Drug Interaction Report

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of ticagrelor, which is primarily metabolized by the isoenzyme. In healthy volunteers, administration of ticagrelor in combination with the moderate CYP450 3A4 inhibitor diltiazem resulted in increased ticagrelor peak plasma concentration (Cmax) and systemic exposure (AUC) by 69% and 174%, respectively. For the active metabolite, the Cmax was decreased by 38% and the AUC was unchanged. Ticagrelor had no effect on the plasma levels of diltiazem.

MANAGEMENT: Although administration with moderate CYP450 3A4 inhibitors is thought to be generally safe, it may be advisable to monitor pharmacologic response to ticagrelor more closely following the addition and withdrawal of these agents. Discontinuation of the concomitant medication may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.