MERCAPTOPURINE ZENTIVA 50 mg TABLETS

Introduction

Package Leaflet: Information for the User

Mercaptopurine Zentiva 50 mg Tablets EFG

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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Mercaptopurine Zentiva tablets are and what they are used for
2. What you need to know before you take Mercaptopurine Zentiva tablets
3. How to take Mercaptopurine Zentiva tablets
4. Possible side effects
5. Storage of Mercaptopurine Zentiva tablets
6. Contents of the pack and other information

1. What Mercaptopurine Zentiva tablets are and what they are used for

This medicine contains the active substance mercaptopurine monohydrate, which belongs to a group of medicines called cytotoxics (also known as chemotherapy).

This medicine is used to treat blood cancer, leukemia in adults, adolescents, and children.

This medicine works by reducing the number of new blood cells produced by the body.

2. What you need to know before you take Mercaptopurine Zentiva tablets

Do not take Mercaptopurine Zentiva tablets:

If you are allergic to the active substance mercaptopurine monohydrate or to any of the other ingredients of this medicine listed in section 6.

Do not get vaccinatedwith the yellow fever vaccine while taking this medicine because it can be fatal.

Warnings and precautions

Talk to your doctor or pharmacist before starting this medicine if:

• you have recently been vaccinated or are going to be vaccinated.
• while taking this medicine, it is not recommended to receive live vaccines (such as flu, mumps, and BCG) until your doctor tells you to do so. This is because some vaccines can cause infection if given while taking mercaptopurine.
• you suffer from a disease that makes your body produce insufficient amounts of an enzyme called TPMT (thiopurine methyltransferase deficiency), as your doctor may need to adjust your dose.
• you are allergic to a medicine called azathioprine (also used to treat cancer).
• you have kidney or liver problems, as your doctor will need to check that your organs are working properly.
• you have a genetic disorder called Lesch-Nyhan syndrome.
• you plan to have a child. This applies to both men and women. This medicine can be harmful to sperm or eggs. You and your partner should use effective contraceptive methods to avoid pregnancy while taking this medicine. Both men and women should use effective contraception for at least 3 months after receiving the last dose of treatment.

If you are receiving immunosuppressive treatment, taking this medicine may increase your risk of:

• tumors, including skin cancer. Therefore, when taking this medicine, avoid excessive sun exposure, wear protective clothing, and use sunscreen with a high protection factor.

• lymphoproliferative disorders:

• treatment with this medicine increases your risk of having a type of cancer called lymphoproliferative disorder and other malignant tumors. With treatment containing multiple immunosuppressants (including thiopurines), this can be fatal.
• the combination of multiple immunosuppressants, given at the same time, increases the risk of lymphatic system disorders due to viral infection (Epstein-Barr virus-associated lymphoproliferative disorders).

Taking this medicine 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.

Blood tests

Treatment with this medicine may affect your bone marrow. This means that the number of white blood cells, platelets, and (less frequently) red blood cells in your blood may decrease. Your doctor will perform blood tests every day during the initial period of your treatment (induction) and at least weekly during the later period of your treatment (maintenance). This is to monitor the levels of these cells in your blood. If you stop taking the treatment soon enough, the levels of your blood cells will return to normal.

Liver function

Mercaptopurine is toxic to the liver. For this reason, your doctor will perform weekly liver function tests while you are taking this medicine. If you have pre-existing liver disease or are taking other medicines that may affect the liver, your doctor will perform tests more frequently. If you notice that the white part of your eyes or your skin turns yellow (jaundice), inform your doctor immediately, as it may be necessary to stop treatment immediately.

Vitamin B3 deficiency (pellagra)

Tell your doctor immediately if you experience diarrhea, pigmented rash (dermatitis), or decreased memory, reasoning, or other thinking abilities (dementia), as these symptoms may suggest a vitamin B3 deficiency. Your doctor may prescribe vitamin supplements (niacin/nicotinamide) to improve this condition.

Infections

When receiving treatment with this medicine, the risk of viral, fungal, and bacterial infections is higher, and these infections can be more severe. See also section 4.

Before starting treatment, tell your doctor if you have had chickenpox, shingles, or hepatitis B (a liver disease caused by a virus). If you think you have an infection, tell your doctor immediately.

Mutation of the NUDT15 gene

If you have an inherited mutation in the NUDT15 gene (a gene involved in the breakdown of mercaptopurine in the body), you have a higher risk of infection and hair loss, and your doctor may give you a lower dose.

Sun and ultraviolet light

When taking this medicine, you are more sensitive to the sun and ultraviolet light. You should limit your exposure to sunlight and ultraviolet light, wear protective clothing, and use sunscreen with a high sun protection factor (SPF).

If you are not sure if any of the above situations apply to you, talk to your doctor or pharmacist before taking this medicine.

Children and adolescents

Low blood sugar levels (more sweating than usual, nausea, dizziness, confusion, etc.) have been seen in children, mainly in children under six years old or with a low body mass index. If this happens, consult your child's doctor.

Other medicines and Mercaptopurine Zentiva tablets

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• ribavirin (used to treat viral infections).
• other cytotoxic medicines (used to treat cancer).
• allopurinol, thiopurinol, oxipurinol, or febuxostat (used to treat gout).
• olsalazine or mesalazine (used to treat Crohn's disease and a bowel condition called ulcerative colitis).
• sulfasalazine (used to treat rheumatoid arthritis or ulcerative colitis).
• methotrexate (used to treat rheumatoid arthritis or severe psoriasis).
• infliximab (used to treat certain bowel diseases [Crohn's disease and ulcerative colitis], rheumatoid arthritis, ankylosing spondylitis, or skin diseases [severe psoriasis]).
• warfarin and acenocoumarol (used to "thin" the blood).
• antiepileptics such as phenytoin, carbamazepine. It may be necessary to monitor blood levels of antiepileptics and adjust the dose if necessary.

Vaccinations during treatment with mercaptopurine

If you are going to be vaccinated, talk to your doctor or nurse before doing so. This is because some live vaccines (such as polio, measles, mumps, and rubella) can cause infection if given while taking this medicine.

Taking Mercaptopurine Zentiva tablets with food and drink

You can take this medicine with food or on an empty stomach, but the method chosen should be the same every day. You should take this medicine at least 1 hour before or 2 hours after consuming milk or dairy products.

Pregnancy, breastfeeding, and fertility

Do not take mercaptopurine if you are planning to have a child without consulting your doctor first. This applies to both men and women. Mercaptopurine can be harmful to sperm or eggs. You and your partner should use effective contraceptive methods to avoid pregnancy while taking this medicine. Both men and women should use effective contraception for at least 3 months after receiving the last dose of treatment.

Mercaptopurine should not be handled by pregnant women, women who are planning to become pregnant, or women who are breastfeeding. Breastfeeding is not recommended during treatment with this medicine. Talk to your doctor, pharmacist, or midwife.

Taking this medicine during pregnancy can cause intense and excessive itching without a skin rash. You may also experience nausea and loss of appetite at the same time, which can indicate a condition called cholestasis of pregnancy (a liver disease during pregnancy). Talk to your doctor immediately, as this condition can harm the fetus.

Driving and using machines

This medicine is not expected to affect your ability to drive or use machines, although no studies have been performed to confirm this.

Mercaptopurine Zentiva contains lactose

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

3. How to take Mercaptopurine Zentiva tablets

This medicine should only be prescribed by a specialist doctor with experience in treating different types of blood cancer.

• When taking this medicine, your doctor will perform regular blood tests to check the number and type of cells in your blood and ensure that your liver is working properly.
• Your doctor may also request other blood and urine tests to monitor your kidney function and measure uric acid levels. Uric acid is a natural substance produced by the body, and its levels may increase during treatment with mercaptopurine. High levels of uric acid can damage the kidneys. Your doctor may sometimes change your mercaptopurine dose based on the results of these tests.
• Your doctor will calculate and adjust your dose based on your weight or body surface area, blood test results, whether or not you are taking other chemotherapy medicines, and your kidney and liver function.

Follow the instructions for taking this medicine exactly as your doctor or pharmacist has told you. If you are unsure, talk to your doctor or pharmacist again. It is important that you take your medicine at the right time. The label on the pack contains information on how many tablets to take and how often. Talk to your doctor, nurse, or pharmacist if this information is missing from the label or if you are not sure.

The usual initial dose in adults and children is 2.5 mg per kg per day (or alternatively 50 to 75 mg per square meter [m2] of body surface area per day). Your doctor will calculate and adjust your dose based on your body weight, blood test results, whether or not you are taking other chemotherapy medicines, and your kidney and liver function.

Swallow the tablets whole. Do not chew the tablets. The tablets should not be broken or crushed. If you or your caregiver handle broken tablets, wash your hands immediately.

Mercaptopurine Zentiva with food and drink

You can take mercaptopurine with food or on an empty stomach, but the method chosen should be the same every day. You should take the medicine at least 1 hour before or 2 hours after consuming milk or dairy products.

It is important that you take mercaptopurine at night for the medicine to be more effective.

If you take more Mercaptopurine Zentiva than you should

If you take more mercaptopurine than you should or if someone else has taken your medicine by mistake, talk to your doctor immediately or go to the hospital immediately. If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

If you forget to take Mercaptopurine Zentiva

If you forget to take a dose, talk to your doctor. Do not take a double dose to make up for forgotten doses.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following side effects, talk to your specialist doctor or go to the hospital immediately:

• An allergic reaction, whose signs may be:
• Skin rash
• High temperature
• Joint pain
• Facial swelling
• Skin nodules (erythema nodosum) (frequency not known)
• Any sign of fever or infection (sore throat, mouth ulcers, or urinary problems)
• Any unexpected bruising or bleeding, as this may indicate that you are producing insufficient numbers of a certain type of blood cell.
• If you suddenly feel unwell (even if your temperature is normal), with abdominal pain and vomiting, as this may be a sign of pancreatitis.
• Yellowing of the white part of the eyes or skin (jaundice)

Talk to your doctor if you experience any of the following side effects that may also occur with this medicine:

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

• Decrease in the number of white blood cells and platelets (can be detected in blood tests)

Common (may affect up to 1 in 10 people)

• Nausea or vomiting
• Decrease in the number of red blood cells, which can cause fatigue, dizziness, or shortness of breath (called anemia)
• Liver damage (can be detected in blood tests)
• Loss of appetite
• Pancreatitis (inflammation of the pancreas) in patients with inflammatory bowel disease

Uncommon (may affect up to 1 in 100 people)

• Joint pain
• Skin rash
• Fever
• Permanent liver damage (liver necrosis)
• Bacterial and viral infections, infections associated with neutropenia

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

• Hair loss
• Mouth ulcers
• In men: temporary decrease in sperm count
• Allergic reaction causing facial swelling
• Various types of cancer, including blood, lymphatic, and skin cancers
• Pancreatitis (inflammation of the pancreas) in patients with leukemia (blood cancer)

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

• A type of leukemia different from the one being treated
• Ulcers in the intestine; symptoms may include abdominal pain and bleeding

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

• A rare type of cancer (hepatosplenic T-cell lymphoma, in patients with a condition called inflammatory bowel disease), (see section 2, Warnings and precautions)
• Sensitivity to sunlight causing skin reactions
• Decrease in blood sugar levels
• Burning or tingling sensation in the mouth or lips (oral mucositis, stomatitis)
• Cracked or swollen lips (cheilitis)
• Vitamin B3 deficiency (pellagra) associated with pigmented rash; diarrhea, decreased memory, reasoning, or thinking abilities
• Decrease in blood clotting factors.

Additional side effects in children

Cases of low blood sugar (more sweating than usual, nausea, dizziness, confusion, etc.) have been reported in children who received this medicine. However, most reported cases were in children under six years old and with a low body mass index.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Mercaptopurina Zentiva tablets

Keep this medicine out of the sight and reach of children, preferably in a locked cabinet. Accidental ingestion can be fatal for children.

Store in the original packaging to protect from light.

Do not use this medicine after the expiration date stated on the packaging and on the blister pack after EXP. The expiration date is the last day of the indicated month.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic agents.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE Point. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Mercaptopurina Zentiva tablets

The active ingredient is mercaptopurine monohydrate. Each tablet contains 50 mg of mercaptopurine monohydrate.

The other ingredients are:

-Lactose

-Corn starch

-Maltodextrin

-Stearic acid (E-570)

-Magnesium stearate (E-572)

Appearance of the product and package contents

This medicine is 6 mm, circular, and yellowish tablets. The scored line is not intended for tablet division.

This medicine is presented in an amber glass bottle with a propylene cap and silica gel, child-resistant.

Package size:

24 tablets in a brown glass bottle

25 tablets in a brown glass bottle

24 tablets/package

25 tablets/package

50 (2x25) tablets/package

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Zentiva, k.s.,

U kabelovny 130,

Prague 10 – Dolní Mecholupy,

102 37 Czech Republic

Manufacturer

Ardena Pamplona S.L.

Polígono Mocholi. C/ Noain 1

Noain 31110 Navarra

Spain

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

This medicine has been authorized in the EU Member States under the following names:

Germany Mercaptopurin Holsten 50 mg Tabletten

Date of the last revision of this leaflet: June 2025

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