A Population‐Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin

Most drug interaction resources suggest that levothyroxine can dramatically potentiate the effect of warfarin. However, the mechanistic basis of the interaction is speculative, and little evidence supports a meaningful drug interaction. We conducted a population-based nested case-control study to examine the risk of hospitalization for hemorrhage following the initiation of levothyroxine in a cohort of 260,076 older patients receiving warfarin. In this group, we identified 10,532 case subjects hospitalized for hemorrhage and 40,595 controls. In the primary analysis, we found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days (adjusted odds ratio 1.11, 95% confidence interval 0.67-1.86). Secondary analyses using more remote initiation of levothyroxine also found no association. These findings suggest that concerns about a clinically meaningful levothyroxine-warfarin drug interaction are not justified. Drug interaction resources that presently characterize this interaction as important should reevaluate this classification.