ONCASPAR 750 U/ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oncaspar 750U/ml solution for injection and infusion

Pegaspargase

Read all of this leaflet carefully before this medicine is administered to you 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.
• If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Oncaspar is and what it is used for

Oncaspar contains pegaspargase, which is an enzyme (asparaginase) that lowers the level of asparagine, an important component of proteins without which cells cannot survive. Normal cells are able to synthesize asparagine themselves, while some cancer cells cannot. Oncaspar decreases the level of asparagine in cancer cells in the blood and prevents cancer cells from growing.

Oncaspar is used together with other medicines to treat acute lymphoblastic leukemia (ALL) in children from birth to 18 years of age and in adults. ALL is a type of blood cancer in which certain immature white blood cells (called lymphoblasts) start growing out of control, preventing the production of functional blood cells. Oncaspar is used together with other medicines.

2. What you need to know before Oncaspar is administered

Do not use Oncaspar

• if you are allergic to pegaspargase or any of the other ingredients of this medicine (listed in section 6).
• if you have severe liver disease.
• if you have ever had pancreatitis.
• if you have had severe bleeding after treatment with asparaginase.
• if you have ever had blood clots after treatment with asparaginase.

Tell your doctor if you have any of these conditions. If you are the parent of a child being treated with Oncaspar, tell the doctor if your child has any of these conditions.

Warnings and precautions

Talk to your doctor before Oncaspar is administered. This medicine may not be suitable for you:

• if you have had severe allergic reactions to other forms of asparaginase, such as itching, redness, or swelling of the airways, as Oncaspar may cause severe allergic reactions
• if you have a bleeding disorder or have had severe blood clots
• if you have a fever. This medicine may make you more susceptible to infections
• if you have any impairment of liver function or are using other medicines that may harm the liver. When Oncaspar is used together with other cancer treatments, liver and central nervous system damage may occur
• if you have abdominal pain. Treatment with Oncaspar may cause pancreas inflammation, which can be life-threatening in some cases.

This medicine may cause changes in blood clotting factors and may increase the risk of bleeding and/or blood clots.

If you are the parent of a child being treated with Oncaspar, talk to the doctor if your child has any of these conditions.

During treatment with Oncaspar

During the administration of Oncaspar, you will be closely monitored for one hour after the start of treatment for any signs of severe allergic reaction. The necessary medical equipment to treat allergic reactions should be available for use.

Additional monitoring tests

You will have frequent blood glucose tests, urine glucose tests, liver and pancreas activity tests, and other tests to monitor your health during and after treatment, as this medicine may affect the blood and some organs.

Using Oncaspar with other medicines

Tell your doctor if you are using, have recently used, or may need to use any other medicine. This is important because Oncaspar may increase the side effects of other medicines due to its effect on the liver, which plays a significant role in the elimination of medicines from the body. Also, it is particularly important to inform your doctor if you are also taking any of the following medicines:

• vaccination with live vaccines in the three months following the end of treatment for leukemia. This will increase the risk of contracting severe infections.
• vincristine, another cancer medicine. If used at the same time as Oncaspar, the risk of side effects or allergic reactions increases.
• medicines that reduce blood clotting, such as anticoagulants (e.g., coumarin/warfarin and heparin), dipyridamole, acetylsalicylic acid, and/or non-steroidal anti-inflammatory medicines (such as ibuprofen or naproxen). If used at the same time as Oncaspar, the risk of bleeding disorders increases.
• medicines that depend on cell division to work, such as methotrexate (a medicine used for cancer and also for treating arthritis), as their effect may be reduced.
• prednisone, a steroid medicine. If used at the same time as Oncaspar, its effects on blood clotting increase.
• cytarabine, a medicine that may be used in cancer treatment and may interfere with the effects of Oncaspar.

Oncaspar may also change liver activity, which can affect how other medicines work.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, talk to your doctor before using this medicine.

Do not use Oncaspar if you are pregnant, as its effects during pregnancy have not been studied. Your doctor will decide if the disease requires treatment. Women who may become pregnant should use effective contraceptive methods during treatment and for at least 6 months after the end of treatment with Oncaspar.

Oral contraceptives are not an effective method of contraception while being treated with Oncaspar. Talk to your doctor about the most suitable contraceptive method for you. Men should also use effective contraception while they or their partners are being treated with Oncaspar.

It is not known if pegaspargase is excreted in breast milk. As a precaution, breastfeeding should be interrupted during treatment with Oncaspar and not resumed until treatment with Oncaspar has been discontinued.

Driving and using machines

Do not drive or use machines while using this medicine because it may cause drowsiness, fatigue, or confusion.

Oncaspar contains sodium

This medicine contains less than 1 mmol of sodium per dose, which is essentially sodium-free.

3. How Oncaspar is administered

Treatment with Oncaspar has been prescribed by a doctor with experience in medicines for treating cancer. The doctor will decide on the necessary dose of the medicine and the frequency of administration, based on your age and body surface area (BSA), which is calculated from your height and weight.

The medicine is administered as a solution by injection into a muscle and, if more convenient, into a vein.

If you are given more Oncaspar than you should

As the medicine will be administered by a doctor, it is unlikely that you will be given more than necessary.

In the unlikely event of accidental overdose, the medical staff will closely monitor you and treat you as necessary.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Tell your doctor immediatelyif you experience any of the following side effects:

Very common (may affect more than 1 in 10 people)

• inflammation or other changes in the pancreas (pancreatitis) accompanied by severe stomach pain that can spread to the back, vomiting, increased blood sugar levels;
• severe allergic reactions with symptoms such as skin rash, itching, swelling, hives, difficulty breathing, rapid pulse, and low blood pressure;
• severe infection with high fever;
• blood clots.

Common (may affect up to 1 in 10 people)

• severe bleeding or bruising;
• seizures and loss of consciousness;
• liver problems (e.g., change in skin color, urine, or stool, and increased liver enzymes or bilirubin in laboratory results).

Rare (may affect up to 1 in 1,000 people)

• liver failure.

Frequency not known (frequency cannot be estimated from available data)

• severe skin reaction called toxic epidermal necrolysis;
• kidney function impairment (e.g., change in urine volume, swelling of the feet and ankles);
• stroke;
• severe allergic reaction that can cause loss of consciousness and may be life-threatening (anaphylactic shock).

Other side effects

Tell your doctor if you experience any of these symptoms:

Very common (may affect more than 1 in 10 people)

• changes in pancreas activity;
• weight loss;
• leg pain (which may be a symptom of thrombosis), chest pain, or difficulty breathing (which may be a symptom of blood clots in the lungs, called pulmonary embolism);
• loss of appetite, general weakness, vomiting, diarrhea, nausea;
• increased blood sugar levels.

Common (may affect up to 1 in 10 people)

• decrease in the number of red blood cells;
• fluid accumulation in the stomach (ascites);
• fever and flu-like symptoms;
• mouth ulcers,
• back, joint, or abdominal pain;
• high levels of fat and cholesterol in the blood; low potassium levels in the blood.

Rare (may affect up to 1 in 1,000 people)

• posterior reversible leukoencephalopathy syndrome (PRES), characterized by symptoms such as headache, confusion, seizures, and loss of vision that resolve over time.

Frequency not known (frequency cannot be estimated from available data)

• decrease in the number of white blood cells and platelets;
• palpitations;
• pancreatic cysts, swelling of the salivary glands;
• high levels of urea in the blood; antibodies against Oncaspar; high levels of ammonia in the blood; decreased blood sugar levels;
• drowsiness, confusion, mild muscle spasms (twitching) in the fingers.

Reporting of side effects

If you experience any side effect that you think may be related to chemotherapy, talk to your doctor, even if it is 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 Oncaspar

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 label and carton after EXP. The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Once the product has been diluted, the solution should be used immediately. If this is not possible, the diluted solution can be stored at a temperature between 2°C and 8°C for a period of up to 48 hours.

Do not use this medicine if you notice that the solution is cloudy or contains visible particles.

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

6. Container contents and additional information

Oncaspar composition

The active ingredient is pegaspargase. One ml of solution contains 750 units of pegaspargase. A 5 ml vial of solution contains 3,750 units of pegaspargase.

The other components are: sodium dihydrogen phosphate (monohydrate), disodium phosphate heptahydrate, sodium chloride, and water for injectable preparations (see section 2: "Oncaspar contains sodium").

Appearance of Oncaspar and container contents

Oncaspar is a clear and colorless injectable solution that comes in a glass vial. Each container contains 1 vial.

Marketing authorization holder

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex

France

Manufacturer

Les Laboratoires Servier Industrie

905 Route de Saran

45520 Gidy

France

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

Date of last revision of this leaflet: <{MM/YYYY}<{Month YYYY}>.

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

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This information is intended only for healthcare professionals:

It is strongly recommended to record the name and batch number of the product each time Oncaspar is administered to a patient, in order to maintain a link between the patient and the product batch.

Given the unpredictability of adverse reactions, Oncaspar should only be administered by physicians and healthcare professionals with experience in the use of cancer chemotherapeutic agents.

Hypersensitivity reactions to Oncaspar may occur during treatment (e.g., anaphylaxis), especially in patients with confirmed hypersensitivity to other forms of L-asparaginase. A routine precaution will be to monitor patients for one hour with cardiopulmonary resuscitation equipment and other necessary items to treat anaphylaxis immediately (epinephrine, oxygen, intravenous corticosteroids, etc.).

Patients should be informed about the possible hypersensitivity reactions to Oncaspar, including immediate-type anaphylaxis. Patients who receive Oncaspar will be at higher risk of bleeding and thrombotic disorders. Patients should be explained that Oncaspar should not be used at the same time as other medications associated with a higher risk of bleeding (see section 2: "Use of Oncaspar with other medications").

This medicinal product may cause skin and eye irritation. Therefore, the solution should be handled and administered with special care. Inhaling vapors and contact with skin and mucous membranes, especially the eyes, should be avoided; if the product comes into contact with the eyes, skin, or mucous membranes, flush immediately with plenty of water for at least 15 minutes.

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Detailed information can be found in the summary of product characteristics or package leaflet.