Umeclidinium and Vilanterol

Umeclidinium and Vilanterol ELLIPTA is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Limitations of Use Umeclidinium and Vilanterol ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma. The safety and effectiveness of Umeclidinium and Vilanterol ELLIPTA in asthma have not been established. Umeclidinium and Vilanterol ELLIPTA is a combination of 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). Limitations of Use: Not indicated for relief of acute bronchospasm or for the treatment of asthma.

Umeclidinium and Vilanterol ELLIPTA Umeclidinium and Vilanterol ELLIPTA contains both umeclidinium and vilanterol. The mechanisms of action described below for the individual components apply to Umeclidinium and Vilanterol ELLIPTA. These drugs represent 2 different classes of medications (an anticholinergic and a LABA) each having different effects on clinical and physiological indices. Umeclidinium Umeclidinium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations.

The recommended dosage of Umeclidinium and Vilanterol ELLIPTA for maintenance treatment of COPD is 62.5 mcg umeclidinium and 25 mcg vilanterol (1 actuation of Umeclidinium and Vilanterol ELLIPTA 62.5/25 mcg) once daily by oral inhalation. • Umeclidinium and Vilanterol ELLIPTA should be used at the same time every day. Do not use Umeclidinium and Vilanterol ELLIPTA more than 1 time every 24 hours. • No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment. • For oral inhalation only. • Maintenance treatment of COPD: 1 actuation of Umeclidinium and Vilanterol ELLIPTA once daily administered by oral inhalation.

Umeclidinium and Vilanterol ELLIPTA is contraindicated in: • patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to umeclidinium, vilanterol, or any of the excipients. • use of a long-acting beta 2 -adrenergic agonist (LABA), including vilanterol, one of the active ingredients in Umeclidinium and Vilanterol ELLIPTA, without an inhaled corticosteroid (ICS), in patients with asthma. Umeclidinium and Vilanterol ELLIPTA is not indicated for the treatment of asthma. • Severe hypersensitivity to milk proteins or any ingredients.

• LABA monotherapy (without an inhaled corticosteroid) for asthma increases the risk of serious asthma-related events. • Do not initiate in acutely deteriorating COPD. Do not use to treat acute symptoms. • Do not use in combination with additional therapy containing a LABA because of risk of overdose. • If paradoxical bronchospasm occurs, discontinue Umeclidinium and Vilanterol ELLIPTA and institute alternative therapy. • Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation. • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. • Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur. • Worsening of urinary retention may occur.

The following clinically significant adverse reactions are described elsewhere in labeling: • Serious asthma-related events–hospitalizations, intubations, death • Paradoxical bronchospasm • Cardiovascular effects • Worsening of narrow-angle glaucoma • Worsening of urinary retention Most common adverse reactions (incidence ≥1% and more common than placebo) are pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, pain in extremity, muscle spasms, neck pain, and chest pain.

• Strong cytochrome P450 3A4 inhibitors (e.g., ketoconazole): Use with caution. May cause 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 Umeclidinium and Vilanterol 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. Umeclidinium and Vilanterol ELLIPTA should be stored inside the unopened moisture-protective foil tray and only removed from the tray immediately before initial use.