Long-acting Anticholinergic Bronchodilator

Aka: Long-acting Anticholinergic Bronchodilator, Long-Acting Muscarinic Antagonist, Tiotropium, Spiriva, Aclidinium, Tudorza, Umeclidinium, Incruse, Anoro Ellipta, Seebri Neohaler, Inhaled Glycopyrolate, Stiolto, Utibron, Lonhala Magnair, Revefenacin, Yupelri

1. Indication
   1. Chronic Obstructive Pulmonary Disease (COPD)
   2. Severe Asthma (third-line agent)
      1. May be added to high dose Inhaled Corticosteroid and long acting beta agonist
      2. However, other standard Asthma agents are preferred first
      3. (2015) Presc Lett 22(12):71-2
      4. Kerstgens (2015) Lancet respir med 3(5):367–76 [PubMed]
2. Mechanism
   1. Long-acting Anticholinergic Bronchodilator or Long-Acting Muscarinic Antagonist (LAMA)
3. Dosing: COPD
   1. Spiriva (Tiotropium) Handihaler (Dry powder)
      1. Inhale one 18 mcg dose once daily
   2. Spiriva (Tiotropium) Respimat (mist)
      1. Two 2.5 mg dose inhalations once daily
   3. Tudorza Pressair (Aclidinium)
      1. Inhale twice daily
      2. May be easier to use than Spiriva (but is twice daily dosing)
   4. Incruse (Umeclidinium)
      1. Inhale one dose once daily
   5. Seebri Neohaler (Glycopyrolate)
      1. Inhale twice daily
   6. Lonhala Magnair (Glycopyrolate) Neb
      1. Lonhala is a LAMA delivered by proprietary, portable nebulizer (Magnair) twice daily
      2. Prescribed as a starter kit (includes nebulizer) and then as a refill kit
      3. Expensive (3 fold increased cost over inhaled LAMA agents) and unlikely to offer added benefit for most
      4. (2018) Presc Lett 25(6): 36
   7. Revefenacin (Yupelri)
      1. LAMA that is nebulized once daily
      2. Expensive ($1000/month) at the time of release in 2019
      3. Consider inhaled LAMA instead for less than half the cost (e.g. Spiriva, Incruse)
      4. Consider nebulized Ipratropium four times daily at $25/month (or combined with Albuterol in duonebs)
      5. (2019) Presc Lett 26(4): 22
4. Dosing: Asthma
   1. Spiriva (Tiotropium) Respimat (half dose of COPD preparation)
      1. Two 1.25 mg dose inhalations once daily
5. Dosing: Combinations
   1. Anoro Ellipta (Umeclidinium/vilanterol)
      1. Long-Acting Beta-2 Agonist (vilanterol) combined with long-acting Anticholinergic (Umeclidinium)
      2. Inhale one dose once daily
   2. Stiolto (Tiotropium/Olodaterol)
      1. Long-Acting Beta-2 Agonist (Olodaterol) combined with long-acting Anticholinergic (Tiotropium)
      2. Inhale once daily
   3. Utibron (Glycopyrolate/Indaceterol)
      1. Long-Acting Beta-2 Agonist (Indaceterol) combined with long-acting Anticholinergic (Glycopyrolate)
      2. Inhale twice daily
   4. Bevespi Aerosphere (Formoterol/Glycopyrrolate)
      1. Two inhalations twice daily
6. Precautions
   1. Avoid use of long-acting Anticholinergic (e.g. Spiriva) with Atrovent or Combivent due to minimal added benefit
      1. Use Albuterol MDI as short acting rescue medication instead of short acting Ipratropium
      2. Exception: May use Atrovent or Combivent while starting Spiriva in first 8-10 days
7. Advantages: Spiriva (likely applies to Tudorza as well)
   1. Improves mean FEV1, Dyspnea and quality of life
   2. Decreased COPD exacerbations and hospitalizations
   3. More effective than Ipratropium Bromide in COPD (10 fold increase in potency)
   4. At least as effective as Salmeterol in COPD
   5. Better compliance due to once daily dosing
8. Disadvantages
   1. Expensive: $220 to as much as $300 per month
   2. May cause Dry Mouth
9. Adverse Effects: Spiriva (likely applies to Tudorza as well)
   1. Serious adverse effects
      1. Angioedema or other Hypersensitivity Reaction
      2. Paradoxical bronchospasm
      3. Glaucoma exacerbation
      4. Cerebrovascular Accident
         1. Initial report suggests risk as high as 2 cases per 1000 patients per year
         2. Confirmatory studies required and patients may continue on Spiriva currently
         3. (2008) Prescriber's Letter 15(4):21
   2. Common adverse effects
      1. Anticholinergic effects (e.g. blurred vision, Constipation, Dry Mouth, Urinary Retention)
      2. Gastrointestinal upset (e.g. Abdominal Pain, Dyspepsia)
      3. Rhinorrhea or Epistaxis
10. References
    1. (2016) Presc Lett 23(2): 10
    2. (2015) Presc Lett 22(1): 4-5
    3. (2012) Presc Lett 19(12): 70
    4. Panning (2003) Pharmacotherapy 23:183-9 [PubMed]
    5. Hutton (2004) Am Fam Physician 69(12):2901-2 [PubMed]