dacarbazine and Arava Interactions

Interactions between dacarbazine and Arava (leflunomide)

dacarbazine and leflunomide (Major Drug-Drug)

MONITOR CLOSELY: The use of leflunomide in combination with other immunosuppressive or myelosuppressive agents may increase the risk of infections. 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 immuno- or myelosuppressive 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 immunosuppressive agents, or who had recently discontinued these therapies.

MONITOR CLOSELY: The concomitant or sequential use (without the recommended leflunomide washout period or procedure) of other agents known to induce hepatotoxicity may potentiate the risk of liver injury associated with leflunomide. Elevated liver transaminases, hepatitis, jaundice/cholestasis, hepatic failure, and acute hepatic necrosis have been reported with leflunomide. Liver enzyme elevations were generally mild (2-fold ULN or less) and resolved while continuing treatment. Marked elevations (greater than 3-fold ULN) occurred infrequently and reversed with dose reduction or discontinuation of treatment. However, fatalities associated with severe liver injury have also been reported rarely. Most cases occurred within six months of therapy and in a setting of multiple risk factors including preexisting liver disease and concomitant use of other hepatotoxins.

MANAGEMENT: Close monitoring is recommended if leflunomide is used in patients who have recently received or are receiving other hepatotoxic and myelosuppressive agents. Liver enzymes, platelet, white blood cell count, and hemoglobin or hematocrit should be evaluated at baseline and regularly during chronic concomitant therapy. If evidence of serious hepatotoxicity (i.e., ALT elevation greater than 3-fold ULN or persistent elevations between 2- and 3-fold ULN despite dose reduction) or bone marrow suppression occurs, treatment with leflunomide should be stopped, and cholestyramine or charcoal administered to accelerate elimination of leflunomide's active metabolite from plasma.