BETA AGONISTS









Albuterol | Proventil HFA® | Ventolin HFA® | ProAir® | Accuneb®

Dosage forms

HFA inhalers
  • Proventil HFA® (6.7 gm/200 actuations)
  • Ventolin HFA® (8 gm/60 actuations and 18 gm/200 actuations)
  • ProAir HFA® (8.5 gm/200 actuations)
  • Each inhaler delivers 90 mcg of albuterol base per actuation
  • HFA stands for Hydrofluoroalkane which is the propellant used in the inhalers
ProAir® RespiClick
  • Delivers 90 mcg of albuterol in a dry powder
  • Inhaler is breath-actuated
  • Each inhaler contains 200 inhalations
ProAir® Digihaler
  • Delivers 90 mcg of albuterol in a dry powder
  • Inhaler is breath-actuated
  • Each inhaler contains 200 inhalations
  • Connects to app and records use and peak inspiratory flow rate (L/min)
Nebulizer solution (Accuneb®)
  • Albuterol 0.50% (2.5 mg/0.5 ml)
  • Albuterol 0.083% (2.5 mg/3 ml)
  • Albuterol 0.042% (1.25 mg/3 ml)
  • Albuterol 0.021% (0.63 mg/3 ml)
  • Comes in box of 25 nebs
Nebulizer solution concentrate
  • Albuterol 0.50% (5 mg/1 ml of concentrate)
  • Comes in 20 ml bottle

Dosing

Acute bronchospasm
  • Inhalers (≥ 4 years old)
    • 2 puffs every 4 - 6 hours as needed
  • Nebulizer
    • Age ≤ 12 years
      • 0.1 - 0.15 mg/kg/dose every 6 - 8 hours as needed
      • Weight 10 - 15 kg: 1.25 mg
      • Weight > 15 kg: 2.5 mg
    • Age 13 years and older
      • 2.5 mg every 6 - 8 hours as needed
Prevention of exercise-induced asthma
  • Inhalers (≥ 4 years)
    • 2 puffs 15 - 30 minutes before exercise

Generic / Price

  • ProAir - YES/$
  • ProAir RespiClick - NO/$$
  • ProAir Digihaler - NO/$$$$
  • Ventolin (8 gm) - NO/$$
  • Ventolin (18 gm) - YES/$ - $$
  • Nebulizer solution - YES/$
  • Nebulizer concentrate - YES/$
  • Combivent Respimat® - NO/$$$$
  • Duoneb® - YES/$

Other

  • Shake inhaler well before use
  • Most inhalers need to be primed before the first use and if they have not been used for > 2 weeks
  • To prime inhalers, release 3-4 sprays into the air (see inhaler instructions for specific directions)
  • Clean inhalers and nebulizers periodically according to instructions

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation

FDA-approved indications

  • Asthma
  • Prevention of exercise-induced asthma
  • Relief of bronchospasm

Side effects



Side effect Albuterol Placebo
Upper respiratory tract infections 21% 18%
Rhinitis 16% 14%
Nausea 10% 5%
Rapid heart rate 7% < 1%
Nervousness 7% 3%
Tremor 7% 2%
Inhalation site sensation 6% 2%
Allergic reactions 6% < 1%


Drug interactions

  • Beta blockers - Beta blockers may block the action of albuterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - albuterol may worsen hypokalemia (low potassium) caused by these drugs
  • Loop diuretics - albuterol may worsen hypokalemia (low potassium) caused by these drugs
  • Digoxin - oral and IV albuterol may decrease digoxin levels. It's unclear if inhaled albuterol has the same effect.
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of albuterol
  • Tricyclic antidepressants - Tricyclic antidepressants may potentiate the cardiovascular effects of albuterol

Contraindications / Precautions

  • Severe allergy to milk proteins (ProAir RespiClick only ) - DO NOT USE, contains lactose
  • Hypokalemia (low potassium) - albuterol may cause potassium levels to decrease
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Hyperglycemia (elevated blood sugar) - albuterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - has not been studied extensively
  • Kidney disease - may decrease albuterol clearance

Levalbuterol (Xopenex®)

Dosage forms

HFA inhalers
  • Each inhaler delivers 45 mcg of levalbuterol base per actuation
  • 200 actuations per inhaler
  • HFA stands for Hydrofluoroalkane which is the propellant used in the inhalers
Nebulizer solution
  • Levalbuterol 0.25% (1.25 mg/0.5 ml)
  • Levalbuterol 0.042% (1.25 mg/3 ml)
  • Levalbuterol 0.021% (0.63 mg/3 ml)
  • Levalbuterol 0.0103% (0.31 mg/3 ml)
  • Comes in box of 24 nebs

Dosing

Acute bronchospasm
  • Inhalers (≥ 4 years)
    • 1 - 2 puffs every 4 - 6 hours as needed
  • Nebulizer
    • Age < 6 years
      • 0.075 mg/kg/dose
    • Age 6 - 11 years
      • 0.31 mg three times a day
    • Age ≥ 12 years
      • 0.63 mg - 1.25 mg every 6 - 8 hrs

Generic / Price

  • Inhalers - YES/$
  • Nebulizer solution - YES/$

Other

  • Shake inhaler well before use
  • Prime inhaler before initial use and if inhaler has not been used for more than 3 days
  • To prime inhaler, release 4 sprays into the air (see inhaler instructions for specific directions)
  • Clean inhalers and nebulizers periodically according to instructions

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation
  • Albuterol contains equal parts of a racemic mixture of R-enantiomers and S-enantiomers. The R-enantiomer is the active form of albuterol where the S-enantiomer is inactive. Levalbuterol contains only the R-enantiomer of albuterol.

FDA-approved indications

  • Asthma
  • Relief of bronchospasm

Side effects



Side effect Levalbuterol Albuterol Placebo
Viral respiratory infection 12.3% 12.2% 9.3%
Muscle spasticity 9.6% 8.1% 0%
Nervousness 6.8% 2.7% 0%
Increased cough 4.1% 2.7% 2.7%
Rapid heart rate 2.7% 2.7% 0%
Tremor 2.7% 0% 0%
Upset stomach 2.7% 1.4% 1.3%


Drug interactions

  • Beta blockers - Beta blockers may block the action of levalbuterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - levalbuterol may worsen hypokalemia (low potassium) caused by these drugs
  • Loop diuretics - levalbuterol may worsen hypokalemia (low potassium) caused by these drugs
  • Digoxin - oral and IV albuterol may decrease digoxin levels. It's unclear if inhaled levalbuterol has the same effect.
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of levalbuterol
  • Tricyclic antidepressants - Tricyclic antidepressants may potentiate the cardiovascular effects of levalbuterol

Contraindications / Precautions

  • Hypokalemia (low potassium) - levalbuterol may cause potassium levels to decrease
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Hyperglycemia (elevated blood sugar) - levalbuterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - has not been studied extensively
  • Kidney disease - may decrease levalbuterol clearance



Formoterol | Arformoterol |Foradil® | Brovana® | Perforomist®

Dosage forms

Inhaler (Foradil®)
  • Foradil® comes in a capsule that has 12 mcg of formoterol powder in the center
  • Powder is inhaled through a device called an aerolizer
  • Comes in package of 60 capsules
Nebulizer solution (Brovana®)
  • 15 mcg/2 ml
  • Comes in package of 60 nebs
  • Brovana is arformoterol
Nebulizer solution (Perforomist®)
  • 20 mcg/2 ml
  • Comes in package of 60 nebs

Dosing - Foradil inhaler

Asthma (≥ 5 years old and adults)
  • One capsule every 12 hours
COPD
  • One capsule every 12 hours
Prevention of exercise-induced asthma (≥ 5 years old and adults)
  • One capsule at least 15 minutes before exercise
  • Protection may last up to 12 hours
  • Effect will diminish if used frequently

Dosing - Brovana and Perforomist

COPD
  • One treatment twice a day

Generic / Price

  • Inhaler - NO/$$$$
  • Nebulizer - NO/$$$$

Other

  • Foradil® - store in refrigerator before dispensing. May store at room temperature. Follow patient instructions for using inhaler.
  • Brovana® - store in refrigerator. May store at room temperature for up to 6 weeks. Protect from light.
  • Perforomist® - store in refrigerator before dispensing. May store at room temperature for up to 3 months. Protect from light.

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation

FDA-approved indications

Foradil® inhaler
  • Asthma (≥ 5 years). Should only be used as concomitant therapy with a long-term asthma control medication like an inhaled corticosteroid
  • Prevention of exercise-induced asthma (≥ 5 years)
  • COPD
  • NOT indicated for relief of acute bronchospasm
Brovana® and Perforomist
  • COPD

Side effects

NOTE: Side effects of formoterol are similar to those seen with albuterol. In trials, formoterol was often added to albuterol, so it is difficult to discern which effects may be attributable to formoterol only.
  • Side effects that demonstrated a dose-response to formoterol included:
    • Tremor
    • Dizziness
    • Voice impairment

Drug interactions

  • Beta blockers - Beta blockers may block the action of formoterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - formoterol may worsen hypokalemia (low potassium) caused by these drugs
  • Drugs that prolong the QT interval - formoterol may potentiate QT prolongation
  • Loop diuretics - formoterol may worsen hypokalemia (low potassium) caused by these drugs
  • Theophylline - may potentiate hypokalemia (low potassium)
  • Corticosteroids - may potentiate hypokalemia (low potassium)
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of formoterol
  • Tricyclic antidepressants - Tricyclic antidepressants may potentiate the cardiovascular effects of formoterol
  • Halogenated hydrocarbons - may increase risk of arrhythmia

Contraindications / Precautions

  • Severe allergy to milk proteins (Foradil® only) - DO NOT USE, contains lactose
  • Increased risk of serious asthma-related events - The use of LABAs as monotherapy to treat asthma has been associated with an increased risk of serious asthma-related events including death. When LABAs are combined with an ICS, the risk of serious asthma-related events is not significantly greater than that of an ICS alone. LABAs should not be used without an ICS to treat asthma. See LABAs and asthma-related death for more. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
  • Hypokalemia (low potassium) - formoterol may cause potassium levels to decrease. The effect is usually transient and insignificant.
  • Hyperglycemia (elevated blood sugar) - formoterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - has not been studied extensively. Use caution.
  • Kidney disease - has not been studied extensively

Indacaterol (Arcapta®)

Dosage forms

Arcapta NeoHaler®
  • Arcapta® comes in a capsule that has 75 mcg of indacaterol powder in the center
  • Powder is inhaled through a device called a Neohaler
  • Comes in package of 30 capsules

Dosing

COPD
  • One capsule via Neohaler once daily

Generic / Price

- NO/$$$$

Other

  • Protect from light and moisture
  • Remove from blister pack immediately before use

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation

FDA-approved indication

  • Chronic Obstructive Pulmonary Disease (COPD)
  • NOT indicated for relief of acute bronchospasm

Side effects



Side effect Indacaterol Placebo
Cough 6.5% 4.5%
Nasopharyngitis 5.3% 2.7%
Headache 5.1% 2.5%
Nausea 2.4% 0.9%
Mouth pain 2.2% 0.7%


Drug interactions

  • Beta blockers - Beta blockers may block the action of indacaterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - indacaterol may worsen hypokalemia (low potassium) caused by these drugs
  • Drugs that prolong the QT interval - indacaterol may potentiate QT prolongation
  • Loop diuretics - indacaterol may worsen hypokalemia (low potassium) caused by these drugs
  • Theophylline - may potentiate hypokalemia (low potassium)
  • Corticosteroids - may potentiate hypokalemia (low potassium)
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of indacaterol
  • Tricyclic antidepressants - Tricyclic antidepressants may potentiate the cardiovascular effects of indacaterol
  • Indacaterol is a CYP3A4 substrate and a minor P-gp substrate. In studies, combined inhibition of CYP3A4 and P-gp did not have a significant effect on indacaterol.

Contraindications / Precautions

  • Severe allergy to milk proteins - DO NOT USE. Contains lactose
  • Prolonged QT interval - DO NOT USE. May worsen QT prolongation.
  • Increased risk of serious asthma-related events - The use of LABAs as monotherapy to treat asthma has been associated with an increased risk of serious asthma-related events including death. When LABAs are combined with an ICS, the risk of serious asthma-related events is not significantly greater than that of an ICS alone. LABAs should not be used without an ICS to treat asthma. See LABAs and asthma-related death for more. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
  • Hypokalemia (low potassium) - indacaterol may cause potassium levels to decrease. The effect is usually transient and insignificant.
  • Hyperglycemia (elevated blood sugar) - indacaterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - mild-moderate - no dose adjustment necessary; severe - has not been studied
  • Kidney disease - has not been studied; indacaterol undergoes minimal kidney elimination

Olodaterol (Striverdi Respimat®)

Dosage forms

Striverdi Respimat® inhaler
  • Each actuation delivers 2.7 mcg olodaterol hydrochloride, equivalent to 2.5 mcg olodaterol
  • Inhaler comes with cartridge that contains 60 sprays (inhalations)

Dosing

COPD
  • Two inhalations once daily at the same time of the day

Generic / Price

- NO/$$$$

Other

  • After assembly, inhaler should be discarded at the latest 3 months after first use

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation

FDA-approved indication

  • Chronic Obstructive Pulmonary Disease (COPD)
  • NOT indicated for relief of acute bronchospasm

Side effects



Side effect Olodaterol Placebo
Nasopharyngitis 11.3% 7.7%
Upper respiratory infection 8.2% 7.5%
Bronchitis 4.7% 3.6%
Cough 4.2% 4.0%


Drug interactions

  • Beta blockers - Beta blockers may block the action of olodaterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - olodaterol may worsen hypokalemia (low potassium) caused by these drugs
  • Drugs that prolong the QT interval - olodaterol may potentiate QT prolongation
  • Loop diuretics - olodaterol may worsen hypokalemia (low potassium) caused by these drugs
  • Theophylline - may potentiate hypokalemia (low potassium)
  • Corticosteroids - may potentiate hypokalemia (low potassium)
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of olodaterol
  • Tricyclic antidepressants - tricyclic antidepressants may potentiate the cardiovascular effects of olodaterol
  • Olodaterol is a CYP2C9 and CYP2C8 substrate. No dose adjustment is recommended when used with inhibitors of these enzymes.

Contraindications / Precautions

  • Congenital long QT syndrome - DO NOT USE. May cause QT prolongation
  • Increased risk of serious asthma-related events - The use of LABAs as monotherapy to treat asthma has been associated with an increased risk of serious asthma-related events including death. When LABAs are combined with an ICS, the risk of serious asthma-related events is not significantly greater than that of an ICS alone. LABAs should not be used without an ICS to treat asthma. See LABAs and asthma-related death for more. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
  • Hypokalemia (low potassium) - olodaterol may cause potassium levels to decrease. The effect is usually transient and insignificant.
  • Hyperglycemia (elevated blood sugar) - olodaterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - mild-moderate - no dose adjustment necessary; severe - has not been studied
  • Kidney disease - no dose adjustment necessary

Salmeterol (Serevent®)

Dosage forms

Inhaler
  • Comes as a powder that is packaged in a diskus device
  • Each dose delivers 50 mcg of salmeterol
  • Each diskus contains 60 doses

Dosing

Asthma (≥ 4 years and adults)
  • One inhalation twice a day
Prevention of exercise-induced asthma (≥ 4 years and adults)
  • One inhalation at least 30 minutes before exercise
  • Protection may last up to 9 hours in adolescents and adults and up to 12 hours in patients aged 4 to 11 years
  • Effect will diminish if used frequently
COPD
  • One inhalation twice a day

Generic / Price

- NO/$$$$

Other

  • Diskus is good for 6 weeks after removing from foil pouch
  • Store at room temperature
  • Protect from sunlight

Mechanism of action

  • Stimulates Beta-2 adrenergic receptors which causes bronchial smooth muscle dilation

FDA-approved indications

  • Asthma (≥ 4 years and adults). Should only be used as concomitant therapy with a long-term asthma control medication like an inhaled corticosteroid.
  • Prevention of exercise-induced asthma in patients ≥ 4 years and adults
  • COPD
  • NOT indicated for relief of acute bronchospasm

Side effects



Side effect Salmeterol Albuterol Placebo
Headache 13% 12% 9%
Sinus congestion 9% 8% 6%
Tracheitis/Bronchitis 7% 3% 4%
Runny nose 5% 4% 4%
Influenza 5% 5% 2%


Drug interactions

  • CYP3A4 strong inhibitors - DO NOT COMBINE. Salmeterol is a CYP3A4 substrate. Strong inhibitors of CYP3A4 may increase salmeterol levels and may cause EKG changes.
  • Beta blockers - Beta blockers may block the action of salmeterol. Nonselective beta blockers may carry a greater risk. Recent studies have found that beta blockers may actually be beneficial in patients with COPD/asthma. See beta blockers in RAD.
  • Thiazide diuretics - salmeterol may worsen hypokalemia (low potassium) caused by these drugs
  • Drugs that prolong the QT interval - salmeterol may potentiate QT prolongation
  • Loop diuretics - salmeterol may worsen hypokalemia (low potassium) caused by these drugs
  • Theophylline - may potentiate hypokalemia (low potassium)
  • Corticosteroids - may potentiate hypokalemia (low potassium)
  • MAO inhibitors - MAO inhibitors may potentiate the cardiovascular effects of salmeterol
  • Tricyclic antidepressants - Tricyclic antidepressants may potentiate the cardiovascular effects of salmeterol

Contraindications / Precautions

  • Severe allergy to milk proteins - DO NOT USE, contains lactose
  • Increased risk of serious asthma-related events - The use of LABAs as monotherapy to treat asthma has been associated with an increased risk of serious asthma-related events including death. When LABAs are combined with an ICS, the risk of serious asthma-related events is not significantly greater than that of an ICS alone. LABAs should not be used without an ICS to treat asthma. See LABAs and asthma-related death for more. Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
  • Hypokalemia (low potassium) - salmeterol may cause potassium levels to decrease. The effect is usually transient and insignificant.
  • Hyperglycemia (elevated blood sugar) - salmeterol may cause an increase in blood sugars. This effect is typically insignificant.
  • Paradoxical bronchospasm - cases of paradoxical bronchospasm have been reported
  • Cardiovascular effects - increases in pulse and blood pressure can occur in some patients. These reactions are rare.
  • EKG changes - flattening of the T-wave, QT-interval prolongation, and ST-segment depression have been reported
  • Cardiovascular disease - use with caution in patients with cardiovascular disease
  • Heart arrhythmias - use with caution in patients with heart arrhythmias
  • Liver disease - has not been studied extensively. Use caution.
  • Kidney disease - has not been studied extensively



Combivent Respimat® | Duoneb® (Albuterol + Ipratropium)

Dosage forms

Inhaler (Combivent Respimat®)
  • Inhaler delivers 100 mcg of albuterol and 20 mcg of ipratropium per actuation
  • Each inhaler contains 120 actuations
Nebulizer solution (Duoneb®)
  • Ipratropium 0.5 mg/Albuterol 3 mg per 3 ml neb
  • Comes in box of 30 or 60 nebs

Dosing

Acute bronchospasm in COPD
  • Combivent Respimat®
    • Dosing: One inhalation four times a day with up to two additional inhalations if required
    • Max: Six inhalations in 24 hours
  • Duoneb®
    • Dosing: One neb four times a day with up to two additional nebs if required
    • Max: Six nebs in 24 hours
Acute asthma exacerbation

Generic / Price

  • Combivent Respimat® - NO/$$$$
  • Duoneb® - YES/$

Other

  • Combivent Respimat® is good for 3 months after first use
  • See Combivent Respimat® patient insert for priming instructions

FDA-approved indications

  • Chronic Obstructive Pulmonary Disease (COPD)
  • Relief of bronchospasm



Advair® | Wixela Inhub® (fluticasone + salmeterol)

Dosage forms

Inhalation powder (Advair® Diskus | Wixela Inhub®)
  • Strength is expressed as fluticasone/salmeterol
  • Advair® 100/50 - 100/50 mcg per inhalation
  • Advair® 250/50 - 250/50 mcg per inhalation
  • Advair® 500/50 - 500/50 mcg per inhalation
  • Inhalation powder packaged in diskus with 60 doses
HFA (Advair®)
  • Strength is expressed as fluticasone/salmeterol
  • Advair HFA® 45/21 - 45/21 mcg per actuation
  • Advair HFA® 115/21 - 115/21 mcg per actuation
  • Advair HFA® 230/21 - 230/21 mcg per actuation
  • Inhaler with 120 actuations per inhaler

Dosing - Diskus

Asthma
  • 4 - 11 years old
    • One inhalation of 100/50 twice daily
  • 12 years of age and older
    • Dose: one inhalation twice daily
    • Starting: strength will depend on asthma severity
    • Max dose: 500/50, one inhalation twice daily
    • Maximum benefit seen after 2 weeks
COPD
  • 1 inhalation of 250/50 twice daily

Dosing - HFA

Asthma in children ≥ 12 years and adults
  • Dose: two inhalations twice daily
  • Starting: strength will depend on asthma severity
  • Max dose: 230/21, two inhalations twice daily
  • Maximum benefit seen after 2 weeks

Generic / Price

  • Diskus - YES/$$$
  • HFA - NO/$$$$

Other

Advair® HFA
  • Shake well for 5 seconds before use
  • Prime before using for the first time by releasing 4 test sprays
  • In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 test sprays
  • Rinse mouth after use
Advair® Diskus
  • The device should be discarded 1 month after removal from the moisture-protective foil overwrap pouch
  • Rinse mouth after use

FDA-approved indications

Advair® Diskus
  • Asthma in children ≥ 4 years and adults
  • Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm
Advair® HFA
  • Asthma in children ≥ 12 years and adults
  • NOT for relief of acute bronchospasm

AirDuo RespiClick® (fluticasone + salmeterol)

Dosage forms

Powder inhaler (fluticasone/salmeterol)
  • AirDuo RespiClick® 55/14 - 55/14 mcg per inhalation
  • AirDuo RespiClick® 113/14 - 113/14 mcg per inhalation
  • AirDuo RespiClick® 232/14 - 232/14 mcg per inhalation
  • Each inhaler contains 60 actuations

Dosing

Asthma (≥ 12 years old)
  • Starting: 55/14 mcg twice daily
  • Maintenance: 55/14 - 232/14 mcg twice daily
  • Max dose: 232/14 mcg twice daily
  • Increase dose at intervals of 2 weeks
  • Inhale at the same time each day
  • Patients switching from other inhaled corticosteroids may require higher starting doses

Generic / Price

- YES/$$

Other

  • Inhaler does not require priming
  • Never wash or put any part of the inhaler in water
  • Do not use with a spacer or volume holding chamber

FDA-approved indications

  • Asthma in children ≥ 12 years and adults
  • NOT for relief of acute bronchospasm

Breo Ellipta® (fluticasone + vilanterol)

Dosage forms

Inhaler
  • Inhaler delivers 100 mcg of fluticasone powder and 25 mcg of vilanterol powder per inhalation
  • Inhaler comes with 30 inhalations

Dosing

COPD
  • One inhalation once daily
Asthma (≥ 18 years old)
  • One inhalation once daily

Generic / Price

- NO/$$$$

Other

  • See Breo Ellipta® PI for complete prescribing information
  • Discard inhaler 6 weeks after opening the foil tray
  • DO NOT USE in patients with severe milk allergy
  • Vilanterol is a CYP3A4 substrate. Use caution with strong CYP3A4 inhibitors.

FDA-approved indications

  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • Asthma in patients ≥ 18 years old that is not well-controlled with other medications
  • NOT for relief of acute bronchospasm

Dulera® (mometasone + formoterol)

Dosage forms

Inhaler (mometasone/formoterol)
  • Dulera® 50/5 - 50 mcg/5 mcg per actuation
  • Dulera® 100/5 - 100 mcg/5 mcg per actuation
  • Dulera® 200/5 - 200 mcg/5 mcg per actuation
  • Comes in inhaler with 120 actuations

Dosing

Asthma
  • 5 - 11 years old
    • Dosing: 2 inhalations of 50 mcg/5 mcg twice daily
    • Max daily dose: 200 mcg/20 mcg
  • ≥ 12 years old
    • Dosing: 2 inhalations twice daily
    • Medium-dose corticosteroids: Dulera® 100 mcg/5 mcg, two inhalations twice daily
    • High-dose corticosteroids: Dulera® 200 mcg/5 mcg, two inhalations twice daily
    • Max daily dose: 800 mcg/20 mcg
    • Maximum benefit seen after 2 weeks

Generic / Price

- NO/$$$$

Other

  • Shake well before use
  • Prime inhaler by releasing 4 test sprays
  • Re-prime if not used for ≥ 5 days

FDA-approved indications

  • Maintenance treatment of Asthma
  • NOT for relief of acute bronchospasm

Symbicort® (budesonide + formoterol)

Dosage forms

Inhaler (budesonide/formoterol)
  • Symbicort® 80/4.5 - 80 mcg/4.5 mcg per actuation
  • Symbicort® 160/4.5 - 160 mcg/4.5 mcg per actuation
  • Comes in inhaler with 120 actuations

Dosing

Asthma
  • 6 to 11 years old
    • Dose: Symbicort 80/4.5 two inhalations twice daily
  • ≥ 12 years old
    • Dose: two inhalations twice daily
    • Starting - may start with 80/4.5 or 160/4.5, depending on severity
    • Max: Symbicort 160/4.5 two inhalations twice daily
    • Maximum benefit seen after 2 weeks
COPD
  • Symbicort 160/4.5 two inhalations twice daily

Generic / Price

- NO/$$$$

Other

  • Shake well for 5 seconds before use
  • Inhaler is good for 3 months after removal from foil pouch
  • If you do not use your inhaler for more than 7 days or if you drop it, you will need to prime again
  • See patient instructions for details

FDA-approved indications

  • Maintenance treatment of Asthma
  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm



Anoro Ellipta® (vilanterol + umeclidinium)

Dosage forms

Inhalation powder
  • Each powder inhalation contains umeclidinium 62.5 mcg and vilanterol 25 mcg
  • Inhaler comes with 30 inhalations

Dosing

COPD
  • One inhalation once daily

Generic / Price

- NO/$$$$

Other

  • See Anoro Ellipta® PI for complete prescribing information
  • Discard inhaler 6 weeks after opening the foil tray
  • DO NOT USE in patients with severe milk allergy
  • Vilanterol is a CYP3A4 substrate. Use caution with strong CYP3A4 inhibitors.
  • DO NOT USE in patients with congenital long QT syndrome [4]

FDA-approved indications

  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm

Bevespi Aerosphere™ (formoterol + glycopyrrolate)

Dosage forms

Inhalation aerosol
  • Device delivers 4.8 mcg of formoterol and 9 mcg of glycopyrrolate per actuation
  • Each inhaler contains 120 inhalations

Dosing

COPD
  • Two inhalations twice a day

Generic / Price

- NO/$$$$

Other

  • Inhaler must be primed. See package insert for instructions.
  • See Bevespi Aerosphere PI for complete prescribing information
  • Inhaler is good for 3 months after removal from foil pouch

FDA-approved indications

  • Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm

Duaklir Pressair® (Aclidinium + Formoterol)

Dosage forms

Inhalation powder
  • Device delivers 400 mcg of aclidinium and 12 mcg of formoterol powder per actuation
  • Comes in 30 dose and 60 dose inhaler
  • Inhaler is breath-actuated

Dosing

COPD
  • One inhalation twice a day

Generic / Price

- NO/$$$$

Other

  • Do not use in patients with severe milk allergy. Contains lactose.
  • Inhaler is good for 2 months after removing from sealed bag

FDA-approved indications

  • Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm

Stiolto® Respimat (olodaterol + tiotropium)

Dosage forms

Inhalation spray
  • Inhaler delivers tiotropium 3.124 mcg (equivalent to 2.5 mcg tiotropium) and olodaterol 2.736 mcg (equivalent to 2.5 mcg olodaterol) per spray
  • Inhaler comes with 60 actuations

Dosing

COPD
  • Two inhalations once daily
  • Use at the same time every day

Generic / Price

- NO/$$$$

Other

  • See Stiolto® PI for complete prescribing information
  • Inhaler should be primed. See patient instructions for details

FDA-approved indications

  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm

Utibron® Neohaler (indacaterol + glycopyrrolate)

Dosage forms

Inhalation powder
  • Each capsule contains 27.5 mcg of indacaterol and 15.6 mcg of glycopyrrolate powder
  • Inhaler comes with 60 inhalation capsules

Dosing

COPD
  • One inhalation twice a day
  • Use at the same time every day

Generic / Price

- NO/$$$$

Other

  • See Utibron® PI for complete prescribing information
  • Use with caution in patients with severe milk allergy. Contains lactose.

FDA-approved indications

  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm



Trelegy Ellipta® (fluticasone + vilanterol + umeclidinium)

Dosage forms

Inhalation powder
  • Inhaler delivers 100 mcg of fluticasone, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol powder per inhalation
  • Inhaler comes with 30 inhalations

Dosing

COPD
  • One inhalation once daily

Generic / Price

- NO/$$$$

Other

  • See Trelegy Ellipta® PI for complete prescribing information
  • Discard inhaler 6 weeks after opening the foil tray
  • DO NOT USE in patients with severe milk allergy
  • Vilanterol is a CYP3A4 substrate. Use caution with strong CYP3A4 inhibitors.

FDA-approved indication

  • Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
  • NOT for relief of acute bronchospasm







SMART Study - Salmeterol vs Placebo in Asthma, CHEST (2006) [PubMed abstract]
  • The SMART trial enrolled 26,355 asthmatics who were ≥ 12 years old
Main inclusion criteria
  • Age ≥ 12 years
  • Diagnosis of asthma per investigator judgement
  • Receiving prescription asthma medication(s)
Main exclusion criteria
  • Previous use of LABA
  • Current use of a beta blocker
Baseline characteristics
  • Average age 39 years
  • Female sex - 64%
  • Caucasian - 71%, African American - 18%, Hispanic - 8%
  • Average duration of asthma - 16 years
  • Baseline ICS use - 47%
  • Average PEF% - 84%
Randomized treatment groups
  • Group 1 (13,176 patients): Salmeterol 42 mcg via MDI twice daily for 28 weeks
  • Group 2 (13,179 patients): Placebo inhaler twice daily for 28 weeks
  • Study drug was added to current asthma medications
  • Patients who were not currently on a SABA were given albuterol inhalers
Primary outcome: Occurrence of combined respiratory-related deaths or respiratory-related life-threatening experiences (defined as intubation and mechanical ventilation)
Results

Duration: After an interim analysis in 26,355 subjects, the trial was stopped early due to findings in African-American patients
Outcome Salmeterol Placebo 1 vs 2
Primary outcome (Overall) 50 events 36 events RR 1.4, 95%CI [0.91 - 2.1], p>0.05
Primary outcome (Caucasians) 29 events 28 events RR 1.05, 95%CI [0.62 - 1.76], p>0.05
Primary outcome (African Americans) 20 events 5 events RR 4.1, 95%CI [1.54 - 11.0], p<0.05
Primary outcome (ICS at baseline, Overall) 23 events 19 events RR 1.21, 95%CI [0.66 - 2.22], p>0.05
Primary outcome (No ICS at baseline, Overall) 27 events 17 events RR 1.60, 95%CI [0.87 - 2.92], p>0.05
Primary outcome (ICS at baseline, African American) 9 events 3 events RR 3.01, 95%CI [0.82 - 11.11], p>0.05
Primary outcome (No ICS at baseline, African American) 11 events 2 events RR 5.61, 95%CI [1.25 - 25.26], p<0.05

Findings: For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.
AUSTRI trial - Fluticasone + Salmeterol vs Fluticasone only in Asthma, NEJM (2016) [PubMed abstract]
  • The AUSTRI trial enrolled 11,679 asthmatics with moderate-to-severe asthma that required daily controller medications
Main inclusion criteria
  • Age ≥ 12 years
  • 1-year history of asthma requiring daily medications
  • Hospitalization or systemic steroids for an asthma exacerbation within last 12 months (excluding previous 30 days)
Main exclusion criteria
  • History of life-threatening asthma (defined as asthma that required invasive or noninvasive ventilatory support)
  • History of unstable asthma (uncontrolled asthma in the 7 days before randomization); hospitalization or systemic steroids for an asthma exacerbation within last 30 days
Baseline characteristics
  • Average age 43 years
  • Black race - 15%
Randomized treatment groups
  • Group 1 (5834 patients): Fluticasone + salmeterol
  • Group 2 (5845 patients): Fluticasone only
  • Salmeterol dose was 50 mcg twice daily
  • Fluticasone dose ranged from 100 - 500 mcg twice daily depending on asthma severity and was not blinded
  • All other asthma meds were stopped at randomization. Albuterol was allowed on an as needed basis. Leukotriene inhibitors, anticholinergics, and methylxanthines were allowed on a short-term basis for exacerbations.
Primary outcome:
  • Primary safety outcome - first serious asthma-related event, a composite endpoint that included death, endotracheal intubation, and hospitalization
  • Primary efficacy outcome - first severe asthma exacerbation, which was defined as asthma deterioration that led to the use of systemic glucocorticoids for at least 3 days or an asthma related hospitalization or emergency department visit that led to the use of systemic glucocorticoids
Results

Duration: After 26 weeks, the following was seen:
Outcome ICS + LABA ICS 1 vs 2
Primary safety outcome 36 events 38 events HR 1.03, 95%CI [0.64 - 1.66]
Primary efficacy outcome 8% 10% HR 0.79, 95%CI [0.70 - 0.89], p<0.001
  • No asthma-related deaths occurred in the trial
  • In subgroup analyses, no significant difference in risk for the primary safety outcome was noted between races and age groups

Findings: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group.




Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability