Citosar

Leaflet accompanying the packaging: information for the user

CYTOSAR, 100 mg/ml, solution for injection/infusion
Cytarabine

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

• Please keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, please consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Cytosar and what is it used for

Cytosar belongs to a group of anticancer medicines. The medicine should only be used by doctors with experience in the field of cancer chemotherapy and only when the benefits of treatment with cytarabine outweigh the risks.
Cytosar is used to treat acute myeloid leukemia in adults and children. It is also indicated for the treatment of acute lymphoblastic leukemia and chronic myeloid leukemia. It can be used as monotherapy (as the only medicine) or in combination with other anticancer medicines.
The best results are achieved with combination therapy.
Cytosar in high doses, administered as an intravenous infusion in combination with other anticancer medicines or as monotherapy, is effective in the treatment of poorly prognostic leukemia, refractory leukemia, and relapses (recurrences) of acute leukemia.
Cytosar is rarely effective in the treatment of patients with solid tumors.

2. Important information before using Cytosar

When not to use Cytosar

• do not use diluents containing benzyl alcohol for the preparation of the medicine in the case of high-dose intravenous therapy or administration in infants and children under 3 years of age.

Warnings and precautions

Before starting treatment with Cytosar, the patient should discuss it with their doctor, pharmacist, or nurse.

• In patients with previously detected drug-induced bone marrow suppression. Cytosar strongly suppresses bone marrow function, causing leukopenia (decreased white blood cell count), thrombocytopenia (decreased platelet count), and anemia. There is a risk of potentially fatal infections associated with granulocytopenia (decreased granulocyte count), a risk of impaired immune function, and bleeding due to thrombocytopenia. The doctor will consider discontinuing the medicine or adjusting the dose if the patient's blood count shows fewer than 50,000 platelets/mm or 1,000 granulocytes/mm. Re-administration of the medicine is possible after bone marrow recovery and an increase in platelet and granulocyte count.

in patients receiving high doses of Cytosar (2-3 g/m2) due to the occurrence of severe and sometimes fatal central nervous system damage (manifested by seizures, among other things), gastrointestinal damage, lung damage (acute respiratory distress syndrome in adults, pulmonary edema), and symptoms of cardiomegaly (enlargement of the heart).

• In patients treated with high doses of Cytosar, as severe eye damage has been observed, as well as a risk of neuropathy (peripheral nerve disease). Changes in the treatment regimen may be necessary to avoid irreversible neurological disorders.
• In patients receiving high doses of Cytosar in combination with cyclophosphamide, as cardiomegaly leading to death has been reported.
• In patients with acute non-lymphocytic leukemia receiving high doses of cytarabine, daunorubicin, and asparaginase, as peripheral motor and sensory neuropathies have been observed.
• During the administration of rapid intravenous injections of high doses of Cytosar, as nausea and vomiting often occur, which can last for several hours. These symptoms are generally less severe when the medicine is administered as an infusion.
• In patients receiving standard doses of Cytosar in combination with other medicines, due to the possibility of peritonitis, colitis with accompanying neutropenia and thrombocytopenia.
• In children with acute myeloid leukemia after intrathecal and intravenous administration of standard doses of cytarabine in combination with other medicines, as delayed progressive ascending paralysis has been observed, which can be fatal.
• In patients with liver or kidney function disorders, in whom the medicine should be used, if possible, in a reduced dose.
• When using Cytosar with other medicines, due to the possibility of acute pancreatitis.
• In patients receiving Cytosar intravenously in combination with methotrexate administered intrathecally, as severe neurological side effects, including headache, paralysis, coma, and stroke-like episodes, have been reported.

Cytosar may cause hyperuricemia (increased uric acid levels in the blood) as a consequence of rapid lysis (breakdown) of cancer cells. The doctor should monitor the patient's uric acid levels and, if necessary, take appropriate pharmacological measures.
Patients receiving Cytosar should undergo periodic checks of bone marrow, liver, and kidney function.
Patients taking Cytosar should not be vaccinated with live vaccines. They can receive killed or inactivated vaccines, but their effectiveness may be reduced.
Administration of live or live attenuated vaccines to patients with impaired immunity due to chemotherapy (including Cytosar) may lead to severe infections, even death.

Cytosar and other medicines

Before using a new medicine with Cytosar, the patient should inform their doctor. They should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Cytosar may affect digoxin levels in the blood.
A lack of rapid improvement in the condition of patients infected with Klebsiella pneumoniaeand treated with Cytosar and gentamicin has been observed. A change in antibacterial treatment is recommended.
Cytosar may reduce the effectiveness of fluorocytosine.
Cytosar administered intravenously in combination with methotrexate administered intrathecally may increase the risk of severe neurological side effects.

Pregnancy and breastfeeding

Pregnancy
If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
In case of pregnancy, the patient should contact their doctor.
Women who are pregnant or of childbearing age may only take Cytosar after careful consideration of the potential benefits and risks to the mother and fetus.
Use of Cytosar in the first trimester of pregnancy may cause fetal developmental abnormalities. The risk of fetal damage is much lower if treatment starts in the second or third trimester.
Contraception in women of childbearing age
Women should always use effective contraception to prevent pregnancy during treatment and for 6 months after the last dose. They should discuss suitable contraception methods with their doctor.
Contraception in men
Men with partners of childbearing age should always use highly effective contraception during treatment and for 3 months after the last dose.
Breastfeeding
There is insufficient data on the penetration of Cytosar into human milk.
Due to the risk of severe side effects in infants breastfed by mothers taking Cytosar, the doctor will consider the decision to stop breastfeeding for the duration of treatment with Cytosar and for at least one week after the last dose or to discontinue the medicine, taking into account the benefit of treatment for the mother.

Driving and using machines

The effect of Cytosar on the ability to drive and use machines has not been studied.
Cytosar may affect the ability to drive and use machines due to possible side effects (e.g., central nervous system disorders, dizziness).

Cytosar contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per 1 ml vial, which means the medicine is considered "sodium-free".
When preparing the medicine for administration, the sodium content from the diluent, i.e., sodium chloride solution, should also be taken into account.

3. How to use Cytosar

The doctor will determine the dose of the medicine that is most suitable for the patient. The scheme and method of administration depend on the treatment regimen used. Cytosar can be administered as an intravenous infusion, intravenous injection, or subcutaneously.

Use of a higher dose of Cytosar than recommended

Cytosar will be used in a hospital setting by doctors with experience in the field of cancer chemotherapy, so the use of a higher dose than recommended is unlikely.

Discontinuation of Cytosar

The decision to stop treatment is made by the doctor. In case of any further doubts related to the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

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

Very common (may occur in more than 1 in 10 people):

• Sepsis (generalized infection), pneumonia, infection.
• Bone marrow suppression, thrombocytopenia (decreased platelet count), anemia, megaloblastic anemia (a set of symptoms resulting from lower than normal hemoglobin values and a lower number of enlarged red blood cells), leukopenia (decreased white blood cell count), decreased reticulocyte count (immature red blood cells).
• Mouth ulceration, oral mucositis, anal mucositis, proctitis, diarrhea, vomiting, nausea, abdominal pain.
• Liver function disorders.
• Hair loss, rash.
• Cytarabine syndrome (fever, muscle pain, bone pain, sometimes chest pain, maculopapular rash, conjunctivitis, and malaise, usually occurring 6 to 12 hours after administration of the medicine).
• Fever.
• Abnormal bone marrow biopsy and blood smear results.
• Central nervous system and cerebellar disorders*, drowsiness*.
• Corneal disorders*.
• Acute respiratory distress syndrome (lung disease)*, pulmonary edema*.

Common (may occur in up to 1 in 10 people):

• Skin ulceration.
• Necrotizing enterocolitis*.
• Exfoliative dermatitis*.

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

• Subcutaneous tissue inflammation at the injection site.
• Anaphylactic reaction (sudden allergic reaction), allergic edema.
• Decreased appetite.
• Neurotoxicity, neuritis, dizziness, headache.
• Conjunctivitis.
• Pericarditis, bradycardia (decreased heart rate), sinus bradycardia.
• Thrombophlebitis.
• Dyspnea, throat pain.
• Pancreatitis, esophageal ulceration, esophagitis.
• Jaundice.
• Painful erythema and blistering on the hands and soles of the feet (palmar-plantar erythrodysesthesia syndrome), urticaria, pruritus, pigmentation.
• Kidney function disorders, urinary retention.
• Chest pain, pain and inflammation at the subcutaneous injection site.
• Hepatic abscess*.
• Personality changes*.
• Coma*, seizures*, peripheral motor neuropathy*, peripheral sensory neuropathy*.
• Cardiomyopathy* (heart disease).
• Gastric or intestinal necrosis*, gastric or intestinal ulcer*, intestinal obstruction*, peritonitis*.
• Liver damage*, hyperbilirubinemia* (increased bilirubin levels in the blood).

* side effects occurring after high-dose treatment, other than after standard doses.

Reporting side effects

If any side effects occur, including any not listed in this leaflet, the patient should inform their doctor or pharmacist, or nurse. 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
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 authorization holder or its representative.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Cytosar

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label, carton, or blister pack: Expiry Date (EXP). The expiry date refers to the last day of the month.
Store below 25°C. Do not freeze.
Store in the original packaging to protect from light.
Storage conditions for the medicine after dilution, see section "Information intended for healthcare professionals only. Shelf-life of the medicine after dilution".

6. Contents of the packaging and other information

What Cytosar contains:

• The active substance of the medicine is cytarabine. One ml of the solution contains 100 mg of cytarabine. One 10 ml vial contains 1000 mg of cytarabine. One 20 ml vial contains 2000 mg of cytarabine.
• The other ingredients are: hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH), water for injections.

What Cytosar looks like and what the pack contains

A clear, colorless or slightly yellowish aqueous solution, free from visible particles, in a polypropylene vial with a chlorobutyl rubber stopper coated with Teflon, with an aluminum seal and a purple, non-transparent, flip-off plastic cap, in a cardboard box.
The pack contains 1 vial of 10 ml or 5 vials of 10 ml, or 1 vial of 20 ml, or 10 vials of 20 ml.
Not all pack sizes may be marketed.

Marketing authorization holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer

Pfizer Service Company BV
Hoge Wei 10
1930 Zaventem
Belgium