Drug Interaction Report

CONTRAINDICATED: Concomitant use of anticoagulants may exacerbate mifepristone-induced vaginal bleeding in women. Prolonged, potentially heavy bleeding lasting approximately 9 to 30 days typically follows mifepristone use in termination of pregnancy. Because it is a progesterone receptor antagonist, mifepristone can also promote unopposed endometrial proliferation that may result in endometrium thickening, cystic dilatation of endometrial glands, and vaginal bleeding when used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome.

MANAGEMENT: Concurrent anticoagulant therapy is considered a contraindication in the use of mifepristone for pregnancy termination. When used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, mifepristone treatment should be administered cautiously in women who are receiving anticoagulant therapy. Patients who experience vaginal bleeding should be referred to a gynecologist for further evaluation.

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.