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.

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: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.