Sulfonylureas hepatotoxicity

The risk of hepatotoxicity with the sulfonylureas varies with both the drug and the dosage. It has been described with chlorpropamide (95), tolazamide (96), tolbutamide (97), glipizide (98), and glibenclamide (99). Anicteric, cytolytic hepatitis has been described after glibenclamide (100). 

There have been several reports of hepatotoxicity of iodipamide, variously characterized by epigastric pain, nausea and vomiting, jaundice, pyrexia, and tenderness over the liver, with abnormal liver function tests. Biopsy has shown centrilobular necrosis (154). The incidence of abnormal liver function tests may be as high as 18% after a dose of 40 ml, and the quantity given should be as small as possible. Prior administration of glucocorticoids or sulfonylureas impairs hepatic excretion of ioglycamide. Both iodoxamate and iotroxate can affect liver function tests in a small series of cases, the degree of intrahepatic cholestasis appeared to be relatively more marked after iodoxamate than after iotroxate (SED-12, 1168) (155). 

Less hypoglycemia than sulfonylureas, but weight gain and edema reported hepatotoxicity of the prototype drug (troglitazone) led to withdrawal. 

The most hepatotoxic sulfonylurea in the dog, for which we also have human data, is cycloheptolamide (Orabeta), in which doses as small as 12.5 mg. per kg. produced mild degenerative changes in the dog livers. However, in over 8000 patient-months experience with cycloheptolamide, not a single... 

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