HIGHLIGHTS OF PRESCRIBING INFORMATION • Risk of impaired adrenal function when transferring from systemic These highlights do not include all the information needed to use BREO corticosteroids. Taper patients slowly from systemic corticosteroids if ELLIPTA safely and effectively. See full prescribing information for transferring to BREO ELLIPTA. (5.7) BREO ELLIPTA. • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such BREO ELLIPTA (fluticasone furoate and vilanterol inhalation powder), changes occur, discontinue BREO ELLIPTA slowly. (5.8) for oral inhalation use • If paradoxical bronchospasm occurs, discontinue BREO ELLIPTA and Initial U.S. Approval: 2013 institute alternative therapy. (5.10) • --------------------------- RECENT MAJOR CHANGES --------------------------- Use with caution in patients with cardiovascular disorders because of Warnings and Precautions, Glaucoma and Cataracts (5.14) 1/2019 beta-adrenergic stimulation. (5.12) Warnings and Precautions, Hyperglycemia and Hypokalemia (5.16) 1/2019 • Assess for decrease in bone mineral density initially and periodically thereafter. (5.13) --------------------------- INDICATIONS AND USAGE ---------------------------- • Glaucoma and cataracts may occur with long-term use of ICS. Consider BREO ELLIPTA is a combination of fluticasone furoate, an inhaled referral to an ophthalmologist in patients who develop ocular symptoms corticosteroid (ICS), and vilanterol, a long-acting beta2-adrenergic agonist or use BREO ELLIPTA long term. (5.14) (LABA), indicated for: • Use with caution in patients with convulsive disorders, thyrotoxicosis, • Long-term, once-daily, maintenance treatment of airflow obstruction and diabetes mellitus, and ketoacidosis. (5.15) reducing exacerbations in patients with chronic obstructive pulmonary • Increased blood glucose levels have been reported. Also, be alert to disease (COPD). (1.1) hypokalemia. (5.16) • Once-daily treatment of asthma in patients aged 18 years and older. (1.2) ------------------------------ ADVERSE REACTIONS ------------------------------ Important limitation of use: Not indicated for relief of acute bronchospasm. • COPD: Most common adverse reactions (incidence ≥3%) are (1.1, 1.2, 5.2) nasopharyngitis, upper respiratory tract infection, headache, oral candidiasis, back pain, pneumonia, bronchitis, sinusitis, cough, ----------------------- DOSAGE AND ADMINISTRATION ----------------------- oropharyngeal pain, arthralgia, hypertension, influenza, pharyngitis, and • For oral inhalation only. (2) pyrexia. (6.1) • Maintenance treatment of COPD: 1 inhalation of BREO ELLIPTA 100/25 • Asthma: Most common adverse reactions (incidence ≥2%) are once daily. (2.1) nasopharyngitis, oral candidiasis, headache, influenza, upper respiratory • Asthma: 1 inhalation of BREO ELLIPTA 100/25 or BREO ELLIPTA tract infection, bronchitis, sinusitis, oropharyngeal pain, dysphonia, and 200/25 once daily. (2.2) cough. (6.2) --------------------- DOSAGE FORMS AND STRENGTHS ---------------------- To report SUSPECTED ADVERSE REACTIONS, contact Inhalation powder: Inhaler containing 2 foil blister strips of powder GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or formulation for oral inhalation. One strip contains fluticasone furoate 100 or www.fda.gov/medwatch. 200 mcg per blister and the other contains vilanterol 25 mcg per blister. (3) ------------------------------ DRUG INTERACTIONS------------------------------- ------------------------------ CONTRAINDICATIONS ------------------------------ • Strong cytochrome P450 3A4 inhibitors (e.g., ketoconazole): Use with • Primary treatment of status asthmaticus or acute episodes of COPD or caution. May cause systemic corticosteroid and cardiovascular effects. asthma requiring intensive measures. (4) (7.1) • Severe hypersensitivity to milk proteins or any ingredients. (4) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with ----------------------- WARNINGS AND PRECAUTIONS ------------------------ extreme caution. May potentiate effect of vilanterol on vascular system. • LABA monotherapy increases the risk of serious asthma-related events. (7.2) (5.1) • Beta-blockers: Use with caution. May block bronchodilatory effects of • Do not initiate in acutely deteriorating COPD or asthma. Do not use to beta-agonists and produce severe bronchospasm. (7.3) treat acute symptoms. (5.2) • Diuretics: Use with caution. Electrocardiographic changes and/or • Do not use in combination with an additional medicine containing a hypokalemia associated with non–potassium-sparing diuretics may LABA because of risk of overdose. (5.3) worsen with concomitant beta-agonists. (7.4) • Candida albicans infection of the mouth and pharynx may occur. Monitor ----------------------- USE IN SPECIFIC POPULATIONS ----------------------- patients periodically. Advise the patient to rinse his/her mouth with water Hepatic impairment: Fluticasone furoate systemic exposure may increase in without swallowing after inhalation to help reduce the risk. (5.4) patients with moderate or severe impairment. Monitor for systemic • Increased risk of pneumonia in patients with COPD. Monitor patients for corticosteroid effects. (8.6, 12.3) signs and symptoms of pneumonia. (5.5) • Potential worsening of infections (e.g., existing tuberculosis; fungal, See 17 for PATIENT COUNSELING INFORMATION and FDA- bacterial, viral, or parasitic infections; ocular herpes simplex). Use with approved patient labeling. caution in patients with these infections. More serious or even fatal course Revised: 1/2019 of chickenpox or measles can occur in susceptible patients. (5.6) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 5.5 Pneumonia 1.1 Maintenance Treatment of Chronic Obstructive Pulmonary 5.6 Immunosuppression Disease 5.7 Transferring Patients from Systemic Corticosteroid Therapy 1.2 Treatment of Asthma 5.8 Hypercorticism and Adrenal Suppression 2 DOSAGE AND ADMINISTRATION 5.9 Drug Interactions with Strong Cytochrome P450 3A4 2.1 Chronic Obstructive Pulmonary Disease Inhibitors 2.2 Asthma 5.10 Paradoxical Bronchospasm 3 DOSAGE FORMS AND STRENGTHS 5.11 Hypersensitivity Reactions, including Anaphylaxis 4 CONTRAINDICATIONS 5.12 Cardiovascular Effects 5 WARNINGS AND PRECAUTIONS 5.13 Reduction in Bone Mineral Density 5.1 Serious Asthma-Related Events – Hospitalizations, 5.14 Glaucoma and Cataracts Intubations, Death 5.15 Coexisting Conditions 5.2 Deterioration of Disease and Acute Episodes 5.16 Hyperglycemia and Hypokalemia 5.3 Excessive Use of BREO ELLIPTA and Use with Other 5.17 Effect on Growth 6 ADVERSE REACTIONS Long-acting Beta2-agonists 5.4 Local Effects of Inhaled Corticosteroids 6.1 Clinical Trials Experience in Chronic Obstructive Pulmonary Disease 1 Reference ID: 4372035 6.2 Clinical Trials Experience in Asthma 10.2 Vilanterol 6.3 Postmarketing Experience 11 DESCRIPTION 7 DRUG INTERACTIONS 12 CLINICAL PHARMACOLOGY 7.1 Inhibitors of Cytochrome P450 3A4 12.1 Mechanism of Action 7.2 Monoamine Oxidase Inhibitors and Tricyclic 12.2 Pharmacodynamics Antidepressants 12.3 Pharmacokinetics 7.3 Beta-adrenergic Receptor Blocking Agents 13 NONCLINICAL TOXICOLOGY 7.4 Non–Potassium-Sparing Diuretics 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 8 USE IN SPECIFIC POPULATIONS 14 CLINICAL STUDIES 8.1 Pregnancy 14.1 Chronic Obstructive Pulmonary Disease 8.2 Lactation 14.2 Asthma 8.4 Pediatric Use 16 HOW SUPPLIED/STORAGE AND HANDLING 8.5 Geriatric Use 17 PATIENT COUNSELING INFORMATION 8.6 Hepatic Impairment *Sections or subsections omitted from the full prescribing information are not 8.7 Renal Impairment listed. 10 OVERDOSAGE 10.1 Fluticasone Furoate FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Maintenance Treatment of Chronic Obstructive Pulmonary Disease BREO ELLIPTA 100/25 is indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. BREO ELLIPTA 100/25 is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations. BREO ELLIPTA 100/25 once daily is the only strength indicated for the treatment of COPD. Important Limitation of Use BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm 1.2 Treatment of Asthma BREO ELLIPTA is indicated for the once-daily treatment of asthma in patients aged 18 years and older. BREO ELLIPTA should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta2-adrenergic agonist (LABA). Important Limitation of Use BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm. 2 DOSAGE AND ADMINISTRATION BREO ELLIPTA should be administered as 1 inhalation once daily by the orally inhaled route only. BREO ELLIPTA should be used at the same time every day. Do not use BREO ELLIPTA more than 1 time every 24 hours. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. More frequent administration or a greater number of inhalations (more than 1 inhalation daily) of the prescribed strength of BREO ELLIPTA is not recommended as some patients are more likely 2 Reference ID: 4372035 to experience adverse effects with higher doses. Patients using BREO ELLIPTA should not use additional LABA for any reason. [See