Implications of Zelnorm's Withdrawl

Zelnorm (tegaserod maleate), a serotonin 5-HT4 receptor partial agonist indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation, was pulled today from the market by Novartis on the recommendation of the FDA. It had previously been reported to have rare instances of ischemic bowel associated with the drug's use and now appears to have rare, but significant, problems with ischemic cardiovascular disease after a retrospective review of 29 studies of the drug.

(CBS News) Earlier this year, Novartis gave the FDA the results of 29 clinical studies of Zelnorm for treatment of a variety of gastrointestinal tract conditions. The analyses showed 13 of 11,614 patients given Zelnorm had serious and life-threatening cardiovascular side effects, while just one of the 7,031 patients given dummy pills did, the FDA and Novartis said in separate statements.

This drug follows closely the pulling of Pergolide yesterday two months after reports in the New England Journal of Medicine demonstrated the problems with this drug causing valvular regurgitation (leakage). It seems we'll be seeing more and more drugs pulled after the Vioxx fiasco and closer scruitiny by the media and Congress. But the incidence of problems (0.012%) vs (0.0014%) is mighty small, especially when one considers that acetominophen (Tylenol®) liver toxicity approaches a 4% incidence in emergency rooms in the US and England. Will Tylenol® be next?

These withdrawls suggest that even retrospective meta-analyses of outcomes that demonstrate almost no side effects will be the expected norm for drug safety in the post-market drug survellance era we have entered. Certainly, the potential for litigation is significant if side effects and potential complications are not disclosed. However, while patient safety is always paramount, the risk/benefit ratio of any drug should be considered when it is prescribed and there may be circumstances when certain drugs with higher side effects are in the patient's best interest.

So now I'm confused. How do we compare the incidence rate of side effects of drugs we prescribe? Are some drugs held to a double standard? What drug safety level should doctors tolerate?

-Wes

via KevinMD.