XALUPRINE 20 mg/ml ORAL SUSPENSION

Introduction

Package Leaflet: Information for the User

Xaluprine 20 mg/ml Oral Suspension

mercaptopurine

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

1. What is Xaluprine and what is it used for

Xaluprine contains mercaptopurine. It belongs to a group of medicines called cytotoxics (also known as chemotherapy).

Xaluprine is used to treat acute lymphoblastic leukemia (also known as acute lymphocytic leukemia or ALL). This is a disease that spreads quickly and causes an increase in the number of new white blood cells. These new white blood cells are immature (not fully formed), so they cannot grow or function properly. As a result, they cannot fight infections and can cause bleeding.

Ask your doctor if you want more information about this disease.

2. What you need to know before you take Xaluprine

• Do not take Xaluprineif you are allergic (hypersensitive) to mercaptopurine or any of the other ingredients of Xaluprine (see section 6).
• Do not get vaccinatedagainst yellow fever while taking Xaluprine, as it can be fatal.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting Xaluprine:

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

• tumors, including skin cancer. Therefore, when taking Xaluprine, avoid excessive exposure to sunlight, wear protective clothing, and use high-protection sunscreens.
• lymphoproliferative disorders

• treatment with Xaluprine increases your risk of having a type of cancer called lymphoproliferative disorder. With treatment that contains multiple immunosuppressants (including thiopurines), this can be fatal.
• The combination of multiple immunosuppressants, administered simultaneously, increases the risk of lymphatic system disorders due to a viral infection (Epstein-Barr virus-associated lymphoproliferative disorders).

Taking Xaluprine 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.

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 appeared (see section 4, Possible side effects).

Infections

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

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

NUDT15 gene mutation

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

Avoid contact between Xaluprine and skin, eyes, or nose. In case of accidental contact with eyes or nose, wash the area with water.

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

Children and adolescents

Low blood sugar levels have occasionally 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.

Using Xaluprine with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. This includes herbal medicines.

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

• other cytotoxic medicines (chemotherapy) - when used with Xaluprine, the likelihood of side effects, such as anemia, increases
• allopurinol or febuxostat (used to treat gout)
• oral anticoagulants (used to thin the blood)
• olsalazine or mesalazine (used for a bowel disorder called ulcerative colitis)
• sulfasalazine (used for rheumatoid arthritis or ulcerative colitis)
• antiepileptics such as phenytoin or carbamazepine. It may be necessary to monitor blood levels of antiepileptics and adjust doses as needed.

Vaccinations during treatment with Xaluprine

If you are going to receive a vaccine, it is important that you consult your doctor or nurse first. The use of vaccines that contain live microorganisms (such as polio, measles, mumps, and rubella vaccines) is not recommended, as they can cause infection while you are taking Xaluprine.

Taking Xaluprine with food and drinks

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

Do not take Xaluprine with milk or dairy products, as they can make the medicine less effective. Xaluprine should be taken at least 1 hour before or 2 hours after consuming milk or dairy products.

Pregnancy, breastfeeding, and fertility

Do not take Xaluprine if you are planning to have a child without consulting your doctor first. This applies to both men and women. Xaluprine can be harmful to sperm or eggs. You and your partner should use effective contraceptive methods to avoid pregnancy while either of you is taking Xaluprine. Both men and women should use an effective contraceptive method for at least 3 months after receiving the last dose of treatment. If you are already pregnant, inform your doctor before taking Xaluprine.

Xaluprine should not be handled by pregnant women, women who plan to become pregnant, or women who are breastfeeding.

Breastfeeding is not recommended during treatment with Xaluprine. Consult your doctor, pharmacist, or midwife.

Driving and using machines

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

Xaluprine contains aspartame, methyl parahydroxybenzoate (E219), ethyl parahydroxybenzoate (E215), and sucrose

Xaluprine can be harmful to people with phenylketonuria because it contains aspartame (E951), which is a source of phenylalanine.

Xaluprine can cause allergic reactions (possibly delayed) because it also contains methyl parahydroxybenzoate (E219) and ethyl parahydroxybenzoate (E215).

Xaluprine contains sucrose. If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine. It can cause tooth decay.

3. How to take Xaluprine

Xaluprine should only be administered by a specialist doctor with experience in treating blood diseases.

• When taking Xaluprine, your doctor will regularly perform blood tests to check the number and type of cells in your blood and to check that your liver is working 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 Xaluprine.
• Your doctor may adjust your dose of Xaluprine depending on the results of these tests.

Follow the instructions for administering this medicine exactly as indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again. 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 your dose of Xaluprine depending on, for example, 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 Xaluprine at night for the medicine to be more effective.

You can take the medicine 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.

Xaluprine is supplied in a box that contains the medicine bottle, a cap, a bottle adapter, and two dosing syringes (one purple 1 ml and one white 5 ml). Always use these syringes to take the medicine.

It is important that you use the correct dosing syringe to take your medication. Your doctor or pharmacist will indicate which syringe you should use depending on the dose prescribed for you.

The smaller 1 ml syringe (purple), graduated between 0.1 and 1 ml, is used to measure doses less than or equal to 1 ml. You should use it if the total amount you need to take is less than or equal to 1 ml (each 0.1 ml mark contains 2 mg of mercaptopurine).

The larger 5 ml syringe (white), graduated between 1 ml and 5 ml, is used to measure doses greater than 1 ml. You should use it if the total amount you need to take is greater than 1 ml (each 0.2 ml mark contains 4 mg of mercaptopurine).

If you are the parent or caregiver administering the medication, wash your hands before and after administering a dose. Clean up spills immediately. To reduce the risk of exposure, use disposable gloves when handling Xaluprine.

If Xaluprine comes into contact with skin, eyes, or nose, wash the area immediately with plenty of water and soap.

Use the medicine according to the following instructions:

1. Put on disposable gloves to handle Xaluprine.
2. Shake the bottle vigorously for at least 30 seconds to ensure the medicine is well mixed (Figure 1).
3. Remove the cap from the bottle (Figure 2), attach the adapter to the neck of the bottle by pressing firmly, and leave it in place for future doses (Figure 3).
4. Insert the tip of the dosing syringe into the adapter opening (Figure 4). Your doctor or pharmacist will indicate whether you should use the 1ml (purple) or 5ml (white) syringe to administer the correct dose.
5. Turn the bottle upside down (Figure 5).
6. Pull the syringe plunger out to withdraw the medicine from the bottle into the syringe. Pull the plunger out to the mark on the scale that matches the prescribed dose (Figure 5). If you have any doubts about the amount of medicine to withdraw from the syringe, always consult your doctor or nurse.
7. Put the bottle back upright and carefully remove the syringe from the adapter, holding it by the cylinder rather than the plunger.
8. Gently place the tip of the syringe in your mouth and towards the inside of your cheek.
9. Slowly and gently push the plunger in to release the medicine into the inside of your cheek and swallow. DO NOT push the plunger in forcefully, or inject the medicine abruptly into the back of your mouth or throat, as you may choke.
10. Remove the syringe from your mouth.
11. After swallowing the dose of oral suspension, drink some water to make sure you don't leave any medicine in your mouth.
12. Put the cap back on the bottle, but leave the adapter in place. Make sure the cap is tightly closed.
13. Wash the syringe with warm soapy water and rinse well. Keep the syringe submerged in water and move the plunger up and down several times to ensure the inside of the syringe is clean. Let the syringe dry completely before using it again to administer another dose. Store the syringe in a hygienic place with the medicine.

Repeat the above procedure each time you need to administer a dose according to the instructions indicated by 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 the hospital immediately. You may have nausea, vomiting, or diarrhea. Bring the medicine package and this leaflet with you.

If you forget to take Xaluprine

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

If you stop taking Xaluprine

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

Allergic reaction, whose signs can be:

• skin rash
• high temperature

• joint pain
• facial swelling

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 too few of a certain type of blood cell.

If you feel unwell suddenly(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 can 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 disease (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, Warnings and precautions).

• sensitivity to sunlight, which causes skin reactions

Other side effects in children

• low blood sugar (hypoglycemia); frequency not known

If you think any of the side effects you are experiencing are serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Xaluprine

• 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 expiration date stated on the packaging after «EXP». The expiration date is the last day of the month indicated.
• Do not store at a temperature above 25°C.
• Keep the container perfectly closed to avoid deterioration of the medicine and reduce the risk of accidental spillage.
• After the first opening of the bottle, discard the unused contents after 56 days.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Xaluprine Composition

The active ingredient is mercaptopurine (as monohydrate). Each milliliter of solution contains 20 mg of mercaptopurine monohydrate.

The other components are xanthan gum, aspartame (E951), concentrated raspberry juice, sucrose, methylparahydroxybenzoate sodium (E219), ethylparahydroxybenzoate sodium (E215), potassium sorbate (E202), sodium hydroxide, and purified water (see section 2 for more information regarding aspartame, methylparahydroxybenzoate sodium (E219), ethylparahydroxybenzoate sodium (E215), and sucrose).

Product Appearance and Package Contents

Xaluprine is a pink to brown suspension. It is presented in 100 ml glass bottles closed with a child-resistant cap. It is supplied in a box containing a bottle, a bottle adapter, and two dosing syringes (one purple graduated up to 1 ml and one white graduated up to 5 ml). Your doctor or pharmacist will indicate which syringe to use, depending on the dose prescribed.

Marketing Authorization Holder

Nova Laboratories Ireland Limited

3rd Floor, Ulysses House

Foley Street, Dublin 1

D01 W2T2

Ireland

Manufacturer

Nova Laboratories Limited

Martin House, Gloucester Crescent

Wigston, Leicester

LE18 4YL

United Kingdom

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

D13H525

Ireland

Date of Last Revision of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.