Prospecto: information for the user

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

pegaspargase

Read this prospect carefully before this medicine is administered to you, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section4.

1.What Oncaspar is and for what it is used

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

3.How Oncaspar is administered

4.Possible adverse effects

5.Storage of Oncaspar

6.Contents of the package and additional information

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 their own asparagine, while some cancer cells, on the other hand, cannot. Oncaspar decreases the level of asparagine in cancerous blood cells and prevents cancerous cells from growing.

Oncaspar is used in combination with other medications to treat acute lymphoblastic leukemia (ALL) in children from birth to 18 years of age and in adults. ALL is a type of leukemic cancer in which certain immature white blood cells (called lymphoblasts) begin to grow uncontrollably, thereby preventing the production of functional blood cells. Oncaspar is used in combination with other medications.

No use Oncaspar

• if you are allergic to pegaspargase or any of the other components of this medication (listed in section6).
• if you have severe liver disease.
• if you have ever had pancreatitis.
• if you have had intense bleeding after treatment with asparaginase.
• if you have ever had thrombosis after treatment with asparaginase.

Inform your doctor if you have any of the mentioned conditions. If you are a parent of a child being treated with Oncaspar, inform your doctor if your child has any of them.

Warnings and precautions

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

• if you have had severe allergic reactions to other forms of asparaginase, for example, itching, redness, or swelling of the airways, as Oncaspar may lead to severe allergic reactions.
• if you have a bleeding disorder or have had severe thrombosis.
• if you have a fever. This medication may make you more vulnerable to infections.
• if you have liver function impairment or are using other medications that may harm the liver.
• if Oncaspar is used with other cancer treatments, it may cause liver damage(severe and potentially fatal veno-occlusive liver disease (VOD)) with Oncaspar.
• if Oncaspar is used in combination therapy, it may cause damageto the central nervous system.
• if you have abdominal pain. With Oncaspar treatment, pancreatitis inflammation may occur, which in some cases can be fatal.

This medication may cause variations in blood clotting factors and may increase the risk of bleeding and/or thrombosis.

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

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

During treatment with Oncaspar

During Oncaspar administration, you will be closely monitored for one hour after treatment initiation for any signs of severe allergic reactions. Medical equipment necessary for treating allergic reactions should be readily available.

Additional monitoring tests

You will undergo frequent blood glucose (blood sugar), glucosuria (urine sugar), liver, and pancreatic activity tests, as well as other tests to monitor your health status during and after treatment, as this medication may affect the blood and some organs.

Use of Oncaspar with other medications

Inform your doctor if you are using, have used recently, or may need to use any other medication. This is important because Oncaspar may increase the adverse effects of other medications by affecting the liver, an organ that plays a crucial role in eliminating medications from the body. Additionally, it is particularly important to inform your doctor if you are also taking any of the following medications:

• vaccination with live-virus vaccines within three months of completing leukemia treatment. This will increase the risk of severe infections.
• vincristine, another cancer medication. If used simultaneously with Oncaspar, the risk of adverse effects or allergic reactions increases.
• blood-thinning medications such as anticoagulants (e.g., warfarin/coumarin and heparin), dipiridamol, acetylsalicylic acid, and/or nonsteroidal anti-inflammatory drugs (e.g., ibuprofen or naproxen). If used simultaneously with Oncaspar, the risk of bleeding disorders increases.
• medications that rely on cell division for their effect, such as methotrexate (a medication used for cancer and also for treating arthritis), as its effect may be reduced.
• prednisone, a steroid medication. If used simultaneously with Oncaspar, its effects on blood clotting increase.
• glucocorticoids, when taken simultaneously as part of the recommended leukemia treatment, 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 (e.g., hip, knee, or back pain), please inform your doctor as soon as possible.
• citarabine, a medication that may be used in cancer treatment and may interfere with the effects of Oncaspar.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication.

You should not use Oncaspar if you are pregnant, as its effects during pregnancy are unknown. Your doctor will decide if the disease requires treatment. Women who may become pregnant should use effective birth control methods during treatment and, at a minimum, for six months after completing Oncaspar treatment.

Oral contraceptives are not an effective method of birth control while being treated with Oncaspar. Consult your doctor about which birth control method may be most suitable for you. Men should also use an effective birth control method while they or their partners are being treated with Oncaspar.

The excretion of pegaspargase in breast milk is unknown. As a precaution, breastfeeding should be interrupted during Oncaspar treatment and not resumed until treatment with Oncaspar has been discontinued.

Driving and operating machinery

Do not drive or operate machinery while using this medication, as it may cause drowsiness, fatigue, or confusion.

Oncaspar contains sodium

This medication contains less than1mmol of sodium per dose, i.e., is essentially sodium-free.

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

Oncaspar treatment has been prescribed by an experienced doctor in cancer medications. The doctor will determine the necessary dose of the medication and the frequency of administration, based on your age and the calculated surface area of your body from your height and weight.

The medication is administered in the form of a solution through injection into a muscle and, if more convenient, through a vein.

If you are given more Oncaspar than you should

Since the doctor will administer the medication, it is very unlikely that you will receive more than necessary.

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

If you have any other questions about the use of this medication, ask your doctor.

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

Severe side effects

Inform your doctor immediately if any of the following side effects occur:

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

• inflammation or other pancreatic changes (pancreatitis) accompanied by severe stomach pain that may radiate to the back, vomiting, and increased blood sugar levels;
• severe allergic reactions with symptoms such as skin rash, itching, swelling, urticaria, shortness of breath, abnormally fast pulse, and low blood pressure;
• blood clots;
• fever with low white blood cell counts.

Common (may affect up to 1 in 10 patients)

• severe bleeding or petechiae;
• violent seizures (convulsions) and loss of consciousness;
• severe infection with high fever;
• liver problems (e.g., skin discoloration, urine or stool color change, and elevated liver enzymes or bilirubin in laboratory results).

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

• hepatic insufficiency.

• jaundice;
• bile duct obstruction from the liver (cholestasis);
• liver cell destruction (hepatic necrosis).

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

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

Other side effects

Consult your doctor if you experience any of the following symptoms:

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

• changes in pancreatic activity;
• weight loss;
• leg pain (which could 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;
• decreased white blood cell count.

Common (may affect up to 1 in 10 patients)

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

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

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

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

• decreased platelet count;
• fever;
• pancreatic cysts, salivary gland swelling;
• elevated urea levels in the blood; Oncaspar antibodies; elevated ammonia levels in the blood; decreased blood sugar levels;
• tendency to sleep, confusion, mild muscle spasms (spasms) in the fingers.

Reporting side effects

If you experience any side effect that you believe may be related to chemotherapy, consult your doctor, even if it is a side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendixV.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and the packaging after EXP. The expiration date is the last day of the month indicated.

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

Do not freeze.

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

Do not use this medication if you observe that the reconstituted solution is cloudy or contains visible particles.

Medications should not be disposed of through drains. Ask your pharmacist how to dispose of unused medications. This will help protect the environment.

Composition of Oncaspar

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

Appearance of Oncaspar and contents of the package

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

Each package 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

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet: <{MM/AAAA}><{month AAAA}>.

For more detailed information about this medication, please visit the website of the European Medicines Agency:http://www.ema.europa.eu.

--------------------------------------------------------------------------------------------------------------------

This information is intended for healthcare professionals only:

It is strongly recommended to register 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 batch of the product.

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

Severe hypersensitivity reactions to Oncaspar may occur during treatment (e.g. anaphylaxis), especially in patients with confirmed hypersensitivity to other forms of L-asparaginase. A standard 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 anaphylaxis of immediate type. Patients receiving Oncaspar will be at a 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 irritation by contact. 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 least15minutes.

The 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. Staff should receive training on handling and transferring the medication (pregnant women should not be part of the staff).
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 during the handling of Oncaspar.
5. All articles 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 injection should be injected into the vial using a syringe and a 21-gauge needle.
2. The vial should be gently shaken until the powder is reconstituted.
3. After reconstitution, the solution should be transparent and colorless, and should not contain any visible foreign particles. Do not use if the solution is cloudy or a precipitate has formed. Do not shake.
4. The solution should be used within 24 hours after reconstitution when stored at a temperature below 25 °C.

Administration

1. Parenteral medications should be examined before administration to check for particles; only transparent, colorless solutions without visible foreign particles should be used.
2. The medication should be administered by intravenous or intramuscular route. 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 0.9% sodium chloride solution or 5% glucose solution.

The diluted solution can be administered over a period of 1 to 2 hours together with an ongoing intravenous infusion, either with 0.9% sodium chloride solution or 5% glucose solution. No other medication should be administered through the same intravenous route 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 can be stored at a temperature of 2 °C to 8 °C for a period of up to 48 hours

Disposal

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

For more detailed information, please refer to the product's technical data sheet or summary of characteristics.