Effects of Tramadol on the International Normalized Ratio of Outpatients Receiving Warfarin: A Prospective Cohort study

Objective: To examine the effects of tramadol concomitantly used with warfarin on the international normalized ratio (INR) levels. Method: This prospective cohort study was conducted in the outpatients who visited Kabinburi Hospital in Prachinburi Province from April to October 2015. Of 206 patients, they were classified into two groups, i.e. 103 patients who did not receive tramadol with warfarin and 103 patients who received both drugs. Patients’ data were collected from the hospital’s online medical records and interviews. The INR levels of patients were monitored before and after they participated in the study. The differences between the two groups were analyzed using the t-test and chi-square test. Moreover, a relative risk (RR) was presented. Results: At the end of the study, patients receiving both drugs had the INRs out of the target range more than those receiving no tramadol (47.57% vs. 26.21%; P < 0.001). The patients receiving both drugs were 1.61 times more likely to experience the INRs out of the target (RR = 1.61; 95% CI: 1.16 – 2.22). No warfarin-associated adverse events were found in either group. Conclusion: The combination use of tramadol and warfarin could cause the out-of-target INR levels. If tramadol is needed, their INR levels should be closely monitored. Keywords: tramadol, warfarin, drug-drug interaction, IN