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
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
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
- 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
- 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.
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
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
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
- 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.