Q&A on the FDA Actions for the COX-2 Inhibitors and NSAIDs
(Suspension of Sales and Marketing of Bextra)

FDA Regulatory Actions for the COX-2 Selective and Non-Selective Non-Steroidal Anti-inflammatory drugs (NSAIDs)

The Food and Drug Administration (FDA) today announced a series of important changes pertaining to the marketing of the nonsteroidal antiinflammatory class of drugs, including COX-2 selective and prescription and non-prescription (over-the-counter (OTC)) non-selective NSAID medications . A list of these products is available on the Internet at http://www.fda.gov/cder/drug/infopage/cox2/default.htm.

After concluding that the overall risk versus benefit profile is unfavorable, FDA has requested Pfizer, Inc. to voluntarily withdraw Bextra (valdecoxib) 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 cardiovascular (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 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.

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

Patients currently taking Bextra should contact their physicians to consider alternative treatments. FDA is also asking manufacturers of all marketed prescription NSAIDs, including Celebrex (celecoxib), a COX-2 selective NSAID, to 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 CV events with these drugs and the well-described, serious, and potentially life-threatening gastrointestinal (GI) bleeding associated with their use. The Medication Guide will accompany every prescription NSAID at the time it is dispensed to better inform patients about the CV and GI risks. Finally, FDA is asking manufacturers of non-prescription (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 announcement does not apply to aspirin as it has clearly been shown to reduce the risk of serious adverse CV events in certain patient populations. 

FDA Q&A

1. What is FDA announcing today?

In follow-up to the February 16-18, 2005, joint meeting of FDA's Arthritis and Drug Safety and Risk Management Advisory Committees, convened to discuss the safety of the "COX-2 selective nonsteroidal anti-inflammatory drugs and related agents," we are announcing our planned regulatory actions for Bextra, Celebrex, and the non-selective prescription and over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs).

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.