MERCAPTOPURINE SILVER 50 mg TABLETS

2. What you need to know before you take Mercaptopurina Silver

Do not take Mercaptopurina Silver:

• if you are allergic to mercaptopurine or any of the other ingredients of this medicine (listed in section 6).
• if you have recently been given the yellow fever vaccine while taking mercaptopurine, as it can be fatal.

Warnings and precautions

Tell your doctor or pharmacist before you start taking Mercaptopurina Silver if:

• you have been vaccinated against yellow fever
• you have kidney or liver problems; your doctor will monitor your kidney and liver function
• you have a disease in which your body produces insufficient amounts of an enzyme called TPMT (thiopurine methyltransferase), as your doctor may need to adjust your dose.
• you plan to have a child. This applies to both men and women. Mercaptopurine can be harmful to sperm or eggs (see 'Pregnancy, breastfeeding, and fertility' below).

In some patients with inflammatory bowel disease who have received treatment with 6-mercaptopurine, a rare and aggressive type of cancer called hepatosplenic T-cell lymphoma has occurred (see section 4).

If you are taking immunosuppressive treatment, taking Mercaptopurina Silver may increase your risk of:

• tumors, including skin cancer. Therefore, when taking Mercaptopurina Silver, avoid excessive exposure to sunlight, wear protective clothing, and use sunscreen with a high protection factor.

• lymphoproliferative disorders

• treatment with Mercaptopurina Silver increases your risk of having a type of cancer called lymphoproliferative disorder. With treatment containing 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).

Infections

When receiving treatment with Mercaptopurina Silver, the risk of suffering from viral, fungal, and bacterial infections is greater, and these infections can be more severe. See also section 4.

Before starting treatment, tell your doctor if you have had chickenpox, herpes, or hepatitis B (a liver disease caused by a virus).

NUDT15 gene mutation

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

Vitamin B3 deficiency (pellagra)

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

Taking Mercaptopurina Silver 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.

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

Taking Mercaptopurina Silver with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription.

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

• other cytotoxic drugs (chemotherapy) - when used with mercaptopurine, there is a greater likelihood of side effects, such as respiratory problems
• other medicines whose primary or secondary toxicity is myelosuppression
• allopurinol, oxipurinol, tiopurinol (used to treat gout)
• warfarin (used to thin the blood)
• olsalazine or mesalazine (used for a bowel problem called ulcerative colitis)
• sulfasalazine (used for rheumatoid arthritis or ulcerative colitis)
• antiepileptics such as phenytoin or carbamazepine. It may be necessary to monitor the blood levels of the antiepileptics and adjust the dose as needed.
• 6-thioguanine (antineoplastic), as there is cross-resistance between the two drugs
• ribavirin, cases of severe myelosuppression have been reported after concomitant administration with mercaptopurine
• methotrexate (used to treat cancer, rheumatoid arthritis, or skin diseases [severe psoriasis]), oral administration of methotrexate increases the blood concentration of mercaptopurine
• infliximab (used to treat certain bowel diseases [Crohn's disease and ulcerative colitis], rheumatoid arthritis, ankylosing spondylitis, or skin diseases [severe psoriasis])

If you are going to be vaccinated while taking mercaptopurine, it is important that you consult your doctor or nurse first. This is because some vaccines (such as polio, measles, mumps, and rubella) can cause you to become infected if given while you are taking mercaptopurine.

Taking Mercaptopurina Silver with food and drinks

Mercaptopurina Silver can be taken with food or on an empty stomach. However, the chosen method should be the same every day.

Do not take mercaptopurine with milk or dairy products, as they may reduce the effectiveness of the medicine. Mercaptopurina Silver should be taken at least 1 hour before or 3 hours after consuming milk or dairy products.

Pregnancy, breastfeeding, and fertility

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

Pregnancy:

If you are planning to have a baby, do not take mercaptopurine. This applies to both men and women. Mercaptopurine can be harmful to your sperm or eggs. You must use effective contraception to avoid pregnancy while you or your partner are taking this medicine. Consult your doctor.

If you are already pregnant, tell your doctor before taking mercaptopurine.

Taking Mercaptopurina Silver 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). Talk to your doctor immediately, as this condition can harm the fetus.

Breastfeeding:

It is not recommended to breastfeed while taking mercaptopurine. Consult your doctor, pharmacist, or midwife.

Driving and using machines

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

Mercaptopurina Silver contains lactose and sodium

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

This medicine contains less than 23 mg of sodium (1mmol) per tablet; this is essentially 'sodium-free'.

3. How to take Mercaptopurina Silver

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

Mercaptopurine should only be administered by a specialist doctor with experience in the treatment of blood diseases.

• Swallow the tablets whole with a glass of water.
• If you need to break the tablet in half, do not inhale the powder from the tablet. Then wash your hands.
• When taking Mercaptopurina Silver, your doctor will periodically perform blood tests to check the number and type of cells in your blood and to ensure that your liver is functioning properly.
• Your doctor may also ask for other blood and urine tests to monitor your uric acid levels. Uric acid is a natural chemical in the body, but its levels can rise during treatment with Mercaptopurina Silver.
• Your doctor may adjust the dose of Mercaptopurina Silver based on the results of these tests.

The usual initial dose in adults, adolescents, and children is 25-75 mg/m2 of body surface area per day. Your doctor will prescribe the correct dose for you. Sometimes, your doctor may change the dose of Mercaptopurina Silver depending on the results of different tests. Consult your doctor or nurse if you have doubts about the dose you should take.

It is important to take Mercaptopurina Silver at night for the medicine to be more effective.

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

If you take more Mercaptopurina Silver than you should

If you take more Mercaptopurina Silver than you should, tell your doctor or go to the hospital immediately. You may have nausea, vomiting, or diarrhea. Bring the medicine pack and this leaflet with you.

In case of overdose, call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Mercaptopurina Silver

Tell your doctor.

Do not take a double dose to make up for forgotten doses.

If you stop taking Mercaptopurina Silver

Do not stop taking your medicine unless your doctor tells you to, or you may suffer a relapse of your disease.

If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

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, contact your specialist doctor or go to the hospital immediately:

Allergic reaction, whose signs may be:

• skin rash
• high temperature
• joint pain
• facial swelling
• skin nodules (erythema nodosum)

Any sign of fever or infection (sore throat, mouth ulcers, or urinary problems).

Any unexpected bruising or bleeding, as it may indicate that you are producing insufficient amounts of a certain type of blood cell.

If you suddenly feel unwell (even if your temperature is normal), with abdominal pain and nausea, as it may be a sign of pancreatitis.

Yellowing of the whites of the eyes or skin (jaundice).

If you have diarrhea.

Tell 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
• liver damage - can be detected in blood tests
• decrease in the number of red blood cells, which can cause fatigue, dizziness, or shortness of breath - a condition called anemia
• loss of appetite
• diarrhea
• mouth inflammation (stomatitis)

Uncommon: may affect up to 1 in 100 people

• mouth ulcers
• pancreatitis
• joint pain
• skin rash
• fever
• permanent liver damage (liver necrosis)

Rare: may affect up to 1 in 1,000 people

• hair loss
• in men: temporary decrease in sperm count
• facial swelling
• various types of cancer, including blood, lymphatic, and skin cancers.

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

Other side effects (frequency not known)

• a rare type of cancer (hepatosplenic T-cell lymphoma), (see Section 2).
• skin nodules (erythema nodosum)
• burning sensation or tingling in the mouth or lips (mucositis, stomatitis)
• cracked or swollen lips (cheilitis)
• vitamin B3 deficiency (pellagra) with localized pigmented skin rash, diarrhea, or decreased memory, reasoning, or thinking ability
• decrease in blood clotting factors

Other side effects in children

• low blood sugar (hypoglycemia); frequency not known

If you experience any side effect that is severe or persistent, or if you notice any side effect not listed in this leaflet, tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Mercaptopurina Silver

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

Do not use this medicine after the expiry date stated on the blister pack or carton after EXP:. The expiry date is the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Return the containers and any unused medicines to the pharmacy's SIGRE collection point . Ask your pharmacist how to dispose of the containers and any unused medicines. This will help protect the environment.

6. Container Content and Additional Information

Mercaptopurina Silver Composition

• The active ingredient is mercaptopurine (as monohydrate). Each tablet contains 50 mg of mercaptopurine monohydrate.

• The other components (excipients) are: microcrystalline cellulose, povidone, sodium croscarmellose, lactose monohydrate, magnesium stearate, and stearic acid.

Product Appearance and Container Content

Mercaptopurina Silver are yellowish circular tablets

Container size: 24 or 25 tablets.

Only some container sizes may be marketed.

In the 24-tablet presentation, Mercaptopurina Silver is packaged in two Alu-PVC or ALU/PVC-PVDC blisters of 12 tablets each, inside a cardboard box.

In the 25-tablet presentation, Mercaptopurina Silver is packaged in an Alu-PVC or ALU/PVC-PVDC blister of 25 tablets, inside a cardboard box.

Marketing Authorization Holder

SILVER PHARMA S.L.

Avda. Camino de lo Cortao 16

28703 San Sebastian de los Reyes, (Madrid)

Spain

Manufacturer

Date of the Last Revision of thisProspectus: August 2024

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