Fluticasone And Vilanterol

Introduction Overview

Generic Name

fluticasone and vilanterol

Brand Name

Breo Ellipta

Dosage Form

inhalation powder via preloaded inhaler device

Drug Class

Bronchodilator combinations

Pharmacokinetics

Absorption

Fluticasone furoate and vilanterol are administered by inhalation, allowing direct delivery to the lungs with minimal systemic absorption. Fluticasone furoate exhibits low oral bioavailability due to extensive first-pass metabolism and low gastrointestinal absorption. Vilanterol, a long-acting beta2-adrenergic receptor agonist, is rapidly absorbed from the lungs following inhalation, achieving peak plasma concentrations within minutes. The inhalation route ensures rapid onset of bronchodilation while minimizing systemic exposure to both agents.

Distribution

Fluticasone furoate demonstrates a large volume of distribution, rapidly partitioning into tissues, particularly lung tissue, where it exerts its anti-inflammatory effects. Plasma protein binding for fluticasone furoate is high, approximately 99%, limiting free drug in the systemic circulation. Vilanterol also has extensive tissue distribution with moderate plasma protein binding. Both agents have affinity for lung tissue receptors, facilitating their therapeutic action in airway inflammation and bronchoconstriction.

Metabolism

Fluticasone furoate is extensively metabolized primarily by the cytochrome P450 3A4 (CYP3A4) enzyme in the liver via oxidative metabolism into inactive metabolites. Vilanterol undergoes hepatic metabolism predominantly through CYP3A4 enzymes as well as other minor pathways including conjugation. Because both drugs are substrates of CYP3A4, coadministration with strong CYP3A4 inhibitors can increase systemic concentrations, potentially leading to enhanced adverse effects.

Elimination

The elimination half-life of fluticasone furoate following inhalation is approximately 24 hours, allowing once-daily dosing. Vilanterol has a plasma half-life of about 21 hours, supporting once-daily administration. Both drugs are primarily eliminated via feces through biliary excretion of metabolites, with negligible renal excretion. The prolonged retention in lung tissues contributes to sustained therapeutic effects.

Dosage Forms

Adults

For maintenance treatment of COPD in adults, the recommended dosage is one actuation of 100/25 mcg (fluticasone furoate/vilanterol) inhaled once daily. For asthma management in adults aged 18 and older, the dose can be either 100/25 mcg or 200/25 mcg once daily, depending on severity and clinical response.

Adolescents

In pediatric patients aged 12 to 17 years with asthma, the recommended dose is one actuation of 100/25 mcg once daily. For children aged 5 to 11 years, a lower dose of 50/25 mcg once daily is recommended for asthma maintenance therapy.

Special Populations

Breo Ellipta is not approved for children younger than 5 years old. In elderly patients, no dosage adjustment is typically necessary; however, regular monitoring of lung function and side effects is advised. No specific dosage recommendations are provided for patients with hepatic or renal impairment, but caution is warranted. Clinical monitoring is important in patients with comorbidities such as cardiovascular disease, glaucoma, or infections due to steroid and beta-agonist effects. The inhaler must be discarded 6 weeks after opening or when the dose counter reaches zero to ensure accurate dosing.

Mechanism Of Action

Breo Ellipta combines two pharmacologically active agents: fluticasone furoate, a corticosteroid, and vilanterol, a long-acting beta2-adrenergic receptor agonist (LABA). Fluticasone furoate exerts its effect by binding to glucocorticoid receptors in the cytoplasm of airway inflammatory cells, leading to translocation into the nucleus and modulation of gene transcription. This results in decreased production and release of pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules, ultimately reducing airway inflammation and hyperresponsiveness seen in asthma and COPD.

Vilanterol binds selectively to beta2-adrenergic receptors on airway smooth muscle cells, activating adenylate cyclase and increasing intracellular cyclic AMP concentrations. This cascade leads to relaxation of bronchial smooth muscle, bronchodilation, and improved airflow. Vilanterol also inhibits the release of mast cell mediators and decreases microvascular permeability, contributing to reduced bronchospasm.

The combination of fluticasone furoate and vilanterol provides complementary actions: the steroid component reduces underlying airway inflammation while the LABA provides sustained airway smooth muscle relaxation. This dual mechanism improves lung function, reduces symptom frequency, and decreases exacerbation rates in patients with asthma and COPD.

Clinically, Breo Ellipta is administered once daily due to the prolonged duration of action of both components, improving patient adherence. Importantly, vilanterol as monotherapy is contraindicated in asthma due to increased mortality risk; the presence of fluticasone mitigates this risk by controlling inflammation effectively.

Pharmacological Actions

Anti-inflammatory action via corticosteroid receptor activation reducing airway inflammation
Long-acting beta2-adrenergic receptor agonism causing sustained bronchodilation
Suppression of pro-inflammatory mediator release from airway cells
Reduction in airway hyperresponsiveness and remodeling
Improvement in pulmonary function by decreasing bronchospasm
Decrease in frequency and severity of COPD and asthma exacerbations
Inhibition of mast cell mediator release reducing allergy symptoms
Improvement of mucociliary clearance through decreased inflammation

Therapeutic Clinical Uses

Maintenance treatment of chronic obstructive pulmonary disease (COPD) to improve lung function and reduce exacerbations
Maintenance treatment of asthma in adults and pediatric patients aged 5 years and older
Reduction and control of asthma symptoms by preventing airway inflammation and bronchospasm
Prevention of COPD flare-ups and exacerbations
Long-term management of airway inflammation and bronchoconstriction in chronic respiratory diseases
Adjunct therapy to improve quality of life in asthma and COPD patients
Not indicated for acute relief of bronchospasm or rescue treatment

Side Or Adverse Effects

Oral thrush (opharyngeal candidiasis) due to local immunosuppression
Hoarseness and dysphonia associated with inhaled corticosteroids
Headache and back pain reported in clinical trials
Increased risk of pneumonia in COPD patients
Elevated blood pressure and palpitations related to beta2-agonist effects
Tachycardia, including fast or pounding heartbeat
Hypokalemia manifesting as muscle cramps or weakness
Hyperglycemia resulting in increased thirst and urination
Cough, sore throat, and nasal congestion
Blurred vision or eye pain indicating possible glaucoma or cataracts
Rare occurrences of hypersensitivity reactions including rash and angioedema
Potential worsening of infections due to immunosuppressive properties
Muscle pain or joint discomfort
Increased risk of osteoporosis with long-term corticosteroid use

Precautions

Not to be used for relief of acute bronchospasm or asthma attacks
Use caution in patients with cardiovascular disorders such as arrhythmias and hypertension
Regular monitoring for signs of glaucoma and cataracts during long-term use
Close observation in patients with diabetes due to potential hyperglycemia
Avoid abrupt discontinuation to prevent exacerbation of symptoms
Rinse mouth with water after inhalation to reduce risk of oral candidiasis
Monitor potassium levels in patients receiving other medications that may cause hypokalemia
Caution in patients with active or latent infections due to immunosuppressive effects
Assess bone mineral density in patients at risk of osteoporosis
Avoid use with other long-acting beta2-agonists unless instructed by a physician
Inform patients to seek immediate medical attention if worsening respiratory symptoms occur
Use lower doses in pediatric populations appropriate to age and severity
Advise patients to avoid exposure to chickenpox or measles infections
Ensure proper inhaler technique to maximize drug delivery and effect

Warnings

Not a rescue inhaler; ineffective for sudden bronchospasm or asthma attacks
Use with caution in patients allergic to fluticasone, vilanterol, or milk proteins
Risk of increased cardiovascular events including heart rate elevation
Potential suppression of the hypothalamic-pituitary-adrenal (HPA) axis with prolonged steroid use
Increased susceptibility to infections including pneumonia and tuberculosis
Potential for paradoxical bronchospasm in rare cases
Risk of glaucoma or cataracts with long-term corticosteroid use
May cause reduction in bone mineral density and osteoporosis
Risk of serious hypersensitivity reactions including anaphylaxis
Use cautiously in patients with seizures or thyroid disorders
Avoid concomitant use with other CYP3A4 inhibitors to prevent systemic toxicity
Potential for hormonal axis disturbances leading to adrenal insufficiency
Monitor for signs of hyperglycemia and electrolyte imbalance
Risk of increased mortality with LABA monotherapy in asthma, mitigated by combination with corticosteroid

Contraindications

Known hypersensitivity to fluticasone, vilanterol, or any excipients including milk proteins
Primary treatment of acute bronchospasm or status asthmaticus requiring immediate bronchodilation
Use of vilanterol as monotherapy in asthma due to increased mortality risk
Severe hypersensitivity to any inhaled corticosteroids or beta-agonists
Patients with untreated systemic fungal, bacterial, viral or parasitic infections
Concurrent use with other LABA-containing medications without physician guidance
Known intolerance or allergy to lactose or milk derivatives present in the device
Patients with acute asthma episodes needing rapid-acting bronchodilators
Children under 5 years old (not approved for use)
Patients with active ocular herpes simplex infection

Drug Interactions

Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) can increase systemic corticosteroid and beta-agonist exposure
Concurrent use with other long-acting beta2-agonists may increase risk of cardiovascular side effects
Use with monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants may potentiate cardiovascular effects
Beta-blockers, especially non-selective, may antagonize vilanterol bronchodilator effect
Other immunosuppressants may enhance risk of infections when used with fluticasone
Drugs that lower serum potassium (e.g., diuretics) may exacerbate hypokalemia risk
Systemic corticosteroids may enhance corticosteroid-related adverse effects
Avoid concomitant use with other medicines containing corticosteroids to prevent cumulative systemic effects
Use cautiously with medications affecting heart rhythm due to risk of arrhythmias
Concurrent use with CYP3A4 inducers (e.g., rifampin) may decrease drug effectiveness
Herbal products affecting CYP3A4 (e.g., St. John's Wort) may reduce plasma concentrations
Potential pharmacodynamic interaction with other sympathomimetic agents
Concurrent use with antifungal agents may alter systemic fluticasone levels

Preparations Of The Drug

Inhalation powder delivered via a preloaded Ellipta inhaler device
Available strengths per actuation: 50 mcg fluticasone furoate / 25 mcg vilanterol
100 mcg fluticasone furoate / 25 mcg vilanterol
200 mcg fluticasone furoate / 25 mcg vilanterol
Single dose blister strips within the inhaler providing measured doses
Unit-dose ready to use inhaler with integrated dose counter
Packaged in sealed foil trays to maintain powder stability until opening
Designed for oral inhalation once daily
Each inhaler device designed for 30 doses (30 days of treatment)
Discard device 6 weeks after opening foil packaging or when doses are exhausted