Tegaserod

drugbox
IUPAC_name = 2-((5-Methoxy-1"H"-indol-3-yl)methylene)-"N"-pentylhydrazinecarboximidamide




width = 143px
CAS_number = 189188-57-6
ATC_prefix = A03
ATC_suffix = AE02
PubChem = 6918369
DrugBank = APRD00096 (wrong structure)
C = 16 | H = 23 | N = 5 | O = 1
molecular_weight = 301.39 g/mol
smiles = CCCCCN=C(/N)N/N=C/c1c [nH] c2ccc(CO)cc12
bioavailability = 10%
protein_bound = 98%
metabolism = Gastric and hepatic
elimination_half-life = 11 ± 5 hours
excretion = Fecal and renal
pregnancy_AU = B3
pregnancy_US = B
legal_status = Withdrawn
routes_of_administration = Oral

Tegaserod is a 5-HT₄ agonist manufactured by Novartis and used for the management of irritable bowel syndrome and constipation. [cite web|url=http://www.pharma.us.novartis.com/newsroom/pressReleases/releaseDetail.jsp?PRID=2004 |title= New Data for Zelnorm |accessmonthday= March 30 |accessyear = 2007] Its use 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. [cite web|url=http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01160.html |title=FDA approves first treatment for women with irritable-bowel syndrome |accessmonthday= March 30 |accessyear= 2007] It is currently marketed by Novartis under the trade names Zelnorm and Zelmac in the United States and abroad, respectively.

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. [cite book |last=Rossi |first=S. |title=Australian Medicines Handbook |year=2004 |publisher=Health Communication Network |location=Adelaide |isbn=ISBN 0-9578521-4-2 ] Additionally, tegaserod is a 5-HT_2B receptor antagonist.cite journal |author=Beattie DT, Smith JA, Marquess D, "et al" |title=The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo |journal=Br. J. Pharmacol. |volume=143 |issue=5 |pages=549–60 |year=2004 |month=November |pmid=15466450 |pmc=1575425 |doi=10.1038/sj.bjp.0705929 |url=http://dx.doi.org/10.1038/sj.bjp.0705929]

Withdrawal from market

On March 30 2007, the U.S. Food and Drug Administration requested that Novartis withdraw Zelnorm from shelves. The FDA alleges a relationship between prescriptions of the drug and increased risks of heart attack or stroke. [cite web|url= http://www.cnn.com/2007/HEALTH/03/30/constipation.drug.ap/|title= Constipation drug pulled at FDA request |accessmonthday= March 30 |accessyear= 2007] 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. [cite web | url = http://www.zelnorm.com/Zelnrom_PR_US_330_Final_12_1007.pdf | title = Zelnorm | publisher = Novartis | accessdate = 2007-03-30] 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. [cite web |url=http://www.newswire.ca/en/releases/archive/March2007/30/c9000.html |title=Novartis suspends Canadian marketing and sales of Zelnorm in response to request from Health Canada |accessdate= 2007-03-30 ] Some manufacturers in India, such as Cipla, seem to still have generic Tegaserod available in their listings [ [http://www.cipla.com/ourproducts/productlist/t.htm Cipla - Product List ] ] and some online merchants may be selling it.

References

http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/public/2007/zelnorm_pc-cp_2_e.html

External links

* [http://www.zelnorm.com Manufacturer's website]