On April 7, 2005 the Food and Drug Administration requested that Pfizer suspend sales of Bextra in the United States. As a result, Bextra will no longer be available to patients in the United States. For more information, click to the Bextra homepage.

Safe use of COX-2 inhibitors and other NSAIDs

Patients who were taking Vioxx or who are currently taking Celebrex, Bextra, Aleve or other NSAIDs may be confused about what action to take in light of recent study findings, FDA recommendations and Merck’s decision to withdraw Vioxx. While staying educated with up-to-date and accurate information, patients should work with a physician to find the safest and most effective medication options for their particular situation.

Should patients meet with their doctor regarding the use of NSAIDs?
Patients who are or were taking COX-2 inhibitors (e.g. Vioxx, Celebrex, Bextra) or naproxen (e.g. Aleve, Naprosyn) should talk with their physician. The physician can evaluate each patient’s individual risk factors (e.g. the patient’s likelihood for developing certain health problems, including heart attack, stroke and gastrointestinal problems) and their treatment needs in order to determine the safest and most effective treatment options. Patients should be sure to tell their physician about all other medications they are taking, including prescribed and non-prescribed drugs, vitamins and nutritional supplements. The physician will also take into account the patient’s previous experience with NSAIDs.

Should all patients stop taking COX-2 inhibitors and other NSAIDs?
In December 2004, the FDA issued the following advisory for physicians for prescribing COX-2 inhibitors, naproxen and other types of NSAIDs to their patients (6):

Physicians should closely evaluate each patient’s risk for cardiovascular events (such as heart attack and stroke) when making decisions about using NSAIDs and COX-2 inhibitor drugs (6).
Some patients with a high risk of gastrointestinal problems, who have a history of intolerance to non-selective NSAIDs (e.g. NSAIDs other than COX-2 inhibitors), or who have not had good results with non-selective NSAIDs may be the most appropriate patients to continue using COX-2 inhibitors Celebrex or Bextra (6).
Patients should be well-advised to follow label directions for over-the-counter pain medications and NSAIDs (e.g. Aleve or brands of ibuprofen), being sure not to use longer than 10 days in a row without consulting a physician. Patients should also be sure not to take a higher dosage of Aleve or other NSAIDs than what is recommended on the label (6). In a separate statement, the FDA also recommended that patients taking Celebrex should take the lowest effective dose in order to avoid overuse (3).

It is important to note that depending on individual risk factors and past experience with NSAIDs, treatment options will vary from patient to patient. After meeting with a physician, some patients will be recommended to continue taking Celebrex and Bextra, while others may switch to other types of NSAIDs (e.g. naproxen or ibuprofen). For others, the safest and most effective option may be to discontinue their use of NSAIDs altogether in favor of other medications and treatment options.

The FDA’s recommendations may change as new studies are conducted and more conclusive information emerges about the potential risks of COX-2 inhibitors and other NSAIDs.

Are there any additional side effects of COX-2 inhibitors and other NSAIDs?
As with all drugs, patients and physicians should remain aware of the previously known side effects for each type of NSAID. Further explanation of known side effects for the drugs can be found on this site at COX-2 inhibitors: Celebrex and Bextra information and NSAIDs.

Who should not take COX-2 inhibitors?
Patients who are allergic to sulfonamide-type drugs and sulfa should not take Celebrex or Bextra. Patients who have had asthma, hives or other allergic reactions from other types of NSAIDs or aspirin also avoid COX-2 inhibitors.

Patients who have serious coronary artery disease or who have had coronary artery bypass graft surgery (CABG) should not take COX-2 inhibitors.

What are other known precautions and side effects of COX-2 inhibitors?
Other known side effects and precautions for COX-2 inhibitors (e.g Celebrex and Bextra) include the following:

A rare side effect of COX-2 inhibitors is stomach problems. The risk increases with a longer duration of taking the drugs, as well as with daily use of alcohol or excessive alcohol consumption
Also rare, but serious, are the known side effects of heart attacks, serious allergic reactions, kidney problems and liver problems
The most common side effects experienced by patients participating in clinical studies for Bextra and Celebrex included stomachache, diarrhea and headache
Elderly patients tend to be more susceptible to the side effects of Celebrex and Bextra
Patients taking NSAIDs (including Celebrex and Bextra) for an extended period of time should have bloodwork monitored routinely by their physician to check for early signs of kidney damage

When should patients stop taking NSAIDs immediately?
Patients taking Bextra, Celebrex or other NSAIDs should stop taking the drugs immediately and call their physician if they experience any of the following warning signs of ulcers:

a burning pain in the stomach
black bowel movements that look like tar
vomit that looks like blood or coffee grounds (7)

Bextra poses a risk of serious (and potentially fatal) skin reactions, including Steven-Johnson Syndrome and toxic epidermal necrolysis. Use of Bextra should be discontinued immediately if the patient develops any of the following symptoms:

a skin rash
mouth sores
any other signs of an allergic reaction (5)

What are some arthritis treatment options besides NSAIDs?
Until the FDA has completed more in-depth and longer-term studies on NSAIDs, patients may also consider non-medicinal treatments for their arthritis pain, such as physical therapy, aquatic exercise therapy or manipulation.

How can patients stay informed about information on COX-2 inhibitors and other NSAIDs?
The most important guideline for safe use of NSAIDs like Celebrex, Bextra and naproxen (e.g. Aleve) is for patients to remain under constant supervision by their physicians and to follow all label directions. Patients should talk to their physicians about any questions or concerns they have and should be aware of their individual risk factors in relation to new study findings.

As new information arises, patients can stay updated by visiting the FDA's Center for Drug Evaluation and Research informational webpage at www.fda.gov/cder or by calling (888) INFO-FDA. Patients can also visit the official websites for the companies manufacturing individual drugs.

By: Peter F. Ullrich, Jr., MD
February 9, 2005

References:

U.S. Food and Drug Administration. “Vioxx (rofecoxib) Questions and Answers.” September 30, 2004. http://www.fda.gov/cder/drug/infopage/vioxx/vioxxQA.htm.
U.S. Food and Drug Administration. FDA News. “FDA Issues Public Health Advisory on Vioxx as its Manufacturer Voluntarily Withdraws the Product.” September 30, 2004. http://www.fda.gov/bbs/topics/news/2004/NEW01122.html.
U.S. Food and Drug Administration. FDA News. “FDA Statement on the Halting of a Clinical Trial of the Cox-2 Inhibitor Celebrex.” December 17, 2004. http://www.fda.gov/bbs/topics/news/2004/NEW01144.html.
U.S. Food and Drug Administration. FDA Talk Paper. “Bextra Label Updated with Boxed Warning Concerning Severe Skin Reactions and Warning Regarding Cardiovascular Risk.” December 9, 2004. http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01331.htm
U.S. Food and Drug Administration. “Questions and Answers: Strengthened Warnings on Bextra.” December 9, 2004. http://www.fda.gov/cder/drug/infopage/bextra/bextraQA.htm.
U.S. Food and Drug Administration. “Public Health Advisory: Non-Steroidal Anti-Inflammatory Drug Products (NSAIDS).” December 23, 2004. http://www.fda.gov/cder/drug/advisory/nsaids.htm
U.S. Food and Drug Administration. “Bextra consumer information.” November 22, 2002. http://www.fda.gov/cder/consumerinfo/druginfo/bextra.htm.