worsen despite recommended doses of PERFOROMIST Inhalation Solution
  • PERFOROMIST Inhalation Solution treatment becomes less effective
  • you need more inhalations of a short-acting beta2-agonist (rescue inhaler or nebulized medicine) than usual.

Do not use PERFOROMIST Inhalation Solution with other LABA medicines for any reason.

How to Use PERFOROMIST Inhalation Solution
Use PERFOROMIST Inhalation Solution exactly as directed by your health care professional. Do not stop using PERFOROMIST Inhalation Solution or other medicines to control or treat your COPD unless told to do so by your health care professional because your symptoms might get worse. Your health care professional will change your medicines as needed.

Co-existing Conditions
The use of PERFOROMIST Inhalation Solution with certain health conditions or with certain medications can cause serious side effects. Tell your health care professional about all of your health conditions, including if you:

  • have heart problems
  • have high blood pressure
  • have diabetes
  • have seizures
  • have thyroid problems
  • have liver problems
  • are pregnant or planning to become pregnant. It is not known if PERFOROMIST Inhalation Solution can harm an unborn baby.
  • are breastfeeding. It is not known if PERFOROMIST Inhalation Solution passes into breast milk and if it can harm your baby.

Drug Interactions
Tell your health care professional about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. PERFOROMIST Inhalation Solution and certain other medicines may interact with each other and cause serious side effects.

Side Effects
The most common side effects reported in patients taking PERFOROMIST Inhalation Solution were diarrhea, nausea, nasopharyngitis, dry mouth, dizziness, and insomnia. Serious side effects may include sudden shortness of breath, serious allergic reactions, chest pain, increased or decreased blood pressure, a fast and irregular heartbeat, low blood potassium, high blood sugar, and high blood acid.

You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.