Azathioprine

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

Overview
Clinicians

Easy-to-read medicine information about azathioprine – what it is, how to take it safely and possible side effects.

Type of medicine	Also called
Immunosuppressant medication (weakens the 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 medication, which means that it weakens the body's defense system or immune response. It is used to treat a number of auto-immune conditions related to an 'over-active' immune system such as Crohn's disease, ulcerative colitis, and rheumatoid arthritis. Auto-immune means that the 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

Always take your azathioprine exactly as your doctor has told you.
The dose of azathioprine will be 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

Take your azathioprine dose once or twice a day, as directed by your doctor. Try to take your dose at the same time each day.
Swallow your tablets whole with a drink of water. Do not break, chew or crush the tablets.
Azathioprine is best taken on an empty stomach, at least 1 hour before or 3 hours after food or milk. But, if you find that azathioprine makes you feel nauseous or sick, or gives you stomach upset, try taking your azathioprine dose after food or at bedtime, or ask if you can divide your dose and take it twice a day.
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, just take the next dose at the right time. Do not take double the dose.
Azathioprine does not work straight away. It usually takes a few weeks or months before you notice the full benefits.

Special instructions

Extra care is needed when taking azathioprine.

Blood tests: while you are taking azathioprine you will need to have regular blood tests to monitor for side effects and to determine if the treatment is working for you. Blood tests are very important during the first few months of treatment.
Risk of infections: since azathioprine weakens your body's defense or immune system, you will be more likely to pickup infections. It is important to avoid anyone who is has chickenpox or shingles.
Alcohol: Azathioprine can affect your liver, so you should avoid heavy alcohol use while taking it. Generally, 1 or 2 standard drinks taken once or twice a week is unlikely to cause problems but drinking more than 4 standard drinks on one occasion, even if its now and again, is strongly discouraged.
Sun protection: azathioprine makes your skin more sensitive to the sun. Protect your skin when you are in the sun, especially between 10 am and 3 pm. If outdoors, 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 given if you are taking azathioprine; always check with your doctor or pharmacist first.

Precautions - before starting azathioprine

Are you pregnant, planning a pregnancy or breast-feeding?
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.

Possible 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 Loss of appetite (don't feeling 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 taking it all at once Tell your doctor if troublesome
Signs of getting an infection such as feeling unwell, fever, shaking chills	Tell you doctor immediately or ring Healthline on 0800 611 116
Signs of changes in your blood cells such as severe sore throat, mouth ulcers, easy bruising, nosebleeds, bleeding gums, short of breath, fever	Tell you 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, yellowing of the skin and eyes	Tell you doctor immediately or ring 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 medications 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 (e.g. Voltaren Rapid), ibuprofen (e.g. Nurofen), naproxen (e.g. 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.

Azamun Medsafe NZ Consumer Information Sheet
Azathioprine Arthritis Research UK
Azathioprine Arthritis Australia

References

azathioprine New Zealand Formulary
Azamun Medsafe data sheet

Credits: Sandra Ponen, Pharmacist. Reviewed By: Angela Lambie, Pharmacist, Auckland Last reviewed: 22 Jan 2018 Page last updated: 21 Feb 2020

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 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, 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	Rheumatoid arthritis - monitoring of DMARDs October 2008
NZ Formulary	Azathioprine
Medsafe datasheet	Azamun Imuran