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 enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.