Ifosfamide and etoposide chemotherapy may interact with warfarin, enhancing the warfarin induced anticoagulant...

To report a case of warfarin-response enhancement during administration of ifosfamide and etoposide chemotherapy.

A 15-yearold boy with rhabdomyosarcoma was treated with a regimen of alternating cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) chemotherapy and ifosfamide and etoposide (IE) chemotherapy. During VDC chemotherapy, occlusion of the left middle cerebral artery occurred, and warfarin was started. On day 3 of IE chemotherapy, the patient's international normalized ratio (INR) transiently increased from baseline 2.61 to 5.45. The INR returned to normal within 3 days after warfarin discontinuation. An increase in INR was observed between days 1 and 3 of subsequent cycles of IE chemotherapy but not during VDC chemotherapy. This INR increase was also observed during concomitant use of aprepitant, an inducer of the CYP2C9.

There are no reports describing the interaction between warfarin and IE chemotherapy because coadministration of warfarin and IE chemotherapy is unusual. The Drug Interaction Probability Scale score of this interaction was 7, and it is probable that the enhancement of the warfarin response was caused by an interaction with IE chemotherapy. Moreover, in the present case, the enhancement of warfarin response was observed during concomitant use of aprepitant, which has been reported to weaken the warfarin response. Therefore, this interaction may be quite powerful and may increase the risk of warfarin toxicity.

A patient who was administered both warfarin and IE chemotherapy experienced a rapid increase in INR, suggesting that INR should be closely monitored in patients receiving warfarin with IE chemotherapy.