What is azathioprine?

Azathioprine is an immunosuppressant drug that was originally developed to prevent graft rejection in transplant patients. It has been available since the 1960s and has been used for many years to treat severe eczema. Two trials in the 1990s provided good evidence that azathioprine is effective for resistant moderate to severe eczema. It has also frequently been used for other skin diseases as a means of reducing oral steroid use. However, azathioprine is not licensed for use in eczema and is prescribed ‘off-licence’ only by dermatologists.

How does azathioprine work?

Azathioprine is an immunosuppressant that is also known as an ‘anti-metabolite’. It interferes with the proliferation of certain types of white blood cells (lymphocytes), which are involved in generating the inflammation associated with eczema. It takes a little longer to become effective than ciclosporin, and benefits are usually not seen until after 4–5 weeks. Therefore, azathioprine is less suitable for acute flares because it takes longer to take effect. Further improvements then occur over the next few months.

When is azathioprine used?

Azathioprine is mainly used in the UK to treat people with severe eczema that is unresponsive to conventional topical treatments. Azathioprine can be prescribed for adults and older children with severe eczema, but only under consultant dermatologist supervision.

Azathioprine is available as 25 mg and 50 mg tablets. People with normal thiopurine methyltransferase levels (see ‘Who should NOT take azathioprine’, below) can take azathioprine as a single dose, but if side effects such as sickness occur, dividing the dose and taking this medication twice a day may help. A starting dose of 2.0 mg/kg is often used initially, and then the dose is gradually increased according to the response. The usual maintenance dose is 100–250 mg per day (i.e. 2.5 mg/kg per day).

Who should NOT take azathioprine?

About 1:200 people have low levels of an enzyme called thiopurine methyltransferase (TPMT). They are unable to break down azathioprine in the normal way and are at high risk of dangerous bone marrow suppression. This can result in severe anaemia and the risk of infection. These people should not receive azathioprine. A blood test is available to determine which people are most at risk of developing this side effect. It is mandatory to perform this blood test before starting to take azathioprine. A further group of people who have intermediate activity of TPMT may be given azathioprine, but it is recommended that a reduced dose be given starting at 0.5 mg/kg increasing to 1.0 mg/kg. If the level of TPMT is normal, the risk of developing these side effects is reduced but they may still occur.

Both men and women must stop taking azathioprine for at least 3 months before trying to conceive. The effectiveness of intrauterine contraceptive devices may be affected by azathioprine, so other or additional forms of contraception are recommended.

Azathioprine should not be used in pregnancy without careful assessment of the risks and benefits.

Those taking azathioprine are advised not to breastfeed.

What are the side effects?

The main risk of treatment with azathioprine is bone marrow suppression (as stated above, people with low levels of TPMT should not receive azathioprine). All people taking azathioprine require blood tests before and during treatment to check for any signs of marrow suppression even if their TPMT level is normal. You should seek medical advice if you become unwell or develop any signs of infection. It is also important to report any unusual bruising or bleeding, which may be a sign that the bone marrow is being affected.

Azathioprine can sometimes cause problems with the liver. Liver function tests are usually checked at the start of treatment and monitored at least every 3 months, but more frequently at the start of treatment.

Long-term treatment predisposes a person to certain types of cancer.

Nausea, diarrhoea and loss of appetite may be a problem for some people, but usually these side effects respond to a reduction in dose.

Hair loss can occur but this is usually mild and is reversible on stopping the drug.

Occasionally, a drug hypersensitivity syndrome may develop – this feels like flu with aches, pains and fever. If this occurs, the drug should be stopped immediately and the prescribing doctor informed.

For more information on azathioprine, please see our Azathioprine factsheet