FDA recommends limiting COX-2 inhibitors use

An advisory committee should meet this month

The questions continue about the safety of COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs).

First Merck withdrew rofecoxib (Vioxx) from the market in late September 2004 because of increased risk of heart attack and stroke. Then, on Dec. 9, the FDA announced that a boxed warning was being added to the label of valdecoxib (Bextra), a COX-2 inhibitor indicated for the treatment of osteoarthritis, rheumatoid arthritis, and dysmenorrhea. The addition strengthens previous warnings about the risk of life-threatening skin reactions and says that the use of valdecoxib in patients undergoing coronary artery bypass graft surgery is contraindicated.

On Dec. 17, the National Institutes of Health (NIH) announced that it was suspending the use of COX-2 inhibitor celecoxib (Celebrex) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib trial, was stopped because analysis by an independent Data Safety and Monitoring Board showed a 2.5-fold increased risk of major fatal and nonfatal cardiovascular events for participants taking the drug compared to those on a placebo. Pfizer has agreed to voluntarily suspend direct-to-consumer advertising of celecoxib while the FDA evaluates the data on adverse events associated with the drug.

Then, on Dec. 20, the NIH halted a clinical trial involving nonsteroidal anti-inflammatory drugs in patients at risk of developing Alzheimer’s disease. Preliminary information from the study showed some evidence of increased risk of cardiovascular events, when compared to placebo, to patients taking naproxen (Aleve).

These announcements frustrated consumers and led some politicians and health care professionals to place partial blame for the potential problems on the FDA’s drug approval process.

The FDA, however, issued statements defending its drug evaluations, and on Dec. 23, issued a Public Health Advisory summarizing the agency’s recent recommendations regarding the use of NSAIDs, including COX-2 inhibitors. The agency says this advisory is an interim measure, pending further review of data.

Here are the FDA’s recommendations:

  • Physicians prescribing celecoxib or valdecoxib should consider this emerging information when weighing the benefits against risks for individual patients. Patients who are at a high risk of gastrointestinal bleeding, have a history of intolerance to nonselective NSAIDs, or are not doing well on nonselective NSAIDs may be appropriate candidates for COX-2 selective agents.
  • Individual patient risk for cardiovascular events and other risks commonly associated with NSAIDs should be taken into account for each prescribing situation.
  • Consumers are advised that all over-the-counter (OTC) pain medications, including NSAIDs, should be used in strict accordance with the label directions. If use of an (OTC) NSAID is needed for longer than 10 days, a physician should be consulted.

The FDA says it is collecting and will be analyzing all available information from the most recent studies of rofecoxib, celecoxib, valdecoxib, and naproxen, and other data for COX-2 selective and nonselective NSAID products to determine whether additional regulatory action is needed. An advisory committee meeting is planned for this month. The Public Health Advisory is available on-line at www.fda.gov/cder/drug/advisory/nsaids.htm.