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Azathioprine

Why is azathioprine used and how does it work?

  • Inflammatory bowel disease is an inflammatory condition of unknown cause.
  • However it is known that there are overactive immune cells in the gut that are causing some of the damage to the lining of the gut.
  • Mostly it seems that these immune cells are over-reacting to the normal environment, particularly to the bacteria that are normally present in the lumen of the gut.
  • Dampening down the immune system is a highly effective way of treating ulcerative colitis OR Crohn's disease (IBD)


  • Azathioprine is currently used in up to 50% of people with IBD at some stage during the treatment
  • Azathioprine leads to complete relief of symptoms in over 80% of patients who are able to tolerate the medication.
  • The effect can take some time – up to 6-9 months although some benefit is usually seen after 3 months.
  • The main benefit is getting off the steroids (Prednisone).  Steroids have side-effects if taken over a long period of time.




What is the recommended duration of use for azathioprine?

  • Azathioprine has been used for Crohn’s disease and ulcerative colitis since the late 1960’s.
    • Treatment was initially continued for many years (5-10 years).
    • In the late 70’s several studies questioned whether the medication worked at all and the treatment become less popular.
    • It is now clear that these studies were not continued for long enough to see an effect (less than 6 months treatment was given).
  • In the late 80’s the medication was used more commonly but only for 2 years then the drug was discontinued even when there was an excellent response.
    • A review of this practice showed that relapse of the disease was common within one year after stopping the medication.
  • There has been a gradually increasing confidence with using azathioprine in recent years and an acceptance of the powerful therapeutic effect (once the correct dose is achieved).
    • The average dose has increased as we have become better at using the drug in an optimum way.
    • Monitoring of 6-TG levels (blood levels of the active metabolite has shown us that we have been underdosing many people in the past.
  • There is now an acceptance that 5 years duration would be a minimum duration of treatment but probably 10-15 years or more is a reasonable safe limit.
    • Treatment beyond this limit may be considered after careful discussion with your specialist.
    • One option is to have a "drug holiday" for 6-12 months if you have had treatment for more than 5 years and the condition is in complete remission.  There is still a risk of relapse and azathioprine will need to be restarted at the first sign of recurrent symptoms
  • There has been an increasing use of azathioprine in the treatment of ulcerative colitis.
    • There is an argument that drugs with any significant risks should not be used the treatment of ulcerative colitis because the results of surgery are good leading to a cure of disease.
    • However the contrary argument is that the results of azathioprine are excellent without the need for major surgery.
    • Most gastroenterologists will now suggest treatment with azathioprine before considering surgery
    • See section on surgery in ulcerative colitis



Drug interactions

  • Azathioprine blood levels may be affected by other drugs.
    • The most significant interaction is with allopurinol (used for gout) – this could significantly increase the levels of azathioprine and lead to serious problems.
    • Minor effects on blood levels have been observed with frusemide and ACE inhibitors (Inhibace, Accupril).
  • Once remission is achieved it is usually possible to stop the 5-ASA drug (Pentasa, Asacol).
    • Occasionally there is a relapse if the 5-ASA is stopped suggesting that the combination was better
    • The other reason for considering continuation of Pentasa or Asacol even when there is excellent control with azathioprine is the effect of these drugs on reducing the risk of colon cancer.
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