Breo Ellipta (Fluticasone Furoate / Vilanterol)
fluticasone furoate and vilanterol inhalation powder
Indications
| Indication | Approved Population | Approved Strength(s) | Status |
|---|---|---|---|
| COPD — maintenance treatment and exacerbation reduction | Adults | 100/25 mcg only | FDA Approved |
| Asthma — once-daily maintenance treatment | ≥5 years | 50/25 (5–11 y); 100/25 (12–17 y); 100/25 or 200/25 (≥18 y) | FDA Approved |
Breo Ellipta is the only ICS/LABA combination approved for once-daily dosing, enabled by the prolonged lung retention of fluticasone furoate (~24-hour apparent half-life) and the sustained bronchodilation of vilanterol (~11-hour half-life). In asthma, it is reserved for patients not adequately controlled on ICS alone or whose severity warrants dual therapy. For COPD, only the 100/25 strength is approved. Breo Ellipta is not for the relief of acute bronchospasm.
Dosing
COPD — Adults
| Clinical Scenario | Dose | Maximum | Notes |
|---|---|---|---|
| COPD maintenance & exacerbation reduction | 1 inhalation of 100/25 mcg once daily | 100/25 mcg once daily | Only approved COPD strength; do not increase dose No priming required for the Ellipta inhaler |
Asthma — Adults (≥18 Years)
| Clinical Scenario | Starting Dose | Maximum Dose | Notes |
|---|---|---|---|
| Persistent asthma — not controlled on ICS alone or warranting dual therapy | 1 inh of 100/25 mcg once daily | 1 inh of 200/25 mcg once daily | Choose strength based on severity and current ICS dose If 100/25 inadequate, step up to 200/25; median onset ~15 min |
Asthma — Adolescents (12–17 Years)
| Clinical Scenario | Dose | Maximum | Notes |
|---|---|---|---|
| Persistent asthma — not controlled on ICS alone | 1 inh of 100/25 mcg once daily | 100/25 mcg once daily | Only strength approved for ages 12–17 200/25 is NOT approved for this age group |
Asthma — Pediatric (5–11 Years)
| Clinical Scenario | Dose | Maximum | Notes |
|---|---|---|---|
| Persistent asthma — not controlled on ICS alone | 1 inh of 50/25 mcg once daily | 50/25 mcg once daily | Only strength approved for ages 5–11 Monitor growth routinely via stadiometry |
Breo Ellipta is unique among ICS/LABA combinations in offering true once-daily dosing. This is supported by fluticasone furoate’s prolonged lung retention — 90% absorption takes 20–30 hours compared with ~8 hours for fluticasone propionate. The Ellipta dry powder inhaler requires no priming and provides consistent dose delivery. Patients should use it at the same time every day and never exceed 1 inhalation per 24 hours.
Pharmacology
Mechanism of Action
Fluticasone furoate (ICS component): A synthetic trifluorinated corticosteroid with enhanced glucocorticoid receptor (GR) binding affinity — approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate. FF demonstrates the largest cellular accumulation and slowest efflux rate among clinically used ICS in vitro, consistent with prolonged tissue retention that supports once-daily efficacy. It suppresses inflammatory mediators and cell recruitment via GR-mediated transcriptional regulation.
Vilanterol (LABA component): A selective, long-acting beta2-adrenergic agonist with an onset of bronchodilation within approximately 15 minutes and sustained activity over 24 hours. Vilanterol relaxes bronchial smooth muscle through beta2-receptor stimulation and increased intracellular cyclic AMP. The ICS/LABA combination provides complementary anti-inflammatory and bronchodilator effects.
ADME Profile
| Parameter | Fluticasone Furoate | Vilanterol |
|---|---|---|
| Absorption | Systemic bioavailability 15.2% (inhaled); oral bioavailability ~1.26% (extensive first-pass); prolonged lung absorption (90% absorption over 20–30 h) | Systemic bioavailability 27.3% (inhaled); rapid absorption; minimal oral bioavailability due to first-pass metabolism |
| Distribution | Vd: ~661 L; protein binding: >99.6%; GR affinity 29.9× dexamethasone | Protein binding: 93.9% |
| Metabolism | Hepatic via CYP3A4 to inactive metabolites; fecal excretion primary | Hepatic via CYP3A4 (O-dealkylation); urinary excretion 70%, fecal 30% |
| Elimination | Apparent t½: ~24 h (absorption-rate limited from lung); IV t½: ~14 h | t½: ~11 h |
Side Effects
COPD (FDA PI Table 2 — 100/25 mcg, 6-Month Trials)
| Adverse Effect | Breo 100/25 | Placebo | Clinical Note |
|---|---|---|---|
| Nasopharyngitis | 9% | 8% | Most common event |
| Upper respiratory tract infection | 7% | 3% | Higher than placebo |
| Headache | 7% | 5% | Dose-related across FF strengths |
| Oropharyngeal candidiasis | 5% | 2% | Includes oral candidiasis and fungal oropharyngitis; emphasize mouth rinsing |
In 12-month COPD trials (n=806 on 100/25), additional adverse events at ≥3% included: back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, influenza, pharyngitis, and pyrexia. In the mortality trial (16,568 patients, median 1.5 years), pneumonia, back pain, hypertension, and influenza occurred at ≥3%.
Asthma (FDA PI Table 3 — 100/25 mcg, Trial 8)
| Adverse Effect | Breo 100/25 | Placebo | Clinical Note |
|---|---|---|---|
| Nasopharyngitis | 10% | 7% | Most common event in asthma trials |
| Headache | 5% | 4% | Similar rate at 200/25 (Table 4: 8%) |
| Oral candidiasis | 2% | 0% | Includes oral and oropharyngeal candidiasis |
| Oropharyngeal pain | 2% | 1% | |
| Dysphonia | 2% | 0% | ICS class effect |
Pediatric Asthma (FDA PI Table 5 — Trial 14, Ages 5–17)
| Adverse Effect | Breo Ellipta | FF Alone | Clinical Note |
|---|---|---|---|
| Nasopharyngitis | 10% | 8% | 100/25 for 12–17 y; 50/25 for 5–11 y |
| Upper respiratory tract infection | 7% | 6% | |
| Allergic rhinitis | 4% | 1% | |
| Headache | 3% | 2% | |
| Rhinitis | 3% | 1% | |
| Viral upper respiratory tract infection | 3% | <1% |
| Adverse Effect | Data | Typical Onset | Required Action |
|---|---|---|---|
| Pneumonia (COPD) | 6% (100/25) vs 3% vilanterol (12-mo trials, 3,255 pts); fatal pneumonia: 1 pt (100/25), 7 pts (200/25) | Variable | Monitor vigilantly; differentiate from COPD exacerbation; chest imaging if suspected |
| Pneumonia (COPD mortality trial) | 3.4/100 pt-yr (100/25) vs 3.2 placebo (16,568 pts, median 1.5 yr); pneumonia deaths: 13 vs 9 | Variable | Risk similar to placebo in mortality trial; however, deaths numerically higher |
| Bone fractures (COPD) | 2% FF/vilanterol vs <1% vilanterol alone (12-mo trials) | Months to years | Assess BMD at initiation (COPD) and periodically; consider osteoporosis therapy |
| Cardiovascular events (COPD mortality trial) | 2.5/100 pt-yr (100/25) vs 2.7 placebo; CV deaths: 82 vs 86 | Variable | No increased CV risk demonstrated vs placebo |
| Adrenal suppression / HPA dysfunction | Rare at recommended doses | Weeks to months | Monitor during steroid taper; cortisol assessment if Cushingoid features |
| Paradoxical bronchospasm | Rare (postmarketing) | Immediately after inhalation | Rescue bronchodilator; discontinue Breo; alternative therapy |
Drug Interactions
Both fluticasone furoate and vilanterol are CYP3A4 substrates. Ketoconazole increases systemic exposure to both components. The PI notes potential for both increased systemic corticosteroid effects and increased cardiovascular adverse effects with strong CYP3A4 inhibitors.
Monitoring
- Lung FunctionBaseline; then q3–12 mo
RoutineMedian onset ~15 min (100 mL FEV1 increase). If 100/25 inadequate in asthma adults, step up to 200/25. Do not increase COPD dose. - Oropharyngeal ExamEach visit
RoutineCandidiasis 5% in COPD, 2% in asthma. Reinforce mouth rinsing after every dose. - Pneumonia (COPD)Ongoing
Routine6% at 12 months (100/25) vs 3% vilanterol. Imaging if suspected; clinical features overlap with COPD exacerbation. - Growth (Pediatric)Every 3–6 months
RoutineICS class effect on growth velocity. Titrate to lowest effective dose. - OphthalmologyAnnually for long-term users
RoutineGlaucoma and cataracts reported with long-term ICS. Consider ophthalmology referral for visual symptoms. - Bone DensityBaseline (COPD); per risk factors
Trigger-basedFractures: 2% FF/vilanterol vs <1% vilanterol alone (12-mo COPD). Similar findings in the 16,568-patient mortality trial. - Adrenal FunctionDuring steroid taper; if Cushingoid features
Trigger-basedHPA effects not observed at therapeutic doses. Exceeding dose or using with strong CYP3A4 inhibitors may cause dysfunction.
Contraindications & Cautions
Absolute Contraindications
- Status asthmaticus or acute episodes of COPD/asthma requiring intensive measures
- Severe hypersensitivity to milk proteins — Breo Ellipta contains lactose monohydrate with milk proteins; anaphylaxis reported in patients with severe milk allergy after inhalation of other lactose-containing powder medications
- Known hypersensitivity to fluticasone furoate, vilanterol, or any excipient
Use with Caution
- Cardiovascular disorders — coronary insufficiency, arrhythmias, hypertension; at 4× recommended vilanterol dose, clinically significant QTc prolongation occurred in healthy subjects
- Convulsive disorders, thyrotoxicosis, diabetes mellitus
- Active or quiescent TB; untreated fungal, bacterial, viral, or parasitic infections; ocular herpes simplex
- Hepatic impairment (moderate-to-severe) — FF systemic exposure may increase; monitor for corticosteroid effects
- Concurrent strong CYP3A4 inhibitors — increased FF and vilanterol exposure
- Do not combine with other LABA-containing products
Long-acting beta2-adrenergic agonists such as vilanterol increase the risk of asthma-related death when used without an ICS. In the SMART trial with salmeterol, 13 asthma-related deaths per 13,176 subjects occurred (vs 3 per 13,179 on placebo; RR 4.37 [95% CI: 1.25, 15.34]). This is considered a class effect of all LABAs including vilanterol. When LABAs are used in fixed-dose combination with ICS, a meta-analysis of 3 trials (n=35,089) did not show a significant increase in serious asthma-related events (HR 1.10 [95% CI: 0.85, 1.44]). A pediatric trial (n=6,208) showed HR 1.29 (95% CI: 0.73, 2.27).
Deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids to ICS. Taper prednisone by 2.5 mg/day on a weekly basis after transferring to Breo Ellipta. Patients previously on ≥20 mg/day prednisone are most susceptible.
Patient Counselling
Purpose of Therapy
Breo Ellipta contains two medicines: fluticasone furoate (a corticosteroid that reduces airway inflammation) and vilanterol (a long-acting bronchodilator that relaxes airway muscles for 24 hours). It is the only ICS/LABA that needs to be taken just once a day. It is a controller — it must be used every day and is not for sudden breathing problems.
How to Take
Take 1 inhalation once daily at the same time each day. The Ellipta inhaler does not require priming or shaking. Open the cover to prepare a dose, exhale fully (not into the mouthpiece), inhale steadily and deeply, then hold your breath for 3–4 seconds. After every dose, rinse the mouth with water and spit it out. Do not take more than 1 inhalation every 24 hours. Always carry a separate rescue inhaler.
Sources
- Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) prescribing information. GlaxoSmithKline. Revised 11/2024. GSK Pro PI Primary source for all dosing, adverse reaction Tables 2–5, pneumonia/fracture/CV data, PK, boxed warning, and drug interaction guidance.
- DailyMed — Breo Ellipta label. National Library of Medicine. DailyMed Current structured FDA-approved labeling.
- Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD. Lancet Respir Med. 2013;1(3):210–223. DOI One of two replicate 12-month exacerbation trials (3,255 patients) providing pneumonia and fracture data.
- Vestbo J, Anderson JA, Brook RD, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT). Lancet. 2016;387(10030):1817–1826. DOI Mortality trial in 16,568 moderate COPD patients (median 1.5 yr); source of CV events and long-term pneumonia data.
- Bleecker ER, Lotvall J, O’Byrne PM, et al. Fluticasone furoate-vilanterol 100/25 mcg compared with fluticasone furoate 100 mcg in asthma (Trial 8). J Allergy Clin Immunol Pract. 2014;2(5):553–561. DOI Pivotal 12-week asthma efficacy trial; source of Table 3 adverse reaction data.
- Woodcock A, Vestbo J, Bakerly ND, et al. Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice (Salford Lung Study). Lancet. 2017;390(10109):2247–2255. DOI Real-world pragmatic trial demonstrating superior asthma control with FF/VI vs usual care ICS.
- Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2024 Update. GINA Reports Positions ICS/LABA at step 3+ in asthma management.
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD. 2024 Report. GOLD Reports COPD guideline; ICS/LABA for patients with exacerbation history and eosinophils ≥100–300.
- Salter M, Biggadike K, Matthews JL, et al. Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammation. Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L660–L667. DOI In vitro data establishing FF GR affinity at 29.9× dexamethasone and 1.7× fluticasone propionate.
- Allen A, Bareille PJ, Rousell VM. Fluticasone furoate, a novel inhaled corticosteroid, demonstrates prolonged lung absorption kinetics in man compared with inhaled fluticasone propionate. Clin Pharmacokinet. 2013;52(1):37–42. DOI Key PK study demonstrating 90% lung absorption over 20–30 h for FF vs 8 h for FP; supports once-daily dosing.
- Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic index. Br J Clin Pharmacol. 2015;80(3):372–380. DOI Comparative review of ICS potency and PK properties including FF: Vd ~661 L, protein binding >99.6%, systemic bioavailability 15.2%.
- Kempsford RD, Oliver A, Bal J, et al. The efficacy of once-daily fluticasone furoate/vilanterol in asthma is comparable with morning or evening dosing. Respir Med. 2013;107(12):1873–1880. DOI Demonstrates equivalent efficacy whether FF/VI is dosed in the morning or evening, supporting dosing flexibility.