Azathioprine

Azathioprine (also known by the brand name Imuran) is one of the most widely used medicines for inflammatory bowel disease (IBD). It has been used for more than 50 years and, although it needs careful monitoring, most people take it safely for many years.

What is it and how does it work?

Azathioprine is an immunosuppressant: it reduces the activity of the immune system, which is overactive in Crohn's disease (CD) and ulcerative colitis (UC). In the body it is converted into a closely related drug, mercaptopurine, which is sometimes prescribed instead.

What is it used for?

• To keep CD or UC in remission once a flare-up has been settled.
• To reduce or stop the need for steroids in people who relapse whenever the steroid dose is reduced, or who need more than one course a year.
• Together with a biologic medicine such as infliximab, to help it work better and to stop the body forming antibodies against it.
• After surgery for CD, in some people, to reduce the chance of the disease coming back.

Before you start

You will have a blood test to measure an enzyme called TPMT, which breaks down azathioprine. People with low TPMT levels need a lower dose, and the very few with no TPMT activity should not take it at all. You will also have a blood count and tests of your liver and kidney function, and you may be checked for immunity to chickenpox and for hepatitis B and C and HIV, as these infections could be made worse by the treatment.

It is a good idea to make sure your vaccinations are up to date before starting, particularly any live vaccines you may need (see Vaccinations below).

How is it taken?

Azathioprine comes as tablets, taken once a day with or after food. The dose depends on your weight, usually around 2 to 2.5 mg per kg of body weight a day, and is often built up over a few weeks. Taking the tablets after a meal, or splitting the dose, can help if they make you feel sick.

It works slowly. It usually takes two to three months to have an effect and up to six months for the full benefit, so you may be given a course of steroids at the start, which is reduced as the azathioprine begins to work.

Blood tests

Azathioprine can affect the bone marrow, where blood cells are made, and the liver. Regular blood tests pick up any problems early, before they cause symptoms. You will usually have a blood test every week or two for the first couple of months, then every three months for as long as you take it. Your IBD nurse or doctor will tell you how often, and will let you know if the dose needs to change.

Keeping to this monitoring is essential for your safety.

Side effects

Many people have no side effects, or only mild ones that settle within a few weeks.

In the first few weeks:

• Nausea, which often improves if the tablets are taken after food
• A flu-like illness with fever, aches, rash or feeling generally unwell. This can be an allergic reaction and you should contact your IBD team straight away.
• Inflammation of the pancreas (pancreatitis), which causes severe pain in the upper abdomen, often going through to the back, usually with vomiting. It affects about 3 in 100 people, usually in the first month. Stop the tablets and seek medical help the same day. Azathioprine should not be restarted after pancreatitis.

At any time:

• A low white cell count, which reduces your ability to fight infection, or a low platelet count. These are usually found on routine blood tests and corrected by changing the dose.
• Abnormal liver tests.
• Hair thinning.
• More frequent or more severe infections, including shingles.

Contact your doctor at once if you develop a sore throat, fever, mouth ulcers, unexplained bruising or bleeding, or yellowing of the skin or eyes, as you may need an urgent blood test.

Long-term risks

Azathioprine slightly increases the risk of some cancers over many years of treatment.

• Skin cancer. The risk of non-melanoma skin cancer is increased, especially with long-term use and sun exposure. Use a high-factor sunscreen, cover up in strong sun, avoid sunbeds and have any new or changing patch of skin checked. Some people also become more sensitive to the sun; see Azathioprine and photosensitivity.
• Lymphoma. There is a small increase in the risk of lymphoma, a cancer of the lymph glands. The risk remains low, and for most people the benefits of controlling their IBD outweigh it. See IBD, risk of bowel cancer and lymphoma.

Your IBD team will review with you from time to time whether you still need azathioprine. See also Azathioprine and the long-term treatment of IBD.

Other medicines

Some medicines interact with azathioprine, so always tell any doctor, dentist or pharmacist that you take it, and check before starting anything new, including medicines bought over the counter.

• Allopurinol and febuxostat (for gout) greatly increase the level of azathioprine in the blood and can be dangerous at normal doses. Some specialists deliberately combine allopurinol with a much lower dose of azathioprine, but this must only ever be done under their supervision.
• Trimethoprim and co-trimoxazole (antibiotics) increase the risk of a low blood count.
• Warfarin may be less effective.

Vaccinations

You should not have live vaccines while taking azathioprine, or for three months after stopping. These include yellow fever, oral typhoid and the MMR vaccine. Non-live vaccines are safe and recommended, including the yearly flu jab (the injection, not the nasal spray), COVID-19, pneumococcal and the non-live shingles vaccine.

If you have never had chickenpox and you come into contact with someone who has chickenpox or shingles, contact your GP or IBD team the same day, as you may need treatment to prevent it.

Pregnancy and breastfeeding

Azathioprine is not thought to harm an unborn baby, and most specialists advise continuing it during pregnancy because a flare-up is a greater risk to mother and baby. It is also considered compatible with breastfeeding. It does not reduce fertility in men or women. If you are planning a pregnancy, talk to your IBD team first; see Pregnancy and Inflammatory Bowel Disease.

Alcohol

Drinking alcohol in moderation is unlikely to cause problems, but as both alcohol and azathioprine can affect the liver it is sensible to keep within the recommended limits.

If azathioprine does not suit you

If you cannot take azathioprine because of side effects, mercaptopurine is sometimes better tolerated. Other options include methotrexate, biologic medicines and, for CD, diet. See Medicines for Crohn's Disease and Ulcerative Colitis.

Never stop taking azathioprine without discussing it with your IBD team first.