XALUPRINE 20 mg /Ml Оральная Суспензия

Содержание инструкции

1. Xaluprine 20 mg/ml oral suspension
   1. What is Xaluprine and what it is used for
   2. What you need to know before taking Xaluprine
   3. How to take Xaluprine
   4. Possible side effects
   5. How to store Xaluprine
   6. Contents of the pack and other information

Xaluprine 20 mg/ml oral suspension

mercaptopurine monohydrate

Read this leaflet carefully before you start to take this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What is Xaluprine and what it is used for

Xaluprine contains mercaptopurine monohydrate. It belongs to a category of medicines defined as
cytotoxic (also known as chemotherapeutic agents).
Xaluprine is used for acute lymphoblastic leukemia (also called acute lymphocytic leukemia or
ALL). This is a disease characterized by rapid progression, which involves an increase in the
number of new white blood cells. These new leukocytes are immature (not
fully formed) and unable to grow and function properly. They are therefore unable to
fight infections and can cause bleeding.
Consult your doctor if you would like further explanations regarding this disease.

2. What you need to know before taking Xaluprine

• Do not take Xaluprineif you are allergic to mercaptopurine or any of the other ingredients of this medicine (listed in section 6).
• Do not get vaccinatedagainst yellow fever while taking Xaluprine as it could be fatal.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Xaluprine

• if you have recently received or are due to receive a vaccination (vaccine).
• if you have been vaccinated with a yellow fever vaccine.
• if you have problems with your kidneys or liver, as your doctor will need to check the function of these organs.
• if you have a condition where your body produces insufficient of the enzyme TPMT (thiopurine methyltransferase) or NUDT15 (nudix hydrolase-15), as a dose adjustment may be necessary by your doctor.
• if you are planning to have a child. This applies to both men and women. Xaluprine may damage sperm or eggs (see “Pregnancy, breastfeeding and fertility” below).

If you are receiving immunosuppressive therapy, taking Xaluprine may increase the
risk of developing:

• tumours, including skin cancer. Therefore, if you are taking Xaluprine you should avoid excessive exposure to sunlight, wear protective clothing and use a sunscreen with a high protection factor.
• lymphoproliferative disorders or treatment with Xaluprine increases the risk of developing a type of cancer called a lymphoproliferative disorder. A treatment regimen based on multiple immunosuppressants (including thiopurines) can cause death. or the simultaneous administration of a combination of multiple immunosuppressants increases the risk of developing disorders of the lymphatic system caused by a viral infection (lymphoproliferative disorders associated with Epstein-Barr virus (EBV)).

Taking Xaluprine may increase the 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 who have received mercaptopurine have
developed a rare and aggressive type of cancer called T-cell hepatosplenic lymphoma (see
section 4, Possible side effects).

Infections
During treatment with Xaluprine, the risk of viral, fungal and bacterial infections is increased and
infections may 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).

Blood tests
Treatment with mercaptopurine can affect the bone marrow. You may therefore have a
reduced number of white blood cells, platelets and (less frequently) red blood cells in your blood. Your
doctor will perform frequent and regular blood tests during treatment. This is to monitor the
levels of these cells in your blood. If treatment is stopped in good time, your blood cells will return to
normal.

Liver function
Mercaptopurine is toxic to the liver. Therefore, your doctor will perform frequent and regular liver
function tests during treatment with mercaptopurine. If you already have liver problems or are taking
other medicines that may affect the liver, your doctor will perform more frequent tests. If you notice
that the whites of your eyes or skin become yellowish (jaundice), tell your doctor immediately as
treatment may need to be stopped immediately.

TPMT and NUDT15 gene variants
If you have an inherited variant of the TPMT and/or NUDT15 gene (genes involved in the
transformation of Xaluprine in the body), you are at a higher risk of infections and hair loss, and in this
case your doctor may give you a lower dose.

Vitamin B3 (pellagra) deficiency
Tell your doctor immediately if you experience diarrhoea, pigmented skin rash (dermatitis)
or deterioration of memory, reasoning and thinking skills (dementia), as these
symptoms may indicate a vitamin B3 deficiency. The doctor will prescribe vitamin supplements
(niacin/nicotinamide) to improve your condition.
Avoid contact of Xaluprine with skin, eyes and nose. If accidental contact occurs with the
eyes or nose, wash with plenty of water.
If you have any doubts about whether any of the above situations apply to you, talk to your doctor or
pharmacist before taking Xaluprine.

Children and adolescents
Low blood sugar levels have sometimes been observed in children, especially in
children under six years of age or with a low body mass index. Talk to your child’s pediatrician if this occurs.

Other medicines and Xaluprine
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
In particular, tell your doctor, nurse or pharmacist if you are taking any of the
following substances:

• ribavirin (used to treat viruses)
• other cytotoxic medicines (chemotherapy) - when used with Xaluprine there is a greater likelihood of side effects, such as anaemia
• allopurinol, thiopurinol, oxipurinol or febuxostat (used to treat gout)
• oral anticoagulants (used to thin the blood)
• olsalazine or mesalazine (used for a bowel condition called ulcerative colitis)
• sulfasalazine (used for rheumatoid arthritis or ulcerative colitis)
• methotrexate (used to treat cancer, rheumatoid arthritis or skin diseases (severe psoriasis))
• antiepileptic medicines such as phenytoin, carbamazepine. It may be necessary to monitor blood levels of antiepileptic medicines and adjust doses accordingly
• infliximab (used to treat certain bowel diseases (Crohn’s disease and ulcerative colitis), rheumatoid arthritis, ankylosing spondylitis or skin diseases (severe psoriasis))

Vaccination during treatment with Xaluprine
It is important to tell your doctor or nurse before having any vaccinations. Vaccination with live vaccines (for example against polio, measles, mumps and rubella) is not
recommended, as these vaccines can cause an infection if given during treatment with
Xaluprine.

Xaluprine with food and drink
Xaluprine can be taken with or without food. However, the chosen method should be
kept consistent from day to day.
Do not take Xaluprine at the same time as milk or dairy products, as they may impair
the effectiveness of the medicine. The intake of Xaluprine should take place at least one hour before or two hours
after the intake of milk or dairy products.

Pregnancy, breastfeeding and fertility
Do not take Xaluprine if you are planning to become pregnant without first asking your
doctor. This applies to both men and women. Xaluprine may damage sperm or
eggs. An effective method of contraception must be used to avoid pregnancy while one of the
partners is taking Xaluprine. Men and women should continue to use effective methods of contraception
for at least three months and six months respectively after stopping the last dose. Ask
your doctor for advice. If you are already pregnant, you should consult your doctor before taking
Xaluprine.
Taking Xaluprine during pregnancy can cause severe and excessive itching without
rash. Nausea and loss of appetite may also occur at the same time, which
may indicate a condition called cholestasis of pregnancy (a liver disease during
pregnancy). Consult your doctor immediately, as this condition can cause harm to the fetus.
Xaluprine should not be handled by pregnant women, breastfeeding women or those
planning a pregnancy.
Do not breastfeed while taking Xaluprine. Ask your doctor, pharmacist or midwife for advice.

Driving and using machines
There are no known effects of Xaluprine on the ability to drive or operate machinery, but this has not
been confirmed in studies.

Xaluprine contains aspartame, sodium methylparahydroxybenzoate (E219),
sodium ethylparahydroxybenzoate (E215) and sucrose
This medicine contains 3 mg of aspartame (E951) per 1 ml. Aspartame is a source of phenylalanine.
It may be harmful if you have phenylketonuria, a rare genetic disorder that causes a build-up of
phenylalanine because the body cannot break it down properly.
Xaluprine also contains sodium methylparahydroxybenzoate (E219) and sodium ethylparahydroxybenzoate
(E215), which may cause allergic reactions (including delayed reactions).
Xaluprine contains sucrose. If you have been diagnosed with an intolerance to certain sugars, contact
your doctor before taking this medicine. It may be harmful to your teeth.

3. How to take Xaluprine

Xaluprine must be prescribed by a specialist doctor experienced in blood diseases.

• During therapy with Xaluprine, the doctor will subject you to regular blood tests to check the number and type of cells in the blood and to verify that the liver is functioning correctly.
• The doctor may also request other blood and urine tests to monitor your uric acid levels. Uric acid is a natural organic chemical agent, the levels of which may increase during therapy with Xaluprine.
• The doctor may sometimes adjust your dose of Xaluprine following these tests.

Take this medicine following the doctor's or pharmacist's instructions exactly. If you have any doubts, consult your doctor or pharmacist. The usual initial dose for adults, adolescents and children varies between 25 and 75 mg/m of body surface area per day. The doctor will prescribe the correct dose for you. Carefully check the prescribed dose and the dosage of the oral suspension to ensure you take the correct amount of medicine, as shown in the following tables. The doctor may sometimes adjust your dose of Xaluprine, for example following various tests. If you have any doubts about the amount of medicine to take, always ask your doctor or nurse. It is important to take Xaluprine in the evening hours to enhance its effectiveness. You can take the medicine with food or on an empty stomach, but the chosen method must be kept consistent from day to day. The medicine should be taken at least one hour before or two hours after taking milk or dairy products. The package of Xaluprine contains a bottle of medicine, a cap, a bottle adapter and two dosing syringes (one 1 ml syringe and one 5 ml syringe). Always use the supplied syringes to take the medicine. It is important to use the correct dosing syringe for the medicine. Your doctor or pharmacist will tell you which syringe to use according to the dose that has been prescribed for you. The smaller1 ml syringe, graduated from 0.1 ml to 1 ml, is for measuring doses equal to or less than 1 ml. You must use this syringe if the total amount to be taken is equal to or less than 1 ml (0.1 ml contains 2 mg of mercaptopurine). The following table shows the conversion from dose (mg) to volume (ml) for the 1 ml syringe. The larger5 ml syringe, graduated from 1 ml to 5 ml, is used to measure doses greater than 1 ml. You must use this syringe if the total amount to be taken is greater than 1 ml (0.2 ml contains 4 mg of mercaptopurine). The following table shows the conversion from dose (mg) to volume (ml) for the 5 ml syringe. Parents or caregivers administering the medicine must wash their hands before and after administering the dose. Immediately clean up any spills. To reduce the risk of exposure, disposable gloves should be used when handling Xaluprine. In case of accidental contact of Xaluprine with the skin, eyes or nose, the affected area should be washed immediately and thoroughly with soap and water. Follow the instructions below for using the medicine:

• 1. Wear disposable gloves before handling Xaluprine.
• 2. Shake the bottle vigorously for at least 30 secondsto ensure the medicine is well mixed (Figure 1).
• 3. Remove the cap from the bottle (Figure 2), place the adapter inserting it firmly into the opening of the bottle and leave it in place for future doses (Figure 3).
• 4. Fully insert the tip of the dosing syringe into the hole in the adapter (Figure 4). The doctor or pharmacist will tell you the correct syringe to use, the 1 ml or the 5 ml one, to administer the correct dose.
• 5. Turn the bottle upside down (Figure 5).
• 6. Pull the plunger of the syringe, drawing the medicine from the bottle into the syringe. Pull the plunger up to the mark corresponding to the prescribed dose (Figure 5). If you have any doubts about the amount of medicine to draw up with the syringe, always ask your doctor or nurse for advice.
• 7. Return the bottle to the vertical position and gently remove the syringe from the adapter, holding it by the body rather than the plunger.
• 8. Gently insert the tip of the syringe into the mouth, inside the cheek.
• 9. Push the plunger slowly and gently to allow the medicine to flow inside the cheek and swallow it. DO NOT push the plunger forcefully or spray the medicine into the back of the mouth or throat, as it may go down the wrong way.
• 10. Remove the syringe from the mouth.
• 11. Swallow the dose of oral suspension and drink some water, making sure that no medicine remains in the mouth.
• 12. Replace the cap on the bottle leaving the adapter in place. Make sure the cap is tightly closed.
• 13. Wash the syringe with warm water and rinse well. Keep the syringe under water and move the plunger up and down several times to ensure the inside of the syringe is clean. Allow the syringe to dry completely in the air before reusing it. Do not dry it with a cloth. Store the syringe in a hygienic place together with the medicine.

Repeat the operations described above for each dose, according to the instructions of your doctor or pharmacist.

If you take more Xaluprine than you should
If you take more Xaluprine than you should, inform your doctor or go to hospital immediately. You may feel unwell, vomit or have diarrhea. Bring the package of the medicine and this

If you forget to take Xaluprine
Inform your doctor. Do not take a double dose to make up for the missed dose.
If you stop taking Xaluprine
Do not stop taking the medicine unless your doctor tells you to, as you may have a relapse.
If you have any questions about using 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 notice any of the following side effects, tell your specialist doctor or go
to hospital immediately:

• Allergic reaction, the signs of which may include: or skin rashes or high fever

or joint pain
or swelling of the face
or skin nodules (erythema nodosum) (frequency unknown)

• Any sign of fever or infection (sore/inflamed throat or mouth or urinary problems)
• Any unexplained bruising or bleeding, as this could mean that there is insufficient production of cells of a particular type
• Any sudden feeling of illness (even with a normal temperature) accompanied by abdominal pain and nausea/vomiting, as this could be a sign of inflammation of the pancreas
• Any yellowing of the whites of the eyes or skin (jaundice)
• In case of diarrhea

Tell your doctor if you notice any of the following side effects, which may
also be caused by this medicine:

Very common (affects more than 1 in 10 people)

• decrease in the number of white blood cells and platelets (which may show up in blood tests)

Common (affects less than 1 in 10 people)

• Nausea or vomiting
• Liver damage (which may show up in blood tests)
• Decrease in red blood cells, which can cause fatigue, weakness or shortness of breath - called anemia
• loss of appetite
• diarrhea
• inflammation of the pancreas (pancreatitis) in patients with inflammatory bowel disease

Uncommon (affects less than 1 in 100 people)

• ulcers in the mouth
• joint pain
• skin rashes
• fever
• permanent liver damage (hepatic necrosis)

Rare (affects less than 1 in 1,000 people)

• hair loss
• in men: temporary decrease in the number of sperm
• allergic reaction leading to swelling of the face
• various types of cancer including blood cancers, lymphomas and skin cancer
• inflammation of the pancreas (pancreatitis) in patients with leukemia (blood cancer)

Very rare (affects less than 1 in 10,000 people)

• a type of leukemia different from the one being treated
• intestinal ulcers

Other side effects (of unknown frequency)

• a rare type of cancer (T-cell hepatosplenic lymphoma, in patients with a disease known as inflammatory bowel disease) (see section 2, Warnings and precautions)
• burning or tingling sensation in the mouth or lips (inflammation of the mucous membrane, stomatitis)
• chapped or swollen lips (cheilitis)
• vitamin B3 deficiency (pellagra) associated with localized pigmented rash, diarrhea or decreased memory, reasoning or other cognitive abilities
• sensitivity to sunlight causing skin reactions
• a decrease in clotting factors

Additional side effects in children and adolescents
Low blood sugar (hypoglycemia) – frequency is unknown.
If any of these side effects get serious, or if you notice any side effect

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side effects you can help to provide more
information on the safety of this medicine.

5. How to store Xaluprine

• Keep this medicine out of the sight and reach of children, preferably locked up. Accidental ingestion may be fatal to children.
• Do not use this medicine after the expiry date which is stated on the carton and the bottle after “exp”. The expiry date refers to the last day of that month.
• Do not store at a temperature above 25˚C.
• Keep the bottle tightly closed to avoid deterioration of the medicine and reduce the risk of accidental spillage.
• Any unused medicine must be disposed of 56 days after the first opening of the bottle.

Do not throw away any medicine in the wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Xaluprine contains
The active ingredient is mercaptopurine (as monohydrate). 1 ml of suspension contains 20 mg of
mercaptopurine monohydrate.
The excipients are xanthan gum, aspartame (E951), concentrated raspberry juice, sucrose,
sodium methylparahydroxybenzoate (E219), sodium ethylparahydroxybenzoate (E215), potassium sorbate
(E202), sodium hydroxide and purified water (see paragraph 2: Xaluprine contains aspartame,
sodium methylparahydroxybenzoate (E219), sodium ethylparahydroxybenzoate (E215) and sucrose).

Description of the appearance of Xaluprine and contents of the pack
Xaluprine is an oral suspension of colour ranging from pink to brown. It is packaged in glass bottles of
100 ml with a child-resistant closure. Each pack contains one bottle, a bottle adapter and two
dosing syringes (one 1 ml graduated syringe and one 5 ml graduated syringe). Your doctor or
pharmacist will advise you which syringe to use according to the dose that has been prescribed for you.

Marketing authorisation holder
Lipomed GmbH
Hegenheimer Strasse 2
79576 Weil am Rhein
Germany

Manufacturer
Pronav Clinical Ltd.
Unit 5
Dublin Road Business Park
Carraroe, Sligo
F91 D439
Ireland
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu