CHICAGO, IL — February 15, 2000- A double-blind, randomized, placebo-controlled study published in this month’s Journal of Clinical Pharmacology concludes that the COX-2 specific inhibitor Celebrex® (celecoxib capsules) does not interfere with platelet function, even at 1200 mg per day, which is six times the recommended daily dose for osteoarthritis. Normal platelet function is important for patients at risk of bleeding and for those who are already taking medications that increase the risk of bleeding. This is significant for the millions of Americans with arthritis who may be taking low-dose aspirin for cardiovascular disease prophylaxis.
Study authors report that “unlike celecoxib or placebo, naproxen produce[s] statistically significant reductions in platelet aggregation…and increased bleeding time.” In contrast, the study notes that even at very high doses, “celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs [nonsteroidal anti-inflammatory drugs].”
The study was designed to compare the platelet effects of very high doses of Celebrex (600 mg bid) to commonly prescribed therapeutic doses of naproxen (500 mg bid) by examining measures of platelet function (e.g., bleeding time) in healthy subjects. Study participants were randomized to receive either Celebrex, naproxen, or placebo at varying doses over a 10-day period. Unlike naproxen, Celebrex was found to have no significant effect on bleeding time, even at six times the recommended daily dose for osteoarthritis patients.
Commenting on the study, rheumatologist Roland Moskowitz, M.D., of University Hospitals of Cleveland, said, “The study, which demonstrates that Celebrex doesn’t affect platelet function, points out one of the safety benefits of this drug. Since osteoarthritis and cardiovascular disease frequently occur together in elderly individuals, lack of platelet inhibition makes the drug a logical choice for patients using low-dose aspirin for cardiovascular disease prevention.” The Celebrex product labeling states that it can be used with low-dose aspirin. “This benefit meshes nicely with the fact that at recommended doses, there doesn’t appear to be any dose-related increase in the cardiovascular-related side effects of hypertension or peripheral edema.”
The Centers for Disease Control and Prevention estimates that one in five people age 35 and older take aspirin to prevent cardiovascular disease. In addition, one in four adults has hypertension in the United States. Moreover, up to one in three hypertensive patients has arthritis (approximately 18 million people). Arthritis is the leading health condition for those over 50 and is the leading cause of disability in the United States.
Celebrex, co-promoted by Searle and Pfizer Inc, is indicated for the relief of the pain and inflammation of osteoarthritis and adult rheumatoid arthritis. The product is also the only COX-2 specific inhibitor with an indication outside of the arthritis and pain therapeutic areas. It was approved as an oral adjunct to usual care (i.e., endoscopic surveillance and surgery) for patients with familial adenomatous polyposis (FAP)-a rare and devastating genetic disease that without surgical removal of the colon and/or endoscopic surveillance almost always results in colorectal cancer by age 40-50.
Patients who have a known allergic reaction to celecoxib, certain sulfa drugs called sulfonamides, aspirin or NSAIDs should not use Celebrex. As with all NSAIDs, serious gastrointestinal (GI) toxicity can occur with or without warning symptoms. Concomitant administration of Celebrex with aspirin does not reduce the GI or other risks associated with aspirin use.
As with all NSAIDs, Celebrex should be used with caution in patients with fluid retention, hypertension, or heart failure. In clinical trials, the most common side effects of Celebrex were dyspepsia, diarrhea and abdominal pain, which were generally mild to moderate.
Source: Searle & Co.