Drug Interaction Report

Coadministration with valdecoxib or its prodrug, parecoxib, may increase the plasma concentrations of omeprazole. The mechanism is valdecoxib inhibition of CYP450 2C19 and 3A4, the isoenzymes responsible for the metabolic clearance of omeprazole. According to product labeling, coadministration of valdecoxib (40 mg twice a day) and omeprazole (40 mg once a day) resulted in a 46% increase in the systemic exposure (AUC) of omeprazole compared to administration of omeprazole alone. The pharmacokinetics of valdecoxib were not significantly affected. Because higher dosages (up to 360 mg/day) of omeprazole are tolerated in Zollinger-Ellison patients, no dosage adjustment for omeprazole is indicated at normally recommended dosages. However, drugs whose absorption is sensitive to pH (e.g., some cephalosporins such as cefditoren, cefpodoxime, and cefuroxime; antiretroviral agents including atazanavir, delavirdine, and fosamprenavir; cyanocobalamin; ketoconazole; enteric coated preparations) may be negatively impacted by concomitant administration of omeprazole and valdecoxib or parecoxib. Coadministration of valdecoxib with dosages of omeprazole higher than 40 mg/day has not been studied.