Drug Interaction Report

GENERALLY AVOID: Coadministration with rifampin may significantly increase the plasma concentrations and pharmacologic effects of romidepsin. The exact mechanism of interaction has not been established, but is likely due to rifampin inhibition of an undetermined hepatic uptake process that is important in the clearance of romidepsin. In patients with advanced cancer, administration of romidepsin 14 mg/m2 (4-hour infusion) with 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%. 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: The use of romidepsin in combination with rifampin should generally be avoided.

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.