title: Incidence, timing, and risk factors of azathioprine hepatotoxicosis in dogs.
abstract: BACKGROUND
  The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
authors: K
authors: K
authors: Wallisch
authors: L A
authors: LA
authors: Trepanier
mesh_terms: D000818:Animals; D001379:Azathioprine / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000662:veterinary*; D004283:Dog Diseases / Q000139:chemically induced* / Q000473:pathology; D004285:Dogs; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: ALT; German shepherd; Liver toxicosis; Thiopurines
references: Lupus. 2013 Dec;22(14):1526-8
references: 24029750
references: Ther Drug Monit. 2012 Dec;34(6):622-8
references: 23128910
references: Clin Pharmacol Ther. 2011 Jun;89(6):806-15
references: 21544079
references: World J Gastroenterol. 2014 Apr 7;20(13):3534-41
references: 24707136
references: Dig Dis. 2013;31(2):233-8
references: 24030232
references: J Am Vet Med Assoc. 2010 Oct 15;237(8):929-35
references: 20946080
references: Pediatr Gastroenterol Hepatol Nutr. 2013 Sep;16(3):171-7
references: 24224150
references: Dig Liver Dis. 2005 Apr;37(4):282-97
references: 15788214
references: Pol Przegl Chir. 1970 Jan;42(1):24-32
references: 5418795
references: J Vet Intern Med. 2004 May-Jun;18(3):339-45
references: 15188821
references: Nat Clin Pract Gastroenterol Hepatol. 2007 Dec;4(12):686-94
references: 18043678
references: Aliment Pharmacol Ther. 2005 Nov 1;22(9):775-82
references: 16225485
references: Gastroenterology. 2002 Apr;122(4):904-15
references: 11910342
references: Gastroenterology. 2000 Apr;118(4):705-13
references: 10734022
references: J Vet Intern Med. 2011 Jul-Aug;25(4):838-45
references: 21689156
references: Vet Rec. 2007 Apr 14;160(15):520-1
references: 17435099
references: Aliment Pharmacol Ther. 2008 Sep 15;28(6):734-41
references: 19145729
references: Can Vet J. 1991 Aug;32(8):496-7
references: 17423844
references: Can Vet J. 1996 Oct;37(10):612-3
references: 8896876
references: Dermatol Clin. 2007 Apr;25(2):195-205, vi-ii
references: 17430756
references: Toxicol Appl Pharmacol. 1968 Jan;12(1):1-6
references: 5660807
references: Eur J Gastroenterol Hepatol. 2004 Jul;16(7):705-10
references: 15201586
references: World J Hepatol. 2014 Jun 27;6(6):410-8
references: 25018851
references: J Hepatol. 2001 Dec;35(6):756-64
references: 11738103
references: J Pharmacol Exp Ther. 2004 Nov;311(2):668-76
references: 15226385
references: J Hepatol. 2004 Mar;40(3):454-63
references: 15123360
references: Inflamm Bowel Dis. 2007 Sep;13(9):1106-14
references: 17455203