Drug Interaction Report

Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of netupitant. When a single 300 mg-0.5 mg dose of netupitant-palonosetron was administered following 400 mg once daily administration of the potent CYP450 3A4 inhibitor ketoconazole for 12 days, mean netupitant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 25% and 140%, respectively, while mean Cmax and AUC of palonosetron increased by 15% and 10%, respectively. No dosage adjustment is necessary for single-dose administration of netupitant-palonosetron when used with potent CYP450 3A4 inhibitors. However, patients may experience increased adverse effects such as headache, asthenia, dyspepsia, fatigue, constipation, and erythema.

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.