Bextra and Celebrex: Risks

9. Why isn't FDA requesting that Celebrex also be withdrawn?
The Advisory Committees were unanimous in their conclusion that an increased risk of CV adverse events has been demonstrated for Celebrex (as for all the Cox-2 selective inhibitors) but strongly supported the continued marketing of the drug. FDA has concluded, based on the available data, that the benefits of Celebrex outweigh its potential risks in properly selected and informed patients. This conclusion is based on our review of the available safety data and the long-term controlled clinical trial comparisons of Celebrex to non-selective NSAIDs. While it appears that Celebrex is associated with an increased risk of serious CV adverse events, the available data do not support a conclusion that Celebrex is significantly worse than the non-selective NSAIDs. The NSAID class boxed warning regarding increased CV and GI risks will be applied to Celebrex, and in addition the labeling will include additional information as described in question 2 above that will inform physicians and patients of the potential risks and allow for informed prescribing decisions.

10. Does FDA anticipate that Vioxx will return to the market at some point?
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.

11. Will Bextra be available to patients on a compassionate use basis?
If the sponsor proposes a program to provide limited access to those patients who believe that this drug is the best option for them, FDA would be willing to consider this.

12. Are there other examples of drug products that have boxed warnings on the prescription indications, but are also available at an OTC dose?
We believe that this is the first time that a product with a boxed warning on the prescription version will also be available for non-prescription use. We believe that the available data support a conclusion that short-term use of low doses of the available OTC NSAIDs is not associated with any increased serious CV risk. When used according to their labeled instructions, we believe that OTC NSAIDs continue to have a very favorable risk benefit profile, and we believe it is important to maintain a range of therapeutic options for the short-term relief of pain in the OTC market.

13. Who may be at higher risk when taking these products?
Those at higher risk would include patients immediately post-operative from cardiovascular bypass surgery (CABG) and people who have coronary artery disease (people who have known angina or who have had a heart attack), people who have cerebrovascular disease (people who have had a stroke or who currently have episodes known as TIA (transient ischemic attacks)), and people with a history of stomach ulcers.

14. Did FDA consult the newly identified Drug Safety Board (DSB) that was to be established by the Agency?
No. The Board has not yet been convened.

15. Is Naproxen safe from a CV standpoint? How does it compare to the COX-2s?
Based on the currently available data FDA has concluded that the potential for increased risk of serious CV adverse events is a class effect of NSAIDs. This conclusion applies to naproxen. As with other members of the NSAID class, additional data from long-term, controlled clinical trials is needed to more definitively determine the magnitude of increased risk, if any, of naproxen over placebo and in relation to other NSAIDs.

16. Some NSAIDs have been associated with serious, potentially life-threatening skin reactions, such as Stevens-Johnson syndrome (SJS). What is FDA doing to warn patients about this risk?
FDA has determined that the labeling for all non-prescription NSAIDs should be updated to warn of the potential for skin reactions. Accordingly, along with the changes to the label to address CV risks, the agency will ask manufacturers of non-prescription NSAIDs to make these changes. FDA also has recently received a Citizens Petition regarding the risk of SJS with ibuprofen (received February 15, 2005). The petition is still under review. After reviewing the data submitted with the petition, FDA will determine whether additional labeling changes with regard to skin reactions are warranted.

17. If I'm taking Bextra, what should I do?
We encourage people taking Bextra to contact their physician to discuss discontinuing use and alternative treatments. Any decision about which drug product to take to treat your symptoms should be made in consultation with your physician based on an assessment of your specific treatment needs.

18. If I have rheumatoid arthritis, what pain medication does FDA recommend?
You should consult your doctor to discuss the best course of action.

19. How can I report serious side effects with COX-2 selective and non-selective NSAIDs to FDA?
FDA encourages anyone aware of a serious adverse reaction to make a MedWatch report. You can report an adverse event in two ways:

•Visit www.fda.gov/medwatch and click on "How to Report"
•Call 1-800-FDA-1088

20. Where can I get more information?
To find out more about all NSAIDs from FDA:

•Visit our Drug Information web page at: www.fda.gov/cder
• Call Drug Information at: 888-INFO-FDA (888-463-6332)

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