Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of vortioxetine, which is primarily metabolized by CYP450 2D6. According to the product labeling, administration of vortioxetine with the potent CYP450 inducer rifampin resulted in an approximately 50% decrease in vortioxetine peak plasma concentration (Cmax) and 75% decrease in systemic exposure (AUC) compared to administration of vortioxetine alone.

MANAGEMENT: An increase in the dosage of vortioxetine should be considered when used in combination with potent CYP450 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifamycins) for greater than 14 days, up to a maximum of three times the original dosage depending on clinical response. Following discontinuation of the potent CYP450 inducer, vortioxetine dosage should be returned to the original level within 14 days. Other known CYP450 inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, enzalutamide, efavirenz, etravirine, nevirapine, somatrem, somatropin, suzetrigine, and various other anticonvulsants, although the extent to which they interact with vortioxetine is unknown. If concomitant use is required, close monitoring for signs of reduced therapeutic efficacy is advised, and the vortioxetine dosage adjusted as necessary.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.