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What to Know About Mixture Bronchial asthma Inhalers

What to Know About Mixture Bronchial asthma Inhalers

Mixture bronchial asthma inhalers are used for long-term management of bronchial asthma signs and remedy and prevention of bronchial asthma assaults. They mix totally different inhaled medicines—a corticosteroid, a long-acting beta-agonist (LABA), a short-acting beta-agonist (SABA), or a long-acting muscarinic antagonist (LAMA).

Corticosteroids management irritation, whereas LABAs, SABAs, and LAMAs are bronchodilators that widen and open constricted airways to permit for the free move of air. When used collectively, these medicines can ease the hyperresponsiveness of airways and assist to stave off an bronchial asthma assault.

Verywell / Danie Drankwalter


There are seven mixture inhalers authorised by the U.S. Meals and Drug Administration (FDA) for treating bronchial asthma:

  • Advair HFA, a mix of the steroid fluticasone and the LABA salmeterol (authorised in 2000)
  • Advair Diskus, a mix of the steroid fluticasone and the LABA salmeterol in dry powder type (authorised in 2000)
  • Airsupra, a mix of the steroid budesonide and SABA albuterol (authorised in 2023)
  • Breo Ellipta, a mix of the steroid fluticasone and the LABA vilanterol (authorised in 2015)
  • Dulera, a mix of the steroid mometasone and the LABA formoterol (authorised in 2010)
  • Symbicort, a mix of the steroid budesonide and the LABA formoterol (authorised in 2006)
  • Trelegy Ellipta, a mix of the steroid fluticasone, the LAMA umeclidinium, and the LABA vilanterol (authorised in 2017)

Generic types of Advair, identified by the model names AirDuo Respiclick, Wixela Inhub, and others, additionally can be found. Symbicort generics (together with the branded generic Breyna, authorised in 2022) are additionally generally bought as a budesonide/formoterol inhaler.

Makes use of

Mixture inhalers are used to regulate bronchial asthma signs and beat back bronchial asthma assaults. Every targets a selected facet of the physiological occasions that comprise an bronchial asthma assault:

  • Corticosteroids, also referred to as steroids, mimic the hormone cortisol, which the physique naturally produces to regulate irritation. When used every day, corticosteroids assist management the irritation that contributes to airway hyperresponsiveness.
  • LABAs, LAMAs, and SABAs are labeled as bronchodilators, which means they assist open (dilate) the airways of the lungs—i.e., the bronchi and bronchioles. Though LABAs and LAMAs mechanism of motion are just like rescue inhalers (SABAs), they’re longer-lasting and, when taken every day, successfully stop bronchospasms and airways’ narrowing.

Different Authorized and Off-Label Makes use of

Symbicort and Breo are also authorised for the every day remedy of persistent obstructive pulmonary illness (COPD). Advair Diskus, the dry powder type of the drug, is authorised for COPD as properly, though its aerosolized type, Advair HFA, isn’t.

Research have proven that salmeterol, the LABA utilized in Advair HFA, will increase the chance of pneumonia in individuals with COPD. Although Advair Diskus additionally comprises salmeterol, the dose is way smaller and is taken into account safer for ongoing use.

Some healthcare suppliers prescribe Dulera off-label to individuals with COPD, though its security and effectiveness for this goal haven’t but been established.

Earlier than Taking

You’re a candidate for a mix bronchial asthma inhaler if a rescue inhaler alone fails to regulate your bronchial asthma, which means you:

  • Should use your rescue inhaler greater than twice per week
  • Awaken at evening with bronchial asthma signs greater than twice a month
  • Need to refill your rescue inhaler prescription greater than twice per week

Initially, inhaled corticosteroids had been the primary medication used as controller medicines if a rescue inhaler failed to supply sufficient management of bronchial asthma signs. Right this moment, as a substitute of ready so as to add a LABA to the remedy plan, many well being authorities—together with the International Initiative for Bronchial asthma (GINA)—endorse the mixed use of an inhaled corticosteroid and an inhaled LABA from the beginning.

That’s not to recommend a mix inhaler is a one-size-fits-all-solution. A 2015 examine within the Annals of the American Thoracic Society argued that inhaled steroids had been simply as efficient in controlling bronchial asthma signs as mixed steroid/LABA remedy and allowed for changes in doses when wanted.

Different research contend that, due to their comfort, individuals are extra possible to make use of them as prescribed, successfully enhancing well being outcomes in individuals with bronchial asthma. Furthermore, mixture inhalers require a smaller dose of steroids to attain the identical advantages in management as single steroid inhalers.

A 2013 evaluation within the Cochrane Database of Systematic Opinions concluded that individuals who used mixture inhalers had been much less prone to be hospitalized or want emergency room visits than those that used two totally different inhalers and had been much less prone to want stronger oral steroids sooner or later.

Precautions and Contrainidications

The one absolute contraindication for using a mix inhaler is a identified allergy to any energetic or inactive ingredient used within the inhaler. This contains an allergy to take advantage of, as milk powder is a central inactive ingredient in each Advair Diskus and Breo Ellipta.

LABAs are identified to have an effect on blood stress, blood sugar, coronary heart charge, thyroid hormone manufacturing, and the firing of mind cells. These results are tempered considerably by inhaled corticosteroids, permitting LABAs to be delivered at smaller doses.

There is also proof the long-term use of inhaled corticosteroids can have an effect on the eyes in addition to impair the physique’s means to struggle infections.

Due to these issues, mixture bronchial asthma inhalers ought to be used with warning in individuals with the next well being circumstances:

Folks with any of those circumstances ought to be routinely monitored to establish modifications of their well being standing whereas on mixture inhalers. In some circumstances, remedy could have to be stopped if signs worsen.

All mixture bronchial asthma inhalers ought to be used with warning throughout being pregnant, as animal research have advised a possible for fetal hurt, however no well-controlled research in people can be found.

Though there is no such thing as a proof of an elevated threat of start defects in being pregnant registries, it’s nonetheless essential to talk together with your healthcare supplier to weigh the advantages and dangers of remedy if you’re pregnant, breastfeeding, or planning to get pregnant.


The mix bronchial asthma inhalers at present authorised by the FDA will be categorized by their supply system:

  • Advair HFA, Airsupra, Dulera, and Symbicort are meter-dose inhalers (MDIs) that ship medicines utilizing an aerosolized propellent.
  • Advair Diskus. Breo Ellipta, and Trelegy Ellipta are dry powder inhalers (DPIs) that ship a dose of the treatment in powder type that you just inhale by means of the mouthpiece.

The really helpful dose can range by age. As a normal rule, smaller doses are prescribed when first beginning remedy and elevated provided that the drug fails to supply sufficient management of signs.

Really helpful Dosages
Drug Formulations in micrograms (mcg) Authorized for Really helpful Dose
Advair HFA •45 mcg fluticasone/230 mcg salmeterol •150 mcg fluticasone/230 mcg salmeterol •230 mcg fluticasone/230 mcg salmeterol Adults and kids 12 and over 2 inhalations twice every day, 12 hours aside
Advair Diskus •100 mcg fluticasone/50 mcg salmeterol •250 mcg fluticasone/50 mcg salmeterol •500 mcg fluticasone/50 mcg salmeterol Adults and kids 4 and over 1 inhalation twice every day, 12 hours aside
Airsupra •90 mcg albuterol/ 80mcg budesonide Adults 18 and older 2 inhalations as wanted; most of 12 inhalations a day
Breo Ellipta •100 mcg fluticasone/25 mcg vilanterol •200 mcg fluticasone/25 mcg vilanterol Adults 18 and over 1 inhalation every day
Dulera •100 mcg mometasone/5 mcg formeterol •200 mcg mometasone/5 mcg formeterol Adults and kids 12 and over  2 inhalations twice every day, 12 hours aside
Symbicort •80 mcg budesonide/4.5 mcg formeterol (kids) •160 mcg budesonide/4.5 mcg formeterol (adults) Adults and kids 6 and over 2 inhalations twice every day, 12 hours aside
Trelegy Ellipta •100 mcg fluticasone/62.5 mcg umeclidinium/ 25 mcg vilanterol •200 mcg fluticasone/62.5 mcg umeclidinium/ 25 mcg vilanterol Adults 18 and over 1 inhalation every day

No mixture bronchial asthma inhaler is inherently “higher” than one other. Some could also be extra acceptable for particular age teams, whereas price, supply system, and dosing necessities (once-daily vs. twice-daily) may additionally issue into the choice.

Have your healthcare supplier totally clarify the advantages and limitations of every choice to find out which inhaler is greatest suited to your wants.

Take and Retailer

MDIs and DPIs have professionals and cons. MDIs ship correct doses and are simple to make use of, however require hand-breath coordination. DPIs don’t have buttons or require hand-breath coordination, however they will ship various doses primarily based on how forcefully you inhale the treatment.

Studying methods to use a tool correctly can assist you reap the optimum advantages.

To make use of an MDI like Advair HFA, Dulera, or Symbicort:

  1. Take away the cap on the mouthpiece.
  2. Prime the inhaler in case you have not used it lately by shaking the canister for 5 seconds and spraying it away out of your face in a brief burst. Repeat as soon as. If the inhaler doesn’t want priming (i.e., you will have used it lately), merely shake properly for 5 seconds.
  3. Exhale totally to empty the lungs.
  4. Put the mouthpiece into your mouth and wrap your lips tightly to create a seal.
  5. Concurrently press the inhaler button whereas taking a deep breath.
  6. Maintain your breath for 10 seconds.
  7. Gently exhale.
  8. Repeat steps 3 by means of 7 to ship your second dose.
  9. Substitute the cap till you hear a click on.
  10. Rinse your mouth with water to clear treatment residue. Don’t swallow.

MDIs have to be cleaned as soon as weekly by wiping the mouthpiece with a dampened tissue and cleansing the aerosol opening with a dry cotton swab. Don’t submerge the canister in water.

To make use of a DPI like Advair Diskus, Breo Ellipta, or Trelegy Ellipta:

  1. Open the mouthpiece cowl. Don’t shake the inhaler.
  2. Push the loading lever till you hear a click on. This delivers the prescribed dose of treatment.
  3. Exhale totally.
  4. Place your lips across the mouthpiece to type a decent seal.
  5. Breathe in shortly solely by means of your mouth to inhale the treatment.
  6. Maintain your breath for 10 seconds.
  7. Gently exhale.
  8. Repeat steps 2 to 7 if you’re utilizing Advair Diskus. You do not want to repeat these if you’re utilizing Breo Ellipta.
  9. Clear the mouthpiece, if wanted, with a dry tissue. (DPIs don’t want routine cleansing.)
  10. Slide the mouthpiece cowl fully to shut the gadget.
  11. Rinse your mouth with water and spit. Don’t swallow.

Each MDIs and DPIs have built-in dose counters that let you know what number of doses are left after every inhalation. Refill your prescription when the counter will get all the way down to “20” (or “10” for Breo Ellipta).

MDIs and DPIs will be saved safely at room temperature, ideally between 68 levels F and 77 levels F. Don’t retailer MDIs close to warmth or an open flame as this will trigger bursting. Hold out of attain of kids or pets.

Don’t use an inhaler or any treatment previous its expiration date.

Facet Results

As with all treatment, mixture bronchial asthma inhalers may cause negative effects. Many of those are comparatively delicate and can progressively resolve as your physique adapts to remedy. Let your healthcare supplier know if any facet impact is extreme, persists, or worsens.


Frequent negative effects are largely the identical between the totally different inhalant formulations. These affecting 2% or extra of customers embrace:

  • Stuffy or runny nostril
  • Sneezing
  • Headache
  • Sore throat
  • Hoarseness
  • Cough
  • Sinus ache
  • Dizziness
  • Flu-like signs
  • Nausea or vomiting
  • Higher respiratory an infection
  • Oral thrush (candidiasis)

Of the varied drug formulations, Dulera has the fewest negative effects (primarily stuffy or runny nostril, sneezing, headache, and sinus ache).

The danger of oral thrush will be decreased through the use of a spacer with a MDI. As a result of DPIs resembling Advair Diskus and Breo Ellipta can’t accommodate a spacer, you possibly can scale back your threat of thrush by rinsing your mouth completely with water after each use.


An unusual however critical facet impact of mixture bronchial asthma inhalers is paradoxical bronchospasm, a situation through which signs of bronchial asthma worsen moderately than enhance. LABAs are accountable for this impact, though the precise explanation for the response is poorly understood.

Paradoxical bronchospasms seem to have an effect on individuals with extreme airway irritation who use an inhalant for the primary time.

The sudden onset of shortness of breath, wheezing, chest ache, and cough after utilizing a mix bronchial asthma inhaler ought to be thought to be a medical emergency. Individuals who expertise paradoxical bronchospasm shouldn’t be rechallenged with the identical drug.

Anaphylaxis, a doubtlessly life-threatening, whole-body allergy, is a uncommon prevalence with mixture bronchial asthma inhalers, however circumstances have been reported in individuals who have used Advair Diskus or Breo Ellita resulting from an underlying milk allergy.

Name 911 or search emergency care for those who expertise the next after utilizing a mix bronchial asthma inhaler:

  • Sudden extreme rash or hives
  • Shortness of breath
  • Wheezing
  • Dizziness
  • Irregular heartbeat
  • Swelling of the face, tongue, or lips
  • A sense of impending doom

If left untreated, anaphylaxis can result in shock, coma, asphyxiation, cardiac or respiratory failure, and dying.

Warnings and Interactions

Corticosteroids are identified to have an effect on bone density, however this seems to be much less a threat with inhaled corticosteroids than with oral corticosteroids. Nonetheless, younger kids ought to be monitored because the long-term use of a mix inhaler could impair development. The dangers seem best amongst toddlers with extreme persistent bronchial asthma.

There are a variety of frequent medication and drug lessons identified to work together with mixture bronchial asthma inhalers.

Corticosteroids and LABAs are each metabolized by a liver enzyme known as cytochrome P450 (CYP450) and might work together with different medication that use the identical enzyme for metabolization. This competitors can sluggish the speed at which a drug is cleared from the physique. This will likely both enhance the focus of a drug (together with its negative effects) or lower the focus of a drug (and scale back its efficacy).

Among the many medication of best concern are:

  • Antibiotics like clarithromycin, telithromycin, and troleandomycin
  • Antifungals like ketoconazole, itraconazole, and voriconazole
  • Atypical antidepressants like Serzone (nefazodone)
  • HIV medication like Kaletra (ritonavir/lopinavir), Crixivan (indinavir), and Invirase (saquinavir)

LABAs on their very own can work together with 4 lessons of medication in numerous methods. These embrace:

  • Beta-blockers like Lopressor (metoprolol) or Sectral (acebutolol) could block the impact of the mix inhaler and even set off bronchospasms.
  • Monoamine oxidase inhibitor (MAOI) antidepressants like Parnate (tranylcypromine) could set off coronary heart rhythm issues.
  • Non-potassium-sparing diuretics like hydrochlorothiazide could result in low potassium (hypokalemia) and set off cardiac irregularities.
  • Tricyclic antidepressants like Elavil (amitriptyline) can even trigger coronary heart rhythm disturbances if used with a LABA.

To keep away from drug interactions, let your healthcare supplier find out about any drug you’re taking, be it prescription, over-the-counter, natural, or leisure.

Black Field Warning

Till late 2017, the FDA issued a black field warning for all corticosteroid/LABA inhalers, advising customers that the medication had been related to an elevated threat of asthma-related deaths. The advisement was primarily based on research through which 13 deaths had been reported amongst 13,176 LABA customers over a 28-week examine interval.

On December 20, 2017, the FDA reversed the order when it was proven that the chance of dying occurred when LABAs had been used on their very own (in monotherapy). Present analysis has proven that the mixed use of a LABA and corticosteroid poses no such hurt.

Though the black field warning has been stripped from the packaging of mixture bronchial asthma inhalers, it stays on all single-ingredient LABA medicines.

Verywell Well being makes use of solely high-quality sources, together with peer-reviewed research, to help the information inside our articles. Learn our editorial course of to be taught extra about how we fact-check and hold our content material correct, dependable, and reliable.
  1. GlaxoSmithKline. Advair HFA (fluticasone propionate and salmeterol inhalation aerosol), for oral inhalation use.

  2. GlaxoSmithKline. Advair Diskus 100/50 (fluticasone propionate 100 mcg and salmeterol 50 mcg inhalation powder), Advair Diskus 250/50 (fluticasone propionate 250 mcg and salmeterol 50 mcg inhalation powder), Advair Diskus 500/50 (fluticasone propionate 500 mcg and salmeterol 50 mcg inhalation powder).

  3. Meals and Drug Administration. Airsupra label.

  4. Teva Pharmaceutical. AirDuo Respiclick (fluticasone propionate and salmeterol) inhalation powder 55 mcg/14 mcg, AirDuo Respiclick(fluticasone propionate and salmeterol) inhalation powder 113 mcg/14 mcg, AirDuo Respiclick (fluticasone propionate and salmeterol) inhalation powder 232 mcg/14 mcg.

  5. Mylan. Wixela Inhub (fluticasone propionate and salmeterol inhalation powder), for oral inhalation use.

  6. Yang HH, Lai CC, Wang YH, et al. Extreme exacerbation and pneumonia in COPD sufferers handled with fastened combos of inhaled corticosteroid and long-acting beta2 agonist. Int J Chron Impede Pulmon Dis. 2017;12:2477-85. doi:10.2147/COPD.S139035

  7. Tang W, Solar L, Fizgerald JM. A paradigm shift within the remedy of delicate bronchial asthma?. J Thorac Dis. 2018;10(10):5655-8. doi:10.21037/jtd.2018.09.127

  8. Israel E, Roche N, Martin RJ, et al. Elevated dose of inhaled corticosteroid versus add-on long-acting β-agonist for step-up remedy in bronchial asthma. Ann Am Thorac Soc. 2015;12(6):798-806. doi:10.1513/AnnalsATS.201412-580OC

  9. Kew KM, Karner C, Mindus SM, Ferrara G. Mixture formoterol and budesonide as upkeep and reliever remedy versus mixture inhaler upkeep for persistent bronchial asthma in adults and kids. Cochrane Database Syst Rev. 2013;12:CD009019. doi:10.1002/14651858.CD009019.pub2

  10. Robles J, Motheral L. Hypersensitivity response after inhalation of a lactose-containing dry powder inhaler. J Pediatr Pharmacol Ther. 2014;19(3):206-11. doi:10.5863/1551-6776-19.3.206

  11. Shroff S, Thomas RK, D’Souza G, Nithyanandan S. The impact of inhaled steroids on the intraocular stress. Digit J Ophthalmol. 2018;24(3):6-9. doi:10.5693/djo.01.2018.04.001

  12. Billington CK, Penn RB, Corridor IP. β Agonists. Handb Exp Pharmacol. 2017;237:23-40. doi:10.1007/164_2016_64

  13. Magee JS, Pittman LM, Jette-Kelly LA. Paradoxical bronchoconstriction with short-acting beta agonist. Am J Case Rep. 2018;19:1204-7. doi:10.12659/AJCR.910888

  14. Philip J. The consequences of inhaled corticosteroids on development in kids. Open Respir Med J. 2014;8:66-73. doi:10.2174/1874306401408010066

  15. Ajimura CM, Jagan N, Morrow LE, Malesker MA. Drug interactions with oral inhaled medicines. J Pharm Technol. 2018;34(6):273-80. doi:10.1177/8755122518788809

  16. Hasford J, Virchow JC. Extra mortality in sufferers with bronchial asthma on long-acting beta2-agonists. Eur Respir J. 2006;28(5):900-2. doi: 10.1183/09031936.00085606

  17. U.S. Meals and Drug Administration. FDA drug security communication: FDA evaluation finds no important enhance in threat of great bronchial asthma outcomes with long-acting beta agonists (LABAs) utilized in mixture with inhaled corticosteroids (ICS).

What to Know About Mixture Bronchial asthma Inhalers

By Pat Bass, MD

Dr. Bass is a board-certified internist, pediatrician, and a Fellow of the American Academy of Pediatrics and the American School of Physicians.

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