Cytosar lyophilizate for preparation of solution for injection, 100mg vials 1pc + solvent ampoules

Composition

1 bottle contains:

Active ingredients:

cytarabine 100 mg.

In a bottle of 100 mg.

In a cardboard package,1 bottle complete with solvent.

Pharmacological action

Pharmacodynamics

Antitumor agent from the group of antimetabolites-analogues of pyrimidine. It is assumed that cytarabine acts by inhibiting DNA polymerase. In addition, it appears to be only partially incorporated into DNA and RNA.

Pharmacokinetics

With rapid intravenous use, cytarabine penetrates the BBB only in moderate amounts, but after continuous intravenous infusion, the concentration in the cerebrospinal fluid reaches 40-50% of the steady-state plasma concentration.

Protein binding is 15%. It is rapidly metabolized by deamination in the blood and tissues, especially in the liver, and in minimal amounts in the cerebrospinal fluid.

T_1/2 is characterized by individual differences. It is excreted by the kidneys, less than 10% unchanged.

Indications

• Acute non-lymphoblastic leukemias;
• blast crisis of chronic myeloid leukemia;
• lymphogranulomatosis;
• erythromyelosis;
• neuroleukemia;
• non-Hodgkin’s lymphomas.

Use during pregnancy and lactation

Cytarabine is contraindicated during pregnancy. If necessary, use during lactation should stop breastfeeding.

Women of childbearing age should use reliable methods of contraception during treatment with cytarabine.

Experimental studies have established the teratogenic and embryotoxic effects of cytarabine.

Contraindications

• Myelodepression;
• pregnancy;
• hypersensitivity to cytarabine.

Side effects

From the hematopoietic system: leukopenia, thrombocytopenia, anemia, megaloblastosis, reticulocytopenia. The decrease in the number of white blood cells is biphasic, with the first maximum decrease being achieved by day 7-9. This is followed by a short ascent with a maximum of pa 12 days. With the second and deeper decrease, the minimum number of white blood cells is noted in 15-24 days. In the next 10 days, the number of white blood cells increases rapidly. A decrease in the number of platelets becomes noticeable by day 5, the minimum occurs between 12-15 days. In the next 10 days, there is a rapid increase in the number of platelets to the initial level.

Infectious complications: Secondary infections may occur due to immunosuppression caused by Cytosar and other cytostatic agents.

From the gastrointestinal tract: nausea, vomiting, loss of appetite, abdominal pain, diarrhea, inflammation or ulceration of the gastrointestinal mucosa. When using high doses (2-3 g/m2), ulceration of the gastrointestinal tract can be severe, it is possible to develop necrotic colitis, necrosis of the small intestine, cystic pneumatosis of the intestine, leading to peritonitis.

From the central and peripheral nervous system: paresthesia, headache, dizziness, neuritis. When using high-dose therapy, CNS function may be impaired (confusion, fatigue, memory loss, seizures, coma) and cerebellar function (difficulty talking, standing or walking, tremor). Cases of paraplegia and necrotic leukoencephalopathy have been reported with intrathecal Cytosar use.

From the liver: impaired liver function with hyperbilirubinemia; with high – dose therapy-sepsis and liver abscess.

From the skin and skin appendages: rash leading to desquamation, itching of the skin, the appearance of spots on the skin, alopecia.

From the side of the organ of vision: when treated with high doses, reversible toxic changes in the cornea and hemorrhagic conjunctivitis may occur. These reactions can be prevented or reduced by topical prophylactic corticosteroid eye drops.

From the cardiovascular and respiratory systems: arrhythmias, cardiomyopathies, pericarditis, bronchospasm, pulmonitis, progressive respiratory distress syndrome leading to pulmonary edema and cardiomegaly with a possible fatal outcome; the frequency of these phenomena increases with the use of high doses of Cytosar and cyclophosphamide.

Other side effects: anaphylaxis, hyperuricemia, rarely-impaired renal function, urinary retention, pain, inflammation of the subcutaneous tissue, thrombophlebitis at the injection site, the so-called cytarabine syndrome, characterized by fever, myalgia, bone pain, sometimes chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 hours after the drug is applied. Corticosteroids have been shown to be effective in preventing and treating this syndrome.

Interaction

Cytosar should not be mixed in the same syringe or dropper with other medications.

The combined use of Cytosar with other antitumor myelosuppressive drugs or radiation therapy in some cases increases the cytotoxic and immunosuppressive activity of these drugs.

When using polychemotherapy with the inclusion of Cytosar, a reversible decrease in the stabilized plasma concentration of digoxin and renal glycoside excretion was noted. An alternative for such patients can be considered the use of digitoxin, a stabilized plasma concentration, which, as it turned out, does not change under similar conditions.

In vitro studies of the interaction between gentamicin and cytarabine revealed the existence of cytarabine-related antagonism with respect to the sensitivity of K. pneumoniae strains to gentamicin.

Clinical data concerning one patient indicate the possibility of reducing the effectiveness of fluorocytosine.

How to take, course of use and dosage

The scheme and method of application vary in different chemotherapy regimens. Before prescribing the drug, it is recommended to consult special literature. Cytosar can be administered intravenously by jet or infusion, subcutaneously or intrathecally.

The average daily dose of Cytosar is 100 mg/m2. Elderly patients or with reduced hematopoietic reserves are prescribed smaller doses of the drug-50-70 mg/m2.

In acute non-lymphoblastic leukemias, Cytosar is prescribed 100 mg/m /day by continuous intravenous infusion for 7 days or 100 mg/m 2 IV every 12 hours for 7 consecutive days to induce remission during chemotherapy with conventional doses in combination with other antitumor drugs. In total,4-7 treatment courses are conducted. The intervals between courses are 14 days or more.

In the treatment of leukemias with a poor prognosis, as well as refractory and recurrent acute leukemias, it is possible to use high doses of Cytosar-2-3 g/m2 in the form of 1-3-hour infusions, every 12 hours for 2-6 days with or without the addition of other antitumor drugs.

Intrathecally, in acute leukemia, Cytosar is most often used at a dose of 30 mg/m2 every 4 days until the composition of the cerebrospinal fluid normalizes, and then another additional use. The dosage (from 5 to 75 mg / m2) and the frequency of use (from once a day for 4 days to once every 4 days) depends on the type and severity of neurological symptoms and the effectiveness of previous therapy.

Preparation of the solution

To obtain a solution with a concentration of 20 mg/ml,5 ml of solvent should be added to the contents of a 100 mg bottle.

To obtain a solution with a concentration of 50 mg/ml,10 ml of solvent should be added to the contents of a 500 mg bottle.

To obtain a solution with a concentration of 100 mg/ml,10 ml of solvent should be added to the contents of an 11 g bottle.

The cytarabine concentration should not exceed 100 mg / ml.

The supplied solvent contains benzyl alcohol: do not use for intrathecal use.

Cytosar dosage form powder for injection can be dissolved in water for injection. 0.9% sodium chloride solution or 5% dextrose solution with or without preservative.

0.9% sodium chloride solution is used as a solvent for intrathecal use. The solvent for intrathecal use and high-dose therapy should not contain preservatives (benzyl alcohol).

Note: In order to open the ampoule, a file is not required The neck of the ampoule is pre-cut at the point of narrowing. A colored dot on the ampoule head helps you orient the ampoule correctly. Take the ampoule in your hands and turn its point towards you, if you easily press your thumb on this point, the ampoule will easily open.

Overdose

In the literature, there is a report that the introduction of 4.5 g/m2 of Cytarabine in the form of an intravenous infusion (during I h) every 12 hours 12 times in a row led to irreversible changes in the central nervous system and even death. There is no specific antidote.

Treatment is symptomatic.

Special instructions

It is not recommended to use cytarabine in patients with chickenpox (including recently transferred or after contact with the sick), with herpes zoster or other acute infectious diseases.

Cytarabine is used with caution in patients with hematopoietic system depression, impaired renal and/or liver function, with bone marrow infiltration by tumor cells, as well as in patients who have previously received cytotoxic drugs or radiation therapy.

During therapy with cytarabine, the picture of peripheral blood, liver and kidney function, and the level of uric acid in blood plasma should be monitored.

24 hours after use, the number of white blood cells decreases, reaches the minimum values on the 7th-9th day, then briefly increases until the 12th day, after which it decreases again more significantly with a minimum on the 15th-24th day. In the next 10 days, the number of white blood cells rapidly increases to the initial level.The platelet count decreases significantly on the 5th day after cytarabine use, the lowest level is reached on the 12th-15th day, reaching the initial level within the next 10 days.

The introduction of corticosteroids can prevent or reduce the manifestations of cytarabine syndrome.

During treatment, especially in the presence of a large number of blast cells or with a large mass of the tumor (lymphoma), it is necessary to carry out mandatory drug prevention of hyperuricemia and ensure that allopurinol and a sufficient amount of fluid are taken.

In experimental studies, the mutagenic effect of cytarabine was established.

Form of production

Lyophilizate for solution preparation for injection

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

5 years

Active ingredient

Cytarabine

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection