Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 may increase the plasma concentrations of bendamustine, which has been shown in vitro to be metabolized by the isoenzyme.

MANAGEMENT: Caution is advised if bendamustine is used in combination with CYP450 1A2 inhibitors. Close monitoring for toxicity (e.g., neutropenia, thrombocytopenia, anemia, leukopenia, infections, bleeding complications) is recommended, and the bendamustine dosage adjusted as necessary.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.