Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of mifepristone, which is primarily metabolized by the isoenzyme. However, the interaction has not been studied, and the clinical impact is unknown.

MANAGEMENT: When mifepristone is prescribed daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, concomitant use with potent CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, and rifamycins should generally be avoided. Other, less potent inducers such as aminoglutethimide, barbiturates, bexarotene, bosentan, dabrafenib, efavirenz, nafcillin, nevirapine, somatrem, somatropin, and various other anticonvulsants may also interact. Caution is advised if they are used with mifepristone.

ADJUST DOSING INTERVAL: Food may significantly increase the plasma concentrations of mifepristone.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mifepristone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, it should be taken with food to achieve consistent plasma drug levels. Patients should be advised to avoid consuming grapefruit or grapefruit juice during treatment with mifepristone, as it may cause increased adverse effects such as headache, dizziness, fatigue, nausea, vomiting, cramping, diarrhea, hypokalemia, adrenal insufficiency, vaginal bleeding, arthralgia, peripheral edema, and hypertension. Because mifepristone is eliminated slowly from the body, the interaction with grapefruit juice may be observed for a prolonged period.