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

Abstract

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.

Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice

“…In addition, none of these studies specifically investigated the effect of potential DDIs on variations of TSH levels, levothyroxine prescriptions and dosage. Pincus et al [23] evaluated the effect of warfarin-levothyroxine interactions on the risk of hospitalisation but did not investigate changes in TSH levels on the trend of levothyroxine prescriptions and/or doses when these drugs were prescribed concurrently. On the other hand, Taylor et al [24] investigated the pattern of levothyroxine use as a function of TSH levels in a UK general population but did not consider the effect of potential DDIs on levothyroxine prescribing.…”

An evaluation of the potential drug interaction between warfarin and levothyroxine

“…Several case reports suggest that concomitant use of warfarin and levothyroxine can result in hospitalization and a need for significant warfarin dosage adjustments to restabilize the INR response . However, a large population‐based, case–control study evaluating the impact of the the warfarin–levothyroxine interaction found no relationship in warfarin‐receiving patients between the initiation of levothyroxine and hospitalization for bleeding, and concluded that this interaction was not clinically significant .…”

“…Increasing the frequency of INR monitoring and reducing the dose of warfarin as needed to prevent excessive anticoagulation following levothyroxine initiation has been suggested as a reasonable clinical management option . It is possible that failure to consider the influence of INR monitoring and warfarin dose adjustments may have led the authors of the aforementioned case–control study to erroneously conclude that there no warfarin–levothyroxine interaction, and thus explain the lack of an association between levothyroxine initiation and bleeding .…”

Reporting and evaluating wait times for urgent hip fracture surgery in Ontario, Canada

“…36 We also considered antiplatelet and anticoagulant prescriptions dispensed to patients within 1 year before surgery for those with Ontario Drug Benefit coverage (i.e., all those > 65 years of age). 37 Each fracture and procedure type were recorded.…”