Drug Interaction Report

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of daclatasvir, which is primarily metabolized by the isoenzyme. When a single 10 mg dose of daclatasvir was administered following pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), daclatasvir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.6- and 3-fold, respectively.

MANAGEMENT: A reduction in the dosage of daclatasvir to 30 mg once daily is recommended when used with potent CYP450 3A4 inhibitors.

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of daclatasvir, which is primarily metabolized by the isoenzyme. When a single 10 mg dose of daclatasvir was administered following pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), daclatasvir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.6- and 3-fold, respectively. No data are available for other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised when daclatasvir is used with moderate CYP450 3A4 inhibitors; however, according to the manufacturer, dose adjustments are not required. Patients should be monitored for adverse effects such as headache, fatigue, nausea, diarrhea, and serum lipase elevations.

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.