Atriance 5 mg/ml solution for infusion

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Atriance 5 mg/ml solution for infusion

nelarabine

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet includes information on how to report adverse reactions.

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Atriance is and what it is used for

Atriance contains nelarabine, which belongs to a group of medicines known as antineoplastic agents used in chemotherapy to destroy certain types of cancer cells.

Atriance is used to treat patients with:

• a type of leukemia called T-cell acute lymphoblastic leukemia. Leukemia causes an abnormal increase in the number of white blood cells. This abnormal increase in white blood cells may occur in the blood or in other parts of the body. The type of leukemia refers to the type of white blood cells mainly affected. In this case, the cells known as lymphoblasts.
• a type of lymphoma called T-cell lymphoblastic lymphoma. This lymphoma is caused by an accumulation of lymphoblasts, a type of white blood cell.

If you have any questions about your disease, please consult your doctor.

2. What you need to know before Atriance is administered to you

You or your child (if he/she is being treated) must not receive Atriance

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

Warnings and Precautions

Serious neurological side effects have been reported with the use of Atriance. Symptoms include altered mental status (e.g., fatigue), nervous system disorders (e.g., seizures, numbness or tingling sensations, weakness, and paralysis). Your doctor will check regularly for these symptoms (see also “Possible side effects”).

Additionally, 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. A dose adjustment of Atriance may be required.
• if you (or your child, if he/she is being treated) have recently been vaccinated or are scheduled to be vaccinated with a live vaccine (for example, polio, varicella, typhoid).
• if you (or your child, if he/she is being treated) have any blood disorders (for example, anemia).

Blood tests during treatment

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

Elderly patients

If you are elderly, you may be more sensitive to adverse effects affecting the nervous system (see the list above under “Warnings and precautions”). Your doctor will monitor these symptoms regularly during treatment.

Inform 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 need to take any other medicines. This includes any herbal products or medicines purchased without a prescription.

Remember to inform your doctor if you start taking any new medicine while undergoing treatment with Atriance.

Pregnancy, breastfeeding, and fertility

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

Men who wish to father a child should seek advice from their doctor regarding family planning or treatment. Inform your doctor immediately if pregnancy occurs during treatment with Atriance.

It is unknown whether Atriance passes into breast milk. Breastfeeding should be discontinued during treatment with Atriance. Consult your doctor before taking any medicine.

Driving and use of machines

Atriance may cause drowsiness during treatment and for several days afterward. If you feel tired or weak, do not drive or operate tools or machinery.

Atriance contains sodium

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

3. How Atriance is administered

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 height and weight).
• the results of blood tests performed before treatment.

Adults and adolescents (16 years of age and older)

The normal dose is 1,500 mg/m² of body surface area per day.

A doctor or nurse will administer the appropriate dose of Atriance to you by infusion (an intravenous drip). It is usually given into the arm and administration typically lasts about 2 hours.

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

Children and adolescents (21 years of age or younger)

The normal dose is 650 mg/m² of body surface area per day.

A doctor or nurse will administer an appropriate dose of Atriance to you/your child (if he/she is being treated) by infusion (an intravenous drip). It is usually given into the arm and administration typically lasts about 1 hour.

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

Discontinuation of Atriance treatment

Your doctor will decide when to discontinue treatment.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Most of the adverse effects reported with Atriance were observed in adults, children, and adolescents. Some adverse effects were reported more frequently in adults. The reason for this is unknown.

If you have any doubts, consult your doctor.

Very common adverse effects

May affect more than 1 in 10 people treated with Atriance.

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

• Fever

• severe deterioration in your general condition

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

Contact your doctor immediately if you notice any of these signs. A blood test will be required to check for a possible reduction in the number of white blood cells.

Other very common adverse effects

• Changes in sensation in hands or feet, muscle weakness presenting as difficulty rising from a chair or difficulty walking (peripheral neuropathy); reduced sensitivity to light touch, or pain; abnormal sensations such as burning and prickling, a tingling sensation in the skin.
• General feeling of weakness and tiredness (transient anemia). In some cases, a blood transfusion may be necessary.
• Unexplained bruising or bleeding, caused by a decrease in the number of cells involved in blood clotting. This may lead to severe bleeding from relatively minor injuries such as small cuts. Rarely, this may result in more serious bleeding (haemorrhage). 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 of discomfort in the stomach (nausea); vomiting; diarrhoea, constipation.
• Muscle pain.
• Swelling in certain areas of the body, caused by retention of abnormal amounts of fluid (oedema).
• Elevated body temperature (fever); tiredness; feeling of weakness/loss of strength.

Inform your doctor if any of these effects become bothersome.

Common adverse effects

May affect up to 1 in 10 people treated with Atriance:

• Violent, uncontrollable muscle contractions, often accompanied by loss of consciousness, possibly due to an epileptic seizure (fit).

• Clumsiness and lack of coordination, affecting balance, walking, movements of limbs or eyes, or speech.

• Involuntary 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, mouth ulcers or inflammation.

• Memory problems, disorientation, blurred vision, loss or alteration of taste (dysgeusia).

• Accumulation of fluid around the lungs, causing chest pain and difficulty breathing (pleural effusion), whistling sounds.

• Increased levels of bilirubin in the blood, which may cause yellowing of the skin and may make you feel drowsy.

• Increased blood levels of liver enzymes.

• Increased levels of creatinine in the blood (a sign of kidney problems, which may result in reduced frequency of urination).

• Release of the contents of tumor cells (tumor lysis syndrome), which may cause stress to your body. Initial symptoms include nausea, vomiting, difficulty breathing, irregular heartbeat, darkening of the urine, numbness and/or joint discomfort. If this occurs, it is most likely to happen with the first dose. Your doctor will take appropriate precautions to minimize the risk of this occurring.

• Decreased blood levels of certain substances:

• decreased calcium levels, which may cause muscle cramps, abdominal cramps, or spasms.

• decreased magnesium levels, which may cause muscle weakness, confusion, jerking movements, high blood pressure, irregular heartbeat, and reduced reflexes with severely decreased magnesium levels.

• decreased potassium levels, which may cause a feeling of weakness.

• decreased glucose levels, which may cause nausea, sweating, weakness, fainting, confusion, or hallucinations.

Inform your doctor if any of these effects become bothersome.

Rare adverse effects

These may affect up to 1 in 1,000 people treated with Atriance.

• Severe illness (rhabdomyolysis) that destroys skeletal muscle, characterized by the presence of myoglobin (a product of muscle cell breakdown) in the urine, and increased blood levels of creatine phosphokinase.

Inform your doctor if any of these effects become bothersome.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Annex V. By reporting adverse 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 stated on the carton and on the vial.

This medicine does not require any special storage conditions.

After opening the vial, Atriance is stable for 8 hours at a temperature of up to 30°C.

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

6. Contents of the pack and other information

Composition of Atriance

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

Appearance of the product and contents of the container

Atriance infusion solution is a clear, colourless solution. It is supplied in clear glass vials with rubber stoppers sealed with an aluminium cap.

Each vial contains 50 ml.

Atriance is available in packs containing 1 vial or 6 vials.

Marketing Authorisation Holder

Sandoz Pharmaceuticals d.d.

Verovškova ulica 57

1000 Ljubljana

Slovenia

Manufacturer responsible

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

This medicinal product has been authorised under "exceptional circumstances".

This type of approval means that, due to the rarity of the disease, it has not been possible to obtain complete information about this medicine.

The European Medicines Agency will review any new information on this medicine annually, and this leaflet will be updated as necessary.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/. The website also provides links to other websites on rare diseases and orphan medicinal products.

This information is intended for healthcare professionals only:

INSTRUCTIONS ON HOW TO STORE AND DISPOSE OF ATRIANCE

Storage of Atriance solution for infusion

This medicine does not require special storage conditions.

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

Instructions for handling and disposal of Atriance

Standard procedures for handling and disposal of antineoplastic agents should be followed:

• Personnel must be trained in how to handle and transfer the medicine.
• Healthcare personnel who are pregnant must not handle this medicine.
• During handling/transfer of the medicine, healthcare personnel must wear protective clothing, including mask, protective goggles, and gloves.
• All materials used for administration or cleaning, including gloves, must be placed in disposable high-risk waste bags for high-temperature incineration. Any liquid waste resulting from the preparation of nelarabine infusion solution may be disposed of with abundant water.
• Accidental contact with skin or eyes must be immediately treated with abundant water.