Drug Interaction Report

MONITOR: Coadministration with alpelisib may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 2B6. The proposed mechanism, based on in vitro data, is increased clearance due to alpelisib-mediated induction of CYP450 2B6.

MANAGEMENT: Caution and monitoring are recommended if alpelisib is used concomitantly with drugs that are substrates of CYP450 2B6, particularly sensitive CYP450 2B6 substrates (e.g. bupropion) or those with a narrow therapeutic window. The potential for diminished therapeutic effects should be considered when alpelisib is prescribed in combination with drugs that are CYP450 2B6 substrates.

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.

One study (n=12) has reported that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. The exact mechanism of this interaction has not been specified. Further research is needed to examine the subjective and physiological interactions between caffeine and nicotine.