Drug Interaction Report

MONITOR: Coadministration with darunavir may increase the plasma concentrations of disopyramide, flecainide and mexiletine. The proposed mechanism is darunavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these antiarrhythmic agents. The interaction has not been studied but could conceivably lead to serious and/or life-threatening reactions including cardiac arrhythmias and other toxicities.

MANAGEMENT: Caution is advised if darunavir, including boosted darunavir, must be used with disopyramide, flecainide or mexiletine. Pharmacologic response and plasma antiarrhythmic drug levels should be monitored more closely whenever darunavir is added to or withdrawn from therapy, and the antiarrhythmic dosage adjusted as necessary.

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.