Drug Interaction Report

MONITOR: Coadministration with maribavir may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is decreased clearance due to maribavir-mediated inhibition of the BCRP transport protein. There are no clinical data regarding the use of maribavir with BCRP substrates.

MANAGEMENT: Caution is advised when maribavir is prescribed with drugs that are BCRP substrates, particularly those with a narrow therapeutic range. Clinical and laboratory monitoring as well as dosage adjustments may be appropriate for some drugs whenever maribavir is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food significantly enhances the oral absorption and bioavailability of alpelisib. When administered with a high-fat high-calorie meal (985 calories with 58.1 g of fat) or a low-fat low-calorie meal (334 calories with 8.7 g of fat) the AUC and Cmax of a single dose of alpelisib was increased by 73% and 84% and 77% and 145%, respectively. There were no clinically significant differences in alpelisib AUC between the two types of meals. In addition, food appears to have a more pronounced effect on the solubility of alpelisib than gastric pH. When coadministered with a single 300 mg dose of alpelisib, ranitidine decreased the absorption and overall exposure of alpelisib. Following administration of ranitidine with a low-fat low-calorie meal, the mean AUC and Cmax of alpelisib was decreased by 21% and 36%, respectively. Administration of ranitidine under fasting conditions reduced the mean AUC and Cmax of alpelisib by 30% and 51%, respectively.

MANAGEMENT: To ensure maximal oral absorption, alpelisib should be administered with a meal.