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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.