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: 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.