Pfizer Suspends Sales of Bextra (cont.)

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.

Non-selective NSAIDs

Based upon the available data, FDA has concluded that an increased risk of CV events may be a class effect for NSAIDs. There are a number of non-selective NSAIDs currently approved for marketing in the United States. Long term controlled clinical trials have not been conducted with most of these NSAIDs. However, the available data suggests that use of these drugs may increase CV risk.

To further evaluate the potential for increased CV risk, all sponsors of non-selective NSAIDs will be asked to conduct and submit to FDA a comprehensive review and analysis of pertinent available controlled clinical trial databases.

In addition, FDA is requesting labeling changes for prescription and OTC non-selective NSAIDs. Because the use and labeling for the prescription products is different from those available without a prescription, they are addressed separately.

Prescription Non-Selective NSAIDs

Based on the available data, the FDA will request the manufacturers of all prescription products containing non-selective NSAIDs to revise their product labeling to include:

  • A boxed warning regarding the potential serious adverse CV events and the serious, and potentially life-threatening GI adverse events associated with the use of this class of drugs.
  • A contraindication for use in patients who have recently undergone coronary artery bypass surgery.
  • A Medication Guide for patients to help make them aware of the potential for CV and GI adverse events associated with the use of this class of drugs. 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 if treatment with an NSAID is warranted in an individual patient.

OTC Non-Selective NSAIDs

The available data do not appear to suggest an increased risk of serious CV events for the short-term, low-dose use of the NSAIDs available over the counter. FDA will request changes to the label to better inform consumers regarding the safe use of these products.

FDA will ask the manufacturers of all non-prescription products containing ibuprofen (Motrin, Advil, Ibu-Tab 200, Medipren, Cap-Profen, Tab-Profen, Profen, Ibuprohm), naproxen (Aleve), and ketoprofen (Orudis, Actron) to revise their labeling to include:

  • More specific information about the potential CV and GI risks,
  • 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.