Trelegy Ellipta - Drug Monograph

Introduction

Trelegy Ellipta is a combination inhaled medication containing three active components: fluticasone furoate (an inhaled corticosteroid), umeclidinium (a long-acting muscarinic antagonist), and vilanterol (a long-acting beta2-adrenergic agonist). It represents the first FDA-approved triple therapy in a single inhaler device for maintenance treatment of specific respiratory conditions. The Ellipta dry powder inhaler delivery system provides simplified dosing for patients requiring multiple inhaled medications.

Mechanism of Action

Trelegy Ellipta combines three mechanistically distinct medications:

The triple combination provides complementary anti-inflammatory and bronchodilatory effects through different pathways.

Indications

• Maintenance treatment of asthma in patients aged 18 years and older
• Maintenance treatment of chronic obstructive pulmonary disease (COPD), including:

- Chronic bronchitis - Emphysema

• Reduction of COPD exacerbations in patients with a history of exacerbations

Dosage and Administration

• One inhalation once daily at the same time each day
• Do not exceed recommended dosage
• Use dry powder inhaler (Ellipta device) only
• Do not shake device
• Rinse mouth with water after inhalation without swallowing to reduce risk of oropharyngeal candidiasis

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution in severe impairment
• Geriatric patients: No dosage adjustment required
• Pediatric patients: Not approved for patients under 18 years

Pharmacokinetics

• Fluticasone furoate: Systemic bioavailability approximately 15.2%
• Umeclidinium: Systemic bioavailability approximately 13%
• Vilanterol: Systemic bioavailability approximately 27%
• Peak plasma concentrations achieved within 5-15 minutes

• All components extensively distributed
• Fluticasone furoate: Volume of distribution ~661 L
• Umeclidinium: Volume of distribution ~86 L
• Vilanterol: Volume of distribution ~213 L
• High plasma protein binding (>96% for all components)

• Extensive hepatic metabolism primarily via CYP3A4
• Fluticasone furoate: Hydrolysis and oxidative metabolism
• Umeclidinium: Hydrolysis and oxidation
• Vilanterol: O-dealkylation followed by conjugation

• Fluticasone furoate: Feces (~101%) and urine (<1%)
• Umeclidinium: Feces (~92%) and urine (~9%)
• Vilanterol: Feces (~70%) and urine (~30%)
• Terminal half-lives: Fluticasone furoate (~24h), Umeclidinium (~19h), Vilanterol (~11h)

Contraindications

• Hypersensitivity to any component or milk proteins
• Primary treatment of status asthmaticus or acute episodes requiring intensive measures
• Significant hypersensitivity to milk proteins (device contains lactose)

Warnings and Precautions

• Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death
• Not indicated for relief of acute symptoms

• Paradoxical bronchospasm: Discontinue immediately if occurs
• Cardiovascular effects: Increased risk of cardiovascular events
• Immunosuppression: Potential increased risk of infections
• Reduced bone mineral density with long-term use
• Glaucoma and cataracts: Regular ophthalmological exams recommended
• Hypokalemia and hyperglycemia: Monitor particularly in diabetic patients
• Coexisting conditions: Use with caution in patients with cardiovascular disorders, seizures, or thyrotoxicosis

Drug Interactions

• Increased systemic corticosteroid and LABA effects
• Avoid concurrent use if possible

• Reduced effectiveness of vilanterol
• May produce severe bronchospasm in patients with asthma

• May exacerbate ECG changes and hypokalemia

• May potentiate cardiovascular effects of vilanterol

• Potential additive effects with umeclidinium

Adverse Effects

• Headache (8%)
• Nasopharyngitis (5%)
• Upper respiratory tract infection (4%)
• COPD exacerbation (3%)
• Cough (3%)
• Back pain (3%)
• Diarrhea (2%)
• Dysphonia (2%)
• Oropharyngeal candidiasis (1%)

• Pneumonia (in COPD patients)
• Cardiovascular events (tachycardia, palpitations, hypertension)
• Systemic corticosteroid effects
• Acute narrow-angle glaucoma
• Paradoxical bronchospasm
• Hypersensitivity reactions (anaphylaxis, angioedema)

Monitoring Parameters

• Pulmonary function tests (FEV1, peak flow)
• Frequency of exacerbations
• Asthma/COPD symptom control
• Oropharyngeal examination for candidiasis
• Blood glucose levels (particularly in diabetic patients)
• Electrolytes (especially potassium)
• Blood pressure and heart rate
• Ophthalmological exams (with long-term use)
• Bone mineral density (with long-term use)
• Growth velocity in pediatric patients (if used off-label)
• Signs/symptoms of infection

Patient Education

• Demonstrate correct use of Ellipta device
• Keep device dry; never wash mouthpiece
• Do not exhale into device
• Close cover after each use

• Use once daily at same time each day
• Do not use for acute symptoms (have rescue inhaler available)
• Rinse mouth after use without swallowing
• Never stop medication abruptly without medical supervision
• Report any vision changes, eye pain, or redness immediately
• Notify healthcare provider if symptoms worsen or if needing more rescue medication
• Keep all appointments for monitoring

• Store at room temperature (68°F-77°F/20°C-25°C)
• Keep in unopened tray until ready for use
• Discard 6 weeks after opening foil tray or when counter reads "0"

References

1. FDA Prescribing Information: Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol). Revised 2023. 2. Lipson DA, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671-1680. 3. Papi A, et al. Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol versus Dual Therapy in Asthma: A Randomized Controlled Trial. Am J Respir Crit Care Med. 2021;204(6):650-659. 4. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2023 Report. 5. Global Initiative for Asthma (GINA). 2023 Update. 6. Kerwin EM, et al. Efficacy and safety of triple therapy with fluticasone furoate/umeclidinium/vilanterol versus dual therapy in COPD: A systematic literature review and meta-analysis. Respir Med. 2020;171:106099. 7. Dransfield MT, et al. Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Outcomes in the IMPACT Trial. Chest. 2021;159(1):138-150.