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Azathioprine is a complex immunosuppressant drug used to treat various autoimmune diseases and prevent organ rejection in dogs. This medication is a type of prodrug, meaning it doesn't become bioactive until it's metabolized through a series of chemical reactions. Azathioprine has several mechanisms of action that have proven successful in treating rheumatoid arthritis, irritable bowel syndrome, and autoimmune anemia.

One of the ways azathioprine inhibits the body's immune system response is by halting the biosynthesis of purines, a necessary component for cell division. Decreasing cell division is vital for certain conditions since it can slow the spread of infection.

This medication also suppresses the production of T-lymphocyte-dependent antibodies. T-cell lymphocytes stimulate other cells to destroy any perceived threat — which, in the case of an autoimmune canine, is their own cells.

By stopping the immune response at the source, azathioprine prevents further cellular destruction and tissue damage. This inhibitory effect is particularly helpful in the treatment of immune-mediated hemolytic anemia, a condition in which the body destroys its own red blood cells.

Finally, azathioprine hinders the production of prostaglandin-producing enzymes. These enzymes are responsible for swelling and pain, which are two of the most common symptoms in autoimmune diseases.

Dosage

The usual dosage guidelines for azathioprine for dogs is between 0.5 and 1 mg per lb of body weight by mouth, once a day. 

Dosage instructions

Pet parents should exercise extreme caution while giving azathioprine for dogs since it is a known cytotoxin. Use gloves when cutting tablets or handling this medication since skin absorption can occur. Do not administer this medication if you're trying to conceive or there's any chance you could be pregnant

Always give this medication with food. Ingesting azathioprine on an empty stomach can cause stomach upset.

Efficacy

A study of dogs with autoimmune-related arthritis found that a combination of corticosteroids and azathioprine improved symptoms and was comparable in efficacy to leflunomide and prednisone. 

A separate study noted that azathioprine is less effective in treating immune-mediated hemolytic anemia compared to other immunosuppressants, especially considering its cytotoxic properties. However, more evidence is needed to determine the drug’s efficacy.

Side effects

Cytotoxic drugs like azathioprine often have much more severe side effects than other pharmaceuticals. These are the most common side effects:

  • Nausea

  • Vomiting

  • Diarrhea 

  • Changes in appetite

  • Hair loss

  • Musculoskeletal pain

  • Dizziness

  • Extreme fatigue

  • Bruising easily

  • Bloody secretions

  • Opportunistic infections

  • Decreased bone marrow activity

  • Gastrointestinal pain

  • Temporary change in fur appearance

  • Sores on mucosal membranes 

  • Edema

  • Low blood cell counts

  • Hepatoxicity 

  • Pancreatitis

Considerations

Long-term use of this medication can increase canines’ vulnerability to opportunistic viral and bacterial infections since it hinders the immune response.

Azathioprine is known to cause birth defects and genetic mutations in both canines and humans. Pregnant and lactating dogs, as well as breeding males, should avoid this medication. If this medication is deemed medically necessary for a nursing canine, the puppies should be switched to formula immediately.

One study of azathioprine for dogs found that German Shepherds may be more prone to developing liver toxicity while taking this medication. 

Drug interactions

Azathioprine is known to have serious contraindications with other common drugs. Tell your vet if your dog is on any of the following medicines:

  • Gout medications (allopurinol)

  • Tumor necrosis factor blockers (humira, infliximab)

  • Cancer medications (mercaptopurine)

  • Medications used to treat ulcerative colitis (mesalamine)

  • Neuropathic pain relievers (pregabalin)

  • NSAIDs

  • Immunosuppressants (cyclosporine)

  • Bone marrow suppressants

Allergic reactions and sensitivity

Allergic responses are common with azathioprine, but these reactions don't always manifest in the same way as other drug reactions. Reactions to this medication are categorized by:

  • Aches and pains

  • Shivering

  • High fever

  • Lesions 

  • Stomach upset

 Take your dog to the vet right away if you think they're reacting to this medicine.

Frequently asked questions

How long does it take azathioprine for dogs to start working?

Azathioprine takes effect within the first few doses, but it may take several weeks or even months to see any symptomatic improvement.

Does azathioprine cause weight gain?

Azathioprine is associated with weight loss but not weight gain. See your vet if your pet packs on a few pounds without no notable cause, since this can indicate water retention.

I forgot to give my dog their azathioprine. Should I give them an extra pill to make up for it?

Unless you remember within an hour or two after their missed dose, you should skip the missed pill entirely and proceed with their dosing schedule as normal. Make sure you're spacing your dog's treatments out according to the vet's orders and giving it at the same time each day.  

Never give extra azathioprine, or two doses close together. This medication is known to cause rapid liver damage, especially in higher dosage strengths.  

Is it normal for dogs to eat less while on azathioprine?

Azathioprine often causes a decrease in appetite, which may make food may less appealing to your dog. There is some anecdotal evidence that this medication can interfere with the taste and smell of food. If your dog no longer shows interest in their food, try switching their brand or try a recipe for homemade dog food.

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Azathioprine Questions and Advice from Veterinary Professionals

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