Azathioprine and mercaptopurine for autoimmune hepatitis

Introduction

Autoimmune hepatitis is a life-long and rare liver disease. It is when your body’s immune system causes damage to its own healthy liver cells. This leads to inflammation and scarring in the liver.

Treatment involves medicines that suppress the immune system and reduce inflammation and scarring. It also reduces the likelihood of your condition getting worse.

If left untreated it can lead to serious scarring of the liver (cirrhosis). This can then lead to liver cancer or liver failure.

Why am I prescribed azathioprine/mercaptopurine?

These are drugs that affect the immune system and help to control autoimmune hepatitis.

Azathioprine and mercaptopurine are chemically closely related. Azathioprine is changed to mercaptopurine in the body and these two medications act in a similar way.

Although they are similar, some people who cannot tolerate azathioprine because of side effects may still be able to take mercaptopurine.

What are other names for these medications?

The brand name for azathioprine is also referred to as 'Imuran'. Mercaptopurine is sometimes called 6-mercaptopurine or 6-MP. It's also known by the brand name Puri-nethol.

How do I take azathioprine/mercaptopurine?

You must swallow the tablets whole with plenty of water.

The exact number of tablets you take will vary depending on your weight and response to treatment. Your medical team will advise you on exactly how many to take.

If you forget a dose, take it as soon as you remember as long as it is within 12 hours. Do not double up on your next dose but continue taking the tablets as directed but make a note of it in your diary and remember to tell your doctor on your next visit that you missed a dose. If you mistakenly take too much, then contact your health professional as soon as possible.

How long do they take to work?

Azathioprine and mercaptopurine take 6 to 12 weeks to work. It is important to keep taking the treatment regularly.

Receiving your tablets

The autoimmune hepatitis team at Addenbrooke's hospital will arrange the first 3 months. Your GP will prescribe subsequent supply. Your usual, nominated community pharmacy will dispense it.

Do I need any special checks or tests whilst on azathioprine/mercaptopurine?

You will need regular blood tests whilst taking azathioprine or mercaptopurine to confirm the treatment is effective and to detect important side effects.

Pre-treatment blood tests and initial monitoring

Before starting treatment, you will need to take some blood tests. These are:

• Full blood count (FBC)
• Liver function tests (LFT)
• Urea and electrolytes (U&Es)
• Varicella zoster (chickenpox) antibodies
• Thiopurine S-methyltransferase (TPMT) activity
• Epstein-Barr Virus (EBV)
• Hepatitis B and C.

When you start taking azathioprine/mercaptopurine tablets, you will need to take the following blood tests every 2 weeks for 2 months or until stable:

• Full blood count (FBC)
• Kidney function tests (U&Es)
• Liver function tests (LFTs)

1. For the blood tests you can attend the drive-through Phlebotomy (blood test facility) located in Newmarket Road Park and Ride in Cambridge (CB5 8AA). A leaflet and more information are available here: Outpatient phlebotomy/blood tests.
   The drop-in service will be available between 09:30 and 16:30, Monday to Fridays. You must attend in a car, as the site is not suitable for walk-ins or bicycles.
2. You can also arrange an appointment to have bloods taken at Addenbrooke's Hospital by calling 01223 256998 (Monday to Friday, 09:00–17:00).

Ongoing blood tests

When the blood tests show that you are stable during treatment (or while receiving your immunotherapy),your local GP surgery will arrange the supply and monitoring of azathioprine/mercaptopurine. If you encounter issues with arranging blood tests, please let us know as soon as possible.

• You will need Full blood count (FBC) and liver function tests (LFTs) monthly for 3 months, then every 3 months thereafter.
• There may be other tests you require in addition to these from time to time for general monitoring and management of your condition.
• If you are asked by your GP to change your dose or to stop your medication, please contact us and we will arrange further appointments with you.

Are there any side effects?

Some people experience diarrhoea, nausea and mild aches and pains when they start taking the drug. These side effects should settle within two weeks. Other side effects are rarer.

If the following side effects occur at any time, then you should contact your GP, hospital doctor or specialist nurse immediately for further advice.

• feeling dizzy, light-headed or weak
• feeling tired or drowsy all the time
• vomiting or diarrhoea
• you have a high temperature with shivering or chills, cough or a sore throat
• a new outbreak of jaundice (yellowing of the skin or eyes)
• you notice new lumps anywhere on your body
• new unexplained bruising or bleeding

Special warnings/precautions

• Azathioprine/mercaptopurine should be avoided if you have previously had an allergic reaction to either.
• You should avoid sunbathing as there are increased risks of skin problems (including skin cancer), whilst you are taking azathioprine/mercaptopurine. We suggest you use a high factor sunscreen (i.e. SPF factor 50 or above) and wear a hat when out in the sunshine.

Are there any problems taking azathioprine/mercaptopurine with other medication?

Drugs that you can buy over the counter (such as in supermarkets) do not interact with azathioprine and mercaptopurine. However, for supplements and herbal medicines, please check with us.

Please note that allopurinol and febuxostat, which are used for gout prevention, interacts with azathioprine and mercaptopurine. However, there are medical reasons why we may intentionally use them together. If this is the case, we will provide you with extra information and monitor you more closely.

Azathioprine and mercaptopurine may also interact with some other prescribed drugs, so it is important that you tell your GP, hospital doctor, specialist nurse and pharmacist about any other medication you are taking.

Vaccines

Taking azathioprine/mercaptopurine is likely to reduce your body's resistance to infection. You can become seriously unwell from the viruses that cause chickenpox, shingles, and pneumococcal disease. If you are not already immune, we will recommend you get shingles (Shingrix brand only) and pneumonia vaccines. We also recommended everyone to get their yearly flu and COVID-19 jabs.

However, you should avoid live vaccines whilst on treatment and for 6 months after the last dose. Live vaccines include the live varicella/shingles immunisation (Zostavax brand), oral polio, oral typhoid, BCG, MMR and yellow fever. We will be able to advise you if you need these.

Pregnancy, breastfeeding and fertility while taking azathioprine/mercaptopurine

Pregnancy

You can take azathioprine/mercaptopurine during pregnancy.

It is particularly important to continue taking it as you need it to keep you healthy. Do not stop taking your medicine without talking to us.

As azathioprine/mercaptopurine affects the immune system, it means that after your baby is born, there is a very small risk it can affect the way they fight infections.

If your baby is unwell, speak to a doctor, your midwife or health visitor for advice. It is important to tell them that you took azathioprine/mercaptopurine during pregnancy.

Breastfeeding

If your doctor, health visitor or midwife says your baby is healthy, you can take azathioprine/mercaptopurine if you are breastfeeding.

It's important to continue taking azathioprine/mercaptopurine to keep you well. Breastfeeding will also benefit both you and your baby.

Azathioprine/mercaptopurine passes into breast milk in tiny amounts. Many breastfeeding mothers have taken it. It usually does not cause side effects in breastfed babies.

As a precaution, if you're taking a high dose of azathioprine/mercaptopurine, your baby might need some extra blood tests.

Talk to your health visitor, midwife, doctor or pharmacist as soon as possible if you have any concerns about your baby. This includes:

• not feeding as well as usual
• getting frequent infections

Fertility

There is no evidence to suggest that taking azathioprine/mercaptopurine reduces fertility in either men or women. Please discuss with us if you are trying to get pregnant.

Further information

This leaflet is only a guide. Further information may be obtained from the manufacturer’s patient information leaflet that you will get with the drug and also from your hospital doctor, GP or specialist nurse.

If you have side-effects or problems with your medication you can contact the specialist nurse/doctor at the hospital.

Contact details

Autoimmune Hepatology Helpline: 01223 216109

Pharmacy Medicines Information Helpline (Monday to Friday, 09:00 to 17:00): 01223 217502

MyChart

We would encourage you to sign up for MyChart. This is the electronic patient portal at Cambridge University Hospitals that enables patients to securely access parts of their health record held within the hospital’s electronic patient record system (Epic). It is available via your home computer or mobile device.

More information is available on our website: MyChart.