The boxed warning for all non-steroidal anti-inflammatory drugs (NSAIDs), including Celebrex, will also contain information regarding gastrointestinal risk that is already included elsewhere in their current labels.

In addition, the FDA is asking manufacturers of all over-the-counter NSAIDs to revise their labeling to include more information on the cardiovascular and gastrointestinal risks as well as a warning about potential skin reactions.

Pfizer and the FDA plan further discussions regarding the precise content of the Celebrex label. Pfizer has accumulated extensive Celebrex clinical data over the past 10 years involving more than 40,000 patients. Pfizer also reaffirmed its commitment to conduct additional long-term clinical studies evaluating the benefits and risks of Celebrex.

Pfizer also said it will work closely with the FDA to develop a guide to assist patients and their healthcare professionals in making the best decisions for treating their arthritis pain.

Regarding Bextra, Pfizer’s other oral Cox-2 inhibitor, the FDA informed Pfizer late yesterday that, in the agency’s view, Bextra’s cardiovascular risk could not be differentiated from other NSAIDs. However, the agency has concluded that the additional, increased risk of rare but serious skin reactions associated with Bextra, already described in its label, warrants its withdrawal from the market.

Pfizer respectfully disagrees with FDA’s position regarding the overall risk/benefit profile of Bextra. However, in deference to the agency’s views, the company has agreed to suspend sales of the medicine pending further discussions with the FDA. Pfizer said it will explore options with the agency under which the company might be permitted to resume making Bextra available to physicians and patients. For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options.

In addition, at the request of European regulators, Pfizer will also suspend sales of Bextra in the European Union. The company is in contact with other regulatory agencies around the world and will take appropriate measures based on those discussions.

Pfizer was informed by the FDA of its conclusions regarding Celebrex and Bextra on Wednesday afternoon, one day after the company held a meeting with financial analysts. Pfizer received the request from the European regulators early Thursday morning. Pfizer said it is evaluating the operational and financial impact of these actions.

The Food and Drug Administration (FDA) learned last night from the National Cancer Institute (NCI) and Pfizer, Inc., that NCI has stopped drug administration in an ongoing clinical trial investigating a new use of Celebrex (celecoxib) to prevent colon polyps because of an increased risk of cardiovascular (CV) events in patients taking Celebrex versus those taking a placebo.

Patients in the clinical trial taking 400 mg. of Celebrex twice daily had a 3.4 times greater risk of CV events compared to placebo. For patients in the trial taking 200 mg. of Celebrex twice daily, the risk was 2.5 times greater. The average duration of treatment in the trial was 33 months.

A similar ongoing study comparing Celebrex 400 mg. once a day versus placebo, in patients followed for a similar period of time, has not shown increased risk.

Although these are important findings, at this point FDA has seen only the preliminary results of the studies. FDA will obtain all available data on these and other ongoing Celebrex trials as soon as possible and will determine the appropriate regulatory action.

While we have not seen all available data on Celebrex, these findings are similar to recent results from a study of Vioxx (rofecoxib), another drug in the same class as Celebrex. Vioxx was recently voluntarily withdrawn by Merck. Another drug in this class, Bextra (valdecoxib) has shown an increased risk for CV events in patients after heart surgery. Bextra and Celebrex are the only two selective COX-2 agents currently on the U.S. market.

Physicians should consider this evolving information in evaluating the risks and benefits of Celebrex in individual patients. FDA advises evaluating alternative therapy. At this time, if physicians determine that continued use is appropriate for individual patients, FDA advises the use of the lowest effective dose of Celebrex.

Patients who are currently taking Celebrex and have questions or concerns about the drug should discuss them with their physicians.

Celebrex was approved in 1998 for the treatment of osteoarthritis and rheumatoid arthritis. Previous large studies of Celebrex, including clinical trials and epidemiology studies, have not suggested the sort of CV risk found in the NCI polyp study. Because similar long-term studies of other products in the class of non-steroidal anti-inflammatory drugs (NSAIDS), other than Cox-2 inhibitors have not been done, it is not known whether other NSAIDS pose a similar risk.

FDA will provide updates on Celebrex in particular and this class of drugs in general as more information becomes available.