Cytosar, lyophilizate 1000 mg

Pharmacodynamics

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

Pharmacokinetics

In rapid IV administration, cytarabine only penetrates the BBB in moderate amounts, but after continuous IV infusion, the concentration in 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. Excreted by the kidneys, less than 10% in unchanged form.

Indications

Active ingredient

Composition

1 vial contains:

Active ingredients:

cytarabine 1000 mg.

In a vial of 1000 mg.

In the carton 1 vial, complete with solvent.

How to take, the dosage

The regimen and method of administration vary among chemotherapy regimens. It is advisable to consult the specific literature before prescribing the drug. Cytosar can be administered by IV or infusion, p/c or intrathecal.

The average daily dose of Cytosar is 100 mg/m2. Patients of advanced age or with reduced hematopoietic reserves are prescribed lower doses of the drug – 50-70 mg/m2.

In acute non-lymphoblastic leukemia, for induction of remission during conventional-dose chemotherapy in combination with other antitumor drugs, Cytosar is prescribed at 100 mg/m/day by continuous IV infusion for 7 days or 100 mg/m2 in/in every 12 h for 7 consecutive days. A total of 4-7 treatment courses are carried out. The intervals between courses are 14 days or more.

In the treatment of leukemia with poor prognosis, as well as refractory and relapsed acute leukemia, high doses of Cytosar – 2-3 g/m2 as 1-3 hour infusions, every 12 h for 2-6 days with or without addition of other anticancer drugs may be used.

Intrathecally in acute leukemia, Cytosar is most commonly used at a dose of 30 mg/m2 every 4 days until cerebrospinal fluid composition normalizes, followed by one additional infusion. The dosage (5 to 75 mg/m2) and the fractional administration (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.

Preparing the solution

In order to obtain a solution with a concentration of 20 mg/ml, 5 ml of diluent must be added to the contents of the 100 mg bottle.

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

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

The concentration of cytarabine must not exceed 100 mg/ml.

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

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

The solvent used for intrathecal administration is 0.9% sodium chloride solution. The solvent for intrathecal and high dose therapy must not contain preservatives (benzyl alcohol).

Note: To open the ampoule, a saw blade is not required The neck of the ampoule is pre-cut at the point of contraction. The colored dot on the head of the ampoule will help you orient it correctly. Hold the ampoule in your hand and with the point facing you, if you press this point lightly with the thumb, the ampoule will open easily.

Interaction

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

The co-administration of Cytozar with other anti-tumor myelosuppressive drugs or radiation therapy in some cases increases the cytotoxic as well as immunosuppressive activity of these drugs.

When using polychemotherapy with Cytozar inclusion, reversible reductions in stabilized plasma concentrations of digoxin and renal excretion of the glycoside have been observed. Digitoxin, whose stabilized plasma concentration appeared to be unchanged under similar conditions, may be considered an alternative for such patients.

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

The clinical data concerning one patient suggest the possibility of reduced efficacy of fluorocytosine.

Special Instructions

The use of cytarabine is not recommended in patients with varicella (including those who have recently had it or after exposure to the disease), with herpes zoster or other acute infectious diseases.

With caution use cytarabine in patients with depression of the hematopoietic system, renal and/or hepatic function disorders, bone marrow infiltration by tumor cells, as well as in patients who have previously received cytotoxic medicines or radiation therapy.

By therapy with cytarabine the peripheral blood count, hepatic and renal function and plasma uric acid level should be monitored.

24 hours after administration, the number of leukocytes decreases, reaches minimum values on the 7th-9th day, then increases briefly 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 leukocyte count rapidly increases to the initial level. The platelet count decreases significantly on day 5 after administration of cytarabine, the lowest level is reached on days 12-15, reaching baseline levels over the next 10 days.

The administration of GCS can prevent or reduce the manifestations of cytarabine syndrome.

At the time of treatment, especially if there are a large number of blast cells or if the tumor (lymphoma) has a large mass, it is necessary to use medication to prevent hyperuricemia and to take allopurinol and enough fluids.

The mutagenic effect of cytarabine has been established in experimental studies.

Contraindications

Side effects

Hepatopoietic system: leukopenia, thrombocytopenia, anemia, megaloblastosis, reticulocytopenia. The decrease in leukocyte count is biphasic, with the first maximum decrease reached by day 7-9. This is followed by a short rise with a maximum on the 12th day. At the second and deeper decrease, the minimum number of leukocytes is noted on days 15-24. In the next 10 days, the leukocyte count increases rapidly. The decrease in platelet count becomes noticeable by day 5, the minimum comes between days 12-15. In the next 10 days, there is a rapid increase in the platelet count to the baseline level.

Infectious complications: secondary infections may develop against immunosuppression caused by Cytozar and other cytostatic agents.

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) gastrointestinal ulceration may be severe; necrotic colitis, necrosis of the small intestine, cystic pneumatosis of the intestine leading to peritonitis may develop.

The central and peripheral nervous system: paresthesias, headache, dizziness, neuritis. When using high-dose therapy CNS dysfunction (confusion, fatigue, memory loss, seizures, coma) and cerebellar function (difficulty speaking, standing or walking, tremor) may be observed. Cases of paraplegia and necrotic leukoencephalopathy have been described with intrathecal administration of Cytosar.

Hepatic disorders: liver dysfunction with hyperbilirubinemia; in high-dose therapy – sepsis and liver abscess.

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

Visual organs: reversible toxic corneal changes and hemorrhagic conjunctivitis may occur when treated with high doses. These reactions can be prevented or reduced by topical prophylactic use of corticosteroid eye drops.

Cardiovascular and respiratory system disorders: arrhythmias, cardiomyopathies, pericarditis, bronchospasm, pulmonitis, progressive respiratory distress syndrome leading to pulmonary edema and cardiomegaly with possible fatal outcome; the frequency of these phenomena increases with high doses of Cytozar and cyclophosphamide.

Other side effects: Anaphylaxis, hyperuricemia, rarely renal dysfunction, urinary retention, pain, inflammation of the subcutaneous tissue, thrombophlebitis at the site of drug administration, the so-called cytarabine syndrome, characterized by fever, myalgia, bone pain, sometimes chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6-12 h after administration of the drug. Corticosteroids have been shown to be effective in the prevention and treatment of this syndrome.

Overdose

There is a report in the literature that administration of 4.5 g/m2 Cytarabine by IV infusion (for I h) every 12 h 12 consecutive times resulted in irreversible CNS changes and even death. There is no specific antidote.

The treatment is symptomatic.

Pregnancy use

Cytarabine is contraindicated in pregnancy. Breast-feeding should be stopped if it is necessary to use it during lactation.

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

The teratogenic and embryotoxic effects of cytarabine have been established in experimental studies.