Cytarabine kabi

Package leaflet: Information for the user

Cytarabine Kabi, 100 mg/ml, solution for injection/infusion
Cytarabinum
Please read all of this leaflet carefully before this medicine is administered, because it contains important information for you.

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

Contents of the leaflet:

1. What Cytarabine Kabi is and what it is used for
2. What you need to know 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 Cytarabine Kabi is and what it is used for

• Cytarabine Kabi is a medicine used in adults and children.
• The active substance in this medicine is cytarabine, which belongs to a group of medicines known as cytotoxic agents. These medicines are used in the treatment of acute leukaemias (blood cancer when the patient has too many white blood cells). Cytarabine interferes with the growth of cancer cells, which are then destroyed.
• Cytarabine is also used to induce and maintain remission of leukaemia.
• Induction of remission is an intensive treatment aimed at reversing the symptoms of leukaemia. When treatment is successful, the balance of blood cells returns to normal and the patient's health improves. This period of disease regression is called remission.
• Maintenance treatment is a milder therapy intended to sustain remission for as long as possible. Low doses of cytarabine are used to keep leukaemia 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 to any of the other ingredients of this medicine (listed in section 6);
• if, for reasons other than cancer, the number of blood cells is very low. The doctor may decide not to administer this medicine if the patient has a non-malignant disease, except for immunosuppression;
• if the patient has experienced severe neurological symptoms (encephalopathy) following radiotherapy or treatment with another anticancer medicine such as methotrexate.

Warnings and precautions
Special caution is required:

• if the patient has impaired bone marrow function, treatment should be initiated under strict medical supervision;
• during treatment with cytarabine, liver and kidney function should be monitored. If the patient had liver function disorders prior to treatment, cytarabine should be administered only under close monitoring;
• if the patient has been vaccinated or is to be vaccinated with a live or live attenuated vaccine;
• cytarabine significantly suppresses blood cell production in the bone marrow. This may increase susceptibility to infections or bleeding. Blood cell counts may decrease for up to one week after completion of treatment. If necessary, the doctor will regularly perform blood and bone marrow examinations;
• severe, sometimes life-threatening adverse reactions may occur affecting the central nervous system, intestines, or lungs;
• during treatment, blood levels of uric acid (indicating destruction of cancer cells) may increase (hyperuricemia). If necessary, the doctor will advise on using medications to control uric acid levels in the blood.

Cytarabine Kabi with other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take:

• if the patient is taking medicines containing 5-fluorocytosine (a medicine used to treat fungal infections);
• if the patient is taking medicines containing digoxin or beta-acetyldigoxin, used in the treatment of certain heart conditions;
• if the patient is taking gentamicin, an antibiotic used to treat bacterial infections;
• if the patient is taking medicines containing cyclophosphamide, vincristine, and prednisone, medicines used in cancer treatment;
• if the patient is receiving cytarabine in combination with intrathecal methotrexate, 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
Avoid becoming pregnant if the female patient or her partner is 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 pregnancy is suspected, as cytarabine may cause congenital malformations. Effective contraception must be used by both women and men treated with cytarabine during treatment and for 6 months after its completion.
Breastfeeding
Due to the potential harmful effects of cytarabine on breastfed infants, breastfeeding must be discontinued before starting treatment.
Consult a doctor or pharmacist before using this medicine.
Driving and operating machinery
If the patient experiences discomfort after administration of Cytarabine Kabi, driving and operating machinery should be avoided.
Cytarabine Kabi contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. the medicine is considered "sodium-free".

3. How to use Cytarabine Kabi

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

Regular examinations
Regular tests, including blood tests, should be performed during treatment. Your doctor will inform you
how often these tests should be carried out. Your doctor will regularly monitor:

• blood, to check whether blood cell counts have not decreased to a level requiring treatment;
• liver function—through blood tests—to check whether cytarabine is adversely affecting liver function;
• kidney function—through blood tests—to check whether cytarabine is adversely affecting kidney function;
• blood uric acid levels—cytarabine may increase blood uric acid levels. Another medicine may be administered if uric acid levels are too high.

Use of a higher than recommended dose of Cytarabine Kabi
High doses may intensify adverse effects, such as oral mucositis or may reduce the number of white blood cells and platelets (which help with blood clotting). If this occurs, antibiotic therapy or blood transfusion may be necessary. To reduce patient discomfort due to oral mucositis, appropriate treatment may be administered.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should immediately contact your doctor or nurse if any of the following occurs:

• an allergic reaction such as sudden wheezing, difficulty in breathing, swelling of the eyelids, face, lips, rash or itching (especially if affecting the whole body);
• feeling tired and drowsy;
• flu-like symptoms, e.g. increased body temperature, fever and chills;
• increased tendency to bruising or greater bleeding after injury. These are symptoms of reduced blood cell count.

Other possible side effects:
If any of the side effects worsen, you should immediately contact your doctor or nurse.
Very common side effects (may affect more than 1 in 10 people):

• lung inflammation, infection (which may worsen and lead to organ failure);
• insufficient production or reduced number of red blood cells, white blood cells or platelets;
• inflammation or ulceration of the mouth, lips or anus, nausea or vomiting, diarrhoea, abdominal pain;
• liver function disorders (visible in blood tests);
• hair loss is common and may be severe. Hair usually regrows after stopping therapy;
• skin rash;
• cytarabine syndrome — sometimes occurring 6–12 hours after administration of the medicine, the following adverse effects may occur: general malaise with fever, bone pain, muscle pain and sometimes chest pain, maculopapular rash, conjunctivitis. This is known as "cytarabine syndrome" and can be treated;
• feeling of warmth and subfebrile condition;
• abnormal results of bone marrow biopsy and blood smear.

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

• skin ulcers;
• abnormally high levels of uric acid 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 (lining of the abdominal cavity).

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

• irregular heartbeat;
• inflammation of sweat glands.

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

• infection or inflammation at the injection site may occur;
• loss of appetite;
• pain or dizziness, tingling sensation, tremors and seizures, drowsiness; eye pain or itching;
• pericarditis (inflammation of the membrane surrounding the heart);
• slower than normal pulse or heart rate;
• vein inflammation (due to blood clot);
• rapid breathing, sore throat, pain or difficulty in swallowing;
• pancreatitis (pain in the upper abdomen), often accompanied by nausea, vomiting, oesophageal inflammation or ulcers causing heartburn and nausea;
• jaundice (yellowing of the skin and whites of the eyes);
• skin redness (similar to sunburn), joint pain and numbness in hands, feet or face, abdominal swelling, swelling of legs, ankles and feet, tingling or burning sensation, skin tenderness and pressure, thick calluses on palms and hands, itchy skin rash, itching or freckles;
• difficulty or pain when passing urine. Blood in urine or impaired kidney function (visible in blood tests).

Side effects occurring after high-dose treatment:
Very common side effects (may affect more than 1 in 10 people):

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

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

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

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

• liver abscess and liver enlargement;
• personality changes;
• coma, seizures, balance disorders due to nerve damage;
• rapid heartbeat, reduced heart function, shortness of breath, dizziness, swelling of legs, ankles, feet and neck veins (cardiomyopathy), which may be fatal;
• vomiting blood or blood in stool (necrosis or ulcer of stomach or intestines), stomach pain or tenderness (peritonitis), hepatic vein thrombosis (Budd-Chiari syndrome);
• muscle damage (rhabdomyolysis), absence of menstruation in women of reproductive age (amenorrhoea), absence of sperm in semen (azoospermia).

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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 authorisation holder. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Cytarabine Kabi

Keep this medicine out of the sight and reach of children.
Store at 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 stated month. After opening, the medicine should be used immediately.
Cytarabine Kabi, solution for injection/infusion, may be diluted using the following solutions: water for injections, glucose 5% for intravenous infusion, or sodium chloride 0.9% for intravenous infusion.
Physico-chemical stability has been demonstrated for 8 days at temperatures below 25°C.
From a microbiological standpoint, the medicine should be used immediately. If not used immediately, the responsibility for storage conditions and duration after preparation lies with the user. The storage period should not exceed 24 hours at a temperature between 2°C and 8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions.
Do not use this medicine if the solution is not clear and colourless or if it contains visible particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Cytarabine Kabi contains

• The active substance is cytarabine. Each ml of 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 injections.

What Cytarabine Kabi looks like and contents of the pack
The medicine is a clear, colourless solution for injection or infusion. The medicine is contained in a clear, colourless, type I glass vial, closed with a bromobutyl rubber stopper and an aluminium seal with a tamper-evident cap in the following colours: green (2 ml), blue (5 ml), red (10 ml), yellow (20 ml).
The pack contains 1 vial with a capacity of 1 ml, 5 ml, 10 ml or 20 ml, respectively.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Poland

Manufacturer
Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany

For further information, please contact the Marketing Authorisation Holder:
Fresenius Kabi Polska Sp. z o.o.
Al. Jerozolimskie 134
02-305 Warsaw
Poland
Tel.: +48 22 345 67 89

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Information intended exclusively for medical professionals:

Medication handling information
For single use only.
Cytarabine is intended for intravenous or subcutaneous administration only.
The diluted solution should be clear and colourless and must not contain visible particles.
Where the solution and container permit, parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration.
The solution should be discarded if it contains solid particles or has changed colour.
Cytarabine for injection may be diluted with Water for Injections, Glucose 5% Intravenous Infusion, or Sodium Chloride 0.9% Intravenous Infusion.
Compatibility testing has been performed using polyolefin infusion bags.
The concentration range in which cytarabine has been shown to be physically and chemically stable is 0.04–4 mg/mL.
If crystallization has occurred due to exposure to low temperatures, dissolve the crystals by heating
to 55°C (for no longer than 30 minutes) with shaking until crystals dissolve completely. Allow to cool to room temperature before use.
The contents of the vial should be used immediately after first opening. Do not store opened vials.
Infusion solutions containing cytarabine should be used immediately.

Handling information for cytotoxic drugs
Administration:
The drug should be administered by, or under the close supervision of, a qualified physician experienced in the use of antineoplastic agents.

Preparation (guidelines):

1. Chemotherapeutic agents should be prepared for administration only by personnel who have been trained in the safe handling of drugs.
2. Procedures such as reconstitution and transfer into syringes should be performed only in a designated area.
3. Personnel performing these tasks should wear appropriate protective clothing, gloves, and eye protection.
4. Pregnant women should avoid contact with chemotherapeutic agents.

Contamination:
In case of contact with skin or eyes, the affected area should be thoroughly rinsed with copious amounts of water or physiological saline solution. A non-irritating cream may be used to treat transient skin burning. If the solution enters the eyes, medical advice must be sought immediately.
In the event of spillage, personnel preparing the drug should wear gloves and clean up the spilled liquid using a sponge kept for this purpose. The surface should be washed twice with water. All solutions and sponges used should be placed in a plastic bag and sealed tightly.

Disposal:
Syringes, containers, absorbent materials, unused solution, and any other contaminated materials should be placed in a thick plastic bag or another impermeable container and incinerated at 1100°C.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.