We have identified MCARE patients who have had a prescription filled for Vioxx in the past 6 months and the prescribing U-M physician. This information, including patient contact information, strength of medication and date of prescription fill has been sent electronically to the Medical Directors of each of our health centers and to Service Chiefs. We are asking that the site directors and service chiefs share this information with you and develop a local plan to contact patients as necessary. Physicians will also receive a second notification by mail, directly from Caremark, the UMHS Pharmacy Benefits Manager. We apologize in advance for the duplicate notification. Patients will also be mailed a letter regarding this situation by Caremark.

What recommendations should be given to patients
Patients should stop taking the medication. If patients ask what is their risk of continuing to take the medication the FDA has stated that "the risk that an individual patient taking Vioxx will suffer a heat attack or stroke related to the drug is very small." In actual terms, the RCT found the increased risk, compared to placebo, was 15 extra events per thousand patients who took 25 mg of Vioxx daily for at least 18 months.

Is this class effect (COX-2 agents) or drug effect (refecoxib)
This appears to be a drug effect. A series of studies has shown the increased risk of cardiovascular events with refecoxib including VIGOR, an RCT with 7500 patients, and three separate retrospective cohort studies involving: 1 million Medicaid patients; 1.4 million patients enrolled in Kaiser Permanente and 50,000 Medicare patients. Similar results have not been found for either Celebrex (celecoxib) or Valdecoxib (Bextra), two other COX-2 agents available in the United States.

Should these patients be switched to another COX-2 agent
Patients on Vioxx may either be switched to acetaminophen, a traditional non-steroidal anti-inflammatory drug (NSAID) or another COX-2 agent. Celebrex and Bextra should not be given to patients who have demonstrated allergic-type reactions to sulfonamides. Acetaminophen, up to four grams daily, provides similar pain relief for many patients with osteoarthritis and should be considered before beginning an NSAID. If acetaminophen is not successful or an option then:

• If your patient is on or needs aspirin do not use a COX-2 agent as there is no additional safety benefit. We also recommend that you do not prescribe ibuprofen for patients requiring aspirin due to interference with aspirin's anti-platelet activity. Such patients may be prescribed naproxen.
  
• If your patient is on a gastroprotective agent regularly (i.e., a proton pump inhibitor or misoprostol), consider using a traditional NSAID as RCT data show similar efficacy for a traditional NSAID + Gastroprotective agent as for a COX-2 inhibitor.
  
• If your patient has a significant increased risk of a GI event (e.g., age > 60 years old, past history of a gastric or duodenal ulcer, on coumadin) and not on aspirin then consider using a COX-2 agent or a traditional NSAID with a gastroprotective agent.
  
• If your patient has a significant increased risk of a GI event and needs aspirin, then consider a traditional NSAID + gastroprotective agent or using other classes of medications (e.g., low dose narcotics)

What are the University Employee Rx Plan and MCARE's preferred COX-2 agents?
Celecoxib (Celebrex) remains a preferred brand name agent for U-M employees and MCARE. The University Benefits office has now temporarily changed Valdecoxib (Bextra) to a preferred agent with respect to co-pay status for UM employees and their families. We have not been notified whether BCBSM will change celecoxib from a non-preferred to preferred brand.

What about prescriptions I recently wrote?
Pharmacies will not fill those prescriptions and will contact your office directly regarding what substitution you would like to make. Please see above recommendations.

What should patients do with unused Vioxx?
Patients wanting a refund for unused Vioxx may return the drug in its original pharmacy packaging to:

NNC Group
Merck Returns
2670 Executive Drive
Indianapolis, IN 46421

Where can I get more information?
More information on this market withdrawal may be found at: http://www.vioxx.com,
http://www.fda.gov/cder/drug/infopage/vioxx/default.htm, or by calling 1-8888-36VIOXX. Please contact the Drug Information Service, 936-8200, should you have any questions regarding this information.

This FGP Gram was prepared by Steven J. Bernstein, MD with assistance from Pharmacy Services and UM Employee Benefits Office. Questions or comments about this FGP Gram may be directed to iCARE@umich.edu or LisaWehr, PharmD at luba@umich.edu. Feedback about any FGP Gram is always appreciated.