Brand name: Incruse Ellipta
Drug class: Antimuscarinics/Antispasmodics

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Bronchodilator; synthetic quaternary ammonium antimuscarinic agent.

Uses for Umeclidinium Bromide (Oral Inhalation)

Bronchospasm in COPD

Long-term maintenance treatment of patients with COPD, including chronic bronchitis and/or emphysema.

Not indicated for treatment of acute bronchospasm (i.e., as rescue therapy for treatment of acute episodes of bronchospasm).

Umeclidinium Bromide (Oral Inhalation) Dosage and Administration

Administration

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

Administer once daily at the same time every day.

Administration

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

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

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

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

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

Dosage

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

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

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

Adults

COPD

Oral Inhalation

62.5 mcg (1 inhalation) once daily.

Do not administer more frequently than once every 24 hours.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with moderate hepatic impairment; not studied in patients with severe hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with renal impairment.

Geriatric Use

No dosage adjustment required in geriatric patients.

Cautions for Umeclidinium Bromide (Oral Inhalation)

Contraindications

• Hypersensitivity to umeclidinium or any ingredient in the formulation.

• Severe hypersensitivity to milk proteins.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions may occur. Anaphylactic reactions reported following oral inhalation of other powder preparations containing lactose in patients with severe hypersensitivity to milk proteins; therefore, patients with severe milk protein allergy should not use umeclidinium.

Deterioration of Disease and Acute Episodes

Do not initiate umeclidinium in patients with acutely deteriorating COPD, which may be life-threatening.

Do not use for relief of acute symptoms. Not studied in patients with acute symptoms; do not use extra doses of the drug in such situations. Use a short-acting, inhaled β₂-agonist as needed for acute symptoms.

Failure to respond to a previously effective dosage of umeclidinium or to a supplemental short-acting, inhaled β₂-agonist may indicate worsening COPD. Immediately reevaluate the patient and treatment regimen. Do not use extra or increased dosages in such situations.

Paradoxical Bronchospasm

Acute, life-threatening paradoxical bronchospasm may occur.

If paradoxical bronchospasm occurs, immediately treat patient with an inhaled, short-acting bronchodilator; discontinue therapy with umeclidinium and institute alternative therapy.

Ocular Effects

Use caution in patients with acute angle-closure glaucoma. Possible worsening of acute angle-closure glaucoma manifested by ocular pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion and corneal edema.

GU Effects

Use caution in patients with urinary retention. May worsen symptoms and signs (e.g., urinary retention, dysuria) associated with prostatic hyperplasia or bladder neck obstruction.

Cardiovascular Effects

Atrial fibrillation reported in <1% of patients.

Prolongation of QT_c not observed in healthy individuals.

Specific Populations

Pregnancy

Insufficient data in pregnant women to inform a drug-associated risk. Adverse embryofetal effects not observed in animal studies.

Lactation

May be distributed into milk in rats; not known whether distributed into human milk or whether the drug has any effects on the breastfed infant or on milk production. Consider benefits of breastfeeding and mother's need for umeclidinium along with potential adverse effects on the infant from the drug or underlying maternal condition.

Pediatric Use

Not indicated for use in pediatric patients. Safety and efficacy not established.

Geriatric Use

No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Exposure not substantially altered in patients with moderate hepatic impairment (Child-Pugh score of 7–9). Not studied in patients with severe hepatic impairment.

Renal Impairment

Exposure not substantially altered in patients with severe renal impairment (Cl_cr <30 mL/minute).

Common Adverse Effects

Most common adverse reactions (≥2%): nasopharyngititis, upper respiratory tract infection, cough, arthralgia.

Drug Interactions

Substrate of CYP2D6 and P-glycoprotein (P-gp).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes and/or the P-gp Transport System

No clinically important effect on umeclidinium exposure in individuals who were poor-metabolizers of CYP2D6 substrates compared with ultrarapid, extensive, and intermediate metabolizers. Therefore, dosage adjustment not required when used concomitantly with CYP2D6 inhibitors.

Specific Drugs

Umeclidinium Bromide (Oral Inhalation) Pharmacokinetics

Absorption

Bioavailability

Exhibits linear pharmacokinetics over dosage range of 62.5–500 mcg.

Peak umeclidinium concentrations reached within 5–15 minutes following oral inhalation; plasma concentrations may not predict therapeutic effect.

Mostly absorbed from the lung following oral inhalation; minimal contribution from oral absorption.

Steady-state plasma concentrations achieved within 14 days; 1.8-fold accumulation following repeated once-daily inhalation.

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

Approximately 89%.

Elimination

Metabolism

Metabolized mainly by CYP2D6; also a substrate for P-gp.

Principal routes of metabolism involve oxidation via hydroxylation and O-dealkylation followed by conjugation (e.g., glucuronidation); low systemic exposure to metabolites.

Elimination Route

Undergoes biliary elimination.

58 and 22% of radiolabeled IV dose excreted in feces and urine, respectively.

Negligible oral absorption; 92 and <1% of radiolabeled oral dose excreted in feces and urine, respectively.

Half-life

Effective half-life following once daily dosing: 11 hours.

Special Populations

No clinically important differences in pharmacokinetics based on age, gender, weight, race, or use of inhaled corticosteroids.

Poor-metabolizers of CYP2D6 substrates: No clinically important effect on umeclidinium exposure following repeated administration of 500 mcg (8 times usual recommended dosage) compared with healthy ultrarapid, extensive, and intermediate metabolizers.

Stability

Storage

Oral Inhalation

20–25°C (excursions permitted to 15–30°C) in a dry place away from direct heat or sunlight.

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

Actions

• Synthetic quaternary ammonium antimuscarinic agent.

• Long-acting, orally inhaled bronchodilator.

• Nonselective competitive antagonist at muscarinic (M₁–M₅) receptors.

• Competitively and reversibly inhibits the actions of acetylcholine and other cholinergic stimuli at M₃ receptors in respiratory tract smooth muscle leading to bronchodilation.

Advice to Patients

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

• Advise patients to inform their clinician of any history of hypersensitivity reactions to umeclidinium or severe allergy to milk proteins.

• Inform patients of proper storage and inhalation techniques, including use of the inhalation delivery systems.

• Advise 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.

• Instruct patients on the use of a short-acting, inhaled β₂-adrenergic agonist as supplemental therapy for acute symptoms.

• Advise patients to contact 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.

• Advise patients not to discontinue therapy without medical supervision, since symptoms may recur after discontinuance.

• Advise patients not to use umeclidinium to relieve acute symptoms or exacerbations of COPD.

• Advise patients to discontinue umeclidinium and inform a clinician if paradoxical bronchospasm occurs.

• Advise patients to inform 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.

• Advise patients to inform a clinician immediately if urinary retention or dysuria occurs.

• Advise patients to inform their 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.

• Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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