Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 2C9 may decrease the plasma concentrations of celecoxib, which is primarily metabolized by the isoenzyme. When a single 200 mg dose of celecoxib was administered to 12 healthy volunteers following pretreatment with the moderate CYP450 2C9 inducer rifampin 600 mg once daily for 5 days, celecoxib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 56% and 64%, respectively, while clearance increased by 185%. Reduced efficacy of celecoxib may occur.

MANAGEMENT: The potential for diminished pharmacologic effects of celecoxib should be considered during coadministration with CYP450 2C9 inducers. Dose adjustments or alternative treatments may be required if an interaction is suspected.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.