Fluticasone furoate, Umeclidinium and Vilanterol

TRELEGY ELLIPTA is a combination of fluticasone furoate, an inhaled corticosteroid (ICS), umeclidinium, an anticholinergic, and vilanterol, a long-acting beta 2 -adrenergic agonist (LABA), indicated for: • the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). • the maintenance treatment of asthma in patients aged 18 years and older. Limitations of Use: Not indicated for relief of acute bronchospasm.

TRELEGY ELLIPTA TRELEGY ELLIPTA contains fluticasone furoate, umeclidinium, and vilanterol. The mechanisms of action described below for the individual components apply to TRELEGY ELLIPTA. These drugs represent 3 different classes of medications (an ICS, an anticholinergic, and a LABA), each having different effects on clinical and physiological indices. Fluticasone Furoate Fluticasone furoate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate. The clinical relevance of these findings is unknown. The precise mechanism through which fluticasone furoate affects COPD and asthma symptoms is not known.

• For oral inhalation only. • Maintenance treatment of COPD: 1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg once daily administered by oral inhalation. • Maintenance treatment of asthma: 1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg or TRELEGY ELLIPTA 200/62.5/25 mcg once daily administered by oral inhalation.

TRELEGY ELLIPTA is contraindicated in the following conditions: • Primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required. • Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, umeclidinium, vilanterol, or any of the excipients. • Primary treatment of status asthmaticus or acute episodes of COPD or asthma requiring intensive measures. • Severe hypersensitivity to milk proteins or any ingredients.

• LABA monotherapy increases the risk of serious asthma-related events. • Do not initiate in acutely deteriorating COPD or asthma. Do not use to treat acute symptoms. • Do not use in combination with additional therapy containing a LABA because of risk of overdose. • Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk. • Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia. • Potential worsening of infections (e.g., existing tuberculosis, fungal, bacterial, viral, or parasitic infections, ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.

The following clinically significant adverse reactions are described elsewhere in labeling: • Serious Asthma-Related Events – Hospitalizations, Intubations, Death • Oropharyngeal Candidiasis • Increased Risk of Pneumonia in COPD • Immunosuppression and Risk of Infections • Hypercorticism and Adrenal Suppression • Paradoxical Bronchospasm • Cardiovascular Effects • Reduction in Bone Mineral Density • Worsening of Narrow-Angle Glaucoma • Worsening of Urinary Retention 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.

• Strong cytochrome P450 3A4 inhibitors (e.g., ketoconazole): Use with caution. May cause systemic corticosteroid and cardiovascular effects. • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of vilanterol on cardiovascular system. • Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists. • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of TRELEGY ELLIPTA with other anticholinergic-containing drugs.

Store at room temperature between 68°F and 77°F (20°C and 25°C), excursions permitted from 59°F to 86°F (15°C to 30°C). Store in a dry place away from direct heat or sunlight. TRELEGY ELLIPTA should be stored inside the unopened moisture-protective foil tray and only removed from the tray immediately before initial use.