Drug Interaction Report

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of romidepsin, which is primarily metabolized by the isoenzyme. In patients with advanced cancer, administration of romidepsin 8 mg/m2 (4-hour infusion) with ketoconazole resulted in a 10% increase in romidepsin peak plasma concentration (Cmax) and 25% increase in systemic exposure (AUC) compared to romidepsin administered alone. The potential for increased risk 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 should be considered.

MANAGEMENT: Caution is advised when romidepsin is used with potent CYP450 3A4 inhibitors. Patients should have complete blood cell counts, electrocardiograms, and serum electrolyte levels performed at baseline and regular intervals as recommended in the product labeling. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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.