Warfarin Resistance Due to Azathioprine

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Warfarin Resistance Due to Azathioprine
A 32-year-old woman with a history of deep vein thrombosis (DVT), steroid-dependent ulcerative colitis, and osteoporosis was prescribed azathioprine for a steroid-sparing effect. Stable, therapeutic international normalized ratios (INRs) were obtained with warfarin 35 mg/week during a 6-week postpartum course to treat an initial DVT. Ten days after completing warfarin therapy, azathioprine was begun. A recurrent DVT occurred 9 days later, and an increase in warfarin dosage to 120 mg/week was necessary to achieve an INR of 2.0-3.0. The patient denied changes in warfarin adherence, dietary vitamin K intake, or medical conditions. The addition of azathioprine was the only change in her regimen. Review of the literature found only limited reports of an interaction between warfarin and azathioprine, with increases in warfarin requirements of 3-4 times. Careful monitoring and caution are recommended when administering these two drugs concomitantly.

Azathioprine is an immunosuppressant that is prescribed for a variety of indications, including prevention of graft rejection and various autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. Venous thrombosis requiring warfarin therapy is a common complication of autoimmune diseases. To date, three reports described an interaction between warfarin sodium and azathioprine resulting in 3- to 4-fold increases in weekly warfarin dosage to achieve a therapeutic international normalized ratio (INR) of 2.0-3.0. A case report of a similar interaction between warfarin and 6-mercaptopurine (6-MP; active metabolite of azathioprine) required an increase in warfarin dosage. The dramatic change in warfarin requirement with the concurrent use of azathioprine may be mistakenly perceived as idiopathic warfarin resistance.

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