Bleeding coxib

Valdecoxib, a diaryl-substituted isoxazole, is a new highly selective COX-2 inhibitor. Pharmacokinetic characteristics and dosage in arthritis are set forth in Table 36-1. In primary dysmenorrhea, dosage is 20 mg twice daily, and the drug is as effective as nonselective NSAIDs for this indication. Gastrointestinal and other toxicities are similar to those of the other coxibs. Valdecoxib has no effect on platelet aggregation or bleeding time. Serious reactions have been reported in sulfonamide-sensitive individuals. 

COX-2-selective inhibitors The COX-2-selective inhibitors may have a reduced risk of gastrointestinal effects, including gastric ulcers and serious gastrointestinal bleeding. Cele-coxib is a sulfonamide and may cause a hypersensitivity reaction in patients who are allergic to other sulfonamides. 

There is some evidence that non-selective NSAn>s such as ibupro-fen antagonise the antipiateiet effects of iow-dose aspirin, but that COX-2-seiective NSAEJs (coxibs) do not. Some, but not other, epidemiological studies have shown that non-selective NSAUfs reduce the cardioprotective effects of low-dose aspirin. Furthermore, some NSAE)s (particularly coxibs) are associated with increased thrombotic risk. Combined use of NSAE)s and low-dose aspirin increases the risk of gastrointestinal bleeds. This seems to apply equally to coxibs. 

A lower gastrointestinal risk with coxibs was confirmed in a retrospective case-control study of the incidence of peptic ulcer bleeding and perforation in users of COX-2 selective and non-selective NSAIDs [3 ]. The study was based on 2.2 million adults taking celecoxib, diclofenac, ibuprofen, naproxen, rofecoxib, or valdecoxib. Adjusted odds ratios (OR) compared with naproxen were ibuprofen 0.86 (95% Cl = 0.68, 1.09), rofecoxib 0.79 (0.62, 1.02), diclofenac 0.66 (0.47, 0.94), valdecoxib 0.50 (0.26, 0.97), and celecoxib 0.45 (0.35, 0.58). The overall... 

OR for peptic ulcer bleeding and perforation of non-selective NSAIDs compared with coxibs was 1.51 (95% Cl = 1.26, 1.98). 

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