Umeclidinium Bromide

1-10%

Nasopharyngitis (8%)

Upper respiratory tract infection (5%)

Cough (3%)

Arthralgia (2%

Toothache (1%)

Pharyngitis (1%)

Viral upper respiratory tract infection (1%)

Tachycardia (1%)

<1%

Atrial fibrillation

Postmarketing Reports

Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, rash, and urticaria

Contraindications

Severe hypersensitivity to milk proteins

Demonstrated hypersensitivity to umeclidinium or any of the excipients

Cautions

Anaphylactic reactions reported in patients with severe milk protein allergy after inhalation of other powder products containing lactose (see Contraindications)

Hypersensitivity reactions such as anaphylaxis, angioedema, pruritus, rash, and urticaria may occur; discontinue if reactions occur

Do not initiate in patients during rapidly deteriorating or potentially life-threatening episodes of COPD; not be used for the relief of acute symptoms (ie, as rescue inhaler) from acute episodes of bronchospasm

Paradoxical bronchospasm reported; discontinue and treat immediately with an inhaled, prompt-acting bronchodilator (eg, albuterol)

Worsening of narrow-angle glaucoma may occur

Worsening of urinary retention may occur; caution in patients with prostatic hyperplasia or bladder-neck obstruction

Mechanism of Action

Long-acting muscarinic antagonist (LAMA) often referred to as an anticholinergic; blocks action of acetylcholine at muscarinic receptors (M1 to M5) in the bronchial airways (M3) by preventing increase in intracellular calcium concentration, leading to relaxation of airway smooth muscle, improved lung function, and decreased mucus secretion; dissociates slowly from M3 muscarinic receptors extending its duration of action

Absorption

Plasma levels not predictive of therapeutic effect

Peak plasma time: 5-15 minutes

Distribution

Following IV administration

Protein bound: 89% (umeclidinium)

Vd: 86 L (umeclidinium)

Metabolism

Primarily metabolized by CYP2D6 and is a substrate for the P-gp transporter

Primary metabolic routes for umeclidinium are oxidative (hydroxylation, O-dealkylation) followed by conjugation (eg, glucuronidation), resulting in a range of metabolites with either reduced pharmacological activity or for which the pharmacological activity has not been established

Systemic exposure to the metabolites is low

Elimination

Half-life: 11 hr

Umeclidinium (IV): 58% feces; 22% urine

Umeclidinium (PO): 92% feces; <1% urine

Administration

Administer umeclidinium by oral inhalation only using a specific oral inhalation device (Incruse Ellipta) that delivers powdered drug from foil-wrapped blisters.1

Administer umeclidinium in fixed combination with vilanterol by oral inhalation only using a specific preloaded inhaler (Anoro Ellipta) that delivers powdered umeclidinium in fixed combination with vilanterol from foil-wrapped blisters.2

Administer umeclidinium alone or in fixed combination with vilanterol once daily at the same time every day.1 2

Oral Inhalation

Oral Inhalation Administration

Before first use of either the Incruse Ellipta or Anoro Ellipta inhaler, remove device from foil tray; discard enclosed desiccant out of reach of children and pets.1 2 Write date the tray is opened and inhaler is to be discarded (6 weeks after opening) on label.1 2 Do not open inhaler cover until immediately before use; to avoid wasting doses, do not close cover again until dose is inhaled.1 2

Open cover fully to expose the mouthpiece and expect to hear a click.1 2 If dose counter does not advance when click is heard, inform clinician that dose is not properly prepared.1 2

Before inhaling dose, exhale completely; do not exhale into mouthpiece of inhaler.1 2 Place mouthpiece between lips and inhale deeply through inhaler with a steady, even breath; do not inhale through nose.1 2 Do not block air vent on inhaler during inhalation.1 2 Remove inhaler from mouth, hold the breath for about 3–4 seconds (or as long as comfortable), then exhale slowly and gently.1 2

Do not administer another dose even if delivery of dose not perceived.1 2 After dose is administered, close inhaler by sliding cover over mouthpiece as far as possible.1 2

Routine cleaning of inhaler is not necessary; may clean mouthpiece with dry tissue if desired.1 2

Dosage

Available as umeclidinium bromide; dosage expressed in terms of umeclidinium.1

Each foil-wrapped blister in the Incruse Ellipta inhaler device contains 74.2 mcg of umeclidinium bromide (equivalent to 62.5 mcg of umeclidinium).1 In vitro, each blister from the inhaler delivered 55 mcg of umeclidinium.1 Precise amount of drug delivered to lungs depends on patient-specific factors (e.g., inspiratory flow).1

Incruse Ellipta inhaler delivers 30 doses (or 7 doses for the sample or institutional package).1

Each foil-wrapped blister in the Anoro Ellipta inhaler device contains 74.2 mcg of umeclidinium bromide (equivalent to 62.5 mcg of umeclidinium) or 40 mcg of vilanterol trifenatate (equivalent to 25 mcg of vilanterol) (in separate blisters).2 In vitro, each pair of blisters from the inhaler delivered 55 mcg of umeclidinium and 22 mcg of vilanterol.2 Precise amount of drug delivered to lungs depends on patient-specific factors (e.g., inspiratory flow).2

Anora Ellipta inhaler delivers 30 doses (or 7 doses for the sample or institutional package).2

Adults

62.5 mcg of umeclidinium (1 inhalation) once daily.1

62.5 mcg of umeclidinium and 25 mcg of vilanterol (1 inhalation) once daily.2

Prescribing Limits

Adults

Do not administer more than once every 24 hours.1

Do not administer more than once every 24 hours.2

Special Populations

When umeclidinium is used in fixed combination with vilanterol, dosage requirements for vilanterol should be considered.2

Hepatic Impairment

No dosage adjustment required in patients with moderate hepatic impairment; not studied in patients with severe hepatic impairment.1 2 (See Absorption under Pharmacokinetics.)

Renal Impairment

No dosage adjustment required.1 2 11 12

Geriatric Patients

No dosage adjustment required.1 2 (See Geriatric Use under Cautions.)

Storage

Oral Inhalation

20–25°C (may be exposed to 15–30°C) in a dry place away from direct heat or sunlight.1 2

Keep inhaler in sealed tray until immediately before use.1 2 Discard inhaler after every blister used or 6 weeks after removal of inhaler from foil tray, whichever comes first.1 2

• When used in fixed combination with vilanterol, importance of informing patients of important cautionary information about vilanterol.2

• Provide copy of the manufacturer’s patient information (medication guide) to all patients each time drug is dispensed.1 2 Importance of instructing patients to read the patient information prior to initiation of therapy and each time prescription is refilled.1 2

• Importance of informing clinician of any history of hypersensitivity reactions to umeclidinium or severe allergy to milk proteins.1 2

• Importance of adequate understanding of proper storage and inhalation techniques, including use of the inhalation delivery systems.1 2

• Importance of advising patients that if a dose is missed, to take the dose as soon as it is remembered; importance of not doubling the dose and of not taking more than one dose in a 24-hour period.1 2

• Importance of all patients being provided with and instructed in the use of a short-acting, inhaled β2-adrenergic agonist as supplemental therapy for acute symptoms.1 2

• Importance of contacting a clinician immediately if symptoms worsen or if the short-acting β2-agonist becomes less effective or more inhalations than usual are required to relieve symptoms.1 2

• Importance of patients not discontinuing therapy without medical supervision, since symptoms may recur after discontinuance.1 2

• Importance of not using umeclidinium to relieve acute symptoms or exacerbations of COPD.1 2

• Importance of discontinuing umeclidinium and informing a clinician if paradoxical bronchospasm occurs.1 2

• Importance of informing a clinician immediately if eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion or corneal edema occur.1 2

• Importance of informing a clinician immediately if urinary retention or dysuria occurs.1 2

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., eye drops) and herbal supplements, as well as any concomitant illnesses (e.g., urinary retention, enlarged prostate, angle-closure glaucoma).1 2

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2

• Importance of informing patients of other important precautionary information.1 2 (See Cautions.)