Drug Interactions between itraconazole and vilazodone

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

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.