Citarabina Accord

Package Leaflet: Information for the Patient

Cytarabina Accord, 20 mg/ml, Solution for Injection/Infusion

Cytarabine

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

• 1. What Cytarabina Accord is and what it is used for
• 2. Before you are given Cytarabina Accord
• 3. How Cytarabina Accord is given
• 4. Possible side effects
• 5. How to store Cytarabina Accord
• 6. Contents of the pack and other information

1. What Cytarabina Accord is and what it is used for

Cytarabina Accord, solution for injection/infusion is used in adults and children.
The active substance is cytarabine.
Cytarabine belongs to a group of medicines called cytotoxic medicines. These are used to treat
acute leukemias (blood cancers where there are too many white blood cells), including
prophylaxis and treatment of meningeal involvement (leukemia with central nervous system involvement). Cytarabine interferes with the development of cancer cells, which are eventually destroyed.

2. Before you are given Cytarabina Accord

When Cytarabina Accord must not be used

• if you are allergic to cytarabine or any of the other ingredients of this medicine (listed in section 6);
• if your blood cell count is very low for reasons other than cancer, unless your doctor decides that cytarabine treatment will be safe;
• if you have increasing difficulty with coordination after radiation therapy or other anti-cancer medicines such as methotrexate;
• if you are pregnant.

Warnings and precautions

Before starting treatment with Cytarabina Accord, tell your doctor, pharmacist or nurse:

• if you have bone marrow problems, as treatment should only be started under close medical supervision.
• if you have liver disease. If you have liver function disorders before starting treatment, cytarabine should only be given under close medical supervision.

During treatment

• Your doctor will regularly check your blood and, if necessary, your bone marrow.
• Your doctor may order regular checks of your liver and kidney function.
• During treatment with this medicine, your doctor may perform tests to check the functioning of your nervous system.
• During treatment, the level of uric acid (indicating that cancer cells are being destroyed) in your blood may increase (hyperuricemia). Your doctor will tell you if you need to take medicines to control uric acid levels in your blood.
• Live or attenuated vaccines should not be given during cytarabine treatment. If necessary, consult your doctor. The use of vaccines containing killed or inactivated microorganisms may not be effective due to the suppression of the immune system by cytarabine.

Cytarabine severely reduces blood cell production in the bone marrow. This can increase your susceptibility to infections or bleeding. Your blood cell count may continue to decrease after treatment has ended.

Cytarabina Accord and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription.

• digoxin or beta-acetyldigoxin (used to treat certain heart conditions);
• gentamicin (an antibiotic used to treat bacterial infections);
• 5-fluorocytosine (a medicine used to treat fungal infections);
• medicines containing cyclophosphamide, vincristine, and prednisone, which are used in cancer treatment regimens;
• any other medicines that may suppress the immune system (e.g., azathioprine or mercaptopurine);
• methotrexate (a medicine used to treat various cancers and certain inflammatory conditions);
• idarubicin (used to treat leukemia and breast cancer).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Pregnancy should be avoided when either you or your partner are being treated with cytarabine. Both men and women of childbearing potential should use effective contraception to prevent pregnancy during treatment. Cytarabine may cause birth defects, so it is essential to inform your doctor if you suspect you are pregnant.
Women of childbearing potential should be advised to use effective contraception to avoid becoming pregnant during treatment with this medicine and for at least 6 months after the end of treatment.
Men should use effective contraception during treatment with cytarabine and for at least 3 months after the end of treatment to prevent their partner from becoming pregnant.

Breastfeeding

Breastfeeding should be discontinued before starting treatment with cytarabine, as this medicine may be harmful to breastfed infants.

Fertility

Cytarabine may lead to suppression of the menstrual cycle and amenorrhea in women and to suppression of sperm production in men.

Driving and using machines

Cytarabine does not affect the ability to drive and use machines. However, cancer treatment may affect your ability to drive and use machines. If you experience symptoms, do not drive or operate machinery.

Cytarabina Accord contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per 5 ml, which is essentially 'sodium-free'.

3. How Cytarabina Accord is given

Cytarabina Accord is given under the supervision of specialists in a hospital. Your doctor will decide on the dose to be given, and the number of days of treatment will depend on your condition.
This medicine can be given by injection (using a syringe) subcutaneously, intravenously, intramuscularly, or into the spine (intrathecally).

Dose

Your doctor will decide on the dose of cytarabine based on your health status, body surface area, and the type of treatment (induction or maintenance). Your body surface area will be calculated based on your weight and height.

Overdose of Cytarabina Accord

High doses may increase side effects, such as mouth ulcers or a decrease in the number of white blood cells and platelets (which help blood to clot), nerve damage, severe lung problems, heart problems, and even death.
In such cases, antibiotics or blood transfusions may be necessary. To reduce discomfort associated with mouth ulcers, appropriate treatment can be applied.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects of cytarabine depend on the dose. The most common side effects affect the digestive system and blood. Gastrointestinal side effects are less common when cytarabine is given by infusion.

If you experience any of the following symptoms, you may need urgent medical attention.

Tell your doctor or nurse immediately if you notice any of the following:

• sudden signs of an allergic reaction, such as rash, itching, or hives on the skin, swelling of the face, lips, or throat, difficulty breathing or wheezing
• a combination of symptoms such as fever or low body temperature, rapid breathing, increased heart rate, confusion, and swelling, which may indicate sepsis
• infection or inflammation at the injection site
• spinal cord injury leading to paralysis of two or more limbs
• weakness or numbness of limbs, sexual dysfunction, seizures, and loss of consciousness, which may be signs of brain or nerve damage
• unusual muscle pain or tenderness
• eye pain, tearing, or burning with bleeding, vision changes, sensitivity to light
• complete loss of vision
• sudden severe chest pain radiating to the shoulders and neck
• severe abdominal pain with vomiting, diarrhea, constipation, or blood in the stool
• sudden weight loss or jaundice (yellow skin and eyes), change in urine or stool color, persistent cough with fever, chills, and difficulty breathing, caused by lung infection
• exacerbation of other infection symptoms, such as sore throat or mouth ulcers, which may be caused by a decrease in white blood cells
• pale skin and fatigue or increased bleeding or bruising, which may be caused by a decrease in other types of blood cells
• difficulty urinating or emptying the bladder

Other possible side effects:

Common: may affect up to 1 in 10 people

• fever
• abnormal blood cells (megaloblastosis)
• loss of appetite
• difficulty swallowing
• abdominal pain
• nausea (feeling sick)
• vomiting
• decreased consciousness (with high doses)
• difficulty speaking (with high doses)
• abnormal eye movements (nystagmus with high doses)
• diarrhea
• inflammation or ulcers of the mouth or anus
• reversible liver effects, such as increased enzyme activity
• reversible skin effects, such as redness (erythema), blistering, rash, hives, vasculitis, hair loss (with high doses)
• kidney problems, which can be detected by blood or urine tests
• abnormal, high levels of uric acid in the blood (hyperuricemia)

Uncommon: may affect up to 1 in 100 people

• sore throat
• headache
• inflammation and ulcers of the esophagus
• brown or black spots on the skin (lentigo)
• skin ulcers
• numbness of hands and feet
• itching
• shortness of breath
• muscle and joint pain

Rare: may affect up to 1 in 10,000 people

• blisters or skin rashes
• irregular heartbeat (arrhythmia)

Frequency not known:frequency cannot be estimated from the available data

• dizziness
• painful swelling of hands or feet
• appearance of freckles on the skin
• rash
• chest pain
• burning pain in hands and feet
• slower than normal heart rate
• low levels of early red blood cell development (reticulocytes) in the blood
• low white blood cell count (neutropenia)
• feeling unwell with high fever due to low white blood cell count (febrile neutropenia)

Other side effects

Cytarabine syndrome may occur 6-12 hours after starting treatment. Symptoms include:

• fever
• bone and muscle pain
• eye pain (conjunctivitis)
• feeling unwell
• occasional chest pain
• rash
• nausea (feeling sick)

After intrathecal (into the space surrounding the spinal cord) administration of cytarabine, the following symptoms may occur:

• inflammation of the membrane surrounding the brain and spinal cord, which can cause symptoms such as severe headache, numbness or tingling of hands and feet, etc.

Your doctor may prescribe corticosteroids (anti-inflammatory medicines, such as hydrocortisone, prednisolone, dexamethasone) to prevent or treat these symptoms. If these medicines are effective, cytarabine treatment can be continued.
The following symptoms, usually reversible, may occur in about one-third of patients after high-dose cytarabine treatment:

• personality changes
• attention disorders
• coordination and balance disorders
• confusion
• drowsiness
• tremors

These side effects may occur more frequently:

• in elderly patients (over 55 years of age)
• in patients with liver and kidney function disorders
• after previous treatment of brain and spinal cord tumors, such as radiation therapy or injection of cytostatic medicines
• with excessive alcohol consumption

The risk of nervous system damage increases with cytarabine treatment:

• at high doses or with short intervals between doses
• in combination with other treatments toxic to the nervous system (such as radiation therapy or methotrexate)

Cytarabine treatment may also cause amenorrhea in women and suppression of sperm production in men.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration 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.

5. How to store Cytarabina Accord

Keep this medicine out of the sight and reach of children.
Do not use Cytarabina Accord if the solution is not clear, colorless, and free of visible particles.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

Expiry date

Do not use this medicine after the expiry date stated on the vial and carton after EXP.
If only the month and year are stated, the expiry date refers to the last day of that month.

Storage

Do not store above 25°C. Do not refrigerate or freeze.
Chemical and physical stability has been demonstrated for concentrations of 0.04 mg/ml, 0.1 mg/ml, 1.0 mg/ml, and 4.0 mg/ml.
The product is stable for 8 days at a temperature below 25°C.
From a microbiological point of view, if the method of dilution does not exclude the risk of microbial contamination, the product should be used immediately. If the product is not used immediately, the user is responsible for the storage conditions and storage time.

6. Contents of the pack and other information

What Cytarabina Accord contains

The active substance is cytarabine. One milliliter (1 ml) of solution contains 20 milligrams (mg) of cytarabine.
The other ingredients are sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injections. See section 2 "Cytarabina Accord contains sodium".

What Cytarabina Accord looks like and contents of the pack

Cytarabina Accord is a clear, colorless solution without visible solid particles.
2 ml: vial made of colorless glass with a rubber stopper and a blue aluminum flip-off seal.
5 ml: vial made of colorless glass with a rubber stopper and a red aluminum flip-off seal.
The glass vial is surrounded by a protective sleeve made of plastic and a non-PVC base.
Pack sizes:
2 ml: 1 vial, 5 vials, or 25 vials
5 ml: 1 vial, 5 vials, or 25 vials
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer

Laboratori Fundació Dau
Pol. Ind. Consorci Zona Franca,
c/ C, 12-14 Barcelona, 08040
Spain
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the leaflet:April 2024
Detailed information on this medicine is available on the website: https://urpl.gov.pl
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Information intended for healthcare professionals only

In addition to the information provided in section 3, practical information on the preparation/handling of the medicine is provided here.
Incompatibilities
Cytarabine solutions are incompatible with various medicines: sodium salt of carbenicillin, sodium salt of cefalotin, fluorouracil, gentamicin sulfate, sodium salt of heparin, sodium salt of hydrocortisone succinate, neutral insulin, sodium salt of methylprednisolone succinate, sodium salt of nafcillin, sodium salt of oxacillin, sodium salt of penicillin G (benzylpenicillin), methotrexate, prednisolone succinate.
Incompatibilities depend on a number of factors (e.g., drug concentration, use of specific diluents, resulting pH, temperature). For detailed information on compatibility, consult specialized literature.
This medicinal product must not be mixed with other medicinal products except for those recommended.
Information on the use and handling of cytotoxic medicines
For single use only. Unused solution should be discarded.
Cytarabina Accord 20 mg/ml solution for injection/infusion is intended for intravenous, intramuscular, subcutaneous, or intrathecal administration.
The diluted solution should be clear, colorless, and free of visible particles.
Parenteral medicines should be inspected visually for particulate matter and color change prior to administration, whenever solution and container permit.
If the solution appears discolored or contains visible particles, it should be discarded.
Cytarabina Accord solution for injection/infusion is a ready-to-use solution, but it can be diluted with sterile water for injections, 5% glucose solution, or 0.9% sodium chloride solution for injection.
Chemical and physical stability has been demonstrated for concentrations of 0.04 mg/ml, 0.1 mg/ml, 1.0 mg/ml, and 4.0 mg/ml.
The product is stable for 8 days at a temperature below 25°C.
From a microbiological point of view, if the method of dilution does not exclude the risk of microbial contamination, the product should be used immediately. If the product is not used immediately, the user is responsible for the storage conditions and storage time.
Cytotoxic medicines should only be prepared for administration by personnel trained in the safe handling of the product. Procedures such as dilution and transfer to syringes should only be carried out in designated areas. Personnel involved in these procedures should wear appropriate protective clothing, gloves, and eye protection.
Pregnant women should avoid contact with cytotoxic medicines.
In case of skin or eye contact with the medicine, the affected area should be rinsed with plenty of water or saline solution. For the treatment of transient skin burning, a mild cream can be applied. If the solution comes into contact with the eyes, medical advice should be sought.
In case of spillage, personnel preparing the medicine should wear gloves and wipe up the spilled liquid with a sponge, which should be disposed of in a designated area. The surface should be rinsed twice with water. All solutions and sponges should be placed in a plastic bag and sealed tightly.
Disposal
For destruction, waste should be placed in a bag designated for high-risk cytotoxic waste and incinerated at 1100°C. In case of spillage, access to the contaminated area should be restricted, and appropriate protection, including gloves and safety glasses, should be used. The spread of the spilled liquid should be prevented, and it should be wiped up with absorbent paper or material. The spilled solution can also be treated with 5% sodium hypochlorite. The surface should be rinsed with plenty of water. Contaminated material should be placed in a sealed bag designated for cytotoxic waste and incinerated at 1100°C.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.