Drug Interactions between eltrombopag and sodium phenylbutyrate / taurursodiol

ADJUST DOSING INTERVAL: Coadministration with a high-fat meal may reduce the rate and extent of absorption of sodium phenylbutyrate. When a single 3 g-1 g dose of sodium phenylbutyrate-taurursodiol (sodium phenylbutyrate-ursodoxicoltaurine) was administered to healthy volunteers in the presence of a high-fat, high-calorie meal (approximately 800 to 1000 calories; 500 to 600 calories from fat, 250 calories from carbohydrate, 150 calories from protein), sodium phenylbutyrate peak plasma concentration (Cmax) decreased by 75% and systemic exposure (AUC) decreased by 55%. The Cmax for taurursodiol was not significantly affected, but AUC was increased by 46%. The clinical significance of these changes has not been established. In premarketing studies, patients were advised to take the drug before a meal.

MANAGEMENT: The prescribing information recommends administration of sodium phenylbutyrate-taurursodiol before a meal or snack, particularly in patients of low body weight (less than 70 kg).

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of eltrombopag. In healthy volunteers, a standard high-fat breakfast significantly decreased plasma eltrombopag peak plasma concentration (Cmax) by 65% and systemic exposure (AUC) by 59% and delayed Tmax by one hour. The calcium content of this meal may have also contributed to this decrease in exposure. In another study, adult subjects administered a single 25 mg dose of eltrombopag for oral suspension with a high-calcium, moderate-fat, moderate-calorie meal exhibited a 79% decrease in Cmax and 75% decrease in AUC of eltrombopag. Administration of eltrombopag 2 hours after the high-calcium meal decreased eltrombopag Cmax by 48% and AUC by 47%, while administration 2 hours before the high-calcium meal decreased eltrombopag Cmax by 14% and AUC by 20%.

ADJUST DOSING INTERVAL: Polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc can significantly reduce the gastrointestinal absorption of eltrombopag due to chelation. In one clinical trial, administration of a single 75 mg dose of eltrombopag with an antacid containing 1524 mg aluminum hydroxide and 1425 mg magnesium carbonate resulted in an approximately 70% decrease in eltrombopag Cmax and AUC.

MANAGEMENT: Eltrombopag should be taken on an empty stomach one hour before or two hours after a meal. Additionally, eltrombopag should be taken at least 2 hours before or 4 hours after any products that contain polyvalent cations such as antacids, mineral supplements, dairy products, and fortified juices.