Tiotropium bromide

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Tiotropium
Tiotropium.svg
Tiotropium-3D-balls.png
Clinical data
Trade namesSpiriva, Braltus[1]
AHFS/Drugs.comMonograph
MedlinePlusa604018
Pregnancy
category
Routes of
administration
Inhalation by mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability19.5% (inhalation)
MetabolismLiver 25%
(CYP2D6, CYP3A4)
Elimination half-life5–6 days
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
ECHA InfoCard100.234.575 Edit this at Wikidata
Chemical and physical data
FormulaC19H22BrNO4S2
Molar mass472.416 g/mol g·mol−1
3D model (JSmol)
  (verify)

Tiotropium bromide, sold under the brandname Spiriva among others, is a long-acting bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and asthma.[2][1] Specifically it is used to try to prevent periods of worsening rather than for those periods themselves.[2] It is used by inhalation through the mouth.[2] Onset typically begins within half an hour and lasts for 24 hours.[2]

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 a 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] In the United States the wholesale cost was about 13.75 USD per dose as of 2019.[5] In the United Kingdom a dose costs the NHS about 0.86 pounds as of 2019.[1] In 2016 it was the 95th most prescribed medication in the United States with more than 8 million prescriptions.[6] There is no generic version available in the United States as of 2019.[7]

Medical uses[edit]

Tiotropium is used for maintenance treatment of chronic obstructive pulmonary disease (COPD) which includes chronic bronchitis and emphysema.[8] It is not however used for acute exacerbations.[8]

Adverse effects[edit]

Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions (≥1% of patients) associated with tiotropium therapy 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/or allergy (rash, angioedema, anaphylaxis).[9]

Tiotropium and another member of its class ipratropium were linked to increased risk of heart attacks, stroke and cardiovascular death.[10] The FDA requested further trials; these are now complete, and adequately resolve the previous safety concerns.[11]

Tiotropium mist inhaler (Respimat) has been found to be associated with an increase of all cause mortality in people with COPD.[12]

Mechanism of action[edit]

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[13] 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.

References[edit]

  1. ^ a b c British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 247–248. ISBN 9780857113382.
  2. ^ a b c d e f g "Tiotropium Bromide Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 31 January 2019.
  3. ^ "Tiotropium Use During Pregnancy". Drugs.com. Retrieved 31 January 2019.
  4. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 447. ISBN 9783527607495.
  5. ^ "NADAC as of 2019-01-30". Centers for Medicare and Medicaid Services. Retrieved 31 January 2019.
  6. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
  7. ^ "Generic Spiriva Availability". Drugs.com. Retrieved 31 January 2019.
  8. ^ a b "Spiriva Handihaler". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  9. ^ Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.
  10. ^ Singh S, Loke YK, Furberg CD (September 2008). "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): 1439–50. doi:10.1001/jama.300.12.1439. PMID 18812535.
  11. ^ FDA. Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler). FDA 2010
  12. ^ Singh, S; Loke, YK; Enright, PL; Furberg, CD (Jun 14, 2011). "Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials". BMJ (Clinical Research Ed.). 342: d3215. doi:10.1136/bmj.d3215. PMC 3114950. PMID 21672999.
  13. ^ Kato M, Komamura K, Kitakaze M (December 2006). "Tiotropium, a novel muscarinic M3 receptor antagonist, improved symptoms of chronic obstructive pulmonary disease complicated by chronic heart failure". Circ. J. 70 (12): 1658–60. doi:10.1253/circj.70.1658. PMID 17127817.

External links[edit]