Mercaptopurinum Vis

Leaflet attached to the packaging: patient information

MERCAPTOPURINUM VIS,

50 mg, tablets
Mercaptopurinum

Please read the contents of the leaflet carefully before using the medicine, as it contains important information for the patient.

• Please keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is MERCAPTOPURINUM VIS and what is it used for
• 2. Important information before taking MERCAPTOPURINUM VIS
• 3. How to take MERCAPTOPURINUM VIS
• 4. Possible side effects
• 5. How to store MERCAPTOPURINUM VIS
• 6. Contents of the packaging and other information

1. What is MERCAPTOPURINUM VIS and what is it used for

Mercaptopurine is a cytotoxic medicine, which means it inhibits cell division and has a toxic effect on rapidly dividing cells.
It is used to achieve remission of the disease and in maintenance treatment, in: - acute lymphoblastic leukemia (excessive growth of lymphocytes),

• acute myeloblastic leukemia (excessive growth of myeloblasts, i.e., immature white blood cells). It may be used in chronic granulocytic leukemia (excessive growth of granulocytes). The medicine is used to treat ulcerative colitis and Crohn's disease (inflammatory bowel disease).

2. Important information before taking MERCAPTOPURINUM VIS

When not to take MERCAPTOPURINUM VIS:

• if the patient is allergic to 6-mercaptopurine or any of the other ingredients of this medicine (listed in section 6)
• pregnancy
• severe leukopenia (white blood cell count is less than 1500/microliter, neutrophil count is less than 200/microliter)
• severe thrombocytopenia (platelet count is less than 75,000/microliter)
• bone marrow suppression
• severe kidney failure
• severe liver failure The doctor will decide whether the medicine can be used, depending on the patient's condition.

Warnings and precautions

Before starting treatment with Mercaptopurinum VIS, the patient should discuss it with their doctor.
In patients taking immunosuppressive therapy, taking Mercaptopurinum VIS may increase the risk of:

• developing tumors, including skin cancer; therefore, during treatment with Mercaptopurinum VIS, the patient should avoid excessive exposure to sunlight, wear protective clothing, and use sunscreens with a high protection factor.
• lymphoproliferative disorders, as treatment with Mercaptopurinum VIS increases the risk of developing a type of tumor called lymphoproliferative disorder; concurrent use of treatment regimens containing multiple immunosuppressive drugs (including thiopurines) may lead to death. The concurrent use of multiple immunosuppressive drugs increases the risk of lymphatic system disorders caused by viral infections [Epstein-Barr virus (EBV)-dependent lymphoproliferative disorders]. Taking Mercaptopurinum VIS may increase the risk of:
• developing a severe condition called macrophage activation syndrome (excessive activation of white blood cells associated with inflammation), usually occurring in people with certain types of arthritis. Particular caution should be exercised in elderly patients, children, and patients with impaired liver or kidney function. In such cases, the doctor will determine the appropriate dose of the medicine, depending on the patient's condition. Treatment with mercaptopurine may cause bone marrow suppression leading to leukopenia (lower than normal white blood cell count), thrombocytopenia (lower than normal platelet count), and less frequently anemia (lower than normal hemoglobin level). During treatment, the doctor will monitor blood parameters, depending on the patient's condition, and may decide to adjust the dose or discontinue treatment if the white blood cell or platelet count is too low. Bone marrow suppression is reversible. After discontinuing mercaptopurine, bone marrow function returns to normal. The action of the medicine may increase the risk of infections, delayed healing, and bleeding from the gums. The patient should maintain good oral hygiene and complete any dental procedures before starting therapy with 6-mercaptopurine. Due to the increased risk of infection during treatment with 6-mercaptopurine, the doctor may prescribe antibiotic prophylaxis in justified cases. Patients with a congenital deficiency of the enzyme methyltransferase tiopurinol (TPMT) may be highly sensitive to the action of 6-mercaptopurine and may experience severe bone marrow suppression caused by this medicine. Mercaptopurine damages the liver, and therefore, liver function parameters, i.e., AspAT, AlAT, and bilirubin, should be monitored, especially in patients who have previously been diagnosed with liver disease or have taken other medicines that may damage liver function. During treatment, there is a risk of excessive increase in uric acid levels in the blood and (or) excessive uric acid excretion, as well as the development of uric acid nephropathy (kidney disease). The doctor will monitor these parameters. If symptoms of jaundice occur, such as yellowing of the skin, mucous membranes, and eye whites, the patient should immediately contact their doctor. The doctor will decide whether to discontinue treatment.

Mercaptopurinum VIS and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Usually, there is cross-resistance between 6-mercaptopurine and 6-thioguanine.
The doctor may decide to adjust the dosage of medicines when 6-mercaptopurine is administered with:

• other medicines that suppress bone marrow function.
• warfarin (6-mercaptopurine inhibits its anticoagulant effect).
• allopurinol, tiopurinol, and oxypurinol (prolong and enhance the action of 6-mercaptopurine).
• medicines that inhibit TPMT, such as olsalazine, mesalazine, or sulfasalazine (enhance bone marrow suppression). Due to decreased immunity, the patient's response to vaccines may be weakened. During treatment with 6-mercaptopurine, the patient should not be vaccinated with live vaccines.

Infections

In patients treated with Mercaptopurinum VIS, there is an increased risk of viral, fungal, and bacterial infections, and these infections may be more severe. See also section 4.
Before starting treatment, the patient should tell their doctor if they have had chickenpox, shingles, or viral hepatitis B (liver disease caused by a virus).

Mutation of the NUDT15 gene

If the patient has a congenital mutation in the NUDT15 gene (a gene responsible for the breakdown of the medicine Xaluprine in the body), they are at increased risk of infection and hair loss, so the doctor may decide to reduce the dose in such cases.

Genotoxicity and carcinogenicity:

During treatment, an increase in the number of chromosomal mutations in peripheral lymphocytes has been observed in patients.
The potential carcinogenic effect of 6-mercaptopurine on DNA should be considered.
Single cases of acute non-lymphocytic leukemia or myeloid leukemia have been reported in patients who received 6-mercaptopurine in combination with other medicines during treatment for non-neoplastic diseases.
During treatment with the medicine, the doctor will periodically check the blood morphology, platelet count, and liver and kidney function parameters.
In case of adverse reactions such as decreased white blood cell or platelet count, the doctor will decide whether to reduce the dose or discontinue treatment with this medicine.

Mercaptopurinum VIS with food and drink:

The medicine should be taken preferably after a meal, with water .

Other:

When dividing the tablet, the patient should not allow the powder to spread or come into contact with the skin, and should not touch it with their bare hands.
Any unused product or waste should be disposed of in accordance with local regulations.

Using Mercaptopurinum VIS in patients with kidney or liver function disorders:

In patients with impaired liver or kidney function, the doctor will determine the dose individually.

Using Mercaptopurinum VIS in elderly patients:

No studies have been conducted in humans in this age group. In these patients, the doctor will monitor kidney and liver function and may decide to adjust the dosage .

Pregnancy, breastfeeding, and fertility

In pregnancy and during breastfeeding, or if pregnancy is suspected, or if the patient is planning to become pregnant, they should consult their doctor before taking this medicine.
In each individual case, the doctor will weigh the potential risk to the fetus against the expected benefits for the mother. The use of appropriate contraceptive measures is recommended if either partner is being treated with mercaptopurine.
Women taking Mercaptopurinum VIS should not breastfeed.

Driving and using machines

There is no data on the effect of 6-mercaptopurine on the ability to drive or operate machines, but during prolonged use, the decision should be left to the doctor.

Mercaptopurinum VIS contains lactose.

If the patient has previously been diagnosed with intolerance to certain sugars, they should contact their doctor before taking the medicine.

3. How to take MERCAPTOPURINUM VIS

This medicine should always be taken according to the doctor's instructions.
In case of doubts, the patient should consult their doctor.
Treatment with the medicine should be started in a hospital or in specialized clinics under the supervision of a doctor experienced in the administration of this medicine.
Mercaptopurinum VIS is administered orally, after a meal.

Using in children

In adults and children, the usual initial dose is 2.5 mg/kg body weight per day or 50 to 75 mg/m² body surface area per day. The tablet can be divided into equal doses. The dose and duration of treatment depend on the type and dosage of other cytotoxic medicines administered concurrently with mercaptopurine. If there is no therapeutic effect observed within 4 weeks, the doctor may decide to increase the dose to a maximum of 5 mg/kg body weight per day.
If it is necessary to administer the medicine with allopurinol, tiopurinol, and oxypurinol, the doctor will determine the dosage individually.
In patients with ulcerative colitis and Crohn's disease, the usual dose of the medicine is 1 to 1.5 mg/kg body weight per day.
If the patient feels that the effect of the medicine is too strong or too weak, they should consult their doctor.

Using a higher than recommended dose of Mercaptopurinum VIS

Early symptoms of overdose may include gastrointestinal disorders, such as: nausea, vomiting, diarrhea, or loss of appetite. As a result of chronic overdose, a more pronounced decrease in the number of certain blood cells (white blood cells and platelets) may occur. Liver damage and stomach and intestinal inflammation may also occur.

Procedure in case of overdose

Since there is no antidote in case of overdose, it is necessary to monitor the patient's blood morphology to apply appropriate treatment, e.g., blood transfusion, if necessary. Activated charcoal or stomach lavage should be used within 60 minutes of taking mercaptopurine, as they will be ineffective otherwise.
In case of taking a higher dose of the medicine than recommended, the patient should immediately consult their doctor or pharmacist.

Missing a dose of Mercaptopurinum VIS

The patient should take the next dose as soon as possible.
The patient should not take a double dose to make up for the missed dose.

Discontinuing Mercaptopurinum VIS

The patient should not stop taking the medicine unless their doctor advises them to do so. In case of any further doubts about the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects are listed below, by system organ class and frequency, from very common to rare:

• very common: occur in more than 1 in 10 patients;
• common: occur in 1 to 10 in 100 patients;
• uncommon: occur in 1 to 10 in 1000 patients;
• rare: occur in 1 to 10 in 10,000 patients;
• very rare: occur in less than 1 in 10,000 patients;
• frequency not known: cannot be estimated from the available data.

Blood and lymphatic system disorders:
During treatment with 6-mercaptopurine, leukopenia (lower than normal white blood cell count) and thrombocytopenia (lower than normal platelet count) often occur, and less frequently: megaloblastic anemia (presence of large immature red blood cells in the blood and bone marrow) and macrocytic anemia (red blood cells are larger than normal), very rarely: bone marrow failure, with an unknown frequency: acute myeloblastic leukemia (excessive growth of myeloblasts, i.e., immature white blood cells) - the relationship with 6-mercaptopurine therapy requires confirmation.
These disorders may occur after many weeks or even months after the end of 6-mercaptopurine therapy. Bone marrow suppression is the primary symptom of the toxic effect of 6-mercaptopurine. It may persist for a long time after discontinuing the medicine and is often related to the activity of the enzyme methyltransferase tiopurinol (TPMT).
Renal and urinary disorders;
During treatment with 6-mercaptopurine, hyperuricemia - elevated uric acid levels in the blood - and (or) hyperuricosuria - elevated uric acid excretion in the urine - often occur, as well as gout attacks. The accumulation of uric acid is a result of cell destruction and the release of substances called purines. The doctor will apply appropriate treatment. Rarely, crystalluria (presence of crystals in the urine) and hematuria (blood in the urine) have been observed, and very rarely: kidney failure, especially after taking high doses
Metabolism and nutrition disorders:
Nausea (especially in the initial period of treatment), vomiting, loss of appetite, and diarrhea are often observed. Less frequently, inflammation of the mucous membranes of the digestive tract and mouth, ulcers in the mouth, increased amylase levels in blood test results, and acute pancreatitis occur.
Liver and biliary disorders:
Jaundice (yellowing of the skin and eye whites) and elevated levels of bilirubin, transaminases, and alkaline phosphatase are often observed. Liver function disorders and cholestatic jaundice (caused by an obstacle to bile flow) usually resolve quickly after discontinuing treatment. Rarely, liver inflammation occurs, and very rarely: liver failure (including cell necrosis) and portal hypertension (increased pressure in the portal vein flowing into the liver).
General disorders and administration site conditions:
Skin and subcutaneous tissue disorders occur rarely during treatment with 6-mercaptopurine. Rarely observed skin changes include skin redness, nodular changes, and changes of the lichen planus type, as well as Sweet's syndrome. Very rarely, hair loss, palmoplantar erythrodysesthesia, and skin discoloration occur.
Also observed rarely: decreased immunity to infections; very rarely: photosensitivity, fatigue, early morning hypoglycemia, and drug fever; with an unknown frequency: pneumonia, shingles, and phlebitis, as well as hypersensitivity reactions.
Very rarely, male infertility has been reported, which resolves after discontinuing treatment.
Other side effects include:
Rarely (occurring in less than 1 in 1000 patients)

• various types of tumors, including blood, lymphatic, and skin cancers.

If any of the following side effects occur, the patient should tell their doctor or go to the hospital immediately:

Any symptoms indicating fever or infection (sore throat, mouth ulcers, or problems urinating).
If any side effects occur, including any side effects not listed in this leaflet, the patient should consult their doctor.

Reporting side effects

If any side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309, e-mail: ndl@urpl.gov.pl
By reporting side effects, more information can be gathered on the safety of the medicine.
Side effects can also be reported to the marketing authorization holder.

5. How to store MERCAPTOPURINUM VIS

The medicine should be stored out of sight and reach of children.
Mercaptopurinum VIS should be stored at a temperature below 25°C, in a dry place.
The medicine should not be used after the expiry date stated on the packaging (label and carton) after "Expiry date". The expiry date refers to the last day of the specified month.

6. Contents of the packaging and other information

What MERCAPTOPURINUM VIS contains

• -The active substance of the medicine is 50 mg of 6-mercaptopurine.
• Other ingredients are: potato starch, lactose, povidone, talc, magnesium stearate.

What MERCAPTOPURINUM VIS looks like and what the pack contains

Packaging: a bottle made of orange glass or a tablet container containing 30 tablets, in a cardboard box.

Marketing authorization holder and manufacturer

Zakłady Chemiczno-Farmaceutyczne "VIS" Spółka z o.o.
ul. Św. Elżbiety 6a
41-905 Bytom
tel./fax (32) 2589555
e-mail: firma@vis-farm.pl
To obtain more detailed information, please contact the local representative of the marketing authorization holder .
Date of last revision of the leaflet: 28.10.2019