Tiotropium

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Mechanism-of-action 8 Clinical-trials 9 Notes 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradename: Spiriva, Respimat ( mist, approved in Europe)

Indications

• chronic bronchitis, 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
  
• 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

• 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 (see inhaled anticholineric agents)
• increased all-cause mortality associated with Respimat ( mist, approved in Europe)* [9]
• increased risk of urinary retention
  

• * mist form achieves higher peak concentrations than powder
  

• drug adverse effects of parasympatholytics

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

• TIPHON study
• INSPIRE trial
• UPLIFT trial

Notes

• also see ipratropium

More General Terms

• antiasthmatic agent
• parasympatholytic (anticholinergic, antimuscarinic agent)

Additional Terms

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

Internet Database

PubChem: 131950
PubChem: 656610
PubChem: 60830
PubChem: 3086654

References

1. New Drug: Spiriva (Tiotropium Bromide) HandiHaler Prescriber's Letter 11(4):24 2004 Detail-Document#: [1] (subscription needed) [2]
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#: [3] (subscription needed) [4]
4. FDA MedWatch [5]
5. Prescriber's Letter 15(4): 2008 Risk of Stroke and Tiotropium (Spiriva HandiHaler) Detail-Document#: [6] (subscription needed) [7]
6. FDA MedWatch [8]
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: [9]
   - Davies L and Calverley PMA. UPLIFTing care for chronic obstructive pulmonary disease. Lancet 2009 Oct 3; 374:1129. PMID: [10]
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 <PubMed> PMID: [11] <Internet> [12]
   - Cates CJ Safety of tiotropium BMJ 2011; 342:d2970 <PubMed> PMID: [13] <Internet> [14]
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: [15]
    - 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: [16]

tiotropium (Spiriva, Respimat)