Tiotropium bromide

Overview

Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening. It is used by inhalation through the mouth. Onset typically begins within half an hour and lasts for 24 hours.[1][2] WP

Common side effects include a dry mouth, runny nose, upper respiratory tract infection, shortness of breath and headache. Severe side effects may include angioedema, worsening bronchospasm, and QT prolongation. Tentative evidence has not found harm during pregnancy, however, such use has not been well studied. It is an anticholinergic medication and works by blocking acetylcholine action on smooth muscle.[1][3] WP

Tiotropium was patented in 1989, and approved for medical use in 2002. It is on the World Health Organization's List of Essential Medicines. In 2023, it was the 163rd most commonly prescribed medication in the United States, with more than 3 million prescriptions.[4–7] WP

Uses, dosage and effects

Medical uses

Tiotropium is used as maintenance treatment of chronic obstructive pulmonary disease (COPD). It may also be used as an add-on therapy in people with moderate-to-severe asthma on medium to high dose inhaled corticosteroids (ICS). It is not however approved for acute exacerbations of COPD or acute worsening of asthma.[1][8–11] WP

Tiotropium is also used in a combination inhaler with olodaterol, a long-acting beta-agonist, for the treatment of COPD, under the brand names Stiolto and Spiolto among others.[12][13][14] WP

Risks and side effects

Adverse effects

Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions (≥1% of people) include: dry mouth and/or throat irritation. Rarely (<0.1% of patients) treatment is associated with: urinary retention, constipation, acute angle closure glaucoma, palpitations (notably supraventricular tachycardia and atrial fibrillation) and allergy (rash, angioedema, anaphylaxis). A 2006 review found the increase in bronchospasm was small and did not reach statistical significance.[15][16] WP

Data regarding some serious side effects is mixed as of 2020. In September 2008 a review found that tiotropium and another member of its class ipratropium may be linked to increased risk of heart attacks, stroke and cardiovascular death. The US FDA reviewed the concern and concluded in 2010 that this association was not supported. A 2011 review of the tiotropium mist inhaler (Respimat), however, still found it associated with an increase in all cause mortality in people with COPD.[1][8][17–20] WP

Pharmacology

Mechanism of action

Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, when topically applied it acts mainly on M₃ muscarinic receptors located on smooth muscle cells and submucosal glands. This leads to a reduction in smooth muscle contraction and mucus secretion and thus produces a bronchodilatory effect.[21] WP⚠ Wikipedia itself has flagged this text: citation needed.

Legal status

Society and culture

Tiotroprium is available in two inhaler formats: a soft mist inhaler (Respimat) and a dry powder inhaler (HandiHaler). The safety and efficacy profiles of both devices are comparable and people's preference should play a role in determining inhaler choice. There is no significant difference in all-cause mortality between tiotropium soft mist inhalers compared to dry powder inhalers, however caution needs to be taken in people with severe heart or kidney problems.[22][23] WP

Chemistry

Formula

C19H22BrNO4S2 PC

CAS number

136310-93-5 PC

Molar mass (g/mol)

472.4 PC

IUPAC name (computed by PubChem)

[(1R,2R,4S,5S)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide PC

SMILES

C[N+]1([C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-] PC

InChIKey

DQHNAVOVODVIMG-RGECMCKFSA-M PC

PubChem CID

5487426

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Tiotropium Bromide Monograph for Professionals
2. Other British national formulary: BNF 76. 2018
3. Other Tiotropium Use During Pregnancy
4. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
5. Other World Health Organization. The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
6. Other Top 300 of 2023
7. Other Tiotropium Drug Usage Statistics, United States, 2014 - 2023
8. Journal / agency Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. The New England Journal of Medicine. October 2008. doi:10.1056/nejmoa0805800 · PMID 18836213
9. Other Pocket Guide to COPD Diagnosis, Management and Prevention [Internet] Fontana, WI The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 [Cited 12 April 2020] Available from. link 2
10. Journal / agency Rodrigo GJ, Castro-Rodríguez JA. What is the role of tiotropium in asthma?: a systematic review with meta-analysis. Chest. February 2015. doi:10.1378/chest.14-1698 · PMID 25322075
11. Other Global Strategy for Asthma Management and Prevention (2020 update). 2020
12. Other Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC). 14 January 2021
13. Other Yanimo Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC). 14 January 2021
14. Journal / agency Stiolto Respimat- tiotropium bromide and olodaterol spray, metered
15. Other Australian Medicines Handbook. 2006
16. Journal / agency Kesten S, Jara M, Wentworth C, Lanes S. Pooled clinical trial analysis of tiotropium safety. Chest. December 2006. doi:10.1378/chest.130.6.1695 · PMID 17166984
17. Journal / agency Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. September 2008. doi:10.1001/jama.300.12.1439 · PMID 18812535
18. Journal / agency Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler). 14 January 2010
19. Journal / agency Singh S, Loke YK, Enright PL, Furberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. BMJ. June 2011. doi:10.1136/bmj.d3215 · PMID 21672999 · PMC3114950
20. Journal / agency Tiotropium bromide. Australian Prescriber. January 2003. doi:10.18773/austprescr.2003.015
21. Journal / agency Kato M, Komamura K, Kitakaze M. Tiotropium, a novel muscarinic M3 receptor antagonist, improved symptoms of chronic obstructive pulmonary disease complicated by chronic heart failure. Circulation Journal. December 2006. doi:10.1253/circj.70.1658 · PMID 17127817
22. Journal / agency Dahl R, Kaplan A. A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?. BMC Pulmonary Medicine. October 2016. doi:10.1186/s12890-016-0291-4 · PMID 27724909 · PMC5057252
23. Journal / agency Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, Dusser D, Joseph E, Kattenbeck S, Koenen-Bergmann M, Pledger G, Calverley P. Tiotropium Respimat inhaler and the risk of death in COPD. The New England Journal of Medicine. October 2013. doi:10.1056/NEJMoa1303342 · PMID 23992515

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