Pulmoclear (Acebrophylline 100 mg + N-Acetylcysteine 600 mg) Tablets
Primary Indication
Pulmoclear is indicated for patients with moderate to severe COPD (FEV₁ 30-79% predicted) who experience ≥2 exacerbations per year despite optimal inhaled bronchodilator therapy. 1, 2
Patient Selection Criteria
- Documented moderate to severe airflow obstruction (post-bronchodilator FEV₁/FVC <0.70 and FEV₁ 30-79% predicted) 1, 2
- History of at least two acute exacerbations in the previous 2 years 1, 2
- Already receiving maximal inhaled therapy (long-acting bronchodilators ± inhaled corticosteroids) 1, 2
- Chronic bronchitis with viscous mucus production 3, 4
Dosing Schedule
Standard dose: One tablet (acebrophylline 100 mg + N-acetylcysteine 600 mg) twice daily for chronic prevention. 2, 3, 4
Key Dosing Considerations
- The N-acetylcysteine 600 mg twice daily component (total 1,200 mg/day) represents the high-dose regimen with proven efficacy in reducing exacerbations (rate ratio 0.69) 1, 2, 5
- Lower doses of N-acetylcysteine (<1,200 mg daily) show significantly less benefit (rate ratio 0.87) and are not recommended 1, 2
- Benefits require at least 6 months of continuous therapy to become significant, with optimal effects seen after 1-3 years of treatment 2, 6
- Acebrophylline 100 mg twice daily improves mucociliary clearance and reduces bronchial hyperresponsiveness 3, 4
Mechanism of Action
N-Acetylcysteine Component
- Reduces viscosity of respiratory secretions through cleavage of disulfide bonds in mucoproteins 2, 7
- Rapidly absorbed from GI tract with peak plasma concentration (0.35-4 mg/L) achieved within 1-2 hours 7
- Appears in active form in lung tissue and respiratory secretions quickly after administration 2, 7
Acebrophylline Component
- Contains ambroxol, which facilitates biosynthesis of pulmonary surfactant 3
- Contains theophylline-7 acetic acid as a carrier that raises blood levels of ambroxol 3
- Reduces mucus viscosity and adhesivity, improving ciliary clearance 3, 4
- Exerts anti-inflammatory effects by deviating phosphatidylcholine toward surfactant synthesis, making it unavailable for leukotriene production 3
Clinical Efficacy
This combination reduces annual COPD exacerbation rates by 22% and decreases hospitalizations from 18.1% to 14.1% (risk ratio 0.76), with a number needed to treat of 25 patients to prevent one hospitalization. 1, 2, 6
Evidence-Based Outcomes
- High-dose mucolytic therapy (≥1,200 mg N-acetylcysteine daily) shows rate ratio of 0.69 for exacerbation reduction 1, 2
- Acebrophylline improves respiratory function parameters (FEV₁, FVC, PaO₂) and reduces PaCO₂ significantly (P < 0.01) 4
- Progressive improvement in cough intensity, dyspnea, and sputum characteristics within 14 days 4
- Reduces frequency of bronchial obstruction episodes and need for β₂-agonists 3
Contraindications and Precautions
Absolute Contraindications
- Do NOT use during acute exacerbations of COPD or chronic bronchitis (Grade I recommendation - no evidence of effectiveness for acute treatment) 2, 6
- Active peptic ulcer disease (acebrophylline component may cause epigastric pain) 4
Relative Contraindications and Cautions
- Use with caution during pregnancy (N-acetylcysteine is less contraindicated than some respiratory medications but requires clinical judgment) 2
- Monitor theophylline levels if patient is on concurrent theophylline therapy, as acebrophylline contains theophylline-7 acetic acid 1, 3
- Patients who stop smoking while on therapy require monitoring, as tobacco use affects theophylline metabolism 1
- Charcoal administration may interfere with N-acetylcysteine absorption (up to 96% adsorption) 7
Adverse Effects
Common Adverse Effects (Well-Tolerated Overall)
- Gastrointestinal symptoms: Nausea, vomiting, diarrhea, epigastric pain (occur no more frequently than placebo even with prolonged use) 2, 6, 7, 4
- Only 3 of 30 patients (10%) in one study reported epigastric pain, which was not severe enough to require discontinuation 4
- Overall adverse event rate of 1.5% reported in large surveillance study of 3,076 patients 8
Serious Adverse Effects
- No clinically relevant changes in routine laboratory parameters (biochemical or hematological) 7, 4
- No evidence of significant harm with prolonged use over multiple years 6
- Excellent long-term safety profile with no increased adverse events compared to placebo 9, 6
Important Clinical Caveats
Treatment Context
- This is for chronic prevention ONLY, not acute exacerbation management 2, 6
- For acute exacerbations, use short-acting bronchodilators (Grade A) and systemic corticosteroids for 10-15 days (Grade A) instead 2
- Mucolytic therapy does not significantly impact mortality in respiratory disease 2, 6
- No demonstrable effect on quality of life in meta-analyses 2
Patient-Specific Factors
- Most effective in patients with moderate COPD (GOLD II) compared to severe disease (GOLD III) 2
- May be more effective in patients NOT receiving inhaled corticosteroids, with benefit potentially reduced in ICS users 2
- Benefits are best established in patients with moderate to severe airflow obstruction; limited data for mild or very severe COPD 9
Monitoring and Follow-Up
- Reassess clinical response after 6 months of continuous therapy, as benefits become significant at this timepoint 2, 6
- Continue long-term (1-3 years minimum) as benefits accumulate over time 1, 2, 6
- Monitor for drug interactions, particularly with theophylline, paracetamol, and anticancer agents 1, 7
Alternative Considerations
While the European Respiratory Society does not endorse routine combination of multiple mucolytic agents due to lack of high-quality evidence for additive benefit 9, the combination of acebrophylline with N-acetylcysteine in Pulmoclear provides complementary mechanisms: N-acetylcysteine's mucolytic action via disulfide bond cleavage 2, 7 and acebrophylline's surfactant enhancement plus anti-inflammatory effects 3, 4. No documented drug-drug interactions or increased adverse events have been reported when these agents are combined 9.