Drug Interactions between Mifeprex and naloxegol

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of naloxegol. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In pharmacokinetic studies, naloxegol systemic exposure (AUC) was increased approximately 3.5-fold by the moderate CYP450 3A4 inhibitor diltiazem and nearly 13-fold by the potent inhibitor ketoconazole. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to naloxegol may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

ADJUST DOSING INTERVAL: Food may increase the rate and extent of naloxegol absorption. When administered with a high-fat meal, naloxegol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 30% and 45%, respectively. In clinical trials, naloxegol was given on an empty stomach approximately 1 hour prior to the first meal in the morning.

MANAGEMENT: Patients treated with naloxegol should avoid consumption of grapefruit and grapefruit juice. Naloxegol should be taken on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.

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.