Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may increase the plasma concentrations of romidepsin. The exact mechanism of interaction has not been established, particularly since romidepsin is a substrate of CYP450 3A4, and induction of the isoenzyme would be expected to reduce its plasma concentration. In patients with advanced cancer, administration of romidepsin 14 mg/m2 (4-hour infusion) with the potent CYP450 3A4 inducer, rifampin, unexpectedly increased romidepsin peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 80%, respectively, compared to romidepsin administered alone. In addition, rifampin decreased romidepsin clearance by 44% and volume of distribution by 52%. It is not known if other potent CYP450 3A4 inducers would alter the pharmacokinetics of romidepsin in the same manner.

MANAGEMENT: The use of romidepsin in combination with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided if possible. Alternative treatment lacking CYP450 3A4-inducing activity should be considered in patients receiving romidepsin. If concomitant use is required, patients should be closely monitored for development of hematologic toxicities such as anemia, leukopenia, and thrombocytopenia as well as electrocardiographic changes such as QT interval prolongation and T-wave and ST-segment changes.

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.