Drug Interaction Report

MONITOR: Coadministration with phenytoin and/or other enzyme-inducing anticonvulsants may decrease the plasma concentrations of valdecoxib. The mechanism is induction of CYP450 2C9 and 3A4, the isoenzymes responsible for the metabolic clearance of valdecoxib. According to product labeling, coadministration of phenytoin (300 mg once daily) and valdecoxib (40 mg twice a day) for 12 days resulted in decreased steady-state systemic exposure (AUC) of valdecoxib by 27% compared to administration of valdecoxib alone. The pharmacokinetics of phenytoin was not significantly affected in the presence of valdecoxib. No data are available for other anticonvulsants.

MANAGEMENT: Patients already stabilized on valdecoxib may experience loss of pain and inflammation control with the coadministration of phenytoin and/or other enzyme-inducing anticonvulsants such as carbamazepine, oxcarbazepine, phenobarbital, and primidone. Pharmacologic response to valdecoxib should be monitored more closely whenever these agents are added to or withdrawn from therapy, and the valdecoxib dosage adjusted as necessary. In addition, because valdecoxib is a moderate inhibitor of CYP450 2C9 and 2C19 and a weak inhibitor of 2D6 and 3A4, valdecoxib labeling recommends that routine monitoring for alteration of antiepileptic efficacy be performed when therapy with valdecoxib is either initiated or discontinued in patients receiving anticonvulsants.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.