Does Side Effects of Breo Ellipta (fluticasone and vilanterol) cause side effects?

Breo Ellipta (fluticasone and vilanterol) is a combination of a glucocorticoid steroid and a bronchodilator of the beta-2 agonist type used to treat chronic obstructive pulmonary disease (COPD). 

Glucocorticoid steroids have potent anti- inflammatory actions. When used as an inhaler, fluticasone travels to the airways in the lung. In COPD patients, the suppression of inflammation within the airways reduces the inflammatory-stimulated spasm of the smooth muscle cells surrounding the airways that narrows the airways and makes getting air into and out of the lungs more difficult. 

When used in lower doses, very little fluticasone is absorbed into the body. When higher doses are used, fluticasone is absorbed and may cause side effects elsewhere in the body. Beta-2 agonists such as Vilanterol stimulate beta-2 receptors on the smooth muscle cells that surround the airways, causing these muscle cells to relax and thereby opening the airways. Breo Ellipta opens the airways and increases air supply to the lungs of COPD patients.

Common side effects of Breo Ellipta include

Serious side effects of Breo Ellipta include

Drug interactions of Breo Ellipta include ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nelfinavir, and telithromycin because they may increase levels of Breo Ellipta in the body by reducing the breakdown of fluticasone and vilanterol by liver enzymes. This may increase side effects of Breo Ellipta.

Beta blockers (for example, atenolol) can block the effects of vilanterol and cause bronchospasm in patients with COPD.

Combining or using Breo Ellipta within two weeks of stopping monoamine oxidase inhibitors (MAOIs, for example, phenelzine), tricyclic antidepressants (for example, amitriptyline), or other drugs that affect heart rate and rhythm, may increase risk of heart-related side effects.

There are insufficient data on the use of Breo Ellipta, fluticasone furoate, or vilanterol in pregnant women.

It is unknown if either of the drugs in Breo Ellipta are secreted in breast milk. Other medications in the same class as fluticasone or vilanterol are secreted into breast milk. Consult your doctor before breastfeeding

What are the important side effects of Breo Ellipta (fluticasone and vilanterol)?

The most common side effects of Brio Ellipta are:

Brio Ellipta also may cause bronchospasms (wheezing). Bronchospasm should be treated with a rescue inhaler.

High doses of inhaled fluticasone may decrease formation and increase breakdown of bone thereby weakening bones and promoting fractures. Higher doses of fluticasone also may cause suppression of the body's ability to make its own natural glucocorticoid in the adrenal gland.

People with suppression of their own 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 when glucocorticoids are particularly important.

Inhaled steroids may cause growth suppression, weaken the immune system, and may increase the risk of glaucoma, increased eye pressure, and cataracts.

Allergic reactions, including swelling of face, throat and tongue, rash, hives, and breathing problems may occur. Use of long acting drugs like vilanterol may increase the risk of asthma-related death. Brio Ellipta should not be used for treatment of asthma.

Other important side effects of Vilanterol include:

Breo Ellipta (fluticasone and vilanterol) side effects list for healthcare professionals

Use of LABA may result in the following:

  • Serious asthma-related events – hospitalizations, intubations, death
  • Cardiovascular effects

Systemic and local corticosteroid use may result in the following:

  • Candida albicans infection
  • Increased risk of pneumonia in COPD
  • Immunosuppression
  • Hypercorticism and adrenal suppression
  • Reduction in bone mineral density

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

Clinical Trials Experience In Chronic Obstructive Pulmonary Disease

The clinical program for Brio Ellipta included more than 24,000 subjects with COPD in two 6-month lung function trials, two 12-month exacerbation trials, 1 mortality trial, and 6 other trials of shorter duration.

  • A total of 6,174 subjects with COPD received at least 1 dose of Brio Ellipta 100/25, and 1,087 subjects received a higher strength of fluticasone furoate/vilanterol. The safety data described below are based on the confirmatory 6- and 12-month trials.
  • Adverse reactions observed in the other trials were similar to those observed in the confirmatory trials.
6-Month Trials

The incidence of adverse reactions associated with Brio Ellipta 100/25 in Table 2 is based on 2 placebo-controlled, 6-month clinical trials (Trials 1 and 2; n = 1,224 and n = 1,030, respectively).

  • Of the 2,254 subjects, 70% were male and 84% were white.
  • They had a mean age of 62 years and an average smoking history of 44 pack years, with 54% identified as current smokers.
  • At screening, the mean postbronchodilator percent predicted FEV1 was 48% (range: 14% to 87%), the mean postbronchodilator FEV1/forced vital capacity (FVC) ratio was
    • 47% (range: 17% to 88%), and
    • the mean percent reversibility was 14% (range: -41% to 152%).
  • Subjects received 1 inhalation once daily of the following:
    • Brio Ellipta 100/25,
    • Brio Ellipta 200/25,
    • fluticasone furoate/vilanterol 50 mcg/25 mcg,
    • fluticasone furoate 100 mcg,
    • fluticasone furoate 200 mcg,
    • vilanterol 25 mcg, or
    • placebo.

Table 2. Adverse Reactions with Brio Ellipta 100/25 with ≥3% Incidence and More Common than Placebo in Subjects with Chronic Obstructive Pulmonary Disease

Adverse Reaction Brio Ellipta
100/25
(n = 410)
%
Vilanterol
25 mcg
(n = 408)
%
Fluticasone Furoate
100 mcg
(n = 410)
%
Placebo
(n = 412)
%
Infections and infestations
  Nasopharyngitis 9 10 8 8
  Upper respiratory tract infection 7 5 4 3
  Oropharyngeal candidiasisa 5 2 3 2
Nervous system disorders
  Headache 7 9 7 5
a Includes oral candidiasis, oropharyngeal candidiasis, candidiasis, and fungal oropharyngitis.

12-Month Trials

Long-term safety data are based on two 12-month trials (Trials 3 and 4; n = 1,633 and n = 1,622, respectively).

  • Trials 3 and 4 included 3,255 subjects, of which 57% were male and 85% were white.
  • They had a mean age of 64 years and an average smoking history of 46 pack years, with 44% identified as current smokers.
  • At screening, the mean postbronchodilator percent predicted FEV1 was 45% (range: 12% to 91%), and the mean postbronchodilator FEV1/FVC ratio was 46% (range: 17% to 81%), indicating that the subject population had moderate to very severely impaired airflow obstruction.
  • Subjects received 1 inhalation once daily of the following:
    • Brio Ellipta 100/25,
    • Brio Ellipta 200/25,
    • fluticasone furoate/vilanterol 50 mcg/25 mcg, or
    • vilanterol 25 mcg.
  • In addition to the reactions shown in Table 2, adverse reactions occurring in =3% of the subjects treated with Brio Ellipta 100/25 (n = 806) for 12 months included
Mortality Trial

Safety data are available from a mortality trial in subjects with moderate COPD (moderate airflow limitation [≥50% and ≤70% predicted FEV1]) who either had a history of, or were at risk of, cardiovascular disease and were treated for up to 4 years (median treatment duration of 1.5 years).

  • The trial included 16,568 subjects, 4,140 of whom received Brio Ellipta 100/25.
  • In addition to the events in COPD trials shown in Table 2, adverse reactions occurring in ≥3% of the subjects treated with Brio Ellipta 100/25 and more common than placebo included pneumonia, back pain, hypertension, and influenza.

Clinical Trials Experience In Asthma

Brio Ellipta for the treatment of asthma was studied in 18 double-blind, parallel-group, controlled trials (11 with placebo) of 4 to 76 weeks' duration, which enrolled 9,969 subjects with asthma.

  • Brio Ellipta 100/25 was studied in 2,369 subjects and Brio Ellipta 200/25 was studied in 956 subjects.
  • While subjects aged 12 to 17 years were included in these trials, Brio Ellipta is not approved for use in this age group.
  • The safety data described below are based on two 12-week efficacy trials, one 24-week efficacy trial, and 2 long-term trials.
12-Week Trials

Trial 1 was a 12-week trial that evaluated the efficacy of Brio Ellipta 100/25 in adult and adolescent subjects with asthma compared with fluticasone furoate 100 mcg and placebo.

  • Of the 609 subjects,
    • 58% were female and
    • 84% were white;
    • the mean age was 40 years.
  • The incidence of adverse reactions associated with Brio Ellipta 100/25 is shown in Table 3.

Table 3. Adverse Reactions with Brio Ellipta 100/25 with ≥2% Incidence and More Common than Placebo in Subjects with Asthma (Trial 1)

Adverse Reaction Brio Ellipta
100/25
(n = 201)
%
Fluticasone Furoate
100 mcg
(n = 205)
%
Placebo
(n = 203)
%
Infections and infestations
  Nasopharyngitis 10 7 7
  Oral candidiasisa 2 2 0
Nervous system disorders
  Headache 5 4 4
Respiratory, thoracic, and mediastinal disorders
  Oropharyngeal pain 2 2 1
  Dysphonia 2 1 0
a Includes oral candidiasis and oropharyngeal candidiasis.

Trial 2 was a 12-week trial that evaluated the efficacy of Brio Ellipta 100/25, Brio Ellipta 200/25, and fluticasone furoate 100 mcg in adult and adolescent subjects with asthma. This trial did not have a placebo arm.

  • Of the 1,039 subjects,
    • 60% were female and
    • 88% were white;
    • the mean age was 46 years.
  • The incidence of adverse reactions associated with Brio Ellipta 100/25 and Brio Ellipta 200/25 is shown in Table 4.

Table 4. Adverse Reactions with Brio Ellipta 100/25 and Brio Ellipta 200/25 with ≥2% Incidence in Subjects with Asthma (Trial 2)

Adverse Reaction Brio Ellipta
200/25
(n = 346)
%
Brio Ellipta
100/25
(n = 346)
%
Fluticasone Furoate
100 mcg
(n = 347)
%
Nervous system disorders
  Headache 8 8 9
Infections and infestations
  Nasopharyngitis 7 6 7
  Influenza 3 3 1
  Upper respiratory tract infection 2 2 3
  Sinusitis 2 1 <1
  Bronchitis 2 <1 2
Respiratory, thoracic and mediastinal disorders
  Oropharyngeal pain 2 2 1
  Cough 1 2 1

24-Week Trial

Trial 3 was a 24-week trial that evaluated the efficacy of Brio Ellipta 200/25 once daily, fluticasone furoate 200 mcg once daily, and fluticasone propionate 500 mcg twice daily in adult and adolescent subjects with asthma.

  • Of the 586 subjects,
    • 59% were female and
    • 84% were white;
    • the mean age was 46 years.
  • This trial did not have a placebo arm.
  • In addition to the reactions shown in Tables 3 and 4, adverse reactions occurring in ≥2% of subjects treated with Brio Ellipta 200/25 included
    • viral respiratory tract infection,
    • pharyngitis,
    • pyrexia, and
    • arthralgia.
12-Month Trial

Long-term safety data are based on a 12-month trial that evaluated the safety of Brio Ellipta 100/25 once daily (n = 201), Brio Ellipta 200/25 once daily (n = 202), and fluticasone propionate 500 mcg twice daily (n = 100) in adult and adolescent subjects with asthma (Trial 4).

  • Overall, 63% were female and 67% were white.
  • The mean age was 39 years;
  • adolescents (aged 12 to 17 years) made up 16% of the population.
  • In addition to the reactions shown in Tables 3 and 4, adverse reactions occurring in ≥2% of the subjects treated with Brio Ellipta 100/25 or Brio Ellipta 200/25 for 12 months included
Exacerbation Trial

In a 24- to 76-week trial, subjects received Brio Ellipta 100/25 (n = 1,009) or fluticasone furoate 100 mcg (n = 1,010) (Trial 5).

  • Subjects participating in this trial had a history of 1 or more asthma exacerbations that required treatment with oral/systemic corticosteroids or emergency department visit or in-patient hospitalization for the treatment of asthma in the year prior to trial entry.
  • Overall,
    • 67% were female and
    • 73% were white;
    • the mean age was 42 years (adolescents aged 12 to 17 years made up 14% of the population).
  • While subjects aged 12 to 17 years were included in this trial, Brio Ellipta is not approved for use in this age group.
  • Asthma-related hospitalizations occurred in 10 subjects (1%) treated with Brio Ellipta 100/25 compared with 7 subjects (0.7%) treated with fluticasone furoate 100 mcg.
  • Among subjects aged 12 to 17 years, asthma-related hospitalizations occurred in 4 subjects (2.6%) treated with Brio Ellipta 100/25 (n = 151) compared with 0 subjects treated with fluticasone furoate 100 mcg (n = 130).
  • There were no asthma-related deaths or asthma-related intubations observed in this trial.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of Brio Ellipta. 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.

These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to Brio Ellipta or a combination of these factors.

Cardiac Disorders

Immune System Disorders

Metabolism and Nutrition Disorders

Musculoskeletal and Connective Tissue Disorders

Nervous System Disorders

Psychiatric Disorders

  • Nervousness.

Respiratory, Thoracic, and Mediastinal Disorders

  • Paradoxical bronchospasm.

What drugs interact with Breo Ellipta (fluticasone and vilanterol)?

Inhibitors Of Cytochrome P450 3A4

  • Fluticasone furoate and vilanterol, the individual components of Brio Ellipta, are both substrates of CYP3A4.
  • Concomitant administration of the strong CYP3A4 inhibitor ketoconazole increases the systemic exposure to fluticasone furoate and vilanterol.
  • Caution should be exercised when considering the coadministration of Brio Ellipta with ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole).

Monoamine Oxidase Inhibitors And Tricyclic Antidepressants

  • Vilanterol, like other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents.
  • Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias.

Beta-Adrenergic Receptor Blocking Agents

  • Beta-blockers not only block the pulmonary effect of beta-agonists, such as vilanterol, a component of Brio Ellipta, but may also produce severe bronchospasm in patients with COPD or asthma.
  • Therefore, patients with COPD or 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 for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.

Non-Potassium-Sparing Diuretics

  • The electrocardiographic 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 beta-agonists with non-potassium-sparing diuretics.

Summary

Breo Ellipta (fluticasone and vilanterol) is a combination of a glucocorticoid steroid and a bronchodilator of the beta-2 agonist type used to treat chronic obstructive pulmonary disease (COPD). Common side effects of Breo Ellipta include headache, upper respiratory tract infections, cold symptoms, oral candidiasis or thrush, and bronchospasms (wheezing). There are insufficient data on the use of Breo Ellipta, fluticasone furoate, or vilanterol in pregnant women. It is unknown if either of the drugs in Breo Ellipta are secreted in breast milk.

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Medically Reviewed on 11/11/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.