Potential Drug Interaction between Warfarin and Linezolid

Objective Warfarin is known to interact with many drugs; however, there are currently no descriptions of an interaction with linezolid in the literature. It was recently brought to our attention, however, that several warfarin-medicated patients have experienced an increase in the prothrombin time international normalized ratio (PT-INR) following the administration of linezolid. We therefore performed a retrospective survey in order to investigate the possibility of an interaction between warfarin and linezolid. Methods The survey items included age, gender, underlying disease, type of surgery, type of infectious disease, duration of linezolid administration, laboratory values and the dose of warfarin. The PT-INR was observed over time before treatment and at days 4 or 5 and 10, completion and one week after the end of concomitant therapy. Patients The subjects included six patients who were recovering from recent heart-related surgery. Results The PT-INR increased from 1.62 +/- 0.32 before concomitant linezolid administration to 3.00 +/- 0.83 at day 4 or 5 after concomitant administration (p<0.01) and significantly decreased from 1.65 +/- 0.45 at the completion of the regimen to 1.26 +/- 0.1 one week later (p<0.05). With respect to the relationship between the dose of warfarin and the PT-INR in five cases, the PT-INR increased following concomitant linezolid treatment in all cases. Conclusion Although it has been reported that linezolid does not influence the metabolism or protein binding of warfarin, our data showed potential drug interactions between warfarin and linezolid. Our data suggest that PT-INR monitoring after the completion of concomitant warfarin and linezolid therapy is important.