Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) may significantly decrease the plasma concentrations of sacituzumab govitecan and its pharmacologically active metabolite, SN-38. The proposed mechanism involves decreased exposure to SN-38, a topoisomerase I inhibitor linked to sacituzumab govitecan, which is metabolized via UGT1A1. Loss of antineoplastic efficacy may occur.

MANAGEMENT: Due to the potential loss of antitumour activity, concomitant use of sacituzumab govitecan with UGT1A1 inducers should be avoided.

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: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.