Drug Interaction Report

MONITOR: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of tofacitinib, which is primarily metabolized by the isoenzyme. The interaction may result in loss of or reduced clinical response; however, the extent to which these medications interact with tofacitinib has not been established. In study subjects, administration with the potent CYP450 3A4 inducer rifampin decreased tofacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 74% and 84%, respectively, compared to administration of tofacitinib alone.

MANAGEMENT: Caution is recommended if tofacitinib is to be used in combination with moderate CYP450 3A4 inducers. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended when possible.

MONITOR: Grapefruit juice may increase the plasma concentrations of tofacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, some authorities recommend avoiding consumption of grapefruit juice during tofacitinib therapy (Canada). Patients receiving tofacitinib therapy who ingest grapefruits or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.