Long-acting beta agonists in Asthma and COPD October 2013

ong-acting beta agonists or COPD patients. In addition Points to Remember    L (LABA) have been to requiring a Black Box demonstrated to be very effective Warning on these products  NEVER use LABAs as first line of therapy in the treatment of asthma and (LABA) and their combinations  NEVER use LABAs as chronic obstructive pulmonary (Advair®, Dulera® and monotherapy for long-term ® disease (COPD). They work Symbicort ), in April 2011, the asthma control through sustained smooth agency ordered drug makers to  Preferred therapy is to muscle relaxation and are potent conduct clinical trials involving combine LABAs with ICS in bronchodilators. However, a total of 53,000 patients to test ages 12 and older for monotherapy with a LABA such the safety of these products. moderate to severe- as salmeterol, formoterol, The FDA expects to receive persistent asthma arformeterol, and indacaterol (the results of these trials in 2017.  NOT recommended for relief of acute symptoms or four current FDA-approved The Global Initiative for exacerbations products in this class) is not Asthma (GINA) 2009  Avoid using combination recommended.1 This is due to the guidelines and the National products prior to trial of agency’s (FDA) meta-analysis Heart, Lung, and Blood inhalation corticosteroids which found that use of LABAs Institute (NHLBI) 2007 asthma  Advise patients to have was associated with an increased guidelines recommend adding short-acting beta agonists at risk of asthma-related LABAs to patients ≥ 12 years ALL times for rescue hospitalization, intubation and old inadequately controlled on therapy death. Subsequent studies did inhaled corticosteroids.2,3  Avoid DUPLICATION of not find significant increase in Overall, systemic reviews and LABAs in patients regimens (see table for available risk in a subset of patients who guidelines consistently products and their contents) used inhalation corticosteroids demonstrate that adding LABA

1 (ICS) with a LABA. There is to ICS in adults and children reduce short-acting rescue however no evidence that with persistent asthma will inhaler use compared to ICS dose escalation.4 There is currently no evidence to support the use of There is however no evidence that supports use of this LABA/ICS as both maintenance combination as first line of therapy for asthma or and quick relief treatment as

COPD patients. opposed to what was recommended in the SMART supports use of this combination improve airway function, asthma (Single inhaler Maintenance And as first line of therapy for asthma symptoms, quality of life, and Reliever Therapy) study.5

Products available in United States (not all inclusive) Drug Active Indication Dosage Dosage and Common Side Effects Ingredient Forms administration Long-acting Beta-2 Agonists Arcapta® indacaterol Long-term maintenance Powder for 75 mcg capsule Post-inhalation cough, maleate bronchodilator treatment of airflow inhalation inhaled orally daily nasopharyngitis, obstruction in patients with COPD, via Max = 75 mcg/24 headache, nausea, including chronic bronchitis and/or Neohaler hrs oropharyngeal pain, etc. emphysema Brovana® aformoterol Long-term maintenance treatment Solution in 15 mcg via Chest pain, back pain, tartrate of bronchoconstriction in patients ready-to-use nebulization twice diarrhea, sinusitis, leg with COPD including chronic vials used daily (morning and cramps, dyspnea, etc. bronchitis and/or emphysema via evening) nebulizer Max = 30 mcg/day Foradil® formoterol Treatment of asthma and Capsule 12 mcg inhaled Viral infection, fumarate prevention of exercise-induced with dry every 12 hours bronchitis, dyspnea, chest bronchospasm (EIB) in patients ≥ 5 powder for pain, tremor, dizziness, years. oral etc. Maintenance treatment of inhalation Perforomist® bronchospasm in patients with 20mcg inhaled via inhalation COPD Solution for nebulizer every 12 solution oral hours inhalation Serevent® salmeterol For the maintenance treatment of Diskus for 50 mcg (1 Headache, nasal asthma and COPD. oral inhalation) twice congestion, bronchitis, For the prevention of exercise- inhalation daily influenza, asthma, etc. induced bronchospasm (EIB) EIB: 1 inhalation 30 minutes before exercise Combination (LA Beta-2 Agonist + Corticosteroid) Advair® salmeterol Maintenance treatment of asthma Diskus Diskus: 50/100, Upper respiratory tract and in patients 4 years and older (powder) 50/250, 50/500* infection, pharyngitis, fluticasone Maintenance treatment of airflow for oral twice daily headache, throat obstruction and reducing inhalation HFA: 21/45, 21/115, irritation, exacerbations in patients with HFA – 21/230 (2 musculoskeletal pain, etc. COPD inhalation inhalations twice aerosol daily (asthma only) Dulera® mometasone Treatment of asthma patients 12 Inhalation 2 inhalations twice Nasopharyngitis, and years of age and older aerosol daily headache, sinusitis, oral formoterol Max = mometasone candidiasis, angiodema 800 mcg/formoterol 20 mcg per day Symbicort® budesonide Treatment of asthma patients 12 Metered 80/4.5, 160/4.5** Headache, and years of age and older. dose inhaler 2 inhalations twice nasopharyngitis, upper formoterol Maintenance treatment of airflow daily resp. infection, obstruction in patients with COPD Max = 640/18/day pharyngolaryngeal pain, including chronic bronchitis and etc. emphysema *Advair Diskus® 50/500 not recommended in the treatment of COPD **Symbicort® 320/9 dose limit for COPD

References 1. Drugs for Asthma and COPD. Treatment Guidelines from The Medical Letter. 2013:11(132):75-86. 2. US Department of Health and Human Services NH, Lung and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. 2007. 3. Oregon State University College of Pharmacy. Drug Use Research & Management Program: Combination Long-Acting Beta-Agonist Inhaled Corticosteroid: Summary of Clinical Evidence and Drug Utilization Evaluation. March 2010 http://pharmacy.oregonstate.edu/drug_policy/sites/default/files/pages/dur_board/evaluations/articles/laba_ics_due.pdf

4. Knox AJ, Mortimer K. Combining inhaled glucocorticoids and long acting β2-adrenoceptor agonists in asthma and COPD. British Journal of Pharmacology 2008;153:1085-1086 5. Chapman KR, et al. Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal. Thorax. 2010;65(8)747-52. http://thorax.bmj.com/content/early/2010/06/26/thx.2009.128504.full 6. Arcapta [package insert]. Stein, Switzerland. Norvatis; 2012. 7. Brovana [package insert]. Marlborough, MA: Sunovion Pharmaceuticals Inc. 2011. 8. Foradil [package insert]. Whitehouse Station, NJ: Merck & Co., Inc: 2010. 9. Serevent [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2008 10. Advair [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2006 11. Dulera [package insert]. Whitehouse Station, NJ: Merck & Co., Inc: 2010. 12. Symbicort [package insert]. Wilmington, DE. AstraZeneca; 2006.

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