Cytarabine accord

Patient Information Leaflet

Cytarabina Accord, 20 mg/ml, solution for injection/infusion
Cytarabinum
Please read all of this leaflet carefully before using this medicine, as 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 or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Cytarabina Accord is and what it is used for
2. Important information before using Cytarabina Accord
3. How to use Cytarabina Accord
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 known as cytotoxic agents. These are used in the treatment of acute leukaemias (blood cancers characterized by excessive white blood cells), including prophylaxis and treatment of disease involving the central nervous system (leukaemia with meningeal involvement). Cytarabine interferes with the growth of cancer cells, which eventually leads to their destruction.

2. Important information before using Cytarabina Accord

When not to use Cytarabina Accord

• if the patient is allergic to cytarabine or any of the other ingredients of this medicine (listed in section 6);
• if, for reasons other than cancer, the blood cell count is very low, unless the doctor decides that treatment with cytarabine is safe;
• if the patient experiences worsening difficulties with motor coordination following radiotherapy or another anticancer medicine such as methotrexate;
• if the patient is pregnant.

Warnings and precautions
Before starting treatment with Cytarabina Accord, talk to your doctor, pharmacist, or nurse:

• if bone marrow is not functioning properly, as treatment should only be started under strict medical supervision.

• if the patient has liver disease. If the patient has impaired liver function before starting treatment, cytarabine should only be administered under close medical supervision.

• if the patient has received radiotherapy.

• if the patient is receiving transfusions of a specific type of blood cells (granulocytes).

• if the patient has undergone or is scheduled to undergo dialysis shortly before or after treatment with cytarabine. If the patient is undergoing dialysis, the doctor may adjust the timing of administration of this medicine, as dialysis may reduce its effectiveness.

During treatment

• The doctor will order regular blood tests and, if necessary, bone marrow examinations.
• The doctor may order frequent monitoring tests of liver and kidney function.
• During treatment with this medicine, the doctor may perform tests to assess nervous system function.
• During treatment with cytarabine, blood levels of uric acid (indicating that tumour cells are being destroyed) may increase (hyperuricaemia). The doctor will inform the patient whether medications to control blood uric acid levels are necessary.
• Administration of live or attenuated vaccines is not recommended during treatment with cytarabine. If vaccination is needed, consult the doctor. Vaccines containing killed or inactivated microorganisms may not provide the desired effectiveness due to immunosuppression caused by cytarabine.

Cytarabine significantly suppresses blood cell production in the bone marrow. This may increase susceptibility to infections or bleeding. Blood cell counts may continue to decrease even after treatment has ended.
Cytarabina Accord and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those available without a prescription.

• digoxin or beta-acetyldigoxin (used in the treatment of 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 in the treatment of various cancers and certain inflammatory conditions);
• idarubicin (used in the treatment of leukaemia and breast cancer).

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Pregnancy should be avoided when the patient or her partner is being treated with cytarabine. Both women and men who are sexually active should use effective contraception methods to prevent pregnancy during treatment. Cytarabine may cause birth defects; therefore, it is important to inform the doctor if the patient suspects she may be pregnant.
Women of reproductive age should be advised by their doctor to use effective contraception to avoid pregnancy during treatment with this medicine and for at least 6 months after completion 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 partners from becoming pregnant.
Breastfeeding
Breastfeeding must be discontinued before starting treatment with cytarabine, as this medicine may be harmful to breastfed infants.
Effect on fertility
Cytarabine may cause menstrual cycle suppression and absence of menstruation in women, and suppression of sperm production in men.
Driving and operating machinery
Cytarabine has no effect on the ability to drive or operate machinery. However, anticancer treatment may affect this ability in some patients. If symptoms occur, the patient should not drive or operate machinery.
Cytarabina Accord contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 5 ml, meaning the medicine is considered "sodium-free".

3. How to use Cytarabina Accord

Cytarabina Accord is administered under the supervision of specialists in a hospital setting. Your doctor will decide the dose to be given, and the number of days of treatment will depend on the patient's condition.
This medicine can be administered by injection (using a syringe) subcutaneously, intravenously, intramuscularly, or into the spinal canal (intrathecally).
Dosage
Your doctor will determine the dose of cytarabine based on the patient's health status, body surface area, and type of treatment (induction or maintenance). Body surface area will be calculated based on the patient's body weight and height.
Overdose of Cytarabina Accord
High doses may intensify adverse effects such as oral ulceration or reduction in white blood cells and platelets (which help blood to clot), nerve damage, severe lung disorders, heart problems, and may even lead to death.
In such cases, antibiotic therapy or blood transfusion may be necessary. To reduce discomfort associated with oral ulceration, appropriate treatment may be used.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions to cytarabine depend on the dose. The most common effects involve the gastrointestinal tract and the blood. Gastrointestinal adverse reactions are less pronounced when cytarabine is administered by infusion.
If any of the following symptoms occur, urgent medical help may be required.
Contact your doctor or nurse immediately if you experience any of the following:

• sudden allergic symptoms 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 blood poisoning (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 indicate brain or nerve damage
• unusual muscle pain or tenderness
• eye pain, tearing or burning with bleeding, visual disturbances, sensitivity to light
• complete loss of vision
• sudden sharp chest pain radiating to shoulders and neck
• severe abdominal pain with vomiting, diarrhea, constipation or presence of blood in stool
• sudden weight loss or jaundice (yellowing of the skin and whites of the eyes), change in urine or stool color, persistent cough with fever, chills and shortness of breath due to lung infection
• worsening of other signs of infection such as sore throat or mouth ulcers, which may be due to reduced number of white blood cells
• pale skin and fatigue or increased bleeding or bruising, which may be due to reduced numbers of other types of blood cells
• difficulty passing urine or emptying the bladder

Other possible adverse reactions:
Common: may affect up to 1 in 10 patients

• fever
• abnormal blood cells (megaloblastosis)
• loss of appetite
• difficulty swallowing
• intestinal pain (abdominal pain)
• nausea
• vomiting
• reduced level of consciousness (with high-dose treatment)
• difficulty speaking (with high-dose treatment)
• abnormal eye movements (nystagmus with high-dose treatment)
• diarrhea
• inflammation or ulceration of the mouth or rectum
• reversible effects on the liver, such as increased enzyme activity
• reversible skin reactions such as redness (erythema), blistering, rash, urticaria, vasculitis, hair loss (with high-dose treatment)
• kidney disorders detectable by blood or urine tests
• abnormally high levels of uric acid in the blood (hyperuricemia)

Uncommon: may affect up to 1 in 100 patients

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

Very rare: may affect up to 1 in 10,000 patients

• blisters or skin eruptions
• irregular heartbeat (arrhythmia)

Frequency not known: frequency cannot be estimated from available data

• dizziness
• painful swelling of hands or feet
• development of freckles on the skin
• rash
• chest pain
• burning pain in palms and soles
• slower than usual heart rate
• low number of early developmental stages of red blood cells (reticulocytes) in the blood
• low number of white blood cells (neutropenia)
• general feeling of illness with high fever due to low number of white blood cells (febrile neutropenia)

Other adverse reactions
Cytarabine syndrome may occur 6–12 hours after starting treatment. Symptoms include:

• fever
• bone and muscle pain
• eye pain (conjunctivitis)
• malaise
• occasional chest pain
• rash
• nausea

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

• inflammation of the membrane covering the brain and spinal cord (meningitis), which may cause symptoms such as severe headache, numbness or tingling in 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 may continue.
The following symptoms, usually reversible, may occur in one third of patients after high-dose cytarabine treatment:

• personality changes
• attention disturbances
• coordination and balance problems
• confusion
• drowsiness
• tremor

These adverse reactions may occur more frequently:

• in elderly patients (over 55 years of age)
• in patients with impaired liver or kidney function
• after previous treatment for brain or spinal cord tumors, such as radiotherapy or cytotoxic drug injection
• with alcohol abuse

The risk of nervous system damage increases with cytarabine treatment:

• at high doses or administered in short intervals
• in combination with other neurotoxic treatments (such as radiotherapy or methotrexate)

Cytarabine treatment may also cause amenorrhea in women and suppression of sperm production in men.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

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, colourless, and free from 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.
Expiry date
Do not use this medicine after the expiry date stated on the vial and outer carton: EXP.
If only the month and year are given, the expiry date refers to the last day of the stated month.
Storage
Do not store above 25°C. Do not store in the refrigerator 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 medicinal product is stable for 8 days at temperatures below 25°C.
From a microbiological standpoint, if the dilution method does not exclude the risk of microbiological contamination, the medicinal product should be used immediately. If the medicinal product is not used immediately, responsibility for storage conditions and duration lies with the user.

6. Contents of the pack and other information

What Cytarabina Accord contains
The active substance is cytarabine. One millilitre (1 ml) of solution contains 20 milligrams (mg) of cytarabine.
The other ingredients are: sodium chloride, sodium hydroxide (for pH adjustment), concentrated 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, colourless solution without visible solid particles.
2 ml: a vial made of colourless glass with a butyl rubber stopper and a blue flip-off aluminium seal.
5 ml: a vial made of colourless glass closed with a butyl rubber stopper and a red flip-off aluminium seal.
The glass vial is surrounded by a secondary plastic protective cover and a non-PVC backing.

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 Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warszawa
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 medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Detailed information about this medicinal product is available on the website: https://urpl.gov.pl

Information intended solely for healthcare professionals or medical personnel

healthcare services
The following practical information on preparation and handling of the medicinal product supplements the information provided in section 3.

Pharmaceutical incompatibilities
Cytarabine solutions are incompatible with various medicinal products: sodium carbenicillin, sodium cephalothin, fluorouracil, gentamicin sulfate, sodium heparin, sodium succinate hydrocortisone, neutral insulin, sodium succinate methylprednisolone, sodium nafcillin, sodium oxacillin, sodium penicillin G (benzylpenicillin), methotrexate, prednisolone succinate.

Incompatibilities depend on several factors (e.g. drug concentration, use of specific diluents, resulting pH, temperature). For detailed information on compatibility, please consult specialized literature.

This medicinal product must not be mixed with other medicinal products except for the recommended diluents.

Information on the use and handling of cytotoxic drugs

For single use only. Any unused solution should be discarded.

The medicinal product 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 from visible particulate matter.

Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

If the solution appears discolored or contains visible particulate matter, it should be discarded.

The medicinal product Cytarabina Accord, solution for injection/infusion, is a ready-to-use solution, but may be diluted with sterile water for injections, 5% glucose solution, or 0.9% sodium chloride solution for injections.

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 medicinal product is stable for 8 days at temperatures below 25°C.

From a microbiological standpoint, if the method of dilution does not exclude the risk of microbiological contamination, the medicinal product should be used immediately. If not used immediately, the user is responsible for the conditions and duration of storage.

Chemotherapeutic agents should be prepared for administration only by specialists trained in the safe handling of such agents. Procedures such as dilution and transfer into syringes should be performed only in designated areas. Personnel performing these procedures should wear appropriate protective clothing, gloves, and eye protection.

Pregnant women should avoid contact with chemotherapeutic agents.

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 mild cream may be used to treat transient skin irritation. If the solution enters the eyes, medical advice must be sought.

In the event of a spill, personnel preparing the drug should wear gloves and wipe up the spilled liquid using a sponge kept in a designated spill kit. The surface should be washed twice with water. All solutions and sponges should be placed in a plastic bag and securely sealed.

Disposal

For destruction, waste should be placed in a bag designated for (cytotoxic) high-risk waste and incinerated at 1100°C. In case of a spill, access to the contaminated area should be restricted, and appropriate protection, including gloves and protective goggles, should be used. The spread of spilled liquid should be prevented and wiped up using absorbent paper or material. Spilled solution may also be treated with 5% sodium hypochlorite. The surface should be rinsed with a large amount of water. Contaminated materials should be placed in a sealed bag designated for cytotoxic waste and incinerated at 1100°C.

Any unused portions of the medicinal product or its waste should be disposed of in accordance with local regulations.