List of long-acting beta agonists: Uses, common brands, and safety info

The recurrent coughing, wheezing, and shortness of breath experienced by those with asthma or chronic obstructive pulmonary disease (COPD) can be life-altering. These symptoms are a function of constricted bronchial tubes. Swelling from airway inflammation and spasm of the smooth muscle around airways combine to produce bronchoconstriction. Targeting the bronchospasm component, beta agonists can provide fast-acting and long-lasting relief for those diagnosed with these pulmonary diseases. Long-acting beta agonists (LABAs) are a subclass of beta agonists that primarily function as preventive maintenance therapy. Their utility, mechanism of action, adverse effects, and cost will be covered here.

Other long-acting beta agonists

• Bevespi Aerosphere (glycopyrrolate-formoterol)

• Breztri Aerosphere (budesonide-glycopyrrolate-formoterol)

• Airduo Respiclick (fluticasone-salmeterol)

• Airduo Digihaler (fluticasone-salmeterol)

• Wixela Inhub (fluticasone-salmeterol)

What are long-acting beta agonists?

Beta agonists (β-agonists) are bronchodilators that come in short-acting and long-acting forms. Albuterol (also known as salbutamol) is the best-known short-acting beta-2 agonist (SABA) and can provide relief from asthma symptoms for up to six hours. Long-acting beta-2 agonist duration of action is two to four times as long as albuterol, providing a method for asthma control instead of simply short-term relief.

To achieve bronchodilation, LABAs must be delivered by the inhaled route. Handheld inhalers provide an easy-to-use, quick, and portable method of getting these drugs to the airways. Either a pressure-activated hydrofluoroalkane (HFA) propellant is used to get the medicine from the inhaler to the airways, or with dry powder inhalers (DPI), a fast, deep inspiration by the user brings the fine powdered drug to the bronchial tubes. When using HFA inhalers, a spacer device is recommended to get more beta agonist to the airways and less in the mouth. Aside from inhalers, nebulizer machines are another option for LABA administration. They use pressurized air to aerosolize the medication, which is inspired over the course of about 10 minutes.

RELATED: Can you use an expired inhaler?

How do long-acting beta agonists work?

LABAs are beta-2 agonists, selectively attaching to the beta-2 adrenergic receptor in the smooth muscle that lines the bronchial tube. By comparison, epinephrine is an example of non-selective SABA; it stimulates both bronchial beta-2 adrenoceptors and cardiac beta-1 adrenoceptors, which can result in tachycardia (fast heart rate). The result of LABA activation of beta adrenoreceptors is the production of cyclic adenosine monophosphate (cAMP) by adenylyl cyclase. Protein kinase A is then triggered by cAMP, which results in shifts in cellular calcium levels. The result of this multi-step mechanism is relaxation of the bronchial smooth muscle, producing bronchodilation.

A molecular structure modification, a lipophilic chain, is what enables a LABA to maintain a presence in the bronchial smooth muscle cell membrane for a longer period of time. Instead of a two- to six-hour duration of action like SABAs, the modification gives LABAs the ability to provide bronchodilation for 12 to 24 hours. However, the onset of action may be slower with LABAs. Salmeterol’s onset of action can take 30 to 45 minutes, compared to five minutes with albuterol. Formoterol and olodaterol, on the other hand, can act as quickly as albuterol.

What are long-acting beta agonists used for?

• Bronchospasm

• Exercise-induced bronchospasm

• Asthma

• COPD, including emphysema and chronic bronchitis

Types of long-acting beta agonists

Long-acting beta agonists

Perforomist, Serevent, and Striverdi Respimat are LABA inhalers without any other active ingredient, containing only formoterol, salmeterol xinafoate, and olodaterol respectively. They are classified as maintenance agents, because the prolonged bronchodilation they produce can prevent symptoms before they start. Striverdi Respimat can be dosed once daily to provide 24 hours of action, while Perforomist and Serevent are dosed twice daily. For COPD management, they can be used as monotherapy, without inhaled steroids, but for management of asthma, they must be used in conjunction with inhaled corticosteroids. 

Combination agents

Most commonly, LABAs are used and produced in combination with other inhaled medications. Inhaled corticosteroids (ICS) are a common addition to LABA therapy. Their anti-inflammatory effect lessens the swelling within bronchial tubes. In addition to bronchospasm, airway inflammation is a primary problem in asthma and COPD. The bronchodilating effects of a LABA together with the anti-inflammatory effects of an ICS has powerful potential for controlling COPD and asthma symptoms and preventing exacerbations of these diseases. Individuals with persistent asthma, meaning those with frequent or severe asthma symptoms, can benefit from combination therapy.

Advair, Airduo, and Wixela combine salmeterol with the glucocorticoid fluticasone propionate. Likewise, the LABA formoterol couples with budesonide, in Symbicort, and mometasone, in Dulera. A 24-hour LABA vilanterol is combined with fluticasone in the Breo Ellipta inhaler, a once daily option for glucocorticoid-LABA therapy.

The glucocorticoid-LABA products are maintenance or controller medications for asthma and COPD. Unique among this group of combination asthma medications, Symbicort and Dulera can potentially fill a bigger role in the treatment of asthma. These glucocorticoid-formoterol products have the advantage of a fast onset of action from formoterol, which in conjunction with an inhaled steroid, create an opportunity for these products to function as a single maintenance and rescue therapy (SMART). Formoterol can provide quick relief, while also assisting the ICS in providing asthma control. This compares to traditional regimens in which a glucocorticoid-LABA inhaler is used for asthma control and a SABA is used for rescue use. Although it is used off-label, the SMART approach is not approved by the U.S. Food and Drug Administration (FDA).

Another drug class that makes a logical addition to long-acting β-agonists is the muscarinic antagonist (also known as anticholinergics) category. The anticholinergics block M1 and M3 muscarinic receptors within the smooth muscle of bronchial tubes, resulting in bronchodilation via a different mechanism than beta agonists. The complimentary airway-opening effects are useful for COPD combination therapy. Specifically, the long-acting muscarinic antagonists (LAMAs) have durations of action that pair nicely with LABAs. Anoro Ellipta (umeclidinium-vilanterol), Stiolto Respimat (tiotropium-olodaterol), and Bevespi Aerosphere (glycopyrrolate-formoterol) are all maintenance LAMA-LABA agents for COPD treatment. 

To adequately control COPD, healthcare providers may recommend all three long-acting inhaled drug varieties, LABA, LAMA, and steroid. The trio is available in the form of Trelegy Ellipta (fluticasone-umeclidinium-vilanterol) and Breztri Aerosphere (budesonide-glycopyrrolate-formoterol) inhalers.

Who can take long-acting beta agonists?

Can both men and women take long-acting beta agonists?

If there are no contraindications to the drug class or specific product, men and women can take long-acting β-agonists. 

Can you take long-acting beta agonists while pregnant or breastfeeding?

Using long-acting beta agonists during pregnancy or breastfeeding may be advisable due to the risks of uncontrolled bronchospasm, but the uncertainties of LABA use in these circumstances should be recognized. There is not much clinical study data on use of LABA in pregnancy and breastfeeding, and there is a concern about uterine contractions being altered during labor.

Can children take long-acting beta agonists?

LABA combination products, but not LABA monotherapy, are FDA-approved for use in children. Combination glucocorticoid-LABA therapy is meant to reduce asthma exacerbations in this age group. The approval extends to children aged 5 for Dulera and age 12 for Advair. Another glucocorticoid-LABA combination Breo Ellipta and the LAMA-LABA products are not approved for use in children. 

Can seniors take long-acting beta agonists?

Seniors can use long-acting beta agonists, but side effects like tachycardia could be more problematic.

Are long-acting beta agonists safe?

Black box warning

The FDA’s black box warning on LABAs is based on two significant concerns in asthmatics. One involves clinical trials showing an increased risk of asthma-related deaths when LABAs are used without concurrent inhaled corticosteroids. 

The second comes from clinical trials in pediatric and adolescent asthmatics, which showed a greater risk of asthma-related hospitalizations with LABA monotherapy. 

Accordingly, the FDA’s drug safety communication advises against LABA monotherapy for asthma treatment and instead advises LABAs to only be used in conjunction with an ICS, preferably with a combination glucocorticoid-LABA inhaler.

Recalls

No beta agonists have current recalls, but the FDA’s database should be searched for updated listings.

Restrictions

Contraindications to long-acting β-agonists include a history of hypersensitivity allergic reactions to the drug or drug class, acute bronchospasm, acute asthma, and acutely deteriorating COPD. In addition, severe milk protein allergy is a contraindication to DPI inhalers.

Are long-acting beta agonists controlled substances?

LABAs are not listed as controlled substances by the Drug Enforcement Agency (DEA).

Common long-acting beta agonists side effects

• Tachycardia, chest pain, or heart palpitations

• Tremor or nervousness

• Throat irritation, hoarseness, upper respiratory infection symptoms, or cough

• Nausea, vomiting, or diarrhea

• Bad taste or dry mouth

• Headache or pain

• Urticaria (hives) or rash

• Insomnia

• Oral candidiasis (thrush) with combination products containing glucocorticoids

RELATED: Symbicort side effects

How much do long-acting beta agonists cost?

The LABA-only products and combination products both carry a significant expense. Most cost around $500 for a single inhaler, and Trelegy can even cost $800. These pricey medications can be an essential element of a medical regimen for controlling asthma or COPD. To help lessen their expense, your SingleCare discount card can be shown to your pharmacist.