Medications in COPD Management

Aka: Medications in COPD Management, COPD Preparations

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II. Preparations: Bronchodilators - Inhaled Anticholinergics (e.g. Tiotropium, Ipratropium Bromide)

  1. Efficacy
    1. Greater bronchodilation than Beta Agonists in COPD
    2. Combined with beta Agonist may offer additive effect
    3. No tachyphylaxis
    4. Decreases bronchoconstriction by inhibiting cGMP
  2. Safety
    1. Short-acting Anticholinergics (e.g. Ipratropium) are associated with increased cardiovascular events
      1. Avoid short acting Anticholinergics (Ipratropium) in comorbid cardiovascular disease
      2. Ogale (2010) Chest 137(1): 13-19 [PubMed]
      3. Singh (2008) JAMA 300(12): 1439-50 [PubMed]
  3. Single Agent Medications
    1. Long-acting agents (LAMA)
      1. Aclidinium (Tudorza) once twice daily
      2. Tiotropium (Spiriva) once daily
    2. Short-acting agents (see safety precautions above)
      1. Ipratropium Bromide (Atrovent) 2-3 puffs qid
        1. In crisis may be used up to 6 to 8 puffs q3-4 hours
      2. Ipratropium Bromide 500 ug vial nebulized four times daily
  4. Combination Medications
    1. Short-Acting Combination agents
      1. Duoneb (Nebulized Ipratropium Bromide and Albuterol)
      2. Combivent (Ipratropium with Albuterol)
        1. Significant cost savings when combined
        2. Benayoun (2001) Chest 119:85-92 [PubMed]
    2. Long-Acting Combination Agents
      1. Anoro Ellipta (Umeclidinium and Vilanterol)
        1. Once daily preparation (2014 release in U.S.)
        2. Long acting Anticholinergic (umeclidinum) and long acting beta Agonist (Vilanterol)
      2. Stiolto Respimat (Tiotropium and olodaterol)
        1. Two inhalations once daily (2015 release in U.S.)
        2. Long acting Anticholinergic (Tiotropium) and long acting beta Agonist (olodaterol)

III. Preparations: Bronchodilators - Inhaled Beta-Agonists

  1. Efficacy
    1. Spirometry improved 15% and decreased rate of annual FEV1 decline with Long-Acting Beta Agonist (LABA)
    2. Significant symptom improvement also suggests benefit
    3. Use with spacer always due to lack of lung excursion
    4. Give prn unless jittery (precedes cardiotoxicity)
  2. Safety
    1. Low risk of precipitating major cardiovascular events in COPD without Asthma
      1. Salpeter (2004) Chest 125:2309-21 [PubMed]
    2. Comorbid Asthma, however, is associated with adverse outcomes with Long-Acting Beta Agonist (LABA)
      1. LABA use in Asthma was associated with increased Asthma deaths, increased intubations and hospitalizations
      2. McMahon (2011) Pediatrics 128(5): e1147-54 [PubMed]
  3. Long-Acting Beta Agonist for maintenance
    1. Arformoterol (Brovana) 15 mcg twice daily
    2. Formoterol (Foradil) once twice daily
    3. Indacaterol (Arcapta) once daily
    4. Salmeterol (Serevent Discus) once twice daily
    5. Effective and safe (no increased vascular events)
    6. Ferguson (2003) Chest 123:1817-24 [PubMed]
  4. Short-acting Beta Agonist for rescue
    1. Albuterol 2 puffs every 4-6 hours prn
      1. In crisis, may be used up to 6-8 puffs q1-2 hours
    2. Levalbuterol (Xopenex hfa) 2 puffs every 4-6 hours
    3. Pirbuterol (Maxair Autohaler) 1-2 pufss every 4-6 hours prn

IV. Preparations: Systemic Corticosteroids

  1. Short course Corticosteroids in severe exacerbation
    1. Increases FEV1 and shortens hospital stay
    2. Avoid use longer than 2 weeks
    3. Protocol (total of 10 day course at full strength)
      1. Solu-Medrol 1-2 mg/kg q6-12 hours IV for 3 days
        1. IV Corticosteroids are not more effective than oral Corticosteroids
      2. Prednisone 40 mg daily for 5 days
        1. Equivalent to 10-14 day courses (see above)
        2. Prolonged Prednisone tapers off over 2 weeks are not indicated in most cases
  2. Long-term Systemic Corticosteroids are not often helpful
    1. Long-term Corticosteroid use is rarely indicated
    2. Beneficial effects seen in only 10-20% COPD patients
    3. Test to see if COPD patient Corticosteroid responsive
      1. Prednisone 40 mg PO for 10 days
      2. Alternative: Theophylline challenge
      3. Test PFTs before and after course
    4. Attempt to slowly discontinue Corticosteroids
      1. Decrease Corticosteroid dose by 5 mg per week
    5. Most patients tolerate taper without rebound
      1. No change in Spirometry
      2. No change in symptoms (e.g. Dyspnea)
    6. Stopping steroids often alleviates adverse effects
      1. Anticipate resolution of prior weight gain
    7. Risk of Osteoporosis with long-term steroid use
      1. See Corticosteroid Associated Osteoporosis
      2. Dubois (2002) Chest 121:1456-63 [PubMed]
    8. References
      1. Rice (2000) Am J Respir Crit Care Med 162:174-8 [PubMed]

V. Preparations: Inhaled Corticosteroids

  1. Corticosteroids are not uniformly effective in COPD
    1. Overall, NNT 16 to reduce one exacerbation in 12 months with triple therapy (compared with dual therapy)
    2. Eosinophil Count >300 cells/ul (>4% of total WBC) predicts steroid responsiveness
    3. Unlikely to be steroid responsive if Eosinophil Count <100 cells/ul
    4. Eosinophil Count only has predictive value if off inhaled and Systemic Corticosteroids
    5. COPD may still respond to steroids despite low Eosinophil Count
    6. Pascoe (2019) Lancet Respir Med 7(9):745-56 [PubMed]
  2. Possible impact on exacerbations and quality of life
    1. May decrease exacerbations by one event per every 4 years
    2. Consider in patients with FEV1 < 1.5 Liters (<50%)
    3. Consider if frequent exacerbations
    4. Consider trial for 6-18 weeks
      1. Check PFTs before and after course
  3. Pulmonary Function Tests do not reflect full benefit
    1. Decrease annual FEV1 decline (44 ml/year, similar to long acting Bronchodilators)
    2. Minimal impact on lung function
    3. No impact on rate of lung function decline
    4. Inhaled Corticosteroids do not reduce mortality
    5. Inhaled Corticosteroids are not recommended as monotherapy in COPD
  4. Adverse effects may outweigh benefits
    1. Agents are expensive (many are over $100 per month)
    2. Mild effects: Bruising, Dysphonia, Candidiasis
    3. Serious effects
      1. Osteoporosis
      2. Cataracts
      3. Pneumonia
        1. Number Needed to Harm (NNH): 50 in 18 months
        2. Kew (2014) Cochrane Database Syst Rev 3:CD010115 [PubMed]
    4. Consider tapering off high dose fluticasone or other Inhaled Corticosteroid in stable COPD patients
      1. Taper over 12 weeks to prevent exacerbation and consider maintaining at low dose if symptoms increase
      2. Avoid discontinuing Inhaled Corticosteroids in oxygen dependent COPD or those on oral Corticosteroids
      3. Magnussen (2014) N Engl J Med 371:1285-94 [PubMed]
  5. Medications
    1. Fluticasone with Salmeterol (Advair Diskus)
      1. Significant benefit compared with either agent alone
      2. Resulted in symptom control and sustained for >1 year
      3. No significant adverse effects seen in studies
      4. Calverly (2003) Lancet 361:449-56 [PubMed]
      5. Hanania (2003) Chest 124:834-43 [PubMed]

VI. Preparations: Home Oxygen

  1. Indications
    1. Stable clinical Status
    2. No end-organ dysfunction: PaO2 < 55 mmHg or O2 < 88%
    3. End Organ changes: PaO2 < 59 mmHg or O2 < 90%
      1. Cor Pulmonale or Right Heart Failure
      2. P-pulmonale on EKG
      3. Polycythemia present (Hematocrit >55%)
  2. Documentation
    1. Arterial Blood Gas (ABG) OR
    2. O2 Sat measured at rest for 30 min on room air OR
    3. O2 Sat after 6 minute ambulation
      1. Document with and without oxygen
  3. Benefits
    1. Home Oxygen use only beneficial if >15-18 hours/day
    2. Decreases exertional and nocturnal Dyspnea
    3. Increases life span in COPD by 6-7 years (if resting PaO2 <55 mmHg)
    4. Goal to keep Oxygen Saturation 88-92% (or PaO2 >60 mmHg)
  4. Adjuncts
    1. Consider Continuous Positive Airway Pressure (CPAP)

VII. Preparations: Systemic Bronchodilators

  1. Leukotriene Receptor Antagonist (e.g. Accolate)
    1. Rarely used in COPD
    2. Some prior data showed efficacy when cobined with Bronchodilator
  2. Theophylline 10-15 mg/kg to drug level 10-12 ug/ml
    1. NOT recommended in exacerbation
    2. Narrow therapeutic range (before reaching toxic levels)
    3. Several serious Drug Interactions (e.g. Quinolones)
      1. Review interactions at every medication change
    4. Efficacy in stable COPD
      1. Weak Bronchodilator
        1. Weaker than Beta Agonists (e.g. Albuterol)
        2. Weaker than Anticholinergics (e.g. Atrovent)
      2. Improves respiratory Muscle Strength and endurance
      3. Improves mucociliary clearance
      4. Increases central respiratory drive
      5. May lead to symptomatic improvement
      6. Associated with reduced hospitalization rate
      7. Appears synergistic with long-acting Bronchodilator
        1. ZuWallack (2001) Chest 119:1661 [PubMed]

VIII. Resources

  1. Global Initiative for Chronic Obstructive Lung Disease
    1. http://www.goldcopd.com

IX. References

  1. (1995) Am J Respir Crit Care Med 152(5 pt 2):S77-121 [PubMed]
  2. Cagle (2023) Am Fam Physician 107(6): 604-12 [PubMed]
  3. Celli (1998) Postgrad Med 103(4):159-76 [PubMed]
  4. Cooper (1997) Ann Thorac Surg 63:312-9 [PubMed]
  5. Donohue (2002) Chest 122:47-55 [PubMed]
  6. Fein (2000) Curr Opin Pulm Med 6:122-6 [PubMed]
  7. Gentry (2017) Am Fam Physician 95(7): 433-41 [PubMed]
  8. Hunter (2001) Am Fam Physician 64(4):603-12 [PubMed]
  9. Lee (2013) Am Fam Physician 88(10): 655-63 [PubMed]
  10. Obrien (1998) Postgrad Med 103(4):179-202 [PubMed]
  11. Qaseem (2011) Ann Intern Med 155(3): 179-91 [PubMed]
  12. Runo (2001) West J Med 175:197-201 [PubMed]
  13. Sayiner (2001) Chest 119:726-30 [PubMed]
  14. Voelkel (2000) Chest 117(5 suppl 2):S376-9 [PubMed]
  15. Weg (1998) Postgrad Med 103(4):143-55 [PubMed]

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