Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of ensartinib, which is primarily metabolized via the isoenzyme in vitro. Clinical data characterizing the extent of this interaction and data with less potent inducers are not available.

MANAGEMENT: Concomitant use of ensartinib with moderate to potent inducers of CYP450 3A4 should generally be avoided. The possibility of diminished therapeutic effects should be considered. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

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.