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Back To Vidyya FDA Advisory Committee Acknowledges GI Safety Data

For Both COX-2 Inhibitors, Vioxx® And Celebrex®


The Arthritis Advisory Committee to the US Food and Drug Administration (FDA) has provided guidance to FDA that the labels for both Vioxx (rofecoxib) and Celebrex ® (celecoxib capsules) should reflect data showing gastrointestinal safety advantages versus the specific comparator NSAIDs studied.

Celebrex is the only COX-2 specific inhibitor approved for osteoarthritis (OA) and adult rheumatoid arthritis (RA).

Celebrex should not be taken by patients who have aspirin-sensitive asthma or allergic reactions to aspirin or other arthritis medicines or certain sulfa drugs called sulfonamides, or who are in their third trimester of pregnancy. As with all NSAIDs, serious GI tract ulcerations can occur without warning symptoms. Physicians and patients should remain alert to the signs and symptoms of GI bleeding. As with all NSAIDs, Celebrex should be used with caution in patients with fluid retention, hypertension, or heart failure. Celebrex does not affect platelet function and therefore should not be used for cardiovascular prophylaxis. In clinical studies the most common side effects of Celebrex were dyspepsia, diarrhea and abdominal pain, which were generally mild to moderate.

The drug is co-promoted by Pharmacia Corporation and Pfizer Inc. Celebrex® (celecoxib capsules) is a registered trademark of Pharmacia Corporation.

The Arthritis Advisory Committee of the Food and Drug Administration yesterday also reviewed Merck & Co., Inc.'s application for changes to the prescribing information for Vioxx® (rofecoxib), Merck's medicine for osteoarthritis and acute pain, to reflect results from the Vioxx Gastrointestinal Outcomes Research (VIGOR) study. The Advisory Committee agreed with Merck and the FDA that results from the study should be included in the labeling for Vioxx. The FDA is not obligated to follow the advice of the Advisory Committee, but usually does. The FDA noted that it will consider all available information, including the information reported and advice received at today's Advisory Committee meeting, before any final decisions are made on Merck's application and other issues discussed by the Committee.

Vioxx was approved by the FDA in May 1999 to treat osteoarthritis and acute pain. The prescribing information for Vioxx currently contains the standard NSAID Warning about GI side effects. Merck's application to the FDA was based on the 8,000-patient VIGOR study, which evaluated the GI profile of Vioxx 50 mg compared to the non-selective NSAID naproxen, and on other studies with Vioxx.

In VIGOR, Vioxx 50 mg, a dose two-times the highest chronic dose approved for osteoarthritis, significantly reduced serious GI side effects by half compared to a commonly used dose of naproxen (1,000 mg) in rheumatoid arthritis patients. The Committee recommended that these results be included in the labeling. Vioxx is not indicated for rheumatoid arthritis.

Although the VIGOR study was a GI outcomes study and was not designed to show differences in cardiovascular effects, significantly fewer heart attacks were observed in patients taking naproxen (0.1 percent) compared to the group taking Vioxx 50 mg (0.5 percent) in this study. There was no difference in cardiovascular mortality between the groups treated with Vioxx or naproxen.

Patients taking aspirin did not participate in VIGOR.

In extensive discussions, the Advisory Committee explored this finding, other studies of Vioxx and possible explanations for this result in VIGOR. In the completed osteoarthritis trials and on-going clinical trials with Vioxx 12.5 mg, 25 mg and 50 mg in 30,000 patients, there was no difference in the incidence of cardiovascular events, such as heart attacks, among patients taking Vioxx, other NSAIDs and placebo.

Merck scientists said the VIGOR finding is consistent with naproxen's ability to block platelet aggregation by inhibiting COX-1 like aspirin, which is used to prevent second cardiac events in patients with a history of heart attack, stroke or other cardiac events. This is the first time this effect of naproxen on cardiovascular events has been observed in a clinical study. Other explanations were advanced by the FDA reviewer and were discussed with the Advisory Committee. The Committee recommended that the data on cardiovascular events in VIGOR be included in the labeling for Vioxx.

In addition, the Committee agreed that the prescribing information for both Vioxx and Celebrex® (celecoxib) should reflect the fact that neither of these selective NSAIDs confer cardioprotective benefits and are not a substitute for low-dose aspirin. The Committee also recommended that other studies be conducted to further explore the safety of concomitant use of selective NSAIDs and low-dose aspirin.

Vioxx is approved in the United States for the relief of the signs and symptoms of osteoarthritis, management of acute pain in adults and treatment of menstrual pain. The recommended starting dose of Vioxx for the treatment of osteoarthritis is 12.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 25 mg once daily, the maximum recommended dose for osteoarthritis.

Vioxx does not block platelet aggregation and should not be used as a substitute for aspirin to prevent cardiac events. Vioxx does not interfere with the ability of low-dose aspirin to block platelet aggregation. Administration of low-dose aspirin with Vioxx may result in an increased rate of GI ulcers or other complications compared to use of Vioxx alone.

In rare cases, serious stomach problems, such as bleeding, can occur without warning symptoms. People who have had an allergic reaction, such as asthma, to Vioxx, aspirin or other arthritis medicines should not take Vioxx. People who have liver or kidney problems, or are pregnant, should tell their doctors. Also, Vioxx should not be used by women in late pregnancy. Common side effects reported in other clinical trials with Vioxx were upper- respiratory infection, diarrhea, nausea and high blood pressure.

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Editor: Susan K. Boyer, RN
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