Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of eravacycline, which undergoes oxidation by CYP450 3A4 and flavin monooxygenase. When eravacycline was given with the potent 3A4 inhibitor, itraconazole, eravacycline peak plasma concentration (Cmax) increased by 5% and systemic exposure (AUC) increased by 32%, while clearance decreased by 32%.

MANAGEMENT: These changes are not considered clinically significant alone, but patients with additional risk factors for increased exposure (e.g., obesity, hepatic impairment) should be monitored closely for adverse effects such as nausea, vomiting, diarrhea, headache, photosensitivity, pseudotumour cerebri, increased BUN, acidosis, hyperphosphatemia, pancreatitis, and/or abnormal liver function tests.

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.