After Vioxx: The Pros and Cons of Other Anti-Inflammatory Drugs

Last Editorial Review: 4/13/2005

All pain relievers have risks as well as benefits. Get the pros and cons of anti-inflammatory medicines here.

By Martin Downs
WebMD Feature

Reviewed By Charlotte Grayson

The recent recall of the pain reliever Vioxx has raised many questions, not the least of which is, what can patients take now?

"It's been an enormous challenge to all of us," says Terence Starz, MD, a clinical professor of medicine and chief of rheumatology at the University of Pittsburgh Medical Center. "Our practice was overwhelmed," he says.

Vioxx maker Merck & Co. voluntarily pulled the drug off the market on Sept. 30, 2004, after a study showed it doubles a person's risk of heart attack and stroke. Nearly 2 million people worldwide were taking Vioxx. Starz says almost 250 of his own patients were on it.

According to Time magazine, in the day following the recall announcement, an estimated 28,800 Americans switched to another drug. Most of them went on Celebrex or Bextra, similar drugs that had been Vioxx's competitors.

Before consumers rush to another medicine, however, experts say they should pause to weigh the pros and cons of each option. All pain relievers, even over-the-counter aspirin, Motrin, or Tylenol, have risks. It's never a good idea to take any pill every day unless you're under your doctor's supervision. Moreover, pain relievers aren't always the best treatment for many causes of chronic pain.

"Getting an accurate diagnosis and reversing known reversible causes is the first part of the treatment," says Jason Theodosakis, MD, an assistant clinical professor at the University of Arizona College of Medicine, and author of the 1996 bestseller The Arthritis Cure, now in a revised edition. "Too often a person will have joint pain, and just assume it's arthritis, or they may have five minutes with their doctor, who says, 'You have a touch of arthritis here. Take a pain reliever.'"

In fact, Theodosakis says lifestyle changes such as weight loss and low-impact exercise are essential to relieve the pain often caused by arthritis. Even treating depression seems to help relieve pain. Pain relievers should be your last resort, he says. "The goal in treatment is really to use those drugs later down the road when everything else fails."

With that caveat, what are your options now if you do need pain relief medicine? Here, briefly, are the pros and cons of each type of common pain relief medicine.

Next: The Pros and Cons of Other Anti-Inflammatory Drugs

The Pros and Cons of Older Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs, or NSAIDs, are some of the most common medicines taken for general aches and pains, as well as for arthritis. There are more than a dozen NSAIDs that you can take for just about every cause of pain, from arthritis to headaches to pulled muscles. The NSAIDs you're probably most familiar with are those available without a prescription. They include aspirin, ibuprofen (Advil, Motrin, Nuprin), ketoprofen (Orudis KT), and naproxen (Aleve).


  • The over-the-counter versions of these pills are inexpensive, costing only pennies per pill.
  • Studies show that low doses of aspirin taken over the long term can also help prevent heart attacks and strokes.
  • These drugs have been around for a long time, so much is known about them. Ibuprofen was approved as a prescription drug in 1974, and made available over the counter 10 years later. Aspirin has been on the market for well over 100 years.


  • NSAIDs tend to cause digestive problems. As many as one-quarter of those who take them regularly will experience some kind of gastric side effect such as nausea, and many people develop stomach ulcers. Depending on how many risk factors a person has, the chance of getting an ulcer from taking NSAIDs can be as high as 18% or as low as less than 1%.
  • Overusing NSAIDs can cause kidney damage, too. Some people may even develop kidney problems from NSAID use even if they don't take too much.
  • Because NSAIDs act as blood thinners, they're also off limits to people taking prescription blood-thinning drugs, such as warfarin (Coumadin), and people with anemia or blood clotting disorders.

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.

Theodosakis, author of The Arthritis Cure, says new studies indicate that acetaminophen may not be an effective pain reliever for arthritis, and he notes the American College of Rheumatology will change its recommendation in its next set of guidelines.

"Shortly after [the college's] guidelines were issued, the first double-blinded studies with Tylenol came out, and one of the studies showed it was no better than placebo. The other study showed that anti-inflammatories are clearly better at relieving pain," he says.

Dietary Supplements for Arthritis

Dietary supplements such as glucosamine and chondroitin are not technically drugs, but many substances you ingest can affect the body like medicine. Glucosamine and chondroitin are substances found naturally in the body, and may be involved the in the making or the repair of cartilage.


  • The supplements are inexpensive and available without a doctor's prescription.
  • Studies have shown that glucosamine and chondroitin may relieve arthritis pain as well as NSAIDs.
  • Studies also show they may help prevent cartilage damage in people with osteoarthritis.


  • Dietary supplements haven't been studied under rigorous standards, as drugs have, so long-term safety and effectiveness is not known.
  • They are not regulated by the FDA, so supplements may not contain the amounts promised on the label or may be substandard in other ways.
  • Doctors may not recommend them because they are dietary supplements.
  • Chondroitin acts like a blood thinner, and may cause bleeding in people who also take prescription blood thinners or NSAIDs for pain relief.

Theodosakis, who serves on the oversight committee of the National Institutes of Health study on glucosamine and chondroitin, recommends these supplements. Over the past several years, extensive research has supported their use, he says.

People with diabetes should check their blood sugar levels more often when taking glucosamine, because it's a sugar. Those with shellfish allergies should ask their doctor about taking glucosamine, because it is derived from shellfish.

Published October 2004.

SOURCES: Terence Starz, MD, clinical professor of medicine, division of rheumatology, University of Pittsburgh School of Medicine; chief of rheumatology, University of Pittsburgh Medical Center. Jason Theodosakis, MD, assistant clinical professor, University of Arizona College of Medicine. Sudhir Diwan, MD, director, division of pain medicine, Weill Cornell Medical Center; and assistant professor of anesthesiology, Weill Medical College of Cornell University. WebMD Medical Reference, "Anti-Inflammatory Painkiller Drugs and Arthritis." Fox Chase Cancer Center, news release, Oct. 4, 2004. Medical News, March 18, 2003, "NSAIDs May Reduce Lung Cancer Risk." Alimentary Pharmacology & Therapeutics, May 2004. The Merck Manual of Diagnosis and Therapy. Arthritis Foundation web site. WebMD Medical News: "Aspirin Lowers Pancreatic Cancer Risk." WebMD Medical News: "Painkillers Help Prevent Breast Cancer." WebMD Medical News: "Vioxx Unsafe: So What About Similar Drugs?" American Family Physician, June 15, 2003. Pfizer, Inc. news releases, Oct. 15 and Oct. 18, 2004. Arthritis & Rheumatism, Sept. 2000, Feb. 2002. Annals of the Rheumatic Diseases, Aug. 2004. FDA news release, Sept. 30, 2004. BMJ, June 2002. Time, Oct. 18, 2004.

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