Package Leaflet: Information for the User

Mercaptopurina Zentiva 50 mg Tablets EFG

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

-Keep this package leaflet, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this package leaflet. See section 4.

This medicine contains the active ingredient 6-mercaptopurine which belongs to a group of medicines called cytotoxics (also known as chemotherapy).

This medicine is used in the treatment of blood cancer, leukaemia in adults, adolescents and children.

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

Do not take Mercaptopurina Zentiva tablets:

If you are allergic to the active ingredient 6-mercaptopurine or to any of the other components of this medicine listed in section 6.

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine:If you have recently received a vaccine or are to be vaccinated.

• If you suffer from a genetic disease called TPMT (thiopurine methyltransferase deficiency)
• If you are allergic to a medicine called azathioprine (which is also used to treat cancer).
• If you have kidney insufficiency.
• If you have liver disease with liver function impairment.
• If you have a genetic disorder called Lesch-Nyhan syndrome.
• If you are planning to have a child. This applies to both men and women. This medicine may be harmful to sperm or eggs (see "Pregnancy, breastfeeding and fertility" below).

The tablets must be handled with care.

Women who are pregnant, planning to become pregnant or breastfeeding should not handlethis medicine.

See "Safe handling of tablets" in section 3 "Taking Mercaptopurina Zentiva".

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

• cancers, including skin cancer. Therefore, when takingthis medicineavoid excessive exposure to sunlight, wear protective clothing and use high-factor sunscreens.

• lymphoproliferative disorders:

-The treatment withthis medicineincreases your risk of having a type of cancer called lymphoproliferative disorder and other malignant tumors. With a treatment containing several immunosuppressants (including thiopurines), this may cause death.

-The combination of multiple immunosuppressants, administered simultaneously, increases the risk of lymphatic system disorders due to viral infection (lymphoproliferative disorders associated with Epstein-Barr virus (EBV)).

•vitamin B3 deficiency (pellagra): report immediately to your doctor if you have diarrhea, localized pigmented rashes (dermatitis) or deterioration of memory, reasoning and thinking ability (dementia), as these symptoms may indicate a vitamin B3 deficiency. Your doctor will prescribe vitamin supplements (niacin/nicotinamide) to improve your condition.

Takingthis medicinemay increase your risk of:

• presenting 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

The treatment with this medicine may affect your bone marrow. Your doctor will perform blood tests every day during the initial period of your treatment and, at least, weekly during the treatment period (maintenance). This is done to control the levels of these cells in your blood.When you finish taking the treatment, the levels of your blood cells will return to normal.

Liver function

Your doctor will perform blood tests regularly while you are takingthis medicine.This is to check the number and type of cells in your blood and to ensure that your liver is functioning correctly.

Infections

When taking this medicine, the risk of contracting viral, fungal and bacterial infections is higher, and these infections may be more severe. See also section 4.

Before starting treatment, inform your doctor if you have had or not chickenpox, shingles or hepatitis B (a liver disease caused by a virus).

NUDT15 gene mutation

If you have a hereditary mutation in the NUDT15 gene (a gene involved in the breakdown of mercaptopurine in the body), you have a higher risk of infections and hair loss, and in this case, 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 ensure that you limit your time of exposure to sunlight and ultraviolet light, wear protective clothing and use a high-factor sunscreen.

If you are unsure whether any of the above situations applies to you, consult your doctor or pharmacist before taking this medicine.

Other medicines and Mercaptopurina Zentiva tablets

Inform your doctor or pharmacist if you are taking, have recently taken or may need to take any other medicine.

Particularly, inform your doctor or pharmacist if you are taking any of the following medicines:

• ribavirin (used in the treatment of viral infections).
• other cytotoxic medicines (used to treat cancer).
• allopurinol, thiopurinol, oxipurinol or febuxostat (used to treat gout).
• olsalazine (used to treat an intestinal disorder called ulcerative colitis).
• mesalazine (used to treat intestinal disorders called Crohn's disease and ulcerative colitis).
• sulfasalazine (used to treat rheumatoid arthritis or ulcerative colitis).
• methotrexate (used to treat cancer, rheumatoid arthritisor skin diseases [severe psoriasis])
• infliximab (used to treat certain intestinal disorders [Crohn's disease and ulcerative colitis], rheumatoid arthritis, ankylosing spondylitis or skin diseases [severe psoriasis]).
• warfarin and acenocoumarol (anticoagulants).

Vaccinations during mercaptopurine treatment

If you are to be vaccinated, speak with your doctor or nurse before doing so. This is because some vaccines with live microorganisms (such as the polio vaccine, measles, mumps and rubella) may cause you to become infected if administered while taking this medicine.

You should not be vaccinated with the yellow fever vaccine while taking this medicine as it can be fatal.

Taking Mercaptopurina Zentiva tablets with food and drinks

You can take this medicine with food or on an empty stomach, but the method chosen must 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

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

If you think you may be pregnant or are planning to become pregnant, consult your doctor before taking this medicine.

It is not recommended to treat with this medicine during pregnancy, mainly during the first trimester, as it may cause harm to the fetus.

If you are pregnant, your doctor will take into account the risks and benefits for you and your baby before prescribing this medicine.

Do not take this medicine if you are planning to have a baby. This applies to both men and women. A reliable contraceptive method should be used to avoid pregnancy during the entire treatment cycle with this medicine and for at least 3 months after receiving the last dose.

It is not recommended to breastfeed during treatment withthis medicine. Consult your doctor, pharmacist or midwife.

Driving and operating machines

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

Mercaptopurina Zentiva tablets contain lactose

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

This medicationshould be prescribed only by a specialist doctor with experience in the treatment of different types of blood cancer.

When takingthis medication, your doctor will perform blood tests periodically to check the number and type of cells in your blood and to ensure that your liver is functioning correctly.

Your doctor may also request other blood and urine tests to measure uric acid levels. Uric acid is a natural substance produced by the body, and its levels may increase during treatment withthis medication.

It is possible that your doctor may change your mercaptopurine dose based on the results of these tests.

Follow exactly the administration instructions forthis medicationcontained in this leaflet or those indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist.It is essential to take the tablets at the correct time.

Your doctor will calculate and adjust the dose based on yourweight or body surface area, blood test results, whether you are taking other chemotherapy medications, and your renal and hepatic function.

The usual initial dose in adults and children is 2.5 mg/kg of body weight per day (or 50-75 mg per m2of body surface area per day).

Swallow the tablets whole with some water. You can take the medication with food or on an empty stomach, but the chosen method must be the same every day. You should takethis medicationat least 1 hour before or 2 hours after consuming milk or dairy products.

Safe handling of Mercaptopurina Zentiva tablets

If you are the parent or caregiver administering the medication, wash your hands before and after giving a dose. Any spilled medication should be cleaned immediately. To reduce the risk of exposure, use disposable gloves when handlingthis medication.

Immediately and thoroughly clean with water and soap ifthis medicationcomes into contact with the skin, eyes, or nose.

Women who are pregnant, planning to become pregnant, or breastfeeding should not handlethis medication. Accidental ingestion can be fatal for children. Keep this medication out of the sight and reach of children, preferably in a locked cabinet.

If you take more MercaptopurinaZentivatablets than you should

If you take more mercaptopurine than you shouldor if someone else takes your medication by mistake,inform your doctor immediately or go to the hospital immediately.If you have any other questions about using this medication, ask your doctor or pharmacist.

If you forget to take MercaptopurinaZentivatablets

If you forget to take a dose,inform your doctor. Do not take a double dose to make up for the missed dose.

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

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

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

• A hypersensitivity reaction with facial swelling and sometimes the mouth and throat (this is a very rare side effect)
• A hypersensitivity reaction with joint pain, skin rash, high temperature (fever) (this is a rare side effect)
• Yellow discoloration of the skin and the white part of the eyes. If you experience these symptoms, you must discontinue treatment withthis medicine
• Any sign of fever or infection (you feel tired or unwell, sore throat, mouth sores, or urinary problems) or any unexpected bruising or bleeding. Treatment withthis medicineaffects the bone marrow and reduces the number of white blood cells and platelets (this is a very frequent side effect)

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

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

• Reduction in the number of leukocytes and platelets (may be detected in blood tests)

Frequent(may affect up to 1 in 10 people)

• Nausea (desire to vomit) or vomiting
• Low red blood cell count (anemia)
• Liver damage (may be detected in blood tests)

Rarely(may affect up to 1 in 100 people)

• Loss of appetite
• Infections, general malaise, tendency to sore throat and fever. They may be severe. If you have a fever, consult a doctor or an emergency service.

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

• Mouth ulcers
• Pancreatitis (inflammation of the pancreas); symptoms may include abdominal pain, nausea, or vomiting
• Severe liver damage (hepatic necrosis)
• Hair loss
• Joint pain, skin rash, fever due to hypersensitivity

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

• Leukemia (blood cancer)
• Lymphoma and liver cancer (in patients with a disease called inflammatory bowel disease)
• Ulcers in the intestines; symptoms may include abdominal pain and bleeding
• In men: reduction in sperm count
• Swollen face due to hypersensitivity

Unknown frequency(frequency cannot be estimated from available data)

• Burning sensation or tingling in the mouth or lips (inflammation of the mucosa, stomatitis)
• Cracked or swollen lips (cheilitis)
• Vitamin B3 deficiency (pellagra) with localized skin rash, diarrhea, or decreased memory, reasoning, or other thinking abilities
• Reduction in coagulation factors
• )

Additional side effects in children

Cases of hypoglycemia (excessive sweating, 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 low body weight.

Reporting of side effects

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

Keep this medication 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 it from light.

Do not usethis medicationafter the expiration date that appears on the packaging and on the blister pack after CAD. The expiration date is the last day of the month indicated.

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

Medications should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. By doing so, you will help protect the environment.

Composition of MercaptopurineZentivatablets

The active ingredient is 6-mercaptopurine. Each tablet contains 50 mg of mercaptopurine.

The other components are:

-Lactose

-Cornstarch

-Maltodextrin

-Stearic acid (E-570)

-Magnesium stearate (E-572)

Appearance of the product and contents of the packaging

This medicinearetablets of 6 mm, circular and yellowish. The marked line is not intended to divide the tablet.

This medicine is presented in an amber-colored glass container with a propylene stopper with silica gel, child-resistant.

Container size:

24 tablets in a brown glass bottle

25 tablets in a brown glass bottle

24 tablets / container

25 tablets / container

50 (2x25) tablets / container

Only some container sizes may be commercially marketed.

Holder of the marketing authorization and responsible manufacturer

Holder of the marketing authorization

Zentiva, k.s.,

U kabelovny 130,

Prague 10 – Dolní Mecholupy,

102 37 Czech Republic

Responsible manufacturer

Ardena Pamplona S.L.

Polígono Mocholi. C/ Noain 1

Noain 31110 Navarra

Spain

For more information about this medicine, please contact the representative of the holder of the marketing authorization:

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 thefollowing names:

GermanyMercaptopurin Holsten 50 mg Tablets

Last review date of this leaflet:July 2022

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