Drug Interaction Report

GENERALLY AVOID: Coadministration of tofacitinib with other immuno- or myelosuppressive agents may potentiate the risk of infections as well as lymphoma and other malignancies. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving tofacitinib, most of whom were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Lymphoma and other malignancies have also been observed with tofacitinib use, with or without concomitant immunosuppressants. Epstein Barr virus-associated posttransplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with tofacitinib and concomitant immunosuppressive agents (basiliximab, high-dose corticosteroids, and mycophenolic acid) relative to cyclosporine plus the same induction regimen (2.3% vs. 0%).

MANAGEMENT: Concomitant use of tofacitinib with immuno- or myelosuppressive agents should generally be avoided. If coadministration is necessary, close monitoring is advised for the development of infections, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Lymphocyte and neutrophil counts as well as hemoglobin should be evaluated at baseline and regularly during therapy, and tofacitinib dosage adjusted as necessary in accordance with the product labeling. Patients should be advised to contact their physician if they develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. If a serious infection, an opportunistic infection, or sepsis develops, tofacitinib should be interrupted until the infection is controlled.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect 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.