Drug Interaction Report

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of alfuzosin, which is primarily metabolized by the isoenzyme. Severe hypotension and priapism may occur. In pharmacokinetic studies, repeated oral administration of 400 mg/day of ketoconazole, a potent CYP450 3A4 inhibitor, increased alfuzosin peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.3- and 3.2-fold, respectively, following a single 10 mg dose. Repeated oral administration of ketoconazole 200 mg/day increased alfuzosin Cmax by 2.1-fold and AUC by 2.5-fold following a single 10 mg dose.

MANAGEMENT: Concomitant use of alfuzosin with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics is considered contraindicated. Some authorities recommend avoiding concomitant use of alfuzosin during and for 2 weeks after treatment with itraconazole.

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.

ADJUST DOSING INTERVAL: Administration of alfuzosin with food enhances oral bioavailability. According to the manufacturer, extent of absorption is 50% higher when administered under fed conditions compared to fasting conditions.

MANAGEMENT: To ensure maximal oral absorption, alfuzosin should be administered with or immediately after a meal.