Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 1A2 may decrease the plasma concentrations of bendamustine and increase the plasma concentrations of its pharmacologically active metabolites. In vitro, bendamustine has been shown to undergo metabolism via CYP450 1A2 to two minor cytotoxic metabolites, M3 and M4. Because concentrations of these metabolites in plasma are normally just 1/10 and 1/100 that of the parent drug, respectively, their overall contribution to the cytotoxicity of bendamustine is unknown. As such, the potential effect of CYP450 1A2 induction is unknown.

MANAGEMENT: Caution is advised if bendamustine is used in combination with CYP450 1A2 inducers. Patients should be monitored for potentially altered effects of bendamustine.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.