INDICATIONS FOR BREO 100/25 FOR COPD AND INCRUSE

BREO 100/25 is for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), and for reducing COPD exacerbations in patients with a history of exacerbations. BREO 100/25 is the only strength indicated for COPD. BREO is NOT indicated for the relief of acute bronchospasm.

INCRUSE is for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).

INDICATIONS FOR BREO 100/25 FOR COPD

BREO 100/25 is for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), and for reducing COPD exacerbations in patients with a history of exacerbations. BREO 100/25 is the only strength indicated for COPD. BREO is NOT indicated for the relief of acute bronchospasm.

INDICATION FOR INCRUSE

INCRUSE is for maintenance treatment of airflow obstruction in patients with COPD.

IMPORTANT SAFETY INFORMATION FOR BREO 100/25 FOR COPD AND INCRUSE

BREO 100/25 for COPD

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.

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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.

INCRUSE

CONTRAINDICATIONS
  • INCRUSE is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium or any of the excipients.
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WARNINGS AND PRECAUTIONS
  • INCRUSE should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.

BREO 100/25 for COPD

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.

CONTRAINDICATIONS
  • BREO is contraindicated for primary treatment of status asthmaticus or other acute episodes of 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 (eg, 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.
  • An increase in the incidence of pneumonia has been observed in subjects with COPD receiving BREO. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal.
  • In replicate 12-month studies of subjects with moderate to severe COPD who had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving BREO 100/25 (6% [51 of 806 subjects]) and BREO 200/25 (7% [55 of 811 subjects]) than in subjects receiving vilanterol 25 mcg (3% [27 of 818 subjects]). There was fatal pneumonia in 1 subject receiving BREO 100/25 and in 7 subjects receiving BREO 200/25 (<1% for each treatment group).
  • In a mortality trial in subjects with moderate COPD and cardiovascular disease, the annualized incidence rate of pneumonia was 3.4 per 100 patient-years for BREO 100/25 vs 3.2 for placebo.
  • Physicians should remain vigilant for the possible development of pneumonia in patients with COPD, as signs and symptoms of pneumonia and COPD exacerbations overlap.
  • 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 (eg, 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.
  • In a mortality trial in subjects with moderate COPD and cardiovascular disease, the annualized incidence rate of cardiovascular adverse events was 2.5 per 100 patient-years for BREO 100/25 vs 2.7 for placebo.
  • 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 (eg, anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care prior to initiating BREO and periodically thereafter.
  • 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, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Be alert to hypokalemia and hyperglycemia.
ADVERSE REACTIONS
  • In subjects with COPD, the most common adverse reactions (≥3% and more common than placebo) reported in two 6-month clinical trials with BREO 100/25 (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).
  • In addition to the events reported in the 6-month studies, adverse reactions occurring in ≥3% of the subjects treated with BREO 100/25 in two 1-year COPD studies included back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, influenza, pharyngitis, and pyrexia.
  • In addition to the events reported in the 6-month studies, in a mortality trial (median treatment duration of 1.5 years) in subjects with moderate COPD and cardiovascular disease, adverse reactions occurring in ≥3% of the subjects treated with BREO 100/25 and more common than placebo included pneumonia, back pain, hypertension, and influenza.
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
  • 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.

BREO ELLIPTA was developed in collaboration with

INCRUSE

CONTRAINDICATIONS
  • INCRUSE is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium or any of the excipients.
WARNINGS AND PRECAUTIONS
  • INCRUSE should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • INCRUSE is not a rescue medication and does not replace fast-acting inhalers to treat acute symptoms.
  • If paradoxical bronchospasm occurs, discontinue INCRUSE immediately and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, pruritus, rash, and urticaria may occur after administration of INCRUSE. Discontinue INCRUSE if such reactions occur.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
ADVERSE REACTIONS
  • The most common adverse reactions ≥1% and more common than placebo with INCRUSE as monotherapy (and placebo) were: nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); pharyngitis, 1% (<1%); viral upper respiratory tract infection, 1% (<1%); cough, 3% (2%); arthralgia, 2% (1%); myalgia, 1% (<1%); upper abdominal pain, 1% (<1%); toothache, 1% (<1%); contusion, 1% (<1%); tachycardia, 1% (<1%).
  • The adverse reactions in a long-term safety trial reported for umeclidinium 125 mcg as monotherapy with incidence ≥1% and exceeding that in placebo were: nasopharyngitis, upper respiratory tract infection, urinary tract infection, pharyngitis, pneumonia, lower respiratory tract infection, rhinitis, supraventricular tachycardia, supraventricular extrasystoles, sinus tachycardia, idioventricular rhythm, headache, dizziness, sinus headache, cough, back pain, arthralgia, pain in extremity, neck pain, myalgia, nausea, dyspepsia, diarrhea, rash, depression, and vertigo.
  • In addition to the adverse reactions reported in the umeclidinium monotherapy trials, adverse reactions reported in trials with INCRUSE in combination with an inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA), at an incidence of ≥1% and exceeding ICS/LABA alone, were oropharyngeal pain and dysgeusia.
DRUG INTERACTIONS
  • Avoid coadministration of INCRUSE with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

Please see complete Prescribing Information, including Patient Information Leaflet, for INCRUSE.

822929R0 October 2017