Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2C9 and/or 3A4 may increase the plasma concentrations of valdecoxib, which is metabolized by these isoenzymes. According to the product labeling for valdecoxib, multi-dose administration of fluconazole (CYP450 2C9/3A4 inhibitor) and ketoconazole (CYP450 3A4 inhibitor) increased the area under the plasma concentration-time curve (AUC) of a single 20 mg dose of valdecoxib by 62% and 38%, respectively. Parecoxib, a prodrug of valdecoxib, may be similarly affected.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of valdecoxib or parecoxib, including serious adverse effects such as gastrointestinal ulceration and bleeding, should be considered during concomitant therapy with CYP450 2C9 or 3A4 inhibitors, particularly combination (2C9/3A4) inhibitors such as fluconazole, fluvoxamine, imatinib, and zafirlukast. Dose reductions of the COX-2 inhibitor may be required.