Xaluprine 20 mg/ml oral suspension

• 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. This includes any possible side effects not listed in this leaflet. See section 4.

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

Talk to your doctor, pharmacist or nurse before taking Xaluprine

• if you have been vaccinated with yellow fever vaccine.
• if you have kidney or liver problems, as your doctor will need to check that they are working properly.
• if you have a condition where your body produces too little of the enzyme called TPMT (thiopurine methyltransferase), as your doctor may need to adjust the dose.
• if you are planning to have a baby. This applies to both men and women. Xaluprine may harm your sperm or eggs (see ‘Pregnancy, breast-feeding and fertility’ below).

If you are receiving immunosuppressive therapy, taking Xaluprine could put you at greater risk of:

• tumours, including skin cancer. Therefore, when taking Xaluprine, avoid excessive exposure to sunlight, wear protective clothing and use protective sunscreen with a high protection factor
• lymphoproliferative disorders
  • treatment with Xaluprine increases your risk of getting a type of cancer called lymphoproliferative disorder. With treatment regimen containing multiple immunosuppressants (including thiopurines), this may lead to death.
  • A combination of multiple immunosuppressants, given concomitantly increases the risk of disorders of the lymph system due to a viral infection (Epstein-Barr virus (EBV)-associated lymphoproliferative disorders).

Taking Xaluprine could put you at greater risk of:

• developing a serious condition called Macrophage Activation Syndrome (excessive activation of white blood cells associated with inflammation), which usually occurs in people who have certain types of arthritis.

Some patients with inflammatory bowel disease who have received 6-mercaptopurine have developed a rare and aggressive type of cancer called Hepatosplenic T-cell Lymphoma (see section 4, Possible side effects).

Infections

When you are treated with Xaluprine the risk of viral, fungal and bacterial infections is increased and the infections may be more serious. See also section 4.

Tell your doctor before starting treatment whether or not you have had chickenpox, shingles 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 which is involved in the break-down of Xaluprine in the body), you have a higher risk of infections and hair loss and your doctor may in this case give you a lower dose.

Vitamin B3 deficiency (pellagra)

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

Avoid contact of Xaluprine with your skin, eyes or nose. If you accidentally get some in your eyes or nose, flush the area with water.

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

Low blood sugar has sometimes been seen in children, mainly in children under the age of six or with a low body mass index. Talk to your child´s doctor if this happens.

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:

• other cytotoxic medicines (chemotherapy) - when used with Xaluprine there is a greater chance of side effects, such as anaemia
• 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)
• methotrexate (used to treat cancer, rheumatoid arthritis or skin disease (severe psoriasis))
• anti-epileptic medicines such as phenytoin, carbamazepine. Blood levels of anti-epileptic medicines may need to be monitored and doses adjusted if necessary
• infliximab (used to treat certain bowel diseases (Crohn’s disease and ulcerative colitis), rheumatoid arthritis, ankylosing spondylitis or skin disease (severe psoriasis))

If you are going to have a vaccination it is important to speak to your doctor or nurse before you have it. Vaccination with live vaccines (like polio, measles, mumps and rubella) is not recommended, as these vaccines may give you an infection if you have them whilst you are taking Xaluprine.

Xaluprine may be taken with food or on an empty stomach. However, the choice of method should be consistent from day to day.

Do not take Xaluprine at the same time as 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 milk or dairy products.

Do not take Xaluprine if you are planning to have a baby without first speaking to your doctor for advice. This applies to both men and women. Xaluprine may harm your sperm or eggs. Reliable contraception must be used to avoid pregnancy whilst you or your partner are taking Xaluprine. Both men and women should continue to use effective contraception for at least 3 months after stopping treatment. If you are already pregnant, you must talk to your doctor before taking Xaluprine.

Taking Xaluprine during pregnancy may cause severe, excessive itching without a rash. You may also experience nausea and loss of appetite at the same time, which may indicate a condition called cholestasis of pregnancy (a disease of the liver during pregnancy). Talk with your doctor immediately, as this condition can cause harm to your unborn child.

Xaluprine should not be handled by women who are or planning to be pregnant or breast-feeding.

Do not breast-feed while taking Xaluprine. Ask your doctor, pharmacist or midwife for advice.

It is not expected that Xaluprine will affect your ability to drive or use machines but no studies have been done to confirm this.

This medicine contains 3 mg aspartame (E951) in each 1 ml. Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

Xaluprine also contains sodium methyl parahydroxybenzoate (E219) and sodium ethyl parahydroxybenzoate (E215) which may cause allergic reactions (possibly delayed).

Xaluprine contains sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. May be harmful to the teeth.

If you take more Xaluprine than you should, tell your doctor or go to a hospital immediately. You may feel sick, vomit or have diarrhoea. Take the medicine pack and this leaflet with you.

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

Do not stop taking your medicine unless your doctor tells you to or you may get a relapse of your condition.

• Allergic reaction, the signs may include:
  • skin rashes
  • high temperature
  • joint pain
  • swollen face
  • skin nodules (erythema nodosum) (the frequency is unknown)
• Any signs of fever or infection (sore throat, sore mouth or urinary problems)
• Any unexpected bruising or bleeding, as this could mean that too few blood cells of a particular type are being produced
• If you suddenly feel unwell (even with a normal temperature) and have abdominal pain and sickness, as this could be a sign of an inflamed pancreas
• Any yellowing of the whites of the eyes or skin (jaundice)
• If you have diarrhoea

Talk to your doctor if you have any of the following side effects which may also happen with this medicine:

Very common (affects more than 1 in 10 people)

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

Common (affects less than 1 in 10 people)

• feeling or being sick (nausea or vomiting)
• liver damage - this may show up in blood tests
• a drop in red blood cells which may make you tired, weak or breathless (called anaemia)
• loss of appetite
• diarrhoea

Uncommon (affects less than 1 in 100 people)

• mouth ulcers
• inflamed pancreas
• joint pain
• skin rash
• fever
• permanent damage to the liver (hepatic necrosis)

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

• hair loss
• in men: temporary low sperm count
• swollen face
• various types of cancers including blood, lymph and skin cancers

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

• a different type of leukaemia to that being treated
• ulcers in the intestines

Other side effects (the frequency is unknown)

• a rare type of cancer (hepatosplenic T-cell lymphoma), (see section 2, Warnings and Precautions).
• burning or tingling sensation in the mouth or lips (inflammation of the mucosa, stomatitis).
• cracked or swollen lips (cheilitis).
• vitamin B3 deficiency (pellagra) associated with a localised pigmented skin rash, diarrhoea or decrease in memory, reasoning or other thinking skills.
• sensitivity to sunlight causing skin reactions.
• a decrease in clotting factors.

Low blood sugar (hypoglycaemia) - the frequency is unknown.

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

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is mercaptopurine (as monohydrate). One ml of suspension contains 20 mg of mercaptopurine monohydrate.

The other ingredients are xanthan gum, aspartame (E951), concentrated raspberry juice, sucrose, sodium methyl parahydroxybenzoate (E219), sodium ethyl parahydroxybenzoate (E215), potassium sorbate (E202), sodium hydroxide and purified water (see section 2 Xaluprine contains aspartame, sodium methyl parahydroxybenzoate (E219), sodium ethyl parahydroxybenzoate (E215) and sucrose).

Xaluprine is a pink to brown oral suspension. It comes in glass bottles of 100 ml capped with a child-resistant closure. Each pack contains one bottle, a bottle adaptor and two dosing syringes (a syringe graduated to 1 ml and a syringe graduated to 5 ml). Your doctor or pharmacist will advise which syringe to use depending on the dose that has been prescribed.