Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of brexpiprazole. In vitro and in vivo data indicate that brexpiprazole is metabolized primarily by CYP450 3A4 and 2D6. When a single 4 mg oral dose of brexpiprazole was administered to healthy study subjects treated with the potent CYP450 3A4 inducer rifampin at 600 mg twice daily for 12 days, mean brexpiprazole peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 31% and 73%, respectively, compared to administration of brexpiprazole alone. Reduced efficacy of brexpiprazole may occur.

MANAGEMENT: The prescribing information for brexpiprazole recommends doubling the usual dosage over 1 to 2 weeks following the addition of a potent CYP450 3A4 inducer. Additional dosage adjustments should be based on clinical evaluation. Upon discontinuation of the inducer, brexpiprazole dosage should be reduced to the original level over 1 to 2 weeks.

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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, 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.

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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.

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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.

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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.

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