Drug Interaction Report

MONITOR CLOSELY: Coadministration of defibrotide with antiplatelet agents or other agents that affect coagulation may increase the risk of bleeding. In vitro, defibrotide increased the activity of fibrinolytic enzymes. In a mouse model of thromboembolism, recombinant tissue plasminogen activator (t-PA) potentiated the antithrombotic effect of defibrotide when given intravenously.

MANAGEMENT: Concomitant use of medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with defibrotide. Close clinical and laboratory observation for bleeding complications is recommended during therapy. If bleeding develops, defibrotide should be discontinued and treatment/supportive care provided until the bleeding stops.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cilostazol. 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, the manufacturer recommends avoiding consumption of grapefruit juice during cilostazol therapy. Orange juice is not expected to interact with cilostazol.