title: Azathioprine and inhibition of the anticoagulant effect of warfarin: evidence from a case report and a literature review.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: St. Joseph's Hospital, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada. ng.heng.joo@sgh.com.sg
authors.forename: Heng Joo
authors.initials: HJ
authors.lastname: Ng
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000037:antagonists & inhibitors*; D001379:Azathioprine / Q000037:antagonists & inhibitors*; D004336:Drug Antagonism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors*; D019934:International Normalized Ratio; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D020246:Venous Thrombosis / Q000188:drug therapy / Q000209:etiology; D014859:Warfarin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D007166:Immunosuppressive Agents; D014859:Warfarin; D001379:Azathioprine