FDA Pulls ZELNORM Off the Market for Safety Reasons

The Food and Drug Administration (FDA) removed tegaserod (ZELNORM), a widely prescribed constipation drug, from the market on March 30, 2007.

At first, the drug’s manufacturer sought approval for tegaserod only for the treatment of constipation-predominant irritable bowel syndrome (IBS). Public Citizen wrote aletter to the FDA opposing the approval of this drug in March 2001 because studies showed it to be only marginally effective for this purpose. Further, the drug exhibited serious safety problems in clinical trials before it was approved, including an increased incidence of non-cancerous ovarian cysts and a five-fold increase in fainting compared to patients receiving a placebo. For the past three years, we have urged readers of Worst Pills not to use the drug.

Despite the aforementioned information, the FDA approved tegaserod in 2002 for patients with constipation-predominant IBS. We have pointed out to the FDA that only highly unusual data manipulation by the company produced a finding of effectiveness, and even then it was marginal. In August 2004, Novartis received approval to also market tegaserod for chronic constipation from unknown causes although questions about the drug’s safety and efficacy remained unresolved at the time of the approval for this second use as well.

Now, Novartis Pharmaceuticals, the drug’s manufacturer, has compiled 29 clinical studies showing an eight-fold increased risk of cardiovascular adverse events, including heart attack, chest pain and stroke with tegaserod. The company submitted these results to the FDA, which, after reviewing this information, asked Novartis to withdraw the drug from the market. The pharmaceutical company agreed almost immediately to stop selling the drug in the U.S., but the drug will continue to be sold overseas.

Tegaserod was one of the top 200 most-prescribed drugs in the country in 2005: more than 2 million prescriptions were dispensed in that year, a 21.5 percent increase from 2004. The pattern continued in 2006, with drug sales reaching a massive $400 million, up 31.1 percent from 2005.

This incident raises questions about both the adequacy of the FDA’s pre-approval review and post-marketing surveillance. These kinds of mistakes are inexcusable, especially when they are avoidable, as in this case.

To read the full text of the FDA’s announcement, visit the FDA’s Web site at: www.fda.gov/cder/drug/advisory/tegaserod.htm.

What You Can Do
If you are currently taking tegaserod, you should contact your physician right away to discuss alternative treatments.

Patients taking tegaserod should be monitored for symptoms of a heart attack or stroke. These include severe chest pain, shortness of breath, dizziness, sudden onset of weakness, difficulty walking or talking, or abnormal vision. You should seek emergency medical care immediately if you experience any of these symptoms.

In addition, patients taking tegaserod are vulnerable to ischemic colitis, which is acute abdominal pain caused by a lack of blood flow to the intestines. If you experience new or worse abdominal pain with or without blood in your stools, stop taking tegaserod right away and tell your doctor. Your doctor may need to do tests to find out if you have a serious problem.

Sometimes tegaserod causes diarrhea. Call your doctor right away if you get so much diarrhea that you get light-headed, dizzy or faint.

According to Novartis Pharmaceuticals, patients who still have a remaining supply of tegaserod can return the drugs and Novartis will reimburse these individuals for out-of-pocket costs. Further details can be obtained by contacting the Novartis Customer Interaction Center at 888-NOW-NOVA (888-669-6682).