Azathioprine and inhibition of the anticoagulant effect of warfarin: evidence from a case report and a literature review.
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.
Ng
Heng Joo
HJ
St. Joseph's Hospital, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada. ng.heng.joo@sgh.com.sg
Crowther
Mark A
MA
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*
D000925:Anticoagulants; D007166:Immunosuppressive Agents; D014859:Warfarin; D001379:Azathioprine