Hepatotoxicity associated with methotrexate therapy in a dog

Abstract

A nine‐year‐old male Newfoundland‐cross was treated with doxorubicin, cyclophosphamide, and methotrexate as adjuvant chemotherapy following the resection of a maxillary osteosarcoma. The dog remained in good health until week 13 of therapy, when he became anorexic, and developed icterus and ascites. Laboratory tests at this time suggested sub‐acute hepatic failure and renal failure. Necropsy revealed severe generalized hepatic necrosis with resultant ascites and intestinal haemorrhage. Since there was no evidence on necropsy of an infectious aetiology, and since there was no history of toxin ingestion, methotrexate which is a known hepatotoxin in man, was considered the probable cause of the hepatic necrosis. This side‐effect of methotrexate has not previously been reported in the dog, and animals undergoing therapy with the drug should be monitored closely for hepatotoxicity.

LD-Aminopterin in the Canine Homologue of Human Atopic Dermatitis: A Randomized, Controlled Trial Reveals Dosing Factors Affecting Optimal Therapy

“…Weekly treatment of five dogs with CAD with an oral anti-inflammatory dose of methotrexate (0.2 mg/kg) for four weeks resulted in severe vomiting in one subject and fatal hepatic necrosis in two subjects (personal communication by Dr. Thierry Olivry, North Carolina State University). Pond and Morrow reported a similar case of fatal hepatic necrosis in a dog with osteosarcoma treated with methotrexate at an oral dose of 5 mg/m 2 (0.25 mg/kg) on the first four days of each week [65]. A four-week toxicology study of LD-aminopterin, L-aminopterin and D-aminopterin in beagle dogs ( N  = 6 per cohort, once-weekly oral gavage of 0.5 mg/kg of each enantiomer or 35-fold the anti-inflammatory dose) found no liver histopathology in any cohort (unpublished data).…”

Suspected robenacoxib‐induced liver injury in a dog

“…11 Described patterns include hepatocellular necrosis (e.g., zonisamide, amiodarone, azathioprine, carprofen, sulfonamides, paracetamol and mebendazole), vacuolisation (e.g., zonisamide, lomustine, mitotane, trazodone and ketoconazole), intrahepatic cholestasis (e.g., azathioprine), fibrosis (e.g., lomustine, phenobarbital and ketoconazole) and inflammation (e.g., lomustine, sulfonamides, trazodone and ketoconazole). 5,[20][21][22][23][24][25][26][27][28][29][30][31][32] The histological pattern documented in this case comprised inflammation and vacuolisation.…”