The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Update on the Safety of Long-acting Beta2-agonists

지속성베타2항진제(LABA)의 안전성

  • Lee, Byung-Jae (Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 이병재 (성균관대학교 의과대학 삼성서울병원 내과)
  • Published : 2011.02.01
⟨ Previous Next ⟩

Abstract

A recent meta-analysis of clinical trials found that long-acting beta2-agonists (LABA) increased life-threatening asthma exacerbations and deaths, which led to warnings concerning regular use of LABA by U.S. Food and Drug Administration (FDA). It is now obvious that LABA monotherapy in asthma increases the risk of serious adverse events. However, the risk is reduced with concomitant use of inhaled corticosteroid (ICS). Hence the FDA' recommendations that LABA should not be used in patients whose asthma is well controlled with a medium dose of ICS, or LABA should be withdrawn once asthma control is achieved, remain still controversial. It seems reasonable to follow current guidelines which recommend the use of LABA when asthma is not controlled with ICS, although more well-designed research on the safety of LABA, especially when combined with ICS, is required.

Keywords

References

  1. Greenstone IR, Ni Chroinin MN, Masse V, et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database Syst Rev: CD005533, 2005.
  2. Masoli M, Weatherall M, Holt S, Beasley R. Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma. Thorax 2005;60:730-734. https://doi.org/10.1136/thx.2004.039180
  3. Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) Report 2009. Available from www.ginasthma.org
  4. Pearce N, Crane J, Burgess C, Beasley R, Jackson R. Fenoterol and asthma mortality. Lancet 1989;1:1196-1197.
  5. van Schayck CP, Cloosterman SG, Bijl-Hofland ID, van den Hoogen H, Folgering HT, van Weel C. Is the increase in bronchial responsiveness or FEV1 shortly after cessation of beta2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting beta2- agonists. Respir Med 2002;96:155-162. https://doi.org/10.1053/rmed.2001.1243
  6. Castle W, Fuller R, Hall J, Palmer J. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993;306:1034-1037. https://doi.org/10.1136/bmj.306.6884.1034
  7. Mann RD, Kubota K, Pearce G, Wilton L. Salmeterol: a study by prescription-event monitoring in a UK cohort of 15,407 patients. J Clin Epidemiol 1996;49:247-250. https://doi.org/10.1016/0895-4356(95)00555-2
  8. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129:15-26. https://doi.org/10.1378/chest.129.1.15
  9. Mann M, Chowdhury B, Sullivan E, Nicklas R, Anthracite R, Meyer RJ. Serious asthma exacerbations in asthmatics treated with high-dose formoterol. Chest 2003;124:70-74. https://doi.org/10.1378/chest.124.1.70
  10. Expert Panel Report 3 (EPR-3): Guideline for the Diagnosis and Management of Asthma. National Heart Lung and Blood Institute (NHLBI) Report 2007. Available from http://www.nhlbi.nih.gov/guidelines/asthma
  11. US Food and Drug Administration. Long-acting beta-agonists and adverse asthma events meta-analysis. Available from http://www. fda.gov/ohrms/dockets/ac/08/briefing/2008-4398b1-01-FDA.pdf
  12. US Food and Drug Administration. FDA Drug Safety Communication:New Safety Requirements for Long-Acting Inhaled Asthma Medications Called Long-Acting Beta-Agonists (LABAs). Available from http://www.fda.gov/Drugs/DrugSafety/postmarketDrugSafety InformationforPatientsandProviders/ucm200776.htm
  13. Anderson HR, Ayres JG, Sturdy PM, et al. Bronchodilator treatment and deaths from asthma: case-control study. BMJ 2005;330: 117. https://doi.org/10.1136/bmj.38316.729907.8F
  14. de Vries F, Setakis E, Zhang B, van Staa TP. Long-acting {beta} 2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: a study using the GPRD. Eur Respir J 2010;36:494-502. https://doi.org/10.1183/09031936.00124209
  15. Price JF, Radner F, Lenney W, Lindberg B. Safety of formoterol in children and adolescents: experience from asthma clinical trials. Arch Dis Child 2010;95:1047-1053. https://doi.org/10.1136/adc.2010.183814
  16. Weatherall M, Wijesinghe M, Perrin K, Harwood M, Beasley R. Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy. Thorax 2010;65:39-43. https://doi.org/10.1136/thx.2009.116608