Drug Interaction Report

GENERALLY AVOID: Coadministration of sacituzumab govitecan with inhibitors of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) may increase the risk of adverse effects, such as nausea, vomiting, diarrhea, and neutropenia. The proposed mechanism involves increased exposure to the pharmacologically active metabolite SN-38, a topoisomerase I inhibitor linked to sacituzumab govitecan, which is metabolized via UGT1A1. Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity and patients who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia from SN-38.

MANAGEMENT: Concomitant use of sacituzumab govitecan with UGT1A1 inhibitors should be avoided. If coadministration is unavoidable, patients should be closely monitored for the development of severe nausea, vomiting, diarrhea, and neutropenia. Patients should be advised to promptly report symptoms such as chills, fever, malaise, sore throat, mouth sores, unusual fatigue, bruising, or bleeding.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.