BREO is the only ICS/LABA that provides
24-hour efficacy with just one daily inhalation …for better breathing all day and night

24-hour BREO is for adult patients with asthma uncontrolled on an ICS or whose disease severity clearly warrants an ICS/LABA. BREO is NOT indicated for the relief of acute bronchospasm.

*Eligibility restrictions apply.

In patients with asthma uncontrolled on an ICS1

BREO is proven to deliver continuous lung-function improvement for a full 24 hours

BREO 100/25
Serial FEV1 (0-24 hours) at Week 121
 

*Zero=dose administered in the evening.

STUDY DESCRIPTION

DESIGN:

12-week, randomized, double-blind study that evaluated the safety and efficacy of BREO 100/25, BREO 200/25, and fluticasone furoate (FF) 100 mcg (each administered once daily in the evening). Patients who reported symptoms and/or rescue beta2-agonist use during a 4-week run-in period on mid- to high-dose ICS (≥250 mcg fluticasone propionate [FP] twice daily or equivalent) were randomized to treatment.

PATIENTS:

1039 patients with asthma aged 12 years and older (mean age: 46 years). At baseline, patients had a mean percent predicted FEV1 of 62%.

BREO is approved for use in patients ≥18 years of age.

PRIMARY ENDPOINT:

wm FEV1 (0-24 hours) at Week 12.

FEV1=forced expiratory volume in 1 second; ICS=inhaled corticosteroid; LABA=long-acting beta2-adrenergic agonist; LS=least squares.

IN A PLACEBO-CONTROLLED 12-WEEK STUDY2:

wm FEV1:

in a subset of patients, BREO 100/25 (n=108) demonstrated a numerically greater improvement in change from baseline in wm FEV1 (0-24 hours) compared with FF 100 mcg (n=106) of 116 mL (95% CI: –5, 236; P=0.06) and a statistically significant 302-mL improvement (P<0.001) compared with placebo (n=95) at Week 12.

STUDY DESCRIPTION:

12-week, randomized, double-blind, placebo-controlled study of 609 patients aged 12 years and older (mean age: 40 years) with asthma, symptomatic on low- to mid-dose ICS (FP 100 mcg to 250 mcg twice daily or equivalent) during a 4-week run-in period (mean baseline percent predicted FEV1 of 70%) randomized to BREO 100/25, FF 100 mcg, or placebo (each administered once daily in the evening). The co-primary endpoints were weighted mean FEV1 (0-24 hours) (in a subset of patients) and trough FEV1 at Week 12.

BREO is approved for use in patients ≥18 years of age.

References: 1. Bernstein DI, et al. J Asthma. 2015;52(10):1073–1083. 2. Bleecker ER, et al. J Allergy Clin lmmunol Pract. 2014;2(5):553–561.

*Eligibility restrictions apply.

Indication

24-hour BREO is for adult patients with asthma uncontrolled on an ICS or whose disease severity clearly warrants an ICS/LABA.
BREO is NOT indicated for the relief of acute bronchospasm.

IMPORTANT SAFETY INFORMATION

    WARNING: ASTHMA-RELATED DEATH
  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in BREO, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids (ICS) 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.
  • When treating patients with asthma, only prescribe BREO for patients not adequately controlled on a long-term asthma control medication, such as an ICS, or whose disease severity clearly warrants initiation of treatment with both an ICS and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue BREO) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an ICS. Do not use BREO for patients whose asthma is adequately controlled on low- or medium-dose ICS.

    CONTRAINDICATIONS

  • BREO is contraindicated for primary treatment of status asthmaticus or other acute episodes of chronic obstructive pulmonary disease (COPD) or asthma where intensive measures are required.
  • BREO is contraindicated in patients with severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, vilanterol, or any of the excipients.
  • WARNINGS AND PRECAUTIONS

  • BREO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD or asthma.
  • BREO is not a rescue medication and should not be used for the relief of acute bronchospasm or symptoms.
  • BREO should not be used more often or at higher doses than recommended, or with another LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Oropharyngeal candidiasis has occurred in patients treated with BREO. Advise patients to rinse the mouth with water without swallowing after inhalation.
  • Use caution in patients who use corticosteroids as they are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients.
  • Particular care is needed for patients transferred from systemic corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREO.
  • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals. If such changes occur, discontinue BREO slowly.
  • Caution should be exercised when considering the coadministration of BREO with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue BREO immediately and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of BREO. Discontinue BREO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO may need to be discontinued. BREO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Decreases in bone mineral density have been observed with long‐term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.
  • Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with COPD or asthma following the long-term administration of inhaled corticosteroids. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Be alert to hypokalemia and hyperglycemia.
  • Orally inhaled corticosteroids may reduce growth velocity in children and adolescents.
  • ADVERSE REACTIONS

  • In a 12-week trial, adverse reactions (≥2% incidence and more common than placebo) reported in subjects taking BREO 100/25 (and placebo) were: nasopharyngitis, 10% (7%); headache, 5% (4%); oropharyngeal pain, 2% (1%); oral candidiasis, 2% (0%); and dysphonia, 2% (0%). In a separate 12-week trial, adverse reactions (≥2% incidence) reported in subjects taking BREO 200/25 (or BREO 100/25) were: headache, 8% (8%); nasopharyngitis, 7% (6%); influenza, 3% (3%); upper respiratory tract infection, 2% (2%); oropharyngeal pain, 2% (2%); sinusitis, 2% (1%); bronchitis, 2% (<1%); and cough, 1% (2%).
  • Additional adverse reactions (≥2% incidence) reported in subjects taking BREO 200/25 in a 24-week trial included viral respiratory tract infection, pharyngitis, pyrexia, and arthralgia; and with BREO 100/25 or 200/25 in a 12-month trial included pyrexia, back pain, extrasystoles, upper abdominal pain, respiratory tract infection, allergic rhinitis, pharyngitis, rhinitis, arthralgia, supraventricular extrasystoles, ventricular extrasystoles, acute sinusitis, and pneumonia.
  • In a 24- to 76-week trial of subjects with ≥1 asthma exacerbations in the past year, asthma-related hospitalizations occurred in 1% of subjects taking BREO 100/25. No asthma-related deaths or intubations were observed.
  • DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of BREO with long‐term ketoconazole and other known strong CYP3A4 inhibitors. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • BREO 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 they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD or asthma.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • USE IN SPECIFIC POPULATIONS

  • BREO is not indicated for children and adolescents; the safety and efficacy in patients aged ≤17 years have not been established.
  • Use BREO with caution in patients with moderate or severe hepatic impairment. Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment. Monitor for corticosteroid-related side effects.

Please see full Prescribing Information, including Boxed Warning and Medication Guide, for BREO ELLIPTA.

 

774510R0 September 2017