Drug Interaction Report

MONITOR: Coadministration with blinatumomab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Initiation of blinatumomab treatment causes transient release of cytokines that may suppress CYP450 enzymes, although the potential for interaction has not been studied. Presumably, the highest drug-drug interaction risk would be during the first 9 days of the first cycle and the first 2 days of the second cycle.

MANAGEMENT: Caution is advised when blinatumomab is prescribed to patients receiving drugs that are metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic index such as carbamazepine, colchicine, cyclosporine, disopyramide, phenytoin, quinidine, theophylline, warfarin, macrolide immunosuppressants, vinca alkaloids, and some narcotic analgesics. Clinical and laboratory monitoring are recommended following the initiation of blinatumomab, and the individual dosage of the concomitant agents adjusted as needed.

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.