Tiotropium bromide explained

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.[1] 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.

Common side effects include a dry mouth, runny nose, upper respiratory tract infection, shortness of breath and headache.[2] Severe side effects may include angioedema, worsening bronchospasm, and QT prolongation.[2] Tentative evidence has not found harm during pregnancy, however, such use has not been well studied.[3] It is an anticholinergic medication and works by blocking acetylcholine action on smooth muscle.[2]

Tiotropium was patented in 1989, and approved for medical use in 2002.[4] It is on the World Health Organization's List of Essential Medicines.[5] In 2021, it was the 134th most commonly prescribed medication in the United States, with more than 4million prescriptions.[6] [7]

Medical uses

Tiotropium is used as maintenance treatment of chronic obstructive pulmonary disease (COPD).[8] [9] 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).[10] [11] It is not however approved for acute exacerbations of COPD or acute worsening of asthma.[2]

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]

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).[15] A 2006 review found the increase in bronchospasm was small and did not reach statistical significance.[16]

Data regarding some serious side effects is mixed as of 2020.[2] 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.[17] The US FDA reviewed the concern and concluded in 2010 that this association was not supported.[8] [18] 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.[19] [20]

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[21] 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.

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.[22] 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.[23]

Notes and References

  1. Book: British national formulary : BNF 76. 2018. Pharmaceutical Press. 9780857113382. 247–248. 76th.
  2. Web site: Tiotropium Bromide Monograph for Professionals . Drugs.com . American Society of Health-System Pharmacists . 31 January 2019 . 14 October 2018 . https://web.archive.org/web/20181014165156/https://www.drugs.com/monograph/tiotropium-bromide.html . live .
  3. Web site: Tiotropium Use During Pregnancy . Drugs.com . 31 January 2019 . 31 January 2019 . https://web.archive.org/web/20190131145317/https://www.drugs.com/pregnancy/tiotropium.html . live .
  4. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 447 .
  5. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  6. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  7. Web site: Tiotropium - Drug Usage Statistics . ClinCalc . 14 January 2024.
  8. 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 . 359 . 15 . 1543–1554 . October 2008 . 18836213 . 10.1056/nejmoa0805800 . free . 2437/111564 .
  9. 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: https://goldcopd.org/wp-content/uploads/2020/03/GOLD-2020-POCKET-GUIDE-ver1.0_FINAL-WMV.pdf
  10. Rodrigo GJ, Castro-Rodríguez JA . What is the role of tiotropium in asthma?: a systematic review with meta-analysis . Chest . 147 . 2 . 388–396 . February 2015 . 25322075 . 10.1378/chest.14-1698 .
  11. Book: Global Strategy for Asthma Management and Prevention (2020 update) . 2020 . GOLD . 10 May 2020 . 19 May 2020 . https://web.archive.org/web/20200519202726/https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf . live .
  12. Web site: Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC) . (emc) . 14 January 2021 . 30 September 2021 . 1 October 2021 . https://web.archive.org/web/20211001201028/https://www.medicines.org.uk/emc/product/6902/smpc . live .
  13. Web site: Yanimo Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC) . (emc) . 14 January 2021 . 30 September 2021 . 1 October 2021 . https://web.archive.org/web/20211001201026/https://www.medicines.org.uk/emc/product/10728/smpc . live .
  14. Web site: Stiolto Respimat- tiotropium bromide and olodaterol spray, metered . DailyMed . 30 September 2021 . 1 October 2021 . https://web.archive.org/web/20211001201023/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01e15aee-40e0-23f3-537f-c96dd63e2cb1 . live .
  15. Book: Rossi S . Australian Medicines Handbook . Adelaide . 2006 . Australian Medicines Handbook .
  16. Kesten S, Jara M, Wentworth C, Lanes S . Pooled clinical trial analysis of tiotropium safety . Chest . 130 . 6 . 1695–1703 . December 2006 . 17166984 . 10.1378/chest.130.6.1695 .
  17. 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 . 300 . 12 . 1439–1450 . September 2008 . 18812535 . 10.1001/jama.300.12.1439 .
  18. Web site: Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler) . U.S. Food and Drug Administration (FDA) . 14 January 2010 . https://web.archive.org/web/20171102214206/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm197429.htm . 2 November 2017 . dead . 20 December 2019.
  19. 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 . 342 . d3215 . June 2011 . 21672999 . 3114950 . 10.1136/bmj.d3215 .
  20. Web site: Tiotropium bromide . Australian Prescriber . 11 July 2024.
  21. 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 . 70 . 12 . 1658–1660 . December 2006 . 17127817 . 10.1253/circj.70.1658 . free .
  22. 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 . 16 . 1 . 135 . October 2016 . 27724909 . 5057252 . 10.1186/s12890-016-0291-4 . free .
  23. 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 . 6 . Tiotropium Respimat inhaler and the risk of death in COPD . The New England Journal of Medicine . 369 . 16 . 1491–1501 . October 2013 . 23992515 . 10.1056/NEJMoa1303342 . free .

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