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response to idelalisib should be monitored more closely whenever a CYP450 3A4/P-gp inhibitor is added to or withdrawn from therapy, and the idelalisib dosing adjusted or interrupted as necessary in accordance with the product labeling.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: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).