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.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.