ONCASPAR 750 U/mL POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the User

Oncaspar 750U/ml powder for solution for injection and infusion

pegaspargase

Read all of this leaflet carefully before this medicine is given 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 or pharmacist. This includes any possible side effects 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 given to you
3. How Oncaspar is given to you
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 leukemia in which certain immature white blood cells (called lymphoblasts) begin to grow out of control, so that they prevent the production of functional blood cells. Oncaspar is used together with other medicines.

2. What you need to know before Oncaspar is given to you

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 a 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 given to you. 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 prone to infections.
• if you have liver damage or are taking other medicines that may harm your liver.
• if Oncaspar is used together with other cancer treatments, it may cause liver damage (severe and potentially life-threatening veno-occlusive hepatic disease (VOD)) with Oncaspar.
• if Oncaspar is used in combination therapy, it may cause damage to the central nervous system.
• if you have abdominal pain. Treatment with Oncaspar may cause pancreatitis, 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.

During post-marketing, an adverse effect called osteonecrosis (bone damage) has been reported in children and adolescents treated with Oncaspar (with a higher incidence in girls), when given simultaneously with glucocorticoids (such as dexamethasone).

If you are a parent of a minor 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. 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 pancreatic activity tests, and other tests to monitor your health during and after treatment, as this medicine may affect your blood and some organs.

Using Oncaspar with other medicines

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This is important because Oncaspar may increase the adverse 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 that you 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, it increases the risk of adverse effects or allergic reactions.
• 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, it increases the risk of bleeding disorders.
• medicines that depend on cell division to work, such as methotrexate (a medicine used for cancer and also for treating arthritis), as its effect may be reduced.
• prednisone, a steroid medicine. If used at the same time as Oncaspar, it increases its effects on blood clotting.
• glucocorticoids, when taken at the same time as part of the recommended treatment for leukemia, Oncaspar may increase the risk of steroid-induced osteonecrosis (bone damage) in children and adolescents, with a higher incidence observed in girls. Therefore, if you experience any new bone pain (i.e., hip, knee, or back pain), please inform your doctor as soon as possible.
• cytarabine, a medicine that may be used in cancer treatment and may interfere with the effects of Oncaspar.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

You should not use Oncaspar if you are pregnant, as it has not been studied during pregnancy. Your doctor will decide if your 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. Ask your doctor which contraceptive method is most suitable 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 discontinued during treatment with Oncaspar and should not be 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 given to you

Before administration, you may receive a combination of medicines to help reduce your chances of developing allergic reactions. Your doctor will decide if this premedication is necessary.

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, which is calculated from your height and weight.

The medicine is given 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 it will be your doctor who gives you the medicine, it is very unlikely that you will be given too much.

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 on 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 get 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, urticaria, difficulty breathing, rapid pulse, and low blood pressure;
• blood clots;
• fever with low white blood cell counts.

Common (may affect up to 1 in 10 people)

• severe bleeding or bruising;
• seizures and loss of consciousness;
• severe infection with high fever;
• liver problems (such as 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.

• jaundice;
• blockage of bile flow from the liver (cholestasis);
• destruction of liver cells (liver necrosis).

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

• a severe skin reaction called toxic epidermal necrolysis;
• loss of kidney function (such as change in urine volume, swelling of the feet and ankles);
• stroke;
• a severe allergic reaction that can cause loss of consciousness and may be life-threatening (anaphylactic shock);
• bone damage (osteonecrosis);
• a severe form of liver damage called veno-occlusive hepatic disease (VOD): symptoms may include rapid weight gain, fluid retention in the abdomen (ascites) causing abdominal swelling, and liver enlargement (hepatomegaly).

Other side effects

Tell your doctor if you have any of these symptoms:

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

• changes in pancreatic 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;
• decrease in white blood cell count.

Common (may affect up to 1 in 10 people)

• decrease in red blood cell count;
• 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 the available data)

• decrease in platelet count;
• fever;
• pancreatic cysts, swelling of the salivary glands;
• high levels of urea in the blood; antibodies against Oncaspar; high levels of ammonia in the blood; low 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 side effects directly through the national reporting system listed 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 medicine has been reconstituted and 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 up to 48 hours.

Do not use this medicine if you notice that the reconstituted 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. Each vial contains 3,750 U of pegaspargase.

After reconstitution, 1 ml of solution contains 750 U of pegaspargase (750 U/ml).

The other components are: disodium phosphate heptahydrate, sodium dihydrogen phosphate (monohydrate), sodium chloride, sucrose, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) (see section 2: "Oncaspar contains sodium").

Appearance of Oncaspar and container contents

Oncaspar is a white to off-white powder. After reconstitution, the solution is clear and colorless, and does not contain any foreign particles.

Each container contains 1 glass vial with 3,750 U of pegaspargase.

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 prospectus: <{MM/YYYY}><{month YYYY}>.

Detailed information about this medication 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 doctors and healthcare professionals with experience in the use of chemotherapeutic agents against cancer.

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

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Instructions for preparation, storage, and disposal of Oncaspar:

Handling instructions

1. Personnel should receive training on handling and transferring the medication (pregnant women who are part of the personnel should avoid working with this medication).
2. Aseptic technique should be used.
3. Procedures for the correct handling of antineoplastic drugs should be observed.
4. It is recommended to use disposable gloves and protective clothing when handling Oncaspar.
5. All items for administration or cleaning, including gloves, should be placed in high-risk waste disposal bags for incineration at high temperatures.

Reconstitution

1. 5.2 ml of water for injectable preparations should be injected into the vial using a syringe and a 21-gauge needle.
2. The vial should be gently rotated until the powder is reconstituted.
3. After reconstitution, the solution should be clear and colorless and should not contain any visible foreign particles. Do not use if the solution is cloudy or if a precipitate has formed. Do not shake.
4. The solution should be used within 24 hours of reconstitution when stored at less than 25 °C.

Administration

1. Parenteral medications should be examined before administration to check for particles; only clear, colorless solutions without visible foreign particles should be used.
2. The medication should be administered intravenously or intramuscularly. The solution should be administered slowly. In the case of intramuscular injection, the volume should not exceed 2 ml in children and adolescents and 3 ml in adults.

In the case of intravenous administration, the reconstituted solution should be diluted in 100 ml of injectable sodium chloride solution at a concentration of 9 mg/ml (0.9%) or a 5% glucose solution.

The diluted solution may be administered over a period of 1 to 2 hours along with an ongoing intravenous infusion, either of a sodium chloride solution at a concentration of 9 mg/ml (0.9%) or a 5% glucose solution. No other medication should be infused through the same intravenous line during the administration of Oncaspar (see section 4.2).

After dilution, the solution should be used immediately. If this is not possible, the diluted solution may be stored at a temperature between 2 °C and 8 °C for up to 48 hours.

Disposal

Oncaspar is for single use. Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

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