Thiopurines for inflammatory bowel disease (IBD)

Azathioprine and 6-Mercaptopurine (6-MP) belong to a group of drugs called thiopurines which are immunosuppressants. These suppress inflammation and slow down the body’s immune response. They are also used to avoid rejection following organ transplantation.

Thiopurines are given once daily in tablet form, sometimes twice daily if drug blood levels indicate twice daily to be better. The dose is calculated according to weight and modified according to drug blood levels.

Both Azathioprine and 6-MP have the same active ingredient, 6-TG, but 6-MP has fewer potential side effects. Patients on Azathioprine need not change. The information below applies to both drugs which are used to help maintain remission in patients with moderate to severe Crohn’s and Colitis, minimising the need for corticosteroids.

The proper name of your medicine is Azathioprine but the label on your medicine may sometimes say Imuran, Azamun, Azahexal, or Azapin. For 6-Mercaptopurine (6-MP) the label on your medicine may say Puri-nethol. These are ‘brand names’. They are available in tablet form, Azathioprine has two strengths, 25mg and 50mg, whereas 6-MP is only available as 50mg tablet.

Do not stop taking your medicine unless advised by your doctor. Azathioprine and 6-MP are generally well tolerated and it is important to remember that most patients do not experience any adverse side effects.

Importantly:

• Do not take more often than directed or vary the dose without specific advice.
• If you miss a dose, take your dose as soon as you remember.
• If it is almost time for your next dose, take only that dose.
• It can take up to three months for thiopurines to have maximum benefits.
• You may need other treatments (such as exclusive enteral nutrition or steroids) during this time to keep your bowel inflammation under control.
• Thiopurines are usually prescribed for long periods, usually for several years.

What are the side effects?

Early adverse side effects may include nausea, vomiting and loss of appetite. These can be reduced by taking your medicine with food or milk. A common side effect is increased skin sensitivity and risk of sunburn. While on these medications, sun-protection measures are vitally important.

Rare adverse side effects may include; difficult-to-clear infections including viral skin warts, allergy, bleeding/bruising, liver problems, pancreas inflammation and bone marrow (white blood cells) suppression.

Serious Side effects

Patients with IBD have increased risk of Lymphoma (cancer of lymphatic glands) and patients on these drugs for longer than 4 years have a further increased risk. The risk of Lymphoma in the community is 1 person in

10,000. Lymphoma risk in patients with IBD is 2/10,000 and those on thiopurines 4/10,000. For comparison, the risk of fatal car crash travelling on the roads is 1/10,000 per year.

Skin cancer is a major health concern in Australia with 70% of the community having a skin cancer removed by 60. This risk is increased in patients on thiopurines so we encourage all patients to take sun precautions.

Report any of the following to your doctor as soon as possible:

• Fever, chills, diarrhoea or sore throat
• Skin rash or itching or mouth ulcers
• Severe Abdominal pain (which may suggest pancreatitis)
• Yellowing of skin or eyes, Dark yellow or brown urine
• Unusual bleeding or bruising or Black, tarry stools

Your child’s doctor will arrange regular blood tests to see how their body is responding to the medication, to monitor their blood count and liver function, and intermittently monitor the level of medication in their blood. Initially blood tests will be every few weeks, then, when your doctor is happy you are tolerating the drugs, tests will be less frequent but never less than four monthly.

It is important to tell your doctor before taking any other medications, including those bought over-the-counter from a pharmacy, supermarket or health food shop. Grapefruit should also be avoided as this increases drug levels in the blood unpredictably. Other medicines can affect how your body handles thiopurines which they may impact safety and reduce effectiveness

Special instructions

Discuss your child’s immunisation status with your doctor before starting as it may be necessary to complete their vaccination schedule prior to commencing thiopurines. LIVE vaccinations (MMR, Chicken Pox, Polio, Yellow Fever) should be avoided while on these drugs. Pneumovax and flu vaccine can be safely given and recommended for anyone taking ‘immunosuppressant’ medications, as they help reduce risk of flu and pneumonia infections.

Thiopurines can affect healing and increase risk of infection so please ensure you:

• Check with your child’s doctor before arranging any further immunisations or treatments (including dental work).
• Try to avoid anyone with severe symptoms of a cold, flu or other infections (particularly chickenpox and measles).
• Report any contact with infections such as confirmed chicken pox, measles or rubella, to your doctor.
• Avoid damage to teeth and gums by brushing and flossing regularly.

Note for carers and schools

Thiopurines are considered cytotoxic with a very small increased risk of cancers in those taking them. Caution is needed when touching the tablets (wear gloves or wash hands promptly afterwards) and with all bodily fluids: stool, urine, vomit, sputum from patients taking them. Any spill should be cleaned with soap and water and the toilet always flushed with the lid down. The chances of any harm to another person from contact with the drug or with body fluids from someone on the drug are extremely rare but caution is required as these drugs have no known minimum safe exposure.

When to seek help

See your GP if your child has any common symptoms.

In an emergency, call Triple Zero (000) and ask for an ambulance.

If you're not sure whether to go to an emergency department, call 13 HEALTH (13 43 25 84) and speak to a registered nurse.

For more information

This fact sheet is about thiopurines for inflammatory bowel disease in children and young people. The information will be different from the manufacturer’s Consumer Medicine Information (CMI).

For more information see your GP or talk to your pharmacist.

Developed by Gastroenterology team, Queensland Children’s Hospital. We acknowledge the input of consumers and carers.

Resource ID: FS120. Reviewed: June 2016.

Disclaimer: This information has been produced by healthcare professionals as a guideline only and is intended to support, not replace, discussion with your child’s doctor or healthcare professionals. Information is updated regularly, so please check you are referring to the most recent version. Seek medical advice, as appropriate, for concerns regarding your child’s health.