Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of vilazodone, which is primarily metabolized by the isoenzyme. According to the product labeling, concomitant use of vilazodone with potent CYP450 3A4 inducers such as carbamazepine can decrease vilazodone systemic exposure by approximately 45%.

MANAGEMENT: The possibility of diminished therapeutic response to vilazodone should be considered during coadministration with potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, phenobarbital, phenytoin, and rifampin. When concomitant use is prescribed for greater than 14 days, an increase in the vilazodone dosage up to 2-fold may be considered depending on clinical response, up to a maximum of 80 mg daily. Following discontinuation of the CYP450 3A4 inducer, the dosage of vilazodone should be returned to the original level in 14 days.

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

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

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.