Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of romidepsin, which is primarily metabolized by the isoenzyme. In patients with advanced cancer, administration of romidepsin 8 mg/m2 (4-hour infusion) with ketoconazole resulted in a 10% increase in romidepsin peak plasma concentration (Cmax) and 25% increase in systemic exposure (AUC) compared to romidepsin administered alone. The potential for increased risk of hematologic toxicities such as anemia, leukopenia, and thrombocytopenia as well as electrocardiographic changes such as QT interval prolongation and T-wave and ST-segment changes should be considered.

MANAGEMENT: Caution is advised when romidepsin is used with potent CYP450 3A4 inhibitors. Patients should have complete blood cell counts, electrocardiograms, and serum electrolyte levels performed at baseline and regular intervals as recommended in the product labeling. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.