COX-2 Inhibitors

A new approach to circumventing the problem of NSAID-induced gastropathy came to fruition with the discovery of two isoforms of cyclooxygenase, COX-1 and COX-2.³¹

Traditional NSAIDs inhibit both COX-1 and COX-2, but two new agents that selectively inhibit COX-2 (celecoxib and rofecoxib) thereby minimizing GI toxicity have recently been introduced.³², ³³, ³⁴ The theory behind the COX-2 inhibitors is that if COX-2 can be selectively inhibited, while sparing COX-1, it may be possible to decrease acute inflammation and pain while sparing the complications in the GI tract, platelets, and other tissues. Because COX-2 is also expressed constitutively in the brain, kidney, and uterus, these agents do not appear to be renally sparing, and like traditional NSAIDs, are associated with renal toxicity when used chronically.

On September 30, 2004, Merck &. Co., Inc. announced a voluntary worldwide withdrawal of VIOXX  (rofecoxib), its arthritis and acute pain medication.  The Company’s decision,  which is effective immediately, is based on new, three year data from a  prospective, randomized, placebo-controlled clinical trial, the APPROVe  (Adenomatous Polyp Prevention on VIOXX) trial.   The trial, which is being stopped, was designed to evaluate the efficacy of VIOXX  25mg in preventing recurrence of colorectal polyps in patients with a history of  colorectal adenomas.  In this study, there was an increased relative risk for  confirmed cardiovascular (CV) events, such as heart attack and stroke,  beginning after 18 months of treatment in the patients taking VIOXX compared to  those taking placebo. The results for the first 18 months of the APPROVe study  did not show any increased risk of confirmed CV events on VIOXX, and in this  respect  are similar to the results of two placebo-controlled studies described in  the current US labeling for VIOXX.

For more information visit

http://www.merck.com/newsroom/vioxx_withdrawal/

Celecoxib

Valdecoxib:
The newest COX-2 inhibitor approved by the FDA 2001.

Insert here in bold:

In December, 2004, The Food and Drug Administration (FDA) announced important new information on side effects associated with the use of Bextra (valdecoxib), a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) which is indicated for the treatment of osteoarthritis, rheumatoid arthritis and dysmenorrhea (menstrual pain). A "boxed" warning, strengthening previous warnings about the risk of life-threatening skin reactions and a new bolded warning contraindicating the use of Bextra in patients undergoing coronary artery bypass graft (CABG) surgery will be added to the label.

In addition, the FDA will also seek input from the public and from outside experts on the appropriate uses for Bextra and other NSAIDs at a previously-announced Advisory Committee meeting, to be held early in 2005.

Boxed and bolded warnings provide healthcare professionals and patients with important information on drugs that may be associated with serious side effects in a way that maximizes the drug’s benefits and minimizes its risks.

For more information, visit:

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

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

Indications:

• For the relief of the signs and symptoms of OA.
• For the relief of the signs and symptoms of RA.

Considerations:

• Contraindicated in patients with demonstrated allergic-type reactions to sulfonamides and patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs
• 8-11 hour half-life
• Metabolized in the liver primarily by P450 3A4 and 2C9.

Available formulations: 10 mg & 20 mg tablets
Usual Dosage: OA or RA: 10 mg once daily

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