Drug Interactions between Mifeprex and stiripentol

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: Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.

GENERALLY AVOID: Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.

GENERALLY AVOID: It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.

MANAGEMENT: Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.