Azathioprine

Sounds like 'ay-za-THYE-oh-preen'

Overview
Clinicians
Clinicians

Azathioprine is used to treat autoimmune conditions such as Crohn's disease, ulcerative colitis and rheumatoid arthritis. Find out how to take it safely and possible side effects. Azathioprine is commonly called Imuran or Azamun.

Type of medicine	Also called
Immunosuppressant medicine (it weakens your body's immune response) Belongs to a class of medicines known as disease-modifying antirheumatic drugs (DMARDs)	Imuran® Azamun®

What is azathioprine?

Azathioprine is an immunosuppressant medicine, which means it weakens your body’s defence (immune) response. It is used to treat a number of autoimmune conditions related to an ‘overactive’ immune system, such as Crohn's disease, ulcerative colitis and rheumatoid arthritis. Autoimmune means that your body ‘attacks’ itself, without any real known cause or reason.

Azathioprine is also used to stop transplant rejection for people who have had transplant surgery. By weakening your immune system, it helps your body accept the new organ as if it were your own. Azathioprine is prescribed by a specialist doctor who is experienced in treating the condition. Azathioprine is available as tablets and as an injection.

Dose

In New Zealand there are 2 strengths of azathioprine tablets – 25 mg and 50 mg.
Always take your azathioprine exactly as your doctor has told you.
The dose of azathioprine is different for different people.
Your doctor will work out your dose based on your condition, your weight and your response to treatment.
The pharmacy label on your medicine will tell you how much azathioprine to take, how often to take it and any special instructions.

How to take azathioprine

Timing: Take your azathioprine dose 1 or 2 times a day, as directed by your doctor. Try to take your dose at the same time each day. Azathioprine is best taken on an empty stomach, at least 1 hour before or 3 hours after food or milk. But if azathioprine makes you feel nauseous (sick), try taking it after food or at bedtime, or ask your doctor if you can divide your dose and take it twice a day.
Swallow your tablets whole with a drink of water. Do not break, chew or crush the tablets.
Avoid or limit alcohol. Heavy drinking can increase your risk of side effects, such as problems with your liver.
Missed dose: If you forget to take your azathioprine dose, take it as soon as you remember. But if it is nearly time for your next dose, take the next dose at the right time. Do not take double the dose.
Keep taking azathioprine regularly. Azathioprine does not work straight away. It usually takes a few weeks or months before you notice the full benefits.

Precautions when taking azathioprine

Before starting azathioprine

Are you pregnant, planning a pregnancy or breastfeeding?
Do you have problems with the way your liver or kidneys work?
Have you had chickenpox or shingles?
Are you taking other medicines?
Have you recently had any vaccinations?

If so, it’s important that you tell your doctor or pharmacist before you start azathioprine. Sometimes a medicine isn’t suitable for a person with certain conditions, or it can only be used with extra care.

While taking azathioprine

Extra care is needed when taking azathioprine.

Blood tests: You will need to have regular blood tests to monitor for side effects and to work out whether the treatment is effective. Blood tests are very important during the first few months of treatment.
Risk of infections: Because azathioprine weakens your body’s defence (immune) system, you are more likely to pick up infections. It is important to avoid anyone who has chickenpox or shingles.
Sun protection: Azathioprine makes your skin more sensitive to the sun. Protect your skin when you are in the sun, especially between 10am and 3pm. Wear protective clothing and use a high factor sunscreen (SPF 30+).
Pregnancy: Make sure you or your partner do not get pregnant if either of you are taking azathioprine. Speak to your doctor about contraception.
Vaccines: Some vaccines should not be taken if you are on azathioprine. Always check with your doctor or pharmacist first. It is safe for you to have the annual flu vaccine.

Side effects

Like all medicines, azathioprine can cause side effects, although not everyone gets them. Often side effects improve as your body gets used to the new medicine.

Side effects*	What should I do?**
Feeling sick (nausea) Vomiting (being sick) Loss of appetite (don't feel like eating)	This is quite common when you first start taking azathioprine. Take your azathioprine with food, or ask your doctor about splitting your dose and taking it twice a day instead of all at once. Tell your doctor if troublesome.
Signs of getting an infection, such as feeling unwell, fever or chills	Tell your doctor immediately or phone Healthline on 0800 611 116.
Signs of changes in your blood cells, such as a severe sore throat, mouth ulcers, easy bruising, nosebleeds, bleeding gums, shortness of breath or fever	Tell your doctor immediately as you may need a blood test.
Signs of problems with your liver, such as sudden pains in your stomach, loss of appetite or yellowing of your skin and eyes	Tell you doctor immediately or phone Healthline on 0800 611 116.
* For more information on side effects, see the Medsafe consumer information leaflets Azamun and Imuran. ** Did you know that you can report a side effect to a medicine to CARM (Centre for Adverse Reactions Monitoring)? Report a side effect to a product

Interactions

Azathioprine interacts with some medicines and herbal supplements, so check with your doctor or pharmacist before you start taking anything new. Check with a pharmacist before taking over-the-counter anti-inflammatories such as diclofenac (eg, Voltaren Rapid), ibuprofen (eg, Nurofen) or naproxen (eg, Naprogesic). Taking these together with azathioprine may increase your risk of side effects.

Learn more

The following links have more information about azathioprine. Be aware that websites from other countries may have information that differs from New Zealand recommendations.

Azathioprine (Azathioprine for transplant patients) NZ Formulary
Azathioprine RheumInfo
Azamun Consumer Information Sheet, Medsafe, NZ
Azathioprine Arthritis Australia

References

Azathioprine NZ Formulary
Azamun Data Sheet, Medsafe, NZ

Resources

Te reo resources

The Māori Pharmacists’ Association Ngā Kaitiaki o Te Puna Rongoā has a free phone line to answer questions whānau have about their medicines. Call 0800 664 688.

Note: This is a non-urgent service and they will get back to you within 24 hours.
For urgent health advice freephone Healthline 0800 611 116.

Brochures

5 questions to ask about your medications

Health Quality and Safety Commission NZ, 2019

Information for clinicians

Monitoring

Monitoring	Frequency	What to look for	Action
CBC	Baseline then weekly for 6 weeks; then every 2 weeks until dose is stable for 6 weeks Then monthly Repeat 2 weeks after a dose change	WBC <3.5 x 109/L Neutrophils <2.0 x 109/L Platelets <150 x 109/L	Withhold until discussed with specialist team. Measure 6-TGN and 6-MMP levels.
		MCV > 105 fL	Check vitamin B12, folate and TSH. If abnormal, treat any underlying abnormality. Check 6-TGN level
LFTs	Baseline then monthly Repeat 2 weeks after a dose change	AST, ALT > twice the upper limit of reference range.	Withhold until discussed with specialist team.
Serum creatine	Baseline then every 6 months	Mild-to-moderate renal impairment (10-50 mL/minute)	Withhold until discussed with specialist team.
Rash or oral ulceration			Withhold until discussed with specialist team.
Abnormal bruising or severe sore throat			Withhold until discussed with specialist team.

Read more: Rheumatoid arthritis – monitoring of DMARDs BPAC, NZ, 2008

Thiopurine methyltransferase

The enzyme thiopurine methyltransferase (TPMT) metabolises thiopurine drugs (azathioprine, mercaptopurine, tioguanine); the risk of myelosuppression is increased in patients with reduced activity of the enzyme, particularly for the few individuals in whom TPMT activity is undetectable. Consider measuring TPMT activity before starting therapy. Patients with absent TPMT activity should not receive thiopurine drugs; those with reduced TPMT activity may be treated under specialist supervision. Close monitoring of blood counts is still necessary regardless of TPMT status.

Bone marrow suppression

Patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. inexplicable bruising or bleeding, infection.

Risk of progressive multifocal leukoencephalopathy (PML)

Immunomodulatory medicines are associated with the development of progressive multifocal leukoencephalopathy (PML). PML is a demyelinating disease of the CNS caused by the JC virus. A diagnosis of PML should be considered in patients taking immunomodulatory medicines who present with progressive neurological symptoms. Read more Immunomodulatory medicines and risk of progressive multifocal leukoencephalopathy Medsafe, NZ, 2016

Other cautions

Different formulations may vary in bioavailability (caution in transplant patients).
Monitor for toxicity throughout treatment. Monitor full blood count weekly (more frequently with higher doses or if severe hepatic or renal impairment) for first 4 weeks (manufacturer advises weekly monitoring for 8 weeks but evidence of practical value unsatisfactory), thereafter reduce frequency of monitoring to at least every 3 months.
Reduce dose in elderly.
Reduce dose if concomitant allopurinol treatment.
Immunisation with live vaccines not recommended.

Resources

Resources	Links
BPAC, NZ	Rheumatoid arthritis – monitoring of DMARDs October 2008
NZ Formulary	Azathioprine
Medsafe, NZ	Azamun Imuran