Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of idelalisib, which is a substrate of both the isoenzyme and efflux transporter. In healthy volunteers, administration of a single 400 mg dose of idelalisib with the potent CYP450 3A4 and P-gp inhibitor ketoconazole (400 mg daily for 4 days) resulted in a 1.8-fold increase in mean idelalisib systemic exposure (AUC). No change was observed in mean peak plasma concentration (Cmax).

MANAGEMENT: Caution is advised if idelalisib is prescribed in combination with CYP450 3A4 and/or P-gp inhibitors. Pharmacologic response to idelalisib should be monitored more closely whenever a CYP450 3A4/P-gp inhibitor is added to or withdrawn from therapy, and the idelalisib dosing adjusted or interrupted as necessary in accordance with the product labeling. Patients should be closely monitored for idelalisib toxicity such as hepatotoxicity, diarrhea, colitis, intestinal perforation, pneumonitis, neutropenia, and thrombocytopenia.

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.