Prolongation of prothrombin time-international normalized ratio in a patient receiving warfarin and gemcitabine: a...

Potential interactions between gemcitabine and warfarin have been described in case reports. However, it has been argued that the available data are insufficient to support this interaction due to the limited number of cases. We present the case of a patient who developed prolongation of prothrombin time/international normalized ratio (PT/INR) following gemcitabine administration while receiving warfarin. The patient was a 58-year-old man with Marfan syndrome who had been receiving warfarin for 30 years, usually at a dose of 8-10 mg. He was diagnosed with primary testicular leiomyosarcoma and subsequently experienced a relapse of pulmonary metastases following orchiectomy. After an inadequate response to doxorubicin, combination therapy with gemcitabine and docetaxel (intravenous gemcitabine 900 mg/m² on days 1 and 8 and intravenous docetaxel 75 mg/m² on day 8 every 3 weeks) was initiated as second-line treatment. At the start of this combination therapy, the patient was receiving a daily warfarin dose of 10 mg. Following initiation of gemcitabine, two consecutive episodes of INR prolongations were observed 2 days after each administration. The INR increased from 2.04 to 2.44 on day 36 and from 1.87 to 2.66 on day 43, accompanied by Grade 2 elevation in aspartate aminotransferase and alanine aminotransferase levels. Total bilirubin remained within normal limits. His daily warfarin dose was reduced and maintained at 6.0 mg, resulting in INR values ranging between 2.0 and 2.5. Although the precise mechanism remains unclear, gemcitabine-induced hepatic dysfunction may have contributed to the enhanced anticoagulant effect of warfarin. Given the potential for early INR elevation, close INR monitoring during the initial phase of gemcitabine therapy may be warranted in patients receiving concomitant warfarin.