What is the best way to break up inhalers for a patient with Chronic Obstructive Pulmonary Disease (COPD) who cannot afford triple therapy, which typically includes a Long-Acting Muscarinic Antagonist (LAMA), a Long-Acting Beta Agonist (LABA), and an Inhaled Corticosteroid (ICS)?

Cost-Effective Alternatives to Single-Inhaler Triple Therapy for COPD

If a patient cannot afford single-inhaler triple therapy (LAMA/LABA/ICS), the most cost-effective approach is to use separate inhalers: one LAMA/LABA dual-therapy inhaler combined with a separate ICS inhaler, though this is explicitly less preferred than single-inhaler triple therapy due to reduced adherence and increased inhalation technique errors. 1

Understanding the Components of Triple Therapy

Triple therapy consists of three medication classes that must all be present: 1

• LAMA (Long-Acting Muscarinic Antagonist) - e.g., tiotropium, umeclidinium, glycopyrronium
• LABA (Long-Acting Beta-Agonist) - e.g., salmeterol, formoterol, vilanterol
• ICS (Inhaled Corticosteroid) - e.g., fluticasone, budesonide, beclometasone

Multiple-Inhaler Approach to Achieve Triple Therapy

Option 1: LAMA/LABA + Separate ICS (Preferred Multiple-Inhaler Strategy)

Use a combination LAMA/LABA inhaler (one device) plus a separate ICS inhaler (second device). 1

Specific combinations:

• LAMA/LABA dual inhaler (e.g., umeclidinium/vilanterol, tiotropium/olodaterol, glycopyrronium/formoterol) PLUS
• Separate ICS inhaler (e.g., fluticasone propionate, budesonide, beclometasone)

Dosing: 2

• LAMA/LABA: typically one inhalation twice daily
• ICS: dosing varies by product, but moderate doses are sufficient (e.g., budesonide 320 mcg showed mortality benefit without requiring higher doses) 1, 3

Option 2: ICS/LABA + Separate LAMA (Alternative Multiple-Inhaler Strategy)

Use a combination ICS/LABA inhaler (one device) plus a separate LAMA inhaler (second device). 1, 2

Specific combinations:

• ICS/LABA dual inhaler (e.g., fluticasone/salmeterol, budesonide/formoterol) PLUS
• Separate LAMA inhaler (e.g., tiotropium)

Important caveat: This approach is less optimal than Option 1 because LAMA/LABA dual therapy is preferred over ICS/LABA due to superior lung function improvements and lower pneumonia rates. 1

Critical Implementation Points

Patient Selection Criteria for Triple Therapy

Only use triple therapy (whether single or multiple inhalers) if the patient meets ALL of the following: 1, 4

• High exacerbation risk: ≥2 moderate exacerbations OR ≥1 severe exacerbation (requiring hospitalization/ED visit) in the past year
• Moderate-to-high symptom burden: CAT score ≥10 OR mMRC score ≥2
• Impaired lung function: FEV1 <80% predicted

If the patient does NOT meet these criteria, triple therapy is not indicated—use LAMA/LABA dual therapy instead. 1

Adherence and Technique Concerns

Multiple-inhaler triple therapy has significant disadvantages: 1, 4

• Reduced medication adherence compared to single-inhaler triple therapy
• Increased risk of inhalation technique errors
• More complex treatment regimen

To mitigate these risks: 1

• Provide thorough inhaler technique training for EACH device
• Schedule regular follow-up to assess adherence and technique
• Consider using devices with dose counters to monitor usage

Safety Monitoring

Pneumonia risk: 1, 4, 3, 5

• ICS-containing regimens increase pneumonia risk (number needed to harm = 33 patients treated for one year)
• Monitor closely if patient is: current smoker, age ≥55 years, BMI <25 kg/m², history of pneumonia, or severe airflow limitation
• Budesonide and beclometasone may have lower pneumonia risk than fluticasone furoate 6

Oral candidiasis prevention: 2

• Instruct patient to rinse mouth with water without swallowing after EVERY inhalation
• Monitor periodically for oral thrush

Dosing Considerations

ICS dosing: 1, 3

• Moderate doses are sufficient—the dose-response curve is relatively flat
• Higher ICS doses increase adverse effects without proportional benefit
• Budesonide 320 mcg demonstrated mortality benefit in the ETHOS trial without requiring higher doses

Timing: 2

• Administer all components twice daily, approximately 12 hours apart
• If using separate inhalers, take them at the same time to maintain simplicity

What NOT to Do

Never use ICS as monotherapy—ICS must always be combined with long-acting bronchodilators. 1, 4

Never add a second LABA—if the patient is already on a LABA-containing inhaler, do not prescribe additional LABA due to overdose risk. 2

Never step down from triple therapy to dual therapy in patients at high exacerbation risk, especially if blood eosinophils ≥300 cells/µL, as this increases exacerbation risk. 1, 3, 7

Do not use systemic oral corticosteroids (e.g., prednisone) for maintenance treatment. 1

Cost-Saving Alternatives If Triple Therapy Is Not Indicated

If the patient does NOT meet criteria for triple therapy (low exacerbation risk): 1, 8

• Use LAMA/LABA dual therapy alone (no ICS needed)
• This avoids ICS-related costs and pneumonia risk
• LAMA/LABA provides superior efficacy and safety compared to ICS/LABA in patients without high exacerbation risk 9