July 30, 2016
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Breo Ellipta

"COPD is a serious lung disease that makes breathing difficult and worsens over time. Symptoms can include wheezing, cough, chest tightness, and shortness of breath. Cigarette smoking is the leading cause of COPD. According to the National Heart, "...

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Breo Ellipta

Side Effects
Interactions

SIDE EFFECTS

LABA, such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Data from a large placebo-controlled US trial that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. [See WARNINGS AND PRECAUTIONS]

Systemic and local corticosteroid use may result in the following:

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 BREO ELLIPTA included 7,700 subjects with COPD in two 6-month lung function trials, two 12-month exacerbation trials, and 6 other trials of shorter duration. A total of 2,034 subjects with COPD received at least 1 dose of BREO 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 BREO ELLIPTA 100/25 in Table 1 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: BREO ELLIPTA 100/25, BREO ELLIPTA 200/25, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate 100 mcg, fluticasone furoate 200 mcg, vilanterol 25 mcg, or placebo.

Table 1: Adverse Reactions with BREO ELLIPTA 100/25 with ≥ 3% Incidence and More Common than Placebo in Subjects with Chronic Obstructive Pulmonary Disease

Adverse Reaction BREO 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
aIncludes oral candidiasis, oropharyngeal candidiasis, candidiasis, and fungal oropharyngitis.

12-Month Trials

Long-term safety data is 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: BREO ELLIPTA 100/25, BREO ELLIPTA 200/25, fluticasone furoate/vilanterol 50 mcg/25 mcg, or vilanterol 25 mcg. In addition to the reactions shown in Table 1, adverse reactions occurring in greater than or equal to 3% of the subjects treated with BREO ELLIPTA 100/25 (n = 806) for 12 months included back pain, pneumonia [see WARNINGS AND PRECAUTIONS], bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, influenza, pharyngitis, and pyrexia.

Clinical Trials Experience In Asthma

BREO 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. BREO ELLIPTA 100/25 was studied in 2,369 subjects and BREO ELLIPTA 200/25 was studied in 956 subjects. While subjects aged 12 to 17 years were included in these trials, BREO ELLIPTA is not approved for use in this age-group [see Use in Specific Populations]. The safety data described below are based on two 12-week efficacy trials, one 24-week efficacy trial, and two long-term trials.

12-Week Trials

Trial 1 was a 12-week trial that evaluated the efficacy of BREO ELLIPTA 100/25 in adolescent and adult 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 BREO ELLIPTA 100/25 is shown in Table 2.

Table 2: Adverse Reactions with BREO ELLIPTA 100/25 with ≥ 2% Incidence and More Common than Placebo in Subjects with Asthma (Trial 1)

Adverse Reaction BREO 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
aIncludes oral candidiasis and oropharyngeal candidiasis.

Trial 2 was a 12-week trial that evaluated the efficacy of BREO ELLIPTA 100/25, BREO ELLIPTA 200/25, and fluticasone furoate 100 mcg in adolescent and adult 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 BREO ELLIPTA 100/25 and BREO ELLIPTA 200/25 is shown in Table 3.

Table 3: Adverse Reactions with BREO ELLIPTA 100/25 and BREO ELLIPTA 200/25 with ≥ 2% Incidence in Subjects with Asthma (Trial 2)

Adverse Reaction BREO ELLIPTA 200/25
(n = 346) %
BREO 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 BREO ELLIPTA 200/25 once daily, fluticasone furoate 200 mcg once daily, and fluticasone propionate 500 mcg twice daily in adolescent and adult 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 2 and 3, adverse reactions occurring in greater than or equal to 2% of subjects treated with BREO ELLIPTA 200/25 included viral respiratory tract infection, pharyngitis, pyrexia, and arthralgia.

12-Month Trial

Long-term safety data is based on a 12-month trial that evaluated the safety of BREO ELLIPTA 100/25 once daily (n = 201), BREO ELLIPTA 200/25 once daily (n = 202), and fluticasone propionate 500 mcg twice daily (n = 100) in adolescent and adult 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 2 and 3, adverse reactions occurring in greater than or equal to 2% of the subjects treated with BREO ELLIPTA 100/25 or BREO ELLIPTA 200/25 for 12 months included pyrexia, back pain, extrasystoles, upper abdominal pain, respiratory tract infection, allergic rhinitis, pharyngitis, rhinitis, arthralgia, supraventricular extrasystoles, ventricular extrasystoles, acute sinusitis, and pneumonia.

Exacerbation Trial

In a 24-to 76-week trial, subjects received BREO 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 one 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, BREO ELLIPTA is not approved for use in this age-group [see Use in Specific Populations]. Asthma-related hospitalizations occurred in 10 subjects (1%) treated with BREO 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 BREO 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 BREO 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 BREO ELLIPTA or a combination of these factors.

Cardiac Disorders

Palpitations, tachycardia.

Immune System Disorders

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria.

Musculoskeletal and Connective Tissue Disorders

Muscle spasms.

Nervous System Disorders

Tremor.

Psychiatric Disorders

Nervousness.

Read the Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Inhibitors Of Cytochrome P450 3A4

Fluticasone furoate and vilanterol, the individual components of BREO 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 BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].

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 BREO 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.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 4/4/2016

Side Effects
Interactions

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