Oncaspar: detailed information

Package leaflet: Information for the user

Oncaspar 750 U/mL powder for solution for injection/infusion

pegaspargase
Please read this leaflet carefully before receiving this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor.
If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

What Oncaspar is and what it is used for
What you need to know before receiving Oncaspar
How Oncaspar is administered
Possible side effects
How to store Oncaspar
Contents of the pack and other information

1. What Oncaspar is and what it is used for

Oncaspar contains pegaspargase, an enzyme (asparaginase) that works by breaking down asparagine, an important component of proteins, without which cells cannot survive. Normal cells can produce asparagine on their own, whereas certain tumour cells are unable to do so. Oncaspar reduces the level of asparagine in blood cells and stops the growth of tumour cells.
Oncaspar is used for the treatment of acute lymphoblastic leukaemia (ALL) in children from birth to 18 years of age and in adults. Acute lymphoblastic leukaemia is a type of blood cancer affecting white blood cells, 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 medicines.

2. What you must know before receiving Oncaspar

Do not use Oncaspar

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

Inform your doctor if you develop any of these conditions. If you are the parent of a child being treated with Oncaspar, inform the doctor if your child develops any of these conditions.

Warnings and precautions

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

if you have previously had severe allergic reactions to other forms of asparaginase, such as itching, redness, or swelling of the airways, because serious allergic reactions may occur with Oncaspar.
if you have a blood clotting disorder or have previously had significant blood clots.
if you have a fever. This medicine may make you more susceptible to infections.
if you have had problems with liver function or are taking other medicines that could damage the liver.
if Oncaspar is used in combination with other anticancer treatments, liver damage may occur (including severe, life-threatening, and potentially fatal cases of hepatic veno-occlusive disease (VOD)).
if Oncaspar is used in combination with other anticancer treatments, damage to the central nervous system may occur.
if you have abdominal pain. Inflammation of the pancreas (pancreatitis) may occur during treatment with Oncaspar, which in some cases has led to death.

This medicine can alter blood clotting factors and may increase the risk of bleeding and/or blood clotting.

Osteonecrosis (bone damage) has been reported during post-marketing surveillance in children and adolescents treated with Oncaspar (with higher incidence observed in girls), particularly when the medicine is taken concomitantly with glucocorticoids (e.g., dexamethasone).

If you are the parent of a child being treated with Oncaspar, inform the doctor if the child develops any of the conditions listed above.

During treatment with Oncaspar

During administration of Oncaspar, you will remain under close observation for one hour after the start of treatment to monitor for signs of severe allergic reactions. Appropriate medical support will be available nearby to manage allergic reactions.

Additional monitoring tests

During and after treatment, regular tests will be performed to monitor your health, including assessments of blood and urine sugar levels, liver and pancreas function, and other tests, as this medicine may affect the blood and other organs.

Other medicines and Oncaspar

Inform your doctor if you are currently using, have recently used, or might use any other medicines.

This is important because Oncaspar may increase the side effects of other medicines due to its effect on the liver, which plays a key role in eliminating medicines from the body. It is particularly important to inform your doctor if you are also taking one or more of the following medicines:

Vaccination with live vaccines within three months after completion of leukemia treatment. This may increase the risk of serious infections.
Vincristine, used to treat certain types of cancer. If used together with Oncaspar, it may increase the risk of side effects or allergic reactions.
Medicines that reduce the blood's ability to clot, such as anticoagulants (e.g., coumarin/warfarin and heparin), dipyridamole, acetylsalicylic acid, or non-steroidal anti-inflammatory drugs (such as ibuprofen or naproxen). When used together with Oncaspar, they may increase the risk of bleeding.
Medicines that require cell division to exert their effect, such as methotrexate (a medicine used to treat cancer and also arthritis), which may have reduced effectiveness.
Prednisone, a steroid medicine. When used together with Oncaspar, its effects on blood clotting ability are increased.
Oncaspar may increase the risk of steroid-induced osteonecrosis (bone damage) in children and adolescents, with a higher incidence observed in girls, when taken concomitantly with glucocorticoids as part of the recommended treatment for leukemia. Therefore, if you experience new bone pain (e.g., hip, knee, or back pain), inform your doctor as soon as possible.
Cytarabine, a medicine that may be used in cancer treatment and which could interfere with the effects of Oncaspar.

Oncaspar may also cause changes in liver function that could affect how other medicines work.

Pregnancy and breastfeeding

If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before using this medicine.

You must not use Oncaspar if you are pregnant, as its effects during pregnancy have not been studied. Your doctor will decide whether your condition requires treatment. Women of childbearing potential must use reliable contraception during treatment and for at least 6 months after stopping treatment with Oncaspar. Oral contraceptives are not an effective contraceptive method during treatment with Oncaspar. Ask your doctor for advice on the most appropriate contraceptive method to use. Men should also use effective contraception when they or their partners are being treated with Oncaspar.

It is not known whether pegaspargase is excreted in breast milk. As a precautionary measure, breastfeeding must be discontinued during treatment with Oncaspar and must not be resumed until after treatment has ended.

Driving and using machines

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

Oncaspar contains sodium

This medicine contains less than 1 mmol of sodium per dose, i.e., it is essentially 'sodium-free'.

3. How Oncaspar is administered

Before administration, you may receive a combination of medicines to reduce the likelihood of allergic reactions. Your doctor will decide whether this pre-treatment is necessary.
Oncaspar has been prescribed to you by a doctor experienced in the use of medicines for cancer treatment. Based on your age and body surface area, which is calculated using your height and weight, your doctor will determine the required dose of the medicine and how frequently it should be administered.
The medicine is administered as an injection solution into a muscle or, if necessary, into a vein.
If you are given too much Oncaspar
Since Oncaspar is administered by healthcare professionals, it is highly unlikely that you will receive more than the required amount.
In the unlikely event of an accidental overdose, you will be closely monitored and appropriately treated by healthcare professionals.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Serious side effects
Inform your doctor immediately if you experience any of the following side effects:
Very common (may affect more than 1 in 10 people)

inflammation or other disorders of the pancreas (pancreatitis) causing severe stomach pain that may spread to the back, vomiting, elevated blood sugar levels;
severe allergic reactions with symptoms such as rash, itching, swelling, hives, shortness of breath, rapid heartbeat, and low blood pressure;
blood clots;
fever with low white blood cell count.

Common (may affect up to 1 in 10 people)

severe bleeding or bruising;
violent muscle contractions (seizures) and loss of consciousness;
severe infection with high fever;
liver problems (e.g. changes in skin, urine or stool color, or elevated liver enzymes or bilirubin in laboratory tests).

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

liver failure;
jaundice;
interruption of bile flow from the liver (cholestasis);
destruction of liver cells (liver cell necrolysis).

Not known (frequency cannot be estimated from the available data)

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

Other side effects
Inform your doctor if you experience any of the following side effects:
Very common (may affect more than 1 in 10 people)

changes in pancreatic function;
weight loss;
pain in the lower limbs (may be a sign of thrombosis), chest pain or shortness of breath (may be symptoms of blood clot in the lungs, a condition called pulmonary embolism);
loss of appetite, general weakness, vomiting, diarrhea, nausea;
elevated blood sugar levels;
reduced number of white blood cells.

Common (may affect up to 1 in 10 people)

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

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

reversible posterior leukoencephalopathy syndrome characterized by headache, confusion, seizures, and loss of vision, which resolves after some time.

Not known (frequency cannot be estimated from the available data)

reduced number of platelets;
fever;
cysts in the pancreas, swelling of the salivary glands;
elevated levels of urea in the blood; anti-Oncaspar antibodies; high levels of ammonia in the blood; low blood sugar levels;
drowsiness, confusion, mild finger contractions.

Reporting of side effects
If you experience any side effect that you think could be related to chemotherapy, including those not listed in this leaflet, talk to your doctor. 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. How to store 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 the carton after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C-8 °C).
Do not freeze.
After the medicine has been reconstituted and diluted, the solution should be used immediately. If this is not possible, the diluted solution may be stored at 2 °C-8 °C for a maximum of 48 hours.
Do not use this medicine if you notice that the reconstituted solution is cloudy or contains visible particles.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Oncaspar contains
The active substance 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 hydrogen 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”).

Description of the appearance of Oncaspar and contents of the pack
Oncaspar is a white or almost white powder. After reconstitution, the solution is clear, colourless and free from visible extraneous particles.
Each pack contains 1 glass vial with 3,750 U of pegaspargase.

Marketing Authorisation Holder
Les Laboratoires Servier
50, rue Carnot
92284 Suresnes cedex
France

Manufacturer
Les Laboratoires Servier Industrie
905 Route de Saran
45520 Gidy
France

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

België/Belgique/Belgien Lietuva
S.A. Servier Benelux N.V. UAB “SERVIER PHARMA”
Tel: +32 (0)2 529 43 11 Tel: +370 (5) 2 63 86 28

България Luxembourg/Luxemburg
Сервие Медикал ЕООД S.A. Servier Benelux N.V.
Тел.: +359 2 921 57 00 Tel: +32 (0)2 529 43 11

Česká republika Magyarország
Servier s.r.o. Servier Hungaria Kft.
Tel: +420 222 118 111 Tel: +36 1 238 7799

Danmark Malta
Servier Danmark A/S V.J. Salomone Pharma Ltd
Tlf: +45 36 44 22 60 Tel: +356 21 22 01 74

Deutschland Nederland
Servier Deutschland GmbH Servier Nederland Farma B.V.
Tel: +49 (0)89 57095 01 Tel: +31 (0)71 5246700

Eesti Norge
Servier Laboratories OÜ Servier Danmark A/S
Tel:+ 372 664 5040 Tlf: +45 36 44 22 60

Eλλάδα Österreich
ΣΕΡΒΙΕ ΕΛΛΑΣ ΦΑΡΜΑΚΕΥΤΙΚΗ ΕΠΕ Servier Austria GmbH
Τηλ: +30 210 939 1000 Tel: +43 (1) 524 39 99

España Polska
Laboratorios Servier S.L. Servier Polska Sp. z o.o.
Tel: +34 91 748 96 30 Tel: +48 (0) 22 594 90 00

France Portugal
Les Laboratoires Servier Servier Portugal, Lda
Tel: +33 (0)1 55 72 60 00 Tel.: +351 21 312 20 00

Hrvatska România
Servier Pharma, d. o. o. Servier Pharma SRL
Tel.: +385 (0)1 3016 222 Tel: +4 021 528 52 80

Ireland Slovenija
Servier Laboratories (Ireland) Ltd. Servier Pharma d. o. o.
Tel: +353 (0)1 663 8110 Tel.: +386 (0)1 563 48 11

Ísland Slovenská republika
Servier Laboratories Servier Slovensko spol. s r.o.
c/o Icepharma hf Tel.:+421 (0) 2 5920 41 11
Sími: +354 540 8000

Italia Suomi/Finland
Servier Italia S.p.A. Servier Finland Oy
Tel: +39 06 669081 P. /Tel: +358 (0)9 279 80 80

Κύπρος Sverige
C.A. Papaellinas Ltd. Servier Sverige AB
Τηλ: +357 22741741 Tel : +46 (0)8 522 508 00

Latvija United Kingdom (Northern Ireland)
SIA Servier Latvia Servier Laboratoires (Ireland) Ltd
Tel: +371 67502039 Tel: +44 (0)1753 666409

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

The following information is intended exclusively for healthcare professionals:

Every time Oncaspar is administered to a patient, it is strongly recommended to record the name and batch number of the medicinal product in order to link the patient to the specific batch of the drug.
Due to the unpredictable nature of adverse reactions, Oncaspar must be administered only by healthcare personnel experienced in the use of antineoplastic chemotherapeutic agents.
Particularly in patients with known hypersensitivity to other forms of L-asparaginase, hypersensitivity reactions to Oncaspar, such as anaphylaxis, may occur during therapy. A routine precautionary measure is to monitor patients for one hour after administration, with appropriate resuscitation equipment and other necessary means for treating anaphylaxis readily available (e.g., epinephrine, oxygen, intravenous steroids, etc.).
Patients should be informed about the possible hypersensitivity reactions to Oncaspar, including immediate anaphylaxis. Patients receiving Oncaspar are at increased risk of bleeding and thrombotic disorders. Patients must be advised that Oncaspar should not be used concurrently with other medicinal products associated with an increased risk of bleeding (see section 2 “Other medicinal products and Oncaspar”).
This medicinal product may cause irritation upon contact. The powder should therefore be handled and administered with particular care. Inhalation of vapors and contact with skin and mucous membranes, especially the eyes, must be avoided. If the product comes into contact with eyes, skin, or mucous membranes, immediately rinse thoroughly with abundant water for at least 15 minutes.
Unused medicine and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.

Instructions on how to prepare, store, and dispose of Oncaspar:
Handling instructions

Personnel must be trained in the handling and transfer of the medicinal product (pregnant personnel should be exempted from handling this medicinal product).
Aseptic technique must be used.
Proper procedures for handling antineoplastic agents must be followed.
During handling of Oncaspar, the use of disposable gloves and protective clothing is recommended.
All administration and cleaning supplies, including gloves, must be placed in a high-risk waste disposal bag for high-temperature incineration.

Reconstitution

5.2 mL of water for injections should be injected into the vial using a syringe and a 21 G needle.
The vial should be gently rotated until the powder is completely dissolved.
After reconstitution, the solution should be clear, colourless, and free from visible foreign particles. Do not use if the reconstituted solution is cloudy or has formed a precipitate. Do not shake.
The solution must be used within 24 hours of reconstitution if stored at a temperature below 25 °C.

Administration

Parenteral medicinal products should be inspected visually for particulate matter prior to administration; only a clear, colourless solution free from visible foreign particles should be used.
The medicinal product must be administered either intravenously or intramuscularly. The solution should be administered slowly. For intramuscular injection, the volume should not exceed 2 mL in children and adolescents and 3 mL in adults. For intravenous administration, the reconstituted solution should be diluted in 100 mL of 9 mg/mL (0.9%) sodium chloride injection or 5% glucose solution. The diluted solution may be administered over 1–2 hours along with an ongoing infusion of 9 mg/mL (0.9%) sodium chloride or 5% glucose solution. Do not infuse other medicinal products through the same intravenous line during administration of Oncaspar. After dilution, the solution should be used immediately. If this is not possible, the diluted solution may be stored at 2 °C–8 °C for up to 48 hours.

Disposal
Oncaspar is for single use only.
Unused medicine and waste materials derived from this product must be disposed of in accordance with local regulations.
Further detailed information is provided in the Summary of Product Characteristics.