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Azathioprine is a purine-antagonist anti-metabolite
that is primarily 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.
Azathioprine is used in dogs for the treatment of inflammatory
bowel disease; immune-mediated anemia, colitis, and skin disease; and
Myasthenia Gravis. Azathioprine is frequently 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.
Azathioprine is occasionally used in the horse for
the treatment of autoimmune skin disease.
• Side effects may include bone-marrow suppression,
including leukopenia and, less commonly, anemia and thrombocytopenia.
GI upset (vomiting and diarrhea), pancreatitis and hepatotoxicosis may
also occur.
• 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 azathioprine presents in the milk of lactating
animals, it should only be used 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.
• Azathioprine is frequently used 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.
• If overdose is recognized promptly, proceed with gut-emptying protocols.
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.
She began to develop her interest in client education and medical writing 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
To help protect veterinary staff and patients from unnecessary exposure to chemotherapy medications and waste, this handling sheet will be included with all chemotherapy prescriptions we dispense.
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