Citarabine Kabi

Package Leaflet: Information for the User

Cytarabine Kabi, 100 mg/ml, Solution for Injection/Infusion

Cytarabine

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

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

• 1. What is Cytarabine Kabi and what is it used for
• 2. Important information before using Cytarabine Kabi
• 3. How to use Cytarabine Kabi
• 4. Possible side effects
• 5. How to store Cytarabine Kabi
• 6. Contents of the pack and other information

1. What is Cytarabine Kabi and what is it used for

• Cytarabine Kabi is a medicine used in adults and children.
• The active substance of the medicine is cytarabine, which belongs to a group of medicines known as cytotoxic medicines. These medicines are used to treat acute leukemias (blood cancer, when the patient has too many white blood cells). Cytarabine disrupts the development of cancer cells, which are then destroyed.
• Cytarabine is also used to induce and maintain remission of leukemia.
• Induction of remission is an intensive treatment aimed at reversing the symptoms of leukemia. When the treatment is effective, the balance of cells in the patient's blood returns to normal, and the patient's health improves. This period of reversal of disease symptoms is called remission.
• Maintenance treatment is a milder treatment aimed at maintaining remission for as long as possible. Small doses of cytarabine are used to keep the leukemia under control and prevent its recurrence.

2. Important information before using Cytarabine Kabi

When not to use Cytarabine Kabi

• if the patient is allergic to cytarabine or any of the other ingredients of this medicine (listed in section 6);
• if the patient has a very low blood cell count for non-cancerous reasons. The doctor may decide not to administer this medicine if the patient has a non-cancerous tumor, except for immunosuppression;
• if the patient has experienced severe brain symptoms (encephalopathy) after radiation therapy or treatment with another anticancer medicine, such as methotrexate.

Warnings and precautions

Particular caution should be exercised:

• if the patient has impaired bone marrow function, treatment should be initiated under close medical supervision;
• during treatment with cytarabine, liver and kidney function should be monitored. If the patient had liver function disorders before treatment, cytarabine should be administered only under close supervision;
• if the patient has been vaccinated or is to be vaccinated with a live or attenuated vaccine;
• cytarabine significantly reduces blood cell production in the bone marrow. This may increase the risk of infections or bleeding. The number of blood cells may decrease for up to a week after the end of treatment. If necessary, the doctor will regularly perform blood and bone marrow tests;
• severe, potentially life-threatening side effects may occur from the central nervous system, intestine, or lungs;
• during treatment, the level of uric acid (indicating that cancer cells have been destroyed) in the blood may increase (hyperuricemia). If necessary, the doctor will inform about the need to use medicines to control uric acid levels in the blood.

Cytarabine Kabi and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take:

• if you are taking medicines containing 5-fluorocytosine (a medicine used to treat fungal infections);
• if you are taking medicines containing digoxin or beta-acetyldigoxin, used to treat certain heart diseases;
• if you are taking gentamicin, an antibiotic used to treat bacterial infections;
• if you are taking medicines containing cyclophosphamide, vincristine, and prednisone, medicines used to treat cancer;
• if you are taking cytarabine in combination with methotrexate administered into the spine, as cases of headache, paralysis, coma, and stroke-like symptoms have been reported in children and young adults who received intravenous cytarabine in combination with intrathecal methotrexate.

Pregnancy and breastfeeding

Pregnancy

It is recommended to avoid becoming pregnant if you or your partner are being treated with cytarabine. During treatment, both women and men who are sexually active should use effective contraceptive methods to prevent pregnancy. Consult your doctor if you suspect pregnancy, as cytarabine may cause birth defects. During treatment and for 6 months after its completion, it is necessary to use effective contraceptive methods for women and men treated with cytarabine.

Breastfeeding

Due to the potential harmful effects of cytarabine on breastfed infants, breastfeeding should be discontinued before starting treatment. Before using this medicine, consult your doctor or pharmacist.

Driving and using machines

If you experience malaise after using Cytarabine Kabi, do not drive or operate machinery.

Cytarabine Kabi contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means that the medicine is considered "sodium-free".

3. How to use Cytarabine Kabi

The medicine should be administered under the supervision of a doctor in the form of intravenous infusion (drip) or injection. Based on the patient's health condition, the doctor will decide on the dose and duration of treatment. Based on the patient's health condition and body surface area, the doctor will decide on the dose of cytarabine and the type of treatment, induction or maintenance. The doctor will calculate the body surface area based on the patient's weight and height.

Regular tests

During treatment, regular tests should be performed, including blood tests. The doctor will inform you how often to perform them. The doctor will regularly check:

• blood to see if the number of blood cells has not decreased to a level requiring treatment;
• liver function - through a blood test - to check if cytarabine does not adversely affect liver function;
• kidney function - through a blood test - to check if cytarabine does not adversely affect kidney function;
• uric acid levels in the blood - cytarabine may increase uric acid levels in the blood. Another medicine may be administered if uric acid levels are too high.

Using a higher dose of Cytarabine Kabi than recommended

High doses may intensify side effects, such as mouth ulcers or decrease the number of white blood cells and platelets (which help blood to clot). If this happens, it may be necessary to administer an antibiotic or a blood transfusion. To reduce patient discomfort due to mouth ulcers, appropriate treatment can be used. If you have any further questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

Inform your doctor or nurse immediately if you experience any of the following symptoms:

• allergic reaction in the form of sudden wheezing, difficulty breathing, swelling of the eyelids, face, lips, rash, or itching (especially covering the whole body);
• feeling of fatigue and drowsiness;
• flu-like symptoms, such as elevated body temperature, fever, and chills;
• more frequent bruising or increased bleeding when cut. These are symptoms of decreased blood cell count.

Other side effects that may occur:

If any of the side effects get worse, consult your doctor or nurse immediately.

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

• pneumonia, infection (which can worsen and lead to organ failure);
• insufficient production or decrease in the number of red blood cells, white blood cells, or platelets;
• inflammation or ulcers of the mouth, lips, or anus, nausea, vomiting, diarrhea, abdominal pain;
• liver function disorders (visible in blood tests);
• hair loss is common and may be severe. Hair usually grows back after the end of therapy;
• skin rash;
• cytarabine syndrome, which sometimes occurs 6-12 hours after administration of the medicine, with the following side effects: general malaise with fever, bone, muscle, and sometimes chest pain, maculopapular rash, conjunctivitis. This is called "cytarabine syndrome" and can be treated;
• feeling of heat and subfebrile state;
• abnormal bone marrow biopsy and blood smear results.

Common side effects (may affect up to 1 in 10 people):

• skin ulcers;
• abnormal, high uric acid levels in the blood;
• difficulty swallowing.

Uncommon side effects (may affect up to 1 in 100 people):

• presence of cysts in the intestinal wall;
• severe intestinal inflammation;
• serious infection of the peritoneum.

Rare side effects (may affect up to 1 in 10,000 people):

• irregular heartbeat;
• inflammation of the sweat glands.

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

• infection or inflammation at the injection site may occur;
• loss of appetite;
• pains or dizziness, feeling of tingling, tremors, and convulsions, drowsiness; eye pain or itching;
• inflammation of the pericardium (inflammation of the membrane surrounding the heart);
• slower than normal heartbeat or heart rate;
• inflammation of the veins (caused by a blood clot);
• rapid breathing, throat pain, difficulty swallowing;
• pancreatitis (pain in the upper abdomen) often with accompanying nausea, vomiting, inflammation, or ulcers in the esophagus, causing heartburn and nausea;
• jaundice (yellowing of the skin and whites of the eyes);
• redness of the skin (similar to sunburn), pain and numbness of the joints, fingers, and toes or face, swelling of the abdomen, legs, ankles, and feet, feeling of tingling or burning, tenderness, and pressure on the skin, thick calluses on the palms and soles, itchy rash, itching, or freckles;
• difficulty or pain when urinating. Blood in the urine or kidney function disorders (visible in blood tests).

Side effects that may occur after treatment with high doses of the medicine:

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

• concentration disorders, speech impairment, involuntary muscle movements, or difficulty controlling muscle movements, involuntary eye movements, headache, confusion, drowsiness, dizziness, etc., caused by brain function disorders;
• eye infections, irritation, pain, and blurred vision, loss of vision;
• sharp or stabbing chest pain, fluid accumulation in the lungs.

Common side effects (may affect up to 1 in 10 people):

• skin peeling;
• infections and intestinal inflammation, most commonly occurring in children.

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

• liver abscess and liver enlargement;
• personality changes;
• coma, convulsions, balance disorders due to nerve damage;
• rapid heartbeat, decreased heart function, shortness of breath, dizziness, swelling of the legs, ankles, feet, and neck veins (cardiomyopathy), which can be fatal;
• bloody vomiting or blood in the stool (necrosis or ulcer of the stomach or intestines), abdominal pain or tenderness (peritonitis), causing heartburn and nausea;
• muscle damage (rhabdomyolysis), absence of menstruation in women of childbearing age (amenorrhea), absence of sperm in the semen (azoospermia).

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 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, you can help provide more information on the safety of this medicine.

5. How to store Cytarabine Kabi

Keep the medicine out of the sight and reach of children. Store in a temperature between 15°C and 25°C. Do not store in the refrigerator, do not freeze. Do not use Cytarabine Kabi after the expiry date stated on the vial or carton. The expiry date refers to the last day of the month stated. After opening, the medicine should be used immediately. Cytarabine Kabi, solution for injection or infusion, can be diluted with water for injection, glucose solution for intravenous infusion (5%), or sodium chloride solution for intravenous infusion (0.9%). Physico-chemical stability has been demonstrated for 8 days at a temperature below 25°C. From a microbiological point of view, the medicine should be used immediately. If the medicine is not used immediately, the user is responsible for the storage conditions after preparation. This time should not exceed 24 hours at a temperature between 2°C and 8°C, unless the reconstitution and dilution of the medicine took place in controlled and validated aseptic conditions. Do not use this medicine if you notice that the solution is not clear and colorless or if it 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. Contents of the pack and other information

What Cytarabine Kabi contains

• The active substance of the medicine is cytarabine. Each ml of the solution contains 100 mg of cytarabine.

Each 1 ml vial contains 100 mg of cytarabine. Each 5 ml vial contains 500 mg of cytarabine. Each 10 ml vial contains 1 g of cytarabine. Each 20 ml vial contains 2 g of cytarabine.

• Other ingredients are: hydrochloric acid, sodium hydroxide, water for injection.

What Cytarabine Kabi looks like and contents of the pack

The medicine is a clear and colorless solution for injection or infusion. The medicine is in a clear, colorless, glass vial type I, closed with a bromobutyl rubber stopper and an aluminum cap with a breakable cap in the following colors: green (2 ml), blue (5 ml), red (10 ml), yellow (20 ml). The pack contains 1 vial of 1 ml, 5 ml, 10 ml, or 20 ml. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Fresenius Kabi Polska Sp. z o.o. Al. Jerozolimskie 134 02-305 Warsaw

Manufacturer

Fresenius Kabi Deutschland GmbH Pfingstweide 53 61169 Friedberg Germany For more detailed information, please contact the marketing authorization holder: Fresenius Kabi Polska Sp. z o.o. Al. Jerozolimskie 134 02-305 Warsaw tel.: +48 22 345 67 89

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

Date of last revision of the package leaflet:14.01.2021

Information intended for healthcare professionals only:

Information on handling the medicine

For single use only. Cytarabine is intended for intravenous or subcutaneous use only. The diluted solution should be clear and colorless and should not contain visible particles. Unless the solution and packaging allow, medicines for parenteral use should be inspected for particulate matter and discoloration prior to administration. The solution should be discarded if it contains particulate matter or has changed color. If the solution comes into contact with the skin or eyes, the affected area should be rinsed with plenty of water or saline solution. To treat transient burning of the skin, a non-irritating cream can be applied. If the solution gets into the eyes, medical advice should be sought. In case of spillage, the person preparing the medicine should wear gloves and wipe up the spilled liquid with a sponge, which should be kept in a designated place. The surface should be rinsed twice with water, and all solutions and sponges should be placed in a bag and sealed tightly.

Disposal

Syringes, containers, absorbent materials, solution, and any other contaminated materials should be placed in a thick plastic bag or other impermeable container, which should then be incinerated at 1100°C. Any unused medicine or waste material should be disposed of in accordance with local requirements.

Information on handling cytotoxic medicines

Administration:

The medicine should be administered by or under the direct supervision of a qualified physician experienced in the use of anticancer medicines.

Preparation (guidelines):

• 1. Cytotoxic medicines should be prepared for administration only by personnel who have been trained in the safe handling of cytotoxic medicines.
• 2. Procedures, such as dissolution and transfer to syringes, should be carried out only in designated areas.
• 3. Personnel handling these procedures should wear appropriate protective clothing, gloves, and eye protection.
• 4. It is recommended that women who are pregnant avoid contact with cytotoxic medicines.

Contamination:

In case of contact with the skin or eyes, the affected area should be rinsed with plenty of water or saline solution. To treat transient burning of the skin, a non-irritating cream can be applied. If the solution gets into the eyes, medical advice should be sought. In case of spillage, the person preparing the medicine should wear gloves and wipe up the spilled liquid with a sponge, which should be kept in a designated place. The surface should be rinsed twice with water, and all solutions and sponges should be placed in a bag and sealed tightly.