Warfarin Drug-Drug Interactions with Amiodarone and Tramadol in a Patient with Paroxysmal Atrial Fibrillation: A Case Report

Amiodarone and tramadol are known to have drug-drug interactions that potentiate the effects of the anticoagulant warfarin. Herein we report a case which suggests increasing prothrombin time-international normalized ratio (PT-INR) and PT-INR/dose ratio due to the concomitant administration of warfarin, amiodarone (a cytochrome P450 2C9 inhibitor) and tramadol (an enhancer of anticoagulant effects of warfarin). A 72-year-old woman underwent emergency surgery following a suspected non-obstructive mesenteric ischemia, and diagnosis was confirmed. After surgery, the patient was given 2 mg/day of WF, and tramadol/acetaminophen, followed by amiodarone. After the concomitant dose of the triple combination, the PT-INR increased to over 7.02 (above the upper limit of the laboratory). The physician consulted the pharmacist for dose adjustment, and the pharmacist recommended a reduction in the dose to 0.5 mg. After restarting warfarin, PT-INR was controlled to 1.66–2.02. However, the PT-INR/dose ratio increased from 1.22 to 3.32–4.04 compared to the initial dose. The results suggest that these enhanced anticoagulant effects may be due to the inhibition of WF metabolism. Although the patient underwent resection of the small intestine, the effects of oral vitamin K1 were observed one day after administration. In conclusion, frequent PT-INR monitoring, and pharmacist intervention such as the assessment and dose adjustment in this report should be beneficial during anticoagulation therapy when multiple concomitant medications with suspected drug-drug interactions are present.