IMUREL 50 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Imurel 50 mg Film-Coated Tablets

Azathioprine

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Imurel and what is it used for
2. What you need to know before you take Imurel
3. How to take Imurel
4. Possible side effects
5. Storing Imurel
6. Contents of the pack and other information

1. What is Imurel and what is it used for

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

Your doctor will prescribe it to you:

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

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

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

4. For severe forms of immune 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 pyoderma gangrenosum).

2. What you need to know before you take Imurel

Do not take Imurel

• if you are allergic to azathioprine, mercaptopurine, or any of the other ingredients of this medicine (listed in section 6). 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 been recently vaccinated with live vaccines, such as against smallpox or yellow fever,

• if you are pregnant (unless your doctor tells you to),
• if you are breast-feeding.

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

Warnings and Precautions

Consult your doctor or pharmacist before starting Imurel:

• If you have any kidney or liver problems.

• If your body produces a low amount of the enzyme thiopurine methyltransferase (TPMT) or produces it with a defect. 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 herpes zoster. Chickenpox or herpes infection can become severe in patients taking immunosuppressive medicines. Therefore, avoid contact with anyone who has chickenpox or herpes. 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 a patient being treated with Imurel, you should be properly monitored by your doctor while you are taking this medicine.

• If you are being treated with Imurel and you notice any evidence of infection, unexpected bruising, bleeding, or any other circulatory problem, you should inform your doctor immediately.

Some patients being treated with Imurel in combination with other immunosuppressive agents have developed an 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 immunodepressive medicines may have a higher risk of developing cancer, especially non-Hodgkin's lymphoma, sarcoma (e.g., Kaposi's sarcoma 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 medicine. Avoid excessive exposure to sunlight, wear protective clothing, and use sunscreens with a high protection factor.

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

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

Taking Imurel may increase your risk of developing 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.

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

Consult your doctor, even if any of the above circumstances have occurred to you in the past.

If the film-coated tablet needs to be broken in half, avoid skin contact with the powder of 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 to have blood tests more frequently if you:

• are elderly,
• are taking a high dose,
• have a liver or kidney disorder,
• have a bone marrow disorder,
• have an overactive spleen (hypersplenism),
• are being treated with certain medicines, such as:
• ACE inhibitors (used mainly to treat high blood pressure and heart failure),
• trimethoprim/sulfamethoxazole (cotrimoxazole) (antibiotic),
• cimetidine (used mainly to treat stomach ulcers and indigestion),
• indomethacin (anti-rheumatic medicine).

It is important that you use an effective contraceptive method (such as condoms), as azathioprine can cause birth defects when taken by men or women.

Liver damage

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

Warning:

Discontinuation of treatment with azathioprine should be done under strict medical supervision. Consult your doctor.

Taking Imurel with other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

Treatment with Imurel 50 mg film-coated tablets may affect your blood cells, so while you are taking this medicine, you may have blood tests. As treatment progresses, the frequency of these tests may be reduced. There are other medicines that also affect the blood, and the effect may increase if taken with Imurel 50 mg film-coated tablets. You should tell your doctor if you are taking any of the following medicines:

• Methotrexate (used mainly to treat cancer).
• Penicillamine (used mainly to treat rheumatoid arthritis).
• ACE inhibitors (used mainly to treat high blood pressure and heart failure).
• Cimetidine (used mainly to treat stomach ulcers and indigestion).
• Indomethacin (used mainly to relieve pain and inflammation).
• Cotrimoxazole (used to treat infections).

The following medicines may interact with Imurel 50 mg film-coated tablets. Tell your doctor if you are taking any of them:

• Vaccines (used to prevent diseases).
• Ribavirin (used to treat viral infections).
• Allopurinol/oxypurinol/thiopurinol or other xanthine oxidase inhibitors such as febuxostat (used mainly to treat gout).
• Anticoagulants such as acenocoumarol or warfarin (used to prevent blood clots).
• Olsalazine, mesalazine, or sulfasalazine (used mainly to treat ulcerative colitis).
• Muscle relaxants such as curare, d-tubocurarine, pancuronium, or suxamethonium.
• Furosemide (may be used to reduce inflammation due to excess fluid).
• Other immunodepressants such as cyclosporine or tacrolimus.
• Infliximab (treatment for Crohn's disease).
• Before undergoing surgery, inform the anesthesiologist that you are taking azathioprine, as the muscle relaxants used during anesthesia may interact with azathioprine.

Pregnancy, breast-feeding, and fertility

If you are pregnant, you should not take azathioprine unless your doctor tells you to. Tell your doctor if you are pregnant or think you may be pregnant. All patients of childbearing age, both men and women, should use a contraceptive method other than an intrauterine device (such as a copper or hormonal IUD). You should continue to use a contraceptive method for three months after stopping treatment with azathioprine.

You should not breast-feed while taking azathioprine, as the metabolic products produced in the body pass into breast milk and may harm your child.

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You can drive and use machines safely while taking azathioprine, unless you feel dizzy. Dizziness can increase if you drink alcohol. Do not drive or use machines if you have consumed alcohol.

Imurel contains lactose

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

3. How to take Imurel

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Your doctor will tell you how long to take Imurel. Do not stop treatment before then.

If you think the effect of Imurel is too strong or too weak, tell 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 the oral route is not possible, a dose of 1-2.5 mg/kg/day will be administered intravenously.

In inflammatory bowel disease: dose within the range of 2-3 mg/kg/day for at least 12 months, as 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 be continued for at least one year. Treatment may be discontinued after five years without new relapses or worsening of the disease. Multiple sclerosis is not a common disease in children, so the use of Imurel 50 mg tablets is not recommended in children with this disease.

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

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

Patients with liver or kidney problems:

In these patients, a dose reduction should be considered. Patients with severe liver problems should not take this medicine (see section 2. Do not take Imurel).

Patients over 65 years of age:

It may be necessary to reduce the dose in elderly patients.

Method of administration:

This medicine is taken orally.

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

If you take more Imurel than you should

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

In case of ingestion of a much higher dose than indicated, go to your doctor immediately or contact the emergency department of the nearest hospital. Bring this leaflet with you.

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

If you forget to take Imurel

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them.

Infections and infestations:

Very frequent (affecting more than 1 in 10 patients): infections caused by viruses, bacteria, and fungi, in transplant recipients who are being treated with Imurel 50 mg film-coated tablets alone or in combination with other immunosuppressants, especially corticosteroids.

Uncommon (affecting 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 (affecting 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.

Benign, malignant, and unspecified neoplasms (including cysts and polyps):

Rare (affecting 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 you develop skin marks or if any of the marks you already have undergo changes.

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

Disorders of the blood and lymphatic system:

Very frequent (affecting more than 1 in 10 patients): bone marrow disorders; decrease in white blood cells.

Frequent (affecting between 1 and 10 in every 100 patients): decrease in platelets.

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

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

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

Disorders of the immune system:

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

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

Frequency not known (cannot be estimated from the 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, rash, 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 emergency department of the nearest hospital.

Disorders of the nervous system:

Very rare (affecting less than 1 in 10,000 patients): worsening of myasthenia gravis (up to producing myasthenic crisis), paresthesia, polyneuritis.

Cardiac disorders:

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

Respiratory, thoracic, and mediastinal disorders:

Very rare (affecting 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:

Frequent (affecting between 1 and 10 in every 100 patients): nausea, in patients who take it for the first time, which can be avoided by taking the tablets after meals. Anorexia with occasional vomiting.

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

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

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

Disorders of the skin and subcutaneous tissue:

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

Frequency not known (cannot be estimated from the available data): acute generalized exanthematous pustulosis (AGEP). It can present with a skin rash (red, pink, or purple bumps that are painful to the touch), especially on the arms, hands, fingers, face, and neck, which can also be accompanied by fever (Sweet's syndrome, also known as acute febrile neutrophilic dermatosis).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Imurel

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

Do not store above 25°C. Store in the original packaging to protect it from light.

Expiration Date

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

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

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, corn starch, pregelatinized corn starch, magnesium stearate, stearic acid, and purified water.

Coating: hypromellose, macrogol 400, and purified water.

Appearance of the Product and Package Contents

Imurel is a film-coated tablet, yellow in color, round, biconvex, scored, and marked with "GX CH1" on one side. The score line should not be used to divide 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

Manufacturer

Excella GmbH & Co. KG

Nürnberger Strasse 12

90537 Feucht.

Germany

or

LABORATOIRES BTT

ZI de Krafft

67150 Erstein.

France

Date of the Last Revision of this Prospectus: March 2025

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/