1. Many of our patients have been asking for advice regarding Celebrex and Bextra. The following is a reasonably complete summary of the controversy surrounding the COX 2 inhibitor medications and now even the traditional NSAID medications. It would seem prudent to minimize the dosage of any of these medications that you are taking and to discuss this with your doctor as soon as convenient for you.

January 11, 2005
Special Edition: AAOS Headline News
Use of Pain Medication/NSAIDs

Recent information about pharmaceutical and over-the-counter (OTC) pain medication used to treat arthritis and other musculoskeletal disorders has caused some concern in the medical community regarding patient use. There currently is conflicting research data on several of the drug agents. The Food and Drug Administration (FDA) will hold an advisory committee meeting on February 16-17, 2005 to discuss the analysis of data on non-steroidal anti-inflammatory drugs (NSAIDs) in response to this controversy. The American Academy of Orthopaedic Surgeons (AAOS) will update its membership with all relevant scientific information as it becomes available.

Background:

• Results from the APPROVe (Adenomatous Polyp Prevention on Vioxx®) clinical trial determined that there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in patients taking Vioxx compared with those taking a placebo. Merck & Co., Inc., the drug's manufacturer, announced a worldwide withdrawal of Vioxx on September 30, 2004.
• On December 9, 2004, the FDA announced label modifications for Bextra®, a Cox-2 inhibitor, requiring that the drug labeling be updated to include warnings for cardiovascular risk and severe skin reactions. A recent study demonstrated an increased cardiovascular risk in patients treated with Bextra compared to placebo. The bolded warning states contraindications for the use of Bextra in patients undergoing coronary artery bypass graft surgery.
• On December 17, 2004, the National Institutes of Health (NIH) announced that it suspended the use of a Cox-2 inhibitor, CelebrexTM(celecoxib), for all participants in a large colorectal cancer prevention trial conducted by the National Cancer Institute (NCI). The Adenoma Prevention with Celecoxib (APC) trial was halted after analysis showed a 2.5-fold increased risk of cardiovascular events for participants taking the drug compared to those receiving a placebo.
• On December 20, 2004, the FDA announced that preliminary information from the clinical trial involving NSAIDs and patients at risk of developing Alzheimer's disease showed an increased risk of cardiovascular events with the use of naproxen, when compared to placebo. The FDA advises that patients currently taking over-the-counter naproxen products should carefully follow the instructions on the label. Patients should not exceed the recommended doses for naproxen. Patients also should not take naproxen for longer than 10 days unless otherwise directed by a physician.

Recent Governmental Recommendations:

On December 23, 2004, the FDA made the following interim recommendations on NSAIDs:

• Physicians prescribing Celebrex (celecoxib) or Bextra (valdecoxib) should consider emerging information when weighing the benefits against risks for individual patients. Patients who are at a high risk for gastrointestinal bleeding, have a history of intolerance to non-selective NSAIDs, or are not doing well on non-selective NSAIDs may be appropriate candidates for Cox-2 selective agents.
• Individual patient risk for cardiovascular events and other risks commonly associated with NSAIDs should be taken into account for each prescribing situation.
• Consumers are advised that all OTC pain medications, including NSAIDs, should be used in strict accordance with the label directions. If use of an OTC NSAID is needed for more than 10 days, a physician should be consulted.

In addition, the AAOS recommends the following:

The use of medication involves a risk/benefit ratio and should be assessed by physicians in conjunction with their patient and in light of their patient's specific condition. The AAOS encourages its Fellows to monitor new research and developments in these therapies because new information continues to develop rapidly. Because NSAID use has been associated with gastrointestinal symptoms, physicians may want to consider therapies that provide protection for the stomach, in addition to those that provide for pain relief. Physical therapy, exercise, and acupuncture may also provide pain relief for some patients. (See list of Additional Resources below for a link to the NIH acupuncture study.)

A selection of additional resources:

The FDA urges health care providers and patients to report adverse event information to FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet: http://www.fda.gov/medwatch/index.html.

Vioxx (rofecoxib)

http://www.fda.gov/cder/drug/infopage/vioxx/default.htm

Bextra Label Updated with Boxed Warning Concerning Severe Skin Reactions and Warning Regarding Cardiovascular Risk

http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01331.html

FDA Statement on the Halting of a Clinical Trial of the Cox-2 Inhibitor Celebrex

http://www.fda.gov/bbs/topics/news/2004/new01144.html

Use of Non-Steroidal Anti-Inflammatory Drugs Suspended in Large Alzheimer's Disease Prevention Trial

http://www.nih.gov/news/pr/dec2004/od-20.htm

Naproxen Information http://www.fda.gov/cder/drug/infopage/naproxen/default.htm

FDA Issues Public Health Advisory Recommending Limited Use of Cox-2 Inhibitors

http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01336.html

NIH Press Release: Acupuncture Relieves Pain and Improves Function in Knee Osteoarthritis

http://www.nih.gov/news/pr/dec2004/nccam-20.htm

NSAIDS
FDA Public Health Advisory on the use of NSAIDS

http://www.fda.gov/cder/drug/advisory/nsaids.htm

Safe Use of Over-the-Counter Pain Relievers (analgesics) and Fever Reducers (antipyretics)

http://www.fda.gov/cder/drug/analgesics/default.htm

FDA adds boxed warning to Bextra label.

The Food and Drug Administration (FDA) is requiring an update to the Bextra label warning of severe skin reactions and increased cardiovascular risk for patients who have just had heart bypass surgery. A study of more than 1,500 heart surgery patients found that people who took Bextra were more likely to have problems such as heart attacks, strokes and blood clots in the legs or lungs, according to the FDA. The severe skin reactions include Steven-Johnson Syndrome and toxic epidermal necrolysis.

For more information: http://www.fda.gov/bbs/topics/ANSWERS/2004/ANS01331.html

FDA warns of misleading ads.

The U.S. Food and Drug Administration (FDA) has issued a warning letter to drug manufacturer Pfizer Inc. that its ads for Celebrex and Bextra are misleading and violate FDA regulations. The letter is dated Jan. 10 and was released yesterday. It charges that the company omitted material facts, including risk information, and made misleading safety and unsubstantiated effectiveness claims. Pfizer suspended advertising for the drugs in December, after a study linked usage of Celebrex to an increased risk of heart problems. To read the warning letter:

http://www.fda.gov/cder/warn/2005/12560-letter.pdf

2. On the positive prospective front, new dietary guidelines call for 30 minutes of exercise daily.

New dietary guidelines released by the U.S. Departments of Agriculture and Health and Human Services call on Americans to eat fewer calories and exercise a minimum of 30 minutes a day. Children should exercise a minimum of 60 minutes a day. The guidelines also stress the importance of consuming whole grains, rather than refined grains, and keeping total fat intake between 20 percent and 35 percent of calories. Only two guidelines include actual limits; maximum sodium intake is recommended at no more than 2,300 mg (approximately 1 tsp) and no more than one alcoholic drink per day for women (two drinks per day for men) is advised. Complete information on the new guidelines can be found at:

http://www.healthierus.gov/dietaryguidelines/

"Go play outside" is good advice says study.

An article in the January issue of Archives of Pediatric & Adolescent Medicine underscores the importance of extended, unstructured outdoor playtime for children and urges that parents and schools resurrect the concept of free play time. Researchers found an estimated 25 percent drop in free playtime among children from 1981 to 1997 and note that free play time has social, emotional and cognitive development advantages in addition to health and fitness benefits. The report also calls on communities to address the issue of safe outdoor play spaces, such as playgrounds. For more information:

http://www.reutershealth.com/archive/2005/01/13/eline/links/20050113elin013.html

3. FDA warns of misleading ads.

The U.S. Food and Drug Administration (FDA) has issued a warning letter to drug manufacturer Pfizer Inc. that its ads for Celebrex and Bextra are misleading and violate FDA regulations. The letter is dated Jan. 10 and was released yesterday. It charges that the company omitted material facts, including risk information, and made misleading safety and unsubstantiated effectiveness claims. Pfizer suspended advertising for the drugs in December, after a study linked usage of Celebrex to an increased risk of heart problems. To read the warning letter:

http://www.fda.gov/cder/warn/2005/12560-letter.pdf

5. New dietary guidelines call for 30 minutes of exercise daily.

New dietary guidelines released by the U.S. Departments of Agriculture and Health and Human Services call on Americans to eat fewer calories and exercise a minimum of 30 minutes a day. Children should exercise a minimum of 60 minutes a day. The guidelines also stress the importance of consuming whole grains, rather than refined grains, and keeping total fat intake between 20 percent and 35 percent of calories. Only two guidelines include actual limits; maximum sodium intake is recommended at no more than 2,300 mg (approximately 1 tsp) and no more than one alcoholic drink per day for women (two drinks per day for men) is advised. Complete information on the new guidelines can be found at:

http://www.healthierus.gov/dietaryguidelines/

4. "Go play outside" is good advice says study.

An article in the January issue of Archives of Pediatric & Adolescent Medicine underscores the importance of extended, unstructured outdoor playtime for children and urges that parents and schools resurrect the concept of free play time. Researchers found an estimated 25 percent drop in free playtime among children from 1981 to 1997 and note that free play time has social, emotional and cognitive development advantages in addition to health and fitness benefits. The report also calls on communities to address the issue of safe outdoor play spaces, such as playgrounds. For more information:

http://www.reutershealth.com/archive/2005/01/13/eline/links/20050113elin013.html

3. Consumer Reports introduces "Best Buy Drugs" Web site.

A new Web site from Consumer Reports compares a variety of prescription drugs on price, effectiveness and safety to help consumers and their doctors identify the most effective and affordable medications. The first reports examine anti-inflammatories used to treat arthritis as well as cholesterol-lowering medications and treatments for heartburn and acid reflux. For treatment of arthritis and pain, generic ibuprofen and generic salsalate are indicated as "Best Buy Drugs." Recommendations are based on scientific evidence from groups such as the Drug Effectiveness Review Project at the Oregon Health & Science University Evidence-based Practice Center. Each of the reports includes a discussion of safety and possible side effects. For more information:

http://www.crbestbuydrugs.org

2. Consumer Reports names "dirty dozen" dietary supplements.

The May issue of Consumer Reports includes a list of 12 dangerous dietary supplements that can be easily purchased over the counter or via the Internet. At least five of the supplements have been banned in Europe, Asia or Canada. On the list are products containing aristolochic acid, comfrey, androstenedione, chapparel, germander, kava, bitter orange, organ/glandular extracts, lobelia, pennyroyal oil, skullcap and yojimbe. The U.S. government has requested that manufacturers of androstenedione stop marketing the product. For more information:

http://www.consumerreports.org

4. FDA offers patient information on medical devices.

The FDA Center for Devices and Radiological Health (CDRH) now offers consumer information Web pages for orthopaedic medical devices such as bone grafts, unicompartmental knee systems and hip prostheses. The information can be accessed from the CDRH home page, which also includes links to articles on choosing medical devices, judging medical Web sites, and reporting problems with medical devices. For specific information on orthopaedic devices, click on "Recently Approved Devices" under "Product Index and Information" at:

http://www.fda.gov/cdrh/consumer/index.html

1. FDA issues warning on drug interaction with warfarin.

The Food and Drug Administration (FDA) has issued a MedWatch alert warning of a drug interaction between Oxandrin® (oxandrolone, USP), which may be prescribed for the relief of bone pain frequently accompanying osteoporosis, and the oral anticoagulant warfarin for systemic anticoagulation. Concurrent dosing of Oxandrin® and warfarin may result in unexpectedly large increases in the International Normalized Ratio (INR) or prothrombin time. When Oxandrin® is prescribed to patients being treated with warfarin, the warfarin dose may need to be decreased significantly to maintain a desirable INR level and diminish the risk of potentially serious bleeding. The MedWatch safety summary and a link to the "Dear Healthcare Professional" letter issued by Savient Pharmaceuticals, Inc. can be found at:

http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#oxandrin

1. EEOC approves reductions in retiree health benefits.

The Equal Employment Opportunity Commission (EEOC) approved a final rule yesterday that would allow employers to reduce or drop retirees' health benefits once the retiree becomes eligible for Medicare without risk of age discrimination. The ruling says that such cuts do not violate workers' rights and could take effect this summer, pending additional federal agency clearances. The decision clears the way for many companies to reduce health care costs by reducing or eliminating coverage for retirees. The decision reverses a 2000 ruling by the 3rd U.S. Circuit Court of Appeals. For more information:

http://www.chicagotribune.com/news/printedition/chi-0404230218apr23,1,7836699.story?coll=chi-printnews-hed (Note: long URL; site registration required)

1. Arthritis taking heavy financial toll, causing untold human suffering.

Approximately one-quarter of American adults have been diagnosed with arthritis and another 17 percent may be suffering from the crippling disease, the Centers for Disease Control and Prevention (CDC) said. Arthritis is the leading cause of disability in the United States and a major financial drain on the nation's health care system. The percentage of those diagnosed with a form of arthritis, rheumatoid arthritis, gout, lupus or Fibromyalgia ranged from a low of 17.8 percent in Hawaii to a high of 35.8 percent in Alabama in 2002, according to a 30-state CDC survey released Thursday and reported today on CNN. The median rate was 27.6 percent. "That is a huge number compared to most other diseases," said Dr. Chad Helmick, a CDC arthritis expert, who noted that the number of Americans with arthritis was expected to increase sharply as the baby boomer generation headed into retirement. The CDC also found that about 20 percent of respondents in a number of states in the survey had chronic joint pain, aching or stiffness indicating possible arthritis that had not been diagnosed. Besides causing untold human suffering, the disease is also exacting a heavy financial toll. The estimated direct and indirect costs of arthritis and other related rheumatic diseases was $86.2 million in 1997, equivalent to about 1 percent of the nation's gross domestic product, the CDC said in a separate study. To learn more: http://www.cnn.com/2004/HEALTH/conditions/05/14/arthritis.reut/index.html or http://www.cdc.gov/od/oc/media/pressrel/fs040513.htm