Lindsay Cook, PharmD is a board-certified consultant pharmacist.

Combination asthma inhalers are used for the long-term control of asthma symptoms. They combine two different inhaled medications—a corticosteroid and a long-acting beta-agonist (LABA). Corticosteroids control inflammation while LABAs are bronchodilators that widen and open constricted airways to allow for the free flow of air. When used in tandem, these medications can ease hyperresponsiveness of airways and help to stave off an asthma attack.

There are five combination inhalers approved by the U.S. Food and Drug Administration (FDA) for treating asthma:

Generic forms of Advair, known by the brand names AirDuo Respiclick, Wixela Inhub, and others, also are available. Symbicort generics (including the branded generic Breyna, approved in 2022) are also commonly sold as a budesonide/formoterol inhaler.

Combination inhalers are used to control asthma symptoms and ward off asthma attacks. They do double duty by each targeting a specific aspect of the physiological events that comprise an asthma attack:

Symbicort and Breo also are approved for the daily treatment of chronic obstructive pulmonary disease (COPD). Advair Diskus, the dry powder form of the drug, is approved for COPD as well, although its aerosolized form, Advair HFA, is not.

Studies have shown that salmeterol, the LABA used in Advair HFA, increases the risk of pneumonia in people with COPD. Though Advair Diskus also contains salmeterol, the dose is far smaller and is considered safer for ongoing use.

Some healthcare providers prescribe Dulera off-label to people with COPD, although its safety and effectiveness for this purpose have not yet been established.

You are a candidate for a combination asthma inhaler if a rescue inhaler alone fails to control your asthma, meaning you:

Originally, inhaled corticosteroids were the first drugs used as controller medications if a rescue inhaler failed to provide adequate control of asthma symptoms. Today, instead of waiting to add a LABA to the treatment plan, many health authorities—including the Global Initiative for Asthma (GINA)—endorse the combined use of an inhaled corticosteroid and an inhaled LABA from the start.

That is not to suggest a combination inhaler is a one-size-fits-all-solution. A 2015 study in the Annals of the American Thoracic Society argued that inhaled steroids were just as effective in controlling asthma symptoms as combined steroid/LABA therapy and allowed for adjustments in doses when needed.

Other studies contend that, because of their convenience, people are more likely to use them as prescribed, effectively improving health outcomes in people with asthma. Moreover, combination inhalers require a smaller dose of steroids to achieve the same benefits in control as single steroid inhalers.

A 2013 review in the Cochrane Database of Systematic Reviews concluded that people who used combination inhalers were less likely to be hospitalized or need emergency room visits than those who used two different inhalers and were less likely to need stronger oral steroids in the future.

The only absolute contraindication for the use of a combination inhaler is a known allergy to any active or inactive ingredient used in the inhaler. This includes an allergy to milk, as milk powder is a central inactive ingredient in both Advair Diskus and Breo Ellipta.

LABAs are known to affect blood pressure, blood sugar, heart rate, thyroid hormone production, and the firing of brain cells. These effects are tempered somewhat by inhaled corticosteroids, allowing LABAs to be delivered at smaller doses.

There also is evidence the long-term use of inhaled corticosteroids can affect the eyes as well as impair the body’s ability to fight infections.

Because of these concerns, combination asthma inhalers should be used with caution in people with the following health conditions:

People with any of these conditions should be routinely monitored to identify changes in their health status while on combination inhalers. In some cases, treatment may need to be stopped if symptoms worsen.

All combination asthma inhalers should be used with caution during pregnancy, as animal studies have suggested a potential for fetal harm, but no well-controlled studies in humans are available.

Although there is no evidence of an increased risk of birth defects in pregnancy registries, it is still important to speak with your healthcare provider to weigh the benefits and risks of treatment if you are pregnant, breastfeeding, or planning to get pregnant.

The combination asthma inhalers currently approved by the FDA can be categorized by their delivery system:

The recommended dose can vary by age. As a general rule, smaller doses are prescribed when first starting treatment and increased only if the drug fails to provide adequate control of symptoms.

No combination asthma inhaler is inherently "better" than another. Some may be more appropriate for specific age groups, while cost, delivery system, and dosing requirements (once-daily vs. twice-daily) may also factor into the decision.

Have your healthcare provider fully explain the benefits and limitations of each option to determine which inhaler is best suited to your needs.

MDIs and DPIs have pros and cons. MDIs deliver accurate doses and are easy to use, but require hand-breath coordination. DPIs don’t have buttons or require hand-breath coordination, but they can deliver varying doses based on how forcefully you inhale the medication.

Learning how to use a device properly can help you reap the optimal benefits.

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

MDIs need to be cleaned once weekly by wiping the mouthpiece with a dampened tissue and cleaning the aerosol opening with a dry cotton swab. Do not submerge the canister in water.

To use a DPI like Advair Diskus or Breo Ellipta:

Both MDIs and DPIs have built-in dose counters that tell you how many doses are left after each inhalation. Refill your prescription when the counter gets down to "20" (or "10" for Breo Ellipta).

MDIs and DPIs can be stored safely at room temperature, ideally between 68 degrees F and 77 degrees F. Do not store MDIs near heat or an open flame as this can cause bursting. Keep out of reach of children or pets.

Do not use an inhaler or any medication past its expiration date.

As with any medication, combination asthma inhalers can cause side effects. Many of these are relatively mild and will gradually resolve as your body adapts to treatment. Let your healthcare provider know if any side effect is severe, persists, or worsens.

Common side effects are largely the same between the different inhalant formulations. Those affecting 2% or more of users include:

Of the various drug formulations, Dulera has the fewest side effects (primarily stuffy or runny nose, sneezing, headache, and sinus pain).

The risk of oral thrush can be reduced by using a spacer with a MDI. Because DPIs such as Advair Diskus and Breo Ellipta cannot accommodate a spacer, you can reduce your risk of thrush by rinsing your mouth thoroughly with water after every use.

An uncommon but serious side effect of combination asthma inhalers is paradoxical bronchospasm, a condition in which symptoms of asthma worsen rather than improve. LABAs are responsible for this effect, although the exact cause of the reaction is poorly understood.

Paradoxical bronchospasms appear to affect people with severe airway inflammation who use an inhalant for the first time. 

The sudden onset of shortness of breath, wheezing, chest pain, and cough after using a combination asthma inhaler should be regarded as a medical emergency. People who experience paradoxical bronchospasm should not be rechallenged with the same drug.

Anaphylaxis, a potentially life-threatening, whole-body allergy, is a rare occurrence with combination asthma inhalers, but cases have been reported in people who have used Advair Diskus or Breo Ellita due to an underlying milk allergy.

Call 911 or seek emergency care if you experience the following after using a combination asthma inhaler:

If left untreated, anaphylaxis can lead to shock, coma, asphyxiation, cardiac or respiratory failure, and death.

Corticosteroids are known to affect bone density, but this appears to be less a risk with inhaled corticosteroids than with oral corticosteroids. Still, young children should be monitored as the long-term use of a combination inhaler may impair growth. The risks appear greatest among toddlers with severe persistent asthma.

There are a number of common drugs and drug classes known to interact with combination asthma inhalers.

Corticosteroids and LABAs are both metabolized by a liver enzyme called cytochrome P450 (CYP450) and can interact with other drugs that use the same enzyme for metabolization. This competition can slow the rate at which a drug is cleared from the body. This may either increase the concentration of a drug (along with its side effects) or decrease the concentration of a drug (and reduce its efficacy).

Among the drugs of greatest concern are:

LABAs on their own can interact with four classes of drugs in different ways. These include:

To avoid drug interactions, let your healthcare provider know about any drug you are taking, be it prescription, over-the-counter, herbal, or recreational.

Until late 2017, the FDA issued a black box warning for all corticosteroid/LABA inhalers, advising consumers that the drugs were associated with an increased risk of asthma-related deaths. The advisement was based on studies in which 13 deaths were reported among 13,176 LABA users over a 28-week study period.

On December 20, 2017, the FDA reversed the order when it was shown that the risk of death occurred when LABAs were used on their own (in monotherapy). Current research has shown that the combined use of a LABA and corticosteroid poses no such harm.

Although the black box warning has been stripped from the packaging of combination asthma inhalers, it remains on all single-ingredient LABA medications.

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GlaxoSmithKline. Advair HFA (fluticasone propionate and salmeterol inhalation aerosol), for oral inhalation use.

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).

AstraZeneca. Symbicort (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol, for oral inhalation use.

Merck & Co. Dulera (mometasone furoate and formoterol fumarate dihydrate) inhalation aerosol, for oral inhalation use.

GlaxoSmithKline. Breo Ellipta (fluticasone furoate and vilanterol inhalation powder), for oral inhalation use.

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.

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

Yang HH, Lai CC, Wang YH, et al. Severe exacerbation and pneumonia in COPD patients treated with fixed combinations of inhaled corticosteroid and long-acting beta2 agonist. Int J Chron Obstruct Pulmon Dis. 2017;12:2477-85. doi:10.2147/COPD.S139035

Tang W, Sun L, Fizgerald JM. A paradigm shift in the treatment of mild asthma?. J Thorac Dis. 2018;10(10):5655-8. doi:10.21037/jtd.2018.09.127

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

Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013;12:CD009019. doi:10.1002/14651858.CD009019.pub2

Robles J, Motheral L. Hypersensitivity reaction 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

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

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

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

Philip J. The effects of inhaled corticosteroids on growth in children. Open Respir Med J. 2014;8:66-73. doi:10.2174/1874306401408010066

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

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

U.S. Food and Drug Administration. FDA drug safety communication: FDA review finds no significant increase in risk of serious asthma outcomes with long-acting beta agonists (LABAs) used in combination with inhaled corticosteroids (ICS).

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