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tiotropium (Spiriva, Respimat)

Tradename: Spiriva, Respimat (mist, approved in Europe) Indications: 1) chronic bronchitis, bronchospasm, COPD a) improves symptoms in early-moderate COPD [8] b) modestly improves FEV1 c) reduces risk of COPD exacerbation d) reduces use of health services 2) asthmatic bronchitis 4) not useful in patients with pure emphysema Contraindications: 1) maintenance therapy; NOT for acute exacerbations 2) combined use with short-acting anticholinergic agent (ipratropium) [3,7] Dosage: - once daily Capsules with HandiHaler that disperses powder for inhalation Do Not swallow [4] Pharmacokinetics: - slower onset & longer duration than ipratropium [3] - mean time to onset is 30 minutes - peak effect occurs in 3 hours - duration > 24 hours - 1 week of daily use to achieve maximum effect [3] Adverse effects: 1) xerostomia (twice as common as ipratropium) 2) diarrhea? 3) increased risk of stroke (excess risk of 0.2%/year) [4,5] - no increased risk of stroke [6] 4) increased cardiovascular risk of inhaled anticholinergics - increased cardiovascular risk in the elderly - highest risk 2-3 weeks after starting treatment [11] 5) increased all-cause mortality associated with Respimat? (mist, approved in Europe)*; conflicting reports [9] - no increased mortality with Respimat [12] 6) increased risk of urinary retention * mist form achieves higher peak concentrations than powder Mechanism of action: 1) anticholinergic agent causing relaxation of the bronchial smooth muscle, especially in the upper bronchial tree 2) inhibits vagally-mediated reflexes 3) prevents increase in cGMP caused by stimulation of muscarinic receptors in bronchial smooth muscle 4) does not affect progression of COPD [8] Notes: also see ipratropium Clinical trials: - TIPHON study - INSPIRE trial - UPLIFT trial

Interactions

drug interactions drug adverse effects of parasympatholytics

Related

INSPIRE trial Tiotropium: Influence on the Perception of the Improvement in Routine Activities Objectified by a Numerical Scale (TIPHON)

General

antiasthmatic agent inhaled anticholinergic agent

Properties

Database Correlations

PUBCHEM correlations

References

  1. New Drug: Spiriva (Tiotropium Bromide) HandiHaler Prescriber's Letter 11(4):24 2004 Detail-Document#: 200411 (subscription needed) http://www.prescribersletter.com
  2. Internal Medicine World Report 20(7) July 2005
  3. Prescriber's Letter 15(1): 2008 Combined Use of Tiotropium (Spiriva) and Ipratropium (Atrovent) Detail-Document#: 240109 (subscription needed) http://www.prescribersletter.com
  4. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Spiriva
  5. Prescriber's Letter 15(4): 2008 Risk of Stroke and Tiotropium (Spiriva HandiHaler) Detail-Document#: 240405 (subscription needed) http://www.prescribersletter.com
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tiotropium
  7. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
  8. Decramer M et al. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): A prespecified subgroup analysis of a randomised controlled trial. Lancet 2009 Oct 3; 374:1171. PMID: 19716598 - Davies L and Calverley PMA. UPLIFTing care for chronic obstructive pulmonary disease. Lancet 2009 Oct 3; 374:1129. PMID: 19716599
  9. Singh S et al Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials BMJ 2011; 342:d3215 PMID: 21672999 http://www.bmj.com/content/342/bmj.d3215.full - Cates CJ Safety of tiotropium BMJ 2011; 342:d2970 PMID: 21672998 http://www.bmj.com/content/342/bmj.d2970 - Wise RA et al Tiotropium Respimat Inhaler and the Risk of Death in COPD. N Engl J Med. September 8, 2013 PMID: 23992515 http://www.nejm.org/doi/full/10.1056/NEJMoa1303342 - Jenkins CR, Beasley R. Tiotropium Respimat increases the risk of mortality. Thorax. 2013 Jan;68(1):5-7 PMID: 23229813
  10. Stephenson A, Seitz D, Bell CM, et al. Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease: A population-based study. Arch Intern Med 2011; 171(10):914-920. PMID: 21606096 - Singh S, Furberg CD. Inhaled anticholinergics for chronic obstructive pulmonary disease: Comment on "Inhaled Anticholinergic Drug Therapy and the Risk of Acute Urinary Retention in Chronic Obstructive Pulmonary Disease". Arch Intern Med 2011; 171(10):920-922. PMID: 21606097
  11. Gershon A et al Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease. JAMA Intern Med. 2013;():1-9. PMID: 23689820 http://archinte.jamanetwork.com/article.aspx?articleid=1689974
  12. Wise RA et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013 Oct 17;369(16):1491-501. PMID: 23992515

Component-of

olodaterol/tiotropium (Stiolto Respimat)