Drug Interaction Report

ADJUST DOSE: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of vilazodone, which is primarily metabolized by the isoenzyme. According to the product labeling, concomitant use of vilazodone with potent CYP450 3A4 inhibitors such as ketoconazole can increase vilazodone plasma concentrations by approximately 50%.

MANAGEMENT: The maintenance dosage of vilazodone should be reduced to 20 mg/day when used with potent CYP450 3A4 inhibitors.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of vilazodone, which is primarily metabolized by the isoenzyme. According to the product labeling, concomitant use of vilazodone with potent CYP450 3A4 inhibitors such as ketoconazole can increase vilazodone plasma concentrations by approximately 50%. No data are available for less potent inhibitors such as aprepitant, diltiazem, erythromycin, and verapamil.

MANAGEMENT: When used with moderate CYP450 3A4 inhibitors, the maintenance dosage of vilazodone should be reduced to 20 mg/day in patients who develop intolerable adverse events.

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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of vilazodone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of vilazodone. According to the product labeling, vilazodone blood concentrations in the fasted state can be decreased by approximately 50% compared to the fed state, which may result in diminished effectiveness in some patients. The absolute bioavailability of vilazodone is 72% with food. In study subjects, administration with food (high-fat or light meal) increased vilazodone peak plasma concentration (Cmax) by approximately 147% to 160% and systemic exposure (AUC) by approximately 64% to 85%.

MANAGEMENT: Patients receiving vilazodone should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how vilazodone affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Vilazodone should be taken with food. Administration without food may result in inadequate drug concentrations and diminished effectiveness.