Citosar

Package Leaflet: Information for the User

CYTOSAR, 100 mg, powder and solvent for solution for injection

Cytarabine

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

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 and other information

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

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

The medicine belongs to a group of anti-cancer medicines. The medicine should only be used by doctors experienced in the administration of anticancer therapy and only when the benefits of treatment 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 obtained with combination therapy.

In monotherapy or in combination with sodium hydrocortisone acetate and methotrexate administered intrathecally, it can be used to treat leukemia with central nervous system involvement.

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

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

2. Important information before you use the medicine

When not to use the medicine

• If you are allergic to cytarabine or any of the other ingredients of this medicine (listed in section 6).

In the case of high-dose therapy administered intravenously or intrathecally, 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 suppresses bone marrow function, causing leukopenia (reduced white blood cell count), thrombocytopenia (reduced platelet count), and anemia. There is a risk of potentially life-threatening infections associated with granulocytopenia (reduced granulocyte count) and 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 increase in platelet and granulocyte counts.
• In patients receiving high doses of the medicine (2-3 g/m2) due to the occurrence of severe and sometimes life-threatening central nervous system damage (manifested by seizures, among other things), gastrointestinal damage, pulmonary damage (adult respiratory distress syndrome, pulmonary edema), and cardiomegaly (heart enlargement).
• In patients treated with high doses of the medicine, as severe eye damage and a risk of neuropathy have been observed. 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 acute non-lymphocytic leukemia receiving high doses of cytarabine, daunorubicin, and asparaginase, as peripheral neuropathies (diseases of the peripheral nerves) 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 as an infusion.
• In patients receiving standard doses of the medicine in combination with other medicines, due to the possibility of pancreatitis, 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 leading to death has been observed.
• In patients with liver or kidney function disorders, in whom the medicine should be used, if possible, in reduced doses.
• During the administration of the medicine with other medicines, due to the possibility of acute pancreatitis.
• During intrathecal administration of the medicine, due to the possibility of systemic toxic symptoms. It is recommended to carefully monitor the patient's hematopoietic system. Dose adjustment may be necessary.
• 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, when 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 adverse reactions, including headache, paralysis, coma, and stroke-like episodes, have been reported.

The medicine may cause hyperuricemia (elevated 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 have periodic checks of their bone marrow, liver, and kidney function.

Patients taking the medicine should not be vaccinated with live vaccines. They may 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 pneumoniaeand 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 adverse reactions.

Pregnancy and breastfeeding

Pregnancy

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 using this medicine.

In case of pregnancy, contact your doctor.

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

Use of the medicine in the first trimester of pregnancy may cause fetal malformations. The risk of fetal damage is significantly lower if treatment is started in the second or third trimester of pregnancy.

The medicine 100 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. Administration to small children is associated with a risk of severe adverse reactions, including 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 disorders, as well as pregnant or breastfeeding women, should consult their doctor or pharmacist before using the medicine, as a large amount of benzyl alcohol may accumulate in their body and cause adverse reactions (metabolic acidosis).

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

Your doctor will determine the dose of the medicine that is right for you. The scheme and method of administration depend on the treatment scheme used. The medicine can be administered as an intravenous infusion, intravenous injection, subcutaneously, or intrathecally.

Using a higher dose of the medicine than recommended

The medicine will be used in a hospital setting by doctors experienced in the administration of anticancer therapy, so the use of a higher dose than recommended is unlikely.

Stopping the use of the medicine

The decision to stop treatment is made by the doctor. 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.

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

• Sepsis (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).
• Mouth ulceration, oral mucositis, rectal 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 6-12 hours after administration of the medicine).
• Fever.
• Abnormal bone marrow biopsy and blood smear results.
• Central nervous system disorders and cerebellar disorders*, drowsiness*.
• Corneal disorders*.
• Acute respiratory distress syndrome*, pulmonary edema*.

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

• Skin ulceration.
• Necrotizing colitis*.
• 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.
• Toxic nerve damage, neuritis, dizziness, headache.
• Conjunctivitis.
• Pericarditis, bradycardia (reduced heart rate), atrial bradycardia.
• Thrombophlebitis.
• Dyspnea, throat pain.
• Pancreatitis, esophagitis, esophageal ulceration.
• Jaundice.
• Painful erythema and blistering on the hands and soles of the feet (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* (elevated bilirubin levels in the blood).

*adverse reactions occurring with high doses of the medicine, other than with standard doses.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. 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.

5. How to store the medicine

Keep the medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Store in a temperature below 25°C.

The prepared solution (using the solvent contained in the package) 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 pack and other information

What the medicine contains

• The active substance is cytarabine. Each vial contains 100 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 pack

White, crystalline powder and colorless solvent.

The pack 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 Bruxelles, Belgium

Manufacturer

Actavis Italy S.p.A., Viale Pasteur 10, 20014 Nerviano (Milan), Italy

For further information, contact the marketing authorization holder or its representative:

Pfizer Polska Sp. z o.o., tel: 22 335 61 00

Date of last revision of the leaflet: 12/2022

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Information intended for healthcare professionals only

Full information about the medicine is contained in the Summary of Product Characteristics.

Dosage and administration

The medicine is inactive when administered orally. The medicine can be administered as an intravenous infusion, intravenous injection, subcutaneously, or intrathecally.

Standard doses

For the initial treatment (induction of remission) of acute non-lymphocytic leukemia, the dose of the medicine used in combination with other anticancer medicines is usually 100 mg/m2 per day as a continuous intravenous infusion (days 1-7) or 100 mg/m2 intravenously every 12 hours (days 1-7).

• 1.

High doses

From 2 g/m2 to 3 g/m2, administered as an intravenous infusion lasting from 1 to 3 hours, used every 12 hours for 2-6 days in combination with other anticancer medicines or as monotherapy. In the case of high-dose therapy, solvents containing benzyl alcohol should not be used.

The dosage of the medicine in acute lymphatic leukemia and non-Hodgkin's lymphoma in children should be in accordance with current guidelines.

For the reconstitution of the product, a preservative-free 0.9% sodium chloride solution for injection should be used. The product should be administered immediately after preparation.

Pharmaceutical incompatibilities

The medicine is physically incompatible with heparin, insulin, 5-fluorouracil, and sodium hydrocortisone acetate, as well as penicillins such as oxacillin and penicillin G.

Pharmaceutical compatibility

Cytarabine is compatible with the following products in the specified concentrations, in a 5% aqueous glucose solution for 8 hours: cytarabine 0.8 mg/ml and cefalotin (sodium) 1.0 mg/ml; cytarabine 0.4 mg/ml and prednisolone (sodium phosphate) 0.2 mg/ml; cytarabine 16 mg/ml and vincristine (sulfate) 4 µg/ml. Cytarabine is also physically compatible with methotrexate.

Special precautions for storage

Stability and compatibility after reconstitution

Studies on the chemical and physical stability of the medicine have shown that cytarabine remains stable for 7 days at a temperature below 25°C in glass bottles and plastic bags for intravenous infusions in a solution with a concentration of 0.5 mg/ml after mixing with the following solvents:

• water for injection,
• 5% glucose solution for injection,
• 0.9% sodium chloride solution for injection.

Cytarabine also remains stable for 7 days at a temperature below 25°C, at 20°C, and at 4°C in glass bottles and plastic bags for intravenous infusions in a solution with a concentration of 8-32 mg/ml after mixing with the following solvents:

• 5% glucose solution for injection,
• 5% glucose in 0.2% sodium chloride solution for injection,
• 0.9% sodium chloride solution for injection.

Cytarabine remains stable for up to 8 days at a temperature below 25°C in a concentration of 2 mg/ml in the presence of KCl at a concentration of 50 mEq/500 ml after mixing with the following solvents:

• 5% glucose solution for injection,
• 0.9% sodium chloride solution for injection.

Cytarabine also remains stable at a temperature below 25°C or at a temperature of 8°C in concentrations of 0.2-1.0 mg/ml in the presence of sodium bicarbonate equivalent to 50 mEq/l in 5% glucose solution or 5% glucose in 0.2% sodium chloride solution for 7 days in glass bottles or plastic bags for intravenous infusions.

Intravenous injections of cytarabine and prepared infusion solutions do not contain antimicrobial preservatives. Therefore, it is recommended to prepare further dilutions immediately before use, and to start the infusion as soon as possible after preparation of the solution. The administration of the infusion should be completed within 24 hours of preparation of the solution, and any remaining solution should be discarded.