Several case studies have reported a possible drug interaction between
warfarin and
tramadol where
tramadol coadministration enhanced the antithrombotic effects of
warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after
tramadol coadministration were investigated in patients receiving
warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with
warfarin for
deep vein thrombosis,
atrial fibrillation,
arteriosclerosis obliterans,
congestive heart failure, and other
vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of
tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or
dose reduction of
warfarin after coadministration of
tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of
albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before
tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that
tramadol coadministration enhanced the antithrombotic effects of
warfarin in patients with higher PT-INR, lower
albumin levels and decreased renal function as the risk factors for this drug interaction.