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Asthma Medications and the New FDA Public Health Advisory
JNP
Asthma Medications and the New FDA Public Health Advisory Public Health Advisory On November 18, 2005, the US Food and Drug Administration (FDA) issued a public health advisory with new warnings for long-acting 2 adrenergic agonists (LABAs).1 The 2 generic drugs affected are salmeterol and formoterol. These drugs are found in Serevent Diskus, Advair Diskus, and Foradil Aerolizer. They may increase the severity of asthma episodes, even though they decrease the frequency. One study reported an increased risk of death for patients who used LABAs.2 It is not known if there are similar concerns when
PRESCRIPTION PAD Maren Mayhew
these drugs are used for exercised-induced asthma or chronic obstructive pulmonary disease. Recommendations for their use follow: 1. LABAs should not be used as a first-line medication for asthma. 2. LABAs should always be used with inhaled corticosteroids. Instructions for patients are: 1. Patients should not use LABAs to treat worsening wheezing. They should call their health care provider if their wheezing worsens while using an LABA. 120
2.
Patients should have a short-acting bronchodilator available to treat sudden wheezing. 3. Patients should not stop their LABA or any other asthma medication without discussing it with their health care provider. The FDA has patient information sheets for these medications at its Web site (www.fda.gov).3 It also has posted an article about asthma for consumers.4
Increased Risk of Death From Asthma Inpatient mortality from asthma is very rare; however, outpatient deaths and hospitalizations remain a problem. Sudden death from an asthma exacerbation may occur after an asthma attack that has worsened over days to weeks. Many occur 30 minutes to 8 hours after onset. However, some deaths occur within minutes. They tend to occur in patients younger than 25 years, especially in adolescents 10 to 14 years old. There are many risk factors for sudden death from asthma, some of which are psychosocial. Psychiatric illnesses such as depression, medication noncompliance, patient/provider conflict, poor perception of dyspnea, and disregard for asthma symptoms and/or severity increase risk. Moreover, many of these are likely to occur in patients 10 to 25 years old. Patients at risk for sudden death from asthma have a strong allergic component to their asthma. They often have increased bronchial hyperreactivity, atopy, and allergy to the mold Alternaria. Another important risk factor is previous episodes of severe asthma attacks. Smoking has not been studied as a risk factor.5 February 2006
In addition to the problem of LABAs being associated with increased risk for sudden death, excessive use of short-acting ‚ agonists (SABAs) may contribute. If a patient finds himself increasing his use of SABAs, he should see his provider. Bronchodilators may mask an increased allergic response to an allergen. Patients must also treat the allergic component of the disease, which is the reason inhaled corticosteroids are so important. Initial treatment of a severe exacerbation of asthma includes intramuscular epinephrine, oxygen, intravenous corticosteroids, and inhaled‚ agonists with or without Atrovent often by nebulization.
Drugs for Asthma LABAs are used for maintenance treatment in asthma patients who use inhaled corticosteroids. Their duration of action is about 12 hours, they may help decrease the dose of inhaled corticosteroids, and they cost about $90 a month.6 SABAs are used as needed for mild, infrequent episodes of asthma and as a rescue medication for mild to severe asthma. Levalbuterol, the R isomer of albuterol, is much more expensive than other SABAs and has not been shown to be more effective. Regular SABAs cost $20 to $185 per month. Inhaled corticosteroids are used on a continuous basis for asthma that is not controlled by intermittent SABAs. They decrease the risk of severe episodes and improve control. They are more effective than LABAs or leukotriene modifiers. Certain inhaled corticosteroids can be used in infants and children. The cost varies from $40 to $150 a month. Oral corticosteroids are effective for severe acute episodes when short-acting bronchodilators are not completely effective. They are used in severe asthma that is not controlled by other medications. These cost $10 to $100 per month. Leukotriene modifiers have not been shown to be as effective as corticosteroids, and LABAs are more effective than leukotriene modifiers as a second-line drug after inhaled corticosteroids. Montelukast is often used as a third-line drug if inhaled corticosteroids and an LABA do not control symptoms. Montelukast (Singulair) is considered safer than zafirlukast and costs about $90 per month. www.npjournal.org
Cromolyn and nedocromil are extremely safe but less effective than inhaled corticosteroids. They may be particularly effective in children. Theophylline is less effective as a second-line drug than are LABAs. Its advantage is cost; it can run as low as $8 per month. The anticholinergic ipratropium (Atrovent) is not approved by the FDA for asthma but is used off label for acute treatment and as a continuous second-line drug. Omalizumab, the anti-immunoglobulin E antibody, is used for moderate to severe persistent asthma, with a strong allergic component. Asthma is increasing in prevalence; approximately 10% of Americans have asthma during their lifetime. It is important to identify patients at risk for sudden severe exacerbations and manage their condition closely. These patients often require referral to asthma specialists. References 1. Food and Drug Administration. Long-acting beta2-adrenergic agonists: Advair Diskus (fluticasone propionate & salmeterol inhalation powder), Foradil Aerolizer (formoterol fumarate inhalation powder), Serevent Diskus (salmeterol xinafoate inhalation powder); November 18, 2005. Available at: http://www.fda.gov/medwatch/safety/2005/safety05.htm#LABA. Accessed December 6, 2005. 2. FDA Medical Officer Review, July 13, 2005. Available at: http://www.fda.gov/ohrms/dockets/ac/05/briefing/20054148B1_03_02-FDA-Smart-Study.pdf. 3. Food and Drug Administration. Salmeterol xinafoate inhalation powder (marketed as Serevent Diskus). Available at: www.fda.gov/cder/drug/InfoSheets/patient/salmeterolPIS.pdf. 4. Flieger K. Controlling asthma. FDA consumer magazine; November 1996, updated June 2000. Available at: www.fda.gov/fdac/features/996_asth.html. Accessed December 6, 2005. 5. O’Hollaren MT. Sudden death from asthma: is your patient at risk. Available at: www.medscape.com/viewprogram/4505_index. Accessed December 6, 2005. 6. Drugs for asthma. Treatment guidelines. Med Lett. 2005;3 (33).
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at maren [email protected]. This will be a monthly column on medication news and controversies. Suggestions for topics are welcome.
1555-4155/06/$ see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.nurpra.2005.12.015
121
Asthma Medications and the New FDA Public Health Advisory Public Health Advisory On November 18, 2005, the US Food and Drug Administration (FDA) issued a public health advisory with new warnings for long-acting 2 adrenergic agonists (LABAs).1 The 2 generic drugs affected are salmeterol and formoterol. These drugs are found in Serevent Diskus, Advair Diskus, and Foradil Aerolizer. They may increase the severity of asthma episodes, even though they decrease the frequency. One study reported an increased risk of death for patients who used LABAs.2 It is not known if there are similar concerns when
PRESCRIPTION PAD Maren Mayhew
these drugs are used for exercised-induced asthma or chronic obstructive pulmonary disease. Recommendations for their use follow: 1. LABAs should not be used as a first-line medication for asthma. 2. LABAs should always be used with inhaled corticosteroids. Instructions for patients are: 1. Patients should not use LABAs to treat worsening wheezing. They should call their health care provider if their wheezing worsens while using an LABA. 120
2.
Patients should have a short-acting bronchodilator available to treat sudden wheezing. 3. Patients should not stop their LABA or any other asthma medication without discussing it with their health care provider. The FDA has patient information sheets for these medications at its Web site (www.fda.gov).3 It also has posted an article about asthma for consumers.4
Increased Risk of Death From Asthma Inpatient mortality from asthma is very rare; however, outpatient deaths and hospitalizations remain a problem. Sudden death from an asthma exacerbation may occur after an asthma attack that has worsened over days to weeks. Many occur 30 minutes to 8 hours after onset. However, some deaths occur within minutes. They tend to occur in patients younger than 25 years, especially in adolescents 10 to 14 years old. There are many risk factors for sudden death from asthma, some of which are psychosocial. Psychiatric illnesses such as depression, medication noncompliance, patient/provider conflict, poor perception of dyspnea, and disregard for asthma symptoms and/or severity increase risk. Moreover, many of these are likely to occur in patients 10 to 25 years old. Patients at risk for sudden death from asthma have a strong allergic component to their asthma. They often have increased bronchial hyperreactivity, atopy, and allergy to the mold Alternaria. Another important risk factor is previous episodes of severe asthma attacks. Smoking has not been studied as a risk factor.5 February 2006
In addition to the problem of LABAs being associated with increased risk for sudden death, excessive use of short-acting ‚ agonists (SABAs) may contribute. If a patient finds himself increasing his use of SABAs, he should see his provider. Bronchodilators may mask an increased allergic response to an allergen. Patients must also treat the allergic component of the disease, which is the reason inhaled corticosteroids are so important. Initial treatment of a severe exacerbation of asthma includes intramuscular epinephrine, oxygen, intravenous corticosteroids, and inhaled‚ agonists with or without Atrovent often by nebulization.
Drugs for Asthma LABAs are used for maintenance treatment in asthma patients who use inhaled corticosteroids. Their duration of action is about 12 hours, they may help decrease the dose of inhaled corticosteroids, and they cost about $90 a month.6 SABAs are used as needed for mild, infrequent episodes of asthma and as a rescue medication for mild to severe asthma. Levalbuterol, the R isomer of albuterol, is much more expensive than other SABAs and has not been shown to be more effective. Regular SABAs cost $20 to $185 per month. Inhaled corticosteroids are used on a continuous basis for asthma that is not controlled by intermittent SABAs. They decrease the risk of severe episodes and improve control. They are more effective than LABAs or leukotriene modifiers. Certain inhaled corticosteroids can be used in infants and children. The cost varies from $40 to $150 a month. Oral corticosteroids are effective for severe acute episodes when short-acting bronchodilators are not completely effective. They are used in severe asthma that is not controlled by other medications. These cost $10 to $100 per month. Leukotriene modifiers have not been shown to be as effective as corticosteroids, and LABAs are more effective than leukotriene modifiers as a second-line drug after inhaled corticosteroids. Montelukast is often used as a third-line drug if inhaled corticosteroids and an LABA do not control symptoms. Montelukast (Singulair) is considered safer than zafirlukast and costs about $90 per month. www.npjournal.org
Cromolyn and nedocromil are extremely safe but less effective than inhaled corticosteroids. They may be particularly effective in children. Theophylline is less effective as a second-line drug than are LABAs. Its advantage is cost; it can run as low as $8 per month. The anticholinergic ipratropium (Atrovent) is not approved by the FDA for asthma but is used off label for acute treatment and as a continuous second-line drug. Omalizumab, the anti-immunoglobulin E antibody, is used for moderate to severe persistent asthma, with a strong allergic component. Asthma is increasing in prevalence; approximately 10% of Americans have asthma during their lifetime. It is important to identify patients at risk for sudden severe exacerbations and manage their condition closely. These patients often require referral to asthma specialists. References 1. Food and Drug Administration. Long-acting beta2-adrenergic agonists: Advair Diskus (fluticasone propionate & salmeterol inhalation powder), Foradil Aerolizer (formoterol fumarate inhalation powder), Serevent Diskus (salmeterol xinafoate inhalation powder); November 18, 2005. Available at: http://www.fda.gov/medwatch/safety/2005/safety05.htm#LABA. Accessed December 6, 2005. 2. FDA Medical Officer Review, July 13, 2005. Available at: http://www.fda.gov/ohrms/dockets/ac/05/briefing/20054148B1_03_02-FDA-Smart-Study.pdf. 3. Food and Drug Administration. Salmeterol xinafoate inhalation powder (marketed as Serevent Diskus). Available at: www.fda.gov/cder/drug/InfoSheets/patient/salmeterolPIS.pdf. 4. Flieger K. Controlling asthma. FDA consumer magazine; November 1996, updated June 2000. Available at: www.fda.gov/fdac/features/996_asth.html. Accessed December 6, 2005. 5. O’Hollaren MT. Sudden death from asthma: is your patient at risk. Available at: www.medscape.com/viewprogram/4505_index. Accessed December 6, 2005. 6. Drugs for asthma. Treatment guidelines. Med Lett. 2005;3 (33).
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at maren [email protected]. This will be a monthly column on medication news and controversies. Suggestions for topics are welcome.
1555-4155/06/$ see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.nurpra.2005.12.015
121