Warfarin Institute of America

Dedicated To Your Health

Joey Lienert, Pharm. D. Candidate

  This is not a reason to stop therapy with warfarin, thyroid hormone, or any other medication which effects thyroid function. This interaction can be managed very effectively by monitoring thyroid function and anticoagulation (INR) appropriately.

  Thyroid hormone increases the metabolism rate of the body. This affects many functions of the body including how quickly the body eliminates protein from the body. Warfarin works by blocking the action of vitamin K dependent clotting factors, which are proteins. When thyroid hormone levels rise, metabolism increases, there are fewer clotting factors making the warfarin present in the body more effective causing an increased risk of bleeding and requiring a decrease in warfarin dose. When thyroid hormone levels fall, metabolism decreases, there are more clotting factors making the warfarin that is already in the body less effective, increasing the risk of forming a clot, and requiring an increase in warfarin dose.

Levothyroxine 

Synthroid

Levoxyl

Levo-T

Eltroxin

Levothroid 

Thyrox 

Liothyronine 

Thyroglobulin 

Thyrotropin 

Armour Thyroid

Desiccated Thyroid

Decreased Thyroid Hormone

Tapazole (methimizole)

Propylthiouracil

Some medications can decrease thyroid function:

Pacerone (amiodarone)

Lithium

Anticonvulsants

Other:

Dextrothyroxine (Choloxin) 

Thyroid hormone increases the rate of metabolism of clotting factors in the body. Therefore, if thyroid hormones are started in a patient stabilized on warfarin for anticoagulation, it can be expected that the dose of warfarin will need to be decreased to account for the increase in metabolism of clotting factors. (1,2,3,4,5)

If a patient who is already stabilized on thyroid hormone needs to initiate anticoagulation with warfarin, they can be expected to respond normally to warfarin therapy. (1,2,3,4)

Anti-thyroid medications decrease the rate of metabolism of clotting factors in the body. Therefore, if anti-thyroid medication is started in a patient stabilized on warfarin for anticoagulation, it can be expected that the dose of warfarin will need to be increased to account for the decrease in metabolism of clotting factors. (1,2,3,6)

Every patient on medication for thyroid and warfarin will respond differently to changes in either therapy. Increased monitoring is warranted for any patient on warfarin with changing thyroid function. (1,4,6)

1. Vagenakis AG, Cote R, Miller ME, Braverman LE, and Stohlman F. Enhancement of warfarin-induced hypoprothrombinemia by thyrotoxicosis. Johns Hopkins Medical Journal. 1972; 131: 69-73.
2. Stephens MA, Self TH, Lancaster D, and Nash T. Hypothyroidism: effect on warfarin anticoagulation. Southern Medical Journal. 1989; 82: 1585-1586.
3. Hansten PD. Oral anticoagulants and drugs which alter thyroid function. Drug Intelligence and Clinical Pharmacy. 1980; 14: 331-334.
4. Constigan DC, Freedman MH, Ehrlich RM. Potentiation of oral anticoagulant effect by L-thyroxine. Clinical Pediatrics. 1984; 23: 172-174.
5. Self TH, Straughn AB, Weisburst MR. Effect of hyperthyroidism on hypoprothrombinemic response to warfarin. American Journal of Hospital Pharmacy. 1976; 33: 387-389.
6. Chute JP, Dahut WL, Shakir KM, Georgiadis MA, and Frame JN. Enhancement of warfarin induced hypoprothrombinemia by hyperthyroidism (abstract). Blood. 1994; 84 (suppl 1): 674a.

© 2002 Josephine Lienert

Editor's Note:  Our thanks to David Willis, a medical student, who was trying to understand this interaction and provided the impetus to get these pages updated.  He also provided the following insights and references.  

The Merck Manual, 17th Edition Centennial Edition

Table 298-1 Extent of binding in plasma for Warfarin

99.5% bound     0.5% unbound

Table 298-3 Substances interact with Cyt. P 450

CYP1A2   Warfarin

Table 301-1 Drugs may produce interactions

Warfarin  -  Extensive metabolism by certain hepatic enzymes

Table 304-2  Effect of aging on drug response

Warfarin  -  Prothrombin time increased as effect of aging

Page 2609  Warfarin effects may be increased due to increased sensitivity to
its anticoagulant effects.

Page 2561 The major thyroid hormone – binding protein is thyroxine binding globulin (TGB), which has high affinity but low capacity for T4 and T3. TBG normally accounts for about 75% of the bound hormones. Other thyroid – binding prealbumin, also called transthyretin has high affinity but low
capacity for T4, albumin has low affinity but high capacity for T4 and T3.

Page 2583  Drugs may be displaced from protein – binding sites when two protein – bound drugs are given concurrently, especially if they can bind
the same site on the protein molecule (competitive displacement).   … The risk of interactions from protein displacement is significant primarily with
drugs that are highly protein – bound (>90%) and that have a small apparent volume of distribution; interactions tend to occur during the first few days of current therapy.

Note:  Clinically significant interactions are most likely to occur between drugs that have potent effects, a narrow safety margin and a steep
dose-response curve (Warfarin).

The Merck Manual of Geriatrics  1990

Table 18-4 Drugs with possible reduced plasma protein binding in the elderly

Warfarin

Page 185 Weakly acid organic compounds, eg, salicylates, barbiturates,
warfarin, theophylline, and sulfonamides, bind principally to plasma albumin.

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Last updated January 2, 2006