What is the interaction between levothyroxine (T4) and warfarin (Coumadin)?

From the Guidelines

Levothyroxine and warfarin can interact significantly, requiring careful monitoring and potential dose adjustments to prevent increased bleeding risk. When considering the interaction between levothyroxine and warfarin, it's crucial to understand that levothyroxine can increase the body's metabolism of clotting factors, potentially enhancing warfarin's anticoagulant effect and increasing bleeding risk 1.

Key Considerations

• Patients taking both medications should have their INR (International Normalized Ratio) monitored more frequently, especially when levothyroxine therapy is initiated, adjusted, or discontinued.
• Typically, INR should be checked within 7-10 days after any change in levothyroxine dosing.
• Warfarin dosage may need to be reduced by 25-50% in some cases to mitigate the risk of excessive anticoagulation.
• The interaction between levothyroxine and warfarin is not directly addressed in the provided study, but the principle of monitoring and adjusting doses based on potential drug interactions is emphasized 1.

Patient Education and Monitoring

• Patients should be educated about signs of excessive anticoagulation such as unusual bruising, nosebleeds, bleeding gums, or blood in urine or stool.
• Healthcare providers should coordinate care between endocrine and anticoagulation management to ensure safe and effective treatment with these medications.

Clinical Decision Making

• The decision to adjust warfarin doses in patients taking levothyroxine should be based on individual patient factors, including their INR levels, bleeding risk, and overall health status.
• Regular monitoring and open communication between healthcare providers and patients are essential for managing the potential interaction between levothyroxine and warfarin effectively.

From the FDA Drug Label

The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: ENDOGENOUS FACTORS: ... hyperthyroidism The following factors, alone or in combination, may be responsible for DECREASED PT/INR response: ENDOGENOUS FACTORS: ... hypothyroidism Potential drug interactions with warfarin sodium tablets are listed below by drug class and by specific drugs... dextrothyroxine

Levothyroxine and Warfarin Interaction:

• Increased PT/INR response is associated with hyperthyroidism.
• Decreased PT/INR response is associated with hypothyroidism.
• Dextrothyroxine (a thyroid hormone) is listed as a potential drug interaction that may increase PT/INR response.
• Since levothyroxine is also a thyroid hormone, similar to dextrothyroxine, it may interact with warfarin, potentially increasing the PT/INR response.
• However, the label does not explicitly mention levothyroxine, so this interaction is inferred based on the similarity with dextrothyroxine and the effect of hyperthyroidism on PT/INR response.
• Monitoring of PT/INR is advisable when concomitantly administering warfarin and levothyroxine due to the potential for an increased PT/INR response 2.

From the Research

Levothyroxine and Warfarin Interaction

• The interaction between levothyroxine and warfarin has been studied to determine if there is a significant effect on warfarin therapy 3, 4.
• A population-based study found no association between hospitalization for hemorrhage during warfarin therapy and initiation of levothyroxine in the preceding 30 days, suggesting that concerns about a clinically meaningful levothyroxine-warfarin drug interaction are not justified 3.
• A retrospective study also found no difference in the mean warfarin dose/INR ratio before and after initiation of levothyroxine, indicating that there is not a clinically significant interaction between warfarin and levothyroxine 4.

Warfarin Therapy Management

• When initiating warfarin therapy, clinicians should avoid loading doses and instead start with a 5-mg dose, with adjustments based on measured INR values and clinical factors 5.
• The International Normalized Ratio (INR) should be monitored frequently, especially after initiation of warfarin, to ensure that the patient is within the therapeutic range 5, 6.
• Patients who have an elevated INR may require more frequent testing and potentially vitamin K1 or clotting factors to prevent bleeding complications 5.

Factors Affecting Anticoagulation Control

• Patient characteristics, such as age, smoking status, and comorbidities, can affect anticoagulation control with warfarin, making it challenging to achieve good control in some patients 7.
• Close laboratory monitoring and adjustment of warfarin doses based on INR values are crucial to minimize the risk of bleeding or thromboembolic events 5, 6.