Drug Interactions between Targretin and vilazodone

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.

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.