Medications listed in the tables and non-FDA approved indications that may be included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.

• Revision history
  • April 28, 2023
  • April 23, 2021
  • March 2019
  • March 2017
  • Oct. 2014
  • Feb. 2013
  • Oct. 2012
  • Jan. 2011
  • July 2007
  • March 2003
  • April 2002
  • March 2001
  • March 2000
  • Feb. 1999
  • March 1998
  • March 1997
  • Aug. 1995.
• Initially developed
  • Jan. 1995

Long-acting, selective beta2-agonists (LABAs) are FDA-approved for use as adjunctive therapy with long-term asthma control medications, such as inhaled corticosteroids (ICS), in managing reversible obstructive airways disease, including asthma and nocturnal asthma, in patients inadequately controlled with long-term asthma control medications. LABAs are contraindicated for use as monotherapy in asthma management due to an increased risk of asthma-related death as well as increased risks in asthma-related hospitalizations in pediatric and adolescent patients. Serevent Diskus® (salmeterol) is FDA-approved for asthma in adults and children four years and older when used with an ICS, and it is also FDA-approved for use to acutely prevent exercise-induced bronchospasm (EIB) on an as-needed basis. LABAs are FDA-approved for use in adults as maintenance therapy for bronchoconstriction associated with chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis. Striverdi Respimat® (olodaterol) is another LABA available without an ICS, and it is FDA-approved for the management of COPD. It does not have an FDA-approval for asthma.

LABAs combined with ICS are FDA-approved for use in adults and children as asthma maintenance therapy: Advair® HFA metered aerosol (fluticasone propionate/salmeterol) is FDA-approved for use in patients 12 years of age and older, and Dulera® (mometasone/formoterol) inhalation aerosol is FDA-approved for use in patients 5 years of age and older.  Advair Diskus® (fluticasone propionate/salmeterol) inhalation powder is FDA-approved for use in asthma maintenance in patients 4 years of age and older. AirDuo RespiClick® and AirDuo Digihaler® (fluticasone/salmeterol) inhalation powders provide additional dosage strengths, and they have been approved for use in patients with asthma who are 12 years and older. Symbicort® (budesonide/formoterol) inhalation aerosol and Advair Diskus® (fluticasone propionate/salmeterol) are FDA-approved for use in adults as COPD maintenance therapy. Symbicort® is also FDA-approved for the management of asthma in adults and children 6 years of age and older. The combination Breo Ellipta® (fluticasone/ vilanterol) is FDA approved for the management of COPD and asthma in patients 18 years of age and older^1,2,11. The Global Initiative for Asthma (GINA) “Global Strategy for Asthma Management and Prevention” guidelines recommend the use of combination ICS-LABA with budesonide and formoterol as maintenance and rescue therapy for most patients¹².

Anoro Ellipta® (umeclidinium/vilanterol), Bevespi Aerosphere® (glycopyrrolate/formoterol), and Stiolto Respimat® (tiotropium/olodaterol) are indicated for use in adults as maintenance therapy for COPD but are not FDA-approved for use in asthma.

Additionally, a triple therapy inhaler containing fluticasone, umeclidinium and vilanterol, Trelegy Ellipta®, is approved for COPD management to treat airway obstruction and reduce exacerbations and for the maintenance treatment of asthma in patients 18 years and older.

Duaklir Pressair® (aclidinium bromide/ formoterol) is a long-acting beta agonist and long-acting muscarinic antagonist combination product approved for the management of COPD in adults.

Generally, LABAs should only be used as maintenance therapy. Recent guideline updates recommend the combined use of formoterol and budesonide as maintenance and rescue therapy for most patients with asthma, including the use of this combination as needed¹².

For maintenance therapy, daily administration of LABAs alone or in combination with ICS is warranted in asthma and COPD. Formoterol combination products, olodaterol monotherapy and combination products, salmeterol monotherapy and combination products, and vilanterol combination products are metered-dose inhalers designed to deliver a set number of inhalations based on the canister size as well as the medication prescribed. Tables 5 and 6 summarize the number of inhalations available LABA and LABA combination products provide, respectively, and the days’ supply per inhaler or blister package based on the maximum dose allowed per day (see Tables 1 through 4). Excessive use may be identified based on refill frequency. Inappropriate supply of salmeterol metered-dose inhalers, salmeterol/fluticasone blister packages, formoterol blister packages, budesonide/formoterol metered-dose inhalers, or mometasone/formoterol metered-dose inhalers will be monitored by reviewing excessive refills.

Legend:

• + calculated based on canister size/blister package size and maximum dose allowed per day
• * Salmeterol inhalation powder, alone or in combination with fluticasone, may be used in children less than 4 years of age

Legend:

• + calculated based on canister size/blister package size and maximum dose allowed per day
• ~ not indicated for use in children
• * Salmeterol inhalation powder, alone or in combination with fluticasone, may be used in children > 4 years of age
• # Budesonide/formoterol indicated for children > 6 years of age
• ^ Fluticasone/salmeterol inhalation aerosol and fluticasone/salmeterol inhalation powder as AirDuo® RespiClick and AirDuo Digihaler® as well as  mometasone/formoterol inhalation aerosols only indicated for children > 12 years of age
• ! Mometasone furoate/ formoterol 50 mcg/ 5mcg/ inhalation is approved for children 5 years of age and older

Acute asthma exacerbations require treatment with short-acting beta2-adrenergic agents even though maintenance therapy with LABAs may be prescribed concomitantly. Patients may receive a long- and short-acting beta2-adrenergic drug concurrently for short time periods to manage acute attacks. LABAs used in conjunction with frequently administered short-acting beta2-adrenergic drugs (i.e., frequent refill of a short-acting beta2-adrenergic agonist within a 30-day time period) will be reviewed.

Current literature does not support the adjunctive use of multiple LABAs for prevention and control of asthma symptoms. Concomitant LABA use will be reviewed as clinical evidence does not validate improved outcome with conjunctive therapy.

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for LABAs and combination products are summarized in Table 7. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Legend:

• +CP = Clinical Pharmacology
• COPD = chronic obstructive pulmonary disease
• ECG = electrocardiogram
• MAOIs = monoamine oxidase inhibitors
• TCAs = tricyclic antidepressants

1. IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.libproxy.uthscsa.edu/ (cited: March 16, 2023).
2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2023. Available at: http://clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed March 16, 2023.
3. Salmeterol xinafoate inhalation powder (Serevent® Diskus®) package insert.  GlaxoSmithKline, February 2022.
4. Olodaterol inhalation spray (Striverdi® Respimat®) package insert.  Boehringer Ingelheim Pharmaceutical, Inc., November 2021.
5. Fluticasone/salmeterol inhalation aerosol (Advair® HFA) package insert.  GlaxoSmithKline, August 2021.
6. Mometasone furoate/formoterol inhalation aerosol (Dulera®) package insert.  Merck & Co., June 2021.
7. Fluticasone/salmeterol inhalation powder (Advair Diskus®) package insert.  GlaxoSmithKline, October 2020.
8. Fluticasone/salmeterol inhalation powder (AirDuo RespiClick®) package insert. Teva Pharmaceuticals, September 2022.
9. Fluticasone/salmeterol inhalation powder (AirDuo Digihaler®) package insert. Teva Pharmaceuticals, April 2022.
10. Budesonide/formoterol fumarate inhalation aerosol (Symbicort®) package insert. AstraZeneca, July 2019.
11. Fluticasone/vilanterol inhalation powder (Breo® Ellipta™) package insert. GlaxoSmithKline, July 2021.
12. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2022. Available from: https://ginasthma.org/gina-reports/. Accessed March 16, 2023.
13. Umeclidinium/vilanterol inhalation powder (Anoro® Ellipta®) package insert.  GlaxoSmithKline, October 2022.
14. Glycopyrrolate/formoterol inhalation aerosol (Bevespi Aerosphere®) package insert. AstraZeneca, November 2020.
15. Tiotropium/olodaterol (Stiolto® Respimat®) package insert. Boehringer-Ingelheim Pharmaceuticals, Inc., November 2021.
16. Fluticasone/umeclidinium/vilanterol inhalation powder (Trelegy® Ellipta®) package insert. GlaxoSmithKline, December 2022.
17. Aclidinium/ formoterol fumarate powder (Duaklir Pressair®) metered dose inhaler package insert. Circassia Pharmaceuticals, Inc., January 2022.
18. Budesonide/ Glycopyrrolate/ formoterol fumarate inhalation aerosol (Breztri Aerosphere®) package insert. January 2022.
19. Fluticasone/salmeterol inhalation powder (Wixela Inhub®) package insert. Mylan Pharmaceuticals, Inc., August 2022.