Drug Interaction Report

GENERALLY AVOID: Coadministration with carbamazepine, phenobarbital, phenytoin, or primidone may significantly reduce the plasma concentrations of darunavir. The proposed mechanism is induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of darunavir.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, darunavir should not be used in combination with carbamazepine, phenobarbital, phenytoin, or primidone.

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.