Drug Interaction Report

MONITOR: Coadministration with alpelisib may decrease the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 2C9, such as warfarin. The proposed mechanism, based on in vitro data, is increased clearance due to alpelisib-mediated induction of CYP450 2C9.

MANAGEMENT: Patient monitoring is recommended if alpelisib is used concomitantly with drugs that are substrates of CYP450 2C9, particularly those with a narrow therapeutic range. The potential for diminished therapeutic effects should be considered when alpelisib is prescribed in combination with drugs that are CYP450 2C9 substrates. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever alpelisib is added to or withdrawn from therapy with these drugs. An alternative agent with no or minimal CYP450 2C9-inducing activity may also be considered.

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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.