DOCTOR'S VIEW ARCHIVEMedical 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a background; and (2) present general guidelines as to what patients should do in response to having their medication withdrawn from the market or even hearing of potential risks of their medications that are reported in the media.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?
- What happened with Vioxx (rofecoxib)?
- What should patients do?
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.
What Happened With Vioxx (rofecoxib)?
On September 30, 2004, Vioxx (rofecoxib), a drug used to quiet the inflammation of arthritis and relieve pain, was withdrawn from the market by its maker, Merck. The reason for the withdrawal was the occurrence of side effects noted in a study that Merck was conducting to see if Vioxx could prevent polyps of the colon and rectum. During this trial, it was noted that there was an increased risk for heart attack and stroke in patients continuing to take Vioxx longer than 18 months.
The risk of heart attack or stroke from taking Vioxx was small, but real. Of note, there has been no indication that any long term damage occurs once the drug is discontinued.
Problems After Vioxx Withdrawal
A natural concern about the potential side effects of other inflammation medications of the same class as Vioxx has arisen. This class (the COX-2 inhibitors) includes Celebrex and Bextra, also popular medications used to stop pain and inflammation.
Currently, there are some reports suggesting that these medications do not increase the risk of heart attack or stroke and a few reports suggesting that they can. There are also media reports and letters in some high profile medical journals suggesting that patients should not be taking some or all COX-2 inhibitors, while ads on television by plaintiff's attorneys only further the agitation.
MedicineNet.com recently surveyed online viewers after the Vioxx drug withdrawal and found that over half of former Vioxx users did not contact their physicians before stopping the medication or shifting to an alternative medication over-the-counter! Moreover, a majority of former Vioxx users expressed "worry" about potential side effects of all medications. Well over half of these viewers experienced side effects from new medications they ended up using, while less than half benefited from the new medication! Click here to read the results of the survey.
What Should Patients Do?
The upcoming (mid February, 2005) FDA hearing on the COX-2 inhibitors may or may not resolve some of the concerns described above. Meanwhile, as doctors and patients, we move on. Below are some methods I suggest as appropriate for patients encountering decisions regarding medications. They are principles that I use as a practicing arthritis specialist in dealing with my patients day to day.
- Now, more than ever, it is important for doctors and patients to communicate with each other. Our MedicineNet.com survey indicates that the media is having a substantial impact on medication decision-making. Patients should absolutely not be directing their medication usage based on media comments without contacting their doctors. This practice can lead to dangerous complications. Doctors must listen carefully to their patients' concerns about safety and review the performance of the prescribed medications in response to the Vioxx withdrawal.
- Patients with chronic pain rely on their pain medication for relief of their symptoms and to improve their quality of life. They should only be taking medications that are truly needed to treat specific conditions for which the medications are used. Should the patients' conditions improve or resolve, then it may or not be the case that their medications could be reduced or discontinued.
- Medications should be used in the lowest dose that is effective for the condition treated. Lower doses of medications are nearly always somewhat safer. However, they are not always optimal. For example, lower doses of NSAIDs (nonsteroidal anti-inflammatory drugs) might be used for degenerative arthritis (osteoarthritis) than for inflammatory forms of arthritis (such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis), which typically require high doses of anti-inflammatory medication for adequate treatment.
- The risks and benefits of taking a medication must be evaluated in an individualized fashion for each patient. The decision to take a medication requires knowledge of the severity of the condition treated, underlying medical conditions, past medication experiences, and the patient's age to adequately appreciate the risks. Likewise, when a patient considers discontinuing a medication, his or her chart needs to be reviewed by a doctor to consider several factors. Why was the patient taking this particular drug? Were there side effects or allergies? How would a substitute drug help the underlying condition and interact with other drugs the patient may be taking. There is no universal substitute for any particular drug. Rather, each patient requires a personal evaluation in considering an alternative medication.
- Finally, controversial research by medical scientists should not be allowed to create unnecessary anxiety for patients who are not communicating with their doctors. Patients' concerns should be minimized by consulting with their doctors, who are in the best position to discuss these issues within the context of their individual case. Similarly, doctors' who have concerns based on new medical knowledge should discuss them openly with their patients.