In adults with chronic obstructive pulmonary disease who remain symptomatic despite optimal inhaled therapy, what is the role of Abiways (acebrophylline 200 mg + montelukast 10 mg) as an adjunctive oral treatment?

Role of Abiways (Acebrophylline + Montelukast) in COPD

Abiways (acebrophylline 200 mg + montelukast 10 mg) is not recommended as adjunctive therapy in COPD patients who remain symptomatic despite optimal inhaled therapy, as neither component is supported by major international COPD guidelines for routine use in this disease. 1

Why This Combination Is Not Guideline-Supported

Montelukast Has No Established Role in COPD

• The European Respiratory Society explicitly advises that montelukast should not be routinely prescribed for COPD patients due to lack of supporting evidence in guidelines and limited research data. 1
• Montelukast is primarily indicated for asthma management as an alternative therapy for mild persistent asthma, not for COPD. 1
• While one small retrospective study in 20 elderly male patients suggested potential benefits with montelukast 10 mg daily over 23 months (reduced exacerbations, symptoms, and healthcare utilization), this was a preliminary observation without controlled design and has not been validated in larger trials or incorporated into guidelines. 2
• A guinea pig model study showed montelukast reduced neutrophilic inflammation in LPS-induced chronic pulmonary inflammation, but animal models do not translate to clinical recommendations. 3

Acebrophylline (Theophylline Derivative) Has Limited, Conditional Use

• The European Respiratory Society suggests considering theophylline only as a third-line option after inhaled treatments have been optimized, and only "with reservations." 4
• Theophylline/aminophylline should be used with extreme caution due to narrow therapeutic window, significant drug interactions, and risk of cardiac arrhythmias, GI upset, and tachycardia. 1, 4
• The American College of Chest Physicians recommends avoiding theophylline-based agents unless patients demonstrate clear failure to respond to optimal standard therapy, due to lack of proven benefit and significant adverse effect risk. 4

What Guidelines Actually Recommend for Symptomatic COPD Despite Optimal Inhaled Therapy

First-Line Approach: Optimize Inhaled Therapy

• Ensure patients are on combination LABA/LAMA therapy as the foundation, which provides superior symptom control and exacerbation reduction compared to monotherapy. 1, 5
• For patients with frequent exacerbations (≥2 per year or ≥1 requiring hospitalization), triple therapy with LABA/LAMA/ICS should be considered. 6, 1, 5

Evidence-Based Oral Add-On Therapies for Persistent Exacerbations

If patients continue to exacerbate despite optimal triple inhaled therapy:

1. Long-term macrolide therapy (Grade 2A recommendation) - For patients with moderate to severe COPD who have ≥1 moderate or severe exacerbation in the previous year despite optimal maintenance inhaler therapy. 6, 1

   • Must check QT interval on ECG, assess for drug interactions, and rule out atypical mycobacterial infection before initiating. 6, 1
   • Long-term azithromycin and erythromycin reduce exacerbations over 1 year. 7

2. Roflumilast - Reduces moderate and severe exacerbations in patients with chronic bronchitis phenotype, severe to very severe COPD, and exacerbation history. 6, 7

3. High-dose oral mucolytic agents (conditional recommendation) - For patients with moderate or severe airflow obstruction (FEV1 30-79% predicted) and exacerbations despite optimal inhaled therapy. 6

   • N-acetylcysteine 600 mg twice daily or carbocysteine reduces hospitalizations and exacerbations. 6, 8
   • The beneficial effect is driven by high-dose regimens. 6

Critical Pitfalls to Avoid

• Do not use ICS monotherapy in COPD - it is not supported by evidence and combination ICS/LABA is superior. 6, 7
• Do not continue long-term oral corticosteroids - risks far outweigh any potential benefits. 7, 5
• Do not prescribe macrolides without checking QT interval and baseline hearing - serious adverse effects including QT prolongation and hearing loss are documented. 6, 7
• Do not add theophylline derivatives as routine therapy - reserve only for refractory cases with close monitoring of serum levels (target 5-15 μg/mL) and cardiac monitoring. 1, 4

Bottom Line

Instead of Abiways, ensure your patient is on optimal LABA/LAMA or triple therapy (LABA/LAMA/ICS if frequent exacerbations), then add evidence-based oral therapies in this order: macrolides (if appropriate after safety screening), roflumilast (for chronic bronchitis phenotype), or high-dose mucolytics. 6, 1, 7