Azathioprine: An Immunosuppressive Medicine

Azathioprine is a prodrug. A prodrug's a drug that's administered and absorbed, but it doesn't trigger any effects until it's metabolized and converted into another molecule. In this case, the molecule is 6-mercaptopurine. Learn more about azathioprine in this article.
Azathioprine: An Immunosuppressive Medicine

Last update: 31 January, 2021

Immunosuppressive medicines weaken your immune system. They do this in order to treat diseases when your immune system is operating in the wrong way. In this article, you’ll learn more specifically about azathioprine, an immunosuppressive medicine.

Your immune system is a mechanism of your body which defends against pathogens or infections. However, sometimes you develop diseases because your immune system mistakenly thinks a natural substance or structure of your body is foreign. Your body then attacks this substance or structure. So, in these situations, your immune system needs to be weakened in order to stop it from attacking.

Azathioprine is a prodrug. A prodrug’s a drug that you absorb, but it doesn’t trigger any effects until you metabolize it and convert it into another molecule, 6-mercaptopurine.

We use azathioprine to treat diseases like Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, multiple sclerosis, or autoimmune hepatitis.

In addition, we originally used this medicine, along with other immunosuppressive agents, in organ transplants. We used it so that the body didn’t think of the new organ as a foreign body and start to attack it. However, nowadays we don’t use azathioprine so much for this particular purpose.

Pharmacokinetics: what happens to azathioprine in the body?

Tablets and a glass of water.

Pharmacokinetics is concerned with the absorption, distribution, metabolism, and elimination of a drug. In the case of azathioprine, you can take it either orally or intravenously. However, if you take it orally you should always take the tablets whole, i.e. you mustn’t break them up. Furthermore, you must take the tablets with food. If you can’t take azathioprine orally you can take it intravenously.

When you take azathioprine orally, it’s absorbed into your upper gastrointestinal tract. It then gets distributed throughout your body. Scientists discovered this from experiments they conducted with mice. In these experiments, they found by-products of the drug in the brains of the mice.

Once the drug reaches your liver you metabolize it to 6-mercaptopurine. This is the active metabolite that triggers your immunosuppressive action. However, the plasma levels of azathioprine and 6-mercaptopurine don’t correlate well with the therapeutic efficacy or toxicity of this drug.

In addition to 6-mercaptopurine, you also metabolize azathioprine into other molecules, such as 6-thiuric acid, although it’s not active. Finally, you excrete both the unmetabolized drug and the metabolites resulting from metabolism in your urine.

How does the immunosuppressive medicine azathioprine affect the body?

We don’t know exactly how this immunosuppressant works on your body. However, there are different hypotheses.

  • 6-mercaptopurine is thought to be an antimetabolite of purines. In other words, it disrupts the synthesis of purines that are necessary for DNA synthesis. This action would weaken immune cells, hence causing an immunosuppressive effect.
  • The active metabolite of azathioprine could alkylate sulphuric groups. This would cause DNA damage to the immune system cells.
  • Another hypothesis is the inhibition of different pathways of nucleic acid synthesis. The consequence of the growth and proliferation of cells involved in the immune response would weaken this defense system and justify the action of azathioprine.
  • Finally, it’s thought to damage the DNA of immune system cells by incorporating traces of purine thiol-analogs.

Side-effects of the immunosuppressive medicine azathioprine

A woman and a pharmacist.

Like all medicines on the market, azathioprine can cause side-effects. We consider side-effects to be the unwanted and unintended occurrences we expect to see when a patient takes a specific drug.

Patients have reported the following side-effects with the use of azathioprine:

  • Digestive problems
  • Neutropenia
  • Pancreatitis
  • Hepatitis


We use azathioprine a lot to treat autoimmune diseases. However, it causes a number of side effects. So, you’d have to tell your doctor about any allergies you have to other medicines before you take it. This is because you could possibly suffer certain complications by taking azathioprine.

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  • Yebra Bango, M., Vargas Nunez, J. A., Gea-Banacloche, J. C., & Romero Pizarro, Y. (1995). TRATAMIENTO DEL LUPUS ERITEMATOSO SISTEMICO. Revista Clinica Espanola.
  • Itxarone, B., & Margarit, C. (2014). La inmunosupresion en el trasplante hepatico. Farmacia Hospitalaria.
  • López-Martín, C., de la Fuente-Fernández, E., Corbatón, P., Sánchez, M. C., & Gisbert, J. P. (2011). Hiperplasia nodular regenerativa: hepatotoxicidad por azatioprina en un paciente con enfermedad de Crohn. Gastroenterologia y Hepatologia.