NSAIDs: FDA Warning on Bextra, Celebrex

Symptoms of Rheumatoid Arthritis

Bextra, Celebrex, NSAIDs, and You

WebMD Live Events Transcript

The FDA has issued warnings on the entire class of NSAIDs (nonsteroidal anti-inflammatory drugs). They have recommended that the Cox-2 inhibitor Bextra be pulled from the market and that all prescription NSAIDs, including Celebrex, get revised labeling, including a boxed warning and a medication guide. Even over-the-counter NSAIDs are asked to issue revised labeling to advise consumers on their safe usage. What does this mean for you in your quest for pain relief? WebMD's Michael Smith, MD, joined us on April 8, 2005 to answer your questions.

The opinions expressed herein are the guests' alone and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.

MODERATOR:
Welcome back to WebMD Live, Dr. Smith. Thank you for joining us today. Yesterday the FDA issued a public health advisory that had important changes and warnings for Cox-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). The first thing they did was ask Pfizer to remove Bextra (valdecoxib) from the market. Can you explain the reasoning behind this request?

SMITH:
The FDA asked Pfizer to remove Bextra from the market because they said that it had more risks than Celebrex and other similar drugs. And since Bextra is not known to treat pain and inflammation better than other drugs, the FDA felt there was no reason to keep it around. In addition, Bextra can cause potentially serious skin reactions.

MEMBER QUESTION:
I was wondering why they pulled Bextra off the market before Celebrex. Wasn't there much controversy about Celebrex before Bextra?

SMITH:
There is more research on Celebrex than on Bextra because it has been around longer. However, all of the research on Celebrex thus far does not show any increased risk if Celebrex is taken at the regular dose of 200 milligrams per day. Bextra was shown to increase risk even at its normal dose. I think that the potential for serious skin reactions may have been what put Bextra over the edge to have the FDA want it removed from the market.

MODERATOR:
The FDA is also asking manufacturers of all marketed prescription NSAIDs, including Celebrex (celecoxib), a Cox-2 selective NSAID, to revise the labeling [package insert] for their products to include a boxed warning and a medication guide. What are they asking the manufacturers to further describe in the additional warnings?

SMITH:
A black box warning is the most severe warning that the FDA applies to drug labels. In this case, the black box warning will warn of the potential risks of heart attacks, strokes, and stomach ulcer bleeding. This warning applies to all prescription anti-inflammatory drugs on the market.

The medication guide will be information provided to the patients at the time these drugs are prescribed to help them understand these risks. The FDA is applying this warning to all prescription anti-inflammatory drugs but the absolute risk isn't really known. This is because there is not a lot of research looking at the heart and stroke risks of all of these drugs.

MEMBER QUESTION:
What kind of skin reactions does Bextra cause?

SMITH:
The most serious skin reaction that has been seen with Bextra is called Stevens-Johnson syndrome. In this condition, the skin essentially sloughs off as if someone sustained a serious burn. It can be widespread over the entire body and has caused death in a few people. Although it's rare, since Bextra doesn't seem to offer any particular advantages over Celebrex or other drugs, the FDA felt it wasn't needed on the market.

There are other minor skin reactions as well -- more in the form of allergies. But we aren't able to determine who is likely to have these serious skin reactions.

MODERATOR:
Is this reaction only with Bextra? What about other Cox-2 inhibitors?

SMITH:
This severe reaction has really only been reported with Bextra. However, Celebrex, the other Cox-2 inhibitor on the market, can cause the more minor skin reactions. All anti-inflammatory drugs have the potential for these minor skin reactions. But the more serious reactions have not been associated with these drugs.

MEMBER QUESTION:
So if a person has been taking Bextra for a period of time, besides stop taking it immediately and talking to your doctor, should one have their heart checked out?

SMITH:
With Vioxx, people asked the same question. Available research and experts believe that once someone stops taking these drugs the risks of heart attacks and strokes goes down fairly rapidly.

One thing I want to be sure that people understand is that other risk factors, such as high cholesterol, high blood pressure, smoking, etc. are much stronger risk factors for heart attack and stroke.

There is no reason to rush to have your heart checked out. However, it's a good idea to discuss your risk with your doctor. If the two of you determine that your risk of heart disease may be elevated, then further testing may be warranted.

MEMBER QUESTION:
I felt that Vioxx and Bextra effectively eased the pain and inflammation of my rheumatoid arthritis (RA), much more than Tylenol. Could it be that there is no pharmaceutical solution to moderate RA pain?

SMITH:
Vioxx and Bextra are anti-inflammatory drugs. Tylenol is not an anti-inflammatory drug. It's unusual for Tylenol to help significantly with RA pain. However, Vioxx, Bextra, and Celebrex have not been shown to relieve pain more than the other prescription anti-inflammatory drugs.

There are about 20 of these drugs available so you have many more options. The only people that may have a more absolute reason to take Celebrex over the other prescription anti-inflammatory drugs are people who have had a stomach ulcer. I have actually had a stomach ulcer from ibuprofen and therefore I am taking Celebrex. But most other people do not need Celebrex and can take one of the other anti-inflammatory drugs.

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MEMBER QUESTION:
I suffer from RA and ulcerative colitis. My doctor put me on Mobic recently and I've been experiencing more intense and more frequent flares. What are my choices now? Are all NSAIDs considered unsafe?

SMITH:
I suspect that your doctor put you on Mobic because it's felt to be a little easier on the stomach and intestines than some of the other drugs. However, there isn't a lot of evidence to back that up.

As far as the risks, all of the prescription anti-inflammatory drugs have been lumped into the same risk category at this point. This means they all carry some risk of heart attack and stroke.

However, it's important to keep in mind that when you have RA or moderate to severe osteoarthritis (OA) you don't really have much choice but to take one of these drugs. I wouldn't call them all unsafe. Yes, they all have risks. But they definitely all have their benefits as well. I think people should take the drugs if that's what they need. And then address other heart disease risk factors, such as diet, exercise, cholesterol, smoking, etc.

MODERATOR:
However, we are not likely to see either Vioxx or Bextra return to the market, are we?

SMITH:
While it's possible, it's highly unlikely. Pfizer says they are going to talk to the FDA more about putting Bextra back on the market. And Merck has also said that they would do the same. However, the FDA said yesterday that they would need a lot more safety data on these drugs to bring them back. This means that if they were to return, which I think is highly unlikely, it would likely be years before that happened. They don't seem to have any advantages over other available drugs.

MEMBER QUESTION:
Is over-the-counter Celebrex as effective as the Rx Celebrex?

SMITH:
There is no over-the-counter version of Celebrex. Celebrex is only available as a prescription.

MEMBER QUESTION:
How come they haven't pulled Celebrex off the market yet? Do they feel it is actually safer than Bextra and Vioxx?

SMITH:
Yes, the FDA says that after looking at all the data the benefits of Celebrex appear to outweigh the risks. At the normal dose of 200 milligrams of Celebrex a day, there doesn't really appear to be much increased risk of heart attacks and strokes. The studies that have shown an increase in risk have been cancer prevention studies. In these studies, Celebrex was taken at doses of 400 to 800 milligrams a day.

MEMBER QUESTION:
RA itself can negatively affect the heart and lungs, correct? Then those of us who have RA already have a risk factor, correct?

SMITH:
That's a good point. People with RA already have a somewhat higher risk of heart problems. However, people with RA also really don't have much of a choice than to take an anti-inflammatory drug. Therefore, you take the drug and just know that there is some risk associated with it but don't beat yourself up about it. I'm taking it because I know I don't really have a choice.

What I hope people will do is address the other risk factors that I've talked about and lower their risk of heart disease and strokes in that way. Also, we don't really know what the real risks are. There is little research done on most of these anti-inflammatory drugs. It's likely that the increase in risk is fairly small and not something that we all need to be constantly worrying about. However, it's something that we should be aware of.

MEMBER QUESTION:
What other medicine besides Bextra can I use with Coumadin?

SMITH:
Celebrex can be used with Coumadin. If that doesn't work for whatever reason, you can talk to your doctor about other possibilities. The older anti-inflammatory drugs may be just as safe as long as you take a drug to suppress acid production in your stomach.

MEMBER QUESTION:
NSAIDs, which I took about 10 years ago, made me feel debilitating nausea. Are there better NSAIDs now?

SMITH:
Yes, some of the more recent NSAIDs are associated with less nausea. Mobic and Relafen are two possibilities. Talk to your doctor if you need to take an NSAID. You may have to try several to find one that works for you as far as the nausea.

MODERATOR:
The FDA is also asking manufacturers of over-the-counter NSAIDs to revise their labeling to include more specific information about the potential gastrointestinal and cardiovascular risks and to add information to assist consumers in the safe use of the drug. Would you comment?

SMITH:
There is little research on the risks of over-the-counter NSAIDs and heart attack and stroke. However, the FDA feels that there is the potential for risk and thus they are asking the makers of these drugs to include information on the labeling. However, the warning will not be as strong as on prescription drugs. It's felt that the lower doses of over-the-counter drugs make them less risky.

In addition, these drugs can be safely taken for up to 10 days at over-the-counter doses without worrying about increased risk of heart attack and stroke. What we don't exactly know is what the risk is if someone takes these drugs for a few days to a week or so, every month, maybe for menstrual pain, headaches etc. It's likely the risk associated with this use is minimal, if any.

If you need these medications for more than 10 days check with your doctor. In addition to the heart risk, taking these drugs for more than 10 days increases the risk of stomach ulcer bleeding which can also be very severe.

MODERATOR:
The one NSAID not included in the warnings is aspirin. Why?

SMITH:
There is much evidence that aspirin decreases the risk of heart disease. That's why aspirin was not included in this warning. Aspirin can increase the risk of stomach ulcer bleeding however. Therefore it should be taken regularly only under the care of a doctor.

It's important to keep in mind that if you're taking aspirin for heart disease prevention it can normally be taken at a low dose of 81 milligrams and give you the same protection as the higher dose.

MODERATOR:
Let's clarify the role of Tylenol (acetaminophen) in all of this discussion of NSAIDs.

SMITH:
Tylenol is not an NSAID. Therefore, it's not included in this warning. Tylenol relieves pain in another way but isn't particularly effective for inflammation. Tylenol can be safely taken at the over-the-counter dose. It's important to not take more Tylenol than recommended as that can lead to liver damage.

MEMBER QUESTION:
Is Plaquenil considered an anti-inflammatory drug? Can Plaquenil and aspirin be taken together?

SMITH:
Plaquenil is not an anti-inflammatory drug and does not apply to this warning. Yes, you can take aspirin and Plaquenil together if your doctor has suggested you do so.

MEMBER QUESTION:
Why is it doctors will keep on giving you anti-inflammatory drugs, just different ones, even though they don't seem to take your inflammation down at all?

SMITH:
We often have to try several different anti-inflammatory drugs to find the right one for an individual. This includes finding one that doesn't cause side effects as well as finding one that best relieves the pain and inflammation.

If you're not having any response to multiple anti-inflammatory drugs, it makes me think you need different and stronger medication. Since I don't know your diagnosis, I can't make suggestions as to what other drugs may be needed.

MEMBER QUESTION:
So if Vioxx is off the market, which I never took, and Celebrex didn't really help, and now with Bextra off the market, people should consult their doctors to see what other alternatives are available for pain relief?

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SMITH:
There are over 20 available prescription anti-inflammatory drugs on the market. There is a complete list of these drugs in the WebMD Special Report on painkillers. You should talk to your doctor about the available options to see which one might work best for you.

MEMBER QUESTION:
I had a double bypass in October of 2004 and am currently on Ibuprofen 600 3-4 times a day for back pain. Should I be concerned with these new warnings?

SMITH:
The new warning does apply to ibuprofen. You are taking a prescription-strength of ibuprofen. Given your previous heart problems that does make it more of a concern.

However, there really is not much, if any, research to directly implicate ibuprofen as causing heart attacks and strokes. Some research has suggested that it may even decrease the risk. But since we really don't know at this point, the FDA is recommending language about the warning on all of these drugs. I would talk to your doctor about this, but again, it may not really be much of an option for you to not take the drug. And any increase in risk is likely small.

MEMBER QUESTION:
What is your opinion of the risk of using 200 milligrams of Celebrex intermittently (maybe once every 4-5 days) to alleviate my joint aches and stiffness? I was diagnosed with OA and Celebrex works better and longer than over-the-counter NSAIDs. Cardiovascular events have occurred in my family of origin, but I am now 66 years old and apparently heart healthy.

SMITH:
Even taking Celebrex on a daily basis at 200 milligrams a day has not been linked to an increase in heart attacks and strokes. Therefore, taking it intermittently is unlikely to be an issue. One thing to keep in mind is that Celebrex has not been shown to relieve pain and inflammation better than other NSAIDs. It is much more expensive if that's a concern for you, however.

MEMBER QUESTION:
If I have kidney problems, how often should I have them checked, being on anti-inflammatory drugs?

SMITH:
All of the NSAIDs can increase the risk of kidney problems. Cox-2 inhibitors, which include Celebrex, were developed to potentially decrease this risk. This hasn't exactly panned out however. As far as how often you need to get your kidneys checked, that depends on how severely your kidneys are affected and what other problems you have. But you definitely need to have regular checkups at least every few months or so.

MODERATOR:
Dr. Smith, we are almost out of time. Before we wrap things up for today, do you have any final words for us?

SMITH:
First of all, if we didn't have a chance to get to your question, check out the WebMD Special Report: Painkillers Under Fire ; hopefully this will help you find your answer.

But I want to be sure to point out that these drugs have their definite benefits. Many of us need to take them in order to maintain our quality of life. If you don't need them every day, don't take them every day.

But if you do, take them and don't worry yourself to death about the risks of heart attacks and strokes. The risk is likely minimal, but it's a real risk. Just talk to your doctor about other ways you can lower your risk of heart disease and stroke. That's my plan and that's what I recommend for all other arthritis and pain sufferers out there.

MODERATOR:
We are out of time. Thank you Dr. Smith for joining us today. And thank you, members, for your great questions.

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Reviewed on 4/20/2005 6:59:22 PM

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