BREO 100/25 for COPD

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 should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta₂-agonist.
• BREO should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BREO should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.
• Oropharyngeal candidiasis has occurred in patients treated with BREO. Advise patients to rinse the mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.
• 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 3255 subjects with 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]), fluticasone furoate (FF)/vilanterol (VI) 50/25 mcg (6% [48 of 820 subjects]), and BREO 200/25 (7% [55 of 811 subjects]) than in subjects receiving VI 25 mcg (3% [27 of 818 subjects]). There was no fatal pneumonia in subjects receiving VI or FF/VI 50/25 mcg. There was fatal pneumonia in 1 subject receiving BREO 100/25 and in 7 subjects receiving BREO 200/25 (<1% for each treatment group).
• Physicians should remain vigilant for the possible development of pneumonia in patients with COPD, as the clinical features of such infections overlap with the symptoms of COPD exacerbations.
• Patients who use corticosteroids 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. Use caution in patients with the above because of the potential for worsening of these infections.
• Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. 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 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 (BMD) 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. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended 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. Therefore, 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.

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.

DRUG INTERACTIONS

• 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.
• 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 the effect of adrenergic agonists, such as vilanterol, on the cardiovascular system may be potentiated by these agents.
• 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 electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing 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.

BREO 100/25 | INCRUSE

INCRUSE

CONTRAINDICATIONS

• The use of INCRUSE is contraindicated in patients with severe hypersensitivity to milk proteins or who have 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 should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta₂-agonist.
• If paradoxical bronchospasm occurs, discontinue INCRUSE and institute alternative therapy.
• 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) reported in one 12-week and one 24-week clinical trial 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%). Other adverse reactions with INCRUSE observed with an incidence <1% but more common than placebo included atrial fibrillation.
• In addition to the two placebo-controlled clinical trials with INCRUSE, a 12-month trial evaluated the safety of umeclidinium 125 mcg as monotherapy in subjects with COPD. Adverse reactions (incidence ≥1% and exceeded that in placebo) in subjects receiving umeclidinium 125 mcg 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 four 12-week 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 full Prescribing Information, including Boxed Warning and Medication Guide, for BREO.

Please see full Prescribing Information and Patient Information Leaflet for INCRUSE.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

BREO ELLIPTA was developed in collaboration with Theravance.

©2016 GSK group of companies. All rights reserved. Produced in USA. 774426R0 October 2016