Drug Interaction Report

GENERALLY AVOID: Coadministration of tofacitinib with biologic DMARDs or potent immunosuppressants (e.g., azathioprine, 6-mercaptopurine, cyclosporine, and tacrolimus) 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, including melanoma and non-melanoma skin cancers, have also been observed with tofacitinib use. 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%). Data on the use of tofacitinib with all biologic DMARDs and/or immunosuppressants are not available.

MANAGEMENT: Concomitant use of tofacitinib with biologic DMARDs or potent immunosuppressants should generally be avoided. If coadministration is necessary, patients should be closely monitored for the development of signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. If a serious infection, an opportunistic infection, or sepsis develops, tofacitinib should be interrupted until the infection is controlled.

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.