Umeclidinium

Generic Name

Umeclidinium

Mechanism

Selective M3 muscarinic receptor blockade in airway smooth muscle.
Prevents acetylcholine‑induced bronchoconstriction, reducing airway resistance.
Sustained bronchodilation (≥24 h) allows once‑daily dosing.
Does not exert any anti‑inflammatory effect; it is purely a bronchodilator.

Pharmacokinetics

Parameter	Typical Value / Note
Absorption	Rapid pulmonary absorption; 40–50 % systemic bioavailability after inhalation.
Distribution	Protein binding ≈ 90 % (primarily to α1‑acid glycoprotein).
Metabolism	Minimal; mainly O‑demethylation via CYP3A4/5 and CYP2C9.
Elimination	Primarily fecal (≈ 70 %), remainder renal.
Half‑life	~24 h (steady state achieved in ~1 week).
Drug interactions	No clinically significant CYP interactions; caution when co‑administering potent CYP3A4 inhibitors.

Indications

Maintenance therapy for COPD (post‑bronchodilator FEV₁ ≥ 30 % predicted, ≥ 20 % predicted improvement).
Not approved for acute exacerbations or asthma.

Contraindications

Hypersensitivity to umeclidinium or any excipient.
Narrow‑angle glaucoma (risk of increased intraocular pressure).
Severe hepatic impairment (data limited).
Urinary retention or history of prostatic hypertrophy (risks of worsening obstruction).

Warnings
• Cardiovascular: tachycardia, bradycardia, orthostatic hypotension; avoid in patients with untreated severe arrhythmias.
• Ophthalmic: can precipitate angle‑closure glaucoma.

Dosing

Adult dose: 62.5 µg or 125 µg once daily via dry‑powder inhaler, preferably taken in the morning.
*Note*: 62.5 µg dose is the preferred formulation; 125 µg is an alternate dosing strategy for patients with poor inspiratory flow.
Pediatric: Not approved.
Administration technique:

1. Shake inhaler.

2. Prime if changed.

3. Deep‑inspiratory breath and hold for 5–10 s.

Adverse Effects

Class	Typical Incidence	Examples
Respiratory	3–7 %	Cough, throat irritation, dry mouth
Cardiovascular	1–3 %	Palpitations, tachycardia, nausea (rare)
Neurologic	< 1 %	Headache, dizziness (rare)
Serious	Rare	Hypersensitivity rash, severe bronchospasm, arrhythmias, acute urinary retention

Monitoring

Pulmonary: FEV₁, FVC at baseline and every 3 months.
Cardiac: Resting heart rate, ECG (QT interval) if taking other QT‑prolonging drugs.
Ophthalmic: In patients with pre‑existing glaucoma, baseline intraocular pressure (IOP) and follow‑up if symptoms arise.

Clinical Pearls

Inhaler Technique: Patients may under‑dose if the inspiratory flow is too slow; the 62.5 µg dose is more forgiving in low‑flow patients.
Combination Therapy: Evidence shows that umeclidinium plus the LABA vilanterol (dual therapy) reduces exacerbations more than umeclidinium alone.
Safety in Renal Disease: Mildly excreted renally; no dose adjustment required for CKD stage 3‑4.
Drug‑Interaction Check: Avoid simultaneous use of strong CYP3A4 inhibitors (ketoconazole, itraconazole) if you suspect increased systemic exposure.
Patient Education: Counsel on reporting new ocular symptoms (blurred vision, eye pain) promptly.
Adherence Boost: Use a reminder app or a daily pillbox “inhaler” to maintain once‑daily regimen.

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• References

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2025 Report.

2. National Comprehensive Cancer Network (NCCN) guidelines, COPD. 2025.

3. Umeclidinium product insert, Boehringer Ingelheim. 2025.

4. Bork, W. *Pharmacology: Drug Absorption and Metabolism*, 9th ed. 2023.

5. ClinicalTrials.gov NCT02929212 – Umeclidinium vs. placebo. 2024.