long-acting beta adrenergic receptor agonist (LABA)
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Indications
- prevention of bronchospasm in patients with COPD or asthma
Contraindications
- not for use in treating asthma without an inhaled glucocorticoid
Benefit/risk
- number needed to treat (NNT) - adults*
- 73 to prevent 1 moderate asthma attack requiring oral glucocorticoids[8]
- number needed to harm - adults*
- 140 to precipitate 1 severe asthma attack requiring hospitalization[8]
- 1400 to precipitate 1 fatal asthma attack[8]
- no benefit for children*
- hospitalization not avoided
- oral glucocorticoids not avoided[8]
- no harms noted in children*[8]
- no mortality benefit in patients with COPD[9]
* in conjunction with inhaled glucocorticoid
Adverse effects
- when taken without an inhaled glucocorticoid, may or may not increase risk for death[4][5][6]*
- Advair Diskus, Foradil Aerolizer, & Serevent Diskus may increase risk of severe asthma episodes, & death when those episodes occur[1][2], odds ratio=2.6-3.5
- increased cardiovascular risk in the elderly
- highest risk 2-3 weeks after starting treatment[7]
* risk for asthmatics > risk for patients with COPD
* FDA has found no significant increase in risk of adverse outcomes when LABA used in combination inhaled glucocorticoid[10][11]
* box warning removed Dec 2017[10][11]
- drug adverse effects of adrenergic receptor agonists
- drug adverse effects of beta-adrenergic receptor agonists
- drug adverse effects of long-acting beta-adrenergic receptor agonists
- drug adverse effects of sympathomimetic(s)
Mechanism of action
More general terms
More specific terms
- formoterol (Foradil, Perforomist)
- indacaterol (Arcapta)
- olodaterol (Striverdi Respimat)
- salmeterol (Serevent, Serevent Diskus)
- vilanterol
Component of
- LABA glucocorticoid combination
- LABA/LAMA glucocorticoid combination (triple therapy)
- LABA/LAMA combination
References
- ↑ 1.0 1.1 FDA Medwatch http://www.fda.gov/medwatch/safety/2005/safety05.htm#LABA
- ↑ 2.0 2.1 Prescriber's Letter 12(9): 2005 The Safety of Long-Acting Beta-2 Agonists in Patients with Asthma Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210907&pb=PRL (subscription needed) http://www.prescribersletter.com
US Department of Health and Human Services. National Institutes of Health. National Heart, Lung and Blood Institute. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma-Update on selected topics 2002. http://www.nhlbi.nih.gov/guidelines/asthma/asthmafullrpt.pdf - ↑ Salpeter SR et al, Meta-analysis: Effect of long-acting beta agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med 2006; 144:904 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16754916
Glassroth J The role of long-acting beta-agonists in the management of asthma. Analysis, meta-analysis, and more analysis, Ann Intern Med 2006; 144:936 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16754915 - ↑ 4.0 4.1 FDA advisory panel meeting Joint Meeting of the Pulmonary-Allergy Drugs Advisory Committee, Drug Safety & Risk Management Advisory Committee, and the Pediatric Advisory Committee December 10 & 11, 2008 http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4398b1-00-index.htm
Bateman E et al Effects of adding salmeterol to inhaled corticosteroids on serious asthma-related events. Ann Intern Med. 2008 Jul 1;149(1):33-42. Epub 2008 Jun 3. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18523132 <Internet> http://www.annals.org/cgi/content/full/0000605-200807010-00229v1
Weiss KB. Drug safety and salmeterol: The controversy continues. Ann Intern Med. 2008 Jul 1;149(1):56-7. Epub 2008 Jun 3. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18523131 <Internet> http://www.annals.org/cgi/content/full/0000605-200807010-00230v1 - ↑ 5.0 5.1 Prescriber's Letter 16(1): 2009 Safety of Long-Acting Beta-Agonists in Asthma Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250102&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Prescriber's Letter 17(4): 2010 New Safety Requirements for Long-Acting Beta-Agonists (LABAs) COMMENTARY: New Safety Requirements for Long-Acting Beta-Agonists (LABAs) COMMENTARY: Childhood Asthma Treatment: The BADGER Study Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260401&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 Gershon A et al Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease. JAMA Intern Med. 2013;():1-9. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23689820 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1689974
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 The NNT: Long-Acting Beta-Agonists with Inhaled Corticosteroids vs. Inhaled Steroids Alone for Adults with Asthma. http://www.thennt.com/nnt/combination-inhalers-steroids-plus-bronchodilators-for-adult-asthma/
The NNT: Long-Acting Beta-Agonists with Inhaled Corticosteroids vs. Inhaled Steroids Alone for Children with Asthma. http://www.thennt.com/nnt/combined-inhalers-vs-steroid-inhalers-for-childhood-asthma/
Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev. 2010 Apr 14;(4):CD005533 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20393943 - ↑ 9.0 9.1 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ 10.0 10.1 10.2 Brooks M FDA Drops Boxed Warning on LABA/ICS Asthma/COPD Meds Medscape - Dec 21, 2017. https://www.medscape.com/viewarticle/890470
FDA Safety Alert. Dec 20, 2017 Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed Warning About Asthma- Related Death Removed. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm590001.htm - ↑ 11.0 11.1 11.2 Busse WW, Bateman ED, Caplan AL et al Combined Analysis of Asthma Safety Trials of Long-Acting beta2- Agonists. N Engl J Med 2018; 378:2497-2505. June 28, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29949492 https://www.nejm.org/doi/full/10.1056/NEJMoa1716868
Seymour SM, Lim R, Xia C. Persepctive. Inhaled Corticosteroids and LABAs - Removal of the FDA's Boxed Warning. N Engl J Med 2018; 378:2461-2463. June 28, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29949485 https://www.nejm.org/doi/full/10.1056/NEJMp1716858