ATRIANCE 5 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you are given Atriance

You or your child (if he/she is being treated) should not be given Atriance

• if you (or your child, if he/she is being treated) are allergic to nelarabine or any of the other ingredients of this medicine (listed in section 6).

Warnings and Precautions

Severe neurological side effects have been reported with the use of Atriance. The symptoms include altered mental state (e.g. fatigue), alterations in the nervous system (e.g. seizures, sensation of numbness or tingling, weakness and paralysis). Your doctor will check for these symptoms regularly (see also “Possible side effects”).

In addition, your doctor needs to know the following information before administering this medicine:

• if you (or your child, if he/she is being treated) have any kidney or liver problems. You may need a dose adjustment of Atriance
• if you (or your child, if he/she is being treated) have recently been vaccinated or are going to be vaccinatedwith a live vaccine (e.g. polio, chickenpox, typhoid).
• if you (or your child, if he/she is being treated) have any blood problems(e.g. anemia).

Blood tests during treatment

Your doctor should perform regular blood tests during treatment to detect blood problems associated with the use of Atriance.

Elderly people

If you are an elderly person, you may be more sensitive to the side effects that affect the nervous system (see the list above in “Warnings and precautions”). Your doctor will check for these symptoms regularly during treatment.

Tell your doctor if you are in any of these situations.

Other medicines and Atriance

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.This includes any herbal products or medicines obtained without a prescription.

Remember to tell your doctor if you start using any medicine while being treated with Atriance.

Pregnancy, breastfeeding and fertility

Atriance is not recommended in pregnant women. It may harm the baby if conceived before, during, or shortly after treatment. It is recommended that you consult your doctor to use appropriate birth control. Do not try to become pregnant or get your partner pregnant until your doctor tells you it is safe to do so.

Men who wish to have a child should ask their doctor for advice on family planning or treatment. Tell your doctor immediately if you become pregnant during treatment with Atriance.

It is not known if Atriance passes into breast milk. Breastfeeding should be interrupted while being treated with Atriance. Consult your doctor before taking any medicine.

Driving and using machines

Atriance may cause drowsiness during and some days after treatment. If you feel tired or weak, do not drive and do not use tools or machines.

Atriance contains sodium

This medicine contains 88.51 mg (3.85 mmol) of sodium (main component of table/cooking salt) per vial (50 ml). This is equivalent to 4.4% of the maximum recommended daily intake of sodium for an adult.

3. How Atriance is given

The dose you will receive of Atriance will be based on:

• your body surface area/your child's body surface area (if he/she is being treated)(which your doctor will calculate based on your height and weight).
• the results of blood testsperformed before treatment

Adults and adolescents (from 16years)

The usual doseis 1,500 mg/m2 of body surface area per day.

A doctor or nursewill give you the appropriate dose of Atriance through an infusion (a drip). It is usually placed in the arm and the administration usually lasts about 2 hours.

You will receive an infusion (a drip) once a day, ondays 1, 3, and 5 of treatment. This treatment schedule will be repeated generally every three weeks. This treatment may vary, depending on the results obtained in your periodic blood tests. Your doctor will decide how many treatment cycles you may need.

Children and adolescents (21years or less)

The usual doseis 650 mg/m2 of body surface area per day.

A doctor or nursewill give you/your child (if he/she is being treated) an appropriate dose of Atriance through an infusion(a drip). It is usually placed in the arm and the administration usually lasts about 1 hour.

You/your child (if he/she is being treated) will be given Atriance through an infusion (a drip) once a day for 5days. This treatment schedule will be repeated generally every three weeks. This treatment may vary, depending on the results obtained in your periodic blood tests. Your doctor will decide how many treatment cycles you may need.

Discontinuation of treatment with Atriance

Your doctor will decide when to discontinue treatment.

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.

Most side effects reported with Atriance were observed in adults, children, and adolescents. Some side effects were reported more frequently in adults. The reason is unknown.

If you are concerned, consult your doctor.

Very common side effects

May affect more than 1 in 10peopletreated with Atriance.

• Signs of infection. Atriance can reduce the number of white blood cells and decrease your resistance to infection (including pneumonia). This can be life-threatening. Signs of infection include:

• Fever
• severe deterioration of your general condition
• local symptoms such as sore throat or mouth problems or urinary problems (e.g. burning sensation when urinating, which may be due to a urinary tract infection)

Tell your doctor immediatelyif you notice any of these signs. You will need to have a blood test to check for a possible decrease in the number of white blood cells.

Other very common side effects

• Changes in touch sensation in hands or feet, muscle weakness that appears as difficulty getting up from a chair or difficulty walking (peripheral neuropathy); reduced sensitivity to light touch, or pain; abnormal sensations such as burning and tingling, a tingling sensation in the skin.
• General weakness and fatigue (temporary anemia). In some cases, you may need a blood transfusion.
• Unexplained bruising or bleeding, caused by a decrease in the number of cells involved in blood clotting. This can lead to severe bleeding from relatively small wounds such as small cuts. Rarely, this can lead to more severe bleeding (hemorrhage). Talk to your doctor for advice on how to minimize the risk of bleeding.
• Drowsiness; headache; dizziness.
• Shortness of breath or difficulty breathing; cough.
• Feeling sick in the stomach (nausea); vomiting; diarrhea, constipation
• Muscle pain.
• Swelling of some areas of the body, caused by retention of abnormal amounts of fluid (edema).
• High body temperature (fever); fatigue; feeling of weakness/loss of strength.

Tell your doctorif any of these effects become troublesome.

Common side effects

May affect up to 1 in 10peopletreated with Atriance:

• Violent, uncontrollable muscle contractions, often accompanied by loss of consciousness that may be due to an epileptic seizure (seizure).
• Clumsiness and lack of coordination, affecting balance, walking, movement of limbs or eyes, or speech.
• Accidental rhythmic shaking of one or more limbs (tremors).
• Muscle weakness (possibly associated with peripheral neuropathy– see above), joint pain, back pain, pain in hands and feet, including tingling and numbness.
• Low blood pressure.
• Weight loss and loss of appetite (anorexia), stomach pain, mouth pain, ulcers or inflammation of the mouth.
• Memory problems, disorientation, blurred vision, loss or alteration of the sense of taste (dygeusia).
• Fluid accumulation around the lungs, causing chest pain and difficulty breathing (pleural effusion), wheezing.
• Increased bilirubin levels in the blood, which can cause yellowish skin and make you feel drowsy.
• Increased levels of liver enzymes in the blood.
• Increased levels of creatinine in the blood (a sign of kidney problems, which can cause decreased urination frequency).
• Release of tumor cell contents (tumor lysis syndrome), which can cause stress to your body. The initial symptoms are nausea, vomiting, difficult breathing, irregular heartbeat, dark urine, numbness and/or joint discomfort. If this happens, it is more likely to occur with the first dose. Your doctor will take the necessary precautions to minimize the risk of this happening.
• Decrease in blood levels of certain substances:

• decrease in calcium levels, which can cause muscle cramps, abdominal cramps, or spasms.
• decrease in magnesium levels, which can cause muscle weakness, confusion, twitching movements, high blood pressure, irregular heartbeat, and decreased reflexes with severely decreased magnesium levels in the blood.
• decrease in potassium levels, which can cause a feeling of weakness.
• decrease in glucose levels, which can cause nausea, sweating, weakness, fainting, confusion, or hallucinations.

Tell your doctorif any of these effects become troublesome.

Rare side effects

May affect up to 1 in 1,000peopletreated with Atriance

• Serious disease (Rhabdomyolysis) that destroys skeletal muscle, characterized by the presence of myoglobin (product of muscle cell breakdown) in the urine, and increased creatine phosphokinase in the blood.

Tell your doctorif any of these effects become troublesome.

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 through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Atriance

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial.

This medicine does not require any special storage conditions.

Once the vial is opened, Atriance is stable for 8 hours at a temperature up to 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container contents and additional information

Atriance composition

• The active ingredient is nelarabine. Each ml of Atriance solution for infusion contains 5 mg of nelarabine. Each vial contains 250 mg of nelarabine.
• The other ingredients are sodium chloride, water for injectable preparations, hydrochloric acid/sodium hydroxide.

Appearance of the product and container contents

Atriance solution for infusion is a clear, colorless solution. It is supplied in transparent glass vials with rubber stoppers sealed with an aluminum ring.

Each vial contains 50 ml.

Atriance is supplied in packs of 1 vial or 6 vials.

Marketing authorization holder

Sandoz Pharmaceuticals d.d.

Verovškova ulica 57

1000 Ljubljana

Slovenia

Manufacturer

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

EBEWE Pharma Ges.m.b.H. Nfg.KG

Mondseestrasse 11

4866 Unterach am Attersee

Austria

FAREVA Unterach GmbH

Mondseestraße 11

Unterach am Attersee, 4866,

Austria

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

This medicinal product has been authorized under “exceptional circumstances”.

This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.

The European Medicines Agency will review any new information that may become available every year and this leaflet will be updated as necessary.

Detailed information on this medicinal product is available on the European Medicines Agency web site http://www.ema.europa.eu/. It also provides links to other web sites on rare diseases and orphan medicines.

This information is intended only for healthcare professionals:

INSTRUCTIONS ON HOW TO STORE AND DISPOSE OF ATRIANCE

Storage of Atriance solution for infusion

This medicinal product does not require any special storage conditions.

Once the vial is opened, Atriance is stable for 8 hours at a temperature up to 30°C.

Instructions for handling and disposal of Atriance

Normal procedures for handling and disposal of antitumor medicinal products should be followed:

• Staff should be trained on how to handle and transfer the medicinal product.
• Healthcare personnel should not handle this medicinal product during pregnancy.
• During handling/transferring of the medicinal product, healthcare personnel should wear protective clothing, including mask, protective glasses, and gloves.
• All items used for administration or cleaning, including gloves, should be placed in high-risk waste disposable bags for high-temperature incineration. Any liquid waste from the preparation of the Atriance infusion solution may be disposed of with copious amounts of water.
• Accidental contact with skin or eyes should be treated immediately with copious amounts of water.