Drug Interactions between Diacomit and elacestrant

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of elacestrant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When elacestrant (172 mg once daily) was administered with itraconazole, a potent CYP450 3A4 inhibitor, elacestrant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 4.4-fold and 5.3-fold, respectively. Concomitant use of fluconazole, a moderate CYP450 3A4 inhibitor, is predicted to increase elacestrant (345 mg single dose) Cmax and AUC by 1.6-fold and 2.3-fold, respectively. 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 elacestrant may increase the risk of adverse reactions such as musculoskeletal pain, nausea, dyslipidemia, increased liver enzymes, fatigue, decreased hemoglobin, and vomiting.

Administration of elacestrant (345 mg) with a high-fat meal (800 to 1000 calories, 50% fat) increased elacestrant Cmax and AUC by 42% and 22%, respectively, compared to fasted conditions.

MANAGEMENT: It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with elacestrant. Elacestrant should be taken with food at approximately the same time each day.

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.