Trelegy Ellipta
Trelegy Ellipta
Generic Name
Trelegy Ellipta
Mechanism
Trelegy Ellipta is a fixed‑dose combination of three bronchodilators:
• Fluticasone furoate – an inhaled glucocorticoid that suppresses airway inflammation by inhibiting NF‑κB‑mediated cytokine production.
• Umeclidinium – a long‑acting muscarinic antagonist (LAMA) that blocks M3 receptors, preventing bronchoconstriction and secretory activity.
• Vilanterol – a long‑acting β₂‑agonist (LABA) that stimulates β₂ receptors, inducing smooth‑muscle relaxation and airway dilation.
Together, they provide anti‑inflammatory, anticholinergic, and β‑agonist bronchodilation, synergistically improving pulmonary function and reducing exacerbations in COPD.
Pharmacokinetics
| Component | Absorption | Distribution | Metabolism | Elimination | Key PK Points |
| Fluticasone furoate | Pulmonary deposition; negligible oral bioavailability (~2%) | High protein binding, lipophilic, extensive lung tissue retention | CYP3A4‑dependent (Hepatic) | Renal/ fecal excretion of metabolites | ~1% systemic exposure; low systemic side‑effects |
| Umeclidinium | Pulmonary; small systemic absorption | Widely distributed, low protein binding | Minimal hepatic metabolism | Renal excretion of unchanged drug | Effective lung concentrations for ~30 h |
| Vilanterol | Pulmonary absorption | Plasma protein binding ~90% | CYP2A6 & 3A4 | Renal and fecal | Peak plasma ~10 min; terminal half‑life ~22 h |
• Bioavailability: ~1–2% systemic; majority remains in the lung.
• Half‑life: 22 h (vilanterol) → 30 h (umeclidinium) → 4–12 h (fluticasone furoate systemically).
• Drug interactions: Strong CYP3A4 inducers (rifampin) reduce fluticasone levels; CYP3A4 inhibitors (ketoconazole) may raise systemic steroids.
Indications
- Maintenance therapy in adults (≥18 y) with symptomatic COPD (FEV₁ < 50% predicted, ≥ 30 % decline in FEV₁ over 1 y, ≥ 1 exacerbation requiring oral corticosteroid or antibiotic in the prior year).
- Use when LABA + LAMA or LABA + inhaled corticosteroid (ICS) regimens do not adequately control symptoms.
*Not indicated for asthma exacerbations, acute bronchospasm, or in pediatric populations.*
Contraindications
- Contraindications
- Hypersensitivity to any component (fluticasone furoate, umeclidinium, vilanterol) or excipients.
- Warnings
- Pneumonia: Higher incidence in COPD patients using inhaled corticosteroids; monitor and treat promptly.
- Risk of systemic steroid effects: Caution in patients with adrenal insufficiency, diabetes, hypertension, osteoporosis.
- Cough or throat irritation: May worsen cough; use spacer if needed.
- Pregnancy/Breastfeeding: Category C; use only if benefits outweigh risks.
- Anticholinergic toxicity: Be alert for tachycardia, urinary retention, constipation in at‑risk patients.
- Cardiac conduction: Rare QT prolongation with high doses; avoid with concomitant QT‑prolonging drugs.
Dosing
- Adult standard dose: 1 inhalation once daily (QD) via Ellipta inhaler.
- Formulation: 200 µg fluticasone furoate + 9 µg vilanterol + 62.5 µg umeclidinium.
- Administration technique
- Inhale slowly and deeply over 3–4 s, hold breath 10 s if possible.
- No spacer needed; ensure proper head position and breathing pattern.
- Switching: Can be transitioned from separate LABA/LAMA/ICS regimens; maintain same total dose.
- Missed dose: Take immediately; do not double‑dose the next dose.
Adverse Effects
| Category | Examples |
| Local (common) | Oral candidiasis, dysphonia, cough, throat irritation, xerostomia |
| Systemic (common) | Hyperglycemia, hypertension, insomnia, adrenal suppression (rare) |
| Serious | Pneumonia, severe infections, acute asthma attack, arrhythmias, severe hypertension, allergic reactions |
• Monitoring of local side‑effects: Educate patients on rinsing mouth post‑dose; provide antifungal prophylaxis if recurrent candidiasis.
Monitoring
- Pulmonary function: FEV₁ and peak expiratory flow (PEF) every 3–6 months.
- Blood glucose & HbA1c: Baseline and annually in diabetics.
- Blood pressure: Baseline and every visit in hypertensive patients.
- Adrenal function: Consider basal cortisol if prolonged high‑dose use or risk of adrenal suppression.
- Exacerbation frequency: Track number of exacerbations per year; assess for treatment efficacy.
- Infection vigilance: Monitor for signs of pneumonia, especially in patients with significant comorbidities.
Clinical Pearls
- Once‑daily convenience → improves adherence compared with separate inhalers.
- Bronchial mucosal de‑beaded: The combination reduces airway hyperreactivity more than beta‑agonist alone.
- Contra‑indicating for “COPD‑only”: Do *not* use for patients with normal lung function or hyper‑responsiveness without COPD; appropriate for people with irreversible airflow limitation.
- Avoid combination with other inhaled steroids unless clinically indicated (e.g., asthma overlap); risk of cumulative systemic side‑effects.
- Use a spacer only for patients with poor inhalation technique or those who experience throat irritation.
- Patient education: Emphasize rinsing mouth to prevent fungal infections; inform them that mild cough or throat discomfort is common and self‑limited.
- Special populations: In patients > 65 y with osteoporosis, assess bone density before long‑term use.
- Interaction with antibiotics: Macrolide antibiotics (e.g., clarithromycin) can increase systemic absorption of steroids → watch blood glucose.
Search‑friendly tags: *COPD treatment, inhaled corticosteroid, LAMA, LABA, oral glucocorticoid side‑effects, pneumonia risk, airway inflammation, drug monitoring.*
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