Drug Interaction Report

GENERALLY AVOID: Theoretically, there is potential for an indirect interaction between asparaginase and oral contraceptives. The mechanism may involve asparaginase's hepatotoxicity, which may impair oral contraceptives' hepatic clearance.

MANAGEMENT: The use of oral contraceptives during asparaginase treatment is not recommended. Other non-oral contraceptive methods should be used in women of childbearing potential. According to the manufacturer, females of reproductive potential should be advised to use effective contraception during asparaginase treatment and for at least 3 to 6 months after the last dose.

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.