Incidence, Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

BACKGROUND The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias. HYPOTHESIS AND OBJECTIVES To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias. ANIMALS Fifty-two dogs treated with AZA with clinical and biochemical follow-up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum. METHODS Retrospective medical record review, from January 2009 through December 2013. RESULTS Hepatotoxicosis (as defined by a >2-fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13-22 days). Dogs had a median 9-fold increase in ALT and 8-fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over-represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow-up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45-196 days) compared to hepatotoxicosis (P = .016). CONCLUSIONS AND CLINICAL IMPORTANCE These results support the routine monitoring of liver enzymes during the first 1-4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.