Bextra and Celebrex: Questions and Answers

We have concluded that the overall risk versus benefit profile for Bextra is unfavorable and we have requested that Pfizer, the manufacturer, voluntarily withdraw the drug from the market. Pfizer has agreed to suspend sales and marketing of Bextra in the U.S., pendng further discussions with the agency. We are requesting that manufacturers of all marketed prescription NSAIDs, including Celebrex, a COX-2 selective NSAID, revise the labeling (package insert) for their products to include a boxed warning and a Medication Guide. The boxed warning will highlight the potential for increased risk of cardiovascular (CV) events and the well-described, serious, and potentially life threatening gastrointestinal (GI) bleeding associated with these drugs.

We are asking manufacturers of OTC NSAIDs to revise their labeling to include more specific information about the potential GI and CV risks, and information to assist consumers in the safe use of the drug. This includes instructions about which patients should seek the advice of a physician before using these drugs, stronger reminders about limiting the dose and duration of treatment in accordance with the package instructions unless otherwise advised by a physician, and a warning about potential skin reactions. We anticipate that our actions will lead to careful and appropriate use of these drugs to maximize their potential benefits and minimize their risks.

2. To what products does FDA's decision apply and what is being requested?
The decision applies to the marketed COX-2 selective drugs (Bextra and Celebrex) as well as the non-selective NSAIDs. A detailed chart listing the chemical name and trade names for the products affected by this announcement is attached and also can be found at http://www.fda.gov/cder/drug/infopage/cox2/default.htm#list.

For the COX-2 selective inhibitor drugs, we have determined the following:

Bextra (valdecoxib tablets): FDA has concluded that the overall risk versus benefit profile is unfavorable at this time and has requested the manufacturer of Bextra, Pfizer, Inc., to voluntarily withdraw Bextra from the market. This request is based on:

•the lack of adequate data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse CV events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use,

•reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The risk of these serious skin reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa allergy, and after both short- and long-term use, and

•the lack of any demonstrated advantages for Bextra compared with other NSAIDs.

Pfizer has agreed to suspend sales and marketing of Bextra in the U.S. pending further discussions with the agency.

Celebrex (celecoxib tablets): We have concluded that the benefits of Celebrex outweigh the potential risks in properly selected and informed patients. FDA has decided to allow Celebrex to remain and has asked Pfizer to take the actions listed below:

•Revise the Celebrex label to include a boxed warning containing the class NSAID warnings and contraindication about CV and GI risk, plus specific information on the controlled clinical trial data that demonstrate an increased risk of adverse CV events for celecoxib.

•Encourage practitioners to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

•Include a Medication Guide as part of the labeling. It will be required to be given at the time the drug is dispensed to inform patients of the potential for CV and GI risk associated with NSAIDS, in general, and Celebrex specifically. The Medication Guide will inform patients of the need to discuss with their doctor the risks and benefits of using NSAIDs and the importance of using the lowest effective dose for the shortest duration possible.

•Commit to conduct a long-term study of the safety of Celebrex compared to naproxen and other appropriate drugs.

Vioxx (rofecoxib tablets and suspension): Vioxx was voluntarily removed from the market by Merck in September 2004. FDA will carefully review any proposal from Merck for resumption of marketing of Vioxx, and would likely discuss the review with the new FDA Drug Safety Oversight Board and an Advisory Committee before making a final decision.

U.S. Food and Drug Administration (FDA)
Department of Health and Human Services
Center for Drug Evaluation and Research
April 7, 2005