Tegaserod

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Tegaserod
Tegaserod structure.svg
Tegaserod ball-and-stick model.png
Systematic (IUPAC) name
(2E)-2-[(5-Methoxy-1H-indol-3-yl)methylene]-N-pentylhydrazinecarboximidamide
Clinical data
Trade names Zelnorm, Zelmac
AHFS/Drugs.com monograph
Pregnancy
category
  • AU: B3
  • US: B (No risk in non-human studies)
Legal status
  • US: Usage requires authorization from the FDA
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability 10%
Protein binding 98%
Metabolism Gastric and hepatic
Biological half-life 11 ± 5 hours
Excretion Fecal and renal
Identifiers
CAS Registry Number 189188-57-6 N
ATC code A06AX06
PubChem CID: 5362436
IUPHAR/BPS 226
DrugBank DB01079 YesY
ChemSpider 10609889 YesY
UNII 458VC51857 YesY
KEGG D02730 YesY
ChEMBL CHEMBL76370 YesY
Chemical data
Formula C16H23N5O
Molecular mass 301.39 g/mol
 N (what is this?)  (verify)

Tegaserod is a 5-HT4 agonist manufactured by Novartis and sold under the names Zelnorm and Zelmac for the management of irritable bowel syndrome and constipation.[1] Approved by the FDA in 2002, it was subsequently removed from the market in 2007 due to FDA concerns about possible adverse cardiovascular effects. Before then, it was the only drug approved by the United States Food and Drug Administration to help relieve the abdominal discomfort, bloating, and constipation associated with irritable bowel syndrome. Its use was also approved to treat chronic idiopathic constipation.[2]

Mechanism of action[edit]

The drug functions as a motility stimulant, achieving its desired therapeutic effects through activation of the 5-HT4 receptors of the enteric nervous system in the gastrointestinal tract. It also stimulates gastrointestinal motility and the peristaltic reflex, and allegedly reduces abdominal pain.[3] Additionally, tegaserod is a 5-HT2B receptor antagonist.[4]

Withdrawal from market[edit]

On 30 March 2007, the United States Food and Drug Administration requested that Novartis withdraw Zelnorm from shelves.[5] The FDA alleges a relationship between prescriptions of the drug and increased risks of heart attack or stroke. An analysis of data collected on over 18,000 patients demonstrated adverse cardiovascular events in 13 of 11,614 patients treated with Zelnorm (a rate of 0.11%) as compared with 1 of 7,031 patients treated with placebo (a rate of 0.01%). Novartis alleges all of the affected patients had preexisting cardiovascular disease or risk factors for such, and further alleges that no causal relationship between tegaserod use and cardiovascular events has been demonstrated.[6] On the same day as the FDA announcement, Novartis Pharmaceuticals Canada announced that it was suspending marketing and sales of the drug in Canada in response to a request from Health Canada.[7] In a large cohort study based on a US health insurance database, no increase in the risk of cardiovascular events were found under tegaserod treatment.[8] Currently, tegaserod may only be used in emergency situations only with prior authorization from the FDA.[9]

References[edit]

  1. ^ "New Data for Zelnorm". Retrieved March 30, 2007. 
  2. ^ "FDA approves first treatment for women with irritable-bowel syndrome". Archived from the original on February 5, 2007. Retrieved March 30, 2007. 
  3. ^ Rossi, S. (2004). Australian Medicines Handbook. Adelaide: Health Communication Network. ISBN 0-9578521-4-2. 
  4. ^ Beattie DT, Smith JA, Marquess D et al. (November 2004). "The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo". Br. J. Pharmacol. 143 (5): 549–60. doi:10.1038/sj.bjp.0705929. PMC 1575425. PMID 15466450. 
  5. ^ "FDA Announces Discontinued Marketing of GI Drug, Zelnorm, for Safety Reasons". FDA Press Release. 30 March 2007. 
  6. ^ "Zelnorm" (PDF). Novartis. Archived from the original (PDF) on 2007-04-10. Retrieved 2007-03-30. 
  7. ^ "Novartis suspends Canadian marketing and sales of Zelnorm in response to request from Health Canada". Retrieved 2007-03-30. 
  8. ^ "Tegaserod and the Risk of Cardiovascular Ischemic Events: An Observational Cohort Study.". Retrieved March 3, 2010. 
  9. ^ http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm