Drug Interaction Report

MONITOR: Coadministration with osimertinib may increase the exposure of breast cancer resistance protein (BCRP) transporter substrates. In vitro studies have shown that osimertinib is a competitive inhibitor of BCRP. In a clinical pharmacokinetic study, concomitant use of osimertinib with the BCRP substrate rosuvastatin increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of rosuvastatin by 35% and 72%, respectively.

MANAGEMENT: Caution is recommended if osimertinib is used in combination with drugs that are substrates of the BCRP transporter, particularly those with a narrow therapeutic index. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever osimertinib is added to or withdrawn from therapy.

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.