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SUBDURAL HEMATOMA DUE TO PROBABLE WARFARIN–FLUOROURACIL INTERACTION
Giovanni Giunta and Francesca Velluti

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OBJECTIVE: To describe the occurrence of a subdural hematoma in a woman undergoing chemotherapy with cyclophosphamide, methotrexate, and fluorouracil combined with warfarin therapy.

CASE SUMMARY: A 60-year-old white woman with atrial fibrillation underwent radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes.Following surgery, the patient received adjuvant chemotherapy with a CMF 1 –8 regimen consisting of cyclophosphamide 100 mg/m 2 orally on days 1 –14, methotrexate 40 mg/m 2 intravenously, and fluorouracil 600 mg/m 2 by intravenous bolus on days 1 and 8 every 4 weeks. Warfarin 5 mg/day was administered concomitantly due to atrial fibrillation. Following the second course of concomitant therapy, the patient developed a headache, hemiparesis, and an international normalized ratio (INR)of 7.6, which was highly suggestive of a drug interaction between fluorouracil and warfarin. A computed tomography scan of the brain revealed a left parieto-occipital subdural hematoma.

DISCUSSION: This case emphasizes the importance of the potentially fatal drug interaction involving warfarin and fluorouracil.

CONCLUSIONS: Several adverse interactions between warfarin and fluorouracil have been reported. Considering the severity of this interaction, close monitoring of the INR is recommended in patients receiving these agents concomitantly.

J Pharm Technol 2004;20:77-9.

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