FDA: Zelnorm® Unsafe

The U.S. Food and Drug Administration (FDA) requested that Novartis Pharmaceuticals Corporation of East Hanover, New Jersey, voluntarily discontinue marketing Zelnorm® (tegaserod) because patients who take the drug may have an increased risk of developing heart problems. Novartis agreed to voluntarily suspend marketing of the drug in the United States.

According to the FDA press release, Zelnorm® is a prescription medicine that was approved in July 2002 for short-term treatment of irritable bowel syndrome (IBS) in women whose primary symptom is constipation. It was subsequently approved in August 2004 for the treatment of chronic constipation for men and women younger than 65 years old. Zelnorm® is marketed in 55 countries.

The FDA is currently advising patients who are using Zelnorm® to contact their healthcare providers to discuss treatment alternatives. Additionally, patients who are taking Zelnorm® should seek emergency medical care if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking or other symptoms of a heart attack or stroke.

Throughout February and March 2007, Novartis reported the results of a new analysis of 29 short-term (one to three months) randomized, controlled clinical trials of Zelnorm® to the FDA. The analysis included more than 11,600 patients treated with Zelnorm® and over 7,000 patients treated with placebo. The data showed that the risk of serious heart-related side effects like chest pain, heart attack and stroke with the use of Zelnorm® is higher than with placebo treatment. Thirteen Zelnorm®-treated patients (or 0.1 percent) experience heart problems, compared with only one patient in the placebo group (or 0.01 percent). Based on these results, the FDA concluded that the benefits of this drug no longer outweigh the risks for most patients.

The FDA announced that it will work with Novartis to allow access to Zelnorm® as an investigational drug for patients who have no other treatment options. In such cases, the benefits may outweigh the risks. The FDA is also considering re-introducing Zelnorm® in the future, if a specific patient population can be identified in which the benefits of the drug outweigh the risks. Any such proposal would be the subject of a public advisory committee meeting before an FDA decision.

In another press release, Novartis announced that it is complying with an FDA request to suspend marketing of Zelnorm®. Novartis reported that the side effects occurred primarily in patients who had pre-existing heart disease and/or heart-related risk factors and insisted that there is no demonstrated causal relationship between Zelnorm® and these events.

Still, Novartis recommends that patients who are taking Zelnorm® speak with their healthcare providers about alternative treatment options. Also, patients can return any unused and unexpired Zelnorm® tablets to Novartis for reimbursement of out-of-pocket costs. More information can be obtained by calling the Novartis Customer Interaction Center at 888.NOW.NOVA (888.669.6682).

For information about integrative therapies for  irritable bowel syndrome  or constipation, please visit Natural Standard's  Condition Center database.

Comments

[J.W.]

I've heard that peppermint oil may improve IBS symptoms. Has anyone ever tried this before? Have any studies evaluated its effectiveness in children?

[J. Kathryn Bryan]

I have two friends with IBS and chronic constipation who have had good luck with peppermint oil tincture for symptoms. In their personal experiences, it reduces their symptoms of cramping and nausea. One of these friends says that the extract makes her tummy feel cool from the inside after ingestion, which I imagine would be nice if one is in the throes of excruciating gi pain.

In children, I'd imagine that you'd need to reduce the dose. Most peppermint oil extract containers explicitly instruct people to mix the drops of extract mixed into a small glass of water. This is because the drops cause a very uncomfortable burning sensation in the mouth when taken alone. (I tried it once, just to test the theory out.) Kids are more sensitive to unusual tastes and have smaller bodies. I'd give them less peppermint oil with more water. Maybe you could even present it as a novelty. For instance, mix it with milk and call the creamy green concoction a "grasshopper drink" to encourage a positive view of the stuff.

Peppermint oil may not have the same effect on you, and you should check with a qualified healthcare professional.

[Dexter Otis Grenne]

I'm not fully educated on the process that leads to the approval of a certain drug, but how can a drug that heightens the risk of heart attacks and strokes get put on the market? I would have assumed they did that sort of testing before they asked the FDA for approval. This leads me to believe that drug companies have a tendency to either not do the proper testing and research, or, like in the Harrison Ford picture "The Fugitive," cover up the bad results just to be able to sell the drug.

[J. Kathryn Bryan]

Aspirin kills a ton of people every year. Every method of healing, conventional or otherwise, has potential risks. No drug or treatment can be guaranteed to never cause adverse effects in anybody. The regulations ascribed to a chemical agent have more to do with a risk-benefit analysis than a guarantee to never do harm.

[Anonymous]

I agree with the fact that drugs like aspirin kill millions and yet they are still readily available over the counter. I feel there needs to be a stronger emphasis on patient counseling with over-the-counter medications, as well as behind-the-counter. All FDA-approved drugs can cause an adverse event even after they've been approved. If you recall, drugs such as Bextra and Zocor have been pulled off the market due to adverse events reported. This might sound bad, but if every single drug had to show a definitive 100% safety profile guaranteed for the life of it being out on the market (which is impossible), there wouldn't be any prescription drugs on the market.

[D. B. Martin]

J Kathryn Bryan and anonymous make very interesting points... no drug is risk free and many offer benefits that are worth their risks. The problem is, drug companies make a practice of obscuring and minimizing the risks with deceptive marketing practices. Consequently, neither physicians or patients are making truly informed decisions. This is why an unacceptable number of unexpected deaths or illnesses occur after a new drug has been on the market for a few years.

Had the medical community been openly educated about potential risks, which populations were most vulnerable to the risks and how to avoid them, some drugs that have been pulled off the market might still be available. But this information is deliberately buried and minimized for fear that it might affect market share and bottom line profits. If this sounds too evil and conspiratorial to be true, I assure you, having worked for the industry for years, it is not. With any newly approved drug, people are well advised to do their homework, scour the prescribing information and perhaps even wait for a year or two to see what crops up in post-marketing reports before taking the drug.

[Dagan B]

In response to Dexter, drug companies go through four phases of clinical trials before a drug is approved to be put out on the market. The limitation of this is that the trials are only involve a select number of people. It is not until the drug hits the market that the effects can truly be observed in the general population. Generally, clinical trials have many exclusion criteria in order to get a "perfect" patient population to initially test the drug out.

I think that doing your homework when prescribed a new drug is a must. There is only so much that we can get from our doctors before we have to do a little research on our own. Besides, there's an enormous amount of statistics on drug safety and efficacy that our doctor's aren't expected to know off the top of their heads.

[Ceadda Wilcox]

Ugh, who to trust then? Hypothetical breakdown...if I try to get all of the facts, I will get overwhelmed because for every positive study, there is an equally opposing study - a frustrating rule of healthcare. So the more I research, the less I'm sure of, the more anxious I am. My doctor prescribes me anti-anxiety pills, which have a side effect of headaches, which I'm afraid to treat because of my anxiety over not knowing whether aspirin will stop my headache or kill me....oh the irony!

[mike]

It looks like everyone is scared these days about medications. What we have to realize is that medications are chemicals. As a pharmacist, I do not take any medication unless I truly need it. This may sound hypocritical to my profession, but people are trying to solve their health problems caused by irresponsible behavior with miracle drugs. There is no such thing as a miracle drug. The drugs just enhance your body’s ability to produce certain results. One side effect is that your body is working overtime to produce these effects, yet people keep doing harmful things to their body. We, as a society, need to change our lifestyles and habits to become a healthier society without taking a drug to fix every problem. This will help prevent many negative side effects of medications on the market.

[Kalyn]

There is no 100% safety profile for any drug. Drugs can cause many side effects. If the physician reviews all the side effects with one drug, the list can go on and on. That would only scare you to take the drug. When in doubt, it is best to check with the pharmacist.

[MV]

It is difficult to discern the long-term side effects of medications, and that is what happened with Zelnorm and other drugs pharmaceutical companies had to remove from the market. Sometimes clinical trials are not sufficient in identifying problems that could arise in the long run. People must be vigilant and take notice of symptoms that arise when using the drug.

[Emily P.]

I realize that there are risks involved with every drug, but it does scare me how downplayed the side effects of many new medications are. How many times so you see or hear a commercial for some of these drugs and the adverse effects are listed in small print or read off quicker than you can follow? How are we supposed to be well educated when the manufacturers are trying to limit the information out there?

[Paul]

This whole thing just reminds me of a couple of episodes of 20/20, which is a fairly reputable news show as far as they go. The first one was about a implantable spinal device to help people that had injuries, but it was later found to cause serious damage and paralysis. The people were all complaining that it made it through the approval process when it could turn out so bad.

The second episode was about a different implantable device that was working its way through the approval process. People were upset that it was taking so long for something that could help people to be allowed on the market. The FDA has a tough line to walk to try and get medications to people that can receive benefit, but not so early as to miss major problems. When side effects occur only in 0.1% of the subjects, you need to have 10s of thousands of subjects to really see it become statistically significant from placebo. Yes, it is sad that this happens, but there is just no way to prove that drugs are conclusively safe before they are approved.

[jon]

I would be very careful with peppermint oil or any essential oil for that matter. Peppermint oil is a class 2 neurotoxin and can cause serious nerve and brain damage. I tried 2 drops in a glass of of water for digestion problems and suffered a serious reaction.
It affected my vision, and I now have chronic tension headache symptoms, which have only slightly improved over the past year. The neurologist thinks it caused nerve damage in the CNS of the brain. Essential oils are pure poison. I would gladly suffer the indigestion
of a year ago than the headache and vision problems 2 drops of peppermint oil caused me.

[Ajlouny]

Too many drugs have come to market bearing pedigrees that imply that they've been clinically tested through peer review rigorous FDA evaluation, and then after millions of patients take the drug, it proves dangerous or even deadly.