Are COX-2 drugs safe for you? An interview with a Mayo Clinic specialist

Bextra is the latest in a string of arthritis pain relievers either withdrawn from the market or relabeled with stricter health warnings. What are your options for pain relief? A Mayo Clinic specialist responds.

First it was Vioxx %u2014 pulled from the market in September 2004 with no advance notice. Then came warnings about Celebrex, Aleve and Bextra. Eric Matteson, M.D., a rheumatologist at Mayo Clinic, Rochester, Minn., discusses the safety implications of these commonly prescribed arthritis pain relievers, known as COX-2 inhibitors, as well as the safety of traditional nonsteroidal anti-inflammatory drugs (NSAIDs).

Why was Vioxx pulled from the market?

The immediate withdrawal of Vioxx was based on data from a three-year trial designed to evaluate the possible effectiveness of this drug in preventing the recurrence of colon polyps. In comparing people taking Vioxx with those taking a placebo %u2014 an inactive medication %u2014 those taking Vioxx had an increased risk of cardiovascular problems, such as heart attack and stroke, after 18 months. Although the risk of a Vioxx-related heart attack or stroke is very small, the degree of risk depends on how much Vioxx you took and for how long.
What are the alternatives to Vioxx?

You can take the COX-2 inhibitor Celebrex or switch to a traditional nonsteroidal anti-inflammatory drug, such as naproxen (Aleve). Until recently, you could also take the COX-2 inhibitor Bextra.

Why was Bextra taken off the market?
According to the Food and Drug Administration (FDA), Bextra was taken off the market because of:

Insufficient data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse cardiovascular events in short-term coronary artery bypass surgery trials. These cardiovascular events may be associated with chronic use of Bextra.

Reports of serious and potentially life-threatening skin reactions %u2014 Stevens-Johnson syndrome and toxic epidermal necrolysis with sloughing of the skin %u2014 in people using Bextra.

Lack of any demonstrated advantages in using Bextra when compared with other NSAIDs.

Is Celebrex safe?

Celebrex, like Vioxx and Bextra, is a COX-2 inhibitor. COX-2 inhibitors don’t cause the stomach bleeding and ulcers that traditional nonsteroidal anti-inflammatory drugs (NSAIDs) might. If you’re susceptible to gastrointestinal bleeding or ulcers, Celebrex may be a safe and appropriate treatment for you. Celebrex also might be an appropriate choice if you take drugs that contain prednisone. Those drugs, like NSAIDs, can cause stomach bleeding. To take traditional NSAIDs on top of those drugs would further increase your risk of bleeding.

If you’ve been taking a COX-2 inhibitor because of your history of stomach bleeding or ulcers, don’t assume that Celebrex is automatically the right choice. Celebrex can cause kidney problems, hypertension and fluid retention. Although the risk of stomach bleeding may be lower if you take Celebrex than if you take a traditional NSAID, it’s important to realize that stomach bleeding can still occur. Older patients may be at higher risk for all of these side effects.

In addition, you shouldn’t take Celebrex if you have sulfa allergies.

Because of concerns that Celebrex, like Vioxx and Bextra, may pose an increased risk of heart attack and stroke, the FDA has asked the drug manufacturer to revise its drug label to include a warning of the medication’s cardiovascular and gastrointestinal risks. The FDA is also encouraging doctors to prescribe the lowest effective dose for the shortest duration possible, in accordance with an individual’s treatment plan.

Are traditional NSAIDs safe?

If you aren’t at risk of stomach bleeding, your first choice for arthritis pain relief should be a traditional NSAID, such as ibuprofen (Advil, Motrin, others). In general, traditional NSAIDs are just as effective as COX-2 inhibitors for reducing pain and inflammation, although as with any group of drugs, there are individual patients who find one drug more effective than another.

If you switch from a COX-2 inhibitor to a traditional NSAID, be aware that some can cause stomach bleeding in a small percentage of people. If you’re concerned about stomach bleeding, consider taking a traditional NSAID along with a proton pump inhibitor, which helps protect your stomach and reduces your risk of ulcers and bleeding. Be aware that NSAIDs also can cause kidney problems, hypertension and fluid retention in some patients.

The FDA has also called for manufacturers of over-the-counter NSAIDs to revise their labels to include more information about their possible risk of cardiovascular events and gastrointestinal bleeding. These label changes don’t apply to aspirin, though, because the evidence clearly shows that aspirin reduces the risk of heart attack and stroke in certain people. However, aspirin, like other NSAIDs, is associated with an increased risk of stomach bleeding.

Aleve has also been in the news. Is it safe?

A recent study of the NSAID naproxen (Aleve, others) for prevention of Alzheimer’s disease has raised concerns that it, too, may be associated with an increased risk of heart attack. If there is an increased risk, this risk is likely small. It has not emerged as a concern in the roughly 30 years that the drug has been available. It’s very possible that the other nonsteroidal anti-inflammatory drugs, such as ibuprofen, pose this same risk. Most patients who are doing well with these drugs can continue to take them.

At this point, the exact degree of increased risk for such problems as heart attack and stroke seems to be low for most patients but higher for others. The FDA has called for the manufacturers of naproxen to revise their labeling, the same as for other NSAIDs.

What should you take if you have arthritis pain but not inflammation?

If you have pain but you don’t have inflammation, you could try over-the-counter or prescription pain relievers such as acetaminophen (Tylenol, others), tramadol (Ultram) and nonaspirin salicylate products (Disalcid, Trilisate, others).

What if Vioxx or Bextra was the only medication that worked for you? What do you do then?

You may need to consider combining other drugs to get the relief you need. Also consider nondrug alternatives, such as physical therapy, acupuncture and massage, to help with your pain and inflammation.

Vioxx was extremely popular. Will this medication eventually return to the market, but with a stronger label warning? What about Bextra?

The FDA has stated that it will review any proposal by the manufacturer for resumption of the sale of Vioxx, with a stronger warning label. The manufacturer has not stated if or when it plans to submit such a proposal. The FDA has stated that the manufacturer of Bextra must further study the drug’s risks before considering resumption of its sale.