Talk:Tiotropium bromide

ELs
I deleted some dead links in the External Link section. Added in hopefully some better links. RonEJ 19:05, 17 March 2007 (UTC)

I have a scanned picture available for use.
RonEJ 13:24, 19 March 2007 (UTC)
 * Thanks User:RonEJ have added. 13 years late but better late than never :-) Doc James  (talk · contribs · email) 06:54, 11 May 2020 (UTC)

Cost
Even with good insurance cost is $2000 a year  — Preceding unsigned comment added by 71.9.22.214 (talk) 21:21, 21 November 2022 (UTC)

Poorly Written Article
The section on medication administration was extremely poorly written - it was as if someone tried to translate the patient information leaflet from another language into English. I have extensively re-written this section, and have de-emphasised the terms "Tiotropium Bromide" and "Spiriva" in the introduction.

Russthomas1515 (talk) 05:17, 29 March 2008 (UTC)

The molecular formula and molecular weight (MW) do not match. The MW is based on the bromide salt. Since tiotropium is a charged species and must always have an anion, I recommend adding the bromide to the formula and the drawing. — Preceding unsigned comment added by Mccooeye (talk • contribs) 19:05, 14 January 2011 (UTC)

Asthma
The Asthma Research Center at Brigham and Women's Hospital is conducting a study (Genotype Stratified Treatment With Anticholinergic vs. Beta-Agonist (Long Acting) and Exacerbations (GABLE)) that involves certain asthmatics (based on results from a blood test) taking Spiriva instead of Advair or Symbicort. The ClinicalTrials.gov identifier for this study is: NCT00706446. I signed up for the research study; my first visit is tomorrow. -- Christopher C. Parker t c 21:48, 18 August 2009 (UTC)

Effectiveness
Missing from this article is any data (or statements) about effectiveness. In fact, the drug doesn't reduce mortality, though it helps (somewhat) with quality of life. The article ought to describe that, including numbers from the large four-year study completed in 2008. Sources:


 * http://www.ncbi.nlm.nih.gov/pubmed/19317104
 * http://www.pulmonaryreviews.com/08nov/UPLIFT.html

-- John Broughton (♫♫) 17:14, 12 August 2010 (UTC)

Edits to Tiotropium Article
Dear Wikipedia community, I noticed some inconsitencies and missing information in the Tiotropium article. Please find attached a proposal what we think summarized the Tiotropium description in a balanced and factual manner:

Introduction Tiotropium bromide is an inhaled, once-daily, long-acting anticholinergic (long-acting muscarinic receptor antagonist [LAMA]) bronchodilator available as an inhalation solution via the Respimat® Soft Mist™ Inhaler (SMI) and as a dry powder for inhalation via the HandiHaler® device.1,2 Tiotropium is marketed under the brand name SPIRIVA® and is indicated for the maintenance therapy of chronic obstructive pulmonary disease (COPD) (via Respimat® and HandiHaler®)1,2 and, in some countries, as add-on therapy for adult patients with poorly controlled asthma (Respimat®).2 It has been available in Europe since 20021 and in the United States since 2004,3 and had accumulated an estimated patient exposure exceeding >40 million patient-years for COPD by 2014.4 Tiotropium has a long duration of bronchodilatory action (for at least 24 hours following administration), which is attributed to its slow dissociation from muscarinic receptors within the airways.1,2,4,5 For both asthma and COPD, in addition to sustained improvements in lung function, tiotropium has established efficacy in reducing exacerbation risk and improving quality of life and symptoms.1,2 Tiotropium has also demonstrated improvements in exercise tolerance compared to placebo for patients with COPD.1,2,5 Tiotropium is generally well tolerated with an established safety profile, as demonstrated by the long-term Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®),6 Tiotropium Safety and Performance in Respimat® (TIOSPIR™)7 and asthma8 studies.

Mode of delivery Tiotropium is available in two formulations:

1.	Solution for inhalation administered via Respimat®2. •	The Respimat® SMI is a propellant-free inhaler that delivers a once-daily metered dosage (5 µg; two puffs of 2.5 µg) of tiotropium as a fine mist, which facilitates high lung and low throat deposition.2,4 After loading the cartridge and preparing the device, the patient breathes out slowly and fully then takes a slow, deep breath while pressing the dose release button. Breath should be held for 10 seconds (or as long as comfortable). This step is repeated once to obtain the full medicinal dose (5 µg).2

2.	Inhalation powder administered via HandiHaler®1. •	A once-daily tiotropium capsule (18 µg) is removed from the protective blister pack and placed in the chamber of the device immediately prior to use. The HandiHaler® pierces the capsule to allow inhalation of the medication. The patient must breathe in slowly and deeply. Following full inhalation, the patient should hold their breath for as long as comfortable, before resuming normal breathing. The process must be repeated in order to empty the capsule.1

Indication COPD Tiotropium Respimat® and HandiHaler® are indicated in Europe as a maintenance bronchodilator treatment to relieve symptoms of patients with COPD.1,2 In the United States, tiotropium Respimat® and HandiHaler® are indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema, and for reducing COPD exacerbations.3,9

Asthma In 2014, tiotropium Respimat® received approval in many European countries for use as add-on maintenance therapy to combination treatment with inhaled corticosteroids (ICS; ≥800 µg budesonide/day, or equivalent) and long-acting β2-agonists (LABAs) in adults with asthma who have experienced one or more severe exacerbations in the previous year.10 Tiotropium Respimat® is also indicated for asthma in other countries (please see local indications for specific details and timings). It is currently being reviewed by other regulatory authorities, including the United States Food and Drug Administration.11

Pharmacology Tiotropium is a once-daily LAMA with a high affinity binding to muscarinic M1, M2 and M3 receptors in the airways.4,5 Binding to the muscarinic M3 receptor subtype prevents the activation of the receptor by endogenous acetylcholine, resulting in relaxation of the bronchial smooth muscle.1-5 Tiotropium demonstrates a very slow dissociation from the M1 and in particular a from the M3 receptors (dissociation constant [KD] 0.041 and 0.014 nM, dissociation half-life 14.6 and 34.7 hours, respectively) compared with the M2 receptor (KD 0.021 nM and dissociation half-life 3.6 hours) resulting in a “kinetic selectivity” to the M3 subtype.4,12 As the bronchodilator effect of tiotropium is mainly through M3 receptor antagonism, this slow dissociation from the M3 receptor therefore accounts for the durability of tiotropium’s bronchodilatory action.1,2,4,5,12 Improvements in lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) are observed within 30 minutes following the first dose of tiotropium and maintained for 24 hours.1,2 The pharmacodynamics and pharmacokinetics of tiotropium Respimat® and HandiHaler® are similar. 13

Efficacy COPD Long-term, randomized, clinical studies in patients with COPD have demonstrated significantly improved and durable lung function responses and significantly lower risk of exacerbations as well as lower exacerbation rates with tiotropium versus placebo.1-6,9 Significant improvements in lung function with tiotropium versus the twice daily LABA salmeterol and ipratropium have been shown in shorter-term studies (<6 months),4,5 while a lower risk of exacerbations and exacerbation rates have been demonstrated versus ipratropium, salmeterol and the once daily LABA indacaterol in 1-year trials.14-16 Additional benefits of tiotropium include improved health-related quality of life, symptom reduction (eg, dyspnoea), less rescue medication use and increased exercise endurance versus placebo.1,2,4,5,17

Asthma The indication of tiotropium Respimat® in asthma is based on the results of two replicate, Phase III, 48-week, randomized, placebo-controlled trials that evaluated the effects of add-on therapy with tiotropium in adults (aged 18–75 years) with asthma who continued to have symptoms, despite taking daily therapy with ICS+LABA.8 Patients had at least a 5-year history of asthma (diagnosed before the age of 40 years) as well as an exacerbation history (≥1 exacerbation treated with systemic corticosteroids in the previous year), and were either life-long non-smokers or had a smoking history of <10 pack-years and had not smoked in the year before taking part in the study.8 The addition of tiotropium Respimat® significantly increased the time to first severe exacerbation (21% risk reduction), decreased the risk for asthma worsening (31% risk reduction), resulted in significant improvements in lung function (up to 154-mL improvement in peak FEV1) over placebo plus ICS+LABA combination therapy8 and patients were 68% more likely to have an improved asthma control score at week 48 versus placebo Respimat®.20

Safety COPD A large body of evidence supports the safety of tiotropium administered via HandiHaler® in patients with COPD;1,5 however, safety concerns with tiotropium Respimat® arose as a result of a pooled analysis of studies, which showed a numerical increase in all-cause mortality with Respimat® versus placebo (2.64 cases/100 patient-years versus 1.98 cases/100 patient-years, with Respimat® versus placebo, respectively), notably in patients with cardiac rhythm disorders.21 The safety concerns were contrary to the findings from the 4-year UPLIFT® study in which fewer deaths were observed with tiotropium HandiHaler® (13% reduced risk) than with placebo.6 The TIOSPIR™ trial was undertaken to evaluate prospectively the long-term safety and exacerbation reduction efficacy of tiotropium Respimat® compared with HandiHaler® in patients with COPD, including those with stable cardiac disease.7 During a mean follow-up of 2.3 years, tiotropium Respimat® was shown to be noninferior to tiotropium HandiHaler® with respect to all-cause mortality (Respimat® 5 µg: 4% reduced risk versus HandiHaler®) 7 Furthermore, there was no increased risk of mortality with Respimat® among the cohort of patients who had a history of cardiac arrhythmia.7 In addition a recent pooled analysis of the HandiHaler® and Respimat® safety databases22 suggested that the risk of mortality did not increase with tiotropium.

Asthma No safety concerns have been observed in clinical trials of tiotropium Respimat® in asthma. In the two key, Phase III randomized controlled trials, tiotropium as add-on therapy to ICS+LABA demonstrated a safety and tolerability profile comparable to placebo.8 Dry mouth is a common side effect of anticholinergics but was only reported in fewer than 2% of patients in these asthma studies8 (and in 1.2% of patients in a pooled analysis of six placebo-controlled trials in asthma2).

References 1.	Spiriva 18 microgram inhalation powder, hard capsule. Summary of product characteristics. Last updated 4 February 2015. Available at: http://www.medicines.org.uk/emc/medicine/10039/SPC/Spiriva+18microgram+inhalation+powder,+hard+capsule [Accessed February 2015]. 2.	Spiriva Respimat 2.5 micrograms, inhalation solution. Summary of product characteristics. Last updated 13 January 2015. Available at: https://www.medicines.org.uk/emc/medicine/20134 [Accessed February 2015]. 3.	SPIRIVA® HandiHaler® (tiotropium bromide inhalation powder) capsules for respiratory inhalation. Prescribing Information. Last updated April 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Spiriva/Spiriva.pdf [Accessed February 2015]. 4.	Keating GM. Tiotropium Respimat® Soft Mist™ inhaler: a review of its use in chronic obstructive pulmonary disease. Drugs. 2014;74:1801–1816. 5.	Keating GM. Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs. 2012;72:273–300. 6.	Tashkin DP, Celli B, Senn S, et al; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543–1554. 7.	Wise RA, Anzueto A, Cotton D, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369:1491–1501. 8.	Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367:1198–1207. 9.	SPIRIVA® RESPIMAT® (tiotropium bromide) inhalation spray for oral inhalation. Prescribing Information. Last updated September 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Spiriva+Respimat/spirivarespimat.pdf [Accessed February 2015]. 10.	Boehringer Ingelheim. Press release: Asthma: new indication for Spiriva® (tiotropium) Respimat® in the EU may offer millions of adults a significant advance in asthma care. 8 September 2014. Available at: http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/08_september_2014_asthma.html [Accessed February 2015]. 11.	Boehringer Ingelheim. Press release: Boehringer Ingelheim Announces US Filing Acceptance of New Drug Application for Spiriva® Respimat® (tiotropium bromide) Inhalation Spray for the Treatment of Asthma. 3 November 2014. Available at: http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/11-03-14-boehringer-ingelheim-announces-us-filing-acceptance-new-drug-application-spiriva-respimat-tiotropium-bromide-inhalation-spray-treatment-asthma.html [Accessed February 2015]. 12.	Disse B, Speck GA, Rominger KL, Witek TJ Jr, Hammer R. Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci. 1999;64:457–464. 13.	Hohlfeld JM, Sharma A, van Noord JA, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54:405–414.

14.	Vincken W, van Noord JA, Greefhorst APM, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J. 2002;19:209–216. 15.	Vogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations in COPD; POET-COPD Investigators. N Engl J Med. 2011;364:1093–1103. 16.	Decramer ML, Chapman KR, Dahl R, et al; INVIGORATE investigators. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study. Lancet Respir Med. 2013;1:524–533. 17.	Maltais F, Hamilton A, Marciniuk D, et al. Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD. Chest. 2005;128:1168–1178. 18.	Anzueto A, Calverley P, Dusser D, et al. The Tiotropium Safety and Performance in Respimat® trial (TIOSPIR®): Bronchodilator efficacy in the TIOSPIR® PFT sub-study; late-breaker abstract, CHEST (ACCP) Congress 2013. 19.	Buhl R, Dunn LJ, Disdier C, et al. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD. Eur Respir J. 2011;38:797–803. 20.	FitzGerald JM, Kerstjens H, Paggiaro P, et al. Once-daily tiotropium Respimat® add-on to ICS ± LABA improves control across asthma severities. Poster 1894, ERS 2014. 21.	Boehringer Ingelheim. Tiotropium (SPIRIVA®) RESPIMAT®: Evaluation of Fatal Events – February 2010. Available at: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/Pooled%20analysis/PA_205.372_251_252_254_255_U10-3255-01.pdf [Accessed November 2014]. 22.	Halpin DMG, Dahl R, Hallmann C, et al. Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis. Int J COPD. 2015;10:1–21. Christoph Hallmann (talk) 12:45, 28 July 2015 (UTC)

Picture of RESPIMAT


Image:Respimat.png

Christoph Hallmann (talk) 12:50, 28 July 2015 (UTC)