1. Dosage
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 older1,2,11. 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.
1.1. Adults
To manage EIB in adults, one salmeterol 50 mcg inhalation is administered at least 30 minutes before exercise on an as needed basis and should not be repeated for at least 12 hours after administration of the previous dose. Patients receiving twice daily LABA doses chronically should not administer additional LABA doses for EIB management.
Maximum recommended adult daily doses for LABA use as monotherapy in asthma and COPD are summarized in Table 1. Prescribed dosages exceeding these guidelines will be reviewed.
LABA/ICS combinations are FDA-approved for use in asthma and COPD maintenance therapy. Advair Diskus® 250 mcg/50 mcg is the only fluticasone/salmeterol dose approved for use in adult patients with COPD. Symbicort® 80 mcg/4.5 mcg and 160 mcg/4.5 mcg are FDA-approved for use in asthma, while 160 mcg/4.5 mcg is the recommended strength for budesonide/formoterol in COPD. Advair HFA®, AirDuo RespiClick®, AirDuo Digihaler®, and Dulera® are FDA-approved for asthma management only.
Maximum adult daily dosages for LABA combination therapy are summarized in Table 2. Dosages exceeding these recommendations will be reviewed.
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
---|---|---|---|
olodaterol hydrochloride (Striverdi Respimat®) | inhalation aerosol: 2.5 mcg/actuation | COPD | 2 actuations once daily; total dose = 5 mcg/day |
salmeterol (Serevent Diskus®) | inhalation powder: 50 mcg/inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 100 mcg/day |
COPD | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 100 mcg/day |
Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
---|---|---|---|
aclidinium bromide/formoterol fumarate (Duaklir Pressair) | inhalation powder: 400 mcg/ 12 mcg/ inhalation | COPD | 2 actuations/day (1 actuation twice daily); total dose = 800 mcg/24 mcg/day |
budesonide/ formoterol ((Symbicort, generics) | inhalation aerosol: 80 mcg/4.5 mcg/ inhalation | Asthma | 4 actuations/day (2 actuations twice daily); total dose = 320 mcg/18 mcg/day |
inhalation aerosol: 160 mcg/4.5 mcg/inhalation | Asthma | 4 actuations/day (2 actuations twice daily); total dose = 640 mcg/18 mcg/day | |
COPD | 4 actuations/day (2 actuations twice daily); total dose = 640 mcg/18 mcg/day | ||
budesonide/ glycopyrrolate/ formoterol fumarate (Breztri Aerosphere) | inhalation aerosol: 160 mcg/9 mcg/4.8 mcg/inhalation | COPD | 4 actuations/day (2 actuations twice daily); total dose = 640 mcg/ 36 mcg/ 19.2 mcg/ day |
fluticasone propionate/salmeterol xinafoate (Advair HFA, generic) | inhalation aerosol: 45 mcg fluticasone/21 mcg salmeterol/inhalation | Asthma | 4 actuations/day (2 actuations twice daily); total dose = 180 mcg/84 mcg/day |
inhalation aerosol: 115 mcg fluticasone/21 mcg salmeterol/inhalation | 4 actuations/day (2 actuations twice daily); total dose = 460 mcg/84 mcg/day | ||
inhalation aerosol: 230 mcg fluticasone/21 mcg salmeterol/inhalation | 4 actuations/day (2 actuations twice daily); total dose = 920 mcg/84 mcg/day | ||
fluticasone propionate/ salmeterol (Advair Diskus, Wixela Inhub, generics) | inhalation powder: 100 mcg fluticasone/50 mcg salmeterol/ inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 200 mcg/100 mcg/day |
inhalation powder: 250 mcg fluticasone/50 mcg salmeterol/inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose =500 mcg/100 mcg/day | |
COPD | 2 actuations/day in divided doses (1 actuation twice daily); total dose =500 mcg/100 mcg/day | ||
inhalation powder: 500 mcg fluticasone/50 mcg salmeterol/inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 1000 mcg/100 mcg/day | |
fluticasone propionate/salmeterol (AirDuo RespiClick) | inhalation powder: 55 mcg fluticasone/14 mcg salmeterol/inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 110 mcg/28 mcg/day |
inhalation powder: 113 mcg fluticasone/14 mcg salmeterol/inhalation | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 226 mcg/28 mcg/day | ||
inhalation powder: 232 mcg fluticasone/14 mcg salmeterol/inhalation | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 464 mcg/28 mcg/day | ||
fluticasone propionate/salmeterol (AirDuo Digihaler) | inhalation powder: 55 mcg fluticasone/ 14 mcg salmeterol/inhalation | Asthma | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 110 mcg/28 mcg/day |
inhalation powder: 113 mcg fluticasone/14 mcg salmeterol/inhalation | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 226 mcg/28 mcg/day | ||
inhalation powder: 232 mcg fluticasone/14 mcg salmeterol/inhalation | 2 actuations/day in divided doses (1 actuation twice daily); total dose = 464 mcg/28 mcg/day | ||
fluticasone furoate/umeclidinium/vilanterol (Trelegy Ellipta) | inhalation powder: 100 mcg/ 62.5 mcg/ 25 mcg/inhalation | Asthma | 1 actuation/day; total dose = 100 mcg/62.5 mcg/ 25 mcg/day |
COPD | 1 actuation/day; total dose = 100 mcg/62.5 mcg/ 25 mcg/day | ||
inhalation powder: 200 mcg/ 62.5 mcg/ 25 mcg/inhalation | Asthma | 1 actuation/day; total dose = 200 mcg/62.5 mcg/ 25 mcg/day | |
fluticasone furoate/vilanterol (Breo Ellipta, generics) | inhalation powder: 100 mcg fluticasone/25 mcg vilanterol/inhalation | Asthma | 1 actuation/day; total dose = 100 mcg/25 mcg/day |
inhalation powder: 200 mcg fluticasone/25 mcg vilanterol/inhalation | 1 actuation/day; total dose = 200 mcg/25 mcg/day | ||
inhalation powder: 100 mcg fluticasone/25 mcg vilanterol/inhalation | COPD | 1 actuation/day; total dose = 100 mcg/25 mcg/day | |
glycopyrrolate/ formoterol (Bevespi Aerosphere) | inhalation aerosol: 9 mcg glycopyrrolate/ 4.8 mcg formoterol/ actuation | COPD | 4 actuations/day in two divided doses (2 actuations twice daily); total dose = 36 mcg/19.2 mcg/day |
mometasone/ formoterol (Dulera) | inhalation aerosol: 100 mcg mometasone/5 mcg formoterol/inhalation | Asthma | for patients on medium-dose inhaled corticosteroids: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 400 mcg/20 mcg/day |
inhalation aerosol: 200 mcg mometasone/5 mcg formoterol/inhalation | patients on high-dose inhaled corticosteroids: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 800 mcg/20 mcg/day | ||
tiotropium/olodaterol (Stiolto Respimat) | inhalation aerosol: 2.5 mcg tiotropium/2.5 mcg olodaterol/inhalation | COPD | 2 actuations once daily (total dose = 5 mcg/5 mcg/day |
umeclidinium/vilanterol (Anoro Ellipta) | inhalation powder: 62.5 mcg umeclidinium/25 mcg vilanterol/inhalation | COPD | 1 actuation/day; total dose = 62.5 mcg/25 mcg/day |
1.2. Pediatrics
The safety and efficacy of inhalational salmeterol in children less than 4 years have not been established. Olodaterol is not approved for use in children as safety and efficacy of these agents have not been established in the pediatric population. Similarly, the glycopyrrolate/formoterol, aclidinium/formoterol, fluticasone/vilanterol, and the umeclidinium/vilanterol combination products are not FDA-approved for pediatric use as safety and efficacy have not been determined in this patient population for these inhalation combinations.
To prevent EIB in pediatric patients 4 years of age and older, one salmeterol 50 mcg inhalation is administered at least 30 minutes before exercise on an as-needed basis; doses should not be repeated for at least 12 hours after administration of the previous dose. Patients receiving twice daily LABA doses chronically should not administer additional LABA doses for EIB management.
Pediatric dosages for LABAs used as maintenance asthma therapy are summarized in Tables 3 and 4.
Drug Name | Dosage Form/Strength | Patient Age/Maximum Recommended Dosage |
---|---|---|
salmeterol (Serevent® Diskus®) | inhalation powder: 50 mcg/inhalation | Greater than or equal to 4 years of age: 2 actuations/day (1 actuation twice daily); total dose = 100 mcg/day |
Drug Name | Dosage Form/Strength | Patient Age/Maximum Recommended Dosage |
---|---|---|
budesonide/formoterol (Symbicort®) | inhalation aerosol: 80 mcg/4.5 mcg/ inhalation | 6 to 11 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 320 mcg/18 mcg/day |
Greater than or equal to 12 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 320 mcg/18 mcg/day | ||
inhalation aerosol: 160 mcg/4.5 mcg/inhalation | Greater than or equal to 12 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 640 mcg/18 mcg /day | |
fluticasone propionate/ salmeterol xinafoate (Advair HFA®) | inhalation aerosol: 45 mcg/21 mcg/ inhalation | Greater than or equal to 12 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 180 mcg/84 mcg/day |
inhalation aerosol: 115 mcg/21 mcg/ inhalation | Greater than or equal to 12 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 460 mcg/84 mcg/day | |
inhalation aerosol: 230 mcg/21 mcg/inhalation | Greater than or equal to 12 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 920 mcg /84 mcg/day | |
fluticasone propionate/ salmeterol (Advair Diskus®) | inhalation powder: 100 mcg/50 mcg/ inhalation | 4-11 years of age: 2 actuations/day (1 actuation twice daily); total dose = 200 mcg/100 mcg/day |
inhalation powder: 100 mcg/50 mcg/inhalation | Greater than or equal to 12 years of age: 2 actuations/day (1 actuation twice daily); total dose = 200 mcg/100 mcg/day | |
inhalation powder: 250 mcg/50 mcg/inhalation | Greater than or equal to 12 years of age: 2 actuations/day (1 actuation twice daily); total dose = 500 mcg/100 mcg/day | |
inhalation powder: 500 mcg/50 mcg/ inhalation | Greater than or equal to 12 years of age: 2 actuations/day (1 actuation twice daily); total dose = 1000 mcg/100 mcg/day | |
fluticasone propionate/salmeterol (AirDuo RespiClick®) | inhalation powder: 55 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 110 mcg/28 mcg/day |
113 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 226 mcg/28 mcg/day | |
232 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 464 mcg/28 mcg/day | |
fluticasone propionate/salmeterol (AirDuo Digihaler®) | 55 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 110 mcg/28 mcg/day |
inhalation powder: 113 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 226 mcg/28 mcg/day | |
inhalation powder: 232 mcg fluticasone/14 mcg salmeterol/inhalation | Greater than or equal to 12 years of age: 2 actuations/day in divided doses (1 actuation twice daily); total dose = 464 mcg/28 mcg/day | |
mometasone/ formoterol (Dulera®) | inhalation aerosol: 50 mcg/5 mcg/ inhalation | 5-11 years of age: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 200 mcg/ 20 mcg/ day |
100 mcg/5 mcg/inhalation | Greater than or equal to 12 years of age: patients on medium-dose inhaled corticosteroids: 4 actuations/day in divided doses (2 actuations twice daily); total dose = 400 mcg/20 mcg/day | |
200 mcg/5 mcg/inhalation |
Legend:
- Number of maximum actuations per day based on dose of salmeterol and formoterol, and independent of inhaled corticosteroid dose.