COX-2 Inhibitors Dilemma
Vioxx, Celebrex, Bextra What Patients Should Do

Medical Author: William C. Shiel, Jr., MD, FACP, FACR
Medical Editor: Jay W. Marks, MD

The recent withdrawal of Vioxx from the market (September, 2004) has resulted in one of the most tumultuous times in history for the pharmaceutical industry, patients, and doctors. At the time of its withdrawal, Vioxx was one of the most widely used medications in the world. The fallout has left the pharmaceutical industry on edge at a minimum, left patients worried and wondering whom to trust, and left doctors out on a limb faced with controversial research data to review with their patients.

In this article, I hope to: (1) clarify issues by using the current dilemma of the COX-2 inhibitor drugs [(rofecoxib) Vioxx, (celecoxib) Celebrex, and (valdecoxib) Bextra] NOTE: April 7, 2005, Pfizer agreed to suspend sales and marketing of Bextra in the U.S., pending further discussions with the with the FDA. For more information, please read the FDA press release. , as a background; and (2) present general guidelines as to what patients should do in response to having their medication withdrawn from the market or even hearing of potential risks of their medications that are reported in the media.

What's so special about COX-2 inhibitors?


Cyclooxygenase-1 (COX-1) is an enzyme that is normally present in a variety of areas of the body, including sites of inflammation and the stomach. The COX-1 enzyme of the stomach produces certain chemical messengers (called prostaglandins) that ensure the natural mucus lining, which protects the inner stomach. Common anti-inflammatory drugs, like aspirin or ibuprofen, block the function of the COX-1 enzyme along with another enzyme, COX-2 (described below). With these traditional antiinflammatory drugs, inflammation is reduced by blocking Cox-2, but the protective mucus lining of the stomach is also reduced because Cox-1 is blocked, which can cause stomach upset, ulceration, and bleeding from the stomach and intestines.


Another enzyme, cyclooxygenase-2 (COX-2), also produces these chemical messenger molecules, but the COX-2 enzyme is located specifically in areas of the body that are responsible for inflammation and not in the stomach. When the COX-2 enzyme is blocked, inflammation is reduced. Since the COX-2 enzyme does not play a role in the normal function of the stomach, medications that selectively block COX-2 do not present the risk of injuring the stomach that medications also blocking COX-1 can.

Newly developed drugs that selectively block the COX-2 enzyme are called COX-2 inhibitors. Blocking this enzyme impedes the production of the prostaglandins that cause the pain and swelling of arthritis inflammation. The common anti-inflammatory drugs (like aspirin, ibuprofen, and naproxen) are all non-selective and act by blocking the action of both the COX-1 and COX-2 enzymes.

The COX-2 inhibitors represent a newer class of anti-inflammatory drugs that do not affect COX-1, but selectively block only COX-2. This selective action provides the benefits of reducing inflammation without the increased risk of stomach irritation, ulceration, and bleeding. A major advantage of the COX-2 inhibitors over traditional non-selective COX-1 and COX-2 NSAIDs (nonsteroidal anti-inflammatory drugs) lies in the fact that they are easier on the stomach. Therefore, they are generally considered safer for patients with a history of stomach (gastrointestinal) problems. Another particular advantage of COX-2 inhibitors is that they do not impair the normal function of an important blood clotting element called platelets. As a result, they may be used in patients taking blood thinning medications, such as warfarin (Coumadin), and they may be used in and around surgical procedures without an increased risk of bleeding.