Citosar

Package Leaflet: Information for the User

CYTOSAR, 1g, Powder 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. 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 cytotoxic drugs 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 (alone) or in combination with other anti-cancer medicines. The best results are obtained when combination therapy is used.

The medicine in high doses, administered as an intravenous infusion in combination with other anti-cancer medicines or as monotherapy, is effective in the treatment of poorly differentiated leukemia, leukemia resistant to treatment, and in exacerbations (relapses) of acute leukemia.

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

2. Before you use the medicine

Contraindications

• 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 administration to infants and children under 3 years of age, solvents containing benzyl alcohol should not be used to prepare the medicine.

Special warnings and precautions for use

• In patients with previously detected drug-induced bone marrow suppression. The medicine 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) 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 less 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 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, pulmonary damage (acute respiratory distress syndrome, pulmonary edema), and cardiomegaly (heart enlargement).
• In patients treated with high doses of the medicine, as severe eye damage and the 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 non-lymphocytic acute 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 and 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.
• In patients receiving the medicine both intrathecally and intravenously at an interval of several 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 (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, use appropriate pharmacological measures.

Patients receiving the medicine should have regular 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 immune function due to chemotherapy (including this medicine) may lead to severe infections, and even death.

Interaction with other medicines

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

Tell your doctor about all medicines you are 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 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.

The use of the medicine in the first trimester of pregnancy may cause fetal malformations. The risk of fetal damage is much lower if treatment begins in the second or third trimester of pregnancy.

Benzyl alcohol contained in some solvents may cross the placenta.

Contraception in women of childbearing potential

Women should always use effective contraception to prevent pregnancy during treatment and for 6 months after the last dose. Discuss with your doctor the contraceptive methods that are suitable for you and your partner.

Contraception in men

Men with female partners of childbearing potential should always use highly effective contraceptive methods during treatment and for 3 months after the last dose.

Breastfeeding

There is insufficient data on the excretion of the medicine into human milk. Due to the risk of serious adverse reactions in nursing infants, the doctor will consider discontinuing breastfeeding for the duration of treatment with the medicine and for at least one week after the last dose or discontinuing the medicine, taking into account the benefit of treatment for the mother.

Driving and using machines

The effect of the medicine on the ability to drive and use machines has not been studied.

The medicine may affect the ability to drive and use machines due to possible adverse reactions (e.g., central nervous system disorders, dizziness).

Benzyl alcohol

The use of benzyl alcohol is associated with the occurrence of severe adverse reactions, including "gasping syndrome" and cases of death in children. Although the amounts of benzyl alcohol administered in standard therapeutic doses of the medicine are significantly lower than those reported in association with "gasping syndrome," the minimum amount of benzyl alcohol that can cause toxic effects is not known. The risk of benzyl alcohol toxicity depends on the dose administered and the liver's ability to eliminate toxins. Premature infants and newborns with low birth weight are at greater risk of toxicity.

Benzyl alcohol can cause toxic and allergic reactions in infants and children under 3 years of age. If the medicine is administered in high doses, solvents containing benzyl alcohol should not be used. The medicine can be dissolved using a preservative-free 0.9% sodium chloride solution.

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 regimen used. The medicine can be administered as an intravenous infusion, intravenous injection, or subcutaneously.

Overdose

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

Discontinuation of treatment

The decision to discontinue 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):

Septicemia (generalized infection), pneumonia, infection.

Bone marrow suppression, thrombocytopenia (decreased platelet count), anemia, megaloblastic anemia (a condition characterized by lower than normal hemoglobin values and a decreased number of enlarged red blood cells), leukopenia (decreased white blood cell count), decreased reticulocyte count (immature red blood cells).

Mouth ulcers, oral mucositis, anal ulcers, 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 occurring usually 6-12 hours after administration of the medicine).

Fever.

Abnormal bone marrow biopsy and blood smear results.

Central nervous system disorders, drowsiness.

Corneal disorders.

Acute respiratory distress syndrome (lung disease), pulmonary edema.

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

Skin ulcers.

Necrotizing enterocolitis.

Exfoliative dermatitis.

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

Subcutaneous tissue inflammation at the injection site.

Anaphylactic reaction (severe allergic reaction), allergic edema.

Decreased appetite.

Toxic nerve damage, neuritis, dizziness, headache.

Conjunctivitis.

Pericarditis, bradycardia (decreased heart rate), atrial.

Thrombophlebitis.

Dyspnea, throat pain.

Pancreatitis, esophageal ulcers, esophagitis.

Jaundice.

Painful erythema and blistering on the hands and soles of the feet (palmar-plantar erythrodysesthesia syndrome), urticaria, pruritus, freckles.

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 ulcers, intestinal obstruction, peritonitis.

Liver damage, hyperbilirubinemia (increased bilirubin levels in the blood).

*Adverse reactions occurring after high-dose treatment with the medicine, other than after 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.

Side effects can also be reported to the marketing authorization holder or its representative.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store the medicine

Store 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.

Medicines should 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.

6. Contents of the pack and other information

What the medicine contains

• The active substance is cytarabine. Each vial contains 1g of cytarabine.
• The other ingredients are: hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH).

What the medicine looks like and contents of the pack

White, crystalline powder.

The pack contains 1 vial of colorless glass closed with a bromobutyl rubber stopper and an aluminum cap 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:

Pfizer Polska Sp. z o.o.

tel: 22 335 61 00

Date of last revision of the leaflet:12/2022

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, or subcutaneously.

When preparing the product for high-dose intravenous administration or for administration to infants and children under 3 years of age, solvents containing benzyl alcohol should not be used. For 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.

High doses of the medicine are better tolerated by patients if administered as a rapid intravenous injection rather than a slow intravenous infusion.

Intravenous administration

Standard doses

At the beginning of treatment (induction of remission) of acute non-lymphocytic leukemia, the dose of the medicine used in combination with other anti-cancer 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).

High doses

From 2 g/m2 to 3 g/m2, administered as an intravenous infusion lasting from 1 to 3 hours, given every 12 hours for 2-6 days, in combination with other anti-cancer medicines or as monotherapy.

Subcutaneous administration

Usually, 20-100 mg/m2 is administered, depending on the indication and the treatment regimen used.

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

Children and adolescents

The dosage of the medicine is similar to that recommended for adults. Current recommendations for dosing in children and adolescents should be consulted in the latest treatment standards.

Incompatibilities

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

Compatibility

Cytarabine is compatible with the following products in the specified concentrations, in 5% 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 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 between 8°C in concentrations of 0.2-1.0 mg/ml in the presence of sodium bicarbonate equal 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.

Cytarabine injections and prepared infusion solutions do not contain antimicrobial preservatives. Therefore, it is recommended that further dilutions be prepared immediately before use, and the infusion started 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 discarded.