Imuran

Leaflet accompanying the packaging: patient information

Imuran, 25 mg, coated tablets

Imuran, 50 mg, coated tablets

Azathioprine

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Imuran and what is it used for
• 2. Important information before taking Imuran
• 3. How to take Imuran
• 4. Possible side effects
• 5. How to store Imuran
• 6. Contents of the packaging and other information

1. What is Imuran and what is it used for

Imuran contains the active substance azathioprine. It belongs to a group of medicines called immunosuppressants, which reduce the activity of the immune system.
Imuran can be used to facilitate the acceptance of a transplanted organ (such as a new kidney, heart, or liver) by the body or to treat certain diseases in which the immune system reacts against its own body (autoimmune diseases).
Autoimmune diseases may include:

• severe rheumatoid arthritis (a disease in which the immune system attacks the cells lining the joints, causing swelling, pain, and stiffness of the joints)
• systemic lupus erythematosus (a disease in which the immune system attacks many organs and tissues, including the skin, joints, kidneys, brain, and other organs, causing excessive fatigue, fever, stiffness, and joint pain),
• dermatomyositis and (or) polymyositis (a group of diseases that cause inflammation of the muscles, muscle weakness, and rash on the skin),
• autoimmune chronic active hepatitis (a disease in which the immune system attacks liver cells, causing liver inflammation, fatigue, muscle pain, yellowing of the skin, and fever)
• common pemphigus (a disease in which the immune system attacks skin cells, causing blisters on the skin, in the mouth, nose, throat, and on the genitals)
• giant cell arteritis (a rare disease that causes inflammation of blood vessels)
• autoimmune hemolytic anemia (a serious blood disorder in which the body destroys red blood cells faster than it produces them, with symptoms of weakness and shortness of breath),
• chronic idiopathic thrombocytopenic purpura resistant to treatment (a condition in which the number of platelets in the blood is low, which can cause easy or excessive bruising and bleeding).

Imuran may also be used to treat inflammatory bowel disease (Crohn's disease or ulcerative colitis).
Your doctor has chosen this medicine because it is suitable for you and your disease.
Imuran can be used as the only medicine, but it is often used in combination with other medicines.

2. Important information before taking Imuran

When not to take Imuran:

• if the patient is allergic to azathioprine or any of the other ingredients of this medicine (listed in section 6)
• if the patient is allergic to mercaptopurine (a medicine that is similar to azathioprine, the active substance of Imuran).

Warnings and precautions

Before starting treatment with Imuran, discuss the following with your doctor or pharmacist:

• if the patient has received or is going to receive a vaccine. If the patient is taking Imuran, they should not receive a live vaccine (e.g., flu vaccine, measles vaccine, BCG vaccine, etc.) until the doctor considers it safe. This is because some vaccines can cause infection if used during treatment with Imuran.
• if the patient has a genetic disease known as Lesch-Nyhan syndrome. This is a rare inherited genetic disease caused by a lack of an enzyme called HPRT or "hypoxanthine-guanine phosphoribosyltransferase".
• if the patient has kidney or liver disease
• if the patient has a genetic disease called TPMT deficiency (the body produces too little of an enzyme called thiopurine methyltransferase)
• if the patient has had chickenpox or shingles
• if the patient has had hepatitis B (a liver disease caused by a virus)
• if the patient is going to have surgery [this is because muscle relaxants used during anesthesia (such as tubocurarine or succinylcholine) may interact with azathioprine]. The patient should inform the anesthesiologist about taking Imuran before surgery.

Liver damage
Treatment with Imuran may affect the liver. The doctor will regularly check the liver function.
If the patient experiences symptoms of liver damage, they should inform the doctor (see section 4 "Possible side effects").
Mutation of the NUDT15 gene
If the patient has a congenital mutation in the NUDT15 gene (a gene responsible for the breakdown of Imuran in the body), there is an increased risk of infections and hair loss, so the doctor may decide to reduce the dose.
In case of doubt about any of the above situations, the patient should consult their doctor, nurse, or pharmacist before starting treatment with Imuran.
During treatment with Imuran, the doctor will perform regular blood tests
to detect any changes (see section 3 "How to take Imuran"). The frequency of blood tests usually decreases over time.
The doctor may also perform genetic tests [i.e., examine the TPMT and (or) NUDT15 genes] before or during treatment to determine if the patient's genes may affect their response to treatment with this medicine. The doctor may change the dose of Imuran after performing these tests.
If the patient is taking immunosuppressants, taking Imuran may increase the risk of:

• developing tumors, including skin cancer. Therefore, during treatment with Imuran, the patient should avoid excessive sun exposure, wear protective clothing, and use sunscreens with a high protection factor.
• lymphoproliferative disorders, as treatment with Imuran increases the risk of developing a type of tumor called lymphoproliferative disorder. In a treatment regimen involving multiple immunosuppressants (including thiopurines), this can lead to death. o The concurrent use of multiple immunosuppressants increases the risk of lymphatic system disorders caused by viral infections [lymphoproliferative disorders dependent on the Epstein-Barr virus (EBV)].
• a severe condition called macrophage activation syndrome (excessive activation of white blood cells associated with inflammation), which usually occurs in people with certain types of arthritis,
• severe chickenpox or shingles infection. Therefore, during treatment with Imuran, the patient should avoid contact with people suffering from chickenpox or shingles.
• reactivation of a previously existing hepatitis B virus infection (the infection becomes active again),
• other infections, such as PML (progressive multifocal leukoencephalopathy), which is an opportunistic infection. If any symptoms of infection occur, the patient should contact their doctor (see section 4 "Possible side effects").

Pellagra

The patient should immediately tell their doctor if they experience diarrhea, local pigmented rash (skin inflammation), worsening of memory, logical thinking, or other cognitive abilities (dementia), as these symptoms may indicate a vitamin B deficiency (niacin deficiency/pellagra).

Imuran and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. This is because Imuran may affect the action of other medicines. Other medicines may also affect the action of Imuran.
The patient should especially tell their doctor if they are taking or plan to take:

• ribavirin (a medicine used to treat viral infections)
• methotrexate (a medicine used mainly to treat cancer)
• allopurinol, oxypurinol, thiopurinol, or other xanthine oxidase inhibitors, such as febuxostat (medicines used mainly to treat gout)
• penicillamine (a medicine used mainly to treat rheumatoid arthritis)
• angiotensin-converting enzyme inhibitors (medicines used mainly to treat high blood pressure and heart failure)
• anticoagulant medicines, such as warfarin or acenocoumarol (medicines that prevent blood clots),
• cimetidine (a medicine used to treat stomach ulcers and indigestion)
• indomethacin (a pain-relieving and anti-inflammatory medicine)
• cytostatic medicines (medicines used to treat various types of cancer)
• aminosalicylates, such as olsalazine, mesalazine, or sulfasalazine (medicines used mainly to treat ulcerative colitis and Crohn's disease)
• co-trimoxazole (an antibiotic used to treat bacterial infections)
• infliximab (a medicine used mainly to treat ulcerative colitis and Crohn's disease)
• muscle relaxants, such as tubocurarine or succinylcholine (medicines used during surgery).

If the patient is taking azathioprine, they should inform their anesthesiologist about it before surgery, as muscle relaxants used during anesthesia may interact with azathioprine.
If the patient is unsure whether they are taking any of the above medicines, they should consult their doctor or pharmacist before taking Imuran.

Vaccination during treatment with Imuran

If the patient is going to receive a vaccine, they should discuss it with their doctor or nurse.
If the patient is taking Imuran, they should not receive a live vaccine (e.g., flu vaccine, measles vaccine, BCG vaccine, etc.) until the doctor considers it safe.
This is because some vaccines can cause infection if used during treatment with Imuran.

Imuran with food and drink

The medicine should be taken no earlier than 1 hour before and 2 hours after consuming milk or dairy products.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before taking this medicine.
Pregnancy
The patient (or their partner) must use effective contraception during treatment with Imuran.
If the patient experiences severe itching without a rash during pregnancy, they should immediately tell their doctor.
They may also experience nausea and loss of appetite with itching, which can indicate a condition called cholestasis of pregnancy (a liver disease during pregnancy).
If the patient is pregnant, the doctor will carefully weigh the benefits and risks of taking this medicine.
Breastfeeding
Imuran passes into breast milk in small amounts. Women should not breastfeed while taking Imuran, unless the expected benefits of breastfeeding for the baby outweigh the possible risk. The patient should consult their doctor before starting breastfeeding.
Fertility
The effect of Imuran on fertility is not known.

Driving and using machines

It is not known whether Imuran affects the ability to drive or use machines.
If the patient experiences any side effects after taking Imuran, they may not be able to drive or use machines.

Imuran contains lactose

If the patient has been diagnosed with an intolerance to some sugars, they should contact their doctor before taking this medicine.

3. How to take Imuran

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If the patient has any doubts, they should consult their doctor or pharmacist.
The amount of Imuran taken may vary from person to person. The dose depends on the disease being treated and is determined by the doctor.
Imuran can be taken with or without food, but the patient should take it the same way every day. Some patients may feel nauseous when taking Imuran for the first time. Taking the tablets with food may alleviate these symptoms.

• During treatment with Imuran, the doctor will perform regular blood tests to check the number and type of blood cells and ensure that the patient's liver is working properly.
• The doctor may also order other blood and urine tests to monitor kidney function and measure uric acid levels. Uric acid is a naturally occurring substance, and its levels may increase during treatment with Imuran. High levels of uric acid can damage the kidneys.

Sometimes the doctor may change the dose of Imuran based on the results of these tests.
The tablets should be swallowed whole. The tablets should not be chewed, divided, or crushed.
It is essential for caregivers to be aware of the need for safe handling of this medicine.
If the patient or their caregiver comes into contact with damaged tablets, they should wash their hands immediately. For advice, they should consult their doctor or pharmacist.

Recommended dose:

Adults after organ transplantation: Usually, up to 5 mg per kilogram of body weight is taken on the first day, and then usually 1 to 3 mg per kilogram of body weight per day. During treatment, the doctor will adjust the dose according to the patient's response to the medicine.
Adults with other diseases: The usual initial dose is 1 to 3 mg per kilogram of body weight, and then usually 1 to 3 mg per kilogram of body weight per day. During treatment, the doctor will adjust the dose according to the patient's response to the medicine.
In elderly patients, a lower dose may be necessary.
In patients with impaired kidney or liver function, a lower dose may be necessary.

Use in children

Children after organ transplantation: The dosing in children after organ transplantation is the same as in adults.
Children with other diseases: The dosing in children with other diseases is the same as in adults.
Children who are overweight may require a higher dose.

Taking a higher dose of Imuran than recommended

In case of taking too many tablets, the patient should immediatelycontact their doctor or pharmacist.

Missing a dose of Imuran

The patient should not take a double dose to make up for a missed dose. If the patient misses a dose, they should inform their doctor.
If it is almost time for the next dose, the patient should skip the missed dose and take the next dose at the usual time. Otherwise, the patient should take the missed dose as soon as they remember, and then return to their regular dosing schedule.

Stopping treatment with Imuran

Before stopping treatment with Imuran, the patient should consult their doctor or pharmacist. The patient should not stop taking Imuran until their doctor considers it safe.

In case of further doubts about taking this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Imuran can cause side effects, although not everybody gets them.
After taking Imuran, the following side effects may occur:

The patient should stop taking Imuran and immediately consult their doctor if they experience any of the following severe side effects, as

immediate medical attention may be necessary:

• allergic reactions (this is an uncommon side effect that may affect up to 1 in 100 people) with symptoms such as: o general fatigue, dizziness, nausea, vomiting, diarrhea, or abdominal pain o swelling of the eyelids, face, or lips o redness of the skin, skin rash, or hives o muscle or joint pain o sudden wheezing, coughing, or difficulty breathing. In rare cases, these reactions can be life-threatening (this is a very rare side effect that may affect up to 1 in 10,000 people) .
• skin rash or redness, which can develop into life-threatening skin reactions, including widespread rash with blisters and peeling of the skin, especially on the mouth, nose, eyes, and genitals ( Stevens-Johnson syndrome), widespread peeling of the skin ( toxic epidermal necrolysis) (these may be very rare side effects that may affect up to 1 in 10,000 people)
• transient pneumonia (causing shortness of breath, cough, and fever) (this may be a very rare side effect that may affect up to 1 in 10,000 people)
• blood or bone marrow problems; symptoms include: weakness, fatigue, pallor, easy bruising, unusual bleeding, or infections (these may be very common side effects that may affect more than 1 in 10 people)
• treatment with Imuran in combination with another immunosuppressant may cause a viral infection that damages the brain. This can cause headaches, changes in behavior, speech disorders, impaired abilities, such as memory, attention, and decision-making (cognitive impairment), and can lead to death (a condition known as progressive multifocal leukoencephalopathy associated with the JC virus) (this may be a very rare side effect that may affect up to 1 in 10,000 people).

The patient should immediately consult their doctor or specialist, as they may need immediate medical attention, if they experience any of the following severe side effects:

• high fever or other signs of infection, such as: sore throat, mouth ulcers, urinary tract problems, or chest infection causing shortness of breath and cough (these may be very common side effects that may affect more than 1 in 10 people)
• liver problems, which can cause yellowing of the skin or whites of the eyes (jaundice) (these may be uncommon side effects that may affect up to 1 in 100 people)
• various types of cancer, including blood, lymphatic system, and skin cancers (see section 2 "Warnings and precautions") (these may be rare side effects that may affect up to 1 in 1,000 people)
• rash (raised, red, pink, or purple bumps that are painful to the touch), especially on the arms, hands, fingers, face, and neck, with accompanying fever (Sweet's syndrome, also known as acute febrile neutrophilic dermatosis). The frequency of these side effects is unknown (cannot be estimated from the available data).
• a specific type of lymphoma ( hepatosplenic T-cell lymphoma). This can cause nosebleeds, fatigue, excessive sweating at night, weight loss, and unexplained fever (the frequency of these side effects is unknown - cannot be estimated from the available data).

If the patient experiences any of the above side effects, they should immediately stop taking Imuran and consult their doctor.

Other side effects:

Very common (may affect more than 1 in 10 people):

• low white blood cell count visible in blood tests, which can cause infection

Common (may affect up to 1 in 10 people):

• nausea

Uncommon (may affect up to 1 in 100 people):

• anemia (low red blood cell count)
• cholestasis of pregnancy, which can cause severe itching, especially on the palms and soles.
• pancreatitis, which can cause severe abdominal pain

Rare (may affect up to 1 in 1,000 people):

• hair loss during treatment with Imuran. Hair usually grows back, even if the patient continues to take Imuran. If the patient has any doubts, they should consult their doctor

Very rare (may affect up to 1 in 10,000 people):

• gastrointestinal disorders leading to diarrhea, abdominal pain, constipation, nausea, and vomiting (intestinal perforation)

Frequency not known (frequency cannot be estimated from the available data):

• photosensitivity (increased sensitivity to light or sunlight)
• pellagra [vitamin B (niacin) deficiency] associated with pigmented rash, diarrhea, or memory loss
• severe liver damage, which can be life-threatening, especially in patients undergoing long-term treatment (e.g., liver injury, non-cirrhotic portal hypertension, portal and sinusoidal vein disease). If the patient experiences any of the following symptoms, they should tell their doctor: yellowing of the skin and whites of the eyes (jaundice), easy bruising, discomfort in the abdomen, loss of appetite, fatigue, nausea, or vomiting.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be gathered on the safety of this medicine.

5. How to store Imuran

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month.
Store at a temperature not exceeding 25°C. Protect from light.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Imuran contains

• The active substance of Imuran is azathioprine. Each tablet contains 25 mg or 50 mg of azathioprine.
• The other ingredients are: lactose monohydrate, cornstarch, pregelatinized starch, stearic acid, magnesium stearate, hypromellose, macrogol 400; Imuran 25 mg tablets also contain titanium dioxide (E171), yellow iron oxide (E172), and red iron oxide (E172).

What Imuran looks like and contents of the pack

Imuran 25 mg has the form of round, biconvex, coated tablets of orange color with the imprint "IM 2".
Imuran 50 mg has the form of round, biconvex, coated tablets of yellow color with the imprint "IM 5".
The packaging contains 100 tablets in blisters in a cardboard box.

Manufacturer

EXCELLA GmbH & Co. KG
Nürnberger Strasse 12
90537 Feucht
Germany

Manufacturer/Importer

Aspen Bad Oldesloe GmbH
Industriestrasse 32-36
23843 Bad Oldesloe
Germany

Date of last revision of the leaflet: 02/2025

Marketing authorization holder

Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24, Ireland
Tel: 008001 211 566