The Zelnorm manufactured by Novartis was the first FDA-approved drug for the treatment of IBS-C , which had additional use in the treatment of functional dyspepsia and gastroparesis. However as there were reported cases on cardiovascular risks on its usage, FDA effectively stopped the marketing of the drug in the U.S. market and finally putting a ban on the product. But eventually it was permitted for restricted use in emergency situations in U.S. This was followed by withdrawl from Canada market by Health Canada and in India by Ministry of Health also.

1. FDA WITHDRAWL OF IBS-C DRUG ZELNORM
DUE TO CARDIOVASCULAR RISKS
PRESENTED BY :
G. Sandhya ,
Regd. No. 617209507007
M. Pharmacy,
Pharmaceutical Management
and Regulatory Affairs
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TEGASEROD
• Tegaserod is a 5-HT4 (Serotonin) agonist manufactured by Novartis, sold
under the name of Zelnorm and Zelnac for the management of Irritable Bowel
Syndrome (IBS) and Chronic Idiopathic Constipation(CIC).
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 normalizes impaired motility in GI tract, inhibits visceral sensitivity and
stimulates intestinal secretion.
•Additionally, Tegaserod is a 5-HT2B receptor antagonist.
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FDA withdrawl from the market :
•The marketed Zelnorm form consists of Tegaserod maleate as the
active ingredient.
•FDA approved the drug under Treatment-IND in 2002, and
subsequently removed from the market in 2007 due to FDA concerns
about possible Cardiovascular effects.
•It was the only drug approved by the USFDA associated with
Constipation and IBS.
TIMELINE:
In 2002 – FDA approved Tegaserod for the short term treatment of
IBS-C in women.
In 2004- its use was expanded to the indications of Idiopathic Chronic
Constipation for both Men and Women younger than 65.
March 2007- FDA withdrawl amid the new evidence that it raises the
risk of heart attack and strokes.
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Basis for withdrawl :
•Within its 5 years release into the market the drug was withdrawn
by FDA authority due to reports on cardiovascular risks .
•The decision was based on a Swiss government analysis
(Safety Review) of 29 Zelnorm studies.
•The 29 studies were pooled and analyzed in more than
11,000 patients.
•Among the 29 studies, 13 patients on Tegaserod
experienced Ischemic cardiovascular events, including
one death as compared with only one non-fatal event in
more than 7000 patients who took placebo.
•The estimated percentage was 3.7% of patients on the
suspected drug V/s 1.3 % of patients on Placebo.
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UNITED STATES MARKET :
•Based on the safety analysis data of the drug manufactured by Novartis,
FDA discontinued the product marketing and sales in the United States from
March 30th,2007.
•But Novartis alleged that the affected patients had pre-existing
cardiovascular risk factors and were not related to the Tegaserod use.
•However , it was unable to provide with sufficient data opposing the reported
heart risks within the given timeframe given by the FDA authorities.
•On the same day as the FDA announcement, Novartis Pharmaceuticals
Canada announced that it was suspending its market and sales of the drug in
response to a request from Health Canada.
•On July 27th,2007 ;the FDA announced that it was permitting the restricted
use of Zelnorm (under emergency-IND) ,marketed by Novartis.
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INDIAN MARKET
Banned in 2011-
•The Drug Technical Advisory Board’s sub-committee had decided to ban
the drug due to increased side effects and sent a proposal to the Health
Ministry for final notification.
•The drug was prohibited for its manufacture, distribution and sales in India
from March,2011.
•Based the global ban of the drug after it showed 10 fold increase in risks
related to heart attacks and strokes
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CONCLUSION:
The Zelnorm manufactured by Novartis was the first FDA-approved drug for
the treatment of IBS-C , which had additional use in the treatment of
functional dyspepsia and gastroparesis.
However as there were reported cases on cardiovascular risks on its
usage, FDA effectively stopped the marketing of the drug in the U.S. market
and finally putting a ban on the product. But eventually it was permitted for
restricted use in emergency situations in U.S.
This was followed by withdrawl from Canada market by Health
Canada and in India by Ministry of Health also.
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REFERENCES:-
•List of banned drugs - http://dic.mspcindia.org
• Zelnorm (tegaserod maleate) Information
- USFDA Official Website
• Heart Risk Prompts FDA to Pull IBS Agent Tegaserod (Zelnorm)
- www.medpagetoday.com/gastroenterology/irritablebowelsyndrome/5366
• Desperately Seeking Serotonin- A Commentary on the Withdrawal of
Tegaserod and the State of Drug Development for Functional and Motility
Disorder
– By Pankaj Jay Pasricha, MD (www.gastrojournal.org)
•Ban on Tegaserod, Gatifloxacine due to side-effects
- (http://timesofindia.indiatimes.com)
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THANKYOU
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