Vioxx: The Pros and Cons of Other Drugs (cont.)

According to the American College of Rheumatology, people with rheumatoid arthritis are more than twice as likely as osteoarthritis patients to have problems with NSAIDs. Factors that increase your risk for gastrointestinal problems from NSAIDs include being over 60, smoking, having a history of ulcers, having heart disease, and taking anti-inflammatory steroids or blood-thinning drugs.

Theodosakis says people taking NSAIDs regularly should also be concerned about the possibility of losing cartilage, the padding between joints. "This is an issue with all the anti-inflammatory drugs," he says. "They really haven't been studied for cartilage loss adequately, and the evidence we do have is very damning."

Cox-2 Inhibitors

Cox-2 inhibitors include Celebrex and Bextra, as well as Vioxx, which was taken off the market due to its heart risks. They are newer kinds of NSAIDs designed to relieve pain without hurting the stomach. They work by inhibiting a specific enzyme called cyclooxygenase-2, or Cox-2. Older NSAIDs covered in the section above not only inhibit Cox-2, but they also suppress Cox-1, an enzyme that may play an important role in protecting the stomach lining.


  • Cox-2 inhibitors may not be as likely to cause stomach ulcers as other forms of NSAIDs.
  • They are longer-lasting drugs. One dose of Celebrex relieves pain for up to 24 hours.
  • Cox-2 inhibitors don't thin the blood, so they can be used by people taking prescription blood-thinning drugs, such as warfarin (Coumadin), and people with anemia or blood clotting disorders.


  • Cox-2 inhibitors are more expensive than traditional NSAIDs, and no better at controlling pain.
  • They have about the same potential to cause kidney problems as other NSAIDs.
  • It's not yet clear whether they all carry the same heart risk, or if Vioxx was unusual in that regard.

Since the Vioxx recall, Celebrex and Bextra have come under even more intense scrutiny. Some doctors suspect that dangers posed by Vioxx may extend to all Cox-2 inhibitors.

Pfizer, the company that makes Celebrex and Bextra, has made two important announcements on this issue. On Oct. 18, 2004, Pfizer said it is confident in Celebrex and announced a major new study to assess Celebrex's affect on the heart. The study is planned to start in early 2005. It will look at more than 4,000 arthritis patients who have had a prior heart attack. Pfizer is a WebMD sponsor.

On Oct. 15, 2004, Pfizer also reported that Bextra appeared to increase the risk of serious complications for people abroad who were recovering from heart bypass surgery. In the U.S., the drug is not approved for use in people recovering from heart bypass surgery.

There is also some controversy over whether Celebrex is really less likely to cause ulcers than older NSAIDs. In a June 2002 BMJ editorial, European researchers asserted that the original study data on Celebrex were interpreted in a misleading way. The data, published in the Journal of the American Medical Association in 2000, showed that at six months of treatment, Celebrex users had significantly fewer ulcer complications than those taking ibuprofen or diclofenac, a prescription NSAID.

The BMJ editorial showed that after six months of treatment, ulcer complications with Celebrex rose steadily, reaching a level only slightly lower than ibuprofen and higher than diclofenac by 12 months. These results were not reported in the 2000 JAMA article.

Some doctors are recommending that former Vioxx users switch to a drug called Mobic, an NSAID that is very similar to a Cox-2 inhibitor, but not classified as one in the U.S.

"I have gone back to [Mobic], which I used to prescribe a couple of years ago," says Sudhir Diwan, MD, director of the pain medicine division at New York's Weill Cornell Medical Center.

But Starz, chief of rheumatology at the University of Pittsburgh Medical Center, still has high hopes for Celebrex and Bextra as arthritis treatments for those who suffer gastrointestinal problems with traditional NSAIDs.

Starz says there is good reason to hope that Celebrex and Bextra may not have the same cardiovascular safety issues that became evident with Vioxx. Its molecular structure clearly differs from that of the other Cox-2s.

"It is very suggestive that there is an inherent characteristic of that [Vioxx] molecule which resulted in the side effect," he says. "It does provide reassurance."

Next: The Pros and Cons of Other Analgesics and Supplements

The Pros and Cons of Other Analgesics

Acetaminophen (Tylenol) is not an NSAID, though you'll find it in the same aisle of the drug store. It's classified as a miscellaneous pain reliever, or analgesic. It reduces fever and relieves pain, but does not affect inflammation.

Opioid drugs, such as codeine (which is combined with acetaminophen in Tylenol 3) or OxyContin, can ease severe pain, but most doctors will not prescribe them in place of Vioxx.

"There are so many downsides," Diwan says. "They don't reduce inflammation, the underlying cause of arthritis pain, for one thing. People also build up tolerances to them over time, and there's a lot of potential for abuse and addiction."

Here are pros and cons for acetaminophen.


  • Like over-the-counter NSAIDs, acetaminophen is inexpensive and available at lower doses without a doctor's prescription.
  • It usually does not cause gastrointestinal problems like aspirin and ibuprofen can.
  • The American College of Rheumatology's 2000 guidelines say that acetaminophen is the first treatment people with osteoarthritis should try.


  • Taking more than the recommended dosage of acetaminophen, 4,000 milligrams per day, can lead to liver failure. The risk for liver failure is especially high if you mix acetaminophen with alcohol.
  • Like NSAIDs, acetaminophen can thin the blood, thus should not be used by people also taking blood-thinning drugs, such as warfarin (Coumadin). People with anemia or blood clotting disorders should use acetaminophen carefully and only under their doctor's supervision.