Drug Interactions between Mifeprex and vilazodone

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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of vilazodone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of vilazodone. According to the product labeling, vilazodone blood concentrations in the fasted state can be decreased by approximately 50% compared to the fed state, which may result in diminished effectiveness in some patients. The absolute bioavailability of vilazodone is 72% with food. In study subjects, administration with food (high-fat or light meal) increased vilazodone peak plasma concentration (Cmax) by approximately 147% to 160% and systemic exposure (AUC) by approximately 64% to 85%.

MANAGEMENT: Patients receiving vilazodone should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how vilazodone affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Vilazodone should be taken with food. Administration without food may result in inadequate drug concentrations and diminished effectiveness.