Tegaserod

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]

Tegaserod
Clinical data
Trade namesZelnorm, Zelmac
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B3
  • US: B (No risk in non-human studies)
    Routes of
    administration    		Oral
    ATC code
    Legal status
    Legal status
    • US: Usage requires authorization from the FDA
    Pharmacokinetic data
    Bioavailability10%
    Protein binding98%
    MetabolismGastric and hepatic
    Elimination half-life11 ± 5 hours
    ExcretionFecal and renal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    CompTox Dashboard (EPA)
    Chemical and physical data
    FormulaC16H23N5O
    Molar mass301.39 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Mechanism of action

    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

    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] In 2019, tegaserod was reintroduced as for use in irritable bowel syndrome with constipation (IBS-C) in women under 65.[10]

    References
    1. "New Data for Zelnorm". Archived from the original on December 9, 2007. 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. Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J, Earnest DL, Seeger JD (2010). "Tegaserod and the Risk of Cardiovascular Ischemic Events: An Observational Cohort Study". J Cardiovasc Pharmacol Ther. 15 (2): 151–7. doi:10.1177/1074248409360357. PMID 20200325.
    9. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm
    10. WorldMeds, U. S. "FDA approves the reintroduction of Zelnorm™ (tegaserod) for Irritable Bowel Syndrome with Constipation (IBS-C) in women under 65". www.prnewswire.com. Retrieved 2019-09-17.
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