Ervinase

Leaflet attached to the packaging: patient information

Crisantaspase Porton Biopharma, 10,000 IU, powder for solution for injection

For infusion
Crisantaspase(L-asparaginase derived from Erwinia chrysanthemi)

Read the contents of the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Crisantaspase Porton Biopharma and what is it used for
• 2. Important information before using Crisantaspase Porton Biopharma
• 3. How to take Crisantaspase Porton Biopharma
• 4. Possible side effects
• 5. How to store Crisantaspase Porton Biopharma
• 6. Contents of the packaging and other information

1. What is Crisantaspase Porton Biopharma and what is it used for

How does Crisantaspase Porton Biopharma work?

Crisantaspase Porton Biopharma is used to treat blood cancer and belongs to a group of medicines called "anticancer and immunomodulating agents". Its action is based on reducing the concentration of asparagine (an amino acid) in the body. Asparagine is a substance that cancer cells need to survive.

What is Crisantaspase Porton Biopharma used for?

This medicine is mainly used to treat children with blood cancer (acute lymphoblastic leukemia) who have had an allergic reaction to other similar medicines. This medicine is used in combination with other treatments.

2. Important information before using Crisantaspase Porton Biopharma

When not to use Crisantaspase Porton Biopharma

• if the patient is allergic to the active substance (crisantaspase) or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe liver function disorders;
• if the patient has had severe pancreatitis (inflammation of the pancreas) caused by a medicine containing L-asparaginase;
• if the patient has pancreatitis (inflammation of the pancreas) not related to the use of L-asparaginase.

Warnings and precautions

Before starting treatment with Crisantaspase Porton Biopharma, discuss it with your doctor, pharmacist, or nurse.

• This medicine should only be used by doctors with experience in this type of treatment;
• Severe, life-threatening allergic reactions have been reported. In case of an allergic reaction to treatment, the hospital must have specialized medicines and equipment to treat them;
• There is a possibility that the patient's body may become sensitized to the active substance after repeated treatment;
• In case of abdominal pain, which may be a sign of pancreatitis (inflammation of the pancreas), the doctor should be notified immediately. Pancreatitis can be life-threatening;
• During treatment, high blood sugar levels (hyperglycemia) may occur. Treatment includes the administration of insulin;
• During treatment, the body may have a reduced ability to prevent severe bleeding. In case of severe bleeding, treatment will be discontinued. The doctor will determine whether and when treatment can be resumed;
• The use of this medicine may cause liver function disorders to worsen. In case of a severe reaction, the doctor will consider discontinuing treatment. Treatment can be resumed under close supervision, but only after sufficient improvement of the patient's condition;
• If the doctor or nurse spills this medicine on the patient or on themselves, especially in the eye area, the affected area should be rinsed with a large amount of water for 15 minutes;
• Neurological disorders (nervous system disorders) leading to death have been reported. Posterior reversible encephalopathy syndrome (characterized by headache, confusion, seizures, and vision loss) may require treatment with blood pressure-lowering medications, and in case of seizures, antiepileptic medications;
• The destruction of cancer cells causes an increased concentration of uric acid (a metabolic product) in the blood. This can lead to kidney function disorders;
• During treatment with this medicine, a weakened immune system has been observed. This can lead to an increased susceptibility to infection.

Blood and urine tests

During treatment, the doctor will regularly perform blood and urine tests to check for possible side effects, such as:

• allergic reactions;
• to check if the function of the pancreas, kidneys, and liver remains normal;
• to check if the number of blood cells is sufficient.

For the purpose of identifiability, medical personnel will record the product name and batch number of each dose of Crisantaspase Porton Biopharma administered to the patient.

Crisantaspase Porton Biopharma and other medicines

• Crisantaspase Porton Biopharma may affect liver function, as well as enzyme activity and protein levels in the blood, so the action of medicines sensitive to these changes may be altered;
• If Crisantaspase Porton Biopharma is administered in combination with other anticancer medicines, the beneficial or harmful effects of these medicines may be enhanced. This applies in particular to the following anticancer medicines: methotrexate, cytarabine, vincristine, imatinib, and prednisone (a corticosteroid);
• Sometimes, to protect the kidneys, it may be necessary to administer allopurinol - a medicine used to treat gout (a painful inflammatory condition of rheumatic origin).

Crisantaspase Porton Biopharma should not be mixed with other medicines before administration. Tell your doctor or pharmacist about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take in the near future, in combination with Crisantaspase Porton Biopharma.

Pregnancy and breastfeeding

If the patient is pregnant, thinks she may be pregnant, or plans to have a child, or is breastfeeding, she should consult her doctor or pharmacist before using this medicine.

• This medicine should not be used during pregnancy, unless absolutely necessary. If the patient is pregnant, becomes pregnant during treatment with this medicine, or plans to become pregnant in the near future, she should inform her doctor immediately.
• During treatment with this medicine, breastfeeding should not be performed.

Fertility and family planning

It cannot be excluded that this medicine may have a negative effect on fertility in men. In appropriate cases, both men and women should use contraception before treatment with Crisantaspase Porton Biopharma and for some time after its completion.

Driving and using machines

When driving or operating machines, consider the delayed reaction time and the possibility of nausea and vomiting.

Crisantaspase Porton Biopharma contains sodium and glucose

The medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., the medicine is considered "sodium-free". This medicine contains 5 mg of glucose per vial. This should be taken into account in patients with diabetes.

3. How to take Crisantaspase Porton Biopharma

Dosage

The doctor will calculate the patient's body surface area in square meters (m²) and determine the appropriate dose based on this. The usual dose is 25,000 IU of Crisantaspase Porton Biopharma per square meter. The amount of medicine taken may change depending on the concentration of asparaginase (the active substance of this medicine) in the patient's blood, which will be measured during treatment.

Method of administration

This medicine will be administered in one of the following ways: a) into a vein as an infusion (intravenous administration); b) into a muscle as an injection (intramuscular administration). This medicine should be administered by a doctor or nurse as an injection or infusion. Before administration, the powder is dissolved very carefully (in a physiological saline solution). The patient's treatment will be continuous. If there is a need to discontinue treatment, it can be resumed with a lower dose.

Duration of treatment

The patient will receive injections three times a week for two weeks. Depending on new results from clinical trials, this regimen may change.

Taking a higher dose of Crisantaspase Porton Biopharma than recommended

If the patient thinks they have taken a higher dose of Crisantaspase Porton Biopharma than recommended, they should contact their doctor or other medical personnel immediately.

Missing a dose of Crisantaspase Porton Biopharma

If the patient thinks they have missed a dose, they should contact their doctor or other healthcare provider immediately. In case of any further doubts about the use of this medicine, consult a doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects presented below have been observed when this medicine was administered with other anticancer medicines. This medicine will be administered under close medical supervision, and the doctor may administer other medicines to the patient to treat these side effects. Most side effects will disappear after discontinuation of treatment with this medicine. Consult a doctor immediatelyif any of the following side effects occur:

• Blue lips, hands, or feet (possible sign of hypoxia - too little oxygen in the blood), redness or inflammation of the skin, increased or decreased blood pressure, swelling of the face, lips, or throat, shortness of breath, increased heart rate, wheezing, difficulty swallowing, runny nose, rash, chills, redness of the skin, difficulty breathing, vomiting, malaise, or paleness of the skin. Repeated treatment increases the risk of an allergic reaction. Redness, pain, swelling, bruising, or hardening at the injection site;
• Symptoms may include: coma, encephalopathy (brain disease); seeing, hearing, or feeling things that do not exist (hallucinations); muscle weakness, decreased level of consciousness, confusion, dizziness, drowsiness, fatigue, anxiety, difficulty speaking - usually secondary to other side effects;
• Crisantaspase Porton Biopharma may increase the risk of blood clots, which can block major blood vessels in the brain, lungs, or legs (symptoms of blood clots in the arms or legs may include swelling). Chest pain radiating to the arms, neck, jaw, back, or abdomen, sweating, and shortness of breath may be symptoms of a heart attack (myocardial infarction);
• More frequent bleeding and bruising, even without prior injury;
• In case of symptoms of severe pancreatitis (inflammation of the pancreas), such as severe abdominal pain with nausea and diarrhea, treatment must be discontinued and cannot be resumed in the future;
• High blood sugar levels (hyperglycemia);
• Changes in liver function (determined by laboratory test results).

Other side effects observed during the use of this medicine are listed below according to their frequency:

Consult a doctor immediately if any of the following side effects occur:
Very common (occurring in more than 1 in 10 people)

• Generalized infection or septic shock (shock due to infection, including life-threatening shock) and other infections;
• Decreased number of blood cells (including platelets and white and red blood cells). This may be due to limited bone marrow function;
• Increased levels of fat, bilirubin (a metabolic product that occurs in the blood when red blood cells stop working), and activity of certain digestive enzymes in the blood (these levels will be monitored by the doctor);
• Weight loss;
• Pain all over the body, including muscle and joint pain;
• Nausea.

Common (occurring in less than 1 in 10 people)

• Diarrhea;
• Inflammation of the mucous membranes (inflammation of the digestive tract);
• Stomach problems;
• Fever;
• Fatigue;
• Headaches.

Uncommon (occurring in less than 1 in 100 people)

• Complications of diabetes (high blood sugar levels);
• Increased levels of ammonia ions in the blood;
• Seizures;
• Fatty liver disease;
• Decreased kidney function.

Rare (occurring in less than 1 in 1,000 people)

• Posterior reversible encephalopathy syndrome (a condition characterized by headache, confusion, seizures, and vision loss);
• Liver failure.

Very rare (occurring in less than 1 in 10,000 people)

• Painful joint disease known as reactive arthritis.

Unknown (frequency cannot be determined from available data)

• Lack of appetite (anorexia);
• Inflammation of the salivary glands in the back of the throat;
• Decreased levels of albumin (a protein) in the blood, causing water retention in the body;
• Formation of blisters and peeling of the skin (toxic epidermal necrolysis);
• Muscle pain;
• Kidney function disorders, manifested by abnormal urine test results (high levels of protein).

Usually, side effects are reversible (they disappear after discontinuation of the medicine).

Additional side effects in children and adolescents

Side effects affecting the liver, pancreas, and blood clotting occur more frequently in adults than in children and adolescents.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Crisantaspase Porton Biopharma

Keep the medicine out of the sight and reach of children. The hospital will store this medicine in a refrigerator (2°C – 8°C). Do not use this medicine after the expiry date stated on the packaging after "Expiry date". The month and year are stated in this leaflet. The expiry date refers to the last day of the stated month.

6. Contents of the packaging and other information

What the medicine contains

• The active substance of the medicine is crisantaspase (L-asparaginase derived from Erwinia chrysanthemi). - Each vial contains 10,000 IU of crisantaspase.
• The other ingredients are: sodium chloride, glucose monohydrate, sodium hydroxide, glacial acetic acid.

What Crisantaspase Porton Biopharma looks like and what the packaging contains

Crisantaspase Porton Biopharma is a white powder in a small glass vial. The vial is made of colorless type I glass (with a capacity of 3 ml) and is closed with a bromobutyl rubber stopper with an aluminum seal, in a cardboard box. Each package contains five small glass vials.

Marketing authorization holder

Porton Biopharma Limited
Lee View House, South Terrace 13
T12 T0CT Cork
Ireland
Tel: +44 1980 745 022
Email: medinfo@portonbiopharma.com

Manufacturer

Almac Pharma Services Limited
Seagoe Industrial Estate
BT63 5UA Portadown, Craigavon
United Kingdom (Northern Ireland)

This medicine is authorized for use in the Member States of the European Economic Area under the following names:

Austria, Belgium, Finland, France, Germany, Ireland, Netherlands, Poland, Portugal, Spain:
Crisantaspase Porton Biopharma

Date of last revision of the leaflet:

TEAR OFF HERE AND GIVE INSTRUCTIONS TO THE PATIENT
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Information intended for healthcare professionals only:
The contents of each vial should be reconstituted in 1 ml to 2 ml of physiological saline solution (0.9%) for injection.
Slowly add the physiological saline solution (0.9%) for injection to the inside of the vial; do not inject directly onto the powder or into the powder. Wait until the contents have dissolved, gently mixing or rotating the vial held in a vertical position. Avoid contact between the solution and the stopper. Avoid foaming due to excessive or violent shaking.
The solution should be clear and free of visible particles. In case of excessive shaking leading to the formation of visible foam, small crystalline or filamentous protein aggregates may be visible. In case of visible particles or protein aggregates, the reconstituted solution should be discarded.
The solution for injection should be administered within 15 minutes of reconstitution. If the solution cannot be administered within 15 minutes of reconstitution, it should be drawn into a sterile glass or polypropylene syringe under aseptic conditions. The syringe containing the reconstituted solution should then be stored at a temperature below 25°C and used within four hours.
In the case of intravenous infusion, the reconstituted solution of Crisantaspase Porton Biopharma should be further diluted in 100 ml of physiological saline solution (0.9%). To facilitate preparation, the reconstituted solution of Crisantaspase Porton Biopharma can be transferred to a bag containing 100 ml of physiological saline solution (0.9%) for injection.
It is recommended to administer the diluted solution for infusion immediately after preparation. If the diluted solution for infusion is not used immediately, it can be stored in a polyvinyl chloride (PVC) infusion bag. The infusion bag should be stored at a temperature below 25°C and used within four hours.
From a microbiological point of view, the reconstituted solution for injection should be used immediately, unless the method of reconstitution precludes the risk of microbial contamination. If the product is not used immediately, the user is responsible for the storage time and conditions.
Crisantaspase Porton Biopharma is not a cytotoxic medicinal product and does not require special precautions for handling such medicinal products. Nevertheless, during the preparation or administration of Crisantaspase Porton Biopharma, it should be considered that it may cause sensitization.
Avoid inhaling the powder or solution. In case of contact with the skin or mucous membranes, especially the eyes, the affected area should be rinsed with a large amount of water for at least 15 minutes.
Any unused medicinal product or waste should be disposed of in accordance with local regulations.
Do not mix this medicinal product with other medicinal products, as compatibility studies have not been performed. Therefore, do not administer other medicinal products intravenously through the same intravenous access during the administration of Crisantaspase Porton Biopharma.