Drug Interactions General: Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done with caution. In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of cytochrome P450 2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by P450 2D6. ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors. This interaction should be given consideration in patients taking CELEBREX concomitantly with ACE-inhibitors. Furosemide: Clinical studies, as well as post marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. Aspirin: CELEBREX can be used with low-dose aspirin. However, concomitant administration of aspirin with CELEBREX increases the rate of GI ulceration or other complications, compared to use of CELEBREX alone (see CLINICAL STUDIES - Special Studies - Use with Aspirin and WARNINGS - Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation - CLASS Study). Because of its lack of platelet effects, CELEBREX is not a substitute for aspirin for cardiovascular prophylaxis. Fluconazole: Concomitant administration of fluconazole at 200 mg QD resulted in a two-fold increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole (see Pharmacokinetics - Metabolism). CELEBREX should be introduced at the lowest recommended dose in patients receiving fluconazole. Lithium: In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with CELEBREX 200 mg BID as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when CELEBREX is introduced or withdrawn. | ||||
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