II. Indications
III. Precautions
- Adverse outcomes in Asthma with Long-acting Beta Agonist (LABA)
- LABA use in Asthma was associated with increased Asthma deaths, increased intubations and hospitalizations
- However FDA review of more recent studies found similar adverse outcomes with Inhaled Corticosteroids
- FDA removed LABA black box warning (see FDA communication link below)
- Risk of increased mortality and of more severe and life threatening Asthma Exacerbations
- Postulated to mask a patients awareness of severe Asthma Exacerbation
- FDA Black Box Warnings placed in 2003, but removed in 2017 (based on newer data as above)
- Not a substitute for Inhaled Corticosteroids
- Steroids are key management of persistent Asthma
- Long-acting Beta Agonists are in addition to Inhaled Corticosteroids
- Lazarus (2001) JAMA 285:2583-93 [PubMed]
- Do NOT exceed dosing schedule (e.g. Serevent bid) except Formoterol in SMART Protocol
- Use a short acting Beta agonist for rescue use
- Exception: See SMART Protocol below
- Tolerance over time to Protective effect
- Effect diminishes over one month of use
- Reference
IV. Preparations: Long-acting Beta Agonists (LABA)
- Salmeterol (Serevent) Dry Powder Diskus (50 ug/inhale)
- One inhalation every 12 hours
- Serevent Inhalation aerosol MDI (21 ug/puff)
- Adults: 2 puffs every 12 hours
- Child: 1-2 puffs every 12 hours
- Formoterol (Foradil)
- One inhalation every 12 hours
- Rapid onset within 5 minutes (contrast 15-30 minutes for other LABAs)
- Indacaterol (Arcapta Neohaler)
- Arformoterol (Brovana)
- Dose: 15 mcg twice daily
V. Preparations: Combination of Long-acting Beta Agonists with Corticosteroids
- Advair Diskus (Fluticasone/Salmeterol: 100/50, 250/50, 500/50)
- Dose: One puff twice daily
- Wixela Inhub (Fluticasone/Salmeterol)
- Released in 2019 at $150/Inhaler
- AirDuo (Fluticasone/Salmeterol: 55/14, 113/14, 232/14)
- Dose: One puff twice daily
- Generic available in 2017 for $90/month (compare with $475/month for Advair)
- (2017) Presc Lett 24(7)
- Symbicort (Budesonide/Formoterol: 80/4.5, 160/4.5)
- Dose: One puff twice daily
- Dulera (Mometasone/Formoterol: 50/5, 100/5, 200/5)
- Dose: Two puffs twice daily
- Breo Ellipta (Fluticasone/Vilanterol: 100/25)
- Trelegy Ellipta (Umeclidinium AND Fluticasone/Vilanterol)
- Indicated for severe COPD when an Inhaled Steroid and a LAMA and LABA are both indicated
- Indicated in Severe Asthma not controlled on medium to high dose Inhaled Corticosteroid and LABA
- Available in 2 strengths of fluticasone component (100 mcg for COPD or Asthma, 200 mcg for Asthma only)
- Dosing 1 puff daily of Dry Powder Inhaler
- (2020) Presc Lett, 27(11): 62
VI. Protocol: Single Maintenance and Reliever Therapy (SMART)
- Indications
- Moderate to Severe Persistent Asthma
- Uses combination Inhaled Corticosteroid with LABA products
- Limited to Formoterol due to short onset of action (5 minutes)
- Protocol uses combination agent for additional prn dose for exacerbation symptoms
- Use 1-2 puffs prn up to maximum based on age (additional doses above the maintenance dose)
- Age over 12 years old: Up to 12 puffs per day (including maintenance)
- Age 4 o 11 years old: Up to 8 puffs per day (including maintenance)
- More than 2 rescue doses per week should prompt reevaluation
- Use 1-2 puffs prn up to maximum based on age (additional doses above the maintenance dose)
- Efficacy
- Reduced systemic steroids, ED Visits, hospitalizations (NNT 16)
- Now a recommended protocol in the NHLBI Asthma Guidelines 2020
- Precautions
- Extra LABA dosing has been cautioned against in past
- Do not use with LABA agents (maintenance or rescue) other than Formoterol
- SMART Protocol has been controversial for >10 years
- Albuterol rescue Inhaler cost is far less than the combination Corticosteroid/LABA
- Extra doses may not be covered by insurance (e.g. early medication refill)
- References
VII. References
- (2013) Presc Lett, 20(8): 43
- (2001) Med Clin North Am 43(1104):39-40 [PubMed]
- Wilson (2001) Chest 119:2021-6 [PubMed]
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Related Studies
serevent (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
SEREVENT DISKUS 50 MCG | $5.61 each | |
arcapta (on 4/1/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ARCAPTA NEOHALER 75 MCG CAP | $7.56 each | |
advair (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ADVAIR 100-50 DISKUS | $4.66 each | |
ADVAIR 250-50 DISKUS | $5.79 each | |
ADVAIR 500-50 DISKUS | $7.62 each | |
ADVAIR HFA 115-21 MCG INHALER | $28.91 per gram | |
ADVAIR HFA 230-21 MCG INHALER | $38.04 per gram | |
ADVAIR HFA 45-21 MCG INHALER | $23.25 per gram | |
symbicort (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
SYMBICORT 160-4.5 MCG INHALER | $29.11 per gram | |
SYMBICORT 80-4.5 MCG INHALER | $25.45 per gram | |
dulera (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
DULERA 100 MCG/5 MCG INHALER | $21.47 per gram | |
DULERA 200 MCG/5 MCG INHALER | $21.48 per gram | |
breo ellipta (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
BREO ELLIPTA 100-25 MCG INH | $5.16 each | |
BREO ELLIPTA 200-25 MCG INH | $5.16 each | |
brovana (on 4/19/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
BROVANA 15 MCG/2 ML SOLUTION | $6.98 per ml |
Ontology: formoterol (C0060657)
Definition (NCI) | A long-acting beta-adrenergic receptor agonist with bronchodilator activity. Formoterol selectively binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and reduce mediator substance release from inflammatory cells, especially from mast cells. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C012629 |
SnomedCT | 320260000, 395969001, 386171009, 414289007 |
English | N-(2-hydroxy-5-(1-hydroxy-2-((2-(4-methoxyphenyl)-1-methylethyl)amino)ethyl)phenyl)formamide, (E)-2-butenedioate (2:1) (salt), eformoterol, formoterol [Chemical/Ingredient], Eformoterol (product), Eformoterol (substance), FORMOTEROL, Formoterol (product), Formoterol, Eformoterol, Formoterol (substance), formoterol |
Spanish | eformoterol, eformoterol (producto), eformoterol (sustancia), formoterol (producto), formoterol, formoterol (sustancia) |
Ontology: salmeterol (C0073992)
Definition (NCI) | A highly selective, long-acting beta-2 adrenergic agonist with bronchodilatory activity. Salmeterol's benzene moiety resembles the structure of catecholamines, and occupies the active site of beta-2 adrenergic receptor, while the long, lipophilic side chain of salmeterol, binds to the so called 'exosite' near the beta-2 adrenergic receptors. The binding at the exosite allows the active portion of the molecule to remain at the receptor site and continually engage and disengage with the receptor, therefore providing a long duration of action. This agent stimulates intracellular adenyl cyclase to catalyze the conversion of adenosine triphosphate to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels result in relaxation of bronchiolar smooth muscle, bronchodilation and increased bronchial airflow. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C057823 |
SnomedCT | 108605008, 372515005 |
English | salmeterol, salmeterol (medication), salmeterol [Chemical/Ingredient], SALMETEROL, Salmeterol, Salmeterol product, Salmeterol (product), Salmeterol (substance) |
Spanish | salmeterol (producto), salmeterol (sustancia), salmeterol |
Ontology: Selective beta-2 adrenoceptor stimulants (C0354671)
Concepts | Pharmacologic Substance (T121) |
SnomedCT | 320073005, 373215002 |
English | Selective beta-2 stimulants, Selective beta-2 adrenoceptor stimulants, Selective beta-2 agonists, Selective beta-2 adrenoceptor stimulants (product), Selective beta-2 adrenoceptor stimulants (substance) |
Spanish | estimulantes selectivos de receptores adrenérgicos beta 2 (sustancia), estimulantes selectivos de receptores adrenérgicos beta 2, estimulantes selectivos beta 2 adrenérgicos (producto), estimulantes selectivos beta 2 adrenérgicos (sustancia), estimulantes selectivos beta 2 adrenérgicos |
Ontology: Foradil (C0592533)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C012629 |
English | Foradil, Schering brand of formoterol fumarate, foradil |
Ontology: Serevent (C0700491)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C057823 |
English | Serevent, Glaxo Wellcome brand of salmeterol xinafoate, serevent |
Ontology: Arcapta (C3162477)
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
English | Arcapta |