Package Leaflet: Information for the User

Imurel 50 mg Film-Coated Tablets

Azathioprine

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Imurel is and what it is used for

2. What you need to know before you start taking Imurel

3. How to take Imurel

4. Possible side effects

5. Storage of Imurel

6. Contents of the pack and additional information

Imurel is a medication with immunosuppressive activity, which means it reduces the activity of the immune system.

Your doctor will prescribe it:

1.- Alone or in combination with other medications, for the prevention of rejection in patients who have received an organ transplant, such as kidney, heart, and liver transplants.

2.- For the treatment of moderate to severe inflammatory bowel disease (ulcerative colitis and Crohn's disease).

3.- For the treatment of certain types of multiple sclerosis (clinically defined relapsing-remitting).

4.- For severe forms of autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis, chronic active autoimmune hepatitis, pemphigus vulgaris, polyarteritis nodosa, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and gangrenous pyoderma).

Do not take Imurel

• If you are allergic to azathioprine, mercaptopurine, or any of the other components of this medication (listed in section6). Allergic reactions include skin rash, itching, difficulty breathing, and swelling of the face, lips, throat, or tongue,
• If you have a severe infection,
• If you have a severe liver or bone marrow disorder,
• If you have pancreatitis (inflammation of the pancreas),
• If you have recently been vaccinated with live vaccines, for example, against smallpox or yellow fever,

• If you are pregnant (unless your doctor tells you to),
• If you are breastfeeding.

Inform your doctor or pharmacist if you have ever had to stop taking this medication due to an allergy or any other problem.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Imurel:

• If you have any kidney or liver problems.

• If your body synthesizes a low amount of the enzyme thiopurine methyltransferase (TPMT) or produces it defectively.It is recommended to evaluate the enzymatic activity of TPMT before starting treatment.

• If you have a deficiency of hypoxanthine-guanine phosphoribosyltransferase (Lesch-Nyhan syndrome).

• If you have had hepatitis B.

• If you have had chickenpox or shingles. The infection can become severe in patients taking immunosuppressive medications. Avoid contact with anyone who has chickenpox or shingles. Consult your doctor if you come into contact with someone who has one of these infections.

• If you are going to be vaccinated, consult your doctor before doing so. Imurel may affect the activity of the vaccine or your response to it.

• If you are being treated with Imurel, you should be adequately monitored by your doctor while taking this medication.

• If you are taking Imurel and observe any evidence of infection, unexpected bleeding, or any other circulatory problem, inform your doctor immediately.

Some patients taking Imurel in combination with other immunosuppressive agents have developed a severe infection (progressive multifocal leukoencephalopathy) caused by a virus known as the JC virus. If you have any symptoms of infection, consult your doctor.

Patients undergoing treatment with immunosuppressive medications may have a higher risk of developing cancer, especially non-Hodgkin's lymphoma, sarcoma (e.g., Kaposi's and others), local cancer in the uterus, and skin cancer. The risk is related to the intensity and duration of treatment rather than the use of a specific medication.Avoid excessive exposure to sunlight, wear protective clothing, and use high-factor sunscreens.

If you are receiving immunosuppressive treatment, taking Imurel may also increase your risk of lymphoproliferative disorders:

• Treatment with Imurel increases your risk of developing a type of cancer called lymphoproliferative disorder. With a treatment that includes multiple immunosuppressants (including thiopurines), this can be fatal.
• The combination of multiple immunosuppressants, administered simultaneously, increases the risk of lymphatic system disorders due to viral infection (Epstein-Barr virus-associated lymphoproliferative disorders).

Taking Imurel may increase your risk of developing 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.

Some patients with inflammatory bowel disease treated with Imurel and anti-TNF medications have developed a severe type of lymphoma that can be fatal.

Consult your doctor, even if any of the above circumstances have occurred at any time.

If the coated tablet has to be split in half, avoid skin contact with the powder from the tablet or the broken area.

Blood tests:

You will need to have a blood test once a week for the first eight weeks of treatment. You may need more frequent blood tests if:

•You are elderly,

•You are taking a high dose,

•You have liver or kidney problems,

•You have bone marrow problems,

•You have an overactive spleen (hypersplenism),

•You are taking certain medications, such as:

•ACE inhibitors (treatments for high blood pressure or heart failure),

•Trimethoprim/sulfamethoxazole (antibiotic),

•Cimetidine (treatment for stomach ulcers and indigestion),

•Indomethacin (anti-inflammatory medication).

It is essential to use a reliable contraceptive method (such as condoms) because azathioprine can cause birth defects when taken by men or women.

Liver damage:

Treatment with Imurel may affect the liver, and your doctor will monitor your liver function regularly. Inform your doctor if you experience symptoms of liver damage (see section 4 "Possible side effects").

Warning:

Discontinuing azathioprine treatment should be done under strict supervision. Consult your doctor.

Imurel with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription.

Imurel 50 mg coated tablets may affect blood cells, so you may need blood tests while taking the medication. As treatment progresses, the frequency of these tests may be reduced. Other medications can also affect blood cells, and the effect may be increased if taken with Imurel 50 mg coated tablets. Inform your doctor if you are taking any of the following medications:

• Methotrexate (used primarily in cancer treatment).
• Penicillamine (used primarily in the treatment of rheumatoid arthritis).
• ACE inhibitors (medications used primarily in the treatment of high blood pressure and heart failure).
• Cimetidine (used primarily in the treatment of stomach ulcers and indigestion).
• Indomethacin (used primarily to relieve pain and inflammation).
• Cotrimoxazole (used in the treatment of infections).

The following medications may interact with Imurel50 mgcoated tablets. Inform your doctor if you are taking any of them:

• Vaccines (used to prevent diseases).
• Ribavirin (used to treat viral infections).
• Alopurinol/oxipurinol/tiopurinol or other xanthine oxidase inhibitors such as febuxostat (used primarily in the treatment of gout).
• Anticoagulants such as acenocoumarol or warfarin (used to prevent blood clots).
• Olsalazine, mesalazine, or sulfasalazine (used primarily in the treatment of ulcerative colitis).
• Relaxants such as curare, d-tubocurarine, pancuronium, or suxamethonium.
• Furosemide (may be used to reduce inflammation due to excess fluids).
• Other immunosuppressants such as cyclosporine or tacrolimus.
• Infliximab (treatment for Crohn's disease).
• Inform the anesthesiologist if you are taking azathioprine before undergoing surgery, as muscle relaxants used during anesthesia may interact with azathioprine.

Pregnancy, lactation, and fertility

If you are pregnant, do not take azathioprine unless your doctor tells you to. Inform your doctor if you are pregnant or suspect you may be. All fertile patients, both men and women, should use a different contraceptive method (such as the copper IUD or hormonal IUD). You should continue using a contraceptive method for three months after completing azathioprine treatment.

Do not breastfeed during treatment with azathioprine, as the metabolic products produced in the body pass into breast milk and may harm your baby.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

You can drive and use machines safely during treatment with azathioprine unless you feel dizzy. Dizziness may increase if you take alcohol. Do not drive or use machines if you have consumed alcohol.

Imurel contains lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will indicate the duration of your treatment with Imurel. Do not discontinue treatment before.

If you estimate that the action of Imurel is too strong or too weak, inform your doctor or pharmacist.

The recommended dose is:

Recommended dose in adults and children:

In transplants:initial dose of 5 mg/kg/day on the first day of treatment. The maintenance dose should be in the range of 1-4 mg/kg/day.

When oral administration is not possible, administer a dose of 1-2.5 mg/kg/day intravenously.

In inflammatory bowel disease:dose within the range of 2-3 mg/kg/day for at least 12 months since the response may not be apparent until 3-4 months after starting treatment.

In multiple sclerosis:the usual dose is 2.5 mg/kg/day administered in one to three doses. Treatment should continue for a minimum of one year. Treatment can be discontinued after five years without new relapses or worsening of the disease. Multiple sclerosis is not a common disease in children, therefore, Imurel 50 mg tablets are not recommended for use in children with this disease.

In chronic active hepatitis:dose of 1-1.5 mg/kg/day.

In other processes:initial dose 2-2.5 mg/kg/day.

Patients with liver or kidney problems::

In these patients, consider reducing the dose. Patients with severe liver problems should not take this medication (see section 2. Do not take Imurel).

Patients over 65 years::

It is possible that elderly patients may need a reduced dose.

Administration form:

This medication is taken orally.

Tablets should not be divided, they must be swallowed whole with at least one glass of liquid (200 ml). It is recommended to administer Imurel tablets during meals to avoid gastrointestinal discomfort.

If you take more Imurel than you should:

It is very important to follow the dose indicated by your doctor.

In case of ingesting a much larger amount than indicated, see your doctor immediately or contact the nearest hospital emergency service. Bring this leaflet with you.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 915 620 420, indicating the medication and the amount ingested.

If you forgot to take Imurel:

Do not take a double dose to compensate for the missed doses. Take the next dose when it is due and inform your doctor about the doses that you may have missed.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can have side effects, although not everyone will experience them.

Infections and infestations:

Very common (affects more than 1 in 10 patients): infections caused by viruses, bacteria, and fungi in transplant recipients being treated with Imurel 50 mg tablets, either alone or in combination with other immunosuppressants, especially corticosteroids.

Uncommon (affects between 1 and 10 in every 1,000 patients): infections caused by viruses, bacteria, and fungi in other patient groups. Reactivation of hepatitis B, varicella-zoster virus, and other infectious agents.

Very rare (affects less than 1 in 10,000 patients): infection caused by the JC virus and associated with a disease called progressive multifocal leukoencephalopathy, in patients treated with Imurel in combination with other immunosuppressants.

Malignant, benign, and unspecified neoplasms (including cysts and polyps):

Rare (affects between 1 and 10 in every 10,000 patients): various tumors, skin cancer, sarcomas (Kaposi's or other), cervical cancer, leukemia. Inform your doctor if new skin marks appear or if existing marks change.

Very rare (affects less than 1 in 10,000 patients): lymphoma (a type of blood cancer).

Blood and lymphatic system disorders:

Very common (affects more than 1 in 10 patients): bone marrow disorders; decreased white blood cells.

Common (affects between 1 and 10 in every 100 patients): decreased platelets.

Uncommon (affects between 1 and 10 in every 1,000 patients): anemia.

Rare (affects between 1 and 10 in every 10,000 patients): other blood disorders (agranulocytosis, pancytopenia, megaloblastic anemia, aplastic anemia, erythroid hypoplasia).

Very rare (affects less than 1 in 10,000 patients): hemolytic anemia, eosinophilia, cases of histiocytosis associated with viruses (CMV, VEB) have been described after the use of azathioprine.

Immune system disorders:

Uncommon (affects between 1 and 10 in every 1,000 patients): allergic reactions that may include the following signs: skin redness, skin nodules, or skin rash (including blisters, itching, or skin peeling).

Very rare (affects less than 1 in 10,000 patients): severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis), anaphylactic reaction, and Sweet syndrome.

Frequency unknown (cannot be estimated from available data): drug hypersensitivity reaction with eosinophilia and systemic symptoms (DRESS).

After administration of Imurel film-coated tablets, clinical manifestations have been described as a consequence of allergic reactions: discomfort, dizziness, nausea, vomiting, diarrhea, fever, numbness, rashes, vasculitis (inflammation of blood vessels), muscle and joint pain, liver and kidney disorders, and hypotension (low blood pressure). If you experience any of these symptoms shortly after taking Imurel 50 mg film-coated tablets, stop taking the medicine and consult your doctor immediately or go to the nearest hospital emergency department.

Nervous system disorders::

Very rare (affects less than 1 in 10,000 patients): worsening of myasthenia gravis (may cause myasthenic crisis), paresthesia, polyneuritis.

Cardiac disorders::

Very rare (affects less than 1 in 10,000 patients): atrial fibrillation.

Respiratory, thoracic, and mediastinal disorders::

Very rare (affects less than 1 in 10,000 patients): reversible pneumonitis (inflammation of lung tissue), alveolitis. Inform your doctor if you develop a cough or difficulty breathing similar to a lung infection.

Gastrointestinal disorders::

Common (affects between 1 and 10 in every 100 patients): nausea in patients taking it for the first time, which can be prevented by taking the tablets after meals. Anorexia with occasional vomiting.

Uncommon (affects between 1 and 10 in every 1,000 patients): pancreatitis (inflammation of the pancreas), especially in renal transplant patients and those with inflammatory bowel disease and diarrhea.

Very rare (affects less than 1 in 10,000 patients): colitis (inflammation of the colon), diverticulitis (inflammation of certain areas of the colon), and intestinal perforation in transplant patients being treated with immunosuppressants and corticosteroids, and severe diarrhea in patients with inflammatory bowel disease.

Hepatobiliary disorders::

Uncommon (affects between 1 and 10 in every 1,000 patients): cholestasis (bile flow disorder, usually caused by obstruction) and liver function deterioration, which disappears when treatment is discontinued.

Rare (affects between 1 and 10 in every 10,000 patients): severe liver damage.

Frequency unknown (cannot be estimated from available data): potentially fatal severe liver damage, especially in patients receiving long-term treatment (such as liver damage, non-cirrhotic portal hypertension, or portosinusoidal vascular disease). Inform your doctor if you experience any of the following symptoms: yellowing of the skin and eyes (jaundice), easy bruising, abdominal discomfort, loss of appetite, fatigue, nausea, or vomiting.

Skin and subcutaneous tissue disorders:

Rare (affects between 1 and 10 in every 10,000 patients): hair loss, which usually resolves spontaneously despite continued treatment.

Frequency unknown (cannot be estimated from available data): acute generalized pustular exanthema (PEAG). It may present with a skin rash (red, pink, or purple bumps that are painful to the touch), especially on your arms, hands, fingers, face, and neck, which may also be accompanied by fever (Sweet syndrome, also known as acute febrile neutrophilic dermatosis).

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above25ºC. Store in the original packaging to protect it from light.

Expiration Date

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash.Deposit the packaging and medications you no longer need at the SIGRE collection pointat the pharmacy.If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longerneed.By doing so, you will help protect the environment.

Composition of Imurel:

• The active ingredient is azathioprine. Each film-coated tablet contains 50 mg of azathioprine.
• The other components (excipients) are:

Core: lactose monohydrate, cornstarch, pregelatinized cornstarch, magnesium stearate, stearic acid, and purified water.

Coating: hypromellose, macrogol 400, and purified water.

Appearance of the product and content of the packaging

Imurel are film-coated tablets, yellow in color, round, biconvex, scored, and with the mark “GX CH1” engraved on one face. The score should not be used to split the tablet.

Each package contains 50 film-coated tablets.

Marketing authorization holder

TEOFARMA S.r.l.

Via F.lli Cervi, 8

27010 Valle Salimbene

Pavia – Italy

Responsible for manufacturing

Excella GmbH & Co. KG

Nürnberger Strasse 12

90537 Feucht.

Germany

or

LABORATOIRES BTT

ZI de Krafft

67150 Erstein.

France

Last review date of this leaflet: March 2025

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/