On October 1, 2004 the University of Michigan Employees prescription plan implemented a ‘Step Therapy’ program for the COX-2 medications, Vioxx®, Celebrex®, and Bextra® to promote appropriate use of the COX-2 medication.

Since, that announcement:

• Vioxx® was removed from the market on September 30, 2004 by the manufacturer, Merck, due to safety concerns. http://www.umich.edu/~benefits/plans/drugs/updates/vioxx.htm
• Bextra® safety concerns, cardiovascular and a serious skin reaction, were reported in October 2004. http://www.umich.edu/~benefits/plans/drugs/updates/bextra.htm In response, the University of Michigan Employee prescription plan will require a prior authorization for Bextra® 20mg as of 2-1-05 and will not cover Bextra® 10mg.
• Celebrex® safety concerns were reported December 17, 2004.
• Naproxen, an older, similar pain medication had safety concerns reported December 21, 2004.

Effective immediately, the University of Michigan Employees prescription plan will require prior authorization medical necessity for Celebrex® doses above 400mg per day. Further changes in plan design may result from pending actions by the FDA with regards to these medications.

Recommendations:

Based on the reports of the most recent data Celecoxib (Celebrex®) has been associated with increased risk of cardiovascular events.

• Celecoxib (Celebrex®) should be used with extreme caution in patients at increased risk of cardiovascular events.
• Recent data with Celecoxib (Celebrex®) suggest that special caution should be used in patients receiving 400 mg per day or more. The manufacturer of Celebrex®, Pfizer, has stopped all direct-to-consumer advertising.

What is the Celecoxib (Celebrex®) recommendation based on?

In the Adenoma Prevention with celecoxib (APC) trial, patients taking 400mg and 800mg of Celebrex daily had an approximately 2.5 fold increase in their risk of experiencing a cardiovascular event compared to those patients taking placebo. Cardiovascular event rates were higher in those taking 800mg compared to 400mg daily. Based on these findings, the sponsor of the trial, the NCI, has suspended the dosing of Celebrex in the study.

Of note, two other studies of celecoxib (prevention of Spontaneous Adenomatous Polyps Trials (PreSAP) and Alzheimer’s disease Anti-Inflammatory prevention Trial (ADAPT), similar in size and duration to APC, have been evaluated by data monitoring committees and are continuing because increased risk of cardiovascular events was not observed.

More information on these safety reports may be obtained at http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm