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 reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.