Azathioprine and inhibition of the anticoagulant effect of warfarin: evidence from a case report and a literature review

Am J Geriatr Pharmacother. 2006 Mar;4(1):75-7. doi: 10.1016/j.amjopharm.2006.03.001.


Background: Warfarin and azathioprine may be prescribed concurrently in patients requiring both anticoagulation and immunosuppression. However, a potential interaction between the 2 drugs, resulting in an increased warfarin requirement, may be overlooked in clinical practice.

Case summary: A 67-year-old woman was treated with warfarin (initial mean dose, 24 mg/wk [3.5 mg/d]) for >3 years for recurrent deep vein thrombosis associated with systemic lupus erythematosus. Soon after commencing warfarin, azathioprine 150 mg/d was introduced for its steroid-sparing effect. Warfarin was titrated to a mean dose of 60 to 75 mg/wk (8.5-10.5 mg/d) over the next 18 months. Her dose of azathioprine was then increased to 200 mg/d. Subtherapeutic international normalized ratio (INR) levels required an increase in the warfarin dose to a mean of 130 mg/wk (18.5 mg/d). Subsequent discontinuation of azathioprine resulted in a dramatic increase in her INR levels (from 1.8 to 14.0 four weeks after discontinuation).

Discussion: A temporal relationship, demonstrating the interaction between warfarin and azathioprine, was evident at various times during therapy for our patient. This case, together with 7 additional published cases, is comprehensively reviewed here using previously described criteria for establishing a definite interaction between warfarin and other drugs.

Conclusions: The evidence supports a clinically important inhibitory action of azathioprine on warfarin and calls for closer monitoring of INR levels when azathioprine doses are altered during concurrent administration with warfarin.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Anticoagulants / antagonists & inhibitors*
  • Azathioprine / antagonists & inhibitors*
  • Drug Antagonism
  • Female
  • Humans
  • Immunosuppressive Agents / antagonists & inhibitors*
  • International Normalized Ratio
  • Lupus Erythematosus, Systemic / complications
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / etiology
  • Warfarin / antagonists & inhibitors*


  • Anticoagulants
  • Immunosuppressive Agents
  • Warfarin
  • Azathioprine