Drug Interaction Report

GENERALLY AVOID: Coadministration of inhibitors of the breast cancer resistance protein (BCRP) transporter with alpelisib may increase the plasma concentrations and risk of adverse effects of alpelisib, which is a substrate of this efflux transporter. Alpelisib has been identified as a substrate of BCRP in in vitro studies. However, clinical data are not available.

MANAGEMENT: If coadministration with BCRP inhibitors is required, patients should be closely monitored for alpelisib-related adverse reactions, including hyperglycemia, diarrhea, rash, acute kidney injury, abdominal pain, and anemia. Some authorities recommend coadministration of alpelisib with BCRP inhibitors be avoided whenever possible (US).

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.