Budesonide and formoterol (inhalation)

Budesonide and formoterol is a combination medicine used for asthma and chronic obstructive pulmonary disease (COPD). Budesonide is an inhaled corticosteroid (ICS) that reduces inflammation in the lungs. Formoterol is a long-acting beta2-agonist (LABA), a bronchodilator that helps the muscles around the airways stay relaxed to prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath.

Budesonide and formoterol is not a rescue medicine. It is not used to relieve sudden breathing problems and will not replace a rescue inhaler.

Two types of budesonide and formoterol inhalers are available in the United States, and they are not interchangeable. Both are pressurized metered-dose inhalers, but they contain different forms of formoterol in slightly different amounts, are approved for different age groups, and are primed and cleaned differently.

If you switch between these inhalers, ask your pharmacist to show you how to use the new device. The instructions are not the same.

Budesonide and formoterol fumarate dihydrate inhaler

This inhaler is used:

• to treat asthma in adults and children 6 years of age and older. It is used for people whose asthma is not adequately controlled on a long-term asthma-control medicine such as an inhaled corticosteroid, or whose asthma warrants starting treatment with both an inhaled corticosteroid and a long-acting beta2-agonist.
• for the maintenance treatment of airflow obstruction in adults with COPD, including chronic bronchitis and emphysema, and to reduce COPD exacerbations. Only the 160 mcg/4.5 mcg strength is approved for COPD.

It is not known if this inhaler is safe and effective in children younger than 6 years of age.

Budesonide and formoterol fumarate aerosphere inhaler (Symbicort Aerosphere)

This inhaler is used:

• to treat asthma in adults and children 12 years of age and older.
• for the maintenance treatment of COPD in adults.

It is not known if this inhaler is safe and effective in children younger than 12 years of age.

Limitations of use

Neither inhaler is indicated for the relief of acute bronchospasm. Neither should be used to treat an asthma attack or sudden severe symptoms of asthma or COPD.

Budesonide and formoterol has been used off-label as SMART therapy (Single Maintenance And Reliever Therapy), which is when a single ICS-formoterol inhaler is used as a daily maintenance dose and also as needed for symptom relief. This is an off-label use. The labels for both types of inhaler state that patients should not use more than 2 inhalations twice daily.

The 2020 focused updates to the National Institutes of Health asthma management guidelines describe SMART therapy as a preferred treatment for people with moderate to severe persistent asthma who are already using a low- or medium-dose inhaled corticosteroid. Suitability depends on age, asthma severity, and the inhaled corticosteroid dose in the ICS-formoterol product.

In the guidelines, the maximum number of puffs per day is 8 (36 mcg formoterol) for children aged 4 to 11 years and 12 puffs (54 mcg formoterol) for people aged 12 years and older. These figures are based on a formoterol dose of 4.5 mcg per inhalation, the preparation most commonly used in the studies of this approach. Budesonide and formoterol is not approved for use in children younger than 6 years of age.

Because the fumarate inhaler delivers 4.8 mcg of formoterol per puff rather than 4.5 mcg, the puff limits above do not apply to it, and its label specifies not using more than 2 inhalations twice daily.

Anyone who feels they need more than the maximum number of puffs should contact their healthcare provider.

Your inhaler comes with a Patient Information leaflet and Instructions for Use, including directions for priming and cleaning the device. Read them before you start, and each time you get a refill. Ask your healthcare provider or pharmacist if anything is unclear.

• Use your inhaler exactly as your healthcare provider tells you to. Do not use it more often than prescribed. Using too much can cause serious side effects.
• Take 2 puffs in the morning and 2 puffs in the evening, about 12 hours apart.
• Do not use more than 2 puffs twice each day.
• Rinse your mouth with water and spit it out after each dose. Do not swallow the water. This helps reduce the chance of a fungal infection (thrush) in the mouth and throat.
• Do not change or stop any of your breathing medicines without your healthcare provider's advice, even if you are feeling well.
• If you also take an oral steroid medicine, do not stop it suddenly. Follow your healthcare provider's instructions about tapering the dose.
• Do not use another medicine containing a long-acting beta2-agonist while you are using budesonide and formoterol. Ask your healthcare provider or pharmacist if you are not sure whether any of your medicines is a long-acting beta2-agonist.
• Do not spray the medicine in your eyes. If it gets in your eyes, rinse them well with water and call your healthcare provider if redness or irritation continues.
• Do not let a young child use the inhaler without help from an adult.
• Your dose needs may change if you have surgery, are ill, are under stress, or have recently had an asthma attack. Do not change your dose or schedule without your healthcare provider's advice.
• If you use a peak flow meter at home, tell your healthcare provider if your numbers are lower than normal.

Priming and cleaning the fumarate dihydrate inhaler (Symbicort and Breyna)

• Prime the inhaler before you use it for the first time by shaking it well for 5 seconds and releasing 2 test sprays into the air away from your face, shaking again between sprays.
• Prime it again if you have not used it for more than 7 days or if you drop it.
• Clean the white mouthpiece every 7 days. Remove the grey mouthpiece cover, wipe the inside and outside of the mouthpiece opening with a clean, dry cloth, then replace the cover.
• Do not put the inhaler into water, and do not try to take it apart.

Priming and cleaning the fumarate inhaler (Symbicort Aerosphere)

• Prime the inhaler before you use it for the first time by releasing 4 test sprays into the air away from your face, shaking well before each spray.
• Re-prime with 2 test sprays if you have not used it for more than 7 days, if you drop it, or after the weekly rinse.
• Rinse the white actuator once each week so medicine does not build up and block the spray. Remove the canister and set it aside, keeping it dry, then remove the mouthpiece cover. Run warm water through the mouthpiece for 30 seconds and then through the top of the actuator for 30 seconds.
• Shake off as much water as you can. Do not dry the actuator with a towel or tissue. Let it air-dry, such as overnight.
• Do not put the canister back into the actuator while it is still wet. When it is completely dry, replace the mouthpiece cover first, then press the canister down into the actuator and re-prime.

How long it takes to work

Improvement in asthma control can begin within 15 minutes of starting budesonide and formoterol, although the maximum benefit may not be reached for 2 weeks or longer. How quickly symptoms improve, and by how much, varies from person to person. Keep using your inhaler as directed. Tell your healthcare provider if your symptoms have not improved after about 1 week of regular use.

Budesonide and formoterol is not a rescue medicine. It will not work fast enough to treat an asthma attack or sudden bronchospasm. Always have a rescue inhaler with you. If you do not have one, ask your healthcare provider to prescribe one.

Seek medical attention if your breathing problems get worse, if you need your rescue inhaler more often than usual, if your rescue inhaler does not work as well as it used to, or if you think your medicines are not working as well.

Long-acting beta2-agonists used on their own, without an inhaled corticosteroid, increase the risk of asthma-related hospitalization and asthma-related death. This is considered a class effect. Budesonide and formoterol contains both an inhaled corticosteroid and a long-acting beta2-agonist. In large clinical trials, using an inhaled corticosteroid and a long-acting beta2-agonist together did not show a significant increase in the risk of serious asthma-related events compared with an inhaled corticosteroid alone. These trials were not designed to rule out all risk.

Budesonide and formoterol should not be started while your asthma or COPD is deteriorating quickly, which can be a life-threatening situation. Treat sudden symptoms with a short-acting inhaled reliever, not with extra doses of budesonide and formoterol.

Do not use another medicine containing a long-acting beta2-agonist while you are using budesonide and formoterol, because an overdose may result.

Do not stop using budesonide and formoterol without talking to your healthcare provider, because your symptoms may come back.

Do not use budesonide and formoterol if you:

• need treatment for sudden severe symptoms of asthma or COPD, including status asthmaticus or other acute episodes that need intensive treatment.
• are allergic to budesonide, formoterol, or any of the other ingredients in your inhaler. See the ingredients section below.

Budesonide can weaken your immune system. Tell your healthcare provider about any illness or infection you have had within the past several weeks.

To make sure budesonide and formoterol is safe for you, tell your healthcare provider if you have or have ever had:

• heart problems or high blood pressure
• seizures or another convulsive disorder
• a weak immune system
• liver problems
• weak bones (osteoporosis)
• eye problems such as glaucoma, increased pressure in the eye, or cataracts
• diabetes
• thyroid problems, including an overactive thyroid
• tuberculosis
• any type of viral, bacterial, parasitic, or fungal infection, or ocular herpes simplex
• an electrolyte imbalance, such as low potassium levels in your blood [FLAG-INSERT: not part of the patient counseling content in the prescribing information for the fumarate dihydrate inhaler. Confirm against the fumarate inhaler prescribing information or remove]
• a drug allergy

Also tell your healthcare provider if you have been exposed to chickenpox or measles.

Pregnancy and breastfeeding

Tell your healthcare provider if you are pregnant or plan to become pregnant. Available data on inhaled budesonide use during pregnancy have not identified a drug-associated risk of major birth defects or miscarriage. There are not enough data on formoterol during pregnancy to know whether it carries a risk. Poorly or moderately controlled asthma during pregnancy is itself linked to a higher risk of problems, including preeclampsia in the mother and prematurity, low birth weight, and small size for gestational age in the baby. Pregnant women with asthma should be monitored closely and their treatment adjusted as needed to keep asthma well controlled.

Because beta-agonists may interfere with contractions of the womb, use during labor should be limited to situations where the benefits clearly outweigh the risks.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. Budesonide, like other inhaled corticosteroids, is present in human milk. The amount available to a breastfed infant is estimated at about 0.3% to 1% of the dose the mother inhales. There are no data on the presence of formoterol in human milk, or on the effects of either medicine on a breastfed child or on milk production. You and your healthcare provider should weigh the benefits of breastfeeding against your need for the medicine.

Budesonide and formoterol pregnancy and breastfeeding warnings (more detail)

Get emergency medical help if you have signs of an allergic reaction: rash, hives, difficulty breathing, or swelling of your face, mouth, lips, tongue, or throat.

Serious side effects

Budesonide and formoterol may cause serious side effects, including:

• Worsening breathing problems. Call your healthcare provider or get emergency medical care right away if your breathing problems get worse, if you need your rescue inhaler more often than usual, or if your rescue inhaler does not work as well to relieve your symptoms.
• Sudden breathing problems right after using your inhaler (paradoxical bronchospasm). This can be life threatening. If it happens, stop using the inhaler, treat the symptoms with a short-acting reliever inhaler, and call your healthcare provider right away.
• Serious allergic reactions, including anaphylaxis. Stop using the inhaler and call your healthcare provider or get emergency medical care if you get a rash, hives, swelling of the face, mouth, lips or tongue, or difficulty breathing or swallowing.
• Fungal infection in your mouth or throat (thrush). Signs include sores or white patches in your mouth and throat, and pain when swallowing. Rinse your mouth with water without swallowing after each dose to help reduce the risk.
• Pneumonia and other lower respiratory tract infections. People with COPD have a higher chance of getting pneumonia. Call your healthcare provider if you notice an increase in mucus, a change in mucus color, fever, chills, increased cough, or increased breathing problems.
• Weakened immune system and a higher chance of infections. Tell your healthcare provider about any signs of infection, such as fever, chills, body aches, pain, unusual tiredness, nausea, or vomiting. Existing tuberculosis and fungal, bacterial, viral or parasitic infections may get worse.
• Reduced adrenal function (adrenal insufficiency). This is a condition in which the adrenal glands do not make enough steroid hormones, and it can happen when you stop taking an oral corticosteroid such as prednisone and start an inhaled corticosteroid. Deaths due to adrenal insufficiency have occurred during and after this change in treatment. When your body is under stress from fever, injury, infection, surgery, or worsening COPD symptoms, adrenal insufficiency can get worse and may be life threatening. Symptoms include feeling tired, lack of energy, weakness, nausea and vomiting, and low blood pressure. If you have been taken off an oral corticosteroid, your healthcare provider may tell you to start taking it again straight away during times of stress, a severe asthma attack, or a severe worsening of COPD, and to contact them for further instructions. You may also be asked to carry a card stating that you could need extra corticosteroid treatment at these times.
• Too much corticosteroid in the body (hypercorticism). This can happen at higher than recommended doses, or at usual doses in people who are sensitive to these effects. If it occurs, your healthcare provider will consider appropriate treatment.
• Effects on your heart, including increased blood pressure, a fast or irregular heartbeat, and chest pain. Budesonide and formoterol should be used with caution if you have a heart condition, particularly reduced blood flow to the heart, an irregular heart rhythm, or high blood pressure.
• Effects on your nervous system, including tremor and nervousness.
• Lower bone mineral density (bone thinning or weakness). This is more likely in people who already have a higher chance of osteoporosis. Bone density should be assessed before starting treatment and from time to time afterwards, particularly in people with COPD.
• Slowed growth in children. Inhaled corticosteroids can slow growth in children. A child's growth should be checked regularly, for example by measuring height, and the dose should be kept as low as possible while still controlling symptoms.
• New or worsened eye problems, including glaucoma and cataracts. Symptoms can include blurred vision, tunnel vision, eye pain or redness, or seeing halos around lights. You should have regular eye exams during long-term treatment, and your healthcare provider may refer you to an eye specialist if you develop eye symptoms.
• Changes in blood test results, including high blood sugar (hyperglycemia) and low potassium (hypokalemia). Signs of high blood sugar include increased thirst, increased urination, dry mouth, and fruity breath odor. Low potassium may cause muscle spasm, muscle weakness, or an abnormal heart rhythm.

The label for the fumarate dihydrate inhaler also lists swelling of the blood vessels (eosinophilic conditions and Churg-Strauss syndrome), which can happen in people with asthma, usually when an oral corticosteroid is reduced or stopped after starting an inhaled corticosteroid. Tell your healthcare provider right away if you have a pins-and-needles feeling or numbness in your arms or legs, a rash, flu-like symptoms, or pain and swelling of the sinuses. This is not listed on the label for the fumarate inhaler.

Common side effects

Common side effects of the fumarate dihydrate inhaler in people with asthma may include nasopharyngitis, headache, upper respiratory tract infection, throat pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and thrush in the mouth and throat.

In children aged 6 to less than 12 years, the common side effects reported with this inhaler were upper respiratory tract infection, sore throat (pharyngitis), headache, and a runny or stuffy nose (rhinitis).

Common side effects of the fumarate dihydrate inhaler in people with COPD may include nasopharyngitis, thrush in the mouth and throat, bronchitis, sinusitis, and upper respiratory tract infection.

Common side effects of the fumarate inhaler in people with asthma may include nasopharyngitis, COVID-19, allergic rhinitis (hay fever), bacterial bronchitis, upper respiratory tract infection, joint pain, gout, high blood pressure, diarrhea, and influenza-like illness.

Common side effects of the fumarate inhaler in people with COPD may include upper respiratory tract infection, COPD symptoms, back pain, headache, bronchitis, thrush in the mouth and throat, hoarseness, and muscle spasms.

This is not a complete list of side effects and others may occur. Tell your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. [FLAG-INSERT: the brand page also gives a manufacturer reporting line. Confirm whether a manufacturer number should appear on a page covering multiple products, and if so which]

FDA-approved dosage

Budesonide and formoterol fumarate dihydrate inhaler:

• Asthma in patients 12 years of age and older: 2 inhalations of the 80/4.5 or 160/4.5 strength twice daily. The starting dosage is based on asthma severity, level of symptom control, and risk of exacerbations on current inhaled corticosteroids.
• Asthma in patients aged 6 to less than 12 years: 2 inhalations of the 80/4.5 strength twice daily.
• Maintenance treatment of COPD in adults: 2 inhalations of the 160/4.5 strength twice daily.

Budesonide and formoterol fumarate inhaler (Symbicort Aerosphere):

• Asthma in patients 12 years of age and older: 2 inhalations of the 80/4.8 or 160/4.8 strength twice daily. The starting dosage is based on asthma severity, level of symptom control, and risk of exacerbations on current inhaled corticosteroids.
• Maintenance treatment of COPD in adults: 2 inhalations of the 160/4.8 strength twice daily.

The label for the fumarate inhaler also describes these doses as a total per dose rather than per puff, so 2 inhalations of the 80/4.8 strength appear as 160 mcg/9.6 mcg, and 2 inhalations of the 160/4.8 strength appear as 320 mcg/9.6 mcg. The carton shows the per-puff strength.

Maximum dose

For both inhalers, do not use more than 2 inhalations twice daily. For adults and children 12 years of age and older, the highest recommended dose of the fumarate dihydrate inhaler is 160/4.5, 2 inhalations twice daily.

Response

If your asthma has not responded well enough after 1 to 2 weeks of treatment with the 80/4.5 strength, your healthcare provider may change you to the 160 mcg strength. If a dose that was previously working stops controlling your symptoms, your healthcare provider should re-evaluate your treatment. Options include changing to the higher strength, adding another inhaled corticosteroid, or starting an oral corticosteroid.

The advice differs between the two inhalers, so follow the instructions for the one you use.

• Fumarate dihydrate inhaler: take your next dose at the time you normally would. Do not use two doses at one time.
• Fumarate inhaler: take the missed dose (2 puffs) as soon as possible, then take your next dose at the usual time. Do not take more than one dose to make up for a missed dose.

If you use too much, call your healthcare provider or go to the nearest hospital emergency room right away if you have any unusual symptoms. In case of an overdose, you can also contact the Poison Help line at 1-800-222-1222.

Overdose symptoms may include worsening shortness of breath, chest pain, fast or irregular heartbeats, increased blood pressure, headache, tremor, muscle cramps, nausea, dizziness, and feeling shaky or nervous.

Do not use a second inhaled medicine that contains a long-acting beta2-agonist, such as arformoterol, formoterol, indacaterol, olodaterol, salmeterol, or vilanterol.

Avoid being near people who are sick or have infections. Call your healthcare provider for preventive treatment if you are exposed to chickenpox or measles. These infections can be serious or even fatal in people using a corticosteroid such as budesonide.

If the medicine gets in your eyes, rinse with water and call your healthcare provider if you have severe eye redness or irritation.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Talk to your healthcare provider before you start any new medicine. No formal drug interaction studies have been carried out with either inhaler.

Especially tell your healthcare provider if you take:

• other long-acting beta2-agonists, including salmeterol, arformoterol tartrate, vilanterol, olodaterol, and indacaterol. Do not use these with budesonide and formoterol, because an overdose may result.
• strong CYP3A4 inhibitors, including ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, saquinavir, and telithromycin. These can increase the amount of budesonide in your body and raise the risk of corticosteroid side effects.
• antifungal or anti-HIV medicines.
• beta-blockers, including eye drops. These can block the effects of budesonide and formoterol and may cause severe bronchospasm.
• diuretics that are not potassium-sparing, such as loop or thiazide diuretics, which may worsen low potassium levels or ECG changes.
• xanthine derivatives, such as theophylline, or steroid medicines, which may add to the effect of formoterol on potassium levels.
• monoamine oxidase inhibitors, tricyclic antidepressants, or other medicines that can prolong the QT interval. [FLAG-INSERT: section 7 of the prescribing information for the fumarate dihydrate inhaler names only monoamine oxidase inhibitors and tricyclic antidepressants. QTc prolongation appears in section 5.12 as an ECG effect of beta-agonists, not as an interaction. Confirm the QT wording against the fumarate inhaler prescribing information or remove]
• other adrenergic medicines, given by any route.
• atropine. [FLAG-INSERT: this item, xanthine derivatives, steroid medicines, and other adrenergic medicines do not appear in section 7 of the prescribing information for the fumarate dihydrate inhaler. Confirm all four against the fumarate inhaler prescribing information or remove]

Not all possible interactions are listed here. Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.

Budesonide and formoterol drug interactions (more detail)

Store both inhalers at room temperature, between 68°F and 77°F (20°C to 25°C). Keep them out of the reach of children.

Fumarate dihydrate inhaler:

• Store the inhaler with the mouthpiece down.
• Throw the inhaler away when the counter reaches zero, or 3 months after you take it out of its foil pouch, whichever comes first.

Fumarate inhaler:

• Keep the inhaler in a dry place away from heat and sunlight. Do not store it in a humid environment such as a bathroom.
• Keep the inhaler in its unopened foil pouch and only open it when you are ready to use it.
• Order a new inhaler when the pointer on the puff indicator is in the yellow zone.
• Throw the inhaler away when the puff indicator reaches zero in the red zone, or 3 months after you open the foil pouch, whichever comes first.

The contents of both canisters are under pressure. Do not puncture the canister and do not throw it into a fire or an incinerator. Do not use or store either inhaler near heat or an open flame. Temperatures above 120°F (49°C) may cause the canister to burst.

Budesonide and formoterol fumarate dihydrate inhaler (Symbicort)

Active ingredients: micronized budesonide and micronized formoterol fumarate dihydrate

Inactive ingredients: hydrofluoroalkane (HFA 227), povidone K25 USP, and polyethylene glycol 1000 NF

Budesonide and formoterol fumarate inhaler (Symbicort Aerosphere)

Active ingredients: micronized budesonide and micronized formoterol fumarate

Inactive ingredients: hydrofluoroalkane (HFA 134a) and porous particles made up of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) and calcium chloride