Does Symbicort (formoterol and budesonide) cause side effects?

Symbicort (formoterol and budesonide) is a combination of a long-acting beta-2 adrenergic agonist (LABA) bronchodilator and an anti-inflammatory corticosteroid used to treat asthma and chronic obstructive pulmonary disease (COPD). 

In patients with asthma or COPD the smaller airways (bronchioles) through which air moves in and out of the lungs can be narrowed by accumulation of mucus, spasm of the muscles that surround these airways, or swelling of the lining of the airways due to inflammation. Airway narrowing leads to symptoms of shortness of breath, wheezing, cough, and congestion

Medications used in treating asthma or COPD include those that open airways, called bronchodilators, and those that reduce inflammation. Beta-2 agonists are medications that attach to beta-2 receptors on the smooth muscle cells that surround the airways, causing the muscle cells to relax and open the airways. 

Budesonide is a synthetic (man-made) corticosteroid of the glucocorticoid family which is related to the natural hormone, cortisol or hydrocortisone, produced by the adrenal glands. Glucocorticoid steroids have potent anti-inflammatory actions.

In asthmatic patients and people with COPD, the suppression of inflammation within the airways reduces the swelling caused by inflammation that narrows the airways. At the same time, production of mucus is reduced. 

When used in lower doses, very little inhaled budesonide is absorbed into the body and side effects are infrequent. When higher doses are used, budesonide is absorbed and may cause side effects elsewhere in the body.

Common side effects of Symbicort include

Serious side effects of Symbicort include

  • suppression of the adrenal glands,
  • growth suppression,
  • weakened immune system,
  • increased risk of glaucoma and cataracts, and
  • allergic reactions (swelling of face, throat and tongue, as well as rash, hives, and breathing problems).

Drug interactions of Symbicort include ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nelfinavir, and telithromycin, because these drugs may increase levels of budesonide in the body by reducing the breakdown of budesonide by liver enzymes. This may increase side effects of Symbicort.

  • Monoamine oxidase inhibitors (for example, tranylcypromine) and tricyclic antidepressants (for example, amitriptyline) may increase the effect of formoterol on the heart and blood pressure.
  • Since Symbicort contains formoterol, it should not be used with or within two weeks of discontinuing monoamine oxidase inhibitors or tricyclic antidepressants.
  • Beta-blockers block the therapeutic effects of beta 2-agonists, such as formoterol, a component of Symbicort, and may produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not be treated with beta-blockers. 

Use of Symbicort during pregnancy has not been adequately evaluated. 

It is unknown if components of Symbicort are secreted in breast milk. Other medications in this class are secreted into breast milk. 

It is unknown if the small amounts of Symbicort components that may appear in breast milk have an effect on the infant. Consult your doctor before breastfeeding.

What are the important side effects of Symbicort (formoterol and budesonide)?

The most common side effects associated with Symbicort are:

Higher doses of budesonide may cause suppression of the body's ability to make its own natural glucocorticoid in the adrenal gland.

People with suppression of their adrenal glands (which can be diagnosed by a doctor) would need increased amounts of glucocorticoids, probably by the oral or intravenous route, during periods of high physical stress or acute illness when glucocorticoids are particularly important.

Inhaled steroids may cause

  • growth suppression,
  • weaken the immune system, and
  • may increase the risk of glaucoma, and cataracts.

Allergic reactions, including swelling of face, throat and tongue, as well as rash, hives, and breathing problems may occur.

Symbicort (formoterol and budesonide) side effects list for healthcare professionals

LABA use may result in the following:

Systemic and inhaled corticosteroid use may result in the following:

  • Candida albicans infection
  • Pneumonia or lower respiratory tract infections in patients with COPD
  • Immunosuppression
  • Hypercorticism and adrenal suppression
  • Growth effects in pediatric patients
  • Glaucoma and cataracts

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience In Asthma

Adult And Adolescent Patients 12 Years Of Age And Older
  • The overall safety data in adults and adolescents are based upon 10 active-and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated with Symbicort 80/4.5 or 160/4.5 taken 2 inhalations once or twice daily for 12 to 52 weeks.
  • In these trials, the patients on Symbicort had a mean age of 38 years and were predominantly Caucasian (82%).
  • The incidence of common adverse events in Table 2 below is based upon pooled data from three 12-week, double-blind, placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years and older were treated with 2 inhalations of Symbicort 80/4.5 or Symbicort 160/4.5 twice daily.
  • The Symbicort group was composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV1 at baseline of 76 and 68 for the 80/4.5 mcg and 160/4.5 mcg treatment groups, respectively.
  • Control arms for comparison included 2 inhalations of budesonide HFA metered dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI) 4.5 mcg, or placebo (MDI and DPI) twice daily.
  • Table 2 includes all adverse events that occurred at an incidence of >3% in any one Symbicort group and more commonly than in the placebo group with twice-daily dosing.
  • In considering these data, the increased average duration of patient exposure for Symbicort patients should be taken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 2 : Adverse reactions occurring at an incidence of ≥ 3% and more commonly than placebo in the Symbicort groups: pooled data from three 12-week, double-blind, placebo-controlled clinical asthma trials in patients 12 years and older

Treatment1 Symbicort Budesonide Formoterol Placebo
N = 400
%
Adverse Event 80/4.5
N = 277
%
160/4.5
N = 124
%
80 mcg
N = 121
%
160 mcg
N = 109
%
4.5 mcg
N = 237
%
Nasopharyngitis 10.5 9.7 14.0 11.0 10.1 9.0
Headache 6.5 11.3 11.6 12.8 8.9 6.5
Upper respiratory tract infection 7.6 10.5 12 8.3 9.2 7.6 7.8
Pharyngolaryngeal pain 6.1 8.9 5.0 7.3 3.0 4.8
Sinusitis 5.8 4.8 5.8 2.8 6.3 4.8
Influenza 3.2 2.4 6.6 0.9 3.0 1.3
Back pain 3.2 1.6 2.5 5.5 2.1 0.8
Nasal congestion 2.5 3.2 2.5 3.7 1.3 1.0
Stomach discomfort 1.1 6.5 2.5 4.6 1.3 1.8
Vomiting 1.4 3.2 0.8 2.8 1.7 1.0
Oral Candidiasis 1.4 3.2 0 0 0 0.8
Average Duration of Exposure (days) 77.7 73.8 77.0 71.4 62.4 55.9
1. All treatments were administered as 2 inhalations twice daily.

Long-Term Safety -Asthma Clinical Trials In Patients 12 Years And Older
  • Long-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year at doses up to 1280/36 mcg/day (640/18 mcg twice daily), revealed neither clinically important changes in the incidence nor new types of adverse events emerging after longer periods of treatment.
  • Similarly, no significant or unexpected patterns of abnormalities were observed for up to 1 year in safety measures including chemistry, hematology, ECG, Holter monitor, and HPA-axis assessments.
Pediatric Patients 6 To Less Than 12 Years Of Age
  • The safety data for pediatric patients aged 6 to less than 12 years is based on 1 trial of 12 weeks treatment duration. Patients (79 female and 105 male) receiving inhaled corticosteroid at trial entry were randomized to Symbicort 80/4.5 (n=92) or budesonide pMDI 80 mcg (n=92), 2 inhalations twice daily.
  • The overall safety profile of these patients was similar to that observed in patients 12 years of age and older who received Symbicort 80/4.5 twice daily in studies of similar design.
  • Common adverse reactions that occurred in patients treated with Symbicort 80/4.5 with a frequency of ≥3% and more frequently than patients treated only with budesonide pMDI 80 mcg included

Clinical Trials Experience In Chronic Obstructive Pulmonary Disease

  • The safety data described below reflect exposure to Symbicort 160/4.5 in 1783 patients.
  • Symbicort 160/4.5 was studied in two placebo-controlled lung function studies (6 and 12 months in duration), and two active-controlled exacerbation studies (6 and 12 months in duration) in patients with COPD.
  • The incidence of common adverse events in Table 3 below is based upon pooled data from two double-blind, placebo-controlled lung function clinical studies (6 and 12 months in duration) in which 771 adult COPD patients (496 males and 275 females) 40 years of age and older were treated with Symbicort 160/4.5, two inhalations twice daily.
  • Of these patients 651 were treated for 6 months and 366 were treated for 12 months.
  • The Symbicort group was composed of mostly Caucasian (93%) patients with a mean age of 63 years, and a mean percent predicted FEV1 at baseline of 33%.
  • Control arms for comparison included 2 inhalations of budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg or placebo (MDI and DPI) twice daily.
  • Table 3 includes all adverse events that occurred at an incidence of ≥3% in the Symbicort group and more commonly than in the placebo group.
  • In considering these data, the increased average duration of patient exposure to Symbicort should be taken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 3 : Adverse reactions occurring at an incidence of ≥ 3% and more commonly than placebo in the Symbicort group: pooled data from two double-blind, placebo-controlled clinical COPD trials

Treatment1 Symbicort Budesonide Formoterol Placebo
N = 781
%
Adverse Event 160/4.5
N = 771
%
160 mcg
N = 275
%
4.5 mcg
N = 779
%
Nasopharyngitis 7.3 3.3 5.8 4.9
Oral candidiasis 6.0 4.4 1.2 1.8
Bronchitis 5.4 4.7 4.5 3.5
Sinusitis 3.5 1.5 3.1 1.8
Upper respiratory tract infection viral 3.5 1.8 3.6 2.7
Average Duration of Exposure (days) 255.2 157.1 240.3 223.7
1. All treatments were administered as 2 inhalations twice daily.

  • Lung infections other than pneumonia (mostly bronchitis) occurred in a greater percentage of subjects treated with Symbicort 160/4.5 compared with placebo (7.9% vs. 5.1%, respectively).
  • There were no clinically important or unexpected patterns of abnormalities observed for up to 1 year in chemistry, hematology, ECG, ECG (Holter) monitoring, HPA-axis, bone mineral density and ophthalmology assessments.
  • The safety findings from the two double-blind, active-controlled exacerbations studies (6 and 12 months in duration) in which 1012 adult COPD patients (616 males and 396 females) 40 years of age and older were treated with Symbicort 160/4.5, two inhalations twice daily were consistent with the lung function studies.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Symbicort. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Some of these adverse reactions may also have been observed in clinical studies with Symbicort.

What drugs interact with Symbicort (formoterol and budesonide)?

In clinical studies, concurrent administration of Symbicort and other drugs, such as short-acting beta2agonists, intranasal corticosteroids, and antihistamines/decongestants has not resulted in an increased frequency of adverse reactions. No formal drug interaction studies have been performed with Symbicort.

Inhibitors Of Cytochrome P4503A4

  • The main route of metabolism of corticosteroids, including budesonide, a component of Symbicort, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4).
  • After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased.
  • Concomitant administration of CYP3A4 may inhibit the metabolism of, and increase the systemic exposure to, budesonide.
  • Caution should be exercised when considering the coadministration of Symbicort with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin).

Monoamine Oxidase Inhibitors And Tricyclic Antidepressants

  • Symbicort should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of formoterol, a component of Symbicort, on the vascular system may be potentiated by these agents.
  • In clinical trials with Symbicort, a limited number of COPD and asthma patients received tricyclic antidepressants, and, therefore, no clinically meaningful conclusions on adverse events can be made.

Beta-Adrenergic Receptor Blocking Agents

  • Beta-blockers (including eye drops) may not only block the pulmonary effect of beta-agonists, such as formoterol, a component of Symbicort, but may produce severe bronchospasm in patients with asthma.
  • Therefore, patients with asthma should not normally be treated with beta-blockers.
  • However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma.
  • In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

Diuretics

  • The ECG changes and/or hypokalemia that may result from the administration of non-potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
  • Although the clinical significance of these effects is not known, caution is advised in the coadministration of Symbicort with non-potassium-sparing diuretics.

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Medically Reviewed on 1/27/2021
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.