Drug Interaction Report

GENERALLY AVOID: Coadministration of leflunomide with other immuno- or myelosuppressive antirheumatic agents may potentiate the risk of infections. The risk is thought to extend to teriflunomide, its principal active metabolite, because recommended dosages of both result in a similar range of plasma concentrations of teriflunomide. Serious infections including sepsis, as well as opportunistic infections like Pneumocystis jiroveci pneumonia, pulmonary and extrapulmonary tuberculosis, and aspergillosis have been reported with the use of leflunomide, particularly in patients on concomitant hematotoxic therapy. There have also been rare reports of pancytopenia, agranulocytosis, and thrombocytopenia in patients receiving leflunomide alone. However, these events occurred more frequently in patients who received concomitant treatment with methotrexate or other hematotoxic agents, or who had recently discontinued these agents.

MANAGEMENT: Concomitant use of leflunomide with other immuno- or myelosuppressive antirheumatic agents should generally be avoided. When switching from leflunomide to one of these agents, consideration should be given to administering a washout procedure with cholestyramine or activated charcoal to accelerate elimination of leflunomide's active metabolite from plasma, which otherwise may take up to two years. This will decrease the overlap of systemic exposure to both compounds and reduce the likelihood of additive hematologic toxicities. However, the washout procedure may also induce disease worsening if the patient had been responding to leflunomide treatment. Patients who do not receive the washout procedure prior to switching should be monitored closely for hematologic toxicity. Although not specified in the product labeling, the same precaution may be applicable to teriflunomide, the principal active metabolite of leflunomide. All patients treated with leflunomide or teriflunomide 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 evidence of serious infection or bone marrow suppression occurs, treatment should be stopped and washout procedure administered.