Citosar

Leaflet accompanying the packaging: information for the user

CYTOSAR, 500 mg, powder and solvent for solution for injection

Cytarabine

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

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• 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 the medicine and what is it used for
• 2. Important information before using the medicine
• 3. How to use the medicine
• 4. Possible side effects
• 5. How to store the medicine
• 6. Contents of the packaging and other information

1. What is the medicine and what is it used for

The medicine belongs to a group of anticancer medicines. The medicine should only be used by doctors with experience in cancer chemotherapy and only when the benefits of treatment with cytarabine outweigh the risks.

The medicine 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.

The medicine in high doses, administered by intravenous infusion in combination with other anticancer medicines or as monotherapy, is effective in the treatment of poorly prognostic leukemia, resistant leukemia, and relapses (recurrences) of acute leukemia.

It is rarely effective in the treatment of patients with solid tumors.

2. Important information before using the medicine

When not to use the medicine

• if the patient is hypersensitive to cytarabine or any of the other ingredients of this medicine (listed in section 6).

In the case of high-dose therapy administered intravenously, solvents containing benzyl alcohol should not be used to prepare the medicine.

Warnings and precautions

• In patients with previously detected drug-induced bone marrow suppression. The medicine strongly inhibits bone marrow function, causing leukopenia (reduced white blood cell count), thrombocytopenia (reduced platelet count), and anemia. There is a risk of potentially fatal infections associated with granulocytopenia (reduced granulocyte count), 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 less than 50,000 platelets/mm or 1000 granulocytes/mm. Re-administration of the medicine is possible after bone marrow recovery and increase in platelet and granulocyte count.

in patients receiving high doses of the medicine (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, pulmonary edema), and cardiomegaly (heart enlargement) symptoms.

• In patients treated with high doses of the medicine, as severe eye damage has been observed, as well as the risk of neuropathy. Changes in the treatment regimen may be necessary to avoid irreversible neurological disorders.
• In patients receiving high doses of cytarabine in combination with cyclophosphamide, as cases of cardiomegaly leading to death have been reported.
• In patients with non-lymphocytic acute leukemia receiving high doses of cytarabine, daunorubicin, and asparaginase, as peripheral neuropathies (peripheral nerve disease) have been observed.
• During the administration of rapid intravenous injections of high doses of the medicine, as nausea and vomiting often occur, which can last for several hours. These symptoms are generally less severe when the medicine is administered by infusion.
• In patients receiving standard doses of the medicine in combination with other medicines, due to the possibility of peritonitis, colitis with neutropenia, and thrombocytopenia.
• In children with acute myeloid leukemia after intrathecal and intravenous administration of standard doses of the medicine in combination with other medicines, a delayed progressive ascending paralysis has been observed, which can be fatal.
• In patients with liver or kidney function disorders, who should use the medicine, if possible, in reduced doses.
• When using the medicine with other medicines, due to the possibility of acute pancreatitis.
• In patients receiving the medicine both intrathecally and intravenously at an interval of a few days, as there is an increased risk of spinal cord damage. In severe cases, where the patient's life is at risk, the decision to administer the medicine both intrathecally and intravenously should be based solely on the doctor's assessment.
• In patients receiving the medicine intravenously in combination with methotrexate administered intrathecally, as cases of severe neurological side effects, including headache, paralysis, coma, and stroke-like episodes, have been reported.

The medicine 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 the medicine should undergo periodic checks of bone marrow, liver, and kidney function.

Patients taking the medicine 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 this medicine) may lead to severe infections and even death.

and other medicines

Before using a new medicine with this medicine, inform your doctor.

Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

The medicine may affect digoxin levels in the blood.

A lack of rapid improvement in the condition of patients infected with Klebsiella pneumoniae and treated with cytarabine and gentamicin has been observed. A change in antibacterial treatment is recommended.

The medicine may reduce the effectiveness of fluorocytosine.

The medicine 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, suspects she may be pregnant, or plans to have a child, she should consult a doctor or pharmacist before using this medicine.

In the event of pregnancy, contact a doctor.

Women who are pregnant or of childbearing age may only take the medicine after careful consideration of the potential benefits and risks to the mother and fetus.

Using the medicine during the first trimester of pregnancy may cause fetal developmental abnormalities. The risk of fetal damage is significantly lower if treatment begins in the second or third trimester of pregnancy.

The 500 mg powder and solvent for solution for injection contains 9 mg of benzyl alcohol per 1 ml of solvent, which corresponds to 9 mg/ml of benzyl alcohol. Benzyl alcohol may cause allergic reactions. Its administration to small children is associated with a risk of severe side effects, including respiratory disorders (gasping syndrome).

Do not administer to newborns (up to 4 weeks of age) without a doctor's recommendation.

Do not administer to small children (under 3 years of age) for more than a week without a doctor's or pharmacist's recommendation.

Patients with liver or kidney disease, as well as pregnant or breastfeeding women, should consult a doctor or pharmacist before using the medicine, as a large amount of benzyl alcohol may accumulate in their body and cause side effects (metabolic acidosis).

If the medicine is administered in high doses, solvents containing benzyl alcohol should not be used. A preservative-free 0.9% sodium chloride solution for injection should be used to reconstitute the medicine.

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

3. How to use the medicine

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 scheme used. The medicine can be administered by intravenous infusion, intravenous injection, or subcutaneously.

Using a higher dose of the medicine than recommended

The medicine will be used in a hospital setting by doctors with experience in cancer chemotherapy, so using a higher dose than recommended is unlikely.

Discontinuing the medicine

The decision to discontinue treatment is made by the doctor. In case of any further doubts about the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

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

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

• Septicemia (generalized infection), pneumonia, infection.
• Bone marrow suppression, thrombocytopenia (reduced platelet count), anemia, megaloblastic anemia (a condition characterized by lower than normal hemoglobin values and fewer, larger red blood cells), leukopenia (reduced white blood cell count), reduced reticulocyte count (immature red blood cells).
• Oral mucositis, oral mucositis ulceration, anal mucositis, anal mucositis, 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 occurring most commonly 6 to 12 hours after administration of the medicine).
• Fever.
• Abnormal bone marrow biopsy and blood smear results.
• Brain and cerebellar disorders*, drowsiness*.
• Corneal disorders*.
• Acute respiratory distress syndrome (lung disease)*, pulmonary edema*.

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

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

Frequency not known(cannot be estimated from the 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 (reduced heart rate), sinus bradycardia.
• Thrombophlebitis.
• Dyspnea, throat pain.
• Pancreatitis, esophageal ulceration, esophagitis.
• Jaundice.
• Painful erythema and blistering on hands and soles (palmar-plantar erythrodysesthesia syndrome), urticaria, pruritus, petechiae.
• 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 you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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 or its representative.

Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store the medicine

Store the medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the label and/or carton after:

EXP. The expiry date refers to the last day of the month stated.

Store below 25°C.

The prepared solution (using the solvent contained in the packaging) can be stored for up to 4 days in the refrigerator (2°C - 8°C) or up to 24 hours at a temperature below 30°C.

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.

6. Contents of the packaging and other information

What the medicine contains

• The active substance of the medicine is cytarabine. Each vial contains 500 mg of cytarabine.
• The other ingredients are: hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH).
• Solvent: water for injection, benzyl alcohol (see section 2 "The medicine contains benzyl alcohol and sodium").

What the medicine looks like and contents of the packaging

White crystalline powder and colorless solvent.

The packaging contains 1 vial of colorless glass closed with a bromobutyl rubber stopper and an aluminum cap, and 1 ampoule of colorless glass with solvent, in a cardboard box.

Marketing authorization holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer

Actavis Italy S.p.A.

Viale Pasteur 10

20014 Nerviano (Milan)

Italy