tiotropium (Spiriva, Respimat)
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Introduction
Tradename: Spiriva, Respimat (mist, approved in Europe)
Indications
- chronic bronchitis, bronchospasm, COPD
- improves symptoms in early-moderate COPD[8]
- modestly improves FEV1
- reduces risk of COPD exacerbation
- reduces use of health services
- asthmatic bronchitis
- not useful in patients with pure emphysema
Contraindications
- maintenance therapy; NOT for acute exacerbations
- combined use with short-acting anticholinergic agent (ipratropium)[3][7]
Dosage
- once daily
Capsules with HandiHaler that disperses powder for inhalation
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
- xerostomia (twice as common as ipratropium)
- diarrhea?
- increased risk of stroke (excess risk of 0.2%/year)[4][5]
- no increased risk of stroke[6]
- increased cardiovascular risk of inhaled anticholinergics
- increased cardiovascular risk in the elderly
- highest risk 2-3 weeks after starting treatment[11]
- increased cardiovascular risk in the elderly
- increased all-cause mortality associated with Respimat? (mist, approved in Europe)*; conflicting reports[9]
- no increased mortality with Respimat[12]
- increased risk of urinary retention
* mist form achieves higher peak concentrations than powder
Mechanism of action
- anticholinergic agent causing relaxation of the bronchial smooth muscle, especially in the upper bronchial tree
- inhibits vagally-mediated reflexes
- prevents increase in cGMP caused by stimulation of muscarinic receptors in bronchial smooth muscle
- does not affect progression of COPD[8]
Clinical trials
Notes
also see ipratropium
More general terms
Additional terms
- INSPIRE trial
- Tiotropium: Influence on the Perception of the Improvement in Routine Activities Objectified by a Numerical Scale (TIPHON)
Component of
References
- ↑ New Drug: Spiriva (Tiotropium Bromide) HandiHaler Prescriber's Letter 11(4):24 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200411&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Internal Medicine World Report 20(7) July 2005
- ↑ 3.0 3.1 3.2 3.3 Prescriber's Letter 15(1): 2008 Combined Use of Tiotropium (Spiriva) and Ipratropium (Atrovent) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240109&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 4.2 FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Spiriva
- ↑ 5.0 5.1 Prescriber's Letter 15(4): 2008 Risk of Stroke and Tiotropium (Spiriva HandiHaler) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240405&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tiotropium
- ↑ 7.0 7.1 Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
- ↑ 8.0 8.1 8.2 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: https://www.ncbi.nlm.nih.gov/pubmed/19716598
Davies L and Calverley PMA. UPLIFTing care for chronic obstructive pulmonary disease. Lancet 2009 Oct 3; 374:1129. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19716599 - ↑ 9.0 9.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21672999 <Internet> http://www.bmj.com/content/342/bmj.d3215.full
Cates CJ Safety of tiotropium BMJ 2011; 342:d2970 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21672998 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23992515 <Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/23229813 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/21606097 - ↑ 11.0 11.1 Gershon A et al Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease. JAMA Intern Med. 2013;():1-9. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23689820 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1689974
- ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23992515