Introduction
Breo Ellipta is a combination inhaled medication containing fluticasone furoate (an inhaled corticosteroid) and vilanterol (a long-acting beta2-adrenergic agonist). It is manufactured by GlaxoSmithKline and delivered via the Ellipta dry powder inhaler device. This fixed-dose combination therapy is designed for the maintenance treatment of chronic obstructive pulmonary disease (COPD) and asthma in specific patient populations.
Mechanism of Action
Fluticasone furoate: A synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. It inhibits multiple inflammatory cells and mediators involved in asthma and COPD pathogenesis, reducing airway inflammation and hyperresponsiveness. Vilanterol: A long-acting beta2-adrenoceptor agonist (LABA) that stimulates intracellular adenylate cyclase, increasing cyclic adenosine monophosphate (cAMP) levels. This results in relaxation of bronchial smooth muscle and inhibition of immediate-release mediators from mast cells.The combination provides complementary mechanisms: anti-inflammatory effects from the corticosteroid and bronchodilation from the LABA.
Indications
FDA-Approved Indications:- Maintenance treatment of asthma in patients aged 18 years and older
- Long-term maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema
- Reduction of COPD exacerbations in patients with a history of exacerbations
Dosage and Administration
Standard dosing: 100 mcg fluticasone furoate/25 mcg vilanterol once daily Alternative strength: 200 mcg fluticasone furoate/25 mcg vilanterol once daily Administration:- Administer once daily at the same time each day
- Use the Ellipta inhaler orally; do not shake the device
- Do not exhale into the device
- Rinse mouth with water after inhalation without swallowing to reduce risk of oropharyngeal candidiasis
- Hepatic impairment: Use with caution in moderate to severe impairment
- Renal impairment: No dosage adjustment required
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Not approved for patients under 18 years
Pharmacokinetics
Absorption:- Fluticasone furoate: Systemic exposure primarily from lung absorption (15-20% of dose)
- Vilanterol: Rapid absorption from lung (70% bioavailability)
- Fluticasone furoate: Extensive tissue distribution, volume of distribution ~661 L
- Vilanterol: High plasma protein binding (94%)
- Fluticasone furoate: Hepatic metabolism via CYP3A4
- Vilanterol: Hepatic metabolism primarily via CYP3A4
- Fluticasone furoate: Primarily fecal excretion (≤2% renal excretion)
- Vilanterol: Renal excretion (70%) and fecal excretion (30%)
- Half-life: Fluticasone furoate ~24 hours; Vilanterol ~11 hours
Contraindications
- Primary treatment of status asthmaticus or acute episodes of COPD or asthma requiring intensive measures
- Hypersensitivity to milk proteins or any component of the formulation
- Significant cardiovascular disorders (arrhythmias, coronary insufficiency) without proper monitoring
Warnings and Precautions
Boxed Warning:- Long-acting beta2-adrenergic agonists increase the risk of asthma-related death
- Not indicated for relief of acute bronchospasm
- Paradoxical bronchospasm: Discontinue immediately if occurs
- Cardiovascular effects: May cause significant cardiovascular effects in some patients
- Immunosuppression: Potential increased risk of infections
- Reduced bone mineral density with long-term use
- Glaucoma and cataracts: Regular eye examinations recommended
- Hypercorticism and adrenal suppression: Monitor for systemic effects
- Hypokalemia and hyperglycemia: Monitor electrolytes and blood glucose
Drug Interactions
Strong CYP3A4 inhibitors:- Ketoconazole, ritonavir, clarithromycin
- May increase systemic corticosteroid and LABA effects
- Use with caution; consider alternative therapies
- May antagonize effects of vilanterol and produce severe bronchospasm
- May potentiate hypokalemia and ECG changes
- May potentiate cardiovascular effects of vilanterol
Adverse Effects
Common adverse reactions (≥1%):- Headache
- Oropharyngeal candidiasis
- Dysphonia
- Cough
- Diarrhea
- Nasopharyngitis
- Upper respiratory tract infection
- Pneumonia (in COPD patients)
- Cardiovascular events (tachycardia, palpitations)
- Paradoxical bronchospasm
- Hypersensitivity reactions
- Adrenal insufficiency
- Increased risk of osteoporosis with long-term use
Monitoring Parameters
- Pulmonary function tests (spirometry)
- Symptom control and exacerbation frequency
- Oropharyngeal examination for candidiasis
- Height and growth velocity in pediatric patients (off-label use)
- Bone mineral density with long-term use
- Electrolytes (potassium)
- Blood glucose levels
- Eye examinations for glaucoma and cataracts
- Signs and symptoms of adrenal insufficiency
Patient Education
Key counseling points:- Use once daily at the same time each day
- Not for relief of acute symptoms (have rescue inhaler available)
- Rinse mouth with water after each use without swallowing
- Do not stop abruptly without medical supervision
- Report any worsening symptoms, chest pain, palpitations, or visual changes
- Keep regular appointments for monitoring
- Proper inhaler technique demonstration essential
- Store in dry place away from moisture
- Discard 6 weeks after opening foil tray or when counter reads "0"
References
1. FDA Prescribing Information: Breo Ellipta (fluticasone furoate and vilanterol inhalation powder). 2022 2. Dransfield MT, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group randomised controlled trials. Lancet Respir Med. 2013 3. Martinez FJ, et al. Effect of fluticasone furoate and vilanterol on exacerbations of COPD in patients with moderate airflow obstruction. Am J Respir Crit Care Med. 2017 4. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2023 Report 5. Global Initiative for Asthma (GINA). 2023 Update 6. Woodcock A, et al. Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/salmeterol combination in patients with persistent asthma. J Allergy Clin Immunol Pract. 2014