Imuran

Package leaflet: Information for the patient

Imuran, 25 mg, coated tablets
Imuran, 50 mg, coated tablets
Azathioprine
Please read carefully the entire leaflet before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

1. What Imuran is and what it is 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 pack and other information

1. What Imuran is and what it is used for

Imuran contains azathioprine as the active substance. It belongs to a group of medicines called immunosuppressants, which reduce the activity of the immune system.
Imuran may be used to help the body accept a transplanted organ (such as a new kidney, heart, or liver) or in the treatment of certain diseases in which the immune system attacks the body itself (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 joint stiffness)
• 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, joint stiffness, and pain)
• dermatomyositis and/or polymyositis (a group of diseases causing inflammation of the muscles, muscle weakness, and skin rash)
• autoimmune chronic active hepatitis (a disease in which the immune system attacks liver cells, causing liver inflammation, fatigue, muscle pain, jaundice, and fever)
• pemphigus vulgaris (a disease in which the immune system attacks skin cells, leading to blister formation on the skin, in the mouth, nose, throat, and genital organs)
• polyarteritis nodosa (a rare disease causing inflammation of blood vessels)
• autoimmune haemolytic anaemia (a serious blood disorder in which the body destroys red blood cells faster than they are produced, leading to weakness and shortness of breath)
• chronic idiopathic thrombocytopenic purpura resistant to treatment (a condition in which the number of blood platelets is low, which may lead to easy or excessive bruising and bleeding)

Imuran may also be used in the treatment of inflammatory bowel disease (Crohn's disease or ulcerative colitis).
Your doctor has chosen this medicine because it is appropriate for you and your condition.
Imuran may be used alone, but more often it is used in combination with other medicines.

2. Important Information Before Using Imuran

When not to use Imuran:

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

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

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

Liver damage
Treatment with Imuran may affect the liver. The doctor will regularly monitor liver function. If the patient develops symptoms of liver damage, they should inform the doctor (see section 4 "Possible side effects").
NUDT15 gene mutation
If the patient has a congenital mutation in the NUDT15 gene (a gene responsible for the breakdown of Imuran in the body), they are at increased risk of infections and hair loss, so the doctor may decide to reduce the dose.
If in doubt whether any of the above situations apply, consult a doctor, nurse, or pharmacist before starting treatment with Imuran.
While taking Imuran, the doctor will perform regular blood tests to detect any changes (see section 3 "How to take Imuran"). The frequency of blood testing usually decreases over time during treatment with Imuran.
The doctor may also perform genetic testing [i.e. test for TPMT and/or NUDT15 genes] before or during treatment to determine whether the patient's genes may affect their response to this medicine. The doctor may adjust the dose of Imuran based on the results of these tests.
If the patient is receiving immunosuppressive medicines, taking Imuran may increase the risk of:

• developing tumours, including skin cancer. Therefore, during treatment with Imuran, avoid excessive sun exposure, wear protective clothing, and use high-protection-factor sunscreen creams.
• lymphoproliferative disorders – treatment with Imuran increases the risk of developing a type of tumour called a lymphoproliferative disorder. In treatment regimens involving multiple immunosuppressive medicines (including thiopurines), this may lead to death. Concurrent use of multiple immunosuppressive medicines increases the risk of lymphatic system disorders caused by viral infection [Epstein-Barr virus (EBV)-related lymphoproliferative disorders].
• a serious 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 infection with chickenpox or shingles. Therefore, during treatment with Imuran, avoid contact with people who have chickenpox or shingles.
• reactivation of pre-existing hepatitis B virus infection,
• other infections, such as PML (progressive multifocal leukoencephalopathy), which is an opportunistic infection. If any signs of infection occur, contact the doctor (see section 4 "Possible side effects").

Niacin (vitamin B3) deficiency (pellagra)
Contact the doctor immediately if the patient develops diarrhoea, pigmented skin rash, memory impairment, logical thinking or other cognitive difficulties, as these symptoms may indicate niacin (nicotinic acid) deficiency (pellagra).
Imuran with other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take. This is because Imuran may affect the action of other medicines, and other medicines may affect the action of Imuran.
In particular, inform the doctor if the patient is taking or planning to take:

• ribavirin (a medicine used to treat viral infections)
• methotrexate (a medicine mainly used in the treatment of cancers)
• allopurinol, oxypurinol, thiopurinol, or other xanthine oxidase inhibitors such as febuxostat (medicines mainly used to treat gout)
• penicillamine (a medicine mainly used to treat rheumatoid arthritis)
• angiotensin-converting enzyme (ACE) inhibitors (medicines mainly used to treat high blood pressure and heart failure)
• anticoagulants such as warfarin or acenocoumarol (medicines that prevent blood clots)
• cimetidine (a medicine used to treat peptic ulcer disease and indigestion)
• indometacin (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 mainly used to treat ulcerative colitis and Crohn's disease)
• co-trimoxazole (an antibiotic used to treat bacterial infections)
• infliximab (a medicine mainly used 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 the anaesthetist before surgery, as muscle relaxants used during anaesthesia may interact with azathioprine.
If the patient is unsure whether they are taking any of the listed medicines, they should consult a doctor or pharmacist before using Imuran.
Vaccination during treatment with Imuran
If the patient is due to receive a vaccine, they should discuss this with their doctor or nurse.
If the patient is taking Imuran, they should not receive a "live" vaccine (e.g. vaccines against influenza, measles, BCG vaccine, etc.) until the doctor considers it safe.
This is because certain vaccines may cause infection if administered 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, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
Pregnancy
The patient (or her partner) must use an effective method of contraception during treatment with Imuran.
If intense itching without rash occurs during pregnancy, contact the doctor immediately. Nausea and loss of appetite may also occur along with itching, indicating a condition called intrahepatic cholestasis of pregnancy (a liver disease occurring during pregnancy). This condition may harm the unborn child.
If the patient is pregnant, the doctor will carefully assess whether she should take this medicine, weighing the benefits against the risks of treatment.
Breastfeeding
Imuran passes into human milk in small amounts. Women should not breastfeed while taking Imuran unless the expected benefits of breastfeeding for the child outweigh the possible risks. Consult a doctor before starting breastfeeding.
Fertility
The effect of Imuran on fertility is unknown.
Driving and operating machinery
It is not known that Imuran affects the ability to drive or operate machinery. However, if the patient experiences any adverse reactions after taking the medicine, they may be unable to drive or operate machinery.
Imuran contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking the medicine.

3. How to take Imuran

This medicine should always be taken exactly as directed by your doctor or pharmacist. If you are unsure,
you should consult your doctor or pharmacist.
The amount of Imuran you take may vary from patient to patient. The dose depends on the condition being treated and is determined by your doctor.
Imuran may be taken with food or on an empty stomach, but the chosen method of administration should be consistent each day. Some patients may experience nausea when first taking Imuran. Taking the tablets with food may help relieve these symptoms.

• While taking Imuran, your doctor will perform regular blood tests. These are intended to monitor the number and types of blood cells and to ensure that your liver is functioning properly.
• Your doctor may also order other blood and urine tests to monitor kidney function and to 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 may damage the kidneys.

Your doctor may adjust your dose of Imuran based on the results of these tests.
Tablets should be swallowed whole. Do not chew, divide, or crush the tablets.
It is important that caregivers are aware of the need to handle this medicine safely.
If a patient or caregiver comes into contact with damaged tablets, hands should be washed immediately. For advice, consult your doctor or pharmacist.
Recommended dose:
Adults after organ transplantation: The usual initial dose is up to 5 mg per kilogram of body weight on the first day, followed by a maintenance dose of usually 1 to 3 mg per kilogram of body weight per day. During treatment, your doctor will adjust the dose according to your body's response to the medicine.
Adults with other diseases: The usual starting dose is 1 to 3 mg per kilogram of body weight, followed by a maintenance dose of usually 1 to 3 mg per kilogram of body weight per day. During treatment, your doctor will adjust the dose according to your body's response to the medicine.
A lower dose may be necessary for elderly patients.
A lower dose may also be required in patients with impaired kidney or liver function.
Use in children
Children after organ transplantation: Dosing in children after organ transplantation is the same as in adults.
Children with other diseases: Dosing in children with other diseases is the same as in adults.
Children who are overweight may require a higher dose.
Taking more Imuran than recommended
If too many tablets are taken, contact your doctor or pharmacist immediately.
Missing a dose of Imuran
Do not take a double dose to make up for a missed dose. Inform your doctor if a dose is missed.
If it is almost time for the next dose, skip the missed dose and take the next dose at the usual time. Otherwise, take the missed dose as soon as you remember, then return to your regular dosing schedule.
Stopping Imuran
Before stopping Imuran, consult your doctor or pharmacist. Do not discontinue taking Imuran unless your doctor considers it safe to do so.
If you have any further questions about the use of this medicine,
consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
The following adverse reactions may occur after taking Imuran:

Discontinue taking Imuran and seek immediate medical attention if
the patient experiences any of the following serious adverse reactions, as
immediate medical intervention may be required:

• Hypersensitivity reactions (this is an uncommon adverse reaction affecting up to 1 in 100 patients), with symptoms such as: general fatigue, dizziness, nausea, vomiting, diarrhoea or abdominal pain; swelling of the eyelids, face or lips; skin redness, skin nodules or skin rash (including blistering, itching or peeling of the skin); muscle or joint pain; sudden wheezing, cough or difficulty breathing; chest pain, shortness of breath or leg swelling (heart function disorders)
• Reversible cerebral edema with symptoms such as severe headache, visual disturbances, seizures, disorientation and decreased level of consciousness, with or without high blood pressure [posterior reversible encephalopathy syndrome (PRES)]. In rare cases, these reactions may be life-threatening (this is a very rare adverse reaction affecting up to 1 in 10,000 patients)
• Skin rash or skin redness which may progress to life-threatening skin reactions, including widespread rash with blisters and peeling of the epidermis, particularly affecting the area around the mouth, nose, eyes and genital organs (Stevens-Johnson syndrome), or extensive peeling of the skin (toxic epidermal necrolysis) (these may be very rare adverse reactions affecting up to 1 in 10,000 patients)
• Transient lung inflammation (causing shortness of breath, cough and fever) (this may be a very rare adverse reaction affecting up to 1 in 10,000 patients)
• Problems with blood or bone marrow; symptoms include weakness, fatigue, pallor, easy bruising, unusual bleeding or infections (these may be very common adverse reactions affecting more than 1 in 10 patients)
• Use of Imuran in combination with another immunosuppressive medicine may lead to infection with a virus that damages the brain. This may cause headaches, changes in behaviour, speech disturbances, worsening of cognitive abilities such as memory, attention and decision-making (cognitive impairment), and may lead to death (a condition known as progressive multifocal leukoencephalopathy associated with JC virus) (this may be a very rare adverse reaction affecting up to 1 in 10,000 patients)

Contact your treating physician or specialist immediately,
as the patient may require immediate medical attention if any of the following serious
adverse reactions occur:

• High temperature (fever) or other signs of infection such as: sore throat, mouth pain, urinary tract symptoms or infection within the chest causing shortness of breath and cough (these may be very common adverse reactions affecting more than 1 in 10 patients)
• Liver problems, which may cause yellowing of the skin or whites of the eyes (jaundice) (these may be uncommon adverse reactions affecting up to 1 in 100 patients)
• Various types of tumours, including blood, lymphatic system and skin cancers (see section 2 "Warnings and precautions") (these may be rare adverse reactions affecting up to 1 in 1,000 patients)
• Rash (raised, red, pink or purple painful lumps), particularly on arms, hands, fingers, face and neck, occurring together with fever (Sweet's syndrome, also known as acute febrile neutrophilic dermatosis). The frequency of these adverse reactions is unknown (cannot be estimated from available data)
• A specific type of lymphoma (hepatosplenic T-cell lymphoma). Symptoms may include nosebleeds, fatigue, excessive night sweats, weight loss and unexplained fever (high temperature) (frequency of these adverse reactions is unknown - cannot be estimated from available data)

If any of the above adverse reactions occur, Imuran should be discontinued immediately and medical advice sought.

Other adverse reactions:
Very common (may affect more than 1 in 10 patients):

• Low white blood cell count seen in blood tests, which may lead to infection

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

• Nausea

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

• Anaemia (low red blood cell count)
• Cholestatic jaundice, which may cause intense itching, especially on palms and soles
• Pancreatitis, which may cause severe upper abdominal pain

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

• Hair loss during treatment with Imuran. Hair usually regrows, even if Imuran treatment continues. Patients should consult their doctor if in doubt

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

• Intestinal disorders leading to diarrhoea, abdominal pain, constipation, nausea and vomiting (intestinal perforation)

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

• Photosensitivity (hypersensitivity to light or sunlight)
• Vitamin B3 deficiency (pellagra) associated with pigmented skin rash, diarrhoea and disturbances in memory, logical thinking and other cognitive functions
• Severe, potentially life-threatening liver damage, particularly in patients undergoing long-term treatment (e.g. liver injury, non-cirrhotic portal hypertension, vascular liver disease and sinusoidal obstruction). If the patient experiences any of the following symptoms, they should inform their doctor: yellowing of the skin and whites of the eyes (jaundice), easy bruising, abdominal discomfort, loss of appetite, fatigue, nausea or vomiting
• Parotitis (inflammation of the salivary gland)
• Tremor

Reporting of adverse reactions
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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-, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Imuran

Keep this medicine out of the 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 stated month.
Store at a temperature not exceeding 25 °C. Protect from light.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Package contents and other information

What Imuran contains

• The active substance is azathioprine. Each tablet contains either 25 mg or 50 mg of azathioprine.
• The other ingredients are: monohydrate lactose, corn starch, pregelatinized starch, stearic acid, magnesium stearate, hypromellose, polyethylene glycol 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 is an orange, film-coated, round, biconvex tablet, embossed with the mark "IM 2".
Imuran 50 mg is a yellow, film-coated, round, biconvex tablet, embossed with the mark "IM 5".
Packaging contains 100 tablets in blister packs within a cardboard box.

Marketing Authorisation Holder Manufacturer
Aspen Pharma Trading Limited EXCELLA GmbH & Co. KG
3016 Lake Drive Nürnberger Strasse 12
Citywest Business Campus 90537 Feucht
Dublin 24, Ireland Germany
Tel: 008001 211 566

Manufacturer/Importer
Aspen Bad Oldesloe GmbH
Industriestrasse 32-36
23843 Bad Oldesloe
Germany