Tiotropium bromide

Source: Wikipedia, the free encyclopedia.

Tiotropium bromide
Clinical data
Trade namesSpiriva, others
AHFS/Drugs.comMonograph
MedlinePlusa604018
License data
Pregnancy
category
Routes of
administration		By mouth, inhalation by mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability19.5% (inhalation)
MetabolismLiver 25%
(CYP2D6, CYP3A4)
Elimination half-life5–6 days
ExcretionKidney
Identifiers
  • (1α,2β,4β,7β)-
    7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-
    3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide
JSmol)
  • C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]

  • C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C
  • InChI=1S/C19H22NO4S2.BrH/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15;/h3-8,11-13,16-17,22H,9-10H2,1-2H3;1H/q+1;/p-1/t11?,12-,13+,16-,17+; checkY
  • Key:DQHNAVOVODVIMG-RGECMCKFSA-M checkY

  • InChI=1S/C19H22NO4S2/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15/h3-8,11-13,16-17,22H,9-10H2,1-2H3/q+1/t11?,12-,13+,16-,17-/m0/s1 checkY
  • Key:LERNTVKEWCAPOY-FPISHFTHSA-N checkY
  (verify)

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.[10][11] Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening.[10] It is used by inhalation through the mouth.[10] Onset typically begins within half an hour and lasts for 24 hours.[10]

Common side effects include a dry mouth, runny nose, upper respiratory tract infection, shortness of breath and headache.

QT prolongation.[10] Tentative evidence has not found harm during pregnancy, however, such use has not been well studied.[1] It is an anticholinergic medication and works by blocking acetylcholine action on smooth muscle.[10]

Tiotropium was patented in 1989, and approved for medical use in 2002.[12] It is on the World Health Organization's List of Essential Medicines.[13] In 2021, it was the 134th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[14][15]

Medical uses

Tiotropium is used as maintenance treatment of chronic obstructive pulmonary disease (COPD).[16][17] 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).[18][19] It is not however approved for acute exacerbations of COPD or acute worsening of asthma.[10]

Tiotropium is also used in a combination inhaler with

long-acting beta-agonist, for the treatment of COPD, under the brand names Stiolto and Spiolto among others.[20][21][22]

Adverse effects

Adverse effects are mainly related to its

angle closure glaucoma, palpitations (notably supraventricular tachycardia and atrial fibrillation) and allergy (rash, angioedema, anaphylaxis).[23] A 2006 review found the increase in bronchospasm was small and did not reach statistical significance.[24]

Data regarding some serious side effects is mixed as of 2020.

ipratropium may be linked to increased risk of heart attacks, stroke and cardiovascular death.[25] The US FDA reviewed the concern and concluded in 2010 that this association was not supported.[16][26] A 2011 review of the tiotropium mist inhaler (Respimat); however, still found an associated with an increase in all cause mortality in people with COPD.[27]

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[28] 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.[citation needed
]

Society and culture

Tiotroprium is available in two inhaler formats: a soft mist inhaler (Respimat) and a dry powder inhaler (HandiHaler).[29] The safety and efficacy profiles of both devices are comparable and people's preference should play a role in determining inhaler choice.[29] 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.[30]

References

  1. ^ a b "Tiotropium Use During Pregnancy". Drugs.com. Archived from the original on 31 January 2019. Retrieved 31 January 2019.
  2. ^ a b "AusPAR: Tiotropium bromide". Therapeutic Goods Administration (TGA). 29 November 2016. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  3. ^ https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=E07D6674E971FA91CA258752004228AF&agid=(PrintDetailsPublic)&actionid=1 [dead link]
  4. ^ "Tiotropium bromide". Therapeutic Goods Administration (TGA). Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  5. ^ "Spiriva 18 microgram inhalation powder, hard capsule - Summary of Product Characteristics (SmPC)". (emc). 15 January 2019. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  6. ^ "Spiriva Respimat 2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  7. ^ "Tiogiva 18 microgram, inhalation powder, hard capsule - Summary of Product Characteristics (SmPC)". (emc). 2 June 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  8. ^ "Spiriva Handihaler- tiotropium bromide capsule". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  9. ^ "Spiriva Respimat- tiotropium bromide inhalation spray spray, metered". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  10. ^ a b c d e f g h i "Tiotropium Bromide Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 14 October 2018. Retrieved 31 January 2019.
  11. ISBN 9780857113382
    .
  12. ISBN 9783527607495
    .
  13. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  14. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  15. ^ "Tiotropium - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  16. ^
    PMID 18836213
    .
  17. ^ 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 Archived 12 July 2020 at the Wayback Machine
  18. PMID 25322075
    .
  19. ^ Global Strategy for Asthma Management and Prevention (2020 update) (PDF). GOLD. 2020. Archived (PDF) from the original on 19 May 2020. Retrieved 10 May 2020.
  20. ^ "Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  21. ^ "Yanimo Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  22. ^ "Stiolto Respimat- tiotropium bromide and olodaterol spray, metered". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  23. ^ Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.{{cite book}}: CS1 maint: location missing publisher (link)
  24. PMID 17166984
    .
  25. PMID 18812535
    .
  26. ^ "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. Archived from the original on 2 November 2017. Retrieved 20 December 2019.
  27. PMID 21672999
    .
  28. PMID 17127817
    .
  29. ^
    PMID 27724909
    .
  30. PMID 23992515
    .
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