Introduction
Umeclidinium is a long-acting muscarinic antagonist (LAMA) bronchodilator used in the maintenance treatment of chronic obstructive pulmonary disease (COPD). Marketed under the brand name Incruse Ellipta, it was approved by the FDA in 2014 as a once-daily inhaled maintenance medication. Umeclidinium represents an important therapeutic option in the management of airflow obstruction in COPD patients.
Mechanism of Action
Umeclidinium competitively inhibits muscarinic receptors (specifically M1, M2, and M3 subtypes) in bronchial smooth muscle. By blocking acetylcholine at these receptors, it prevents bronchoconstriction and reduces mucus secretion. The primary therapeutic effect comes from M3 receptor antagonism in airway smooth muscle, leading to bronchodilation. Unlike short-acting agents, umeclidinium provides sustained bronchodilation through prolonged receptor occupancy.
Indications
- Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
- Not indicated for the relief of acute bronchospasm or for the treatment of asthma
Dosage and Administration
Standard dosing: 62.5 mcg (delivered as 55 mcg from the mouthpiece) via oral inhalation once daily using the Ellipta dry powder inhaler Administration instructions:- Use at the same time each day
- Do not exceed one inhalation per day
- Prime device before first use
- Rinse mouth with water after inhalation to reduce risk of oropharyngeal side effects
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment necessary
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Systemic absorption occurs primarily through the lungs with low oral bioavailability (<1%) due to extensive first-pass metabolism Distribution: Extensive tissue distribution with steady-state volume of distribution approximately 86 L; plasma protein binding is approximately 89% Metabolism: Primarily metabolized by cytochrome P450 2D6 (CYP2D6) and 3A4 (CYP3A4) enzymes through oxidation and hydrolysis Elimination: Terminal half-life of approximately 11 hours; primarily excreted in feces (≈58%) and urine (≈22%) as metabolitesContraindications
- Hypersensitivity to umeclidinium or any component of the formulation
- History of hypersensitivity reactions to atropine or its derivatives
Warnings and Precautions
Paradoxical bronchospasm: May occur with immediate increase in wheezing after dosing; discontinue immediately if occurs Cardiovascular effects: May increase risk of cardiovascular events including stroke and myocardial infarction; use with caution in patients with cardiovascular disorders Narrow-angle glaucoma: May increase intraocular pressure; advise patients to avoid contacting eyes with medication Urinary retention: May occur, particularly in patients with bladder outflow obstruction or prostatic hyperplasia Acute exacerbations: Not indicated for relief of acute symptoms; patients should have rescue medication available Hypersensitivity reactions: Immediate hypersensitivity reactions may occur, including urticaria, angioedema, rash, and bronchospasmDrug Interactions
Strong CYP450 2D6 inhibitors: (e.g., paroxetine, quinidine) - May increase umeclidinium exposure; monitor for increased anticholinergic effects Other anticholinergic medications: (e.g., ipratropium, tiotropium) - Increased risk of additive anticholinergic adverse effects; avoid concomitant use β-blockers: May reduce bronchodilator effect; use with caution Diuretics: May potentiate hypokalemia when used with other drugs that cause hypokalemiaAdverse Effects
Common (≥1%):- Upper respiratory tract infection
- Pharyngitis
- Sinusitis
- Headache
- Cough
- Dry mouth
- Paradoxical bronchospasm
- Worsening of narrow-angle glaucoma
- Worsening of urinary retention
- Cardiovascular events (tachycardia, palpitations)
- Hypersensitivity reactions
Monitoring Parameters
- Pulmonary function tests (FEV1, peak flow)
- Symptom control and exacerbation frequency
- Oropharyngeal examination for candidiasis
- Intraocular pressure in patients with glaucoma
- Urinary symptoms in patients with prostatic hyperplasia
- Cardiovascular status in high-risk patients
- Proper inhaler technique at each visit
Patient Education
Proper administration:- Demonstrate correct use of Ellipta inhaler
- Do not exhale into device
- Close lips firmly around mouthpiece
- Inhale deeply and steadily
- Hold breath for 3-4 seconds after inhalation
- Use regularly once daily, even when feeling well
- Do not use for acute breathing problems
- Keep rescue inhaler available at all times
- Rinse mouth with water after each use to prevent oral thrush
- Do not stop using without consulting healthcare provider
- Worsening breathing problems
- Eye pain or vision changes
- Urinary difficulty or pain
- Signs of allergic reaction (rash, swelling, difficulty breathing)
- Chest pain or palpitations
- Store at room temperature in dry place
- Keep in sealed foil tray until ready to use
- Do not expose to moisture
- Discard 6 weeks after opening foil tray
References
1. FDA Prescribing Information: Incruse Ellipta (umeclidinium inhalation powder) 2. Donohue JF, et al. Efficacy and safety of once-daily umeclidinium/vilanterol versus tiotropium in COPD. Respir Med. 2013;107(10):1538-1546 3. Decramer ML, et al. Safety and efficacy of umeclidinium plus vilanterol versus tiotropium in COPD. Eur Respir J. 2013;42(Suppl 57) 4. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD. 2023 Report 5. Kerwin EM, et al. Efficacy and safety of once-daily umeclidinium/vilanterol in COPD. Respir Med. 2013;107(7):1103-1109 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Umeclidinium. Updated 2023