Drug General Information (ID: DDI0CPUWJH)
Drug Name			Levothyroxine		Drug Info		Warfarin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antithyroid Agents				Anticoagulants
Structure

Mechanism of Levothyroxine-Warfarin Interaction (Severity Level: Moderate)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Levothyroxine				Warfarin
Mechanism		Potentiate the hypoprothrombinemic effect of vitamin K antagonist				Vitamin K antagonist
Key Mechanism Factor 1
		Factor Name		Bleeding
		Factor Description		Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
Mechanism Description		Increased risk of bleeding by the combination of Levothyroxine and Warfarin

Recommended Action
Management		INR or prothrombin time should be monitored closely when initiating, discontinuing, or changing the dosage of thyroid hormone therapy in patients stabilized on their oral anticoagulant regimen. Patients should be advised to notify their physician if they develop signs and symptoms of excessive anticoagulation, such as unusual or prolonged bleeding, bruising, vomiting, change in stool or urine color, headache, dizziness, or weakness.

References
1	Costigan DC, Freedman MH, Ehrlich RM "Potentiation of oral anticoagulant effect by l-thyroxine." Clin Pediatr (Phila) 23 (1984): 172-4. [PMID: 6697623]
2	Product Information. Synthroid (levothyroxine). Abbott Pharmaceutical, Abbott Park, IL.
3	Rice AJ, McIntosh TJ, Fouts JR, et al "Decrease sensitivity to warfarin in patients with myxedema." Am J Med Sci 262 (1971): 211-5. [PMID: 5142577]
4	Vagenakis AG, Cote R, Miller ME, et al "Enhancement of warfarin-induced hypoprothrombinemia by thyrotoxicosis." Johns Hopkins Med J 131 (1972): 69-73. [PMID: 4114451]
5	van Oosterom AT, Mattie H, Hermens WT, Veltkamp JJ "The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and factor X in the rat." Thromb Haemost 35 (1976): 607-19. [PMID: 989968]
6	Walters MB "The relationship between thyroid function and anticoagulant therapy." Am J Cardiol 11 (1963): 112-4. [PMID: 13998701]