When do you prescribe Trelegy (fluticasone furoate/umeclidinium/vilanterol) for asthma?

When to Prescribe Trelegy for Asthma

Trelegy (fluticasone furoate/umeclidinium/vilanterol) should be prescribed for patients with inadequately controlled moderate to severe asthma who remain symptomatic despite treatment with medium-to-high dose inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combination therapy. 1

Primary Indication

Trelegy is indicated for patients with uncontrolled asthma on ICS/LABA therapy who require additional bronchodilation. The addition of the long-acting muscarinic antagonist (LAMA) umeclidinium to the ICS/LABA combination provides enhanced lung function improvements, particularly in patients with fixed airway obstruction. 1, 2

Specific Clinical Scenarios for Prescribing

Step-Up from ICS/LABA Therapy

• Prescribe Trelegy when patients on medium-to-high dose ICS/LABA (such as fluticasone furoate/vilanterol 100/25 mcg or 200/25 mcg) continue to have inadequate symptom control, suboptimal lung function, or frequent exacerbations. 1

• The triple therapy combination (FF/UMEC/VI) demonstrated clinically meaningful improvements in trough FEV1 compared to dual therapy (FF/VI), with treatment differences of 69-105 mL in clinical trials. 1

Patients with Fixed Airway Obstruction

• Trelegy may provide the greatest benefit in asthma patients with fixed airway obstruction, where improvements in trough FEV1 ranged from 0.095-0.304 L compared to ICS alone. 2

• In contrast, patients without fixed obstruction showed minimal benefit (-0.084 to 0.041 L), suggesting that the presence of fixed obstruction should guide the decision to add LAMA therapy. 2

Dosing Options

Available strengths for asthma include: 1

• FF/UMEC/VI 100/31.25/25 mcg
• FF/UMEC/VI 100/62.5/25 mcg
• FF/UMEC/VI 200/31.25/25 mcg
• FF/UMEC/VI 200/62.5/25 mcg

The choice between 31.25 mcg and 62.5 mcg umeclidinium doses should be based on the degree of bronchodilation needed, with higher doses (62.5 mcg) showing greater FEV1 improvements. 1, 2

When NOT to Prescribe Trelegy

Contraindications and Inappropriate Use

• Do not prescribe Trelegy as initial controller therapy for asthma. Current guidelines recommend starting with low-dose ICS for mild persistent asthma and low-to-medium dose ICS/LABA for moderate persistent asthma. 3, 4

• Do not use Trelegy for acute symptom relief or status asthmaticus. 5

• Avoid in patients with severe hypersensitivity to milk proteins or any ingredients. 5

• Do not prescribe in combination with other LABA-containing medications due to overdose risk. 5

Guideline-Based Treatment Algorithm

The stepwise approach to asthma management dictates the following progression: 3, 4

1. Step 3 (Moderate Persistent): Low-to-medium dose ICS/LABA is the preferred first-line treatment 3
2. Step 4 (Severe Persistent): High-dose ICS/LABA is recommended 3, 4
3. Beyond Step 4: When high-dose ICS/LABA fails to achieve control, consider adding a third controller medication (such as LAMA) or oral corticosteroids 6

Trelegy fits into the treatment algorithm as a step-up option when dual ICS/LABA therapy at appropriate doses has proven insufficient. 1

Important Clinical Considerations

Safety Profile

• The safety profile of Trelegy in asthma patients is consistent with its individual components, with no new safety concerns identified. 1

• Common adverse events include nasopharyngitis, oral candidiasis, headache, and upper respiratory tract infections. 5

• Monitor for systemic corticosteroid effects, particularly in patients with hepatic impairment, as fluticasone furoate exposure may increase. 5

Pharmacokinetic Considerations

• Systemic exposures of fluticasone furoate and vilanterol are similar whether administered as triple therapy (FF/UMEC/VI) or dual therapy (FF/VI), indicating no pharmacokinetic interaction when adding umeclidinium. 7

• No dose adjustments are necessary based on body weight, creatinine clearance, or race, as covariate effects were marginal. 7

Common Pitfalls to Avoid

• Do not prescribe Trelegy before optimizing ICS/LABA therapy and confirming adequate inhaler technique and adherence. 6

• Do not use Trelegy in patients who have not demonstrated inadequate control on ICS/LABA, as this represents inappropriate step-up therapy. 1

• Avoid using strong CYP3A4 inhibitors (e.g., ketoconazole) concurrently, as they may cause systemic corticosteroid and cardiovascular effects. 5

• Do not overlook treatable comorbidities (allergic rhinitis, GERD, sinusitis) that may contribute to poor asthma control before adding triple therapy. 4