10 Side Effects of Combination Inhalers: Voice Changes, Sore Throat, and More

If you’re living with a lung condition, such as asthma or chronic obstructive pulmonary disease (COPD), it’s important to have the right maintenance medications to manage your symptoms. Combination inhalers can be a convenient part of your treatment plan. They contain two or three different medications that work as a team in one device.

Combination inhalers often consist of an inhaled corticosteroid (ICS), a long-acting beta agonist (LABA), and/or a long-acting muscarinic antagonist (LAMA). ICS medications lower inflammation (swelling) in the airways of the lungs. LABAs and LAMAs are bronchodilators — meaning they open and relax the airways.

Common examples of combination inhalers include Advair (fluticasone / salmeterol), Anoro Ellipta (umeclidinium / vilanterol), and Trelegy Ellipta (fluticasone / umeclidinium / vilanterol). These types of combination inhalers are effective for many people. But like all medications, they have possible side effects to be aware of.

Combination inhaler side effects at a glance

The side effects of combination inhalers are generally dose- and ingredient-related. This means that higher doses are more likely to cause side effects. Side effects may resolve after stopping the medication or lowering your dose.

Relatively common combination inhaler side effects include:

• Oral thrush

• Cough

• Dysphonia (hoarseness)

• Sore and dry throat

• Dry mouth

• Bitter taste

• Skin bruises

• Muscle cramps

• Heart palpitations

• Tremor

• Increased appetite

Rare but serious side effects may include:

• Pneumonia

• Glaucoma

• Cataracts

• Adrenal insufficiency (adrenal glands don’t make enough of hormone cortisol)

• Osteoporosis

• Mood changes

• New or worsening diabetes

• Serious heart problems

• Delayed growth in children

Many of these side effects are related to the steroid portion of combination inhalers. Thankfully, ICS side effects are usually less intense (and less likely) than the side effects of oral corticosteroids, such as prednisone.

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Below, we’ll cover 10 notable combination inhaler side effects in more detail.

1. Oral thrush

Oral thrush is one of the most common steroid inhaler side effects. It’s not common to occur, however, when using a combination inhaler that doesn’t contain an ICS.

Thrush can look like white patches anywhere in the mouth and throat, including the tongue. It can make swallowing and eating painful. In one review of 16 studies, people using an ICS had an almost 3 times higher risk of getting thrush.

Rinsing your mouth with water and spitting it out after inhaling a dose can help lower the amount of steroid that remains in the mouth. In turn, this lowers the risk of thrush. If you have a metered-dose inhaler, spacers can also prevent thrush. Spacers help the medications reach your lungs rather than your mouth and throat.

If you do develop thrush, your healthcare professional may recommend an antifungal treatment to help treat the infection. Clotrimazole and nystatin are a couple of examples.

2. Voice changes

Hoarseness is another possible side effect of ICS-containing combination inhalers. This can happen if the medication affects your vocal cords. You may notice this within hours of inhaling your first dose, or it could develop months down the line. Thankfully, it’s generally short-lived.

Just like with oral thrush, prevention is key. Rinsing your mouth with water after using a steroid inhaler can lower the chance of experiencing hoarseness or voice changes.

3. Sore or dry throat

You may develop a sore throat after administering a dose of your combination inhaler — especially if it contains an ICS. This isn’t typically a big issue. But rinsing your mouth after each inhaler dose and/or using a spacer can help prevent this from happening.

Dry mouth, or a dry throat, is a more common LAMA side effect. Umeclidinium is one example of a LAMA, which is found in combination inhalers like Anoro Ellipta and Trelegy Ellipta. Staying hydrated and chewing sugar-free gum are a couple of ways to manage dry mouth.

4. Muscle cramps or spasms

It can be unsettling to experience muscle cramps or spasms — especially if they wake you up in the middle of the night. But if your combination inhaler contains a LABA, that may be a culprit for why it’s happening.

LABAs are thought to activate beta receptors in the muscles, which may lead to cramps or spasms. One common LABA is formoterol, and it's found in inhalers such as Symbicort, Dulera, and Breztri Aerosphere.

In one small study, over 60% of people reported experiencing muscle cramps with LABAs. In the same study, muscle spasms (or “muscle twisting”) happened in nearly 40% of people. Thankfully, muscle-related side effects tend to improve when the LABA dose is lowered.

5. Tremors

Shakiness, or tremors, can happen from the LABA portion of your combination inhaler. But it’s not common overall. In one review of over 8,500 people living with COPD, tremors occurred in less than 1% of people.

If you experience a tremor, it typically happens when you first start a LABA-containing combination inhaler. It usually gets better within a few days. If it doesn’t, reach out to your prescriber.

6. Heart palpitations or faster heart rate

LABAs may speed up your heart rate. It’s more likely with high doses, and the risk to your heart might be higher within the first 30 days (1 month) of starting a LABA. That being said, studies of people with COPD have found that LABAs and LAMAs don’t cause long-term heart problems.

Still, if you have high blood pressure, heart failure, or any other heart problems, talk to a healthcare professional before starting a combination inhaler. They can help you weigh the pros and cons of these medications.

7. Pneumonia

Pneumonia is a rare but serious steroid inhaler side effect. Corticosteroids can weaken your immune system, so they unintentionally increase the risk of infection.

The risk of pneumonia is greater with higher steroid doses. For instance, fluticasone doses greater than 500 mcg per day are considered to be on the higher end of the spectrum. People living with COPD who use ICS-containing combination inhalers may have a greater chance of developing pneumonia compared to those who use non-ICS medications. There may also be a higher risk with fluticasone compared to other steroids.

To reduce your risk of pneumonia, work with your prescriber to ensure you’re using the lowest effective steroid dose for your symptoms. Staying up to date on vaccines, including pneumonia and flu shots, can also help prevent infections. And if you ever develop pneumonia symptoms such as persistent cough, fever, or shortness of breath, report them to a healthcare professional right away.

Good to know: Cleaning your inhaler removes germs that build up in your inhaler device. This may help prevent infections too. But how you clean it depends on what type of inhaler you have. Reach out to your pharmacist to review cleaning instructions.

8. Adrenal insufficiency

Adrenal insufficiency happens when your adrenal glands don’t produce enough of the hormones cortisol or aldosterone. ICS-containing inhalers can cause adrenal insufficiency if your body absorbs too much of the medication, reducing its natural cortisol production.

Adrenal insufficiency is rare with ICS combination inhalers. But it’s more likely with high doses used over a long period of time.

Reach out to your prescriber if you notice any symptoms of adrenal insufficiency. This may include muscle weakness, sudden stomach pain, or loss of appetite. They can check your cortisol levels with a blood test to see if you’re experiencing adrenal insufficiency.

9. Bone fractures

Combination inhalers that contain an ICS may lower your bone density. Your bone density is a marker of how strong your bones are.

Some studies have shown a link between long-term ICS use and lower bone density. This can lead to a higher risk of fractures. The risk of bone fracture is greater with higher ICS doses, but it’s lower than with oral corticosteroids.

If you have any existing risk factors for osteoporosis — like a family history of osteoporosis or a medical condition that makes you unable to move — talk to a healthcare professional. They’ll review the risks and benefits of using a combination inhaler that contains an ICS.

10. Bruises

Skin bruising occasionally happens with combination inhalers that contain an ICS. Multiple studies have linked long-term ICS inhaler use to bruising. It may be more likely to occur in older adults and people who use higher doses for a long period of time.

If you notice any abnormal bruising while using your combination inhaler, let your healthcare professional know.

Good to know: Keep a current list of your prescription and over-the-counter (OTC) medications handy. Your pharmacist and prescriber can check if any interactions could raise your risk of bruising or bleeding. One example is with anticoagulants such as Eliquis (apixaban).

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Written by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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