Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 1A2, P-glycoprotein (P-gp), and/or uridine diphosphate glucuronosyltransferase (UGT) 1A1 or 2B7 may decrease the plasma levels and therapeutic efficacy of binimetinib. The proposed mechanism involves enhanced metabolic clearance of binimetinib through induction of CYP450 1A2, P-gp, and/or UGT 1A1 or 2B7. The clinical significance of this interaction is unknown as no clinically relevant drug interactions have been demonstrated with binimetinib.

MANAGEMENT: Until further information is available, caution is recommended if binimetinib must be used concomitantly with CYP450 1A2, P-gp, and/or UGT 1A1 or 2B7 inducers. Pharmacologic response to binimetinib should be monitored more closely whenever a CYP450 1A2, P-gp, and/or UGT 1A1 or 2B7 inducer is added to or withdrawn from therapy, and the binimetinib dosage adjusted as necessary.

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.