Umeclidinium and vilanterol
Umeclidinium
Generic Name
Umeclidinium
Mechanism
- Umeclidinium: Selective antagonist of β2‑adrenergic receptors? Actually it's a LAMA—antagonist of muscarinic M3 receptors, preventing acetylcholine‑induced bronchoconstriction and mucus secretion.
- Vilanterol: Full agonist at β2‑adrenergic receptors, increasing cAMP → smooth‑muscle relaxation and bronchodilation.
- Combined therapy provides additive, rapid, and prolonged bronchodilation, improving airflow for patients with limited single‑agent control.
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Pharmacokinetics
| Parameter | Umeclidinium | Vilanterol |
| Absorption | Rapid pulmonary deposition; systemic absorption ≈2–3 % after inhalation. | Same; systemic uptake ≈3 %. |
| Distribution | Highly lipophilic; binds to lung tissue (e.g., regional depots). | Similar; extensive pulmonary distribution. |
| Metabolism | Primarily through CYP3A4 and CYP1A2; hepatic metabolism of minor fraction. | Extensive first‑pass metabolism via CYP3A4/2D6. |
| Elimination | Renal (≈30 %) and biliary excretion; terminal half‑life ≈30 h. | 24‑hour half‑life; renal (≈40 %) and hepatic exit. |
| Drug‑Drug Interactions | Strong CYP3A4 inhibitors can ↑ plasma concentrations of both agents. | Same; monitor for QT prolongation with CYP3A4 inhibitors. |
*Key take‑away*: Because both drugs are substantially cleared by the liver, caution with hepatotoxic agents and renal dysfunction is warranted.
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Indications
- Chronic Obstructive Pulmonary Disease (COPD) – maintenance bronchodilation for patients who remain symptomatic on LABA or LAMA monotherapy.
- Moderate to Severe Asthma – used as a long‑term controller for patients with uncontrolled disease on inhaled corticosteroids (ICS) ± LAMA/LABA.
- Early COPD – evidence of added benefit in high‑risk patients (e.g., smoking history, reduced FEV1).
> *Note*: Not approved for acute rescue or exacerbations.
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Contraindications
- Absolute contraindication: Hypersensitivity to any component (clic-1?).
- Pregnancy: Category D; pregnancy‑testing recommended prior to therapy.
- Breastfeeding: Unknown; generally not recommended.
- CYP3A4 inhibitors (ketoconazole, ritonavir) – significant interaction → adverse events ↑.
- QT prolongation: Monitor ECG in patients with cardiac comorbidities.
> *Warn*: Use with caution in patients with significant hepatic impairment; monitor liver enzymes regularly.
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Dosing
- Device: Dry‑powder inhaler.
- Adult/Adolescent (≥12 y):
- ≤ 360 µg umeclidinium + 107 µg vilanterol once daily (twice‑daily dosing in some approvals).
- Children (6–11 y): Dose adjusted per weight; commonly 120 µg umeclidinium + 30 µg vilanterol once daily.
- Administration:
- Shake inhaler before use.
- Load dose, hold breath for 5–6 s, then rinse mouth to minimize local irritation.
> *Tip*: Consistency of technique is essential; provide step‑by‑step guidance for trainees.
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Adverse Effects
| Adverse Effect | Frequency | Typical Dose | Notes |
| Dry mouth, throat irritation | Common | All doses | Use rinse water; consider antihistamine antagonist for severe cases. |
| Headache | Common | All doses | Usually mild. |
| Tachycardia, palpitations | Occasional | All doses | Monitor in patients with arrhythmias. |
| Hypertension | Rare | All doses | Check BP in hypertensive patients. |
| Cough, wheezing | Rare | All doses | May mimic asthma exacerbation. |
| Serious: Severe bronchospasm, anaphylaxis (uncommon) | Very rare | High doses | Immediate discontinuation + emergency treatment. |
*Key point*: Systemic antimuscarinic toxicity is minimal; only lower‑dose adverse events reported.
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Monitoring
- Spirometry: FEV1/FVC baseline → 12, 24, 48 h after initiation; then every 3–6 mo for COPD; every 6–12 mo for asthma.
- Liver function tests: baseline, +3 months, then every 6 mo.
- ECG: baseline in patients with QT risks; repeat if symptomatic.
- Blood pressure & heart rate: baseline & 3‑month follow‑up.
- Adherence & technique: quarterly patient review; provide inhaler technique correction.
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Clinical Pearls
- Dual‑acting synergy: LABA + LAMA confers faster onset, longer duration, and additive bronchodilation ≥30 % higher than monotherapy in label‑evidence.
- Simplified regimen: Once‑daily dosing improves adherence over BID regimens, particularly critical in COPD where poly‑pharmacy burdens patients.
- Asthma use is off‑label—you need to confirm with local guidelines; publishers often advise use only when LABA + LABA or LABA + LAMA are unavailable.
- CNI‑CYP3A4 inhibitors: awareness of drug‑drug interactions reduces risk of tachycardia, hepatotoxicity, or overdose.
- Technique over drug: Flawed inhalation technique is the commonest cause of inadequate bronchodilation; periodic skills assessment can save costs and improve outcomes.
> *Final thought*: In your next teaching session, highlight that the combination is a maintenance therapy—not a rescue inhaler. Emphasise correct scheduling (morning vs evening) according to patient preferences and chronobiology of COPD exacerbations.