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Azathioprine for Veterinary Use

by Barbara Forney, VMD

Basic Information

Azathioprine is a purine-antagonist anti-metabolite that primarily is used as an immunosuppressant in dogs. It competes with purine in the synthesis of nucleic acids. It also inhibits the synthesis of T-lymphocyte-dependent antibodies and cyclo-oxygenase. Azathioprine is absorbed from the GI tract and metabolized to mercaptopurine. The incidence of bone-marrow suppression is thought to be related to levels of one of the important enzymes involved in the metabolism of azathioprine-thiopurine methyltransferase (TMPT). Cats have low TMPT-activity and are prone to azathioprine toxicity. Humans with low TMPT-levels are more likely to experience bone-marrow suppression. There is conflicting research regarding TMPT activity in dogs and the incidence of myelotoxicity. Metabolites of azathioprine and mercaptopurine are excreted by the kidneys.

Dogs

Azathioprine is used in dogs to treat inflammatory bowel disease; immune-mediated anemia, colitis and skin disease; and Myasthenia Gravis. Azathioprine frequently is used with corticosteroids (prednisolone), with the goal of reducing the dose of both drugs and moving towards alternate-day therapy. Azathioprine has a delayed onset of action of about three weeks and clinical response may take as long as six weeks. Azathioprine should be given with food to minimize GI side-effects.

Horses

Azathioprine occasionally is used in the horse to treat autoimmune skin-disease.

Azathioprine Side Effects

•       Side effects may include bone-marrow suppression, including leukopenia and, less commonly, anemia and thrombocytopenia.

•       GI upset (vomiting and diarrhea), pancreatitis and hepatotoxicosis also may occur.

Precautions

•       Patients are at increased risk for infection and neoplasia due to immunsuppression.

•       Azathioprine should be used with additional caution in animals with decreased liver function.

•       CBC and blood chemistry should be performed before treatment and at regular intervals to monitor bone-marrow and liver function.

•       Azathioprine has been found to be mutagenic and teratogenic in laboratory animals. Because azathioprinen presents in the milk of lactating animals, it should be used only in pregnant animals when the benefit of therapy outweighs the possible risk. Milk replacer should be used in lactating animals.

•       Chlorambucil is a safer immunosuppressant in cats.

Drug Interactions

•       Azathioprine is used frequently with corticosteroids. When used together, however, there is an increased risk of toxicity.

•       There is an increased risk of toxicity when used with ACE inhibitors and aminosalicylates.
  
•       Azathioprine may inhibit the neuromuscular blockade effects of non-depolarizing muscle relaxants (pancuronium, tubocurarine).

•       The risk of bone-marrow suppression increases when azathioprine is used with other myelosuppressive drugs (trimethoprim-sulfa, cyclophosphamide).

•       Azathioprine may reduce the anticoagulant effects of warfarin.

•       Allopurinal may decrease the hepatic metabolism of azathioprine. The dose of azathioprine may need to be decreased.

Overdose

Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.