TRELEGY ELLIPTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRELEGY ELLIPTA (TRELEGY ELLIPTA).
Trelegy Ellipta is a fixed-dose combination of fluticasone furoate (a corticosteroid), umeclidinium (an anticholinergic), and vilanterol (a long-acting beta2-adrenergic agonist). Fluticasone furoate reduces inflammation by binding to glucocorticoid receptors, leading to anti-inflammatory gene transcription. Umeclidinium blocks muscarinic receptors (M3 subtype) on bronchial smooth muscle, inhibiting cholinergic-mediated bronchoconstriction. Vilanterol stimulates beta2-adrenergic receptors, activating adenylate cyclase and increasing cyclic AMP, resulting in bronchodilation.
| Metabolism | Fluticasone furoate is metabolized primarily by CYP3A4. Umeclidinium is metabolized by CYP2D6 and CYP3A4. Vilanterol is metabolized by CYP3A4. |
| Excretion | Fluticasone furoate: primarily fecal (approx. 90%) with <1% renal; Umeclidinium: primarily fecal (approx. 58%) and renal (approx. 22%); Vilanterol: primarily fecal (approx. 70%) and renal (approx. 22%) |
| Half-life | Fluticasone furoate: ~24 hours; Umeclidinium: ~19 hours; Vilanterol: ~11 hours; allows once-daily dosing |
| Protein binding | Fluticasone furoate: >99.8% (primarily albumin); Umeclidinium: ~89% (albumin and alpha-1-acid glycoprotein); Vilanterol: ~94% (albumin and alpha-1-acid glycoprotein) |
| Volume of Distribution | Fluticasone furoate: ~4.5 L/kg (large, indicating extensive tissue distribution); Umeclidinium: ~80 L (not weight-adjusted; approx 1.1 L/kg for 70kg); Vilanterol: ~165 L (not weight-adjusted; approx 2.4 L/kg for 70kg) |
| Bioavailability | Inhaled: absolute bioavailability <1% for fluticasone furoate, ~6% for umeclidinium, ~27% for vilanterol; oral: negligible systemic absorption |
| Onset of Action | Inhalation: within 5-15 minutes (based on bronchodilation for Umeclidinium/Vilanterol); full clinical benefit over days to weeks |
| Duration of Action | Clinically effective over 24 hours with once-daily dosing; sustained bronchodilation maintained |
One inhalation (100 mcg fluticasone furoate, 62.5 mcg umeclidinium, 25 mcg vilanterol) once daily via oral inhalation.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for GFR >=30 mL/min; insufficient data for GFR <30 mL/min, use with caution. |
| Liver impairment | Child-Pugh A or B: no adjustment; Child-Pugh C: use with caution or avoid due to increased fluticasone furoate exposure. |
| Pediatric use | Not approved for pediatric patients <18 years of age; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; initiate at recommended dose due to age-related renal impairment and comorbidities; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRELEGY ELLIPTA (TRELEGY ELLIPTA).
| Breastfeeding | Unknown whether components (fluticasone furoate, umeclidinium, vilanterol) are excreted in human milk. Caution advised; consider risk-benefit. M/P ratio not available. |
| Teratogenic Risk | Insufficient human data; animal studies indicate fetal harm at high doses. First trimester: No adequate studies; potential risk based on animal data. Second/third trimester: Avoid use unless clearly needed; corticosteroids may cause fetal growth restriction, adrenal suppression. |
| Fetal Monitoring |
■ FDA Black Box Warning
Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death. Therefore, Trelegy Ellipta is contraindicated in asthma without concomitant use of a long-term asthma control medication. The safety and efficacy of Trelegy Ellipta in asthma have not been established in pediatric patients.
| Serious Effects |
["Severe hypersensitivity to milk proteins or any ingredient","Primary treatment of status asthmaticus or acute episodes of COPD or asthma","Patients with asthma not on a long-term asthma control medication"]
| Precautions | ["Risk of asthma-related death","Deterioration of disease and acute episodes: not for relief of acute bronchospasm","Cardiovascular effects (e.g., increased heart rate, hypertension)"] |
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| Monitor maternal respiratory status, fetal growth (serial ultrasound), and neonatal adrenal function if used chronically. Assess for signs of adrenal insufficiency in neonate if maternal corticosteroids used. |
| Fertility Effects | No human data; animal studies show no impairment of fertility at clinically relevant doses. |